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Sci Rep Sci Rep Scientific Reports 2045-2322 Nature Publishing Group UK London 29428 10.1038/s41598-023-29428-9 Matters Arising Genome-wide association studies of polygenic risk score-derived phenotypes may lead to inflated false positive rates Uffelmann Emil [email protected] 1 Posthuma Danielle 12 Peyrot Wouter J. 13 1 grid.12380.38 0000 0004 1754 9227 Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands 2 grid.509540.d 0000 0004 6880 3010 Department of Child and Adolescent Psychiatry and Pediatric Psychology, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam University Medical Center, Amsterdam, The Netherlands 3 grid.509540.d 0000 0004 6880 3010 Department of Psychiatry, Amsterdam UMC, Amsterdam, The Netherlands 14 3 2023 14 3 2023 2023 13 421925 7 2022 3 2 2023 (c) The Author(s) 2023 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit Subject terms Genome-wide association studies Disease genetics Alzheimer's disease 100010663 EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ERC-2018-ADG 834057 Uffelmann Emil 501100003246 Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) 024.004.012 Posthuma Danielle 100010663 EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ERC-2018-ADG 834057 Posthuma Danielle 501100003246 Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) 91619152 Peyrot Wouter J. issue-copyright-statement(c) The Author(s) 2023 pmcIntroduction arising from: C. Gouveia et al.; Scientific Reports 10.1038/s41598-022-12391-2 (2022). Gouveia and colleagues (2022)1 conducted a genome-wide association study (GWAS) of a polygenic risk score (PRS)-derived phenotype (N = 37,784), in which they identified 246 independent loci and 473 lead SNPs. This is an enormous increase compared to the most recent and largest GWAS of AD2 (N = 1,126,563), which identified 38 loci. Here we show that the applied approach by Gouveia and colleagues may lead to an inflated false positive rate. In this approach, beta-estimates from a recent GWAS of Alzheimer's disease (AD)3 were used to construct PRSs in the European UK Biobank4 sample, using pruning and thresholding5 with a p-value threshold of 5%. Next, a new case-control phenotype was constructed based on the bottom and top 5% of the PRS distribution, removing 90% of their initial sample. Lastly, a GWAS was conducted on this new PRS-derived phenotype. The authors reasoned that by enriching the sample for individuals with known AD-associated variants, you may also enrich for unknown AD-associated variants. Our major concern is that the applied approach used the same single-nucleotide polymorphisms (SNPs) to construct, as well as to predict the phenotype. In other words, the phenotype was partly regressed on itself, which can inflate test statistics. We performed simulations roughly emulating the approach (see Methods). In short, we simulated individual phenotypes under a liability threshold model and genotypes that loosely reflect the genetic architecture of AD2,3,6 (excluding the APOE locus) including 170,000 independent SNPs of which 1200 were causal and 168,800 were non-causal (null-SNPs). We then simulated a discovery sample such that the PRS explains approximately 5% of the phenotypic variance on the liability scale (N = 366,771). We ran a GWAS of AD in this discovery sample and used the estimated betas to construct a PRS in a target sample (N = 300,000). We then selected individuals in the top and bottom 5% of the PRS distribution (N = 30,000) and ran a second GWAS on this new PRS-derived case-control phenotype. The target cohort overlapped to varying degrees with the discovery cohort (i.e. 0%, 50%, and 100%), noting the AD GWAS summary statistics used by Gouveia and colleagues (2022)1 also contained the UK Biobank. Our results show highly inflated false positive rates in the GWAS of the PRS-derived phenotype (see Fig. 1 and Supplementary Table). Across all null-SNPs and when there is no overlap between discovery and target cohort, the false positive rate was 0.0024 (s.e.m. = 1 x 10-5), which constitutes a 48,000-fold increase compared to a well-controlled false positive rate of 5 x 10-8 (see Supplementary Fig. 1 for a = 0.05). This inflation is driven by null-SNPs that were used to construct the PRS-derived phenotype. The false positive rate of these null-SNPs was equal to 0.05 (s.e.m. = 0.0002, a 1 x 106-fold increase) when there was no overlap, while null-SNPs which were not used to construct the PRS-derived phenotype did not show any inflation. We also looked at the number of false positive associations per study (i.e. false positive rate times the number of null-SNPs considered), which was 402 on average when there was no overlap and was fully driven by SNPs used to construct the PRS-derived phenotype. Decreasing the significance threshold does not protect from inflation in false positive rates. At a significance threshold of 1 x 10-15, we observe a mean false positive rate of 9.48 x 10-6 (s.e.m. = 8.7 x 10-7), a 9.5 x 109-fold increase.Figure 1 Inflated false positive rates in GWAS of PRS-derived phenotype. The false positive rates (a-c) are displayed for varying degrees of sample overlap between discovery and target cohort in a GWAS of a PRS-derived phenotype. Across 100 simulation runs, we observe highly inflated false positive rates. For all null-SNPs, the mean false positive rate ranges between 0.0024 (0% overlap) and 0.0039 (100% overlap) at a significance threshold of 5 x 10-8 (a). Null-SNPs used to construct the PRS-derived phenotype show the highest inflation (b), while all other null-SNPs do not show any inflation (c). As such, the inflation in all null-SNPs is driven by SNPs used to construct the PRS-derived phenotype. Increasing overlap between the target and discovery cohort exacerbates the inflation. We additionally plot the number of false positive associations per study (i.e. false positive rate per SNP times the number of SNPs considered). The mean number of false positives ranged between 402 and 659, and is driven by null-SNPs used to construct the PRS-derived phenotype. The error-bars show the 99.9%-confidence interval of the mean. See Supplementary Table for descriptive statistics. Overlap between the discovery and target cohort exacerbated false positive rate inflation, increasing the false positive rate to 0.004 (s.e.m. = 1.5 x 10-5) across all null-SNPs when there was complete overlap. Similarly, the number of false positive associations increased to 659 (s.e.m. = 2.6). Interestingly, overlap between the discovery and target cohort inflated the false positive rate for null-SNPs used to construct the PRS-derived phenotype but deflated it for all other null-SNPs (see Supplementary Fig. 1). The reason for this is that p-values for null-SNPs will be correlated between the GWAS for AD and the GWAS for the PRS-derived phenotype when there is sample overlap (because AD and the PRS-derived phenotype are correlated and the same individuals are used). Selecting SNPs with p-values smaller than 0.05 for the PRS similarly selects SNPs not part of the PRS with p-values larger than 0.05. As a consequence, the GWAS of the PRS-derived phenotype will have deflated test statistics at null-SNPs not included in the PRS. Next, we varied the p-value threshold for inclusion in the PRS (i.e. varying the threshold from 0.05 to 1 and 5 x 10-8, thus including either all SNPs or only genome-wide significant SNPs, respectively). We found that using all SNPs in constructing the PRS-derived phenotype reduced the inflation of false positive rates (as well as the number of false positives, see Supplementary Fig. 2). This reduction is observed because the bias is diluted across all null-SNPs and so the mean false positive rate decreases. Reducing the p-value threshold to 5 x 10-8 resulted in false positive rates that are not inflated. This is because almost no null-SNP had such a low p-value for AD, and thus almost no null-SNPs were used to construct the PRS-derived phenotype. Lastly, we evaluated a potential power gain for causal SNPs that were not included in the PRS. We calculated the difference in test statistics between the two GWAS (i.e. ZPRS-derived phenotype - ZAD) and found a strong power decrease (mean difference = - 0.14, p < 2.2 * 10-16) in the GWAS of the PRS-derived phenotype. This can be explained by the reduction in sample size and only a partial phenotypic correlation between AD and the PRS-derived phenotype. Thus, an increase in power can only be observed for causal SNPs included in the PRS. But because it is not known which SNPs are causal, true associations cannot be distinguished reliably from false positives. To summarize, Gouveia and colleagues (2022)1 used a new study design with the aim to improve the power for a GWAS of Alzheimer's disease. Based on simulations, we showed that this approach may lead to inflated false positive rates of 80,000-fold increases at a genome-wide significance threshold of 5 x 10-8. The reason for this is that the same SNPs used to construct the PRS-derived phenotype were subsequently tested for association with this newly constructed phenotype. We found the false positive rate inflation was more pronounced in the case of sample overlap between the discovery and target cohort. Our results show that false positive rates are not inflated when the GWAS of the PRS-derived phenotype is performed on SNPs that were not also used to construct the PRS. However, we note that when there is linkage disequilibrium between SNPs included in the PRS and null-SNPs not included in the PRS this could still result in an inflated false positive rate. An appealing approach may be to use a leave-one-chromosome-out approach, where the PRS is constructed using 21 chromosomes, and the GWAS of the PRS-derived phenotype only uses the 22nd left-out chromosome (repeated 22 times so that all chromosomes are left out once). However, in our simulations we found a power decrease for causal SNPs that were not included in the PRS. Moreover, we note SNPs can also be correlated across chromosomes due to e.g. non-random mating7 which could in theory also lead to inflated false positive rates for this approach, but we are not certain about the extent of this inflation which could well be negligible. See the Supplementary Note for a short discussion of some other approaches analyzing (partly) PRS-derived phenotypes, including an approach to improve power8,9. To conclude, phenotype definitions based on PRSs require careful consideration in subsequent GWAS. While excluding any SNP (and those in linkage disequilibrium) from the GWAS that was used to construct the PRS-derived phenotype prevents inflation of false positive rates, it also leads to a loss of power for causal SNPs. Methods Simulation We simulated individual genotype and phenotype data based on the liability threshold model. Our chosen parameters were loosely based on Alzheimer's disease2,3,6, with a population and sample prevalence of 5%, SNP-heritability (h2SNP) of 10% on the liability scale, and a PRS that explains 5% of the variance (R2) on the liability scale. We simulated a total of 170,000 SNPs in linkage equilibrium with a minimum minor allele frequency of 0.1%, as this was the number of pruned SNPs used by Gouveia et al. (2022)1. Out of these, 1200 SNPs were causal, as previously estimated for Alzheimer's disease6, and 168,800 were non-causal. We used the avengeme R package to calculate the number of individuals required for the discovery cohort to produce a PRS that explains the desired R2 value on the liability scale10. We simulated individuals and their liabilities, such that individuals with liabilities larger than the liability-threshold are designated cases, and otherwise controls. We repeatedly simulated individuals until we reached the desired number of individuals (N = 366,771 discovery, N = 300,000 target). We repeated the simulation for three target cohorts. That is, within the same simulation run, one target cohort was fully independent of the discovery cohort (0% sample overlap), in the other 50% (and 100%) of individuals were also present in the discovery cohort. Next, we ran a GWAS in the discovery cohort using plink version 1.911. Using the estimated betas, we calculated PRS in the target cohorts to determine the top and bottom 5% of the PRS distribution to define the PRS extremes (i.e. the PRS-derived phenotype), and thus removed 90% of the sample. Lastly, we ran a second GWAS of the PRS-derived phenotype (N = 30,000) and recorded the false positive rate and the variance of test statistics. We repeated the simulation 100 times. We performed several model checks to ensure our simulations have the desired characteristics; specifically, we verified that the false positive rate and test statistics are not inflated for the primary GWAS of Alzheimer's disease. Supplementary Information Supplementary Information. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-023-29428-9. Acknowledgements D.P. is supported by the Netherlands Organization for Scientific Research Gravitation project 'BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology' (024.004.012) and the European Research Council advanced grant 'From GWAS to Function' (ERC-2018-ADG 834057). W.J.P is supported by a NWO Veni Grant (91619152). Author contributions E.U. conceived the project, wrote the manuscript text and prepared the figures. W.J.P. and E.U. wrote the analysis code. W.J.P. and D.P. supervised the project. All authors discussed and commented on the manuscript. Data availability All code used for this manuscript is available at Simulation results can be downloaded from Competing interests The authors declare no competing interests. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Gouveia C Genome-wide association of polygenic risk extremes for Alzheimer's disease in the UK Biobank Sci. Rep. 2022 12 8404 10.1038/s41598-022-12391-2 35589863 2. Wightman DP A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease Nat. Genet. 2021 53 1276 1282 10.1038/s41588-021-00921-z 34493870 3. Jansen IE Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk Nat. Genet. 2019 51 404 413 10.1038/s41588-018-0311-9 30617256 4. Sudlow C UK biobank: An open access resource for identifying the causes of a wide range of complex diseases of middle and old age PLOS Med. 2015 12 e1001779 10.1371/journal.pmed.1001779 25826379 5. Euesden J Lewis CM O'Reilly PF PRSice: Polygenic Risk Score software Bioinformatics 2015 31 1466 1468 10.1093/bioinformatics/btu848 25550326 6. Holland D Beyond SNP heritability: Polygenicity and discoverability of phenotypes estimated with a univariate Gaussian mixture model PLOS Genet. 2020 16 e1008612 10.1371/journal.pgen.1008612 32427991 7. Yengo L Imprint of assortative mating on the human genome Nat. Hum. Behav. 2018 2 948 954 10.1038/s41562-018-0476-3 30988446 8. the Schizophrenia Working Group of the Psychiatric Genomics Consortium et al A polygenic resilience score moderates the genetic risk for schizophrenia Mol. Psychiatry 2019 10.1038/s41380-019-0463-8 9. Zaitlen N Analysis of case-control association studies with known risk variants Bioinform. Oxf. Engl. 2012 28 1729 1737 10.1093/bioinformatics/bts259 10. Dudbridge F Power and predictive accuracy of polygenic risk scores PLOS Genet. 2013 9 e1003348 10.1371/journal.pgen.1003348 23555274 11. Purcell S PLINK: A tool set for whole-genome association and population-based linkage analyses Am. J. Hum. Genet. 2007 81 559 575 10.1086/519795 17701901
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Blood Cancer J Blood Cancer J Blood Cancer Journal 2044-5385 Nature Publishing Group UK London 811 10.1038/s41408-023-00811-z Editorial Current CML guidelines overemphasize second generation TKIs: revisiting the paradigm Walia Anushka 1 Prasad Vinay [email protected] 2 1 grid.266102.1 0000 0001 2297 6811 School of Medicine, University of California, San Francisco, CA USA 2 grid.266102.1 0000 0001 2297 6811 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA USA 15 3 2023 15 3 2023 12 2023 13 1 3612 1 2023 23 2 2023 28 2 2023 (c) The Author(s) 2023 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Subject terms Targeted therapies Chronic myeloid leukaemia issue-copyright-statement(c) The Author(s) 2023 pmcCurrent National Comprehensive Cancer Network guidelines (NCCN version 1.2023) for chronic-phase chronic myeloid leukemia (CML) recommend second-generation tyrosine kinase inhibitors (2G-TKIs) as first-line therapy for patients with intermediate or high-risk Sokal or Euro scores. In this editorial, we discuss why imatinib should be the preferred first-line drug for all risk groups. Risk scores do not accurately predict prognosis First, CML risk stratification scores are imprecise. It remains unclear whether Sokal scores are associated with CML-related survival in patients receiving TKIs. Analysis of data from the German CML Study IV showed that cumulative incidence probabilities (CIPs) of death due to CML did not differ between low, intermediate, or high-risk groups defined by Sokal scores . 8-year CIPs were found to be 4%, 4%, and 5% for low, intermediate, and high-risk patients, respectively. For Euro scores, high-risk patients had the highest CIPs (12%) but CIPs were lower in the intermediate-risk group than in the low-risk group (2% vs 5%). This suggests that prognostic scores fail to stratify patients by survival outcomes. Outcomes in patients with higher risk scores remain excellent, with a 9-year overall survival (OS) rate of 88% among Sokal non-low-risk patients . The unreliability of Sokal and Euro predictions for patients receiving TKIs is not unexpected. These scores were initially derived based on outcomes of patients receiving chemotherapy or interferon-alpha treatment, and may be less relevant in the TKI area. Sokal and Euro scores show low concordance with each other and the ELTS score (developed for patients receiving imatinib), which better discriminates risk and is currently recommended by European Leukemia Net for baseline risk assessment . The Sokal score is particularly unreliable and is known to over-classify patients as high-risk. Over half of patients classified as high-risk based on Sokal score were found to be non-high risk by ELTS score in one study . Second-generation-TKIs have no survival benefit but have greater adverse effects The basis of the NCCN recommendation is that 2G-TKIs lead to improved molecular and cytogenetic responses in CML patients. A meta-analysis of randomized controlled trials comparing second and third-generation TKIs to imatinib showed risk ratios of CCyR (defined as the absence of Ph+ metaphases) and MMR (defined as 3-log reduction in BCR-ABL1 transcripts) at 12 months to be 1.13 and 1.50, respectively . However, it is unclear whether deeper molecular and cytogenic responses translate to improved patient-centered outcomes, and recent evidence suggests the contrary. Bidikian et al. reported long-term outcomes of 131 patients who did not achieve MMR after 2 years of treatment with TKIs, finding that 10-year CML-related OS was 95% if MCyR was achieved and 80% if MCyR was not achieved . MMR is a poor measure of treatment failure, as patients who fail to achieve MMR can still achieve good outcomes. There is very limited data on correlations between CCyR and MMR with OS across multiple randomized controlled trials (i.e. level-1 evidence). Importantly, 2G-TKIs have failed to demonstrate any improvement in OS or health-related quality of life over imatinib in randomized controlled trials . The ENESTnd study comparing imatinib and nilotinib reported a 10-year OS of 88.3% in the imatinib arm vs 90.3% in the nilotinib (400 mg) arm . No significant difference in OS was found, even though the incidence of progression to accelerated phase/blast phase was suppressed in the nilotinib group. In the DASISION study on imatinib vs dasatinib, 5-year OS was 90.0% and 91.0% in the imatinib and dasatinib arms, respectively . The BFORE trial on imatinib vs bosutinib found similar 12-month OS between treatment groups. While rates of treatment-free remission (TFR) eligibility as defined by molecular measurements by RT-PCR were higher with nilotinib in the ENESTnd study, data on overall TFR success rates was not provided. Actual rates of TFR with imatinib, nilotinib, and dasatinib have been found to be similar (~50%) in discontinuation trials . Based on current data, first-line use of 2G-TKIs provides no real clinical benefit to the patient but adds significant toxicity and cost. 2G-TKIs are arguably more toxic. Specifically, they are associated with cardiovascular, pulmonary, pancreatic, and hepatic toxicities . In the ENESETnd study, 10-year cumulative incidence of cardiovascular events was 24.8% in the nilotinib (300 mg bid) arm as opposed to 6.3% in the imatinib arm . Nilotinib is also associated with glucose tolerance and dyslipidemia, and its use in patients with cardiovascular risk factors or diabetes requires careful consideration. In the DASISION study, dasatinib was found to be a risk factor for pleural effusion and pulmonary hypertension, and patients should be evaluated for pulmonary disease before treatment. The exclusion criteria for trials assessing the efficacy of 2G-TKIs were broader than those used for imatinib alone given their toxicity profiles . Toxicity rates may thus be higher than what trials of 2G-TKIs report. Given that the median age of diagnosis of CML is greater than 60 years, many patients have comorbidities resulting in high risk of treatment-related adverse effects. Patients with comorbidities who are treated with 2G-TKIs require monitoring, resulting in additional medical expenses and time. 2G-TKIs may also be associated with higher likelihood of treatment interruptions. One study using real world data from a claims database found that 59% of patients who received 2G-TKIs had treatment interruptions compared to 45% for imatinib . Similar treatment interruption rates were reported in the ENESTnd and DASISION trials. These studies could not evaluate the reasons for treatment interruption, but toxicity is likely a key factor. Minimizing 2G-TKI treatment interruptions has been shown to lead to better outcomes including greater failure-free survival. Pregnancy Treatment of CML before and during pregnancy requires special consideration, as TKIs are teratogenic and contraindicated during pregnancy. Current guidelines suggest that 2G-TKIs may be preferred in patients assigned female at birth who desire to become pregnant in order to achieve faster molecular responses so that treatment can be safely halted during pregnancy. These recommendations are based on limited observational data suggesting that patients who achieve deep responses prior to conception are more likely to remain in molecular remission if treatment is paused. However, data on long-term effects of losing response during pregnancy is lacking, and the largest analysis of more than 300 pregnancies from the ELN database showed that patients diagnosed with CML during pregnancy or patients with <=MR3 prior to becoming pregnant still had good outcomes . Interferon remains a safe treatment option during pregnancy that can induce or maintain remission. Moreover, no studies have directly compared outcomes of 2G-TKI and imatinib use prior to pregnancy; such data is necessary to clarify treatment recommendations for younger CML patients who desire to have children. Cost Finally, the much higher cost of 2G-TKIs does not justify any potential benefit as a front-line therapy for CML. Imatinib is the only TKI that is currently off patent, and its price has consequently dropped dramatically in recent years. Generic imatinib costs as low as $4400 per year (average, $35,000/year) without loss of efficacy, while the lowest cost 2G-TKI (nilotinib, Novartis) costs $152,814 per year a 35-fold difference. Ya-Chen et al. used a decision analytical model to examine the value of 2G-TKIs as opposed to imatinib for frontline therapy in CML from the payer's perspective . Considering multiple willingness-to-pay thresholds, they reported that the current cost of 2G-TKIs did not justify the higher likelihood of treatment-free remission. Under a very high willingness-to-pay threshold of 200,000/QALY and a 50% difference in 5-year deep molecular response, 2G-TKIs must cost less than $25,000/year to be favorable. It is important to note that the prices of nilotinib and dasatinib are expected to drop after US patents expire in 2023 and 2025, respectively. However even if cost profiles are similar to imatinib, their use as frontline therapy is not justified on the basis of higher treatment-related toxicities without survival benefit. Conclusions Imatinib should be the preferred first-line drug for chronic phase CML regardless of risk category. Imatinib has a superior toxicity profile than 2G-TKIs and is safer in patients with multiple comorbidities. Currently, in a generic form, imatinib is less than one-thirtieth the cost of the cheapest 2G-TKI. For those who do not respond to imatinib, switching to second-line treatments can still result in good outcomes. The cost and safety benefits of imatinib do not compromise survival, as no differences in OS between imatinib and 2G-TKIs have been established. Author contributions Both authors contributed to this editorial's conception and implementation. The first draft of the manuscript was written by AW with input from VP. Both authors read and approved the final version of the manuscript. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Data availability Data sharing is not applicable to this article as no new data were created or analyzed in this study. Competing interests Disclosure: Vinay Prasad's Disclosures. (Research funding) Arnold Ventures (Royalties) Johns Hopkins Press, Medscape, and MedPage (Honoraria) Grand Rounds/lectures from universities, medical centers, non-profits, and professional societies. (Consulting) UnitedHealthcare and OptumRX. (Other) Plenary Session podcast has Patreon backers, YouTube, and Substack. All other authors have no financial nor non-financial conflicts of interest to report. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Pfirrmann M Lauseker M Hoffmann VS Hasford J Prognostic scores for patients with chronic myeloid leukemia under particular consideration of competing causes of death Ann Hematol 2015 94 209 18 10.1007/s00277-015-2316-0 2. Pfirrmann M Clark RE Prejzner W Lauseker M Baccarani M Saussele S The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia Leukemia 2020 34 2138 49 10.1038/s41375-020-0931-9 32601376 3. Vener C Banzi R Ambrogi F Ferrero A Saglio G Pravettoni G First-line imatinib vs third-generation TKIs for chronic-phase CML: a systematic review and meta-analysis Blood Adv 2020 4 2723 35 10.1182/bloodadvances.2019001329 32559295 4. Bidikian A, Jabbour E, Issa GC, Short NJ, Sasaki K, Kantarjian H. Chronic myeloid leukemia without major molecular response after 2 years of treatment with tyrosine kinase inhibitor. Am J Hematol. 2023. 10.1002/ajh.26836. 5. Kantarjian HM Hughes TP Larson RA Kim DW Issaragrisil S le Coutre P Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis Leukemia 2021 35 440 53 10.1038/s41375-020-01111-2 33414482 6. Atallah E Schiffer CA Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when and for whom? Haematologica 2020 105 2738 45 10.3324/haematol.2019.242891 33054106 7. Ono T Which tyrosine kinase inhibitors should be selected as the first-line treatment for chronic myelogenous leukemia in chronic phase? Cancers 2021 13 5116 10.3390/cancers13205116 34680265 8. Hantel A Larson RA Imatinib is still recommended for frontline therapy for CML Blood Adv 2018 2 3648 52 10.1182/bloodadvances.2018018614 30587493 9. Ward MA Fang G Richards KL Walko CM Earnshaw SR Happe LE Treatment interruption and regimen change in first generation versus second-generation tyrosine kinase inhibitors used as first-line therapy for chronic myeloid leukemia JHEOR 2015 2 181 91 10.36469/9899 10. Abruzzese E Turkina AG Apperley JF Bondanini F de Fabritiis P Kim DW Pregnancy management in CML patients: to treat or not to treat? Report of 224 outcomes of the European Leukemia Net (ELN) Database Blood 2019 134 498 10.1182/blood-2019-124430 31395582 11. Treatment value of second-generation BCR-ABL1 tyrosine kinase inhibitors compared with imatinib to achieve treatment-free remission in patients with chronic myeloid leukaemia: a modelling study. 2022.
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Data Brief Data Brief Data in Brief 2352-3409 Elsevier S2352-3409(23)00120-8 10.1016/j.dib.2023.109002 109002 Data Article Field oriented control dataset of a 3-phase permanent magnet synchronous motor Nustes Juan Camilo [email protected] ab* Pau Danilo Pietro a Gruosso Giambattista b a STMicroelectronics, via C. Olivetti 2, Agrate Brianza, I-20864, Italy b Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Piazza Leonardo da Vinci, 32-20133, Italy * Corresponding author. [email protected] 24 2 2023 4 2023 24 2 2023 47 10900229 12 2022 10 2 2023 14 2 2023 (c) 2023 The Author(s) 2023 This is an open access article under the CC BY license ). This paper presents a dataset of a 3-phase Permanent Magnet Synchronous Motor (PMSM) controlled by a Field Oriented Control (FOC) scheme. The data set was generated from a simulated FOC motor control environment developed in Simulink; the model is available in the public GitHub repository1. The dataset includes the motor response to various input signal shapes that are fed to the control scheme to verify the control capabilities when the motor is subjected to real life scenarios and corner conditions. Motor control is one of the most widespread fields in control engineering as it is widely used in machine tools and robots, the FOC scheme is one of the most used control approaches thanks to its performance in speed and torque control, with the drawback of having to handcraft the Proportional-Integrative-Derivative (PID) regulators using Look Up Tables (LUT). The test conditions are designed by setting a motor desired speed. Different input speed variations shapes are proposed as well as extreme scenarios where the linear behaviour of the PID regulator is challenged by applying fast and high magnitude speed variations so that the PID controller is not able to correctly follow the reference. The measured data includes both the outer and inner-loop signals of the FOC, which opens the possibility to develop non-linear control approaches such as Machine Learning (ML) and Neural Networks (NN) with different topologies to replace the linear controllers in the FOC scheme. Keywords Motor control Simulink ID control Neural networks pmc Specifications Table Subject Control and Systems Engineering Specific subject area Motor Control Type of data Dataset files: *.mat files Motor response images: *.jpg files How data were acquired Developed Simulink environment considering the FOC scheme and a PMSM motor model. Different signals were applied as an input to the model and the internal signals were measured and stored into files by using matlab scripts. Data format Raw Description of data collection Data generated in a mathematical model of the 3-phase motor inside the Simulink environment. The simulated motor is a 7 poles PMSM, with a maximum speed of 15000rpm (Full parameters table in Section 2.1). Different input signals of the desired speed were considered. Data source location Data was generated at ST Microelectronics, Agrate Brianza, Italy Data accessibility Repository name: PMSM_FOC datastet Direct URL to data: Value of the Data This dataset simulates the behaviour of a 3-phase PMSM motor controlled using the FOC scheme , the signal values of the rotating DQ frame voltage and current are gathered both for the reference and measured signal. The dataset also includes the signal value of the reference and measured speed which is a valuable tool for the development and validation of ML algorithms for motor control without the need of having a physical motor to produce data.* It contains data generated for both real life scenarios and corner conditions to stress to the maximum the linear controllers (PID) deployed in the FOC scheme. * Practitioners working on motor control applying a ML or NN approach can benefit greatly from this dataset, as it removes the need to dump measurements directly from a physical motor. * The dataset can be used, for example, in ML tasks such as training, testing, and validating a NN. The dataset can be used to train and test various architectures of ML and NN based regressors. * ML approaches can be adopted for defining the actual operating conditions of the controller [step-generated], and then test the performance when applying an extreme condition scenario [random-generated] , . 1 Objective This dataset was created to mimic the response of a PMSM when subjected to a wide set of input speed shapes as well as test conditions specifically designed to highlight how the nonlinearities affect the PID controller present in the FOC scheme, in this way, a physical motor to gather data is no longer needed. The inclusion of non-linear boundary brings the possibility to design a non-linear control approach such as ML or NN based control, capable of matching and, if possible, outperforming the behavior of a PID regulator in certain situations . 2 Data Description The dataset consists of .mat data arrays, along with .jpg images for each test case in order to easily preview the speed control outcomes. Each test case corresponds to a desired speed input scenario fed to the motor control scheme. The main folder Motor_Control_Dataset is divided in four branches, each one corresponding to the type of signal that the system has as input. The first branch 1_Step_Input contains data gathered when a step input is applied to the system, the second branch presents data obtained through ramp inputs (2_Ramp_Input) with different slopes. The content of 3_Random_Signal and 4_Generated_Signal is a set of test cases based on a random and a graphically designed signal respectively. The directory tree is organized as follows:- Motor_Control_Dataset* 1_Step_Input * 2_Ramp_Input * 3_Random_Signal * 4_Generated_Signal 2.1 Step Input Branch The subfolder 1_Step_Input contains five test cases obtained by setting a step input with the value of the desired speed of the motor. Each test folder contains the .mat data array as well as a .jpg image comparing the reference and measured speed. The data is normalized considering that the maximum motor speed is 15000rpm. The directory tree is shown below:- Motor_Control_Dataset* 1_Step_Input# 25_step* 25_step.jpg * 25_step.mat # 40_step # 60_step # 80_step # 100_step * 2_Ramp_Input * 3_Random_Signal * 4_Generated_Signal Each test case is named as it follows: <max. speed percentage>_<input type>.extension Fig. 1 shows examples of the .jpg files contained in two test folders, which are useful as a preview of the data array by showing the comparison between the reference and measured speed. Fig. 1a shows the step response for a target speed of 20% (3000 rpm), while Fig. 1b presents the response to a step of an 80% (12000 rpm) speed reference.Fig 1 Motor speed measured (blue) vs reference (red) with a step input. Fig 1 The description of every dataset parameter is reported in Table 2 and is valid for all dataset branches. An example of the test case 25_step.mat is shown in Table 2. The columns correspond to the parameters described in table 1.Table 1 Description of the dataset parameters, valid for all four dataset branches, with reference to section 2.2. Table 1Parameter Abbreviation Description Measure unit Speed Reference SpeedRef Desired speed of the motor, set by the user % Measured Speed SpeedMeas Actual speed of the motor product of the FOC % D current reference Id_ref Reference value of current for torque control, set to zero A Q current reference Iq_ref Reference value of current for torque control, obtained through the speed control regulator (outer loop) A Measured D current Id_meas Feedback current value obtained from Park transform A Measured Q current Iq_meas Feedback current value obtained from Park transform A Measured D voltage Vd Output voltage value from the PID torque regulator V Measured Q voltage Vq Output voltage value from the PID torque regulator V 2.2 Ramp Input Branch The directory structure is very similar to the step input branch and is reported below. The difference is the type of signal that will be input to the system, in this case is a ramp that will increase the motor speed from the open loop value (10% of max speed) with a constant slope. The test cases are defined by changing the slope value, which is expressed as a percentage of the maximum motor speed (15000 rpm).- Motor_Control_Dataset* 1_Step_Input * 2_Ramp_Input# 10_ramp* 10_ramp.jpg * 10_ramp.mat # 20_ramp # 40_ramp # 80_ramp # 100_ramp * 3_Random_Signal * 4_Generated_Signal The ramp data set contains five different cases where the slope is varying from a 10% to a 100% slope value, changing the time needed to reach the maximum speed value that the motor can provide. Fig. 2a shows the ramp response for a slope of 20% (3000 rpm/s), while Fig. 2b presents the response to a ramp with a slope of 80% (12000 rpm/s).Fig 2 Motor speed measured (blue) vs reference (red) with a ramp input. Fig 2 2.3 Random Signal Input Branch The third directory follows the same format as the previous two and it is shown below. In this case, the test cases are defined by applying a random signal generated around a random mean value. The motor runs for 10 seconds in each test considering the first second as the open loop start. The four test cases are named by considering the mean speed value around which the signal was generated (In this case: 20%, 40%, 70% and 100%). Multiple random test cases are considered to verify how the system reacts to fast speed changes, and if this behaviour varies when the mean value of the speed changes, recalling that the speed is normalized considering the maximum motor speed of 15000 rpm.- Motor_Control_Dataset* 1_Step_Input * 2_Ramp_Input * 3_Random_Signal# 20_random* 20_random.jpg * 20_random.mat # 40_random # 70_random # 100_random * 4_Generated_Signal In Fig. 3 are presented two examples of the .jpg files contained in the test folders, showing the behaviour of random signal generated around a mean value of a 70% (Fig. 3a), and Fig. 3b is generated around a 100% mean value (15000 rpm/s).Fig 3 Motor speed measured (blue) vs reference (red) with a random signal generator. Fig 3 2.4 Graphically Designed Signal Input Branch The fourth and last directory keeps the same format as the first three directories mentioned above. The difference with this branch is that the input signal is a graphically designed signal generated through the "signal builder" block in Simulink, where the user can design the shape of a signal by "drawing" the waveform. This input shape gives the possibility to the user to test the control performance of the system when subjected to a desired input, while also opening the possibility to test specific conditions to highlight the controller flaws to nonlinearities, which are present when the controller is subjected to high magnitude speed variations, or very fast transitions. The directory tree is shown below:- Motor_Control_Dataset* 1_Step_Input * 2_Ramp_Input * 3_Random_Signal * 4_Generated_Signal# 1_generated* 1_generated.jpg * 1_generated.mat # 2_generated # 3_generated # 4_generated # 5_generated # 6_generated # 7_generated Fig. 4 shows examples of the .jpg files contained in two generated signal test folders, which are useful as a preview of the data array by showing the comparison between the reference and measured speed.Fig 4 Motor speed measured (blue) vs reference (red) with a manually generated signal. Fig 4 Fig. 4a shows the response for the test case 1_generated, while Fig. 4b presents the response to the test case 3_generated. Both signals were built to show the overshoot caused by high magnitude speed variations. 3 Experimental Design, Materials and Methods The dataset is based on a simulated environment of a FOC scheme implemented in Simulink to control the speed of a 7 pole Permanent Magnet Synchronous Machine with a maximum speed of 15000rpm when no torque is applied. To gather data from the deigned environment, a test set of inputs was designed to verify how the controller reacts to the target speed. The Simulink model is available in . 3.1 Motor Model For the model of the motor, the "Surface mounted PMSM" block (Fig. 5) was used, which is part of the Motor Control Block set provided by Matlab, it internally considers all the machine dynamics and the final transfer function. Then, this block was tuned with the parameters of the motor (Table 3) obtained through the Motor Profiler software available at2.Fig. 5 Surface mounted PMSM block. Fig 5 3.2 FOC Scheme The FOC scheme is shown in Fig. 6, where the acquired signals (defined in Table 2) are labeled for an easier understanding of the process. Some blocks such as the Clarke, Park, and Inverse Clarke transform are also included within the motor control block set. The model implementation in Simulink is based on the sensorless FOC scheme developed by Mathworks3, and the controller gains for the PID where obtained using the Motor Control Workbench provided by ST .Fig 6 Field Oriented Control Block-scheme representation. Fig 6 Table 2 Example of 25_step.mat file Table 2SpeedRef SpeedMeas Id_ref Iq_ref Id_meas Iq_meas Vd Vq 0.03 0.0 0.0 0.00000 0.000488 0.000846 0.15 0.0 0.03 0.0 0.0 0.00825 0.000494 0.000842 0.15 0.0 0.03 0.0 0.0 0.00825 0.010257 0.000131 0.15 0.0 0.03 0.0 0.0 0.00825 0.030278 -0.000105 0.15 0.0 0.03 0.0 0.0 0.00825 0.049320 -0.000606 0.15 0.0 Table 3 Motor parameters gathered from the Motor Profiler tool. Table 3Parameter Abbreviation Value Measure unit Pole Pairs p 7 - Max. Speed wmax 15000 Rpm Nominal Current In 1.20 Apk Nominal DC voltage VDC 12.0 V Stator Resistance Rs 0.11 Ohm Stator Inductance Ls 0.018 mH Back-Emf Constant B-Emf 0.4 Vms/krpm Remark: This FOC scheme requires that that the motor starts in open-loop control, which is achieved when the desired speed is under the 10% of the maximum motor speed. This is considered in every test case, where the first simulation second of every data array corresponds to open-loop control. This data points may be deleted before incurring into ML applications to avoid overfitting with the same data values in every test case instead of considering more valuable data. 3.3 Test Cases Generation In this section, the input signals for the Simulink environment are defined. The test cases are variations of target speed when a step, ramp and random signals are applied to the system; Then, also specific signals are manually generated to verify the controller behavior to nonlinear dynamics. 3.3.1 Step Input For the first branch, a step block is used as an input to the FOC scheme where the starting point is the open loop speed (10% of maximum motor speed), and then after one simulation second has elapsed, the final value of the step is the desired motor speed. As an example, the target speed from test case 40_step.mat (Fig. 7) is set up with the following values:- Initial value: Open loop speed (1500 rpm). - Step time: 1 second. - Final value: 40% of the maximum speed value (6000rpm). Fig 7 Step input for a 40% speed value. Fig 7 The five test cases present in the dataset are related to five different speed targets corresponding to 20, 40, 60, 80, and 100% of the maximum motor speed, which is 15000 rpm as mentioned in previous sections. 3.3.2 Ramp Input The second branch uses a ramp block for the input signal, the considerations of an open-loop start for the motor still hold. In every test case, the block is parametrized as follows:- Initial output: Open loop speed (1500 rpm) - Start time: 1 second (Open loop start of the motor) To variate the testing, the slope value in each test case is set to a percentage of the maximum motor speed. An example slope value for the test case 80_ramp.mat is presented below, and the overall target speed signal is shown in Fig. 8.Fig 8 Ramp input with an 80% slope value. Fig 8 Case: : 80% (Speed increases 12000rpm per second) 3.3.3 Random Signal Input The third branch uses a random source block for the input signal, this block sets a random mean value in a given range [1500 - 15000 rpm], the signal is generated on this mean value. To guarantee that the motor starts in open-loop control, a step input like the one presented in the test case step_10 is applied with the following values:- Initial value: Open loop speed (1500 rpm). - Step time: 1 second (Open loop start of the motor). - Final value: 0 rpm. The random signal needs to be delayed 1 second while the motor is starting in open loop, the developed input block scheme is presented in Fig. 9. Four random signals are included in the dataset, each of which is generated around a different mean value (20%, 40%, 70%, and 100%) of the maximum motor speed. The goal is to verify if the system is able to react at fast speed variations, and also, verify how the controller reacts when having speed variations around low speeds (e.g. 20% mean value) compared to high speed variations (e.g. 100% mean value). As an example, the target speed from test case 70_random.mat is shown in Fig. 10.Fig 9 Random signal generator input with delay - Simulink block scheme. Fig 9 Fig 10 Random signal generated around a mean value of a 70% maximum motor speed. Fig 10 3.3.4 Graphically Designed Signal Input For the fourth and final branch, the input signal is graphically designed using the "signal builder" block, where the user can graphically generate the desired input signal and adjust its duration. In this test cases the signals were defined by designing high magnitude speed changes, and in some cases, fast speed transitions to bring the system out of control. An example of a generated signal is shown in Fig. 11, during the first second, the motor is under 10% of the maximum speed to start in open loop. The signal never falls under the 10% speed limit to keep the closed-loop control.Fig 11 Manually generated signal from the signal builder block. Fig 11 Ethics Statement The authors declare that the data presented in this article did not involve any use of human subjects, animal experiments nor data collected from social media platforms. CRediT authorship contribution statement Juan Camilo Nustes: Conceptualization, Methodology, Software, Formal analysis, Investigation, Writing - original draft, Writing - review & editing. Danilo Pietro Pau: Conceptualization, Validation, Writing - original draft, Writing - review & editing, Supervision, Project administration. Giambattista Gruosso: Conceptualization, Validation, Writing - original draft, Writing - review & editing, Supervision, Project administration. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article. Data Availability Motor_control_dataset (Original data) (Mendeley Data). 1 2 3 References 1 Korkmaz F. Comparative performance evaluation of FOC and DTC controlled PMSM drives 4th POWERENG May 2013 705 708 2 Cheon K. On Replacing PID Controller with Deep Learning Controller for DC Motor System J. Autom. Control Eng. 3 2015 452 456 3 Flah A. Lassaad S. An improved PMSM drive architecture based on BFO and neural network: Regular paper IJARS 10 2013 4 Federici N. Pau D. Adami N. Benini S. Tiny Reservoir Computing for Extreme Learning of Motor Control 2021 International Joint Conference on Neural Networks (IJCNN) 2021 1 8 5 Sensorless FOC scheme. Mathworks. URL: 6 STMicroelectronics. ST Motor Control Workbench. URL:
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34905 Emergency Medicine Family/General Practice Internal Medicine Heyde Syndrome Complicated by Essential Thrombocythemia: A Case Report Muacevic Alexander Adler John R Imawaka Motoaki 1 Tanaka Yudai 2 Mishiro Tsuyoshi 3 Sano Chiaki 4 Ohta Ryuichi 5 1 Family Medicine, Shimane University Medical School, Izumo, JPN 2 Commnity Care, Unnan City Hospital, Unnan, JPN 3 Internal Medicine, Unnan City Hospital, Unnan, JPN 4 Community Medicine Management, Shimane University Faculty of Medicine, Izumo, JPN 5 Communiy Care, Unnan City Hospital, Unnan, JPN Ryuichi Ohta [email protected] 12 2 2023 2 2023 15 2 e3490512 2 2023 Copyright (c) 2023, Imawaka et al. 2023 Imawaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Heyde syndrome is a multisystem disorder characterized by the triad of aortic stenosis (AS), gastrointestinal bleeding, and acquired von Willebrand syndrome. Age-related degeneration is the most common cause of aortic stenosis and is frequently encountered in today's aging society. Approximately 20% of patients with severe aortic stenosis have Heyde syndrome. We encountered an older patient with primary thrombocytosis who was brought to a rural community hospital with bloody stools and was diagnosed with bleeding from an intestinal arteriovenous malformation. A final diagnosis of Heyde syndrome was made based on the presence of severe aortic stenosis and the presence of schistocytes in peripheral blood smears. Valvular diseases can complicate chronic hematological diseases. When the rapid progression of anemia and segmented red blood cells in the peripheral blood are observed in patients with severe aortic stenosis, Heyde syndrome should be considered based on peripheral blood smears and clinical course. family medicine rural hospital general medicine von willebrand disease primary thrombocytosis heyde syndrome gastrointestinal bleeding aortic stenosis The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Heyde syndrome is a syndrome of severe aortic stenosis complicated by gastrointestinal bleeding . In an aging society, the prevalence of aortic stenosis increases and, if severe, the likelihood of developing Heyde syndrome increases . In addition, complications of chronic hematologic diseases may increase the incidence of Heyde syndrome. Chronic hematologic diseases increase the fragility of blood cell components, leading to the progressive destruction of blood cells at the site of aortic stenosis . In this process, further destruction of large multimers of von Willebrand factor may lead to coagulation disorders and gastrointestinal bleeding, such as Heyde syndrome . We report a case of Hyde syndrome in an 82-year-old woman with essential thrombocythemia, whose chief complaint was lower intestinal bleeding. The patient had persistent anemia that could not be explained by essential thrombocythemia alone. Through this case report, we discuss how to manage a potentially fatal disease, such as Heyde syndrome, while appropriately managing the general condition of older patients. Case presentation An 82-year-old woman presented to a rural community hospital with a chief complaint of bloody stools. On the day of admission, her daughter noticed bloody stools and took the patient to the hospital. She had a medical history of essential thrombocythemia from a bone marrow biopsy 10 years ago, chronic renal failure with renal anemia, Alzheimer's disease, and hypertension. Other medical history included spinal canal stenosis. She was taking aspirin 100 mg, famotidine 20 mg, and spironolactone 50 mg. On admission, the patient's vital signs were as follows: blood pressure, 125/71 mmHg; pulse, 87 beats/min, temperature 37.2degC, respiratory rate, 19 breaths/min; and SpO2 99%. Eyelid conjunctival pallor, external jugular vein distension, internal jugular vein pulsation, a cardiac systolic murmur radiating to both sides of the neck, and leg edema were observed. A digital rectal examination revealed black stools. Laboratory data showed a hemoglobin (Hb) level of 4.3 g/dL, erythrocyte count of 1.37 107/mL, reticulocyte count of 5.2%, lactate dehydrogenase (LDH) of 627 U/L, blood urea nitrogen of 38.8 mg/dl, and serum creatinine of 1.13 mg/dL (Table 1). Table 1 Initial laboratory data of the patient PT, prothrombin time; INR, international normalized ratio; APTT, activated partial thromboplastin time; eGFR, estimated glomerular filtration rate; ADAMTS, A Disintegrin and Metalloproteinase with Thrombospondin Motifs; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Cl, Chloride Parameters Level Reference White blood cells 6.30 3.5-9.1 x 103/mL Neutrophils 61.3 44.0-72.0% Lymphocytes 15.6 18.0-59.0% Monocytes 20.7 0.0-12.0% Eosinophils 1.2 0.0-10.0% Basophils 1.2 0.0-3.0% Red blood cells 1.37 3.76-5.50 x 106/mL Hemoglobin 4.3 11.3-15.2 g/dL Hematocrit 12.5 33.4-44.9% Mean corpuscular volume 91.1 79.0-100.0 fl Platelets 35.5 13.0-36.9 x 104/mL Total protein 5.5 6.5-8.3 g/dL Albumin 3.0 3.8-5.3 g/dL Total bilirubin 0.4 0.2-1.2 mg/dL Aspartate aminotransferase 23 8-38 IU/L Alanine aminotransferase 10 4-43 IU/L g-Glutamyl transpeptidase 23 <48 IU/L Lactate dehydrogenase 627 121-245 U/L Blood urea nitrogen 38.8 8-20 mg/dL Creatinine 1.13 0.40-1.10 mg/dL eGFR 35.4 >60.0 mL/min/L Serum sodium 137 135-150 mEq/L Serum potassium 4.8 3.5-5.3 mEq/L Serum Cl 106 98-110 mEq/L Serum glucose 123 70-110 mg/dL Creatinine kinase 1782 56-244 U/L C-reactive protein 1.74 <0.30 mg/dL PT 80.3 70-130% PT-INR 10.99 APTT 27.9 25-40 s Fibrinogen degradation products 2.8 <5 mg/mL SARS-CoV-2 Negative Negative Urine test Leukocyte Negative Negative Nitrite Negative Negative Protein Negative Negative Glucose Negative Negative Urobilinogen (1+) Negative Bilirubin Negative Negative Ketone Negative Negative Blood Negative Negative Contrast-enhanced computed tomography showed high density in the lumen of the ascending colon, indicating active bleeding. An urgent lower gastrointestinal endoscopy was performed, which revealed that the source was an intestinal arteriovenous malformation . Figure 1 Emergency colonoscopy clarifying that the source of bleeding was an arteriovenous malformation (white arrow) Analysis of the von Willebrand factor showed that the MEDIUM and SMALL multimers were positive, and the LARGE multimer was negative, exhibiting an abnormal multimer distribution. We performed echocardiography showing severe aortic stenosis (aortic valve area, 0.7 cm2; aortic flow velocity, 4.1 m/second). With normal coagulation factor levels and an abnormal result of von Willebrand factor analysis, we suspected acquired von Willebrand disease due to essential thrombocythemia, and this, along with aortic stenosis and gastrointestinal bleeding, formed the triad of Heyde syndrome. . On the second day of hospitalization, the patient's Hb increased to 5.6 g/dL, and after two more units of blood cell transfusions were administered, it further improved to 7.8 g/dL on the third day. Examination of the peripheral blood smear showed anisocytosis, nucleated erythrocytes, juvenile granulocytes, acanthocytes, and tear-drop erythrocytes . Figure 2 Fragmented red blood cells in the patient's blood smear (black arrows) The patient had a mild fever on admission, which increased to 40.0 degC on the sixth day of hospitalization, with mild tenderness and tapping pain in the left upper abdomen. Based on abdominal computed tomography findings, we suspected a splenic abscess and considered the possibility of bacterial translocation . Figure 3 Computer tomography showing a splenic abscess (white arrow). The patient was started on piperacillin/tazobactam (13.5 g/day) as empirical therapy. In addition to infection, tumor and drug-induced fever were also considered differential diagnoses. The fever subsided and the blood cultures were negative. Piperacillin/tazobactam was discontinued on the 12th day of hospitalization. On the 23rd day, the anemia and fever due to gastrointestinal hemorrhage improved, and the patient was discharged. Discussion This case shows that the large multimers of von Willebrand factor may be mechanically disrupted by aortic valve stenosis, resulting in coagulation disorder and bleeding from an intestinal arteriovenous malformation . Here, we discuss the difficulty in diagnosing Heyde syndrome in patients with chronic hematologic diseases and the optimal medical treatment for this syndrome. The incidence of Heyde syndrome may increase among patients with hematologic diseases because of the fragility of their blood cells; therefore, clinicians should consider this disease among older patients with hematologic diseases . The patient, in this case, had an extreme elevation of LDH, abnormal renal function, and anemia that could not be explained by essential thrombocythemia alone. Chronic hematological diseases, such as essential thrombocythemia and polycythemia, may increase the vulnerability of the blood cell components. Population aging may also increase the vulnerability of blood cell components . In addition, aging is often associated with increased calcification and sclerosis of the aortic valve . Therefore, older patients with chronic hematologic diseases may be at a higher risk of Heyde syndrome. Therefore, clinicians should consider this disease in older patients with aortic stenosis. As the aging population makes invasive treatment of Heyde syndrome more complex, various treatment options need to be considered. Aortic valve replacement is regarded as the most promising treatment for Heyde syndrome as a long-term treatment for bleeding . However, its invasive nature may make it risky to administer postoperative antiplatelet and anticoagulant medication. There are reports of cases in which the disease was controlled by the administration of bevacizumab, an angiogenic therapy, and octreotide, which lowers venous pressure in the portal system and treats bleeding from angiodysplasia . These treatments can reduce the need for blood transfusions and decrease the risk of bleeding. Recently, transcatheter arterial valve implantation (TAVI), in which aortic valve replacement is performed by catheterization, has become common in elderly patients with aortic valve disease . Considering TAVI in older patients with severe aortic stenosis in uncomplicated settings may improve the quality of life. Aortic stenosis is changing from a disease that causes sudden death to a chronic condition that causes various complaints. Prompt detection and treatment of aortic stenosis are essential for preventing various complaints among older patients. When a patient presents with abnormal LDH levels, prolonged renal dysfunction, and anemia that cannot be explained by the primary disease, as in our case, the possibility of Heyde syndrome should be considered. As a general practitioner, it is necessary to consider systemic findings, arrive at an early diagnosis, and initiate early treatment of a severe condition by early detection of angiodysplasia in the gastrointestinal tract . An aging society makes it difficult for organ-specific specialists to treat patients with multiple coexisting diseases. It is, therefore, necessary for general practice physicians, as system specialists, to understand each patient's condition comprehensively, view the patient as a system, and manage all of their conditions . General physicians as system-specific specialists can treat patients with multiple coexisting diseases, such as our patients, with circulatory, hematological, and intestinal abnormalities in a multidisciplinary manner. System-focused approaches to general medicine can help increase the possibility of early detection of gastrointestinal vascular dysplasia. Conclusions The development and progression of aortic stenosis in older patients with hematologic comorbidities may lead to Heyde syndrome. The coexistence of multiple diseases in the elderly is becoming increasingly more common as the population ages. As systemic specialists, general practice physicians should manage the general conditions of older patients and provide continuous care in smooth collaboration with organ-specific specialists. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Acquired von Willebrand syndrome associated with cardiovascular diseases J Atheroscler Thromb Horiuchi H Doman T Kokame K Saiki Y Matsumoto M 303 314 26 2019 30867356 2 Extracellular histones induce erythrocyte fragility and anemia Blood Kordbacheh F O'Meara CH Coupland LA Lelliott PM Parish CR 2884 2888 130 2017 29133350 3 Acquired von Willebrand syndrome in aortic stenosis N Engl J Med Vincentelli A Susen S Le Tourneau T 343 349 349 2003 12878741 4 von Willebrand disease: a concise review and update for the practicing physician Clin Appl Thromb Hemost Swami A Kaur V 900 910 23 2017 27920237 5 Systemic bevacizumab for refractory bleeding and transfusion-dependent anemia in Heyde syndrome Blood Adv Song AB Sakhuja R Gracin NM Weinger R Kasthuri RS Al-Samkari H 3850 3854 5 2021 34500461 6 Metabolic footprint of aging and obesity in red blood cells Aging (Albany NY) Domingo-Orti I Lamas-Domingo R Ciudin A Hernandez C Herance JR Palomino-Schatzlein M Pineda-Lucena A 4850 4880 13 2021 33609087 7 Aortic valve stenosis: from basic mechanisms to novel therapeutic targets Arterioscler Thromb Vasc Biol Goody PR Hosen MR Christmann D 885 900 40 2020 32160774 8 A prospective controlled evaluation of endoscopic detection of angiodysplasia and its association with aortic valve disease Gastrointest Endosc Bhutani MS Gupta SC Markert RJ Barde CJ Donese R Gopalswamy N 398 402 42 1995 8566626 9 Octreotide in the treatment of gastrointestinal bleeding caused by angiodysplasia in two patients with von Willebrand's disease Br J Haematol Bowers M McNulty O Mayne E 524 527 108 2000 10759709 10 Device-related thrombotic microangiopathy in an elderly patient with a history of aortic surgery Cureus Tanaka C Naito Y Suehiro S Sano C Ohta R 0 14 2022 11 Family physicians as system-specific specialists in Japan's aging society Cureus Ohta R Sano C 0 14 2022 12 Family medicine education at a rural hospital in Japan: impact on institution and trainees Int J Environ Res Public Health Ohta R Ryu Y Sano C 18 2021
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34906 Dermatology Genetics Pediatrics Haber's Syndrome: A Case Report Muacevic Alexander Adler John R Aljoudi Sarah B 1 Tallab Mawaddah 2 Al Hawsawi Khalid 3 1 Dermatology, King Abdulaziz University Faculty of Medicine, Jeddah, SAU 2 Dermatology, King Fahad General Hospital, Jeddah, SAU 3 Dermatology, King Abdulaziz Hospital, Makkah, SAU Sarah B. Aljoudi [email protected] 13 2 2023 2 2023 15 2 e3490612 2 2023 Copyright (c) 2023, Aljoudi et al. 2023 Aljoudi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Haber's syndrome is an autosomal dominant, rare genodermatosis characterized by photosensitive, persistent facial erythema associated with reticulated hyperpigmentation. We present a case of an eight-year-old healthy Saudi girl who presented with facial erythema and generalized reticulated hyperpigmentation. Systematic review and laboratory studies were unremarkable. Histopathological examination revealed hyperpigmentation of the basilar keratinocytes with mild digitated elongations of the rete ridges. The patient was diagnosed with early-onset clinical presentation of Haber's syndrome. In this report, Haber's syndrome is reviewed, and differential diagnoses of reticulated hyperpigmentation are discussed. hyperpigmentation photosensitivity haber's syndrome dowling degos disease reticulate pigmentary disorders The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Reticulate pigmentary disorders are a group of genodermatoses inherited mostly in an autosomal dominant fashion . They include the reticulate acropigmentation of Kitamura; Dowling-Degos disease and its variant, Galli-Galli disease; and Haber's syndrome (HS). HS is characterized by persistent, photosensitive, rosacea-like facial lesions manifesting in early adolescence , followed by the appearance of reticulate hyperpigmentation on the trunk, proximal extremities, and axillae. Other features include keratotic papules, comedo-like lesions, and pitted scars. There have been few reports of HS worldwide. Here we present a case of early-onset HS in a patient with rosacea-like facial eruptions and generalized reticulate hyperpigmentation. Case presentation An eight-year-old female Saudi patient, otherwise healthy, visited the dermatology clinic with a four-year history of progressive, hyperpigmented skin lesions that started on the upper extremities and progressed to the trunk, face, and lower extremities. She reported a history of persistent, photosensitive facial eruption with no associated pain or burning sensation, noticed earlier than the hyperpigmented skin lesions. The patient had no history of recurrent infection or hospital admissions. The patient's mother had similar rosacea-like skin lesions. The rest of her family was healthy, and all marriages on her paternal side were non-consanguineous. Dermatological examination revealed diffuse, hyperpigmented macules and patches in a reticulate pattern involving the face, extremities, and trunk, with prominent follicles under dermoscopy. Facial erythema, telangiectasia, and a few erythematous papules were observed on the patient's cheeks, which is exacerbated by sun exposure . No alopecia, comedones, or pitted scars were observed. Hair, nail, mucous-membrane, ocular, and dental examinations were all unremarkable. Her neonatal history was insignificant, her physical development was age-appropriate, and her academic performance was excellent. Figure 1 Haber's syndrome. Rosacea-like facial eruption with telangiectasia in the studied case. Figure 2 Haber's syndrome. Reticulated hyperpigmentation of the trunk in the studied case. Histopathological examination of a skin biopsy of the patient's right lateral forearm revealed hyperpigmentation of the basal keratinocytes, with mild digitate elongations of the hyperpigmented rete ridges. A slight, patchy infiltration of lymphocytes was observed in the adjacent dermis . Amyloid staining results were negative. Figure 3 Haber's syndrome. Histology of a macule in the right forearm revealing hyperpigmentation of the basal keratinocytes with mild digitate elongations of the rete ridges (arrow) (hematoxylin and eosin stain; magnification x100) Complete blood count, liver function, urea, creatinine, and electrolytes were all within normal limits. Genetic testing could not be performed at the facility due to limited resources, and the patient's father declined such testing at another medical center. A diagnosis of HS was made, and the patient was counseled and advised to follow sun-protective measures. The patient was followed-up every six months and instructed to visit the clinic if new lesions or symptoms appeared. Written consent was taken from the patient and her guardian. Discussion HS was first described in 1965 as a rosacea-like eruption in three family members, and diagnostic criteria were suggested in 1988 . It is an exceedingly rare genodermatosis. To our knowledge, only a few cases have been reported and published worldwide. The typical onset is during adolescence, when patients experience rosacea-like eruptions, potentially followed by hyperpigmented skin lesions later in life. However, the onset was much earlier in our patient, and the reticulate hyperpigmentation was generalized rather than localized to acral or flexural areas; this may be because of "genetic anticipation," which occurs with autosomal dominant disorders, causing an earlier age and more severe phenotype than normal. In reported cases [2-5], the clinical features of HS are inconsistent. All reported cases exhibited rosacea-like facial eruptions and familial concordance of similar skin lesions. Pigmentary skin lesions vary considerably among cases. Reported extra-facial features include keratotic lesions reminiscent of seborrheic keratosis, palmoplantar keratoderma, pitted scars, and comedones. In this case, histological examinations were of a supportive rather than diagnostic nature. However, the biopsy was obtained from an early lesion, which may explain the subtle changes observed in the histological examination. The differential diagnosis in our case included diseases of generalized reticulate hyperpigmentation with onset in infancy and childhood, including dyskeratosis congenita, Naegeli-Franceschetti-Jadassohn syndrome, dermatopathia pigmentosa reticularis, and X-linked reticulate pigmentary disorder. It also included diseases with acral and flexural distributions, including Dowling-Degos disease and reticulate acropigmentation of Kitamura. However, these two types of diseases may appear together and are considered by certain authors to be different expressions of the same disorder . The differential diagnosis of these reticulate pigmentary diseases is presented in Table 1. Table 1 Differential diagnosis of Haber's syndrome. AD: Autosomal dominant; DDD: Dowling-Degos disease; PPK: Palmoplantar keratoderma; SCC: Squamous cell carcinoma; XLR: X-linked recessive. Disorder Key features Histopathology Haber's syndrome Rosacea-like facial eruption plus the clinical features of Dowling-Degos disease. Digitate elongations of the hyperpigmented rete ridges. Dyskeratosis congenita XLR (commonest form), the clinical triad of nail dystrophy, reticulated hyperpigmentation of the flexures, and oral leukoplakia. Other features: pancytopenia and increased risk of SCC. Atrophy of the epidermis, mild interface vacuolization with melanophages in the upper dermis, and telangiectasia of the superficial vessels. Naegeli-Franceschetti-Jadassohn syndrome AD, fading reticulated hyperpigmentation, dental anomalies, PPK, hypohidrosis, and absent dermatoglyphics. Clumps of melanin-laden melanophages are observed in the papillary dermis in a patchy distribution without overlying epidermal hyperpigmentation. Dermatopathia pigmentosa reticularis AD, persistent reticulated hyperpigmentation, PPK, alopecia, and hypoplastic dermatoglyphics. X-linked reticulate pigmentary disorder XLR, early manifestations are neonatal colitis and recurrent pneumonia. Adults manifest generalized reticulated hyperpigmentation. Amyloid deposits. Dowling-Degos disease AD, reticulated hyperpigmentation of flexural regions. Digitate elongations of the hyperpigmented rete ridges. In DDD, thin, branching, heavily pigmented, downward proliferation also involves the infundibula of follicles and horn cysts. Reticulate acropigmentation of Kitamura AD, atrophic acral pigmentation, and palmoplantar pits. HS exhibits a considerable overlap of both histopathologic and clinical features with Dowling-Degos disease, which suggests that HS may be one of the facets of Dowling-Degos disease . In Dowling-Degos disease, the pigmented macules and patches tend to coalesce and may involve the face, chest, and abdomen or be more extensive . Associated features include pitted perioral scars, hyperpigmented comedones, hidradenitis suppurativa, multiple cysts and abscesses, and keratoacanthoma . Neither HS nor Dowling-Degos disease exhibits substantial systemic involvement. However, certain authors consider the two to be clinically different entities [5-8]. This hypothesis is based on the fact that most of the reported cases of HS lack reticulate hyperpigmentation, and the hereditary onset of multiple seborrheic keratoses is not a common feature in reported cases of Dowling-Degos disease. However, the pigmentary changes observed in Dowling-Degos disease are caused primarily by mutations in keratin 5, which may be present in some cases of HS . Additionally, the onset of multiple seborrheic keratoses during the first decade of life, as in our patient, is unusual. Therapeutic options for HS include broad-spectrum sunscreen and other sun-protective measures, as well as the avoidance of triggers of facial erythema, such as smoking, alcohol ingestion, and excessive and prolonged application of corticosteroid ointment. Symptomatic treatment includes short-term use of topical steroids to alleviate any facial burning sensation . Treatment of facial erythema includes classical therapies used to treat rosacea: the daily use of minocycline (100 mg) and metronidazole gel (0.75%) reportedly yields a satisfactory response . Treatment of reticulate hyperpigmentation is often unsatisfactory: hydroquinone, tretinoin, and azelaic acid have been used with variable success. In cases exhibiting inflammation, topical corticosteroids, and calcineurin inhibitors may be used. Treatment is important to initiate to alleviate symptoms and enhance life quality. Genetic counseling can be offered to patients after genetic testing. Conclusions Haber's syndrome typically manifests as a rosacea-like facial eruption at an early age and is exacerbated by sun exposure. A family history and histological features are further indications of this condition. Physicians should be aware of its manifestation and differential diagnosis, and research must continue to improve and find the most effective treatment of the disease beyond mere symptomatic treatment. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Reticulate pigmentary disorders: a review Pigment Int Sinha S Kulhari A 67 76 6 2019 2 Haber's syndrome Australas J Dermatol McCormack CJ Cowen P 82 84 38 1997 9159964 3 Haber's syndrome and Dowling-Degos disease Int J Dermatol Kikuchi I Crovato F Rebora A 96 97 27 1988 2966131 4 Reticulate acropigmentation of Kitamura-Dowling Degos disease overlap: a case report Int J Dermatol Al Hawsawi K Al Aboud K Alfadley A Al Aboud D 518 520 41 2002 12207773 5 Haber's syndrome or Dowling-Degos disease? Arch Dermatol Crovato F Rebora A 214 118 1982 6 Dowling-Degos disease (reticulate pigmented anomaly of the flexures): a clinical and histopathologic study of 6 cases J Am Acad Dermatol Kim YC Davis MD Schanbacher CF Su WP 462 467 40 1999 10071319 7 Lever's Histopathology of the Skin Elder DE Philadelphia: Wolters Kluwer 2015 8 Haber's syndrome may be a clinical entity different from Dowling-Degos disease Br J Dermatol Nishizawa A Nakano H Satoh T Takayama K Sawamura D Yokozeki H 215 217 160 2009 19067693 9 Haber's syndrome. Report of a new family Arch Dermatol Kikuchi I Saita B Inoue S 321 324 117 1981 6454393 10 Haber's syndrome: Familial Rosacea-like dermatosis with keratotic plaques and pitted scars Arch Dermatol Seiji M Otaki N 452 455 103 1971 4253720
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Infect Control Hosp Epidemiol Infect Control Hosp Epidemiol ICE Infection Control and Hospital Epidemiology 0899-823X 1559-6834 Cambridge University Press New York, USA 35098915 S0899823X21005249 10.1017/ice.2021.524 Concise Communication Carriage of vancomycin-resistant Enterococcus faecium in infants following an outbreak in the neonatal intensive care unit: time to clearance of carriage and use of molecular methods to detect colonization Schechner Vered MD 1 2 3 a Lellouche Jonathan PhD 3 4 a Stepansky Sarit MPHA 1 Mandel Dror MD 2 5 Grisaru-Soen Galia MD 2 6 Wullfhart Liat MSc 3 Schwartz David PhD 3 Carmeli Yehuda MD 1 2 3 1 Division of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Israel 2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 3 National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv, Israel 4 The Adelson School of Medicine, Ariel University, Ariel, Israel 5 Department of Neonatology, Dana Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Israel 6 Pediatric Infectious Disease Unit, Dana Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Israel Author for correspondence: Vered Schechner, E-mail: [email protected] a Authors of equal contribution. 3 2023 31 1 2022 44 3 497500 17 10 2021 25 11 2021 15 12 2021 (c) The Author(s) 2022 2022 The Author(s) This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence ), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited. Among 46 infants colonized with vancomycin-resistant Enterococcus faecium during an outbreak in a neonatal intensive care unit, the estimated time until half had achieved clearance was 217 days. All 40 infants who completed follow-up cleared carriage by 1 year. No predictors of prolonged carriage (> 6 months) were identified. pmcAcquired resistance to vancomycin among Enterococcus faecium and E. fecalis is a public health concern. The WHO classified vancomycin-resistant E. faecium (VRE-fm) as a pathogen of high priority in its list of antibiotic-resistant bacteria for which research and development of new antibiotics are needed. 1 VRE fecal colonization often precedes infection. 2 Duration of fecal carriage among adult patients may last months and years, and may depend on antibiotic exposure and interaction with the healthcare system after hospital discharge. 3 Reports of VRE outbreaks in neonatal intensive care units (NICU) are few, 4-7 and data about the duration of carriage after NICU discharge are lacking. In 2017, a monoclonal outbreak of VRE-fm harboring the vanA gene involving 49 NICU patients occurred at Tel Aviv Sourasky Medical Center (TASMC), Israel. 8 In all cases, the infants had only VRE colonization, without clinical infection. To determine colonization status, stool samples were taken periodically after discharge to inform parents and end the need for contact isolation if infants continued interactions with the healthcare system. In this study, we aimed (1) to determine time to clearance of VRE-fm carriage after discharge from NICU, (2) to identify factors associated with prolonged carriage, and (3) to compare the time to clearance using molecular versus culture-based methods. Methods Setting, study design, and sample The sample for this retrospective cohort study consisted of the 49 newborns in the NICU who were identified as colonized with VRE-fm between February 20, 2017, and April 11, 2017. After discharge, the infants underwent sequential stool tests to determine VRE clearance. For this study, follow-up ended on September 1, 2018. Data collection Data on characteristics of the infants, the delivery, and the NICU hospitalization were collected from electronic medical records. Antimicrobial agents given during hospitalization in the NICU were divided into first-line (ampicillin and gentamicin) and second-line antibiotics (all others). Results of stool tests for VRE and any clinical cultures taken during the follow-up period were examined. Microbiological methods and testing protocol VRE-fm was tested on fresh stool specimens. VRE-fm presence was determined after enrichment in brain heart infusion (BHI) broth by 2 different methods: standard microbiological culture using selective and chromogenic media (CHROMagar VRE, Mast Diagnostica GmbH, Reinfeld, Germany) and PCR detection of the vanA and housekeeping ddl-fm genes (see Supplementary Material online). A positive stool test for VRE-fm was defined as a positive culture for VRE-fm and/or positive PCR tests for both vanA and ddl. A stool test was defined as negative if all 3 tests were negative or if the culture was negative and either vanA or ddl was negative. Testing began no sooner than 3 months after the initial positive test. A negative test was confirmed by repeat testing 2 weeks later. A positive test was followed by repeat testing 2 months later. Outcome The outcome of interest was time until VRE-fm clearance. Clearance was defined as negative stool tests for VRE-fm on two consecutive specimens at least 2 weeks apart. The date of the initial positive VRE-fm test was the starting point and the date of the first of the 2 negative tests was the end point. We also calculated time until VRE clearance based on culture results only. Statistical analysis Median time to clearance was determined using a nonparametric maximum likelihood estimation (NPMLE) of survival. A paired t test was used to compare time to clearance based on culture versus culture plus PCR. The kh 2 test and multivariable logistic regression were used to identify risk factors for prolonged VRE carriage (>6 months). Analyses were performed using Python version 3.7.4 software (Python, Wilmington, DE) and R Studio version 3.6.3 software (R Foundation for Statistical Computing, Vienna, Austria). Ethics This study was approved by the TASMC Institutional Review Board. Results Patient characteristics Among the 49 infants studied, 34 were preterm. Median length of stay was 24 days (IQR 12-45 days). Antibiotics were given to 80% of the infants received antibiotics. Patients are described in detail in Table S1 (online). Duration of VRE-fm colonization In total, 46 patients performed stool tests for VRE clearance after discharge (range, 1-8 tests). Among them, 6 patients were lost to follow-up before clearance was achieved. Thus, 40 patients cleared VRE as defined by culture and PCR after a median of 4 tests. Time from initial positive test to clearance ranged between 91 and 361 days. The estimated time until 50% of patients achieved clearance was 217 days (Fig. 1). Fig. 1. Nonparametric maximun likelihood (NPMLE) of survival for the duration of VRE-fm carriage, based on culture and PCR tests. The gray boxes indicate the intervals during which VRE clearance was not tested. The grey lines are confidence intervals. Based on culture alone, 41 patients achieved clearance between 91 and 294 days after the initial positive test. The estimated time until half of patients achieved clearance was 113 days (Fig. S1). The difference in time to clearance using the two methods was significant (P < .0001). After 1 negative test, the next test was also negative in 32 (80%) of 40 patients. A negative culture was followed by a positive culture for VRE-fm in only 1 case; the negative culture test was positive for vanA and negative for ddl. During a follow-up period of 16-18 months, no patients had a VRE clinical infection detected by our hospital's laboratory. Factors associated with prolonged carriage Time to VRE-fm clearance was <=6 months for 19 patients and >6 months for 26 patients. In bivariate analysis, mechanical ventilation, having a central line, receiving an oral iron supplement, and receiving second-line antibiotics protected against prolonged VRE-fm carriage (P < .10), but none remained significant in multivariable analysis (Table 1). Table 1. Association Between Patient Characteristics and Duration of VRE-fm Carriage a Variables Carriage <=6 mo (n=19), No. (%) Carriage > 6 mo (n=26), No. (%) Bivariate Analysis Multivariate Analysis OR (95% CI) P Value OR (95% CI) P Value Baseline characteristics Female 8 (42.1) 15 (57.7) 1.88 (0.57-6.21) .302 Gestational age, weeks Extremely and very preterm (<32) 6 (31.6) 7 (26.9) 0.73 (0.15-3.47) .691 Moderate to late preterm (32 0/7 to 36 6/7) 8 (42.1) 11 (42.3) 0.86 (0.20-3.64) .821 Term (>=37) 5 (26.3) 8 (30.8) Reference Birth weight, g <1,500 7 (36.8) 7 (26.9) 0.70 (0.17-2.91) .623 1,500-2,500 5 (26.3) 9 (34.6) 1.26 (0.29-5.42) .445 >2,500 7 (36.8) 10 (38.5) Ref Delivery by caesarean section 12 (63.2) 14 (53.8) 0.68 (0.20-2.28) .532 Rupture of membranes >=12 hours 3/18 (16.7) 5/25 (20.0) 1.25 (0.26-6.07) .782 Maternal antibiotic exposure during delivery 16/18 (88.9) 19/25 (76.0) 0.40 (0.07-2.24) .284 Is part of twins 3/18 (16.7) 6/26 (23.1) 1.50 (0.32-7.00) .604 Having siblings 10/17 (58.8) 15/25 (60.0) 1.05 (0.30-3.68) .939 Any comorbidity b 13 (68.4) 17 (65.4) 0.87 (0.25-3.08) .83 Hospitalization characteristics Length of stay >=30 days 12 (63.2) 10 (38.5) 0.37 (0.11-1.24) .102 Time from initial VRE positive test to discharge >=14 d 4/18 (22.2) 8/25 (32.0) 1.65 (0.41-6.63) .48 Mechanical ventilation 9 (47.4) 4 (15.4) 0.20 (0.05-0.82) .019 0.28 (0.06-1.37) .116 Presence of CVC 12 (63.2) 9 (34.6) 0.31 (0.09-1.06) .058 0.44 (0.08-2.54) .364 NGT >=10 d 10/18 (55.6) 12 (46.2) 0.69 (0.21-2.30) .540 TPN days > 0 11 (57.9) 9 (34.6) 0.39 (0.11-1.30) .121 Breast milk (>=50% of hospital days) 11 (57.9) 17/23 (73.9) 2.06 (0.56-7.58) .273 Receipt of PPI or H2RA 4/17 (23.5) 4 (15.4) 0.59 (0.13-2.77) .502 Erythropoietin therapy 4/18 (22.2) 6 (23.1) 1.05 (0.25-4.42) .947 Oral iron supplement 13/18 (72.2) 12 (46.2) 0.33 (0.09-1.20) .086 0.94 (0.14-6.15) .946 Antibiotic treatment (>=10 d of therapy) 7/18 (38.9) 6 (23.1) 0.47 (0.13-1.76) .258 First-line antibiotics 16 (84.2) 18 (69.2) 0.42 (0.10-1.87) .248 Second-line antibiotics 9 (47.4) 6 (23.1) 0.33 (0.09-1.20) .088 0.76 (0.14-4.18) .750 IV vancomycin 4 (21.1) 1 (3.8) 0.15 (0.02-1.47) .070 Note: CVC, central venous catheter; NGT, nasogastric tube; TPN, total parenteral nutrition; PPI, proton-pump inhibitor; H2RA, histamine-2 receptor antagonist. a Denominators are listed if data were missing. b Respiratory distress syndrome or broncho-pulmonary dysplasia or intraventricular hemorrhage or cardiovascular disease or retinopathy of prematurity or anemia of prematurity or neonatal jaundice or necrotizing enterocolitis. Discussion To our knowledge, this is the first study to show the natural history of VRE carriage among NICU patients after discharge from the hospital. This information is important to inform concerned parents of colonized infants, and it may help clinicians and infection control teams. At 90 days, ~30% of infant carriers cleared carriage. In 1 year, all 40 patients who completed follow-up had cleared carriage. In another study that examined VRE carriage duration among adults, median time from discharge to first negative culture was 33 days, as compared to 113 days by culture in our study. 9 The difference between the 2 studies may reflect differences in the start date (initial detection date versus discharge date) and in laboratory methods. It may also reflect differences between adults and infants in maturity of the microbiome, whose restoration is important to support clearance of carriage. Our patients were not tested until at least 3 months after initial detection, so clearance might have occurred earlier in some patients. However, 31 of 46 were still carriers at their first follow-up test, which is similar to other reports of >50% positivity 3-6 months after initial VRE detection. 10 Given these findings, we recommend testing colonized infants for VRE clearance beginning at 3 months after the first positive test. Strengths of our study include a unique cohort of infants involved in a clonal VRE-fm outbreak, high compliance with follow-up testing, and a sensitive method for VRE detection. This study had several limitations. First, this was not a prospective study in which infants were retested at uniform intervals. Second, PCR tests may be falsely positive if the genetic resistance element was detected in nonenterococcal organisms or a nonviable Enterococcus. To minimize the risk of false positives, we defined PCR testing as positive if both vanA and ddl genes were present. Third, we had no information on potential risk factors for prolonged carriage after discharge In summary, we have shown that infants who acquired VRE-fm during an outbreak in the NICU cleared carriage by 1 year after initial diagnosis. Acknowledgments None. Supplementary material For supplementary material accompanying this paper visit click here to view supplementary material Financial support No financial support was provided relevant to this article. Conflict of interest Y.C. has received grants and personal fees from MSD, Pfizer, Allecra Therapeutics, Nabriva, Roche, Shinogi, Qpex Pharmaceuticals, and Spero Therapeutics. All other authors report no potential conflicts of interest. References 1. World Health Organization. Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics. Geneva: WHO; 2017. Accessed January 19, 2022. 2. Alevizakos M , Gaitanidis A , Nasioudis D , Tori K , Flokas ME , Mylonakis E. Colonization with vancomycin-resistant enterococci and risk for bloodstream infection among patients with malignancy: a systematic review and meta-analysis. Open Forum Infect Dis 2017;4 (1 ):ofw246.28480243 3. Karki S , Land G , Aitchison S , et al. Long-term carriage of vancomycin-resistant enterococci in patients discharged from hospitals: a 12-year retrospective cohort study. J Clin Microbiol 2013;51 :3374-3379.23926167 4. Iosifidis E , Evdoridou I , Agakidou E , et al. Vancomycin-resistant Enterococcus outbreak in a neonatal intensive care unit: epidemiology, molecular analysis and risk factors. Am J Infect Control 2013;41 :857-861.23669299 5. Andersson P , Beckingham W , Gorrie CL , et al. Vancomycin-resistant Enterococcus (VRE) outbreak in a neonatal intensive care unit and special care nursery at a tertiary-care hospital in Australia a retrospective case-control study. Infect Control Hosp Epidemiol 2019;40 :551-558.30868978 6. Ergaz Z , Arad I , Bar-Oz B , et al. Elimination of vancomycin-resistant enterococci from a neonatal intensive care unit following an outbreak. J Hosp Infect 2010;74 :370-376.19932526 7. Pusch T , Kemp D , Trevino S , et al. Controlling outbreak of vancomycin-resistant Enterococcus faecium among infants caused by an endemic strain in adult inpatients. Am J Infect Control 2013;41 :51-56.22727513 8. Marom R , Mandel D , Haham A , et al. A silent outbreak of vancomycin-resistant Enterococcus faecium in a neonatal intensive care unit. Antimicrob Resist Infect Control 2020;9 :87.32546210 9. Sohn KM , Peck KR , Joo E-J , et al. Duration of colonization and risk factors for prolonged carriage of vancomycin-resistant enterococci after discharge from the hospital. Int J Infect Dis 2013;17 :e240-e246.23195640 10. Saegeman V , Melussi P , Duerinckx R , et al. When is it safe to stop contact precautions for vancomycin-resistant Enterococcus faecium carriage? J Hosp Infect 2018;100 :114-115.29870750
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JAMA Netw Open JAMA Netw Open JAMA Network Open 2574-3805 American Medical Association 36917113 10.1001/jamanetworkopen.2023.3002 zld230020 Research Research Letter Online Only Public Health Factors Associated With Public Trust in Pharmaceutical Manufacturers Factors Associated With Public Trust in Pharmaceutical Manufacturers Factors Associated With Public Trust in Pharmaceutical Manufacturers Singh Yashaswini MPA 1 Eisenberg Matthew D. PhD 1 Sood Neeraj PhD 2 1 Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 2 Sol Price School of Public Policy, University of Southern California, Los Angeles Article Information Accepted for Publication: January 30, 2023. Published: March 14, 2023. doi:10.1001/jamanetworkopen.2023.3002 Open Access: This is an open access article distributed under the terms of the CC-BY License. (c) 2023 Singh Y et al. JAMA Network Open. Corresponding Author: Yashaswini Singh, MPA, Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, 624 N Broadway, Baltimore, MD 21205 ([email protected]). Author Contributions: Ms Singh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Singh. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: All authors. Obtained funding: Eisenberg, Sood. Supervision: Eisenberg, Sood. Conflict of Interest Disclosures: Dr Eisenberg reported receiving grants from the National Institute on Drug Abuse, the National Institute on Nursing Research, the Agency for Healthcare Research and Quality, Arnold Ventures, and the National Institute on Aging outside the submitted work. Dr Sood reported being a visiting scholar at Amazon. No other disclosures were reported. Funding/Support: This study was supported by a grant from Blue Cross Blue Shield Affordability Cures Consortium. Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Data Sharing Statement: See the Supplement. Additional Contributions: We thank GFK/Knowledge Networks for assistance in fielding the experiment. We thank Nikhilesh Kumar, BA, University of Southern California, and students from the Southern California Health Outreach Club for assistance with questionnaire design; they were not compensated for their contributions. 14 3 2023 3 2023 14 3 2023 6 3 e23300210 10 2022 30 1 2023 Copyright 2023 Singh Y et al. JAMA Network Open. This is an open access article distributed under the terms of the CC-BY License. jamanetwopen-e233002.pdf This cross-sectional study examines how key demographic and predisposing factors are associated with consumer trust in pharmaceutical manufacturers. pmcIntroduction Public distrust in the pharmaceutical industry has increased, in part due to perceptions of pharmaceutical manufacturers as profit seeking and in part due to the actions of pharmaceutical manufacturers, including off-label marketing, overcharging government programs, and concealing data.1 Notwithstanding the underlying mechanism, an unfavorable public perception of pharmaceutical manufacturers is concerning if it translates into poor medication adherence,2 lack of participation in clinical trials,3 and rejection of effective health interventions, including vaccine campaigns.4 In this cross-sectional study, we examined how key demographic and predisposing factors are associated with consumer trust in pharmaceutical manufacturers. Methods A nationally representative sample of individuals at high risk of cardiovascular disease (US residents aged 40-64 years, who currently smoke, with high cholesterol, or with a body mass index >25 [calculated as weight in kilograms divided by height in meters squared]) were recruited from the Ipsos Public Affairs LLC KnowledgePanel. Participants completed a survey fielded to 4933 respondents, of whom 3026 respondents started and completed the survey (response rate of 61%). Further details on the survey design are described in an earlier study using the same sample.5 Our cross-sectional study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline and received institutional review board approval from the University of Southern California. All participants provided electronic informed consent. The dependent variable measured individuals' trust in pharmaceutical manufacturers on a 5-point Likert scale (ranging from 1 [always distrust] to 5 [always trust]). Independent variables included demographic characteristics (such as gender, race and ethnicity, age, and geographic location) and other predisposing factors, including political affiliation, household income, educational level, self-reported health, and source of health information (including whether they have a regular source of care and whether they rely on digital media for health information). Characteristics of individuals with high and low levels of trust were compared using kh2 tests. All P values were from 2-sided tests and results were deemed statistically significant at P < .05. The association between demographic characteristics and trust was estimated using adjusted odds ratios (ORs) from an ordered logit regression model. Results This cross-sectional study used a nationally representative survey of 2867 individuals at risk of cardiovascular disease (mean [SD] age, 54 years; 1324 women [46%] and 2119 White individuals [74%]). A total of 1145 individuals (40%) considered pharmaceutical manufacturers to be sometimes (1036 [36%]) or always (109 [4%]) trustworthy (Table 1). Table 1. Perceptions of Pharmaceutical Manufacturers by Individual Characteristics Characteristic No. (%) P valueb Total (N = 2867) Low trust (n = 1722)a High trust (n = 1145)a Female 1324 (46) 790 (46) 534 (47) .69 White 2118 (74) 1276 (74) 842 (74) .74 Age, mean (SD), y 54 (7) 54 (7) 54 (7) .06 Political affiliation Democrat 779 (27) 426 (25) 353 (31) <.001 Independent or other 1121 (39) 728 (42) 393 (34) Republican 956 (33) 561 (33) 395 (35) Household income, $ 10 000-24 999 289 (10) 183 (11) 106 (9) .02 25 000-49 999 427 (15) 274 (16) 153 (13) 50 000-74 999 439 (15) 269 (16) 170 (15) 75 000-99 999 422 (15) 261 (15) 161 (14) >100 000 1290 (45) 735 (43) 555 (49) Educational level No high school diploma or GED 145 (5) 89 (5) 56 (5) .09 High school graduate 770 (27) 462 (27) 308 (27) Some college or Associate's degree 940 (33) 587 (34) 353 (31) Bachelor's degree 593 (21) 356 (21) 237 (21) Master's degree or higher 419 (15) 228 (13) 191 (17) Used the internet, television, or social media as a source of health information 1447 (51) 849 (49) 598 (52) .13 Had a usual source of health care in the past year 2226 (78) 1306 (76) 920 (80) .005 Self-reported health Excellent 175 (6) 97 (6) 78 (7) .008 Very good 950 (33) 545 (32) 405 (35) Good 1242 (43) 749 (44) 493 (43) Fair 417 (15) 270 (16) 147 (13) Poor 81 (3) 59 (3) 22 (2) Rural 579 (20) 348 (20) 231 (20) .98 Region Northeast 538 (19) 295 (17) 243 (21) .03 Midwest 638 (22) 389 (23) 249 (22) South 1059 (37) 638 (37) 421 (37) West 632 (22) 400 (23) 232 (20) Abbreviation: GED, General Educational Development certification. a Trust in pharmaceutical manufacturers was measured using a survey question that asks about individuals' trust in pharmaceutical manufacturers on a 5-point Likert scale (ranging from 1 [always distrust] to 5 [always trust]). Of 2874 individuals, 167 (6%) reported always distrusting pharmaceutical manufacturers, 766 (27%) reported sometimes distrusting, 789 (27%) reported neither trusting nor distrusting, 1036 (36%) reported sometimes trusting, and 109 (4%) reported always trusting pharmaceutical manufacturers. "High" trust represents individuals who report that they sometimes or always trust pharmaceutical manufacturers. b Results from kh2 tests. Excellent health (OR, 1.70 [95% CI, 1.05-2.75]; P = .03) and having a regular source of care (OR, 1.19 [95% CI, 1.01-1.40]; P = .03) were associated with higher trust in pharmaceutical manufacturers (Table 2). Individuals with Democratic (OR, 1.35 [95% CI, 1.15-1.61]; P < .001) or Republican party affiliation (OR, 1.27 [95% CI, 1.09-1.49]; P = .003) had higher trust relative to those with Independent affiliation. Relative to the west, individuals in the northeast had higher trust (OR, 1.43 [95% C, 1.16-1.77]; P = .001). There were no differences across gender, race and ethnicity, age, income, or educational level. Table 2. Adjusted Associations Between Individual Characteristics and Trust in Pharmaceutical Manufacturers Characteristic Adjusted odds ratio (95% CI)a P value Female 1.01 (0.88-1.16) .87 Race and ethnicity White 0.87 (0.74-1.02) .09 Non-Whiteb 1 [Reference] Age 1.01 (0.99-1.02) .12 Educational level Bachelor's degree or higher 0.96 (0.82-1.13) .66 Some college, high school, or GED 1 [Reference] Political affiliation Democrat 1.35 (1.15-1.61) <.001 Republican 1.27 (1.09-1.49) .003 Independent or other 1 [Reference] NA Household income, $ <24 999 1 [Reference] NA 25 000-49 999 0.78 (0.59-1.02) .09 50 000-74 999 0.99 (0.79-1.24) .96 75 000-99 999 1.01 (0.80-1.26) .92 >100 000 1.20 (0.99-1.45) .06 Used the internet, television, or social media for health information 0.92 (0.81-1.06) .29 Had a usual source of health care in the past year 1.19 (1.01-1.40) .03 Self-reported health Excellent 1.70 (1.05-2.75) .03 Very good 1.48 (0.98-2.24) .06 Good 1.38 (0.92-2.06) .11 Fair 1.21 (0.79-1.86) .35 Poor 1 [Reference] NA Region Northeast 1.43 (1.16-1.77) .001 Midwest 1.17 (0.96-1.44) .11 South 1.15 (0.96-1.37) .18 West 1 [Reference] NA Abbreviations: GED, General Educational Development certification; NA, not applicable. a Estimates represent adjusted odds ratios from an ordered logit regression with pharmaceutical trust as the dependent variable. Pharmaceutical trust is measured on a 5-point Likert scale (ranging from 1 [always distrust] to 5 [always trust]). b Included individuals who self-reported race and ethnicity as Hispanic, Asian, Black, 2 or more races, or other. Discussion Approximately 60% of individuals at high risk for cardiovascular disease did not trust pharmaceutical manufacturers. Lack of trust was higher among those in poor health or without a usual source of care, raising concerns that vulnerable populations have experiences where trust has been broken. This also raises concerns about poor medication adherence and lack of treatment-seeking behavior in vulnerable populations. Those with Independent political affiliation had lower trust than those with Republican or Democratic affiliation, suggesting that mainstream political discourse might be associated with pharmaceutical trust. However, those with Independent affiliation might represent different ideological backgrounds. There were significant regional differences, with those in the northeast, where several pharmaceutical firms have a major presence, having higher trust. Limitations to this study include limited generalizability, cross-sectional design, and self-reported data in a survey-based design with potential for nonresponse bias. Supplement. Data Sharing Statement Click here for additional data file. References 1 McCarthy J. Big pharma sinks to the bottom of U.S. industry rankings. Gallup News. September 3, 2019. Accessed January 27, 2023. 2 Brown MT, Bussell J, Dutta S, Davis K, Strong S, Mathew S. Medication adherence: truth and consequences. Am J Med Sci. 2016;351 (4 ):387-399. doi:10.1016/j.amjms.2016.01.010 27079345 3 Pahus L, Suehs CM, Halimi L, . Patient distrust in pharmaceutical companies: an explanation for women under-representation in respiratory clinical trials? BMC Med Ethics. 2020;21 (1 ):72. doi:10.1186/s12910-020-00509-y 32791969 4 Lyman S. Pharma's tarnished reputation helps fuel the anti-vaccine movement. Stat News. February 26, 2019. Accessed January 27, 2023. 5 Eisenberg MD, Singh Y, Sood N. Association of direct-to-consumer advertising of prescription drugs with consumer health-related intentions and beliefs among individuals at risk of cardiovascular disease. JAMA Health Forum. 2022;3(8):e222570. doi:10.1001/jamahealthforum.2022.2570
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34908 Pathology Pediatric Surgery Orthopedics Chondroblastoma Affecting the Apophysis of the Greater Trochanter in a Child Muacevic Alexander Adler John R Slavchev Svetoslav A 1 O'Connor Philip J 1 Georgiev Georgi P 1 1 Orthopaedics and Traumatology, Medical University of Sofia, Sofia, BGR Svetoslav A. Slavchev [email protected] 13 2 2023 2 2023 15 2 e3490810 2 2023 Copyright (c) 2023, Slavchev et al. 2023 Slavchev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Chondroblastomas are rare primary bone tumours typically affecting the epiphyses and less frequently the apophyses of the growing skeleton. Most cases are treated by intralesional curettage with or without local adjuvants and this technique can produce good long-term outcomes. Herein, we describe a case of chondroblastoma of the greater trochanter in a 12-year-old male child that was treated by intralesional curettage and grafting with calcium phosphate bone cement (Neocement Inject(r) P, Bioceramed, Loures, Portugal). A brief review of the literature is also presented. pediatric orthopedic surgery denosumab growth plate physis bone grafting synthetic bone substitute greater trochanter apophysis chondroblastoma The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Chondroblastomas are rare cartilaginous tumours arising typically in the epiphyses or apophyses of long bones, usually the proximal humerus and around the knee . Currently, it is defined by the World Health Organisation as "a benign tumour of bone that has a predilection for epiphyseal or apophyseal regions, composed of chondroblastic cells and islands of eosinophilic chondroid matrix" . In spite of its benign histological nature, metastases to the lungs, bones, and soft tissues have been reported . Open surgery is the principal treatment modality but curative percutaneous radiofrequency thermoablation or cryoablation has also been reported . Rarely, in multiple recurrences or malignant transformation, amputation could be considered . The reported recurrence rates after curettage range from 9.5% to 32% . Case presentation A 12-year-old Caucasian male child was brought to our institution complaining of pain and limited motion in his left hip. The symptoms had a duration of about a year. The patient reported that initially the pain was mild and occurred only during physical activities, followed by worsening limitation of motion in the hip joint. Over the course of several months, it had become severe and constant, virtually insusceptible to non-steroid anti-inflammatory medication. Clinical examination revealed the inability of weight-bearing of the affected limb, hypotrophy of the gluteal and thigh muscles, and severe pain in the trochanteric region, which was extremely tender with a normal appearance of the overlying skin. On plain radiography, the greater trochanter appeared to be somewhat enlarged as compared to the normal side and almost completely occupied by an ovoid lesion with radiodense and radiolucent areas surrounded by an osteosclerotic rim . On magnetic resonance tomography (MRT), the lesion was well-demarcated, heterogeneous, slightly lobulated, and breaching both the growth plate and the lateral cortex of the greater trochanter . Figure 1 Imaging studies before and after surgery. 1a: Plain radiograph (anteroposterior) of the proximal femur at presentation. 1b, 1c: Frontal oblique and axial T1 weighted magnetic resonance tomography (MRT) images of the proximal femur at presentation. The growth plate and the lateral cortex are breached (arrows). 1d: Plain radiograph (anteroposterior) of the proximal femur after surgery. As it was deemed that the lesion showed signs of local aggressiveness, an open biopsy was performed through a lateral approach and the diagnosis of chondroblastoma was made . Figure 2 Hematoxylin and eosin staining of chondroblastoma (x200). Lobules of chondroid matrix (asterisks) populated by irregularly shaped chondroblasts adjacent to hypercellular areas (circle) with histiocyte-like cells. Multinucleated giant cells that are typically a feature of chondroblastomas are not present in this slide. In the second stage, the lesion was thoroughly curetted and rinsed with hydrogen peroxide as an adjuvant. The bone defect was filled with calcium phosphate bone cement (Neocement Inject(r) P, Bioceramed, Loures, Portugal) and the wound was closed in the usual manner. The postoperative course was uneventful with a resolution of pain and gradual restoration of limb function. The patient was lost to follow-up after one month. Discussion Chondroblastoma is a rare benign bone tumour that represents less than 1% of all primary bone tumours occurring mainly in the epiphyses, and less frequently in the apophyses, of the immature skeleton with 60% of cases developing in the second decade of life and with a male predilection of 2-3:1 . Their purely metaphyseal location is exceptionally rare . They could, however, develop in any skeletal location . Chondroblastomas are usually symptomatic and rarely discovered incidentally on plain radiographs . The typical symptoms are pain and local tenderness followed by swelling and limitation of motion in adjacent joints . While the clinical and imaging features might suffice for making a precise diagnosis in most cases, the differential diagnosis includes other tumours such as giant cell tumour of bone (GCTB) and aneurysmal bone cyst (ABC) that might share some common characteristics in clinical presentation, and radiological and even histological appearance, especially multinucleated giant cells and hemosiderin deposits . An H3K36M mutation in either H3F3A or H3F3B gene has been discovered which is 70-95% specific for chondroblastoma . In GCTB, another mutation H3G34W in H3F3A gene has been discovered that can be detected through immunohistochemistry and is deemed to be specific to this tumour . In primary ABCs, typical translocations t(16; 17) (q22; p13) and 7(17; 17) (q22; p 13) have been identified while in secondary ABCs that are present alongside chondroblastomas or other tumours, no genetic abnormalities exist . Surgery is the principal treatment modality, and aggressive curettage has been advocated despite the proximity of the growth plate, followed by packing the defect with bone graft, synthetic bone substitute, or polymethylmethacrylate bone cement . Compared to morselized bone graft or calcium phosphate granules, calcium phosphate bone cement has the advantage of superior mechanical strength and, furthermore, its homogeneity allows for easier radiographic detection of a local recurrence. Radiofrequency ablation has also been used as a primary treatment of chondroblastoma but the mechanical failure of weight-bearing articular surfaces is possible as well as thermal damage of uninvolved compartments of the joint . Cryosurgery, too, has been used, both as an adjuvant to intralesional curettage (liquid nitrogen) and as a standalone procedure (percutaneous cryoablation), in the treatment of chondroblastoma . Local recurrence rates after treatment vary considerably and the presence of an ABC component, biologic aggressiveness, atypical location, and the presence of an open physis are thought to increase the risk of recurrence . According to Zekry et al., the risk factors include tumour location around the hip joint, an active physis, incomplete removal, and aggressive behaviour of the lesions . However, some authors argue that an open physis is not a risk factor for recurrence per se but rather its presence might discourage the surgeon to perform sufficiently aggressive curettage . As local recurrence is considered to be a major risk factor for metastasising, since metastatic disease virtually always develops after at least one episode of local recurrence, it is advisable that patients with local recurrences undergo a total work-up similar to that for a malignant disease . Recently, the use of denosumab has been reported in cases of metastatic chondroblastoma to the lungs . Due to the epiphyseal location of most chondroblastomas, late post-surgical complications may occur such as limb length discrepancies, angular deformities, and osteoarthritis . The management of these complications may require additional surgery, e.g. limb lengthening, correction osteotomies, or arthroplasty . The interposition of polymethylmethacrylate bone cement across the growth plate has been proposed as a means of preventing premature physeal closure . Conclusions Herein, we described an interesting case of a chondroblastoma that affected the apophysis of the greater trochanter in a child. The treatment included extended intralesional curettage and grafting with calcium phosphate bone cement. Using such a graft substance is an excellent option because of early restoration of the mechanical properties of the bone together with good potential for bone remodelling and earlier detection of an eventual local recurrence. Despite the benign histological characteristics and usually uncomplicated clinical course of chondroblastoma, its biological aggressiveness should not be underestimated by clinicians, especially in cases of a local recurrence. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Chondroblastoma in pelvis and signle centre study of 177 cases J Bone Oncol Laitinen MK Stevenson JD Evans S Abudu A Sumathi V Jeys LM Parry MC 100248 17 2019 31428555 2 WHO Classification of Tumours. Soft Tissue and Bone Tumours WHO Classification of Tumours: Soft Tissue and Bone Tumours, 5th Edition Lyon, France International Agency for Research on Cancer 2020 3 Malignant chondroblastoma of the os calcis Sarcoma Elek EM Grimer RJ Mangham DC Davies AM Carter SR Tillman RM 45 48 2 1998 18521232 4 Image guided radiofrequency thermo-ablation therapy of chondroblastomas: should it replace surgery? Skeletal Radiol Lalam RK Cribb GL Tins BJ Cool WP Singh J Tyrrell PN Cassar-Pullicino VN 513 522 43 2014 24477425 5 Percutaneous cryoablation of chondroblastoma and osteoblastoma in pediatric patients Insights Imaging Serrano E Zarco F Gill AE 106 12 2021 34313884 6 Chondroblastoma in the children treated with intralesional curettage and bone grafting: outcomes and risk factors for local recurrence Orthop Surg Huang C Lu XM Fu G Yang Z 2102 2110 13 2021 34599644 7 Chondroblastoma Atlas of Musculoskeletal Tumors and Tumorlike Lesions Ferraro A 99 102 Cham Springer 2014 8 Surgical treatment of chondroblastoma using extended intralesional curettage with phenol as a local adjuvant J Orthop Surg (Hong Kong) Zekry KM Yamamoto N Hayashi K 2309499019861031 27 2019 31315494 9 Chondroblastoma of bone: long-term results and functional outcome after intralesional curettage J Bone Joint Surg Br Suneja R Grimer RJ Belthur M Jeys L Carter SR Tillman RM Davies AM 974 978 87 2005 15972914 10 Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy Cancer Cytopathol Schaefer IM Fletcher JA Nielsen GP Shih AR Ferrone ML Hornick JL Qian X 552 566 126 2018 29757500 11 Aneurysmal bone cyst (ABC) Atlas of Musculoskeletal Tumors and Tumorlike Lesions Campanacci L 85 89 Cham Springer 2014 12 Radiofrequency ablation of chondroblastoma using a multi-tined expandable electrode system: initial results Eur Radiol Tins B Cassar-Pullicino V McCall I Cool P Williams D Mangham D 804 810 16 2006 16267666 13 Lower recurrence rate in chondroblastoma using extended curettage and cryosurgery Int Orthop Mashhour MA Abdel Rahman M 1019 1024 38 2014 24248272 14 Pulmonary metastases of chondroblastoma in a pediatric patient: a case report and review of literature Cureus Wing C Watal P Epelman M Infante J Chandra T 0 14 2022 15 Chondroblastoma's lung metastases treated with denosumab in pediatric patient Cancer Res Treat Focaccia M Gambarotti M Hakim R 279 282 53 2021 32777878 16 Treatment and prognosis of chondroblastoma Clin Orthop Relat Res Lin PP Thenappan A Deavers MT Lewis VO Yasko AW 103 109 438 2005 16131877
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J R Soc Interface J R Soc Interface RSIF royinterface Journal of the Royal Society Interface 1742-5689 1742-5662 The Royal Society 36919416 10.1098/rsif.2023.0078 rsif20230078 1004151617Editorial Editorial Reviewers in 2022 Reviewers in 2022 Cogdell Richard [email protected] Editor-in-Chief 15 3 2023 March 15, 2023 3 2023 15 3 2023 March 15, 2023 20 200 2023007815 2 2023 February 15, 2023 15 2 2023 February 15, 2023 (c) 2023 The Authors. 2023 Published by the Royal Society under the terms of the Creative Commons Attribution License which permits unrestricted use, provided the original author and source are credited. pmc Editor-in-Chief I thank all those referees who helped assess submissions to Journal of the Royal Society Interface (volume 19) in 2022. The editorial team very much appreciates the time and dedication given by academics to the peer review process and recognizes their efforts. 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Abbass H Abbey B Abe T Aberg C Ackerman A Adam I Adams P Adouni M Aflalo C Agostinelli D Agrawal D Ahator SD Alampounti A Alburez-Gutierrez D Alegana V Alessandretti L Alexov E Alshareef A Altmann E Amlani F an der Heiden M Anderson C Anderson M Anderson P Andersson E Ando N Andraud M Androulakis I Ansell B Aono H Araujo-Estrada S Arzani A Ashmore J Auth T Avazmohammadi R Avgar T Avital E Backholm M Baines C Balabani S Balint Z Balmain A Banerjee S Banga JR Banker R Banzhaf W Barakat A Bardwell L Baron J Bartlett M Bartumeus F Bastard J Bauch C Beatus T Beckman R Bekiranov S Bellomo N Benitez M Benko Z Bennett M Ben-Nun M Berbert J Bertram J Bertrand O Beskos A Betta M Bhagat R Bhatia S Bhattacharya K Bhavnani D Bianconi G Bienfait A Biga V Binder W Biswas D Blanch-Mercader C Blinder P Bluthgen N Bodzioch M Boiani M Bonasoro F Boos C Booth D Borowska A Boyer D Bravi B Brembs B Breto C Breuer K Britton T Brook B Brooks L Brown A Brown S Brownell W Bruijn S Brunner J Bulens D Bull J Bursa J Byrnes G Cadiou H Canal-Bruland R Caponi S Capraro V Carbone G Cardini A Carre M Casas J Catalan P Catoni M Chamorro L Champredon D Chandran Suja V Chapman J Checa A Chechkin A Chen J Chen Y Cheney J Cheong KH Chesler NC Chevalier N Chico T Chinappi M Cho H Chraibi M Christians J Ciaccio E Cinquemani E Claessen B Clemente C Coccia M Codding B Colnaghi M Conlan A Connizzo B Conradi C Convertino M Conway J Cool L Corbat A Cornuault P-H Courau T Cowan N Crauste F Cribellier A Cutsforth-Gregory J Czosnyka Z Dabagh M Dal Corso F D'Alba L Davies P de Jong H de Jong M de los Reyes VA De Luca P Debarre F Delgado Chaves F Delhaye B Delitala M Demers J Dentz M Deregnaucourt S Deziel E Di Stefano A Dickerson B Dickinson G Dingli D Ditlevsen P Dolson E Domenech de Celles M Donatelli C Drake A Duan Y Dunlop J Durand B Dushoff J Dutta P Dymond M Edwards A Elliott K Ellison N Eloy C Emani P Ene-Iordache B Engelstaedter J Epari D Erdi P Errington T Espino D Evans S Farid M Fadikar A Farris D Federle M Figueiredo S Finlayson E Fouda M Fox-Kemper B Franco E Frank M Franklin D Franzese G Frasca P Frei T Fried S Friedman M Friedrich B Friston K Fromen C Fruleux A Fu B Fuhrmann-Lieker T Gadhoumi K Gallos L Garcia Guirao JL Garcia-Aznar J Garcia-Martin JA Garira W Garnier S Gaucherel C Geard N Geitmann A Genin G Georgiades M Gerringer M Gerstein A Ghajari M Ghandiali S Gholami A Ghomlaghi M Gil JP Gilan O Gilet T Girard M Gohain Barua A Golchin M Gomez-Nava L Gompper G Gonzalez-Parra G Goodman J Gopinath A Gorbunov M Gordon M Gordus A Goris R Gorzelak P Gosler A Gosselin F Grabowski A Graf A Grant A Gray K Grebenkov D Griffen B Grima R Groom D Gruber P Gubbins S Gueorguiev D Guerrero P Guillon V Guimapi R Guo B Gupta A Gurarie D Guttal V Haaland T Haider N Hall I Hamelin F Hamilton M Han TA Hare P Harries K Hartmann M Hatala K Hatna E Havlicek V Hawdon JM He D Hedwig B Heeney M Hein J Held N Hellmich C Henderson A Henningsson P Herbst E Hickson R Hills T Hiscock T Hladish TJ Ho S-H Hoi H Hoinville T Holder C Holle A Holowka N Holten-Andersen N Hossain MS Howell L Hoyle A Hoyle R Hsieh T Hu D Hu K Huettmann F Hulsey CD Iaparov B Ibanez-Guzman J Ikeda K Iliff J Imai H Imhof L Ingalls B Irback A Islam MR Issah I Jackson J Jacobberger J Jacobson A Jaganathan GK Jain H Jankauski M Jansson F Jaqaman K Jashnsaz H Jensen O Ji S Johansson C Johnson E Jones A Jones E Jones L Jong ICd Junttila S Jurisch-Yaksi N Kadish D Kaimaki D-M Kainz M Kandil K Kang V Kangas J Kasper R Katzner T Kelly S Kenah E Kennedy WG Kenney L Kenny M Ketcheson D Keyel A Khain E Khaluf Y King H King M Kitagawa H Kleiven S Klumpp S Knight G Koch T Kohn-Luque A Kokash N Kolomenskiy D Kornev K Kostylev M Kraikivski P Kratochvilova I Krauland M Kremling A Kretzberg J Krishnan J Krishnan L Kuchenbecker K Kumar A Kumar P Kunaal J Kurasaki M Kurian P Kurniawan N Kwiatkowska D Labouta H Labra-Vazquez P Lacquaniti F Lafferty K Lagergren J Lai Y-C Lamata P Lancia L Langeslay B Laradji M Larkum A Larsen PS Laubrie J Laurino M Lautenschlager S Lazebnik T Le Rouzic A Leander R Lecheval V Lee DS Lefevre P Lega J Legallais C Lehmann L Lemaire K Lenormand M Leon T Lerma C Lerma-Hernandez SA Levien E Levinson D Lewandowska K Li H-W Li L Li W Liechti F Lilleri D Limjeerajarus N Lin J Lingam M Linhart P Linkov I Lisicki M Liu B Liu J Liu Y Loder A Loman B Lombardi F Long Y Lovkvist C Lu J Lucassen P Lurig M Lyutova R M. Wood C Macnamara C Madera R Madhusudhana S Magpantay F Maier C Mandal S Mangkalaphiban K Manhart A Manikandan MS Manley E Marchisio M Marcotti S Marini G Marino J Markov D Marsland S Martelli C Martino C Martin O Martins J Marxer R Matijevich E Matrajt L Mauksch M Mayalu M Mazzoli M Mbaeyi C McCarthy M McCarthy K McCoy D McCullough J McDonald K McFadden J McGinty S McHenry M McKeegan P McMeeking R Meaud J Medina Cruz D Meehan M Mehandia V Menci M Metzler H Metzler R Meyer CA Michaelian K Mideo N Milligan K Minas G Mirkhalaf M Mitra B Mognetti B Moiseff A Mok W Mongeau J-M Montgomerie R Monzem S Moore S Morbiducci U Moreno AJ Mueller B Muller R Munasinghe M Mundt CC Murawaki Y Murray A Myrgiotis V Nabawy M Nakao H Nakata T Navajas J Nax H Nayak A Neal P Neuriter N Nguyen D Nguyen L Niewiarowski P Nikishova A Ning N Nixon E Novak D Nuckols R Obeng-Odoom F Obrist D Oettmeier C Oidtman R Oiwa K Okada I Olsen R Omelon S O'Neill M Opatowski L Ouellet-Plamondon C Ozden S Pagnacco M Pain R Palavalli-Nettimi R Paldi A Palmer R Palombo F Pan M Pandith A Papageorgiou D Papangelo A Pardo-Pastor C Parolini N Parry M Passerini T Pastore D Patten M Payne S Peixoto P Pekkan K Peleg O Penzel T Pereira CC Perkins M Perovic S Perrino G Perumal A Peters K Petri G Pfeuty B Phillips B Phillips J Piarroux R Picardi S Pietruszka M Pigolotti S Pinheiro PG Pires R Pisor A Pitsillides A Pleimling M Plenz D Ponce de Leon M Pons A Pons-Salort M Pooley C Poon A Porro L Porter M Potgieter P Prada F Prakash V Prasad A Priede I Prince R Pujo-Menjouet L Purwidyantri A Puthoff J Putman N Qiao M Raffa V Rainbow M Raj D Rajan R Ramirez Avila M Rammer W Rappel W-J Ratcliff W Ray E Rayfield E Read J Rebora M Reconditi M Reeves D Rennie M Reppert M Rezgui D Ribak G Ribeiro F Riede T Rienmuller T Rimbaud L Riveline D Roberts M Robertson DJ Rockne R Rode C Rodrigo G Rodrigues M Rodriguez Arguelles MC Rodriguez J Roh S Woon Romhild R Routier A-L Roy A Rudorf S Ruess J Ruocco G Rychtar J Saal H Sacco P Safaei S Saha S Sahasranaman A Saito K Salje H Salvioli M Samee MDAH Sanchez JA Sandev T Sankey DWE Santi P Santillan M Santon M Sapudom J Saracco F Saranathan V Schadschneider A Schiavazzi D Schlusser N Schmal C Schmitt D Schmitt S Schofield A Schroeder T Scott J Scott M Shahrezaei V Shaman J Shan Y Shen S-F Shepherd J Shera C Shibasaki S Shirtcliffe N Shiu Y Shrivastava A Sieber J Sierra C Silva CJ Singh M Singh P Singh V Skinner M Smith SM Sodt A Sokolis D Sommer G Sone E Spedding G Spencer N Spill F Spitzen J Spool J Springborn M Squires A Sridharan V Stan G-B Stayton T Steel H Steinmann T Stelling M Stenroth L Stone C Strauch C Strychalski W Stubbs C Sturla F Su Q Suki B Sulc P Suzuki R Szamado S Szorkovszky A Taboada P Takeda M Tamm K Tanaka M Tanaka Y Tang H Tapia Munoz NE Taylor J Teo SK Testori M Thomas P Thompson J Thompson K Thompson M Thomson R Thurner P Tilman A Timashev P Timerman D Tizzoni M Tobalske B Tonkovic Z Toxvaerd F Traulsen A Tribastone M Trzaskowska M Turunen M Tytell E Uyeno T Vaidya NK Valdespino Q van Belzen J Vardar Y Verstrepen K Villani M Villaverde A Villinger J Vitas M Vlach J Voigt D Volpert V von der Haar T Voronina L Wacker C Waclaw B Wade M Wagshul M Walani N Waldherr S Waller L Wan L Wang B Wang VY Wang X Wang Z Wardenaar K Wardley W Watanebe N Wegener M Wegst UGK Weickenmeier J Weinans E Weiss J Werth A Willemet L Williams H Williams-Hatala EM Willinger R Wilts B Winfield A Winters J Wolf L Wood R Woodward J Woolley T Wu A Wu JH Wysokowski M Xavier J Xiao F Yadav P Yamamoto T Yamazaki S Yang K-C Yang Q Yeomans J Yi H Yoshihara M Young J Youssofzadeh V Yu P Y Yunker P Zachos L Zachreson C Zadeh-Haghighi H Zahradka D Zahradnikova A Zajdel T Zamponi F zaslansky p Zavodszky G Zelner J Zenit R Zhang F Zhang J Zhao H Zhdanov O Zheng X Zuluaga M Zuriguel I
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Hortic Res Hortic Res hr Horticulture Research 2662-6810 2052-7276 Oxford University Press 10.1093/hr/uhac285 uhac285 AcademicSubjects/SCI01140 Letter to the Editor Soil and fine root-associated microbial communities are niche dependent and influenced by copper fungicide treatment during tea plant cultivation Mallano Ali Inayat State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China Yu Jie Sericultural Research Institute, Anhui Academy of Agricultural Sciences, Hefei 230061, China Dina Tabys School of Medicine, Nazarbayev University, Nur-Sultan 020000, Kazakhstan Li Fangdong State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China School of Science, Anhui Agricultural University, Hefei 230036, China Ling Tiejun State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China Ahmad Naveed Institute of Crop Germplasm Resources, Shandong Academy of Agricultural Sciences, Jinan 250100, China Bennetzen Jeffrey State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China Department of Genetics, University of Georgia, Athens, GA, 30602, USA Tong Wei State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China Corresponding authors. E-mail: [email protected]; [email protected] Equal contributions. 3 2023 29 12 2022 29 12 2022 10 3 uhac28527 6 2022 8 12 2022 01 3 2023 (c) The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University. 2023 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. pmcDear Editor, Fungicide treatment has a profound effect on controlling plant pathogens in modern agriculture, however, it also carries the risk of undesirable outcomes. For decades, scientists have been concerned about the harmful impacts of heavy metals like copper (Cu) on crop performance and soil microorganisms. Use of various copper fungicides, like Bordeaux mixture, have been a component of conventional agricultural practices to control fungal and bacterial pathogens, especially in vineyards, tea gardens, or fruit tree orchards . This treatment increases the accumulation of high levels of Cu in surface soils, and despite the critical role of Cu as an essential trace element in wide biological and metabolic processes, it becomes toxic to plants when applied at high levels . The regular application of copper fungicides has also been linked to affecting microbial communities at the levels of diversity , population structure , abundance, and growth . Understanding the undesired effects of fungicides on microorganisms' beneficial activities is therefore important for evaluating the hazards associated with the fungicide used in agriculture. Yet, the effects of copper fungicide on full microbial communities remains relatively understudied, especially in tea plants. Thus, we herein explored the influence of Bordeaux mixture under different management regimes (raking or without raking leaf litter) on microbial communities of root, bulk soil, and rhizosphere compartments of tea plants planted in a ten-year-old tea garden. We provided insights into the ecological consequences of tea management practices that might help to identify specific fungicide treatment regimens, environmental characteristics, and microbial community members to minimize the negative environmental outcomes and optimize the positive anti-pathogen aspects of fungicide treatment. Figure 1 Microbial community, composition and diversity of rhizosphere, root and bulk soil compartments under fungicide treatment. A A graphical scheme of treatments and sample collection of tea plant microbiome in current study. Microbiomes of three compartments of tea plant including bulk soil, fine roots and rhizosphere under different conditions (control, fungicide treatment, and fungicide after raking leaf litter) were prepared and collected. B, C Alpha diversity assessment of tea plant roots, rhizosphere, and bulk soil microbiome under copper fungicide treatments. Boxplots showing the Shannon diversity for bacteria and fungi grouped by compartment. Kruskal-Wallis test was applied for the significance tests between different comparisons. *P-value <0.05. D, E Bacterial and fungal community composition in the three tea plant habitats (roots, bulk soil, and rhizosphere) under fungicide treatment at phylum level. F Percentage of microbial sequences (bacteria, viral and fungi), plant host sequences and unclassified sequences in tea plant using reads based metagenomic sequencing. G, H Heatmaps showing the distribution of bacterial and fungal species obtained from three plant compartments root, rhizosphere, and bulk soil under fungicide treatments. The color code is representing the relative abundance ranging from high abundance (red) to low abundance (blue) grouped by treatment. I Functional enrichment of KEGG annotation of the genes identified in the metagenomic analysis and the significance tests between different comparisons among compartments and fungicide treatments. *P-value <0.05; **P-value <0.01. J Fifty copper-resistant gene categories identified against BacMet database across the three compartments under fungicide treatments in tea plant. The topside panel illustrates the number of genes harbored by the categories. Arrows of different colors and asterisks indicate the differential abundance copper categories among different comparisons between compartments and fungicide treatments. The lower panel heatmap indicates the overall gene abundances within each category related to copper resistance. *P-value <0.05; **P-value <0.01; ***P-value <0.001. C: control; F: fungicide treatment; FR: fungicide with raking treatment. We assessed fine root-associated microbial communities in three-year-old field-grown tea plants treated with fungicide Bordeaux mixture (final concentration of 0.6% copper and 0.3% lime powder, with a 1:0.5:100 per liter water ratio) before and after raking leaf litter. Compartments of bulk soil, rhizosphere and fine root samples were taken after 10 days of fungicide treatment (Fig. 1A). We detected the physiochemical composition of bulk soil and found that only nitrogen, zinc, and copper, as expected, displayed a significant difference after treatment. Amplicon sequencing of bacteria and fungi were then conducted by amplifying the V3-V4 of 16S and ITS2 gene regions. After data trimming and clustering, a total of 3 886 877 and 2 197 386 reads for 16S and ITS were generated, further assigned to 13 615 bacterial and 1723 fungal RSVs (ribosomal sequence variants). Alpha diversity of different compartments under treatments varied significantly in bacteria and fungi, revealing a gradient of diversity from bulk soil to rhizosphere and then to roots (Fig. 1B and C). Fungicide treatments generally increased the bacteria and fungi alpha diversity in roots and bulk soil, but critically decreased the diversity in the rhizosphere samples (Fig. 1B and C). This indicates that fungicide may affect the rhizosphere most in tea plants by directly decreasing their microbial diversity. Interestingly, the lowest alpha diversity was found in fungicide after raking treatment samples for the rhizosphere compartment of both bacteria and fungi. We then investigated the microbiome composition and abundance of different compartments samples. A total of 28 bacterial phyla and seven fungal phyla were identified. The bacteria were predominately colonized by Proteobacteria (45.90%), Firmicutes (31.21%), Actinobacteriota (7.60%), Acidobacteriota (4.80%), and unknown bacteria (2.47%), accounting for >90% of the total detected sequences (Fig. 1D). We found that Actinobacteriota and Acidobacteriota show increased abundances under fungicide treatment in root samples, but decreased patterns in the other compartments. Planctomycetota and Gemmatimonadota in soil and Proteobacteria in rhizosphere showed higher abundances under fungicide treatments, respectively. Ascomycota was the most dominant phylum across all the samples and contributed to an average abundance of 87.57% of the total fungal diversity (Fig. 1E). Fungicide treatment decreased the abundance of Ascomycota generally in all the compartments. Abundance of Basidiomycota was clearly reduced under fungicide treatment in rhizosphere and soil samples, but not in the root compartment. Glomeromycota showed low abundance in rhizosphere and root samples with a decreasing trend under fungicide, but higher abundance in soil compartment with higher amounts after fungicide treatment. This revealed that the microbial responses of tea plants after fungicide treatment in bulk soil are different from that in the root and rhizosphere. Reads-based metagenomics of bulk soil, rhizosphere, and root compartments were also performed to validate the composition and abundances. Approximately 9.8 Gb metagenomic sequences per sample were generated. Among all the reads, an average 6.34% in root, 31.96% in rhizosphere, and 27.73% in soil were classified as microbial sequences, in which a high proportion of the microbial sequences (root: 6.21%; rhizosphere: 31.75%; soil: 27.16% of all the reads) was assigned to bacteria (Fig. 1F). This gave us a general landscape and composition of the microbial communities in tea plant roots, rhizosphere, and bulk soil. Similar to the result in amplicon sequencing, Proteobacteria (62.28%), Actinobacteria (29.39%), Firmicutes (3.33%), Acidobacteria (1.92%), and Bacteroidetes (1.45%) in bacteria and Ascomycota (92.17%), Basidiomycota (7.67%) in fungi were detected as the most abundant phylum across the samples. Species, such as Rhodanobacter denitrificans, Brucella ovis, and Arthrobacter sp. had clearly higher abundances in bulk soil under fungicide and fungicide with raking treatments, while low abundances were observed in rhizosphere and root compartments (Fig. 1G). Burkholderia, which is necessary for protein repair and turnover under copper stress and possess antagonistic properties against fungal pathogens, were enriched in rhizosphere and root under fungicide raking treatment but not in bulk soil . Simultaneously, fungicide boosted the abundance of Niastella koreensis and Vibrio tubiashii in the root and rhizosphere compartments, while Alteromonas australica, Dehalobacter sp. CF and Bathymodiolus septemdierumwere more abundant in control samples (Fig. 1G). Fungicide treatment increased the fungal abundance of Botrytis cinerea, a well-known tea plant pathogen that causes Gray-mold disease , along with Malassezia restricta, only in bulk soil but not in the roots and rhizosphere (Fig. 1H). Meanwhile, Encephalitozoon cuniculi and Fusarium fujikuroi in roots, as well as Fusarium verticillioides and Fusarium oxysporum in rhizosphere were enriched and showed increased abundance under fungicide treatments compared to control (Fig. 1H). To further investigate the functional responses of microbiota in bulk soil, rhizosphere, and root of tea plant under cupper fungicide treatment, we conducted functional assessment of the metagenomic genes in the microbial population. Functional annotations of the predicted genes using Kyoto Encyclopedia of Genes and Genomes (KEGG) identified 29 pathways. Among them 3, 27, and 29 pathways were found to be differentially enriched between soil and rhizosphere, soil and root, rhizosphere and root (P < 0.05); however, we didn't find significant differences in pathways among the fungicide and raking treatments (Fig. 1I). A collection of 25 917 microbial genes associated with 922 biocide and metal-resistance categories against the BacMet database were characterized, of which 50 categories were related to copper (Fig. 1J). Among them, Copper-translocating P-type ATPase (155 genes), Copper (Cu, 62 genes), and copper homeostasis protein CutC (93 genes) were the most abundant categories (Fig. 1J). Comparative abundance analysis revealed 22 categories that were differentially presented among the fungicide treatments and different compartments (Fig. 1J). We found more differentially expressed gene categories between compartments than under the fungicide treatment, suggesting the diverse responses of tea plant root compartments against the fungicide treatment (Fig. 1J). Herein, we provided taxonomic evidence of copper responses in tea plant under natural habitats of soil, rhizosphere, and fine root gradient. We revealed that copper fungicide treatments not only increased the abundance of bacteria, including Rhodanobacter denitrificans, B. ovis, Arthrobacter and phytopathogens fungi, including Pyricularia oryzae, Botrytis cinerea, Fusarium species, but also could suppress the abundances of fungal taxa, such as beneficial fungi Talaromyces rugulosus. This suggested that copper fungicide treatment induces a much more complex shift in soil-associated microbiomes than expected from a simple anti-fungal model. Together with further investigations on the response mechanisms of tea plant against fungicides, these reported findings will serve to improve crop management strategies and decrease negative environmental outcomes. Acknowledgments This work was supported by the National Natural Science Foundation of China (No. 32002086), the Natural Science Research Project of University in Anhui Province (No. 202244), the Top Talent Team Project of Anhui Agriculture University (No. 03082021), and Key Program in the Joint Funds of National Natural Science Foundation of China (No U19A2034). Author contributions J.B., W.T., and A.I.M. designed and supervised the study; W.T. and A.I.M. collected the samples and did the formal analysis; A.I.M., J.Y., and W.T. wrote the manuscript; F.L., T.D., J.Y., and N.A. helped to do the analysing; A.I.M., J.Y., J.B., T.L., and W.T. revised the manuscript. Data availability Raw reads of the amplicon and metagenomic sequences reported in this study have been deposited into the National Center for Biotechnology Information BioProject database under accession number of PRJNA703764. Conflict of interest The authors declare that they have no conflict of interest. References 1. Dell'Amico E , MazzocchiM, CavalcaLet al. Assessment of bacterial community structure in a long-term copper-polluted ex-vineyard soil. Microbiol Res 2008;163 :671-83.17207985 2. Fernandez-Calvino D , MartinA, Arias-EstevezMet al. Microbial community structure of vineyard soils with different ph and copper content. Appl Soil Ecol 2010;46 :276-82. 3. Gobbi A , KyrkouI, FilippiEet al. Seasonal epiphytic microbial dynamics on grapevine leaves under biocontrol and copper fungicide treatments. Sci Rep 2020;10 :681.31959791 4. Griffiths BS , PhilippotL. Insights into the resistance and resilience of the soil microbial community. FEMS Microbiol Rev 2013;37 :112-29.22568555 5. Higgins S , GualdiS, Pinto-CarboMet al. Copper resistance genes of burkholderia cenocepacia h111 identified by transposon sequencing. Environ Microbiol Rep 2020;12 :241-9.32090500 6. Karakaya A , BayraktarH. Botrytis disease of tea in Turkey. J Phytopathol 2010;158 :705-7. 7. Kong P , RichardsonP, HongC. Burkholderia sp. Ssg is a broad-spectrum antagonist against plant diseases caused by diverse pathogens. Biol Control 2020;151 :104380. 8. Nunes I , JacquiodS, BrejnrodAet al. Coping with copper: legacy effect of copper on potential activity of soil bacteria following a century of exposure. FEMS Microbiol Ecol 2016;92 :fiw175.27543319 9. Seenivasan S , MuraleedharanN. Cumulative effect of foliar application of copper oxychloride on pb content in black tea. Journal of Tea Science Research 2015;5 :1-4. 10. Wightwick AM , WaltersRD, AllinsonGet al. Environmental risks of fungicides used in horticultural production systems. In: Odile Carisse (Eds.), Fungicides, Chapter 14: 272-303 (InTechOpen, 2010).
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Hortic Res Hortic Res hr Horticulture Research 2662-6810 2052-7276 Oxford University Press 10.1093/hr/uhac289 uhac289 AcademicSubjects/SCI01140 Letter to the Editor The high-quality Pinellia pedatisecta genome reveals a key role of tandem duplication in the expansion of its agglutinin genes Qian Zhihao Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China University of Chinese Academy of Sciences, Beijing 100049, China Ding Jun CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Innovative Academy of Seed Design, Chinese Academy of Sciences, Wuhan, China Li Zhizhong Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China Chen Jinming Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China Corresponding authors. E-mail: [email protected], [email protected] 3 2023 30 12 2022 30 12 2022 10 3 uhac28919 10 2022 17 12 2022 01 3 2023 (c) The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University. 2023 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. pmcDear Editor, Pinellia Tenore, a small genus of the monocot family Araceae, consists of only nine perennial herbaceous species and is mainly distributed in East Asia . Pinellia plants have been widely used as herbal medicines in Asia for over 2000 years. Among these species, P. ternata and P. pedatisecta are most widely used as traditional medicinal herbs . In China, the medicinal utilization of P. ternata and P. pedatisecta was first documented in the Divine Farmer's Materia Medica (Chinese name: 'Shennong Bencao Jing') during the Eastern Han dynasty (25-250 AD). Tubers produced by these plants have been traditionally utilized to treat vomiting, infection, and inflammation . Modern pharmacological studies have indicated that the pharmacological effects of Pinellia plants are closely related to endogenous components, such as plant lectins, alkaloids, amino acids, nucleosides, and polysaccharides . P. ternata has been listed in the Chinese Pharmacopoeia as a common traditional Chinese medicine. However, to date no genomic resources have been reported in the genus Pinellia, which greatly limits further studies on this valuable resource. Here we report a high-quality P. pedatisecta genome using Illumina, PacBio, and Hi-C sequencing technologies. The assembled genome was 1182.37 Mb in size, consistent with the estimated results of flow cytometry and k-mer analysis, comprising 13 pseudochromosomes with a contig N50 and scaffold N50 length of 17.26 and 85.81 Mb, respectively (Fig. 1A, Supplementary Data Figs S1-S3). A total of 77.66% repetitive regions were identified in the P. pedatisecta genome. Approximately 39.23% of the repetitive elements were long terminal repeat retrotransposons (LTR-RTs), including Gypsy (24.67%) and Copia (14.53%;Supplementary Data Table S1). Also, we observed that both Gypsy and Copia experienced two obvious bursts at ~0.4 and ~2 million years ago (Mya), respectively (Supplementary Data Fig. S4). Moreover, 26 113 protein-coding genes were predicted in the genome, of which 92.39% were functionally annotated among six public databases (Supplementary Data Table S2). Additionally, Benchmarking Universal Single-Copy Orthologs (BUSCO) assessment revealed there were 91.3 and 96.2% complete BUSCOs in P. pedatisecta genome and gene sets, respectively (Supplementary Data Table S3). The QV score of the P. pedatisecta genome is 33.37, corresponding to 99.38% accuracy, indicating that the P. pedatisecta genome was nearly complete and highly accurate (Fig. 1A). Figure 1 The P. pedatisecta genome. (A) Statistics of P. pedatisecta genome assembly. (B) Phylogenetic tree showing divergence times and the evolution of gene families in P. pedatisecta. Estimated divergence times (Mya) are shown at each node. Expansion and contraction of gene families are denoted as numbers in green and red, respectively. The red triangles denote the two WGDs reported in Wang et al. . (C) Syntenic depths between P. pedatisecta and C. esculenta. (D) Syntenic depths between P. pedatisecta and O. sativa. (E) Ks distribution of syntenic genes from S. polyrhiza, P. pedatisecta, and C. esculenta. (F) 4DTv density profiles of paralogs and orthologs for S. polyrhiza, P. pedatisecta, and C. esculenta. (G) Chromosomal distribution of 87 PPA genes. Red font represents tandem-duplicated PPA genes. Asterisks indicate that the gene is supported by transcriptome evidence. PPA genes generated by WGDs are linked by lines. (H) Expression differences of tandem-duplicated PPA genes and non-tandem-replicated PPA genes in three tissues (P-value is from the Wilcoxon test). (I) Phylogenetic tree of PPA genes from 16 Pinellia lectins downloaded from NCBI and 87 PPA genes. (J) Heat map showing three tissues with P. pedatisecta-specific expressions of PPA genes. The phylogenetic tree constructed for P. pedatisecta and 14 other representative plants using 485 common single-copy ortholog genes showed that P. pedatisecta diverged from the close relative species Colocasia esculenta ~29.26 Mya (Fig. 1B). Furthermore, gene family clustering analysis revealed that 252 and 280 gene families showed significant expansion and contraction in the P. pedatisecta genome, respectively. GO and KEGG enrichment analyses showed that 280 significantly expanded gene families were enriched for the GO terms 'secondary metabolic process', 'cellular amide metabolic process', and 'amide biosynthetic process', as well as the KEGG pathways 'isoflavonoid biosynthesis', 'phenylpropanoid biosynthesis', and 'metabolic pathways', which likely associate with the synthesis and accumulation of secondary metabolites (Supplementary Data Fig. S5). Whole-genome duplication (WGD) events have been inferred to play important roles in plant genome evolution and function . Our syntenic analysis showed that the syntenic depth between P. pedatisecta and C. esculenta and between P. pedatisecta and Spirodela polyrhiza (two WGDs) was 1:1, and that between P. pedatisecta and Oryza sativa (three WGDs) was 2:4, indicating that there were two rounds of WGDs in P. pedatisecta (Fig. 1C and D, Supplementary Data Fig. S6A). Syntenic dotplots also provided clearly visual evidence for two WGDs in P. pedatisecta (Supplementary Data Fig. S6B-E). Previous studies have shown that two WGDs (aSP/bSP) occurred within a short period at 95 Mya in S. polyrhiza, and were shared between C. esculenta and S. polyrhiza . In this study, S. polyrhiza diverged to the most recent common ancestor of P. pedatisecta and C. esculenta at ~80.78 Mya. Also, the Ks and 4DTv (four-fold synonymous third-codon transversion) distributions showed a single peak at the identical position for P. pedatisecta, S. polyrhiza, and C. esculenta, indicating that the two WGDs occurring within a short period were shared in these three species (Fig. 1B, E, and F). In addition, GO and KEGG enrichment analyses were performed to determine the functional roles of the 3448 genes retained after WGD events. These genes retained after WGDs were significantly enriched in 'regulation of the biosynthetic process', 'heterocycle biosynthetic process', 'nucleobase-containing compound biosynthetic process', and 'aromatic compound biosynthetic process' (Supplementary Data Fig. S7), suggesting that WGDs likely contribute to the diversification of metabolites and the accumulation of medicinal activities in the medicinal plant P. pedatisecta. Pinellia pedatisecta agglutinin (PPA), belonging to the Galanthus nivalis agglutinin (GNA) family, is a specific mannose-binding plant lectin, as well as an important medicinal component of P. pedatisecta with physiological effects such as bacteriostatic, insecticidal, and antitumor activities . In our study, 87 PPA genes were identified across the whole genome using PF01453 as a query. Chromosomal localization showed an uneven distribution of PPA genes, with the most distributed on chromosome 10, with 37 PPA genes. In addition, 68.97% (60) and 11.49% (10) of the PPA genes were classified to have undergone tandem duplication (TD) and WGD events based on intraspecific syntenic analysis, respectively, and eight genes were replicated in both TD and WGD events (Fig. 1G). These results suggested that the formation and expansion of the PPA genes in P. pedatisecta were mainly driven by TD events to generate new gene copies in tightly linked genomic clusters. A similar evolutionary pattern was also found in the study of Cucumis sativus lectins . Furthermore, 45 out of 60 tandem-duplicated PPA genes were supported by transcripts (Fig. 1G). Notably, the expression of tandem-duplicated PPA genes was significantly higher than that of non-tandem-duplicated PPA genes in stems and tubers (Fig. 1H), indicating that gene duplication greatly affects gene dosage and generally leads to high gene expression . The Ka/Ks ratios of both TD and WGD gene pairs were estimated to be <1 (Supplementary Data Table S4), revealing that most PPA genes underwent purifying selection to maintain their functionality. To obtain a more comprehensive insight into the GNA gene family in P. pedatisecta, we performed a phylogenetic analysis of P. pedatisecta and four closely related species in Araceae (Supplementary Data Fig. S8). All identified GNA genes of five species were clustered into four major groups (A-D). We detected that the GNA genes in P. pedatisecta underwent lineage-specific expansions, especially in group B, which was likely to be associated with recent TD events. To understand the evolutionary relationships among the GNA genes in Pinellia, a phylogenetic tree was constructed by combing 16 GNA genes from four Pinellia species retrieved from NCBI with 87 PPA genes newly identified here (Fig. 1I). Conserved motif analysis detected 10 conserved protein motifs, and motif 2, as part of the B_lectin domain, was present in all PPA genes. Meanwhile, genes within the same phylogenetic group presented similar conserved structural characteristics (Supplementary Data Fig. S9). In addition, all 16 retrieved GNA genes and 15 PPA genes newly identified here were clustered into group B (Fig. 1I). In previous studies, some of PPA genes in group B were proven to enhance resistance to aphids in transgenic plants and inhibit cancer cell proliferation . Notably, all PPA genes from P. pedatisecta in group B (except PIPE20294) included two B_lectin structural domains, which likely associated with aphid resistance and anticancer. Additionally, all PPA genes in group B were relatively highly expressed in tubers (Fig. 1J), which can explain why the dried tubers of P. pedatisecta are the main tissues used in folk medicine. In summary, the high-quality assembly of the P. pedatisecta genome provides a forceful reference for studying Pinellia spp. herbs. Also, the identification of P. pedatisecta agglutinin genes in this study will give a large potential for novel investigations and practical applications in biomedicine and agriculture. Acknowledgements This work was supported by grants from the Strategic Priority Research Program of Chinese Academy of Sciences (No. XDB31000000). Author details J.M.C. and Z.Z.L. designed the study and led the research. Z.H.Q. wrote the draft manuscript and analyzed the data. J.M.C., J.D., and Z.Z.L. contributed substantially to the revisions. The final manuscript has been read and approved by all authors. Data availability All data sets (Illumina, PacBio, Hi-C, RNA-seq and the genome assembly) have been deposited at the China National GeneBank DataBase (CNGBdb, ) website under the accessions CNS0561814-CNS0561818 with CNGB-Project ID CNP0003127. Conflict of interest The authors declare that they have no conflict of interest. Supplementary data Supplementary data is available at Horticulture Research Journal online. Supplementary Material Web_Material_uhac289 Click here for additional data file. References 1. Li H , BognerJ. Flora of China (English version) 2010;23 :39-43. 2. Ji X , HuangBK, WangGWet al. The ethnobotanical, phytochemical and pharmacological profile of the genus Pinellia. Fitoterapia. 2014;93 :1-17.24370664 3. Editorial Committee of Compendium of National Herbal Medicine . Compendium of National Herbal Medicine (Second Edition) (Part I). Beijing: People's Medical Publishing House, 1996. 4. Qiao X , LiQH, YinHet al. Gene duplication and evolution in recurring polyploidization-diploidization cycles in plants. Genome Biol. 2019;20 :38.30791939 5. Wang W , HabererG, GundlachHet al. The Spirodela polyrhiza genome reveals insights into its neotenous reduction fast growth and aquatic lifestyle. Nat Commun. 2014;5 :3311.24548928 6. Yin JM , JiangL, WangLet al. A high-quality genome of taro (Colocasia esculenta (L.) Schott), one of the world's oldest crops. Mol Ecol Resour. 2021;21 :68-77.32790213 7. Li G , LiX, WuHet al. CD123 targeting oncolytic adenoviruses suppress acute myeloid leukemia cell proliferation in vitro and in vivo. Blood Cancer J. 2014;4 :e194.24658372 8. Dang L , Van DammeEJM. Genome-wide identification and domain organization of lectin domains in cucumber. Plant Physiol Biochem. 2016;108 :165-76.27434144 9. Kondrashov FA . Gene duplication as a mechanism of genomic adaptation to a changing environment. Proc R Soc B. 2012;279 :5048-57. 10. Wu ZM , YanHB, PanWLet al. Transform of an ectopically expressed bulb lectin gene from Pinellia pedatisecta into tobacco plants conferring resistance to aphids. Aust J Crop Sci. 2012;6 :904-11. 11. Lu Q , LiN, LuoJet al. Pinellia pedatisecta agglutinin interacts with the methylosome and induces cancer cell death. Oncogene. 2012;1 :e29.
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34911 Cardiac/Thoracic/Vascular Surgery Use of a Closure Device for the Management of Inadvertent Placement of a Central Venous Catheter in the Carotid Artery: A Case Report and Literature Review Muacevic Alexander Adler John R Giagtzidis Ioakeim 1 Soteriou Andrea 1 Papadimitriou Christina 1 Papoutsis Ioakeim 1 Karkos Christos 1 1 5th Surgical Department/Vascular Surgery, Hippokrateio General Hospital/Aristotle University of Thessaloniki, Thessaloniki, GRC Ioakeim Giagtzidis [email protected] 13 2 2023 2 2023 15 2 e3491112 2 2023 Copyright (c) 2023, Giagtzidis et al. 2023 Giagtzidis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from The placement of a central venous catheter (CVC) is a common intervention in hospitalized patients. Several adverse events have been reported in this "blind" procedure when it is performed without the aid of ultrasound, including artery catheterization, which although uncommon, is a serious complication. Potential treatment options include manual compression, open surgical repair, and endovascular treatment. A 62-year-old critically ill patient with accidental arterial catheterization of the right common carotid artery (CCA) during placement of CVC is presented. The catheter was removed successfully with the use of a Perclose-ProGlide closure device. A systematic literature review was performed to identify similar cases treated with the same technique. This case presents an alternative minimally invasive treatment option, using a Perclose Proglide (Abbott) closure device for the removal of a misplaced CVC in the right CCA. Although this is an off-label use of the device it can be an effective alternative treatment option, especially in unstable patients. central venous catheter (cvc) catheter-related complications direct carotid artery puncture percutaneous arterial closure device inadvertent puncture The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Central venous access is a common procedure providing necessary vascular access. Its implementation increased proportionally, especially during the pandemic, where approximately 25% of COVID-19 patients required access through a central vein . There are many complications associated with central venous catheterization which can lead to a prolonged hospital stay, increased costs for the healthcare system, and decreased quality of life . Specifically, complications of internal jugular vein cannulation include infection, embolism, thrombosis, arrhythmias, hematoma, pneumothorax, cardiac perforation and tamponade, fistula formation, and arterial and nerve injury . To reduce or minimize the incidence of these complications, the ultrasound-guided puncture is nowadays mandatory ; however, inadvertent arterial puncture during central venous catheter (CVC) placement occurs in 2%-4.5%, causing arterial injury in 0.1%-0.5% of patients . Specifically, when access involves the jugular vein, incidental arterial puncture is reported between 6.3% and 9.4% of the cases with the incidence of arterial cannulation being around 1% . Several case reports and case series have described different treatment strategies for injury to the aortic arch, subclavian, brachiocephalic, or carotid artery during the attempted placement of jugular or subclavian venous catheters. Manual compression can be used but it can lead to devastating complications such as hematoma, stroke, and death especially if the catheter is 7Fr and above . Traditionally open surgical repair has been the treatment of choice, however endovascular surgery with the use of covered stents is gaining popularity due to its minimally invasive approach and easier access to difficult anatomic areas . Since endovascular procedures are becoming the standard of care and they continue to evolve, several closure devices have been available to achieve hemostasis after the percutaneous approach . Although not described in their instructions for use (IFU), there have been few reports of the use of these devices, for treating accidental arterial placement of CVCs. This study is a case report of using a Perclose-ProGlide (Abbott Vascular Inc., Santa Clara, CA, USA) closure device to remove a mispositioned CVC in the right CCA, and review of the relevant literature. Case presentation A 62-year-old male came to the ER with signs of acute respiratory failure triggered by a lower respiratory infection. The patient had a past medical history of atrial fibrillation (AF), hypertension, cardiac failure, and morbid obesity. A few hours after his arrival, he became unstable, so he was intubated and transferred to the ICU. During attempted catheterization of his right internal jugular vein, a triple lumen 7Fr CVC was accidentally placed in his right common carotid artery (CCA). Initial clinical suspicion of inadvertent placement of the catheter was raised from pulsating back-bleeding. A bedside duplex ultrasound was performed by a vascular surgeon where the misplaced catheter was identified in the right CCA . Figure 1 Duplex ultrasound identifying the misplaced catheter Because of the patient's severe condition and short wide neck , he was transferred to the operating room, where it was decided to remove the CVC with the use of a Perclose-ProGlide system. A hydrophilic stiff guidewire 0.035''-180cm was introduced through the distal lumen of the CVC and it was removed over the wire with manual compression. A Perclose-ProGlide device was advanced over the wire and successfully deployed according to IFU. Hemostasis was achieved and verified with ultrasound on the table , through the absence of direct flow outside the CCA. No further manual compression was required, and the patient returned to ICU. No complications were identified postoperatively. Figure 2 Hostile wide and short neck Figure 3 Duplex ultrasound verifying hemostasis after use of the closure device A review was performed using the PubMed database between 2000 and 2022. The following terms were used: "central venous catheter" OR "central line" AND "closure device". Inclusion criteria included any case reports or case series with misplaced CVC in the carotid artery, treated with any percutaneous closure device. The search returned 72 results. Each article was independently reviewed along with their references, to verify that the injured artery was the carotid and to extract the number of patients treated, the size of the CVC, the closure device that was used and the results. Any misplaced catheter in an anatomic area other than the CCA, or in the carotid artery treated with no use of a closure device was excluded from the study. Overall, eight publications with 15 patients described accidental cannulation of their carotid artery with a CVC and treated with a closure device (Table 1) [5-12]. In six cases (40%) the inserted catheter was 7Fr, in another six cases (40%) was 8.5Fr, in one case (6.6%) it was 9Fr in another one 6Fr (6.6%) and in one last case (6.6%) it was 12Fr. Regarding the devices that were used, Perclose-Proglide was used in the majority (n=8, 53.3%) of the cases. Two patients (n=2, 13.3%) were managed with Boomerang (Cardiva Medical, Mountain View, California) and two more (n=2, 13.3%) with Exoseal (Cordis Corporation, Bridgewater, NJ). In the final three cases one (n=1, 6.6%) Mynx (AccessClosure, Mountain View, CA) one (n=1, 6.6%) StarClose (Abbott Vascular, Santa Clara, CA) and one (n=1, 6.6%%) AngioSeal (St. Jude Medical, St. Paul, MI) were deployed. An embolic protection device (Spider FX, Medtronic, Dublin, Ireland) was used in just one case were the AngioSeal was placed. Overall technical success was 93.3% (n=14). In one patient with a 9FR catheter misplaced in the common carotid, the ExoSeal could not achieve complete sealing, so a secondary endovascular intervention was performed with the deployment of a stent graft (Fluency 10x40mm, BARD Medical, Covington, GA). Table 1 Cases of carotid artery injury treated with closure devices. n=number of patients, Fr=French Study Year Patients (n) Catheter size (Fr) Symptoms Closure Device Complications Yoon et al 2015 1 7 No Mynx None Pikwer et al 2009 1 12 No Perclose None Kirkwood et al 2008 2 7 No Boomerang None Stellmes et al 2014 2 7,9 N/A Exoseal None, Exoseal failed secondary Fluency stent graft Bechara et al 2014 6 8.5 N/A Percose None Gandhi et al 2016 1 7 No Angioseal None Lorenzo et al 2020 1 7 No Perclose None Pua et al 2015 1 6 No StarClose None Discussion Insertion of a CVC or a dialysis catheter is a common procedure in hospitalized, surgical, and renal patients for the administration of medications, intravenous fluids, parental nutrition, hemodialysis, and monitoring. In the United States, more than 5 million CVCs are placed annually . Despite the efforts to avoid adverse events, mainly with the recommendation of ultrasound guidance, their placement is associated with infectious, thromboembolic, and mechanical complications increasing significantly in-hospital morbidity and mortality . Complications of arterial puncture and cannulation of a CVC, include bleeding, hematoma, pseudoaneurysm, dissection, arterio-venous fistula formation, arrhythmia, stroke, and even death . Several factors have been associated with mechanical complications such as obesity or very low BMI, hypotension, duration of the procedure, and insertion of a CVC in an emergency setting or during the night . Furthermore, adverse events are related to the male gender, and the number of punctures per attempt, when more than two punctures can lead to up to 54% of failure or mechanical complication . Interestingly regarding the insertion site, there is some evidence that there are more arterial punctures (3.0% vs 0.5%) but less catheter malpositions (5.3% vs 9.3%) in the internal jugular compared with the subclavian access . Early detection of an arterial injury during CVC placement is of great importance and can prevent more catastrophic complications . If there is clinical or laboratory suspicion of a misplaced catheter, this should be confirmed with any imaging modality, and the catheter should be left in place . Withdrawal of a catheter located in the carotid artery and manual compression should also be avoided since it may result in hemorrhage, hematoma, airway obstruction, stroke, or pseudoaneurysm formation . Open surgical repair is safe and seems to be the standard of care but can add to morbidity since these patients are already critically ill and require general anesthesia . Furthermore, these operations add a significant workload to any vascular unit and anesthesiology department. Technical advancement and collective experience in endovascular procedures offer a safe alternative for managing misplaced catheters. Different endovascular options, like balloon tamponade, tract embolization and covered stent provide excellent technical success with a minimally invasive approach and local anesthesia ; however, balloon tamponade might be inadequate and in case of stent graft use, long-term patency and lifelong use of antiplatelets or anticoagulation might be an issue . Another endovascular solution that can be offered is the use of closure devices. The exponential growth of endovascular procedures created the need for an alternative or additional method for managing postprocedural access sites besides manual compression. In 1995 Vasoseal (St Jude Medical, St. Paul, MN) was the first FDA-approved vascular closure device and over the past 25 years, several other devices have become commercially available . Overall, these devices can be divided into three categories. The active ones physically close the arteriotomy with sutures or clips, the passive ones deploy a plug of some kind on the arteriotomy site, and one last category promotes coagulation externally via patches or pads with clotting factors . Overall, their use is shortening the time to hemostasis, patient ambulation, and discharge while according to Boghal et al., their complication rate is non-inferior to manual compression . Despite their extensive utilization, their IFUs still include only the common femoral artery. However, there have been numerous publications on the successful use of closure devices in many off-label locations such as superficial and profunda femoral artery, brachial, subclavian, and carotid artery following percutaneous endovascular procedures . Furthermore, in a recent systematic review of the management all inadvertent arterial placement of CVCs, the authors suggest the use of percutaneous closure devices as the first line approach in case femoral, subclavian, brachial, and carotid artery is involved . Conclusions The use of CVCs in everyday medical practice is increased especially during the Covid-19 pandemic, resulting in an increased number of iatrogenic vascular injuries. CVC placement especially in the internal jugular vein should be performed under ultrasound guidance. Even if all necessary precautions are taken, arterial and especially carotid injury and accidental catheterization can lead to devastating complications. Percutaneous closure devices although widely used in endovascular procedures, are not frequently utilized as a treatment option for inadvertent placement of CVC especially when the carotid artery is involved. This is probably due to their strict IFU, and the learning curve experience needed for their successful deployment. They seem to be however a safe, quick, minimally invasive, and effective treatment option for misplaced catheters in frail or unstable patients, that can be performed even bedside. Several publications suggest that these devices should be used as first-line treatment in such cases but in order to be widely implemented and not presented as merely case reports and small case series, further comparative studies should be designed between several devices and treatment options. This report examines the use of percutaneous closure devices as a treatment option for the inadvertent placement of CVCs, especially in the carotid artery. Including the patient in this case report, only 16 patients treated with the same technique can be found in the literature. The use of these devices provides many advantages, that justify their wider and more frequent use. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 A protocol for central venous access in patients with coronavirus disease 2019 J Vasc Surg Jasinski PT Tzavellas G Rubano JA Rutigliano DN Skripochnik E Tassiopoulos AK 1507 1509 72 2020 2 Ultrasound guidance versus anatomical landmarks for internal jugular vein catheterization Cochrane Database Syst Rev Brass P Hellmich M Kolodziej L Schick G Smith AF 0 1 2015 3 Mechanical complications of central venous catheters J Intensive Care Med Eisen LA Narasimhan M Berger JS Mayo PH Rosen MJ Schneider RF 40 46 21 2006 16698743 4 Management of inadvertent supra-aortic arterial lesions during central venous access procedures: report of six cases and proposed algorithm Ann Vasc Surg Gabriele P Emanuele G Ilenia DS Carlo GC Luca F Luciano C 308 314 75 2021 33819587 5 Inadvertent arterial placement of central venous catheters: diagnostic and therapeutic strategies Ann Vasc Surg Yoon DY Annambhotla S Resnick SA Eskandari MK Rodriguez HE 1567 1574 29 2015 26256713 6 Management of inadvertent arterial catheterisation associated with central venous access procedures Eur J Vasc Endovasc Surg Pikwer A Acosta S Kolbel T Malina M Sonesson B Akeson J 707 714 38 2009 19800822 7 The use of arterial closure devices for incidental arterial injury Vasc Endovascular Surg Kirkwood ML Wahlgren CM Desai TR 471 476 42 2008 18621878 8 Arterial closure devices for treatment of inadvertent large-caliber catheter insertion into the subclavian or carotid artery: a case series of five patients J Cardiothorac Vasc Anesth Stellmes A Diehm N Book M Schmidli J Do DD Gralla J 1319 1322 28 2014 24016686 9 Management of inadvertent carotid artery sheath insertion during central venous catheter placement JAMA Surg Bechara CF Barshes NR Pisimisis G Kougias P Lin PH 1063 1066 148 2013 24068206 10 Management of inadvertent placement of a central line in the carotid artery with a closure device and embolic protection device Cath Lab Digest Ripal T Gandhi MD 24 1 2016 11 Off-label use of Proglide percutaneous closure device in iatrogenic arterial catheterizations: Our experience Vascular Lorenzo JF Rey JV Arquillo IL Encisa de Sa JM 756 759 28 2020 32437239 12 Use of StarClose device under ultrasound guidance in inadvertent carotid artery puncture J Vasc Interv Radiol Pua U Tan GW Punamiya S 1410 1412 26 2015 26314652 13 Central Venous Access of The Subclavian Vein Deere M Singh A Burns B Treasure Island StatPearls Publishing 2022 14 Preventing complications of central venous catheterization N Engl J Med McGee DC Gould MK 1123 1133 348 2003 12646670 15 Practice guidelines for central venous access: a report by the American Society of Anesthesiologists task force on central venous access Anesthesiology Rupp SM Apfelbaum JL Blitt C 539 573 116 2012 22307320 16 Inadvertent central arterial catheterization: an unusual cause of ischemic stroke J Neurosci Rural Pract Katyal N Korzep A Newey C 155 158 9 2018 29456363 17 Managing inadvertent arterial catheterization during central venous access procedures Cardiovasc Intervent Radiol Nicholson T Ettles D Robinson G 21 25 27 2004 15109223 18 Inadvertent arterial placement of central venous catheter: salvage using endovascular treatment BMJ Case Rep Shaw M Chandrashekhara SH Sharma A Kumar S 231751 12 2019 19 Vascular closure: the ABC's Curr Cardiol Rep Bhogal S Waksman R 355 364 24 2022 35239082 20 Inadvertent arterial placement of central venous catheters: systematic review and guidelines for treatment J Vasc Interv Radiol Dornbos DL 3rd Nimjee SM Smith TP 1785 1794 30 2019 31530491
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34914 Otolaryngology Preventive Medicine Epidemiology/Public Health The Prevalence and Management of Chronic Tonsillitis: Experience From Secondary Care Hospitals in Rabak City, Sudan Muacevic Alexander Adler John R Alrayah Mujtaba 12 1 Otolaryngology - Head and Neck Surgery, Al-Baha University, Al-Baha, SAU 2 Otolaryngology, Faculty of Medicine, El Emam El Mahadi University, Al-Baha, SAU Mujtaba Alrayah [email protected] 13 2 2023 2 2023 15 2 e3491413 2 2023 Copyright (c) 2023, Alrayah et al. 2023 Alrayah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Background Tonsillitis is defined as an inflammation of the tonsils, which is a common clinical condition caused by either bacterial or viral infections. It affects a significant percentage of the population especially children. Chronic tonsillitis (CT) is described as when an individual suffers from seven or more attacks of tonsillitis per year. Aim This study aimed to determine the prevalence and management of CT among patients attending all secondary care hospitals in Rabak city, Sudan. Methods A cross-sectional descriptive study was conducted in June-September 2022. A structured questionnaire was used to screen 297 Patients who presented to all ENT clinics within the study period. Out of the 297 patients, 77 patients were confirmed to be having CT based on the inclusion criteria. Data collected were analyzed using SPSS version 21 and arranged into a simple frequency table. Results The prevalence of CT was found to be 25.9 % (77) among all screened patients. The majority (67.5%) of the patients with CT were male, and mostly between the age of 11-20 years (32.4%). A considerable number of them (32.4%) were residing in the urban-industrial part of the city, and about 36.3% are not working. All the patients with CT complained of throat pain, while 88% presented with red inflamed tonsils. Laboratory investigations of these patients revealed 64% to have Neutrophilia, while 54 and 50% had high ESR and positive ASO titer, respectively. 57% of the patients underwent tonsillectomy while (30%) were managed medically. Conclusion The prevalence of CT was found to be high in the agro-industrial area of Rabak city and more among teenagers, and most cases were managed by tonsillectomy. tonsillectomy sore throat rabak city incidence chronic tonsillitis The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Ear, nose, and throat (ENT) disease particularly tonsillitis represent a considerable health burden in Sudan with the high cost to the Sudanese National Health Service. This is due to high incidence, cost of treatment, and complications . Understanding the knowledge and magnitude of ENT diseases will aid the health authorities to implement its management and preventive programs. Tonsillitis is inflammation of the tonsils, a common clinical condition caused by either bacterial or viral infection . It affects a significant percentage of the population, especially children. Chronic tonsillitis (CT) is described as when an individual suffers from seven or more attacks of acute tonsillitis per year . Acute tonsillitis is characterized by visible streaks of pus or cheesy material on the tonsillar surface, and the entire tonsil may become enlarged and hyperemic suggestive of an inflammatory process. Tonsillitis is caused mainly by b-hemolytic Streptococcus, called strep throat, and to a lesser extent by Staphylococcus aureus and several other bacteria. The more common symptoms of acute tonsillitis are sore throat, red swollen tonsils, pain when swallowing, fever, cough, headache, tiredness, chills, swollen lymph nodes in the neck, and pain in the ears or neck, and the less common symptoms include nausea, stomachache, vomiting, furry tongue, bad breath, and change in voice and difficulty in opening the mouth . There are three approaches to the management of CT: conservative, use of antibiotics, or by tonsillectomy. Surgical removal of the tonsils provides the definitive treatment . Although the CT rate was expected to be high in the agro-industrial area of Rabak city in Sudan because of the environmental pollution, there are not enough data on its epidemiology in the area. This study aimed to determine the prevalence, clinical features, laboratory findings, and treatment modalities of patients with CT among patients reporting to secondary care hospitals in Rabak city, Sudan. Materials and methods Ethical considerations This research was approved by the Ministry of Health Research Committee, White Nile province, with ethical clearance no (5). Moreover, verbal notified consent was obtained from all participants and or their informants. Study design A cross-sectional, observational hospital-based research was performed in the time of June to September 2022 including all patients who visited the secondary ENT hospital of Rabak city, Sudan, who suffered from sore throats (297). Patients were seen by two ENT consultants, and diagnosis of CT was done in the ENT clinics using a head mirror, light source, and tongue depressors. Any patient with a sore throat and who had seven or more attacks of acute tonsillitis was diagnosed with CT (77 out of 297). Demographic data, clinical features, lab investigations, and treatment modalities of CT were reported in this study. Study population Patients visiting Rabak secondary ENT hospital complaining of sore throat and who were diagnosed later with chronic tonsillitis (seven or more attacks of acute tonsillitis) during the research period who fit the research inclusion criteria were joined voluntarily. Inclusion Criteria The research inclusion criteria comprise both sex and all age groups, who lived in Rabak town, Sudan, and who were diagnosed with CT by ENT consultants. The whole number of permitted participants was 77 out of 297 patients. Exclusion Criteria The study exclusion criteria comprise any participants with deficient investigations. (n=3) were excluded. Sample size estimation The formula of sample size calculation (N = PQZ2/d2) was used to calculate the sample size (N = 77). Where N = sample size, P = prevalence of CT disorders factor, Q = 1-p, Z = constant 95% occurred 1.96, and d = desired margin. Data collection procedure Data were collected using a structured questionnaire. The participants were approached with questions concerning their sociodemographic details, and ENT-related complaints such as sore throat (estimated with a scale system of severity graded from 1 to 10), whilst the ENT professionals applied and reported clinical examinations, ENT-related diagnosis, investigations, and management. Moreover, checking the records of the treated patients. All patients had gone through a comprehensive history and a full physical examination by ENT professionals. Relevant investigations were carried out according to the patient's complaint. Data analysis The patients' data were processed statistically using the SPSS version 21. A descriptive statistical summarization was performed. The result was considered significant at a p-value less than 0.05. Results A total number of 297 patients were screened within the study period out of which 77 (25.9 %) patients were diagnosed with CT. The majority 22 (28.6%) of patients were between the age of 11-20 years (Table 1). Table 1 Age characteristics of study participants with CT in Rabak city, Sudan (n=77). Age Frequency/Percentage < 10 6(7.8) 11 -20 22(28.6) 21-30 20(26) 31-40 15(19.5) 41-50 12(28.6) >50 2(2.6) Males accounted for 52 (67.5%) while females accounted for 25 (32.4%) of the patients (Table 2). Table 2 Sex characteristics of study participants with CT in Rabak city, Sudan (n=77). Sex Frequency/Percentage Male 52(67.5) Female 25(32.4) Most of the patients 25 (32.4%) lived in the urban-industrial part of the city (Table 3). Table 3 Residence characteristics of study participants with CT in Rabak city, Sudan (n=77). Residence Frequency/Percentage Urban 20(25.9) Urban-industrial 25(32.4) Rural 16(20.9) Rural industrial 12(15.5) Others 5(6.4) While most of the patients 28 (36.3%) had no work to do, a very appreciable percentage 26(33.7%) were found to be working (Table 4). Table 4 Occupation characteristics of participants with CT in Rabak city, Sudan (n=77). Occupation Frequency/Percentage Industrial worker 2(2.6) Farmer 5(6.5) Office job 4(5.2) Marginal employment 7(9) Security office 1(1.3) Others 4(5.2) Not working 28(36.3) Students 26(33.7) All patients with CT 77 (100%) presented with complaints of throat pain, and during examination of the oropharynx, 88% of them presented with red swollen tonsils (Table 5). Table 5 CT symptoms percentage among the participants with CT in Rabak city, Sudan (n=77). CT symptoms Percentage Sore throat 100 Fever 67 Odynophagia 46 Constitutional symptoms 56 Red swollen tonsils 88 Jugulodigastric lymph nodes 65 Regarding lab investigations, 64% of patients showed neutrophilia in their blood film, while 54 and 50% had high ESR and positive ASO titer, respectively (Table 6). Table 6 CT lab investigations percentage among the participants with CT in Rabak city, Sudan (n=77). Lab. investigations Percentage Neutrophilia (+ve/-ve) 64 ESR (+ve/-ve) 54 ASO Titer 50 Low HB 22 Most of the patients (44%) underwent tonsillectomy while 30% were managed medically (Table 7). Table 7 CT treatment modality percentage among participants with CT in Rabak city, Sudan (n=77). Treatment modality/Frequency/Percentage Medical 30(39%) Surgical 44(57%) Referred 3(4%) Discussion The incidence rate of CT was expected to be high among Sudanese in the area of Rabak city. This might be due to environmental pollution as in this area there are many factories and farms. Its exact rate, clinical features, and management are not well-reported. The total number of participants who were diagnosed with CT was 77 which accounted for 25.9% of all patients attending ENT clinics at secondary care facilities in Rabak city, Sudan. This is higher than all ENT diseases attending our clinics in Rabak city. More so, the prevalence we got is higher than what was obtained by Anekpo and Modebe in a retrospective study done in Nigeria where the incidence rate was 2.7% out of 396 patients . Our incidence rate was equally found to be higher than what Nanda and Bhalke obtained in a retrospective study done in India involving 690 patients where the rate was found to be 15.5% . The present study revealed that the majority of the participants suffering from CT were teenagers between the age of 11-20 years. This is in line with a cross-sectional hospital-based study done in India by Sarode D and Bhole A who concluded that CT is more prevalent in the age group of 11-20 years . The present findings are contrary to those determined by Mattila et al. who reported CT is more prevalent among adults above 20 years of age, while lesser in those less than 10 years of age . In this study this may likely be due to missed diagnosis as most patients less than 10 years are seen by pediatricians not by ENT professionals, as such, they may miss the diagnosis. In relation to a previous study, the age group of 10-20 years is also reported to have a high incidence of CT, and this finding was explained by their low immunity, and cross-infection because of overcrowded classrooms and poor ventilation of the classrooms . In this study, CT was found to be higher among the male gender residing in the urban-industrial part of Rabak city, this finding is in contrast to the study done by Abouzied and Massoud as well as Bismi et al. who reported female preponderance in their studies. Males are frequently stayed outdoors and exposed to infecting microorganisms and have more direct contact with diseased people, as well as the possibility of having allergies attributed to exposure to urban-industrial pollution in Rabak city. All these factors could likely be the reason for the male preponderance in this study. A considerable number of the patients 28 (36.3%) with CT in this study are unemployed, and this could actually translate to poor nourishment, unhygienic condition, illiteracy, and improper medical care. The present findings are in line with Somro et al., who stated that CT is more prevalent among populations with low socioeconomic status . The current study revealed that sore throat was a presenting symptom among all patients, this is in line with a prospective study undertaken by Batra et al. among 50 patients with CT . Regarding laboratory investigations that were carried out among the studied patients, 64% showed neutrophilia in their blood film, while 54% and 50% have high ESR and positive ASO titer, respectively. All these findings were relatively high which are all in consonance with a descriptive study done by Roos, who reported that total WBC count, polymorphonuclear leucocytes, ESR, and ASO titer were found to be high in the majority of their study population with CT . The marked neutrophilia and high ESR among the majority of the patients in this study may be due to the fact that infective causes are the leading cause of tonsillitis among our patients. Moreso, ASO titer was high among these patients suffering from tonsillitis, this may be a predictor of the known complications of Group A beta-hemolytic streptococci (GABS), which are rheumatic heart disease and glomerulonephritis. Pal'chun and on the other hand Alasmari et al. stated that patients with fewer attacks of CT from GABA infection are best treated conservatively with penicillin and co-amoxiclav if there are no complications . The surgical modality of treatment is the mainstay of treatment for patients with frequent attacks of CT as this proved to be the suitable modality for avoiding complications and averting future costs of medical treatment . These previous conclusions explain the diversity of the treatment modalities in the current study. Limitations This study has some potential limitations. First, the small size of the study patients. Second, the patients recruited are mostly men with few women involved. Finally, this study did not implement methodologies for bacterial investigation using cultures or rapid diagnostic tests to rule out GABS. Conclusions In this study, the majority of the patients with CT are teenagers, residing within urban-industrial areas, and are unemployed. Most of them having CT are males. The majority presented with a sore throat and Red Swollen Tonsils on throat examination. Most patients show high Neutrophilia, high ESR, and ASO titer on laboratory investigations. CT treatment modalities vary from medical treatment to surgical tonsillectomy. Recommendation We recommend that Governmental projects and educational programs are crucial for improving the health system in Rabak city, and these should be implemented to hasten solutions to some health challenges like CT. Furthermore, prevention of tonsillitis particularly among pediatric age groups with overcrowded poor living conditions should be encouraged to reduce the risk and complications of CT. Finally, there is a need for further research in Rabak city to determine the risk factors for the high incidence of CT in Rabak city. Human Ethics Animal Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study. Ministry of Health Research Committee, White Nile State, Rabak city, Sudan issued approval 5 Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. References 1 Effect of tonsillitis on pre-school and basic school children and their mothers knowledge, attitude and practice towards it in Marngan Aloamal, Gezira State, Sudan eMedihealth Mahmoud NE 33 34 8 2013 2 Microbiological profile of chronic tonsillitis in the pediatric age group Cureus Kalaiarasi R Subramanian KS Vijayakumar C Venkataramanan R 0 10 2018 3 Pharyngitis and sore throat: a review Afr J Biotechnol Somro A Akram M Khan MI 6190 6197 10 2011 4 Pattern of paediatric ear, nose and throat diseases in Port Harcourt, South-South, Nigeria Niger Health J Mbalaso OC 48 54 15 2015 5 Correlation between throat-related symptoms and histological examination in adults with chronic tonsillitis Medicina (Kaunas) Pribuisiene R Sarauskas V Kuzminiene A Uloza V 286 290 51 2015 26674146 6 Clinical practice guideline: tonsillectomy in children Otolaryngol Head Neck Surg Baugh RF Archer SM Mitchell RB 0 30 144 2011 7 Pattern of ear nose and throat (ENT) diseases seen by Otorhinolarynologist at Bishop Sanahan specialist hospital out patient clinics, Nsukka South East Nigeria J Med Res Health Sci Anekpo CC Modebe EO 2112 2118 5 2022 8 Epidemiology of Otorhinolaryngology diseases seen in health camps in rural backward areas of Himachal Pradesh Otolaryngol Online J Nanda MS Bhalke ST 106 6 2016 9 Prevalence of chronic tonsillitis at ENT inpatient department: a hospital-based study Medpulse-Int J Sarode D Bhole A 766 788 2 2015 10 Causes of tonsillar disease and frequency of tonsillectomy operations Arch Otolaryngol Head Neck Surg Mattila PS Tahkokallio O Tarkkanen J Pitkaniemi J Karvonen M Tuomilehto J 37 44 127 2001 11177012 11 Sex differences in tonsillitis Dalhousie Med J Abouzied A Massoud E 44 47 2 2008 12 Prevalence, pattern and management of tonsilitis in students-an online survey Int J Res Hospital Clin Pharmacy Bismi S Dharman D Manohar D Dharan SS Rajalekshmi K Dhanya SS 82 84 1 2019 13 Sore throat - a review of presentation and etiology Indian J Otolaryngol Head Neck Surg Batra K Safaya A Nair D Capoor M 14 19 56 2004 23120018 14 The diagnostic value of symptoms and signs in acute tonsillitis in children over the age of 10 and in adults Scand J Infect Dis Roos K 259 267 17 1985 4059866 15 Classification and therapeutic strategy for chronic tonsillitis Vestnik Otorinolaringologii Pal'chun V 8 11 2 2013 16 Causes and treatment of tonsillitis Egyptian J Hospital Med Alasmari NS Bamashmous RO Alshuwaykan RM 2975 2980 69 2017 17 Economic benefit of tonsillectomy in adults with chronic tonsillitis Ann Otol Rhinol Laryngol Bhattacharyya N Kepnes LJ 983 988 111 2002 12450171 18 Benefit from tonsillectomy in adult patients with chronic tonsillitis Eur Arch Otorhinolaryngol Baumann I Kucheida H Blumenstock G Zalaman IM Maassen MM Plinkert PK 556 559 263 2006 16491389
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Signal Transduct Target Ther Signal Transduct Target Ther Signal Transduction and Targeted Therapy 2095-9907 2059-3635 Nature Publishing Group UK London 1391 10.1038/s41392-023-01391-x Letter Antigenic characterization of SARS-CoV-2 Omicron subvariants XBB.1.5, BQ.1, BQ.1.1, BF.7 and BA.2.75.2 Zhu Airu 1 Wei Peilan 1 Man Miao 2 Liu Xuesong 1 Ji Tianxing 3 Chen Jiantao 1 Chen Canjie 1 Huo Jiandong [email protected] 1 Wang Yanqun [email protected] 1 Zhao Jincun [email protected] 145 1 grid.470124.4 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 2 grid.259384.1 0000 0000 8945 4455 University Hospital and Center for Biomedicine and Innovations, Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China 3 grid.412534.5 Clinical Laboratory Medicine Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 4 Guangzhou laboratory, Bio-island, Guangzhou, China 5 grid.440637.2 0000 0004 4657 8879 Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China 15 3 2023 15 3 2023 2023 8 1253 1 2023 1 3 2023 3 3 2023 (c) The Author(s) 2023 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Subject terms Infection Vaccines National Natural Science Foundation of China (National Science Foundation of China) 82172240 Zhao Jincun issue-copyright-statement(c) The Author(s) 2023 pmc Dear Editor, Recently, a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities, in particular BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5.1 Unsurprisingly, these new subvariants are quickly gaining prevalence worldwide. In fact, some of them have outcompeted BA.5 in the USA according to CDC's national genomic surveillance data in which, as of 6th February 2023, XBB.1.5, BQ.1.1, BQ.1, XBB and BF.7 have achieved a dominance of 66.4%, 19.9%, 7.3%, 2.3% and 0.5% in the USA, as compared to 0.5% for BA.5. In this report, using plasma samples collected from individuals following different vaccination strategies and COVID-19 convalescent donors, we performed pseudoviral neutralization assays to confirm severe reductions in neutralization titers against BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5 in comparison to other Omicron sub-lineages. XBB and XBB.1.5 were shown to be remarkably resistant to plasma neutralization in all tested cohorts. By comparing the differential neutralization profiles, we found that a heterologous booster with an aerosolized vaccine following 2 doses of inactivated vaccine seemed to be superior to other vaccination strategies. To evaluate the antibody evasion capacity of the new variants, we constructed a panel of pseudotyped vesicular stomatitis virus (VSV)2 expressing the S gene from BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5 and other SARS-CoV-2 variants together with early pandemic wild type (WT) strain, used as a control. We first accessed the neutralization profile for plasma samples collected 4-6 weeks following symptom onset from unvaccinated convalescents infected with WT (WC group, n = 15) or Delta (DC group, n = 17), or plasma collected from vaccinees who had received 2 doses of inactivated vaccine CoronaVac (BA.2 group, n = 17) following BA.2 breakthrough infection or those who had received 3 doses of inactivated vaccine CoronaVac (BA.5 group, n = 19) following BA.5 breakthrough infection (Fig. 1a). Neutralization titers against BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5 were below or close to the limit of detection [given an arbitrary pVNT50 (the reciprocal dilution of plasma that neutralizes 50% of the input virus) value of 30] in both the WC and DC groups, although the titers to BA.2 and BA.4/5 were comparably low in both groups (Fig. 1b). In the BA.2 and BA.5 group, XBB and XBB.1.5 remained resistant to neutralization by plasma, but the titers against other variants were markedly increased as compared to the WC and DC group (Fig. 1b). Titers against BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5 were 3.2 to 9.8-fold lower than BA.4/5 in the BA.2 group, and 3.7 to 14.5-fold lower than BA.4/5 in the BA.5 group respectively.Fig. 1 Plasma neutralization titers against Omicron variants in convalescents, BA.2 and BA.5 breakthrough infection and vaccinees. a Grouping information and timing of plasma sample acquisition from convalescents, BA.2 and BA.5 breakthrough infection patients, w represented week, m represented month. b Neutralizing titers against various SARS-CoV-2 pseudovirus in plasma from convalescents from prototype or Delta SARS-CoV-2 (WC, DC) and Omicron BA.2 or BA.5 breakthrough infection groups (BA.2, BA.5). c Grouping information and timing of plasma sample acquisition from vaccinees who received homologous (I-I-I, B-B-B) or heterologous (I-I-B, I-I-A) booster vaccination. I represented an inactivated vaccine CoronaVac, B represented an mRNA vaccine BNT162b2, and A represented an aerosolized vaccine Ad5-nCoV. d Neutralizing titers against various SARS-CoV-2 pseudovirus in plasma from vaccinees in homologous or heterologous COVID-19 booster vaccination groups as described in panel c. e Grouping information and timing of plasma sample acquisition from vaccinees who received a second booster vaccination (I-I-I-B, I-I-I-A). f Neutralizing titers against various SARS-CoV-2 pseudovirus in plasma from vaccinees receiving second COVID-19 booster vaccination as described in panel e. In panel b, d and f, SARS-CoV-2 pseudovirus used for neutralizing assay included WT, BA.2, BA.4/5, BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5. The geometric mean neutralizing titers (GMTs) were shown at the bottom in each panel, and fold changes of GMTs against Omicron BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5 relative to BA.4/5 were labeled. g Comparison of immune escape properties against diverse Omicron subvariants from vaccinees, convalescents and breakthrough infection were summarized in the heatmap of GMTs. h. The immune escape assessments of different variants were performed as the ratio of their GMTs to that of BA.4/5. Data distribution was confirmed with Shapiro-Wilk normality test, Friedman test with Dunn's multiple comparisons test and Kruskal-Wallis test with Dunn's multiple comparisons test were used for evaluating differences among the experimental groups. p values are displayed as ns for p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 Vaccine plasma were taken from four different groups of individuals, including the I-I-I group (vaccinees who had received 3 doses of inactivated vaccine CoronaVac, n = 20), the B-B-B group (vaccinees who had received 3 doses of mRNA vaccine BNT162b2, n = 20), the I-I-B group (vaccinees who had received 2 doses of inactivated vaccine CoronaVac followed by a heterologous booster with mRNA vaccine BNT162b2, n = 19) and the I-I-A group (vaccinees who had received 2 doses of inactivated vaccine CoronaVac followed by a heterologous booster with aerosolized vaccine Ad5-nCoV, n = 17) (Fig. 1c). The I-I-I group showed a very similar profile to that observed in the WC group (Fig. 1d) such that only low neutralization titers [geometric mean pVNT50 = 97] were elicited against WT and responses against the Omicron subvariants were below or close to the limit of detection. By contrast, much higher titers were induced in the B-B-B group (Fig. 1d). While the tripled dosed inactivated virus vaccination performed poorly, sequential vaccination of two doses of inactivated vaccine and a single dose of mRNA vaccine or aerosolized vaccine substantially increased the neutralization titers against the new subvariants (Fig. 1d). As observed in the BA.2 and BA.5 group, neutralization titers against the new variants were consistently higher for BF.7, followed by BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5 in B-B-B, I-I-B and I-I-A group. Next, neutralization assays were performed using plasma samples obtained from vaccinees who had received 3 doses of inactivated vaccine CoronaVac followed by a heterologous booster with mRNA vaccine BNT162b2 (I-I-I-B group, n = 7) or aerosolized vaccine Ad5-nCoV (I-I-I-A group, n = 17) (Fig. 1e). The neutralization profile for the two groups are similar (Fig. 1f), the new subvariants showed greater resistance than BA.4/5 in both groups, with a 2.0 to 6.3-fold reduction in titers in the I-I-I-B group and a 1.7 to 6.3-fold reduction in the I-I-I-A group, except that the I-I-I-A strategy elicited lower titers against the WT strain compared to I-I-I-B. In fact, not only for the WT strain, the neutralization titers induced by BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5 were consistently lower in the I-I-I-A group compared to I-I-A where a booster with aerosolized vaccine was administered following two doses of inactivated vaccine rather than three doses (Fig. 1g). Considering the comparable age and sex distribution between these two groups, the difference may be caused by the vaccination strategies. According to a new study,3 pre-existing high-affinity antibodies would inhibit immune responses by lowering the activation threshold for B cells and direct masking of their cognate epitopes, thus B cell responses induced by the heterologous Ad5-nCoV booster vaccine may be dampened by a higher pre-existing high-affinity antibody levels in I-I-I-A individuals when compared to the I-I-A ones. Similar trends were observed for both infection-induced plasma, regardless of the vaccination status (Fig. 1 g, h), enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BF.7, BQ.1, BQ.1.1, BA.2.75.2, XBB and XBB.1.5 was observed when compared with their parent BA.2 and BA.4/5. Multiple vaccination strategies, including I-I-I, B-B-B, I-I-B, I-I-I-B, I-I-A and I-I-I-A, failed to elicit high neutralizing antibody titer against the newly emerged Omicron subvariant and the rank of neutralization evasion is in the order of BA.2/BA.5 < BF.7 < BQ.1 < BQ.1.1 < BA.2.75.2 < XBB/XBB.1.5, especially XBB/XBB.1.5 which shows superior antibody escaping capability. Consistent to our results, antibody evasion to new subvariants BA.2.75.2, BQ.1.1, XBB.1.5, CH.1.1, and CA.3.1 have been reported in parental mRNA vaccine or BA.5-bivalent booster,4,5 calling urgently for new bivalent vaccines and better-off vaccination strategies. In summary, we study the neutralization of these new subvariants using a range of plasma samples from natural and breakthrough infections, as well as homologous and heterologous vaccinations. Compared to BA.5, the new subvariants showed stronger antibody escape in all tested cohorts, and the rank of neutralization evasion is in the order of BA.2/BA.4/5 < BF.7 < BQ.1 < BQ.1.1 < BA.2.75.2 < XBB/XBB.1.5 based on the geometric mean neutralizing titers (GMTs). Notably, neutralization activity was exceptionally low against XBB/XBB.1.5 in all cases. Whilst triple-dosed inactivated vaccine elicited very low neutralizing antibody responses against the Omicron subvariants, a heterologous booster with an aerosolized vaccine or an mRNA vaccine following 2 or 3 doses of inactivated vaccine substantially improved the neutralization profiles, although taking a heterologous booster of aerosolized vaccine following 2 doses of inactivated vaccine seemed to generate superior results to others. Our study thus provides valuable information that may help to guide the design of vaccination strategy. Supplementary information supplemental material Supplementary information The online version contains supplementary material available at 10.1038/s41392-023-01391-x. Acknowledgements This work was supported by grants from National Key R&D Program of China (2021YFC2300101 YW), the National Natural Science Foundation of China (82172240 YW, 82025001 JZ), Self-supporting Program of Guangzhou Laboratory (SRPG22-001, SRPG22-006), Guangdong Basic and Applied Research Projects (2023B1515020040 YW, 2020A0505100063 JZ, 2019B1515120068 JZ), ZhongNanShan Medical Foundation of Guangdong Province (ZNSA-2020001, ZNSA-2020013), State Key Laboratory of Respiratory Disease (SKLRD-Z-202214 YW, SKLRD-OP-202309 YW) and Guangzhou Medical University (YP2022005 YW). Author contributions J.Z., Y.W., and J.H. designed and supervised the experiments; Y.W., J.H., A.Z. and P.W. wrote the manuscript. A.Z., P.L., M.M., X.L., T.J., J.C., and C.C. performed the neutralization experiments and provided plasma samples and information. All authors have read and approved the article. Data availability The data and materials used in the current study are available from the corresponding authors upon reasonable request. Competing interests The authors declare no competing interests. Ethics declarations This study was performed in strict accordance with human subject protection guidance proved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (2022-G-42). These authors contributed equally: Airu Zhu, Peilan Wei, Miao Man, Xuesong Liu, Tianxing Ji References 1. Tuekprakhon A Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum Cell. 2022 185 2422 2433.e2413 10.1016/j.cell.2022.06.005 35772405 2. Nie J Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay Nat. Protoc. 2020 15 3699 3715 10.1038/s41596-020-0394-5 32978602 3. Schaefer-Babajew D Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination Nature. 2023 613 735 742 10.1038/s41586-022-05609-w 36473496 4. Kurhade C Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster Nat. Med. 2023 29 344 347 10.1038/s41591-022-02162-x 36473500 5. Qu, P. et al. Extraordinary Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1 and CA.3.1 Variants. Preprint at 10.1101/2023.01.16.524244 (2023).
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J Med Life J Med Life JMedLife Journal of Medicine and Life 1844-122X 1844-3117 Carol Davila University Press Romania JMedLife-16-325 10.25122/jml-2022-0248 Case Report A single session of education for a patient with negative beliefs about low back pain: A case report of 16-month follow-up Alshami Ali Muteb 1* 1 Department of Physical Therapy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia * Corresponding Author: Ali Muteb Alshami, Department of Physical Therapy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. E-mail: [email protected] 2 2023 16 2 325328 23 9 2022 22 1 2023 (c)2023 JOURNAL of MEDICINE and LIFE 2023 This article is distributed under the terms of the Creative Commons Attribution License ), which permits unrestricted use and redistribution provided that the original author and source are credited. The effectiveness of education in patients with low back pain (LBP) remains controversial and inconclusive. This case report describes the long-term effects of a single educational session on the rehabilitation of a patient with chronic LBP (CLBP). A 57-year-old woman presented with the main complaint of LBP and inability to prostrate for several years. The intervention consisted of a single session of patient-specific education that targeted negative cognitive beliefs. This education included instructions about the obtained findings, spinal anatomy, patient reassurance, the relationship between imaging findings and patient symptoms, proposed treatment, and a home exercise program. The patient was able to independently complete the prostration task immediately after the session without pain. This improvement was maintained for at least 16 months, as demonstrated by the Numeric Pain Rate Scale, Patient-Specific Functional Scale, Fear Avoidance Belief Questionnaire, and the Keele STarT Back Screening Tool. In conclusion, a single session of patient-specific education was effective, both immediately and over the long term, in addressing pain and function in patients with CLBP. case report long-term musculoskeletal physical therapy rehabilitation ABBREVIATIONS CLBP - chronic low back pain FABQ - Fear Avoidance Belief Questionnaire LBP - low back pain MRI - magnetic resonance imaging NPRS - numeric pain rating scale PSFS - patient specific functional scale RCT - randomized controlled trial SBST - Keele STarT Back Screening Tool pmcINTRODUCTION Low back pain (LBP) is the single principal cause of disability in 160 countries worldwide. Clinical practice guidelines for LBP recommend physical and psychosocial therapies with less focus on pharmacological and surgical treatments. These therapies include methods of patient education such as traditional biomedical education, cognitive behavioral therapy, and pain neuroscience education, typically delivered by a trained therapist over several sessions . Although patient education has been recommended as a first-line treatment for acute and chronic LBP, its effectiveness in patients with LBP is conflicting and inconclusive. For example, a recent systematic review concluded that patient education improves pain, disability, and quality of life in patients with LBP. Out of five studies reviewed, only two showed significant improvement after the education program . A previous systematic review included 13 randomized controlled trials (RCTs) and concluded that education programs were not effective in reducing pain, disability, and quality of life in patients with LBP . More studies are needed to provide evidence of the effectiveness of education in patients with LBP, owing to a lack of evidence and a limited number of RCTs . Although several education methods can be provided to patients with LBP, no single method has been found to be superior. In addition, these methods may have various limitations, such as time, cost, and availability . Studies on the long-term effects of a single education session on patients with CLBP are lacking. Lower-intensity treatment options with a single session may be sufficient for a group of patients. Furthermore, a single-session intervention may be no less effective than multiple long-term sessions of intervention that have several obstacles, such as limited patient access, time, costs, and therapist availability . Therefore, the current study aimed to describe the outcomes of a patient with persistent LBP who did not respond to previous conservative interventions. However, she responded favorably over the long term to a single educational session. CASE REPORT The patient was a 57-year-old woman who had been unemployed for the last ten years and had worked as a teacher for 5-6 years. She presented to the clinic for consultation regarding her chief complaint of left-sided LBP with occasional numbness in the lateral left thigh . This pain prevented her from sitting on her left buttock or prostration. Prostration involves the position in which the person kneels and bows until the forehead, nose, and palms of the hands contact the ground. She reported that the initial pain started approximately three years ago at home while lying on her left side in bed. The patient attempted several medications and physical therapy techniques, but the results were unsatisfactory. The patient had a previous diagnosis of benign multiple sclerosis 18 years ago, with full recovery 2 years later. She was advised by her physician to take Neurontin once daily for five months to prevent seizures that may be associated with multiple sclerosis. This medication was discontinued before the time of the session. She was diagnosed with bilateral knee osteoarthritis 10 years ago. Figure 1 Body chart of the patient showing the main complaint of left-sided low back pain and occasional numbness of the left thigh. The patient described the intensity of her current LBP as 3/10 on the numeric pain rating scale (NPRS). Her numbness on the lateral thigh was described as a "cotton feeling" . The patient had not been able to prostrate for the last 10 years. She believed that the reasons for not being able to prostrate were knee osteoarthritis and recent magnetic resonance imaging (MRI) results showing that the discs may "bulge with doing this movement". She was told by a physician not to prostrate because of knee osteoarthritis. Recently, another physician advised her not to prostrate because this movement could worsen the lumbar disc bulge. Assessments Initial radiography revealed spondylotic changes in the form of marginal osteophytes detected at L2, L3, L4, and L5. MRI showed diffuse disc bulges at L2-3, L3-4, L4-5, and L5-S1, with narrowing of the neural foramina and abutting of both exiting nerves at L4-5. Multiple facet joint arthropathies and ligamentum flavum thickening were also observed. Physical examination and tests The author, a consultant physical therapist with more than 20 years of experience in the management of musculoskeletal pain disorders, conducted the clinical examinations. Initial observation and posture The patient walked independently in the clinic and did not appear to experience pain. Formal observation of posture was not performed because of the priority of other tests and its poor relationship with nonspecific LBP . Movement testing Examination of the lumbar spine while standing included active movement testing for forward bending (flexion), extension, lateral flexion, and rotation on both sides with/without overpressure . All movements were within the normal range, except for flexion, which was within the 75% range and reproduced severe LBP at the end of the range and with a return from flexion. Neurodynamic provocation test Straight leg raise was passively tested on both legs in the supine position. The hips were flexed to 80deg and reproduced tightness behind the thigh after performing ankle dorsiflexion as a distal sensitizing movement. The test was considered negative because it did not reproduce the symptoms . Manual testing In the prone position, the central posterior-anterior vertebral pressures from L1 to S1 reproduced moderate pain over L4 and L5. Left unilateral posterior-anterior vertebral pressure reproduced moderate pain over the L4/L5 and L5/S1 facet joints. The test did not reproduce the thigh numbness. Abnormal vertebral motion is moderately helpful for predicting responses to particular conservative treatments . Knee testing Since the patient reported that she had been diagnosed with knee osteoarthritis over the last 10 years, the author decided to quickly screen her hips and knees. Manual muscle testing for hip and knee extension was 4-/5 and 4/5, respectively. No range of motion deficits was found in any hip or knee movement. Mild tightness was reported by the patient in the anterior thighs at the end range of knee flexion during the prone knee-bend test. Self-report and outcome measures NPRS was used to assess pain intensity at rest . In addition, the patient was asked to rate up to three activities that were challenging to perform or could not be accomplished due to LBP by completing the Patient Specific Functional Scale (PSFS) . The Fear Avoidance Belief Questionnaire (FABQ) was used to evaluate patients' perceived fear of movement due to the presence of LBP with regard to predicting physical activity (FABQ-PA) and work loss (FABQ-W) . Moreover, the Keele STarT back screening tool (SBST) was used to screen prognostic indicators for persistent disabling LBP with categories of low, medium, or high risk . Table 1 shows the self-reported and outcome measures, including the minimal clinically important difference (MCID) and minimal detectable change (MDC). At the initial session, the patient had moderate pain and high fear avoidance beliefs that adversely affected physical activity and was classified as having a high risk of poor outcomes and developing persistent LBP. Table 1 Self-reported outcome measurements during the follow-up period. Outcome Baseline 16 months Test-retest reliability MCID/MDC NPRS (0-10) 7-8 (at rest) 0 (at rest) 3 (after 5 hours of standing) ICC=0.72 2 PSFS (0-10) ICC=0.92 1.4 Bending in prayer 8 10 - - Sitting 5 10 - - FABQ-W (0-42) 30 1 ICC=0.95 5.95 FABQ-PA (0-24) 24 4 ICC=0.90 3.69 SBST ICC=0.89 N/A Total (0-9) 8 0 - - Subscale (0-5) 5 0 - - NPRS - Numerical Pain Rating Scale (0-10); PSFS - Patient Specific Functional Scale; FABQ - Fear-Avoidance Beliefs Questionnaire (W - Work subscale; PA - Physical Activity subscale); SBST - Keele STarT Back Screening Tool; MCID - minimal clinically important difference; MDC - minimal detectable change. Diagnosis, evaluation, and clinical reasoning The author believed that the patient's severe LBP and inability to prostrate for the last 10 years were primarily related to cognitive function associated with negative beliefs about her condition. The patient's impairments (such as pain on lumbar flexion testing, pain in the lower lumbar spine with pressure, and mild tightness and weakness of the quadriceps) did not seem to be the main cause of the patient's symptoms and functional disability. Active movement testing of the lumbar spine and knees revealed unremarkable results. All movements of the lumbar spine were within normal limits except for mild range limitation and pain with flexion. The patient showed above-average muscle strength and complete knee range of motion. In addition, the patient visited different clinicians and attempted several treatments, but with unsatisfactory results. Moreover, the patient had high FABQ and SBST scores. Intervention Based on the clinical examination and reasoning process of this patient, the author explained the findings, suspected disorder, and proposed treatment to the patient. The patient was instructed to perform the following exercises once per day at home for 2 sets of 15 repetitions: active straight leg raise in the supine position and active flexion in the prone position. Moreover, as the patient's daughter was a physical therapist, she was instructed to perform lumbar spine mobilization, which consisted of central and left unilateral posterior-anterior pressure (grade III) on the lower lumbar spine with three sets of 30 repetitions, once daily. The patient was mainly concerned about the MRI findings of the lumbar spine and the disc bulge. The patient was unable to prostrate for several years due to her negative belief about the relationship between the bulging disc in her lumbar spine and knee osteoarthritis and her symptoms. Patient education was the main goal of the session. Patient-specific education comprised information about the obtained findings, spinal anatomy, patient reassurance, the relationship between the MRI findings and patient symptoms, the proposed treatment, and a home exercise program. At the end of the session, the patient was asked to perform prostration. The session lasted approximately 1.5 hours, including the patient's history, examination, and education. Outcomes Interestingly, after the session, the patient performed prostration with no pain in the lower back, left thigh, or knee. Accordingly, the patient was instructed to immediately pray normally at home, which included prostration and no need to use a chair. Although there were no follow-up sessions, the author contacted the patient five days after the initial session to ask about her progression. The patient reported that she had been performing a prostration task normally without pain since the initial session. To examine the long-term effect of this session, the patient was asked to complete self-report measures after 16 months. Clinically meaningful improvements were observed in all outcomes: NPRS=0/10 (at rest) and 3/10 (after 5 hours of standing), PSFS=10/10 (prostration and sitting), FABQ-W=1/42, FABQ-PA=4/24, and SBST=0/9 (total) and 0/5 (subscale) (Table 1). The patient reported that the home exercise program was performed for only one month and that lumbar spine mobilization was performed only twice. No adverse or unanticipated events were reported. The patient declared that she did not use any other interventions throughout the study. DISCUSSION The patient in this case report, who complained of recalcitrant LBP and a long history of bilateral knee osteoarthritis, was able to independently prostrate without pain immediately after a single session of patient-specific education. Interestingly, this rapid and clinically meaningful improvement in pain and function lasted at least 16 months. Improvements in pain intensity (NPRS), related disability (PSFS), perceived fear of movement for work (FABQ-W), and physical activity (FABQ-PA) exceeded the MCID/MDC of 2 cm , 1.4 points , 5.95 points, and 3.69 points , respectively. The patient was at high risk for developing persistent LBP and activity limitation (SBST) at the initial session, which improved to a low risk for at least 16 months. A 1.5-hour session of education was provided by a physical therapist who was not specially trained in psychology. The education was not structured; it was patient-specific and included information about the obtained findings, spine anatomy, patient reassurance, the relationship between MRI findings and patient symptoms, proposed treatment, and home exercise programs. This type of education aimed to target patients' negative cognitive beliefs about their condition. It is recommended that patient education alone may be insufficient and best combined with other modalities, such as exercises . Typically, patient education methods are time-consuming and require psychologists or specially trained therapists . However, the current case report demonstrated that a short single session of patient-specific education resulted in an immediate and long-term clinically meaningful change in pain and related disability. The clinical relevance of this case report is the importance of patient-specific education in the rehabilitation of patients with chronic musculoskeletal pain, especially LBP and knee osteoarthritis. This case report provides preliminary evidence regarding the long-term effects of a single session of patient-specific education. However, future RCTs are needed to further examine the clinical cost-effectiveness of this educational method. A limitation of this case report was that the author did not use Waddell's sign to classify this patient with negative beliefs about her LBP. However, a pilot study suggested that Waddell's "non-organic signs" is questionable and may not exclusively be non-organic tests . Inter-observer reliability of the signs ranged from fair (K=0.33) to good (K=0.74) and was moderate (K=0.48-0.49) for the overall Waddell score. Intra-observer reliability varied from moderate (K=0.43) to very good (K=0.84) for the signs and good (K=0.65-0.68) for the overall Waddell score. Internal consistency was good for both the categories (K=0.65-0.72) and the signs (K=0.71-0.78) . CONCLUSION With a single 1.5-hour session of patient-specific education, the patient demonstrated an immediate return to a pain-free prostration task and improvements in functional status that lasted 16 months. Further RCTs are needed to determine the cost-effectiveness of single or minimal sessions in patients with chronic pain syndrome. ACKNOWLEDGEMENTS Conflict of interest The author declares no conflict of interest. Consent to participate Informed consent was obtained from the patient to participate in this case report and to publish any accompanying images or data. Data availability Further data is available from the corresponding author on reasonable request. Authorship AMA contributed to the conception and design of the manuscript and the acquisition, analysis, and interpretation of the data. AMA drafted the manuscript, revised it critically, and approved the final version of the manuscript. Finally, the author is responsible for the integrity of this research. 1 Darnall BD Roy A Chen AL Ziadni MS Comparison of a Single-Session Pain Management Skills Intervention With a Single-Session Health Education Intervention and 8 Sessions of Cognitive Behavioral Therapy in Adults With Chronic Low Back Pain: A Randomized Clinical Trial JAMA Netw Open 2021 Aug 2 4 8 e2113401 10.1001/jamanetworkopen.2021.13401 34398206 2 Zahari Z Ishak A Justine M The effectiveness of patient education in improving pain, disability and quality of life among older people with low back pain: A systematic review J Back Musculoskelet Rehabil 2020 33 2 245 254 10.3233/BMR-181305 31356191 3 Ainpradub K Sitthipornvorakul E Janwantanakul P van der Beek AJ Effect of education on non-specific neck and low back pain: A meta-analysis of randomized controlled trials Man Ther 2016 Apr 22 31 41 10.1016/j.math.2015.10.012 26585295 4 Cleland J Koppenhaver S Su J Netter's orthopaedic clinical examination: An evidence-based approach 2022 4th ed Philadelphia Elsevier 5 Maughan EF Lewis JS Outcome measures in chronic low back pain Eur Spine J 2010 Sep 19 9 1484 94 10.1007/s00586-010-1353-6 20397032 6 Monticone M Frigau L Vernon H Rocca B Reliability, responsiveness and minimal clinically important difference of the two Fear Avoidance and Beliefs Questionnaire scales in Italian subjects with chronic low back pain undergoing multidisciplinary rehabilitation Eur J Phys Rehabil Med 2020 Oct 56 5 600 606 10.23736/S1973-9087.20.06158-4 32420712 7 Robinson HS Dagfinrud H Reliability and screening ability of the StarT Back screening tool in patients with low back pain in physiotherapy practice, a cohort study BMC Musculoskelet Disord 2017 May 31 18 1 232 10.1186/s12891-017-1553-x 28569152 8 Farrar JT Berlin JA Strom BL Clinically important changes in acute pain outcome measures: a validation study J Pain Symptom Manage 2003 May 25 5 406 11 10.1016/s0885-3924(03)00162-3 12727037 9 Echeita JA Dijkhof M Grootenboer F van der Wurff P A pilot study in the association between Waddell Non-organic Signs and Central Sensitization Musculoskelet Sci Pract 2020 Oct 49 102200 10.1016/j.msksp.2020.102200 32861362 10 Apeldoorn AT Bosselaar H Blom-Luberti T Twisk JW Lankhorst GJ The reliability of nonorganic sign-testing and the Waddell score in patients with chronic low back pain Spine (Phila Pa 1976) 2008 Apr 1 33 7 821 6 10.1097/BRS.0b013e318169502a 18379412
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J Med Life J Med Life JMedLife Journal of Medicine and Life 1844-122X 1844-3117 Carol Davila University Press Romania JMedLife-16-173 10.25122/jml-2022-0111 Editorial Alzheimer's disease: 120 years of research and progress Ciurea Vlad Alexandru 12 Covache-Busuioc Razvan-Adrian 3 Mohan Aurel George 45 Costin Horia Petre 3 Voicu Victor 67 1 Neurosurgery Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 2 Neurosurgery Department, Sanador Clinical Hospital, Bucharest, Romania 3 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 4 Department of Neurosurgery, Bihor County Emergency Clinical Hospital, Oradea, Romania 5 Neurosurgery Department, Faculty of Medicine, Oradea University, Oradea, Romania 6 Pharmacology, Toxicology and Clinical Psychopharmacology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 7 Romanian Academy, Bucharest, Romania 2 2023 16 2 173177 26 9 2022 29 12 2022 (c)2023 JOURNAL of MEDICINE and LIFE 2023 This article is distributed under the terms of the Creative Commons Attribution License ), which permits unrestricted use and redistribution provided that the original author and source are credited. pmcTHE HISTORY OF DEMENTIA: FROM ANTIQUITY TO MODERN TIMES Cognitive disorders have fascinated people since antiquity, as they often present with memory impairment and diminished social interactions. Dementia was the common name for all cognitive disorders that had an impact on the psychological and social aspects of the patient long before Alzheimer's disease was discovered. The history of dementia can be traced back to the Greco-Roman period when it was considered a disease of the elders. The term 'dementia' is derived from the Latin word "demens", which describes a person being out of their mind . The famous philosopher Pythagoras classified human life into five stages, with the last two age groups being regarded as "senium", involving both psychological and physical deterioration . Meanwhile, Hippocrates supposed that mental decline was a consequence of decreased body fluids in the brain of elders, leading progressively to an unfavorable outcome when the patient cannot memorize or have any social interactions . Until the 19th century, there were only a few papers written about dementia in medical books and writings, and poets and playwrights described characters with cognitive disorders without explicitly stating dementia as the pathology involved. However, in the 19th century, thanks to Philippe Pinel, a French physician regarded as the "Father of modern psychiatry", who militated against the prosecution of alienated patients, cognitive disorders were transformed into clinical pathologies that could be treated . The 20th century marked a significant moment in the classification of cognitive disorders as clinical pathologies. During this time, neurosyphilis was the main cause of dementia, but it was easily curable if diagnosed early. ALOIS ALZHEIMER: LIFE AND CONTRIBUTIONS TO PSYCHIATRY AND NEUROSCIENCE Alzheimer's disease was discovered in the early 20th century by the German psychiatrist and neuropathologist Alois Alzheimer after a study that started in 1901. Alois Alzheimer, born in 1864 in Marktbreit, Bavaria, studied medicine at the University of Berlin, the University of Tubingen, and the University of Wurzburg, where he graduated in 1887 with a Doctor of Medicine degree. He later assumed a position at the Frankfurt asylum, where he had the opportunity to meet Emil Kraepelin , a well-known German psychiatrist who was investigating psychosis in senile patients at that time. Kraepelin became a mentor to Alzheimer and is regarded as the founder of modern scientific psychiatry, psychopharmacology, and psychiatric genetics, advocating for biological and genetic malfunction as the etiology of cognitive disorders . Figure 1 Emil Kraepelin, about 1920. (c) Munchener Medizinische Wochenschrift (1926). In 1908, Alzheimer became a professor at Ludwig Maximilian University of Munich, and in 1912, he became a psychiatry professor and director of the neurologic and Psychiatric Institute in Breslau for the Silesian Friedrich Wilhelm University in Breslau. Unfortunately, despite his numerous academic achievements, Alzheimer's life was cut short when he died on December 19th, 1915, at the age of 51 due to a streptococcal infection that led to heart failure. Nevertheless, his contributions to the field of psychiatry and neuroscience continue to inspire researchers and clinicians to this day. THE FIRST STUDY ON ALZHEIMER'S DISEASE AND THE FIRST PATIENT DIAGNOSED In 1901, Alois Alzheimer became interested in a patient at Frankfurt asylum named Auguste Deter , a 51-year-old female with unique symptomatology compared to normal dementia cases. She presented progressive confusion, sleep disorders, and, most importantly, memory loss . Alzheimer became fascinated by this clinical case as the patient was not so old, and she did not present arteriosclerosis since no signs of vessel structure were found. Moreover, her symptoms developed progressively, which excluded the case of an arteriosclerotic brain . Figure 2 Alois Alzheimer, about 1909. (c) Archive for History of Psychiatry, Department of Psychiatry University of Munich (left) and Auguste Deter (right). Alzheimer described Auguste Deter's symptomatology in a paper for the "37th Meeting of South-West German Psychiatrists in Tubingen", but unfortunately, it was not appreciated by the academic community. However, it was later published in 1907 entitled "Uber eigenartige Krankheitsfalle des spateren Alters" (On certain peculiar diseases of old age). He stated the following report: "Her memory is seriously impaired. If objects are shown to her, she names them correctly, but almost immediately afterwards she has forgotten everything. When reading a test, she skips from line to line or reads by spelling the words individually, or by making them meaningless through her pronunciation. In writing, she repeats separate syllables many times, omits others and quickly breaks down completely. In speaking, she uses gap-fills and a few paraphrased expressions ("milk-pourer" instead of cup); sometimes it is obvious she cannot go on. Plainly, she does not understand certain questions. She does not remember the use of some objects". . After Auguste Deter's death in 1906 due to infected bedsores, Alzheimer examined her brain and noticed the presence of neuritic plaques and neurofibrillary tangles using silver staining, one of the newest techniques at that time. He concluded that there was a link between these abnormal structures and the cause of the disease . Figure 3 Presence of neurofibrillary tangles in the early stage (left) and terminal stage (right) of the disease . In the 19th century, the Romanian neurologist Gheorghe Marinescu , along with French pathologist Paul Blocq, discovered the existence of senile plaques (beta-amyloids) in the grey matter of eight epileptic patients' brains using hematoxylin-eosin, acidic fuchsin, and carmine staining. Later on, this discovery paved the way for Alzheimer's correlation between the discovery of senile plaques with the etiology of Alzheimer's disease . Figure 4 Gheorghe Marinescu (1863-1938). Neuritic plaques are the outcome of a spontaneous or genetic disorder that consists of a protein misfolding leading to aggregation of beta amyloids which comes from an amyloid precursor protein (APP) cleaved by beta and gamma-secretase. Neurofibrillary tangles are aggregates of hyperphosphorylated tau protein that represent nowadays the most accurate paraclinical investigation that determines a clear diagnosis of Alzheimer's disease. Today, according to the updated Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), Alzheimer's disease can be diagnosed by fulfilling one of the following criteria: (1) the patient undergoes genetic tests that state the disease, especially if another member of the family had Alzheimer's disease or (2) all of the following three conditions are fulfilled: (a) a clear objective observation of learning or memory impairment, (b) a progressive cognitive deterioration, and (c) no evidence of other disorders such as cerebrovascular diseases, cognitive disorders, or any other neurological conditions that can assist the cognitive decline. THE GROWING BURDEN OF ALZHEIMER'S DISEASE According to a European Union statistic, the death rate related to dementias, including Alzheimer's disease, has been on a progressively ascending path year by year, from 198,320 deaths in 2011 to 316,989 deaths in 2017, representing a 59.83% increase during these six years . Alzheimer's disease is by far the most common type of dementia, representing about 60-80% of all diagnosed cases of cognitive disorders . In 2020, around 6.2 million Americans aged 65 or older had Alzheimer's disease, and this number is predicted to increase to 12.7 million Americans by 2050. Figure 5 A graphic representation of the death rate among patients with dementias, including Alzheimer's disease, across the European Union (according to Eurostat). To comprehend this alarming statistic, we need to understand the symptoms of this pathology, the factors that can lead to Alzheimer's disease, and the currently available treatments and their benefits. UNDERSTANDING ALZHEIMER'S DISEASE: SYMPTOMS, RISK FACTORS, AND PREVENTION METHODS Alzheimer's disease is a cognitive disorder that is characterized by memory loss, confusion, and difficulties completing tasks. The most prominent symptom of Alzheimer's disease is memory loss, which is caused by the presence of neurofibrillary tangles in the hippocampal neurons . As the tangles spread, they change the shape of the neurons, leading to dysfunctional synapses and decreased encryption of information. Alzheimer's patients may also experience confusion when locating themselves in space and time and have difficulties completing tasks or planning events . While Alzheimer's disease is easy to diagnose, there are many other factors that can lead to memory loss, including drugs, alcohol, vitamin B12 deficiency, or different brain tumors . To determine whether a patient has Alzheimer's disease, a physician may ask for the family record and conduct PET/MRI scans to look for amyloids . These scans can determine the presence of beta-amyloids up to 15 years before symptoms appear . Alzheimer's disease is a multifactorial pathology with both genetic and environmental factors contributing to its development. However, the most significant risk factor is age, as the majority of patients with Alzheimer's are over 65 years old. According to a study conducted by Hebert L. E. et al. (2013) , the predicted prevalence for 2020 is 3.1% for people aged 65-74 years old, 16.7% for people aged 75-84 years old, and 32.2% for people aged 85 years old or more. This clearly states that an increased age determines an increased risk of developing Alzheimer's disease. Genetics can also play a role, but less than 1% of patients have a genetic abnormality that causes Alzheimer's disease. In those rare cases, however, a mutation to the presenilin 1 gene can almost for sure lead to Alzheimer's since this mutation will induce a protein misfolding that will produce beta-amyloid aggregation . Prevention methods for Alzheimer's disease include avoiding high consumption of alcohol and cigarettes, keeping the brain active, and maintaining a healthy diet . A ketogenic diet with a low carbohydrate and high fat intake can improve glucose metabolism in the brain and decrease brain amyloid-beta levels, which may prevent the occurrence of Alzheimer's disease . TREATMENT OF ALZHEIMER'S DISEASE: CURRENT AVAILABLE MEDICATIONS AND FUTURE RESEARCH Alzheimer's disease currently has a few classes of medication available for treatment. Cholinesterase inhibitors, such as Donepezil, Rivastigmine, and Galantamine, are the first possible treatment plan for patients with Alzheimer's disease. These drugs prevent the enzyme cholinesterase from destroying the acetylcholine molecules found in abnormally small quantities in the brains of patients with Alzheimer's disease. However, physicians should prescribe these drugs in the early or moderate stages of the disease . In more severe cases, Memantine can be used alone or in combination with cholinesterase inhibitors to treat both cognitive and behavioral disorders, which are common symptoms in the advanced stages of the disease. Selective serotonin reuptake inhibitors (SSRIs) can also be used to treat behavioral problems and regulate mood changes in patients . However, the biggest challenge in treating Alzheimer's disease is to target the beta-amyloid plaques and neurofibrillary tangles from the first occurrence to prevent the disease . While there are multiple etiopathogenic explanations for this specific type of dementia, appropriate treatments for prevention have not been found yet. Alois Alzheimer's discovery of the first patient's brain with Alzheimer's disease led to a better understanding of this new type of dementia, including its incidence, clinical manifestation, and predictive outcomes, particularly in the elderly. By sharing his findings with the scientific community, Alzheimer significantly increased knowledge about this new type of dementia and raised awareness regarding its unique clinical manifestations and prevalence. Although no appropriate treatments have been found yet, research on Alzheimer's disease is focused on finding ways to prevent the formation of beta-amyloid plaques and neurofibrillary tangles as a form of prevention. The dedication and collaborative efforts of researchers, healthcare professionals, caregivers, and advocacy groups are critical in the fight against Alzheimer's disease, and it is our hope that continued efforts in research and treatment will lead to better outcomes for those affected by this devastating disease. 1 Vatanabe IP Manzine PR Cominetti MR Historic concepts of dementia and Alzheimer's disease: From ancient times to the present Rev Neurol (Paris) 2020 176 3 140 7 10.1016/j.neurol.2019.03.004 31174886 2 Assal F History of Dementia Front Neurol Neurosci 2019 44 118 126 10.1159/000494959 31220848 3 Deva MP Psychosocial rehabilitation models in the Asia-Pacific region Psychiatry Clin Neurosci 1998 Dec 52 Suppl S364 6 10.1111/j.1440-1819.1998.tb03270.x 9895195 4 Ebert A Bar KJ Emil Kraepelin: A pioneer of scientific understanding of psychiatry and psychopharmacology Indian J Psychiatry 2010 Apr 52 2 191 2 10.4103/0019-5545.64591. 20838510 5 Soria Lopez JA Gonzalez HM Leger GC Alzheimer's disease Handb Clin Neurol 2019 167 231 255 10.1016/B978-0-12-804766-8.00013-3 31753135 6 A Alzheimer A Forstl H Levy R On certain peculiar diseases of old age Hist Psychiatry 1991 Mar 2 5 Pt 1 71 101 10.1177/0957154X9100200505 11622845 7 Bondi MW Edmonds EC Jak AJ Clark LR Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates J Alzheimers Dis 2014 42 1 275 89 10.3233/JAD-140276 24844687 8 Opris I Nestianu VS Nestianu A Bilteanu L Ciurea J George Marinesco in the Constellation of Modern Neuroscience Front Neurosci 2017 Dec 25 11 726 10.3389/fnins.2017.00726 29317856 9 Buda O Arsene D Ceausu M Dermengiu D Curca GC Georges Marinesco and the early research in neuropathology Neurology 2009 Jan 6 72 1 88 91 10.1212/01.wnl.0000338626.93425.74 19122036 10 Crous-Bou M Minguillon C Gramunt N Molinuevo JL Alzheimer's disease prevention: from risk factors to early intervention Alzheimers Res Ther 2017 Sep 12 9 1 71 10.1186/s13195-017-0297-z 28899416 11 Jellinger KA Alzheimer 100 highlights in the history of Alzheimer research J Neural Transm (Vienna) 2006 Nov 113 11 1603 23 10.1007/s00702-006-0578-3 17039299 12 Lane CA Hardy J Schott JM Alzheimer's disease Eur J Neurol 2018 Jan 25 1 59 70 10.1111/ene.13439 28872215 13 Watwood C Alzheimer ' s Disease 2011 DLPS Faculty Publications Paper 39 14 Ehman EC Johnson GB Villanueva-Meyer JE Cha S PET/MRI: Where might it replace PET/CT? J Magn Reson Imaging 2017 Nov 46 5 1247 1262 10.1002/jmri.25711 28370695 15 Bateman RJ Xiong C Benzinger TL Fagan AM Clinical and biomarker changes in dominantly inherited Alzheimer's disease N Engl J Med 2012 Aug 30 367 9 795 804 10.1056/NEJMoa1202753 22784036 16 Hebert LE Weuve J Scherr PA Evans DA Alzheimer disease in the United States (2010-2050) estimated using the 2010 census Neurology 2013 May 7 80 19 1778 83 10.1212/WNL.0b013e31828726f5 23390181 17 Gaugler J James B Johnson T Scholz K Weuve J 2016 Alzheimer's disease facts and figures Alzheimer's Dement 2016 12 4 459 509 10.1016/j.jalz.2016.03.001 27570871 18 Naumenko AA Gromova DO Trofimova NV Preobrazhenskaya IS Alzheimer's disease: Diagnosis and treatment. Nevrol Neiropsikhiatriya Psikhosomatika 2016 8 4 91 7 19 Broom GM Shaw IC Rucklidge JJ The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease Nutrition 2019 60 118 21 10.1016/j.nut.2018.10.003 30554068 20 Van der Auwera I Wera S Van Leuven F Henderson ST A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease Nutr Metab (Lond) 2005 Oct 17 2 28 10.1186/1743-7075-2-28 16229744 21 Weller J Budson A Current understanding of Alzheimer's disease diagnosis and treatment F1000Res 2018 Jul 31 7 F1000 Faculty Rev-1161 10.12688/f1000research.14506.1 22 Chen L Huang H Duan WM Mao G Clinical neurorestorative progress in Parkinson's disease J Neurorestoratology 2015 101 107 10.2147/JN.S74144
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J Med Life J Med Life JMedLife Journal of Medicine and Life 1844-122X 1844-3117 Carol Davila University Press Romania JMedLife-16-186 10.25122/jml-2022-0173 Review The importance of CA 72-4 and CA 19-9 dosing in gastric cancer Rosu Mihai Catalin 12* Ardelean Andrei 12 Moldovan Silviu Daniel 1 Faur Flaviu Ionut 14 Nesiu Alexandru 13 Totoloci Bogdan Dan 12 1 Department of General Surgery, Faculty of Medicine, Vasile Goldis Western University of Arad, Arad, Romania 2 Department of General Surgery, Arad County Emergency University Hospital, Arad, Romania 3 Department of Urology, Arad County Emergency University Hospital, Arad, Romania 4 2nd General Surgery Clinic, Pius Brinzeu Emergency Clinical Hospital, Timisoara, Romania * Corresponding Author: Mihai Catalin Rosu, Department of General Surgery, Faculty of Medicine, Vasile Goldis Western University of Arad, Arad, Romania. E-mail: [email protected] 2 2023 16 2 186188 25 9 2022 01 2 2023 (c)2023 JOURNAL of MEDICINE and LIFE 2023 This article is distributed under the terms of the Creative Commons Attribution License ), which permits unrestricted use and redistribution provided that the original author and source are credited. Serological analysis of tumor markers has emerged as a non-invasive method for monitoring cancer patients, including tumor recurrence and response to treatment. Tumor markers have the potential to aid in both the diagnosis and prognosis of cancer, but their most important role currently lies in the monitoring of tumor progression. Tumor markers can also provide valuable information on treatment effectiveness, with changes in plasma values indicating tumor regression or progression. This research aimed to investigate the correlation between the serum detection values of three tumor markers - CEA, CA 19-9, and CA 72-4 - and their utility in the diagnosis and prognosis of patients with gastric cancer. The study seeks to uncover the relationship between these tumor markers and the evolution of gastric cancer, providing insights into their potential use in clinical practice. CA 72-4 CA 19-9 gastric cancer tumour marker pmcINTRODUCTION Gastric cancer is a major health concern worldwide, and serum markers have been investigated for their potential utility in diagnosis, prognosis, and follow-up of patients. Studies have reported elevated serum levels of CEA and CA19-9 in a significant proportion of patients with gastric cancer, ranging from 15% to 72%. However, the use of these markers for follow-up has shown some limitations, indicating a need for more sensitive performance markers to enhance gastric cancer treatment [1-3]. The monoclonal antibodies B72.3 and CC49 have been used to characterize high molecular weight mucus protein, formerly known as tumor-associated glycoprotein-72 (TAG-72), as a potential marker for various types of cancer since 1986. In particular, elevated serum levels of CA 72-4 have been observed in a significant proportion of patients with gastrointestinal malignancies, and ovarian, endometrial, lung, and breast cancer [4-6]. Some studies have rated CA 72-4 as a serological tumor marker for gastric cancer and have compared its clinical utility with other markers such as CEA or CA19-9. Multiple studies have found that serum levels of CA 72-4 show a strong correlation with tumor stage and the presence of lymph node involvement in gastric carcinoma. As a result, measuring serum levels of CA 72-4 is not considered useful for early assessment, but it can provide valuable insights into the potential recurrence of cancer. While previous research has investigated the correlation between preoperative CEA and CA 19-9 concentration and prognosis, there are limited reports on the prognostic value of CA 72-4 in gastric cancer . In this literature review, we explored the current understanding of serum markers for gastric cancer, with a particular focus on CA72-4, CEA, and CA19-9. We reviewed the literature related to their diagnostic accuracy, sensitivity, and specificity, as well as their potential for use in prognosis and follow-up. We also considered and compared the sensitivity of CA72-4 in different gastric cancer disorders and compared it to the sensitivity of CEA or CA19-9. By synthesizing the existing literature, we aimed to provide an overview of the current state of knowledge and identify areas for future research. MATERIAL AND METHODS To achieve the objectives of this study, a systematic search of the PubMed database was conducted. The search was limited to articles published between March 1st, 2015, and May 2022, and included the following keywords: "CEA", "CA 72-4", and "CA 19-9". Only articles written in English were evaluated. The final set of articles included in this study underwent a thorough review and analysis to provide a comprehensive overview of the current understanding of the sensitivity and prognostic value of these markers in the context of gastric cancer using a descriptive analysis. RESULTS CA72-4 as a prognostic marker Despite the multitude of markers that have been identified, CA 72-4 is of particular interest. Some preliminary studies have shown that CA 72-4 has elevated levels mainly in patients with gastrointestinal and ovarian cancer, while low values have been documented in patients with other types of cancer, such as breast, prostate, and lung cancer . Numerous other studies have outlined the clinical importance of the serological marker CA 72-4 in terms of the management of patients with gastric and gynecological cancer. Some preliminary studies have suggested that the presence of serum CA 72-4 was detected in 40% of patients with gastrointestinal adenocarcinoma, while subsequent reports focused on exploring potential correlations between CA 72-4 and other markers such as CEA and CA 19-9 . CA19-9 as a prognostic marker CA19-9 is an oligosaccharide present in both tissues and serum in the form of mucin-rich carbohydrates. It was first isolated in 1979 from colorectal carcinoma (Kaprowski) and is normally found in the fetal cells from the stomach, the intestine, the liver, and the pancreas. In adults, it is present in small amounts in the pancreas, the liver, the gallbladder, and the lungs and is an important component of many mucous cells and secretion products. CA 19-9 is used predominantly for the prognosis of pancreatic adenocarcinoma, but it is not a specific biomarker, its expression is also used in gastric cancer. High levels of CA 19-9 depend on the staging degree of gastric cancer, as shown by numerous studies in Japan . In the later stages of gastric cancer, CA 19-9 can be useful for both prediction and diagnosis. A recent study found that only 4.8% of patients who underwent radical (total) gastrectomy had elevated CA 19-9 values. Another study conducted in India reported a sensitivity of 42% and a negative predictive value of 63% for the CA 19-9 test in gastric cancer. A separate study involving 1,600 gastric cancer patients who underwent gastrectomy found that CA 19-9, CA 125, and CEA positivity rates were 20%, 42.3%, and 19.2%, respectively. The researchers also observed that CA 19-9 levels tended to increase more significantly in older and female patients compared to younger and male patients . CA72-4 as a prognostic marker CA 72-4 was first identified by Colcher in 1981 and has since been identified as a tumor-associated glycoprotein-72 antigen (TAG-72) in several epithelial cancers. Several recent studies have demonstrated the usefulness of CA 72-4 in the diagnosis and prognosis of gastric cancer. One study found that serum levels of TAG-72 expressed as CA 72-4 have a significant impact on the diagnosis of gastric cancer . An Italian longitudinal study with over 160 patients has highlighted the importance of monitoring serum levels of CA 72-4 in gastric cancer. The study demonstrated that CA 72-4 is an independent marker that can be used for the prognosis and assessment of recurrences in gastric cancer . The results showed that nearly half of the patients with recurrent gastric cancer had elevated serum levels of CA 72-4 before surgical interventions, compared to approximately 24 percent of patients without recurrence. These findings suggest that monitoring CA 72-4 levels could be valuable in detecting early signs of recurrence in gastric cancer patients. One French study reported that serum levels of CA 72-4 were associated with a poor prognosis in male patients with gastric cancer, even when their CA 19-9 and CEA levels were within the normal range before the start of treatment . In another recent study, 216 patients with gastric adenocarcinoma were examined to evaluate the serum levels of CEA, CA 19-9, and CA 72-4. The findings showed no significant differences in the values of CA 72-4, CEA, or CA 19-9 with regard to sex, age, or histological classification . Other markers associated with gastric cancer stem cells Recent studies have suggested a potential association between markers typically associated with gastric cancer stem cells, such as Lgr5 and Dclk1, and other cancer markers . For example, studies have shown that Lgr5 is overexpressed in gastric cancer and may play a role in the development and progression of the disease . Similarly, Dclk1 is upregulated in gastric cancer and may also play a role in the growth and spread of the disease . However, more research is needed to fully understand the connections between these markers and the role they play in gastric cancer development. Lgr5 (Leucine-rich repeat-containing G protein-coupled receptor 5) is a transmembrane protein that is considered a marker for cancer stem cells (CSCs) in various types of cancer, including gastric cancer. Lgr5 is a member of the G protein-coupled receptor (GPCR) family and is involved in signaling pathways related to cell growth, differentiation, and survival. Studies have shown that Lgr5 is overexpressed in gastric cancer and may play a role in the development and progression of the disease . It has been found that Lgr5+ cells can initiate and maintain tumors, and they are resistant to chemotherapy, making Lgr5 a promising therapeutic target for gastric cancer treatment. Therefore, Lgr5 may provide a potential target for developing new therapies for gastric cancer, as well as a diagnostic marker for identifying CSCs in gastric cancer . Dclk1 (doublecortin-like kinase 1) is a protein kinase that has been identified as a marker for cancer stem cells (CSCs) in various types of cancer, including gastric cancer. It is a member of the doublecortin-like kinase (DCLK) family, which is involved in the regulation of cell division, migration, and differentiation . Studies have shown that Dclk1 is upregulated in gastric cancer and may play a role in the growth and spread of the disease . Dclk1+ cells have been found to have higher tumorigenic and metastatic potential than . Furthermore, Dclk1+ cells are more resistant to chemotherapy and radiation, making Dclk1 a promising therapeutic target for gastric cancer treatment. Therefore, Dclk1 may provide a potential target for developing new therapies for gastric cancer, as well as a diagnostic marker for identifying CSCs in gastric cancer . DISCUSSION In this study, we aimed to evaluate the diagnostic and prognostic value of CEA, CA 19-9, and CA 72-4 in gastric cancer. Previous research has shown that elevated serum CEA levels are frequently predictive of advanced gastrointestinal carcinoma and are correlated with it . In addition, a persistent postoperative increase in CEA may signal the need for a second opinion procedure and the potential existence of local recurrence or metastasis . It is important to note, however, that not all patients with GI adenocarcinoma display positive preoperative or increasing postoperative serum CEA levels, and some do not experience disease recurrence . Compared to isolated biomarkers 72-4, combinations in GC patients show less co-presentation of CEA, CA 19-9, and CA . The combination of CEA, CA 19-9, and CA 72-4 is the most efficient option for staging surgery or chemotherapy for GC patients, according to the findings of this review. Higher sensitivity and specificity were demonstrated by the simultaneous detection of serum CEA, CA 19-9, CA 24-2, and CA 72-4 in people with GC and cardiac cancer . The specificity may be improved by routinely measuring the levels of serum CA 19-9, CA 72-4, and CEA at suitable intervals. However, it is important to note that this study has several limitations. The participant characteristics in the included studies varied, which could have affected the diagnostic utility of CA 19-9, CA 72-4, and CEA. Stratified analysis based on patient traits like blood type was not carried out due to the lack of available data. Additionally, the source of heterogeneity among the included studies was incomplete, as studies and patient characteristics were infrequently reported. Finally, publication bias is a problem that cannot be avoided in meta-analyses of published studies. To confirm the clinical importance of serum CA 72-4, CA 19-9, and CEA in gastric cancer, large prospective studies are required. These studies should focus on addressing the limitations of previous research, including controlling for patient characteristics, reporting complete study details, and avoiding publication bias. CONCLUSION The use of serum markers like CA 72-4 and CA 19-9, in addition to CEA, can aid in the diagnosis and monitoring of advanced gastric cancer, especially in cases where CEA levels are not detectable. Simultaneous measurement of these markers can improve the precision of treatment options like chemotherapy or second eye surgery. While these markers are not useful for screening early gastric cancer, they are important in detecting recurrent metastases and for post-therapeutic follow-up. However, careful consideration should be given to the combined measurements of CEA, CA 19-9, and CA 72-4, particularly when the values are at the limit or not significantly elevated. Further studies are needed to fully understand the clinical importance of these serum markers in gastric cancer and to develop more effective diagnostic and treatment strategies. 1 Liang Y Wang W Fang C Raj SS Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer Oncotarget 2016 7 49565 49573 10.18632/oncotarget.10391 27385101 2 Yang AP Liu J Lei HY Zhang QW CA72-4 combined with CEA, CA125 and CAl9-9 improves the sensitivity for the early diagnosis of gastric cancer Clin Chim Acta 2014 437 183 186 10.1016/j.cca.2014.07.034 25086284 3 Yu J Zhang S Zhao B Differences and correlation of serum CEA, CA19-9 and CA72-4 in gastric cancer Mol Clin Oncol 2016 4 441 449 10.3892/mco.2015.712 26998301 4 Yin LK Sun XQ Mou DZ Value of combined detection of serum CEA, CA72-4, CA19-9 and TSGF in the diagnosis of gastric cancer Asian Pac J Cancer Prev 2015 16 3867 3870 10.7314/apjcp.2015.16.9.3867 25987051 5 Korse CM Taal BG Bonfrer JM Vincent A An elevated progastrin-releasing peptide level in patients with well-differentiated neuroendocrine tumours indicates a primary tumour in the lung and predicts a shorter survival Ann Oncol 2011 22 2625 2630 10.1093/annonc/mdr007 21415235 6 Molina R Bosch X Auge JM Filella X Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site Tumour Biol 2012 33 463 474 10.1007/s13277-011-0275-1 22161237 7 Molina R Auge JM Alicarte J Filella X Pro-gastrin-releasing peptide in patients with benign and malignant disease Tumour Biol 2004 25 56 61 15192313 8 Guadagni F Roselli M Cosimelli M Mannella E TAG-72 (CA 72-4 assay) as a complementary serum tumor antigen to CEA in monitoring patients with colorectal cancer Cancer 1993 Oct 1 72 7 2098 106 10.1002/1097-0142(19931001)72:7<2098::aid-cncr2820720707>3.0.co;2-g 8374868 9 Guadagni F Roselli M Cosimelli M Ferroni P CA 72-4 serum marker a new tool in the management of carcinoma patients Cancer Invest 1995 13 2 227 38 10.3109/07357909509011692 7874576 10 Yu J Zhang S Zhao B Differences and correlation of serum CEA, CA19-9 and CA72-4 in gastric cancer Mol Clin Oncol 2016 Mar 4 3 441 449 10.3892/mco.2015.712 26998301 11 Gero EJ Colcher D Ferroni P Melsheimer R CA 72-4 radioimmunoassay for the detection of the TAG-72 carcinoma-associated antigen in serum of patients J Clin Lab Anal 1989 3 6 360 9 10.1002/jcla.1860030609 2614571 12 Ferroni P Szpak C Greiner JW Simpson JF CA 72-4 radioimmunoassay in the diagnosis of malignant effusions. Comparison of various tumor markers Int J Cancer 1990 Sep 15 46 3 445 51 10.1002/ijc.2910460320 2394511 13 Ohuchi N Takahashi K Matoba N Sato T Comparison of serum assays for TAG-72, CA19-9 and CEA in gastrointestinal carcinoma patients Jpn J Clin Oncol 1989 Sep 19 3 242 8 2810823 14 Ychou M Duffour J Kramar A Gourgou S Grenier J Clinical significance and prognostic value of CA72-4 compared with CEA and CA19-9 in patients with gastric cancer Dis Markers 2000 16 105 110 10.1155/2000/595492 11381189 15 Chen XZ Zhang WK Yang K Wang LL Correlation between serum CA724 and gastric cancer: multiple analyses based on Chinese population Mol Biol Rep 2012 39 9031 9039 10.1007/s11033-012-1774-x 22752725 16 Jing JX Wang Y Xu XQ Sun T Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer Asian Pac J Cancer Prev 2014 15 10267 10272 10.7314/apjcp.2014.15.23.10267 25556459 17 Guadagni F Roselli M Cosimelli M Ferroni P Correlation between positive CA 72-4 serum levels and lymph node involvement in patients with gastric carcinoma Anticancer Res 1993 Nov-Dec 13 6B 2409 13 8135475 18 Takahashi Y Takeuchi T Sakamoto J Touge T The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study Gastric Cancer 2003 6 142 145 10.1007/s10120-003-0240-9 14520526 19 Wu XS Xi HQ Chen L Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival World J Surg Oncol 2012 Nov 15 10 244 10.1186/1477-7819-10-244 23153436
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34916 Internal Medicine Radiology Pulmonology Viral Myocarditis in the Setting of Delayed Manifestation of Hamman-Rich Syndrome Muacevic Alexander Adler John R Kabra Ruchita 1 Kumar Sunil 1 Acharya Sourya 1 Bhansali Pratik J 2 Daiya Varun 1 1 Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, IND 2 Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, IND Ruchita Kabra [email protected] 13 2 2023 2 2023 15 2 e3491618 10 2022 13 2 2023 Copyright 2023, Kabra et al. 2023 Kabra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Acute respiratory distress syndrome (ARDS)-like symptoms and rapid progression characterize the interstitial lung disease known as acute interstitial pneumonitis, also known as Hamman-Rich syndrome. It has a bad prognosis and a high incidence of mortality. We describe the case of a 25-year-old male patient with acute-onset type I respiratory failure with detrimental X-ray abnormalities who presented to the emergency room without any history of pulmonary disease or smoking. The provisional diagnosis of Hamman-Rich syndrome was reached after other clinical entities were ruled out based on CT findings. Myocardial hypokinesis of the apex and septum, as well as a modest systolic dysfunction (ejection fraction: 50%) similar to acute myocarditis, were detected by echocardiogram. Acute myocarditis in the setting of Hamman-Rich syndrome has been anecdotally reported and its mechanism remains to be elucidated. interstitial pulmonary diagnosis rapidly progressive acute respiratory distress syndrome The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction The term "acute interstitial pneumonia" (AIP) refers to an idiopathic clinical and pathological disorder. Clinically, it can be differentiated from other, more enduring forms of interstitial pneumonia that develop quickly and resultin respiratory failure. It is also knownas Hamman-Rich syndrome and affects those who do not already have lung illness. Thehistopathological findings show diffuse alveolar injury. Hamman-Rich syndrome is characterized by the sudden onset of dyspnoea or tachypnoea with severe hypoxia or acute respiratory failure, as well as bilateral lung infiltrates on chest X-ray. Patientsusually presentwith flu-like symptoms, which develop quickly. The etiology of Hamman-Rich syndrome is not well understood; however, it can result from a single trauma. This trait sets it apart from other similar disorders. Acute and chronic interstitial pneumonia differin terms ofpathologic lesions of varying ages and include interstitial inflammation in diverse lung locations, normal parenchyma, fibroblast foci, and honeycomb change . Three phases of alveolar damage are associated with AIP: an initial exudative phase, a later organized proliferative phase, and a final fibrotic phase . With a reported three-month mortality rate of 70% , the condition has a bad prognosis. The primary goal of treatment for this illness involves managing respiratory failure and its consequences. For the most part, the recommendations, which are based on a wealth of currently available evidence on the treatment of acute respiratory distress syndrome (ARDS), are directed toward concomitant respiratory dysfunction. Despite its ubiquity and the virus's poor prognosis, there is scarce information available on its cardiac consequences. Case presentation A 25-year-old male, a welder by occupation,presented to the hospital with a cough that had started suddenly and worsened progressively, eventually becoming productive and accompanied by shortness of breath. He had a history of fever for two days and loss of appetite for six to seven days, but no history of chest discomfort, palpitations, orthopnea, or paroxysmal nocturnal dyspnea during coughing. There was no previous history of similar episodes. The patient did not have any complaints of headaches, loss of consciousness, or seizures. He was admitted to the intensive care unit based on the above complaints and was extensively evaluated; the initial findings were as follows: a body temperature of 39 C, pulse rate of 116 beats/minute, and blood pressure of 98/70 mmHg. On room air, oxygen saturation was 84%, while it was 96% on high-flow oxygen, with a respiratory rate of 38 beats/minute. The patient was kept on intermittent bilevel positive airway pressure (BiPAP) support due to tachycardia, tachypnoea, and dyspnoea. Chest radiography revealed opacities in the bilateral lower lung field . Figure 1 Chest X-ray showing bilateral opacities (arrows) His laboratory reports showed a normal white blood cell count of10,300/cumm with predominant cells neutrophils, platelets count of 60,000/ul, high C-reactive protein (CRP) of 102.02 mg/L, aspartate aminotransferase (AST) of 84 u/L, alanine aminotransferase (ALT) of 98 u/L, alkaline phosphatase (ALP) of 195 u/L, erythrocyte sedimentation rate (ESR) of 110, and D-dimer of 581 mg/ml. To rule out infective etiology, antibodies for the malarial parasite, dengue, leptospira, and scrub typhus were done, which were negative. His condition rapidly deteriorated on day two of admission with tightening of his chest and dyspnoea. His electrocardiogram suggested sinus tachycardia with cardiac enzymes CKMB-40 and negative troponin-I. Chest X-ray revealed diffuse bilateral opacities. Echocardiography showed standard valves, mildly dilated left ventricle, and mild global hypokinesia with pericardial effusion suggestive of myocarditis with an ejection fraction of 47%. CT of the thorax suggested multifocal ground-glass opacities with patchy areas of consolidation and tractional bronchiectasis . Figure 2 HRCT thorax image showing ground-glass opacities with patchy areas of consolidation (left arrow) and traction bronchiectasis (right arrow) HRCT: high-resolution computed tomography A reverse transcription-polymerase chain reaction (RT-PCR) for coronavirus disease 2019 (COVID-19) was done, which was negative. Taking the above clinical evidence together with the patient's occupational history into account, he was diagnosed with AIP, aka Hamman-Rich Syndrome. He was treated with higher levels of intravenous antibiotics, steroids, diuretics, nebulization, and intermittent BiPAP with oxygen support. After six days of aggressive treatment, there was a subtle relief in his symptoms, and oxygen support was tapered and weaned off. The patient was shifted to the general ward for observation and was discharged after nine days of hospital stay. On follow-up, the patient was found to be doing well. His blood counts were repeated and were within normal limits. Discussion Hamman-Rich syndrome is a clinicopathological condition described as sudden-onset widespread fibrosis of interstitial lungs, acute interstitial pneumonia, and an accelerated variant of interstitial pneumonitis. Current diagnostic criteria for AIP includeidiopathic ARDS,clinical condition, andhistological evidence of organized diffuse alveolar damage. It is also defined as the quick onset of respiratory failure in a previously healthy person who has never had a respiratory illness. The clinical presentation of AIP has been described in the literature . The disease frequently strikes suddenly, with a prodromal sickness lasting one to two weeks before presentation. Cough, fever, and dyspnoea are the most prevalent signs . It is not linked to cigarette smoking and affects men and women equally. The bulk of the patients is between the ages of 50 and 55 years . While the exact cause of interstitial pneumonia is unknown, current research has indicated some plausible pathogenetic processes . Thediagnosis of AIP can be made clinically based on the idiopathic ARDS clinical presentation and the absence of other diagnoses after investigation. AIP diagnosis in many patients is made according to clinical history, physical examination, and noninvasive investigations. Biopsy of the lung should be avoided in these patients since it will not change their treatment plan . A widespread, bilateral air-space opacification feature might be seen on a chest X-ray of the patients. Patchy ground-glass opacities with symmetrical and bilateral involvement are seen on the CT of the thorax. As a result, AIP is clinically and radiologically similar to ARDS. This AIP may be exacerbated by any viral infection, which must be ruled out . In this case, viral markers for COVID-19 and H1N1 influenza were done, which were negative; however, in light of the persistent tachycardia, myocarditis was kept as one of the possibilities. Supportive care, such as supplemental oxygen and ventilatory support, is usually the core aspect of therapy. Several studies have found that using glucocorticoids in treating AIP is beneficial, although others have reached the opposite conclusion . Even with extensive therapy, such as mechanical ventilation, AIP has a high mortality rate (>60%), with the majority of the patients dying within six months of diagnosis . For example, one who survives AIP has a near-zero recurrence rate and has complete recovery or near-total recovery of lung function . In this case, we lost the patient to follow-up after two months. Hence, we could not perform a pulmonary function test. Clinicians frequently use corticosteroids in conjunction with ventilation; however, their usefulness is debatable. Some studies have demonstrated that immunosuppressive therapy has a modest effect, while others have shown a beneficial effect and a better prognosis . Even though lung-protective measures have been found to reduce mortality, AIP is still linked with a dismal prognosis. This sheds light on our limited understanding of the condition and, consequently, our inability to manage it effectively. Conclusions In the event of an ARDS pattern, Hamman-Rich syndrome is frequently a diagnosis of exclusion. This case report illustrates thechallenges clinicians facein correctly diagnosing and treating AIP. Early diagnosis may be hampered by the need to rule out any identified cause or predisposing factor. As an exclusionary diagnosis, a high index of suspicion is required to evaluate with clinical investigations, particularly in the early stages of the disease. AIP should be firmly kept as a differential diagnosis when encountering cases of quickly progressing interstitial pneumonia. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Hamman-Rich syndrome: a forgotten entity Monaldi Arch Chest Dis Newmarch W Puopolo A Weiler M Casserly B 799 87 2017 28635201 2 Erratum to "Diagnosis of usual interstitial pneumonia and distinction from other fibrosing interstitial lung diseases" [Hum Pathol 39 (2008) 1275-1294] Hum Pathol Katzenstein AL Mukhopadhyay S Myers JL 1562 1581 39 2008 19653362 3 Acute interstitial pneumonia Eur Respir J Bouros D Nicholson AC Polychronopoulos V 412 418 15 2000 10706513 4 Acute interstitial pneumonitis. Case series and review of the literature Medicine (Baltimore) Vourlekis JS Brown KK Cool CD Young DA Cherniack RM King TE Schwarz MI 369 378 79 2000 11144035 5 Acute interstitial pneumonia Clin Chest Med Vourlekis JS 739 747 25 2004 15564019 6 Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia Blood Okamoto M Kato S Oizumi K 1289 1298 99 2002 11830478 7 Low hospital mortality in patients with acute interstitial pneumonia Chest Quefatieh A Stone CH DiGiovine B Toews GB Hyzy RC 554 559 124 2003 12907542 8 Acute interstitial pneumonia: report of a series Eur Respir J Bonaccorsi A Cancellieri A Chilosi M Trisolini R Boaron M Crimi N Poletti V 187 191 21 2003 12570127 9 Acute interstitial pneumonia-Hamman-Rich syndrome: clinical characteristics and diagnostic and therapeutic considerations Anesth Analg Avnon LS Pikovsky O Sion-Vardy N Almog Y 232 237 108 2009 19095855 10 Myopericarditis - a catastrophic complication of dengue fever J Family Med Prim Care Giri A Acharya S Kamat S Shukla S Kumar S 6553 6555 11 2022 36618179 11 Pericarditis in Covid 19 an unusual presentation J Evol Med Dent Sci Wadekar A Hepat S Acharya S Kumar S 2532 2535 10 2021 12 Acute exacerbation of idiopathic pulmonary fibrosis with pirfenidone and nintedanib: a friend or foe Cureus Kaushal M Talwar D Prajapat D Kumar S Acharya S Talwar D 0 14 2022
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As the accuracy and throughput of nanopore sequencing improve, it is increasingly common to perform long-read first de novo genome assemblies followed by polishing with accurate short reads. We briefly introduce FMLRC2, the successor to the original FM-index Long Read Corrector (FMLRC), and illustrate its performance as a fast and accurate de novo assembly polisher for both bacterial and eukaryotic genomes. de novo assembly polishing nanopore National Institutes of Health 10.13039/100000002 K01DK119582 pmcIntroduction Long-read, third-generation sequencing technologies including Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio) are increasingly the workhorse and backbone of de novo genome assemblies (Kim et al. 2021; Pollard et al. 2018; Amarasinghe et al. 2020). Median read lengths from 10 to 100 s of kilobases are routinely achieved (Shi et al. 2016; Michael et al. 2018), with which modern assemblers produce much more contiguous and complete de novo assemblies than those from short-read next-generation sequencing (NGS) alone (Pollard et al. 2018; Amarasinghe et al. 2020). Despite continuous improvement in nucleotide-level accuracy of long-read sequencing, residual errors both single-nucleotide mismatches and short insertions and deletions (indels) still exceed short-read sequencing-by-synthesis technologies (Pollard et al. 2018; Amarasinghe et al. 2020). Residual consensus errors in long-read assemblies are dominated by indels which hinder gene annotation (Watson and Warr 2019). A "hybrid" assembly approach is commonly taken to maximize assembly accuracy and contiguity by first producing a draft assembly from long-read sequences, followed by polishing with accurate short reads (Jain et al. 2018). FM-index Long Read Corrector (FMLRC; Wang et al. 2018) is a hybrid error-correction method that employs a Full-text Minute-space (FM) index of a Burrows-Wheeler transform (BWT) built from accurate reads to dynamically reassemble erroneous subregions of error-prone long sequences. FMLRC has proven a consistently accurate and efficient method for correcting sequencing errors in raw long reads (Fu et al. 2019; Zhang et al. 2020). FMLRC2 produces largely identical results to FMLRC albeit with improved speed and stability. In addition to its proven utility for raw error correction, we demonstrate the effectiveness of FMLRC2 as a de novo assembly polisher for diverse prokaryotic and eukaryotic genomes. FMLRC2 consistently outperforms extant genome polishing tools in minimizing residual assembly errors (mismatches and indels) and computational requirements. Methods FMLRC2 FMLRC2 represents a reimplementation of the original FMLRC from C++ to Rust, without major changes to the underlying algorithm. In benchmark tests, it is about 50% faster than FMLRC (supplementary table S1, Supplementary Material online). FMLRC2 is open source and publicly available at Datasets We evaluated FMLRC2 against de novo assemblies from 24 bacterial and 6 eukaryotic datasets. Bacterial datasets include four independent datasets from each of six bacterial isolates (A. baumannii J9, C. koseri MINF_9D, E. kobei MSB1_1B, Haemophilus M1C132_1, K. oxytoca MSB1_2C, and K. variicola INF345) (Wick et al. 2021b). Long-read-only assemblies for each were performed using Trycycler v0.5.0 (Wick et al. 2021a) and Medaka v1.4.3 ). These data are publicly available at We additionally used two publicly available sets of ONT sequence data from each of three well-established model eukaryotic organisms: Saccharomyces cerevisiae (S288C), Arabidopsis thaliana (Columbia; TAIR10.1), and Drosophila melanogaster (ISO-1) [table 1]. Experimental sequencing datasets (ONT and Illumina/BGI) were obtained from NCBI (table 2). We simulated ONT data and the corresponding paired-end Illumina dataset using Badread v0.2.0 (Wick 2019) and ART v2016-06-05 (Huang et al. 2011) as previously described (Wick and Holt 2022). Briefly, short reads were simulated using ART with HiSeqX TruSeq preset, to 100X effective sequencing depth, 150 bp read length, 400 +- 50(sd) bp mean fragment. Long reads were simulated using Badread with parameters "-length 20000,12000-identity 90,98,4". These eukaryotic simulated data are available from Dryad: Basic statistics and coverage of simulated data are described in table 3. FastQC v0.11.9 (Andrews 2010) was used to check for quality issues among experimental short-read datasets. Where necessary, fastp v0.23.2 (Chen et al. 2018) was used to clean the short-read datasets and remove Ns prior to downstream polishing. Long-read-only assemblies were generated for each of the nine experimental and simulated eukaryotic ONT datasets using Flye v2.8.1 (Kolmogorov et al. 2019) followed by Medaka v1.4.3 with default parameters. Table 1. Eukaryotic Model Organisms Used for Assembly Polishing Evaluation. Species Strain/Genome Refseq Accession Genome Size (Mbp) Saccharomyces cerevisiae S288C GCF_000146045.2 12.16 Arabidopsis thaliana Columbia (TAIR10.1) GCF_000001735.4 119.67 Drosophila melanogaster ISO-1 GCF_000001215.4 143.73 Table 2. Experimental Datasets Used for Performance Evaluation. Species Sequence Type Accession Number Number of Reads Average Read Length (bp) Mean Coverage Saccharomyces cerevisiae ONT SRR17374240* 105,371 13,726 106x ONT ERR1883398 49,617 8,322 17x BGI SRR17374239 48.6m 150 600x Arabidopsis thaliana ONT SRR12136402 2,551,376 4,473 73x ONT SRR16832054** 512,896 27,757 104x Illumina SRR12136403 141m 150 177x Drosophila melanogaster ONT SRR13070614 372,834 13,741 34x ONT SRR13070625 640,215 11,142 47x Illumina SRR6702604 41.2m 151 43x Note. Seqtk was used to subsample. *15% or **30% of the ONT reads for initial assembly. Table 3. Simulated Datasets Used for Performance Evaluation. Species Simulator Number of Reads Average Read Length (bp) Mean Coverage Saccharomyces cerevisiae Badread (long reads) 19,185 24,841 102x ART (short reads) 8.1m 150 100x Arabidopsis thaliana Badread (long reads) 19,540 24,306 100x ART (short reads) 79.6m 150 100x Drosophila melanogaster Badread (long reads) 16,268 24,162 98x ART (short reads) 94.8m 150 100x Polishing and Performance Assessment FMLRC2 v0.1.6 using RopeBWT2 (r187; Li 2014), HyPo v1.0.3 (Kundu et al. 2019), NextPolish v1.4.0 (Hu et al. 2020), ntEdit v1.3.5 (Warren et al. 2019), Pilon v.1.24 (Walker et al. 2014), POLCA v4.0.8 (Zimin and Salzberg 2020), Polypolish v0.5.0 (Wick and Holt 2022), Racon v1.5.0 (Vaser et al. 2017), and wtpoa (Ruan and Li 2019) were used to polish nanopore-only bacterial and eukaryotic assemblies. Each polisher was run once on each assembly using the default parameters, unless otherwise specified. The resulting polished eukaryotic assemblies were then compared against their respective reference genomes using QUAST v5.0.2 (Gurevich et al. 2013). Bacterial assemblies were compared against the respective reference for simulated data or in a pairwise fashion for experimental data as described in Wick and Holt (2022). Briefly, global alignments were computed between polished assemblies and the reference or species-matches assemblies for the simulated and experimental datasets, respectively. Total residual errors or total pairwise distance are equivalent to the edit distance, including mismatches and indels. Computational performance (CPU time and memory usage) was determined using "/usr/bin/time -v." For eukaryote assemblies, Pilon was run four times in succession, showing iterative improvements. As previously shown by Wick and Holt (2022), Pilon rarely produced significant improvement after the first iteration for bacterial assemblies. Results We evaluated FMLRC2 against seven other state-of-the-art assembly polishing methods using a combination of simulated and experimental short-read datasets spanning a wide variety of bacterial species and three eukaryotes. Since the ground truth is known for the simulated datasets and reference lines of eukaryotes, we evaluated based on total residual errors among polishing results for simulated bacteria and all eukaryotic datasets (fig. 1 and fig. 2, respectively). Table 4 presents the average residual errors per 100 kbp among simulated and experimental datasets from eukaryotes and the average CPU time and memory usage per polishing run. For experimental bacterial data, we use the total pairwise distance among technical replicates as an indicator of polishing accuracy (fig. 3). Polishing with FMLRC2 results in a dramatically lower residual error and pairwise distance among bacterial datasets. Likewise, it produces the fewest residual errors among eukaryotic datasets, albeit not dramatically lower than the other best-performing methods. However, FMLRC2 requires far less CPU time than the other methods, and 15x faster than the next best-performing method, NextPolish. The memory (RAM) usage is comparable to the other high-performing methods (except ntEdit and wtpoa, which have noticeably poor polishing accuracy). Fig. 1. Overall residual errors for polished simulated bacterial genomes. The solid line indicates the mean; dashed indicates the median. Fig. 2. Residual errors per 100 kbp after polishing for experimental and simulated eukaryotic datasets. The solid line indicates the mean; dashed indicates the median. Fig. 3. Sum of pairwise differences among replicates from experimental bacterial datasets. The solid line indicates the mean; dashed indicates the median. Table 4. Performance of Assembly Polishers Averaged Over Two Experimental and One Simulated Dataset From Each of the Three Species. Method Mismatches Indels Combined CPU Time (s) RAM (GB) unpolished 65.9 299.5 365.4 - - HyPo 29.7 19.4 49.0 32924 29.6 NextPolish 31.4 14.7 46.1 59209 10.5 ntEdit 52.2 99.1 151.2 7185 1.7 Pilon (x1) 34.5 24.3 58.8 33268 26.2 Pilon (x2) 28.7 21.1 49.8 - - Pilon (x3) 28.5 19.9 48.4 - - Pilon (x4) 28.5 19.8 48.3 141615 65.6 POLCA 30.5 20.2 50.7 27166 15.7 Polypolish 29.3 27.5 56.8 107703 165.3 Racon 30.1 62.9 92.9 84497 69.3 wtpoa 56.9 127.2 184.1 32061 2.7 FMLRC2 (default) 31.0 12.7 43.7 3955 14.2 FMLRC2 (eukaryote) 27.8 13.1 40.9 4387 14.3 Bold values indicate the best performing method for each metric. Note. Mismatches and indels represent the average residual errors per 100 kbp. Resource usage was not recorded for intermediate iterations of Pilon after the first, but run time is expected to scale linearly with the number of iterations. Results of polishing the Drosophila melanogaster datasets with FMLRC2 using its default parameters (-branch_factor 4, -cache_size 8, -k 21 59, -min_count 5, -min_frac 0.1) showed relatively poor performance correcting mismatch errors, especially among simulated datasets. We hypothesized that these errors occur in highly repetitive sequences (the likes of which do not exist in most bacterial genomes) when the representation of the true "version" of the repeat falls below the absolute or relative minimum count (min_count and min_frac, respectively). To address this, we evaluated all eukaryotic datasets using alternate parameter settings optimized for resolving these repetitive element problems (-k 21 59 80, -min_frac 0), dubbed "eukaryote mode." With these settings, the average residual error across eukaryotic assemblies polished with FMLRC2 is further reduced at the cost of a ~10% increase in CPU time (fig. 2, table 4). Of note, however, FMLRC2 using the default settings still outperforms all other evaluated methods. Discussion and Conclusion While the cost of third-generation long-read sequencing, including ONT, continues to decrease, and accuracy increases, hybrid multi-technology methods remain an efficient and effective approach for de novo genome assembly. Following FMLRC's proven performance as an error correction tool for raw reads, we demonstrate FMLRC2's exceptional performance as a polishing tool for de novo nanopore-based assemblies in both bacteria and simple eukaryotes. FMLRC2 outperforms the other tested polishing tools in reducing the residual assembly error, as illustrated using simulated and real ONT sequencing datasets. Assemblies polished with FMLRC2 have the fewest mean residual errors, while FMLRC2 is also the fastest method over an order of magnitude faster than the next most accurate tool. Supplementary Material msad048_Supplementary_Data Click here for additional data file. Supplementary Material Supplementary data are available at Molecular Biology and Evolution online. Funding This work was supported in part by the National Institutes of Health (K01DK119582 to JRW). Data Availability FMLRC2 is open source and publicly available at Bacterial data are publicly available at and simulated eukaryotic data at
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Skin Appendage Disord Skin Appendage Disord SAD Skin Appendage Disorders 2296-9195 2296-9160 S. Karger AG Allschwilerstrasse 10, P.O. Box * Postfach * Case postale, CH-4009, Basel, Switzerland * Schweiz * Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, [email protected] 10.1159/000528253 sad-0009-0094 Research Article Low Rates of Psychosocial Screening and Lifestyle Counseling in Hidradenitis Suppurativa Patients in the USA Shih Terri a De Devea R. b Rick Jonathan c Shi Vivian Y. c Hsiao Jennifer L. d * aDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA bUniversity at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA cDepartment of Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA dDepartment of Dermatology, University of Southern California, Los Angeles, California, USA *Jennifer L. Hsiao, [email protected] Terri Shih and Devea R. De contributed equally to this work. 3 2023 5 1 2023 1 3 2024 9 2 9498 21 6 2022 7 11 2022 2023 Copyright (c) 2023 by The Author(s). Published by S. Karger AG, Basel 2023 This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher. Introduction Although hidradenitis suppurativa (HS) is associated with psychosocial comorbidities such as depression as well as modifiable comorbidities such as obesity, rates of psychosocial screening and lifestyle counseling in the USA have not been characterized. Methods This cross-sectional study utilized publicly available data from the National Ambulatory Medical Care Survey (NAMCS) between 2008 and 2018 to identify visits with a diagnosis of HS (ICD-9 code 705.83, ICD-10 code L73.2). T tests and multivariate logistic regressions analyzed trends in rates of screening and counseling while controlling for race, sex, and age. Survey weights are applied to each visit to represent a national sample. Results Depression screening was completed in only 2% of reported visits. No visits reported screening for alcohol misuse, substance abuse, or domestic violence. There were low rates of counseling for weight reduction (7.8%), diet and nutrition (3.3%), exercise (2.4%), smoking (1.0%), and substance abuse (0.7%). Black patients and individuals with public health insurance received less screening and counseling overall. Conclusion Rates of psychosocial screening and counseling on lifestyle modifications are low in ambulatory clinic visits for HS patients, and there are disparities based on race and insurance status. Implementing strategies to incorporate routine psychosocial screening and lifestyle counseling into visits may improve HS patient outcomes. Keywords Hidradenitis suppurativa Psychosocial screening Lifestyle counseling This article has no funding source. pmcIntroduction Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin condition characterized by painful nodules, abscesses, sinus tracts, and scarring that imparts significant physical and psychosocial burdens. Associated comorbidities include smoking, obesity, metabolic syndrome, cardiovascular disease, depression, anxiety, and substance use disorder, among others . Risk of intimate partner violence has been reported to be 2.4 times more likely in individuals with HS as compared to those with acne . Screening for psychosocial conditions such as depression and domestic abuse and counseling for lifestyle modifications such as diet and exercise are important components of a comprehensive care strategy for HS. However, few studies have characterized how frequently this screening or counseling occurs for patients with HS. Herein, we examine characteristics of HS ambulatory visits and the rates of psychosocial screening and counseling in patients with HS in the USA. Methods The National Ambulatory Medical Care Survey (NAMCS) is conducted annually by the National Center for Health Statistics from the Centers for Disease Control and Prevention, which utilizes a stratified, random sample of patient visits to nonfederal, ambulatory office-based physicians. Physicians are randomly assigned a 1-week reporting period. A random sample of visits is assessed for data on patient demographics and symptoms and physician diagnoses and management, including screening and counseling, medications prescribed, and procedures completed. Survey weights are applied to each visit to represent a national sample. In this study, we searched publicly available NAMCS data between 2008 and 2018 (2017 was unavailable) for visits with a diagnosis of HS (ICD-9 code 705.83, ICD-10 code L73.2). Descriptive statistics were completed for demographic data and rates of psychosocial screening and lifestyle modification counseling. T tests and multivariate logistic regressions analyzed trends in rates of screening and counseling while controlling for race, sex, and age. Multivariate race comparisons excluded the category of race reported as "other" due to small sample size. Visits with missing data in relevant analyses were excluded. All data analyses were performed using SAS Studio 9.04.01 (SAS Institute, Cary, NC, USA). Variance in the complex survey design is accounted for by utilizing survey weights to create national estimates and confidence intervals (CI). Results From the 2008-2018 NAMCS datasets, an estimated 2.33 million visits (95% CI, 1.95 million-2.71 million) had a diagnosis of HS. Of these, 71.1% of the patients were female, 75.6% were white, and the mean age was 37.9 +- 1.0 (range 12-69) (Table 1). Depression screening was completed in a small minority (2.0%) of visits, none of which were completed in black patients (Table 2). Depression screenings were slightly less likely to be conducted in older patients (OR, 0.94 [95% CI, 0.91-0.98], p = 0.003). No visits reported screening for alcohol misuse, substance abuse, or domestic violence. Physicians reported overall low rates of counseling for weight reduction (7.8%), diet and nutrition (3.3%), exercise (2.4%), smoking (1.0%), and substance abuse (0.7%) (Table 2). Black patients were more likely to be counseled on weight reduction (OR, 4.95 [95% CI, 2.02-12.13], p = 0.003) but less likely to receive diet and nutrition counseling (OR, 0.52 [95% CI, 0.32-0.85], p = 0.01). Of visits that reported counseling on exercise, substance abuse, and tobacco use, none were completed in black patients. Older patients were slightly less likely to receive counseling on diet/nutrition (OR, 0.98 [95% CI, 0.96-1.00], p = 0.01), exercise (OR, 0.94 [95% CI, 0.91-0.97], p = 0.001), and weight reduction (OR, 0.90 [95% CI, 0.87-0.94], p < 0.001). There was no statistically significant difference in rates of counseling between men and women. Patients with higher BMI were more likely to receive counseling on exercise (OR, 1.24 [95% CI, 1.09-1.41], p = 0.002), weight reduction (OR, 1.09 [95% CI, 1.06-1.12], p < 0.001), and diet/nutrition (OR, 1.07 [95% CI, 1.05-1.08], p < 0.001) after controlling for age, sex, and race. Visits funded by public insurance including Medicare and Medicaid less frequently received counseling overall. They were significantly less likely to receive counseling on weight reduction (OR, 0.08 [95% CI, 0.01-0.79], p = 0.03). Discussion Rates of psychosocial screening and lifestyle counseling at ambulatory visits were low among patients with HS. Overall, individuals who were black or had public health insurance received less depression screening and lifestyle counseling. Given rates of depression in HS patients have been found to be as high as 26% and there is an increased risk of suicide in HS patients , routine depression screening is warranted . However, the rate of depression screening was found to be only 2% in ambulatory clinic visits for HS patients in our study. The rate of substance use disorder in the USA has been found to be 4% in HS patients versus 2% in control patients . One cross-sectional study interviewed 243 Canadian patients (128 with HS, 115 with acne) and found 2.4 times of risk of intimate partner violence compared to patients with acne . However, none of the visits across the 10-year span of our study reported screenings on substance use and domestic violence, highlighting a potential practice gap. HS is associated with smoking, obesity, and poor cardiovascular outcomes . Though more data are needed, studies have suggested a correlation between smoking status and HS severity and duration , and weight reduction has been linked to HS disease improvement . Regardless of impact on HS disease activity, counseling on lifestyle modifications for diet, exercise, and smoking cessation should be performed for the overall health of HS patients. Of note, addressing lifestyle changes after the first establishing rapport with patients is helpful . Racial and socioeconomic disparities were observed in the rates of depression screening and lifestyle counseling in patients with HS. Black patients and individuals with public health insurance received less screening and lifestyle counseling overall. It is imperative that depression screening and lifestyle counseling increase for all patients with HS, with particular attention paid to underserved populations. This is especially noteworthy as black patients and patients with low socioeconomic status are disproportionately affected with HS . Limitations of the NAMCS database include lack of data on HS severity. Given HS is associated with delayed and missed diagnoses , the number of HS ambulatory visits may be underrepresented. The NAMCS database may not capture all performed screenings for depression and other psychosocial conditions or counseling of lifestyle modifications. Given overall low-estimated total HS visits and screening and counseling rates, comparisons were not made across provider specialties. In addition, visits with missing data were excluded in our analyses. Underscreening for depression and substance abuse in HS patients may be due to lack of awareness. Additionally, integrating mental health screening and lifestyle modification counseling into time-constrained clinic visits may be challenging. Quick screening measures such as the Patient Health Questionnaire-2 for depression and implementation of streamlined mental health referral pathways may be useful . Providing handouts on lifestyle modifications can increase patient's understanding of their comprehensive management plan in an efficient manner . All specialties caring for HS patients should aim to incorporate psychosocial screening and lifestyle counseling into their care to improve patient outcomes. Statement of Ethics Ethical approval and consent were not required as this study was based on publicly available data. The National Center for Health Statistics (NCHS) Ethics Review Board reviews the content of the National Ambulatory Medical Care Surveys to ensure compliance with NCHS practices and procedures. Additional information can be found on www.cdc.gov/nchs/ahcd/index.htm. The National Ambulatory Medical Care Surveys fall under Title 42, US Code, section 242K, which permits data collection for health research. NCHS will not disclose responses in identifiable form without the consent of the individual or establishment in accordance with section 308(d) of the Public Health Service Act and the Confidential Information Protection and Statistical Efficiency Act of 2018. Additional information can be found on www.cdc.gov/nchs/ahcd/index.htm. Conflict of Interest Statement Jennifer L. Hsiao is on the board of directors for the Hidradenitis Suppurativa Foundation; has served as a consultant for Boehringer Ingelheim, Novartis, and UCB; and has served as a consultant and speaker for AbbVie. Vivian Y. Shi is on the board of directors for the Hidradenitis Suppurativa Foundation (HSF); is a stock shareholder of Learn Health; and has served as an advisory board member, investigator, speaker, and/or received research funding from Sanofi Genzyme, Regeneron, AbbVie, Eli Lilly, Novartis, SUN Pharma, LEO Pharma, Pfizer, Incyte, Boehringer Ingelheim, Aristea Therapeutics, Menlo Therapeutics, Dermira, Burt's Bees, Galderma, Kiniksa, UCB, WebMD, TARGET Pharmasolutions, Altus Lab, MYOR, Polyfin, GpSkin, and Skin Actives Scientific. There was no financial transaction for the preparation of this manuscript. All other authors report no conflicts of interest. Funding Sources This article has no funding source. Author Contributions Terri Shih and Jonathan Rick completed data analysis. Terri Shih and Devea R. De drafted the manuscript. Jonathan Rick, Vivian Shi, and Jennifer Hsiao edited and reviewed the manuscript. Vivian Shi and Jennifer Hsiao conceptualized and led the project. Data Availability Statement All data files are available from publicly available websites accessible through the CDC website, www.cdc.gov/nchs/ahcd/index.htm. Further inquiries can be directed to the corresponding author. Table 1 Survey-weighted visit demographics and characteristics of HS visits Demographics % of total 95% CI Age, years, mean+-SD (range) 37.9+-1.0 (12-69) 0-17 3.7 0.0-7.5 18-39 54.7 45.2-64.2 40-59 31.5 20.8-42.3 60+ 10.1 6.3-13.9 Female 71.1 59.6-82.6 Hispanic or Latino 5.7 0.4-11.0 Race White 75.6 67.9-83.3 Black 23.0 15.4-30.6 Other 1.4 0.6-2.2 Types of payment Private insurance 57.2 45.6-68.7 Non-Medicare public health insurance program 29.7 18.6-40.7 Medicare 8.8 5.0-12.6 Self-pay 1.1 0.0-2.6 Specialty of visit provider Dermatology 30.2 20.5-39.9 Family practice 24.2 16.4-32.0 General surgery 18.9 13.2-24.6 Internal medicine 6.6 0.0-15.8 Pediatrics 1.2 0.1-2.4 Obstetrics and gynecology 0.4 0.3-0.4 Table 2 Multivariate comparisons of screening and counseling rates during survey-weighted ambulatory visits* Overall Sex Race Insurance statusa female male p value white black p value Public other p value Depression screeningb 2.0 (1.3-2.7) 1.7 (1.4-2.0) 0.3 (0.0-1.0) 048 2.0 (1.3-2.8) 0 - 0.3 (0.0-1.0) 1.7 (1.4-2.0) 0.45 Weight reduction counseling 7.8 (6.4-9.2) 7.1 (5.9-8.2) 0.7 (0.1-1.4) 0.72 3.1 (2.3-3.9) 4.8 (4.0-5.6) 0.001 0.3 (0.0-1.0) 7.5 (6.3-8.7) 0.03 Diet/nutrition counseling 3.3 (2.1-4.6) 2.2 (1.8-2.5) 1.2 (0.0-2.3) 0.58 2.9 (1.7-4.1) 0.5 (0.4-0.5) 0.01 0.8 (0.1-1.4) 2.5 (1.5-3.5) 0.27 Exercise counseling 2.4 (1.7-3.2) 1.7 (1.4-2.0) 0.7 (0.1-1.4) 0.94 2.5 (1.7-3.2) 0 - 0.3 (0.0-1.0) 2.1 (1.8-2.5) 0.33 Tobacco use/exposure counseling 1.0 (0.3-1.6) 0.6 (0.5-0.7) 0.3 (0.0-1.0) 0.97 1.0 (0.3-1.6) 0 - 0.3 (0.0-1.0) 0.6 (0.5-0.7) 0.78 Substance abuse counseling 0.7 (0.0-2.1) 0 0.7 (0.0-2.1) - 0.7 (0.0-2.2) 0 - 0.7 (0.0-2.1) 0 - a Public insurance includes Medicare, Medicaid, Children's Health Insurance Program, and other state-based programs. "Other" includes all other types of payment method. b No visits reported screening for alcohol misuse, substance abuse, or domestic violence. * Data are presented as percentage of total visits (95% confidence interval). References 1 Garg A Malviya N Strunk A Wright S Alavi A Alhusayen R Comorbidity screening in hidradenitis suppurativa evidence-based recommendations from the US and Canadian hidradenitis suppurativa foundations J Am Acad Dermatol 2022 May 86 (5) 1092 1101 33493574 2 Sisic M Tan J Lafreniere KD Hidradenitis suppurativa intimate partner violence and sexual assault J Cutan Med Surg 2017 Oct 21 (5) 383 387 28481644 3 Patel KR Lee HH Rastogi S Vakharia PP Hua T Chhiba K Association between hidradenitis suppurativa and suicidality a systematic review and meta-analysis J Am Acad Dermatol 2020 Sep 83 (3) 737 744 31862404 4 Garg A Papagermanos V Midura M Strunk A Merson J Opioid and cannabis misuse among patients with hidradenitis suppurativa a population-based analysis in the United States J Am Acad Dermatol 2018 Sep 79 (3) 495.e1 500.e1 29499293 5 Egeberg A Gislason GH Hansen PR Risk of major adverse cardiovascular events and all-cause mortality in patients with hidradenitis suppurativa JAMA Dermatol 2016 Apr 152 (4) 429 434 26885728 6 Sartorius K Emtestam L Jemec GBE Lapins J Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity Br J Dermatol 2009 Oct 161 (4) 831 839 19438453 7 Schrader AMR Deckers IE van der Zee HH Boer J Prens EP Hidradenitis suppurativa a retrospective study of 846 Dutch patients to identify factors associated with disease severity J Am Acad Dermatol 2014 Sep 71 (3) 460 467 24880664 8 Kromann CB Ibler KS Kristiansen VB Jemec GB The influence of body weight on the prevalence and severity of hidradenitis suppurativa Acta Derm Venereol 2014 Sep 94 (5) 553 557 24577555 9 Shih T De DR Brooks B Fixsen D Shi VY Hsiao JL Optimizing hidradenitis suppurativa clinic visits patient perspectives Int J Womens Dermatol 2022 Aug 18 8 (3) e040 36000014 10 Garg A Kirby JS Lavian J Lin G Strunk A age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the United States JAMA Dermatol 2017 Aug 1 153 (8) 760 764 28492923 11 Wertenteil S Strunk A Garg A Association of low socioeconomic status with hidradenitis suppurativa in the United States JAMA Dermatol 2018 Sep 1 154 (9) 1086 1088 30073254 12 Rick JW Thompson AM Fernandez JM Maarouf M Seivright JR Hsiao JL Misdiagnoses and barriers to care in hidradenitis suppurativa a patient survey Australas J Dermatol 2021 Nov 62 (4) e592 e594 34314017 13 Kroenke K Spitzer RL Williams JBW The Patient Health Questionnaire-2 validity of a two-item depression screener Med Care 2003 Nov 41 (11) 1284 1292 14583691 14 Thompson AM Fernandez JM Shih T Hamzavi I Hsiao JL Shi VY Improving hidradenitis suppurativa patient education using written action plan a randomized controlled trial J Dermatolog Treat 2021 Sep 27 33 (5) 2677 2679 34579620
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BMC Ophthalmol BMC Ophthalmol BMC Ophthalmology 1471-2415 BioMed Central London 2854 10.1186/s12886-023-02854-z Case Report Long-term course with iris changes after trabeculectomy for uveitic glaucoma associated with iris mammillation: a case report Usui Shinichi [email protected] 1 Okazaki Tomoyuki 1 Fujino Takahiro 1 Kawashima Rumi 1 Hashida Noriyasu 1 Matsushita Kenji 1 Morii Eiichi 2 Nishida Kohji 13 1 grid.136593.b 0000 0004 0373 3971 Department of Ophthalmology, Osaka University Graduate School of Medicine, E7, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan 2 grid.136593.b 0000 0004 0373 3971 Department of Pathology, Graduate School of Medicine and Faculty of Medicine, Osaka University, Osaka, Japan 3 grid.136593.b 0000 0004 0373 3971 Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan 15 3 2023 15 3 2023 2023 23 10330 8 2022 9 3 2023 (c) The Author(s) 2023 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Background Iris mammillation is a rare disease characterized by the distribution of multiple nodules on the iris surface. The course of uveitic glaucoma with iris mammillation has never been reported. Case presentation A 56-year-old woman, who presented with unilateral decreased vision, visited our hospital for treatment of uveitic glaucoma in the right eye. Multiple nodules were scattered over the iris surface in that eye. This case was diagnosed as iris mammillation on clinical findings. After excluding malignant tumors such as melanoma, trabeculectomy was performed. The resected iris had no pathologically malignant findings. The iris nodules evolved to a sand-like appearance, and the intraocular pressure remained stable without recurrent inflammation 7 years after trabeculectomy. Conclusions In a case of unilateral uveitic glaucoma with iris mammillation, filtration surgery was performed after excluding the presence of a malignancy, and the long-term postoperative course has been stable. Keywords Iris nodule Uveitic glaucoma Iris mammillation Japan Society for the Promotion of Science KAKENHI grant 22K09791 Usui Shinichi issue-copyright-statement(c) The Author(s) 2023 pmcBackground Iris mammillation is a rare disease in which multiple nodules are distributed on the iris surface; the disease is generally unilateral and usually found on a dark iris or a nevus on the iris. Iris mammillation can be associated with ocular melanocytosis or phakomatosis pigmentovascularis type IIb and neurofibromatosis type I, which is usually sporadic but also may have an autosomal dominant inheritance pattern [1-6]. It has been suggested that iris mammillations may be an external sign of intraocular malignancy. In the case of associated melanocytosis of the iris, long-term follow-up is necessary because of the risk of uveal melanoma. Recently, an association between iris mammillation and prognosis of keratoconus has been reported, but its clinical significance has not been established . Here, we report a case of glaucoma associated with inflammation, which has never been reported. Case presentation A 56-year-old woman with iritis and high intraocular pressure (IOP) visited our hospital and reported visual loss in her right eye. The visual acuity (VA) was 20/2000 in the right eye and 20/13 in the left eye. The respective IOPs were 56 mmHg and 18 mmHg measured using Goldmann applanation tonometry. Slit-lamp microscopy revealed a large number of iris nodules of different sizes over the entire surface of the iris with keratic precipitates and mild inflammatory cells in the anterior chamber of the right eye (Fig. 1A). The grade of anterior chamber cells was + 1 based on the Standardization of Uveitis Nomenclature Working group. Peripheral anterior synechiae were seen all around by the gonioscopy. Anterior-segment optical coherence tomography (AS-OCT) (CASIA, Tomey, Nagoya, Japan) showed a thickened inferior iris in the right eye on a B-scan image (Fig. 1B). Ultrasound biomicroscopy (UBM) (Tomey) showed angle closure at the 4 o'clock position in the right eye (Fig. 1C). A late-phase fundus fluorescein angiography image showed hyper-fluorescence of the optic nerve in the right eye characteristic of severe glaucomatous optic neuropathy (Fig. 1D, E). Goldmann visual field perimetry found only central 5 degrees of vision remaining in the right eye (Fig. 1F). In contrast, the Humphrey Field Analyzer (Carl Zeiss Meditec Inc., Dublin, CA, USA) showed that the visual field in the left eye was normal using the 30-2 SITA-Standard program in standard automated perimetry.Fig. 1 Slit-lamp examination of the anterior ocular segment in the right eye. Numerous iris nodules of different shapes and sizes cover the entire surface of the iris with keratic precipitates. Enlarged views are seen in the separated images (A). An AS-OCT image shows thickening of the inferior iris of the right eye (arrow) (B). UBM shows angle closure at the 4 o'clock position in the right eye (C). A fundus image shows severe glaucomatous optic neuropathy in the right eye (D). A late-phase fundus fluorescein angiography image shows hyper-fluorescence of the optic nerve in the right eye (E). Goldmann visual field perimetry found that only 5 degrees of the visual field remains functional (F) The family history was unremarkable. The medical history showed urethral stones and a suspected autoimmune disease 1 year previously, but the details were unknown. Serum testing showed a high rheumatoid factor value (46 IU/mL), high antinuclear antibody titers (1:640), and high Immunoglobulin E levels (226.1 IU/mL). No abnormalities were found on chest radiographs and electrocardiograms. Five-S cysteinyl-dopa (5-S-CD), a melanin-related metabolite, was measured in the serum and aqueous humor to identify a melanin-related tumor such as malignant melanoma . The value was 6 nmol/L in the serum, which was within the normal range (1.5-8.0 nmol/L); however, the value was 9.5 nmol/L in the aqueous humor, which was slightly higher than the normal range . To determine if the tumor was malignant, brain magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) were performed but showed no obvious findings suggestive of a malignancy (Fig. 2A-C). In the brain, an early single photon emission computed tomography (SPECT) image showed slight accumulation of fluorodeoxyglucose in the right eye compared with the left eye, but there was no difference between both eyes in the late images (Fig. 2D). These results suggested the low possibility of a malignancy.Fig. 2 Identification of malignancy by imaging studies. A cranial MRI image shows no abnormality on a T1-weighted image (A) and a high signal in the optic nerve of the right eye on a short tau inversion recovery image, but no findings suggestive of malignancy are seen (B). A PET-CT also shows no signs of malignancy (C). Brain SPECT shows that fluorodeoxyglucose is slightly more concentrated in the right eye than in the left eye in the early images, but no difference is seen between the left and right eyes in the late image and there is no significant accumulation in the trunk (D) The IOP in the right eye decreased to within the normal range by treatment with a dexamethasone eye drops 4 times daily and multiple anti-glaucoma eye drops, but a few months later the IOP increased to over 40 mmHg and was unresponsive to therapy. We performed a trabeculectomy, and an iris specimen obtained during iridectomy was pathologically diagnosed. Giemsa staining did not show an obvious papillary structure (Fig. 3A). Furthermore, the pigment epithelial cells showed little nuclear dysplasia, and no cells with a high degree of atypia causing stromal infiltration were seen by de-melaninization treatment (Fig. 3B). Slight chronic inflammatory infiltration was found in the interstitium, but there were no positive findings of malignancy. Seven years postoperatively, the inflammation has not recurred. Slit-lamp and AS-OCT evaluations showed that the filtering bleb was maintained, and the IOP was stable at around 10 mmHg with timolol eye drops (Fig. 3C, D). The numerous iris nodules of different sizes seen at the first visit gradually shrank and had a sand-like appearance and were inconspicuous after trabeculectomy; posterior iris synechiae were observed around the pupil (Fig. 3E, F). It was difficult to maintain the VA and residual visual field because of the severe degree of preoperative glaucomatous optic neuropathy. In contrast, small linear keratic precipitates were seen in the left eye; however, no obvious inflammation or increased IOP occurred during the entire course (Fig. 3G, H).Fig. 3 Histology of the intraoperatively resected iris is shown in A and B. A Giemsa stained image shows no obvious papillary structures (A). After de-melaninization, pigment epithelial cells show little nuclear atypia and no highly atypical cells causing stromal infiltration. The stroma is edematous and slightly infiltrated by chronic inflammatory cells. No findings suggest malignancy (B). A slit-lamp image and morphology of the filtering bleb by AS-OCT 7 years postoperatively are shown in C and D. A photograph of the anterior segment shows a well-maintained filtration bleb (C). The filtration bleb contains a large reticular layer and is in good condition in the AS-OCT bleb image (dotted arrow in Fig. C) (D). An anterior image shows no hyperemia or obvious inflammation. Posterior iris synechiae are visualized around the pupil (E). The multiple iris nodules at disease onset resolved, and the nodules are irregular (F). An anterior image of the fellow eye shows no hyperemia or obvious inflammation (G), but small linear keratic precipitates are seen (white arrows in Fig. H) (H) Discussion and conclusion We experienced a case of advanced visual field loss with secondary glaucoma associated with multiple iris nodules and iritis. Based on previous reports, this case was diagnosed as iris mammillation. The disease generally is unilateral, but in the current case mild findings appeared in the opposite eye over time. The IOP in the right eye decreased to within the normal range by treatment with a dexamethasone eye drops for inflammation and multiple anti-glaucoma eye drops, but finally, the IOP increased again and was unresponsive to therapy because of peripheral anterior synechiae. The patient underwent filtration surgery after a malignancy, such as melanosis, was ruled out because of the potential for metastasis resulting from surgical intervention. Melanin is a characteristic of malignant melanoma, and 5-S-CD most sensitively reflects the clinical pathology of melanoma, leading to early detection and recurrence of malignant melanoma. Measurement of 5-S-CD is useful for determining the therapeutic effect as an index for estimating metastasis. Normally, 5-S-CD is determined by quantifying the amount in the serum, but quantification in the anterior chamber is useful . The serum 5-S-CD level in this case was 6 mol/L, which was within the normal range, but it was 9.5 nmol/L in the aqueous humor, which was slightly above the normal range. Furthermore, PET-CT and brain SPECT were performed to rule out findings suggestive of obvious malignancy. Filtration surgery was performed without lensectomy to minimize surgical invasiveness. An iris specimen excised by iris peripheral iridectomy was treated with de-melaninization as a pathological tissue, and no obvious malignancy was identified. While, inflammatory cell infiltration was observed in the resected iris, which may have contributed to the series of elevated IOP. Furthermore, multiple nodules on the iris surface gradually shrank and were inconspicuous after trabeculectomy, suggesting that uveitic glaucoma is associated with iris mammillation. The filtering bleb was well maintained with low IOP for 7 years postoperatively, but the VA eventually deteriorated because less than the central 5 degrees of the visual field remained at the first visit. In addition, there was no recurrence of inflammation, and no obvious malignant findings were observed locally or systemically, but careful follow-up is required for the dominant left eye . Iris mammillation is generally unilateral, but a bilateral case was reported . We experienced a case of multiple iris nodules that developed inflammatory secondary glaucoma and were able to control the IOP for a long period after filtration surgery. A preoperative examination to rule out a malignancy is important both locally and systemically when performing filtration surgery with neoplastic lesions. Furthermore, careful follow-up is necessary during a long postoperative period. Abbreviations IOP Intraocular pressure VA Visual acuity AS-OCT Anterior-segment optical coherence tomography MRI Magnetic resonance imaging 5-S-CD Five-S cysteinyl-dopa PET-CT Positron emission tomography-computed tomography SPECT Single photon emission computed tomography Acknowledgements We thank the patient for granting permission to publish this information. Authors' contributions S.U. and K.M. participated in drafting the manuscript and collection, analysis, and interpretation of the data. S.U. and N.H. participated in diagnosis and treatment of the patient, drafting the manuscript, and revising the manuscript. E.M. commented on the histopathology. T.O., T.F., R.K., K.M. and K.N. critically reviewed the manuscript and reviewed the literature. All authors consented to their names being published in this report and insist on the intellectual honesty and validity of the data provided. All authors read and approved the final version of the paper. Funding The research was supported by JSPS KAKENHI grant 22K09791 (S.U.) Availability of data and materials All data generated or analyzed during this study are included in this published article. Declarations Ethics approval and consent to participate Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor of this journal. The Institutional Review Board of the Osaka University Medical School approved the research protocol, and the procedures conformed to the tenets of the Declaration of Helsinki. Consent for publication Written informed consent was obtained from the patient for publication of this case report and all accompanying images. A copy of the written consent is available for review. Competing interests The authors declare that there are no conflicts of interest regarding the publication of this paper. The authors have no proprietary or commercial interest in any material discussed in this manuscript. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Ragge NK Acheson J Murphree AL Iris mammillations: significance and associations Eye 1996 10 Pt 1 86 91 10.1038/eye.1996.13 8763309 2. Peyman M Ong MJ Iqbal T Subrayan V Iris mammillations in two female siblings with congenital adrenal hyperplasia BMJ Case Rep 2010 2010 bcr0820103266 10.1136/bcr.08.2010.3266 22802477 3. Gilliam AC Ragge NK Perez MI Bolognia JL Phakomatosis pigmentovascularis type IIb with iris mammillations Arch Dermatol 1993 129 340 342 10.1001/archderm.1993.01680240080011 8447671 4. Gunduz K Shields CL Shields JA Eagle RC Jr Singh AD Iris mammillations as the only sign of ocular melanocytosis in a child with choroidal melanoma Arch Ophthalmol 2000 118 716 717 10.1001/archopht.118.5.716 10815167 5. Ceuterick SD Van Den Ende JJ Smets RM Clinical and genetic significance of unilateral Lisch nodules Bull Soc Belge Ophtalmol 2005 295 49 53 6. Adams EG Stewart KM Borges OA Darling T Multiple, unilateral Lisch nodules in the absence of other manifestations of neurofibromatosis type 1 Case Rep Ophthalmol Med 2011 2011 854784 22606479 7. Antunes-Foschini RMS Costa RMS Faria-E-Sousa SJ Rocha EM Are iris mammillations correlated with keratoconus? Am J Ophthalmol Case Rep 2019 14 16 18 10.1016/j.ajoc.2019.01.011 30793057 8. Goto H Usui M Wakamatsu K Ito S 5-S-cysteinyldopa as diagnostic tumor marker for uveal malignant melanoma Jpn J Ophthalmol 2001 45 538 542 10.1016/S0021-5155(01)00393-8 11583680 9. Inoue R Saishin Y Shima C Yoshikawa H Ohguro N Tano Y A case of iris melanocytoma transformed to malignant melanoma Jpn J Ophthalmol 2009 53 271 273 10.1007/s10384-008-0649-0 19484449 10. Yamamoto M Mimura T Matsumoto K Hamano S Nanba H Ubukata S Bilateral iris mammillations in amblyopic eyes without oculodermal melanocytosis or neurofibromatosis Case Rep Ophthalmol Med 2018 2018 2534042 30510826
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J Med Case Rep J Med Case Rep Journal of Medical Case Reports 1752-1947 BioMed Central London 36918898 3803 10.1186/s13256-023-03803-6 Case Report Retroperitoneal lymphangioma as the final diagnosis of a middle-aged woman with abdominal pain: a case report Asadzadeh Aghdaei Hamid [email protected] 1 Rabbani Amirhassan [email protected] 2 Sadeghi Amir [email protected] 1 Rezvani Hamid [email protected] 3 Sherkat Ghazal [email protected] 4 Salarieh Naghmeh [email protected] 1 Ketabi Moghadam Pardis [email protected] 1 1 grid.411600.2 Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 grid.411600.2 Surgery Department of Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 grid.411600.2 Division of Medical Oncology, Taleghani Hospital Cancer Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 grid.411768.d 0000 0004 1756 1744 Medicine Faculty of Mashhad Branch, Islamic Azad University, Mashhad, Iran 15 3 2023 15 3 2023 2023 17 931 11 2022 31 1 2023 (c) The Author(s) 2023 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Background Lymphangiomas are lesions attributed to congenital malformations of the lymphatic system, or acquired chronic obstruction of the lymphatic network due to trauma, radiation, surgical manipulation, inflammation, or infection. Overall, lymaphangiomas are rare, and particularly, retroperitoneal lymphangiomas are far more uncommon per reported cases. Case presentation A 49-year-old Iranian woman presented with a progressive abdominal pain since approximately 1 month before admission. She was found to have a retroperitoneal lymphangioma after a precise radiological and surgical workup. Conclusion Retroperitoneal lymphangiomas are rare lesions, sometimes indistinguishable from malignant lesions originating from pancreas and adjacent organs. Complete surgical removal and histologic evaluation of the lesion is the gold standard of treatment and diagnosis. Keywords Retroperitoneal lymphangioma Pancreatic ductal adenocarcinoma Pancreatic cystic neoplasm issue-copyright-statement(c) The Author(s) 2023 pmcIntroduction Lymphangiomas are rare benign lesions originating from lymphatic system . They can be detected at any age, but the infantile type is more common. Any part of the body can be involved, although head and neck, and axilla are more commonly affected. Abdominal lymphangiomas, especially retroperitoneal forms, are found to be rare. It is estimated that less than 1% of overall detected lymphangiomas are located in retroperitoneum . Their clinical presentation is entirely dependent on the place they have arisen from. The compressive effect of the tumor on the adjacent organs determines the symptoms. Of note, retroperitoneal forms are usually manifested by abdominal pain and palpable masses . Ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are modalities used for evaluation of these tumors, which clearly manifest their cystic nature. However, the diagnostic accuracy of imaging is not sufficient to differentiate these lesions from other cystic/solid-cystic lesions. This may be in part due to their inflammatory changes which obscures their lymphatic origin. Given that, histologic confirmation is a necessity for definite diagnosis of lymphangiomas . Complete resection of these lesions is recognized as the treatment of choice . Case presentation A 49-year-old woman presented to the gastroenterology clinic of Taleghani Hospital, a tertiary academic hospital with a persistent epigastric pain radiating to the back for 1 month before admission. The nature of the abdominal pain was exacerbating over time. It did not alter by fasting or eating. She denied any alteration in bowel habits, but recently suffered from poor appetite, early satiety, and nausea after eating. She did not have any systemic signs and symptoms. Her past medical history was unremarkable except for uterine fibroids. Her family history was positive for pancreatic ductal adenocarcinoma and gastric adenocarcinoma in her second-degree-relatives. On admission, she was uncomfortable but her vital signs were within normal limits. Her physical examination revealed only a mild to moderate tenderness in epigastrium, without any rebound tenderness or guarding. A complete blood count revealed mild anemia with white blood cells (WBC) 5100 cells/mm3, hemoglobin (Hb) 11.2 g/dl, and platelets (plt) 210,000/ml. Further evaluations for anemia demonstrated a microcytic and hypochromic anemia with a serum iron profile compatible with iron-deficient anemia. Erythrocyte sedimentation rate (ESR), renal function tests, liver function tests, pancreatic enzymes, coagulation tests, and serum bilirubin level were all within normal limits. Tumor markers such as cancer antigen 19-9 (CA19-9), a-fetoprotein, and carcinoembryonic antigen (CEA) were all within normal ranges. Abdominopelvic ultrasound revealed a heterogeneous hyperechoic lesion about 48 x 40 mm2 at the head of the pancreas, adjacent to the liver hilum. Color Doppler study of major abdominal vessels was unremarkable. Spiral chest CT scan was normal. Abdominopelvic CT scan showed a well-defined hypodense lesion measuring about 45 x 46 mm2 in size, which resembled a soft-tissue mass of unknown origin, without clear enhancement, near celiac trunk with abutment of left gastric artery. Adjacent mesenteric vessels were severely engorged. An increased gastric wall thickness was noted and porta hepatis lymph nodes (smaller than 10 mm) were also detected (Fig. 1). To precisely assess the mentioned lesion, an endoscopic ultrasound (EUS) was utilized, which demonstrated a hypoechoic lesion measuring about 43 x 45 mm2 lying at the posterior wall of the stomach. Abutment of the left gastric artery, and a short segment of celiac trunk without clear obstruction by the lesion was detected. Abutment of celiac branches made us worried about the malignant and progressive potential of the lesion, although normal size of pancreatic duct (PD) and common bile duct (CBD) was against the diagnosis of adenocarcinoma. Elastography strain ratio of the lesion was estimated to be 22 (Fig. 2). To have a definite diagnosis, fine needle aspiration (FNA) using EUS-FNA needle 19-gauge was performed, which was unfortunately indeterminate for malignant cells or other diagnoses (Fig. 3). Inconclusive results of FNA made us proceed with surgical resection of the lesion. Surgical exploration revealed a retroperitoneal tumor adherent to celiac trunk, pancreas, and left gastric artery. It was resected and was sent for pathologic evaluation. Damaged arteries were reconstructed. Histologic assessment of the resected mass revealed large lymphatic channels with peripheral lymphoid aggregations embedded in a loose connective tissue stroma, which are diagnostic for benign vascular neoplasms, including lymphangioma (Fig. 4). The patient hereby signed a written informed consent for participation in this report, as she was explained that her name and data will completely be omitted from the documents and images.Fig. 1 A-D Abdominopelvic CT scan reveals a well-defined hypodense lesion (A marked with red arrow) measuring about 45 x 26 mm2 in size, which resembles a soft-tissue mass of unknown origin, without clear enhancement near celiac trunk (A marked with blue arrow), and abutting left gastric artery (B its origin is marked with yellow arrow) Fig. 2 Endoscopic ultrasound study demonstrated a hypoechoic lesion measuring 43 x 35 mm2 lying at the posterior wall of the stomach. Tumor encasement of the left gastric artery and a short segment of celiac trunk without obstruction was detected. Elastography strain ratio of the lesion was estimated to be 22 Fig. 3 Fine needle aspiration of the lesion Fig. 4 Large lymphatic channels in loose connective tissue stroma with peripheral lymphoid aggregations compatible with lymphangioma Discussion Lymphangiomas are slow-progressing tumors that are not reported to harbor malignant potential . The known etiologies of lymphangioma are the anomalous connection between lymphatic and venous network, which is commonly seen in children, as well as traumatic degeneration of lymphatic system by radiation, inflammation, infection, and surgical resection, resulting in chronic obstruction of lymphatic system . Histologically, they can be cystic, capillary, or cavernous . Retroperitoneal lymphangiomas are rare and are more commonly seen before the age of 20 years. Our case was a 49-year-old woman with retroperitoneal lymphangioma, presenting with abdominal pain. Our patient's age, her positive family history for pancreatic ductal adenocarcinoma, and location of the tumor, which was adjacent to the head of the pancreas, raised suspicion of other cystic neoplastic tumors like intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and pancreatic adenocarcinomas. Other benign lesions including pseudocysts, hydatid cysts, and cavernous hemangiomas were included in the differential diagnosis of the reported lesion since further findings, such as normal appearance of PD and CBD, abutment of celiac branches, and elastography strain ratio of about 22, were confusing and not truly indicative of malignant or benign lesions. The wide range of differential diagnoses for the detected lesion made us proceed with EUS-FNA, which is a more accurate diagnostic technique for evaluation of pancreatobiliary region. Unfortunately, samples obtained from FNA did not provide a definite diagnosis. Inconclusive results and significant symptoms of the patient, which were attributed to the lesion, necessitated the surgical resection of the tumor. Histologic evaluation eventually revealed the lymphatic origin of the lesion, including large lymphatic channels in loose connective tissue stroma with peripheral lymphoid aggregations, which were compatible with lymphangioma. A large number of cases with retroperitoneal lymphangioma are asymptomatic, so these tumors are incidentally discovered when imaging has been performed for other reasons. Among the rare reported symptoms, abdominal pain is more common and is attributed to the compressive effect of the mass to the adjacent organs. An acute abdomen would be anticipated following probable complications like intestinal obstruction, cystic infection, intracystic/intraperitoneal/retroperitoneal hemorrhage, torsion, and cystic rupture . Per the revised literature, hematoma, abscesses, duplication cysts, ovarian cysts, teratoma, mesothelioma, cystic metastases, lymphangiosarcoma, and pancreatic cystic neoplasms are considered as differential diagnoses of retroperitoneal lymphangioma . In the literature, US study of lymphangioma usually reveals well demarcated, unilocular, or multilocular cysts with scattered echoes . CT images reveal well-defined homogeneous cysts with prominent walls and distinct septations. These images can accurately provide definite information on the structure and location of these tumors . MRIs also help to visualize these cysts, as they have distinct characteristics in T1 and T2 images . Recurrence after complete and incomplete resection of the lymphangioma has been reported to be about 7% and 50%, respectively. So, free margin of surgically resected tumor is the cornerstone of the treatment . One-year follow-up of the patient revealed complete resolution of the abdominal pain and no diagnostic features of recurrence on CT imaging. Conclusion Retroperitoneal lymphangiomas are rare lesions with nonspecific symptoms and indistinct imaging clues, which make the diagnosis challenging. When located adjacent to the pancreas or peripancreatic major vessels, differentiation of pancreatic adenocarcinoma or pancreatic cystic lesions, which harbor a malignant potential, is of clinical importance. Histologic evaluation of the lesion maybe the gold standard of definite diagnosis. Surgical removal of the lesion is the standard method of therapy for symptomatic lesions. Acknowledgements We are kindly grateful for the help of the staff of Research Institute for Gastroenterology and Liver Diseases (RIGLD) in gathering required data and providing required equipment. Author contributions HAA: ERCP, EUS, preparing Figs. 1, 2, 3, and critical review. AR: surgery of the patient, and preparing Fig. 4. AS: ERCP, EUS, preparing Figs. 1, 2, and 3. HR: writing discussion. GS: writing manuscript. NS: writing manuscript. PKM: corresponding author, and writing manuscript. All authors read and approved the final manuscript. Funding All the procedures and equipment in this study were supported by the budget of gastroenterology and hepatology research center of Shahid Beheshti University of Medical Sciences (RIGLD). Availability of data and materials All the laboratory tests, imaging reports, and images are available in the archives of the patients referred to the Research Institute for Gastroenterology and Liver Diseases (RIGLD). Declarations Ethics approval and consent to participate The reported patient in the study was demanded to read and sign a written informed consent for participating in the study. It was explained that the name and data of the patient would be omitted from all images in the study. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests There is no conflict of interest in the study. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Chaker K Sellami A Ouanes Y Retroperitoneal cystic lymphangioma in an adult: a case report Urol Case Rep 2018 18 33 34 10.1016/j.eucr.2018.02.019 29785367 2. Fattahi AS Maddah G Motamedolshariati M Chronic low back pain due to retroperitoneal cystic lymphangioma Arch Bone Jt Surg 2014 2 72 74 25207319 3. Davidson AJ Hartman DS Lymphangioma of the retroperitoneum: CT and sonographic characteristic Radiology 1990 175 507 510 10.1148/radiology.175.2.2183287 2183287 4. Surlin V Georgescu E Dumitrescu C Retropancreatic cystic lymphangioma-considerations upon a case Rom J Morphol Embryol 2011 52 Suppl 493 496 21424100 5. Bhavsar T Saeed-Vafa D Harbison S Retroperitoneal cystic lymphangioma in an adult: a case report and review of the literature World J Gastrointest Pathophysiol 2010 1 171 176 10.4291/wjgp.v1.i5.171 21607159 6. Serrano BV Bernal NA Moreno BC Romero RR Ortega FS Abdominal cystic lymphangiomas: US and CT findings Eur J Radiol 1995 19 3 183 187 10.1016/0720-048X(95)00604-O 7601168 7. Gachabayov M Kubachev K Abdullaev E A huge cystic retroperitoneal lymphangioma presenting with back pain Case Rep Med 2016 2016 1 3 10.1155/2016/1618393 8. Faul JL Berry GJ Colby TV Thoracic lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome Am J Respir Crit Care Med 2000 161 3 1037 1046 10.1164/ajrccm.161.3.9904056 10712360 9. Kasza J Brody FJ Khambaty F Laparoscopic resection of a retroperitoneal cystic lymphangioma in an adult Surg Laparosc Endosc Percutan Tech 2010 20 e114 e116 10.1097/SLE.0b013e3181db79a7 20551789 10. Bonhomme A Broeders A Oyen RH Cystic lymphangioma of the retroperitoneum Clin Radiol 2001 56 156 158 10.1053/crad.2000.0162 11222077 11. Ionescu C Ionescu M Dumitrascu T Retroperitoneal cystic lymphangioma in a patient with previous surgery for seminoma: a case report Maedica 2012 7 180 182 23399992 12. Wang X Meng S Duan K Hu Y Wei F Treatment of retroperitoneal cavernous lymphangioma: a case report Chin Med Sci J 2020 35 3 283 328 10.24920/003760 32972507
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]) OR (AMD[Title / Abstract]) AND ("Alzheimer's disease"[MeSH Terms]) AND ("Alzheimer's"[MeSH Terms])))))). Furthermore, we screened the references list of potentially relevant studies to seek additional studies. Studies retrieved from these electronic searches and relevant references included in the bibliography of those studies were reviewed. We retrieved a total of 21,895 articles from the database. After screening by title, abstract and full-text availability, 326 articles remained. Amongst these, a total of 38 articles were finally included for the synthesis of evidence in this review article based on inclusion and exclusion criteria . Figure 1 Search Methodology The figure is authors' own creation. Pathophysiology The retina, a transparent neural tissue layer that lines the inside of the eye's rear wall, is crucial for vision. The macula, which is the central region of the retina, gives humans their sharpest and most detailed image. The fovea, located in the macula's centre, is crucial for preserving the basic visual abilities required for tasks like identifying faces, driving vehicles and reading. AMD primarily impacts the outer retinal layers. These include RPE, Bruch's membrane and choriocapillaris, along with underlying choroid. Bruch's membrane is crucial in forming neovascular lesions in AMD by mediating connections between the retinal pigment epithelium and choriocapillaris. AMD causes dysfunction and atrophy of the RPE, which also affects the photoreceptor layer of the retina and interferes with phototransduction. Such malfunction causes a breakdown in the signal pathway between the retina and the brain, which results in visual loss . Additionally, microvascular insults that occur in conditions like hypertension and hyperlipidaemia are hypothesized to impact the choroidal vasculature. These microvascular injuries imply that the pathophysiology of the illness is influenced by both ischemic and inflammatory components . In advanced neovascular AMD, abnormal angiogenesis, mediated by vascular endothelial growth factor (VEGF), is crucial for developing choroidal neovascular membranes (CNVs). For healthy choroidal and retinal vasculature, normal retinal circulation needs VEGF. However, hypoxia causes particular VEGF subtypes to express abnormally, resulting in the proliferation of new vascular channels which are vulnerable to bleeding and leaking that characterize neovascular AMD . Numerous genes have also been implicated in the pathogenic mechanism of AMD . The complement factor H gene was discovered as a primary culprit behind the development of AMD. It is also believed that drusen development is influenced by disruptions in complement-mediated regulatory function. The development of AMD is also linked to the non-complement mediated age-related maculopathy susceptibility 2 gene . Ocular manifestations The appearance of specific macular alterations, notably the accumulation of drusen, which are yellow-coloured extracellular localized deposits, is a pathognomonic sign of AMD. The likelihood of the illness progressing is influenced by the size and number of drusen. The diameter ranges for small, medium and giant drusen are 63 mm to 125 mm, respectively. Drusen may also be classified into two varieties: hard and soft. Hard drusen are often smaller and have more pronounced edges, whereas soft drusen can merge to produce larger, more dangerous lesions since their borders are less well-defined . The Beaver Dam Eye Study revealed that individuals with larger soft drusen had nearly a 30% chance of developing advanced AMD . AMD may also be classified into the following three types: early, intermediate and advanced neovascular AMD. Small macular drusen or a sparse cluster of medium-sized drusen have a lower propensity to progress to severe AMD and may not impair vision. Alterations in macular pigmentation may be a symptom of the initial stages of the disease, which also sets the stage for the advanced stage of the disease. A significant number of medium-sized drusen or only single large drusen, classified as intermediate AMD, carry a higher chance of developing into advanced illness and call for more careful monitoring . According to the Age-Related Eye Disease Study (AREDS), age-related macular degeneration can be classified as shown in Figure 2. Figure 2 Classification of Age-Related Macular Degeneration The figure is authors' own creation. Non-Neovascular (Dry) AMD Amongst the initial signs of AMD is a drusen, which is clinically diagnosed as localized, pale yellow excrescences deep inside the retina, underneath the Bruch's membrane and RPE. Most drusen are hard or soft and range in size from 20 to 100 mm . Hard drusen may be characterized as distinct, rounded yellowish spots. They are not influenced by ageing and are not associated with an increase in the incidence of neovascularization . On the contrary, soft drusen are poorly defined with non-discrete boundaries, which measure 63 mm or more . Clinically, geographic atrophy can be distinguished by a patch of the retina that is noticeably thinner than the surrounding retina and by a relative colour change that makes it easier to see the underlying choroidal capillaries. Good visual acuity may be retained if the foveal centre remains unharmed, yet reading vision may still be affected due to a restricted macular visual field . Neovascular (Wet) AMD A characteristic feature of wet AMD is neovascularization in the macula. The growth of new arteries from the choriocapillaris into the sub-pigment epithelial area following the tearing of Bruch's membrane is known as choroidal neovascularization (CNV) . Within the last phase of the illness, neovascularization causes a disc-shaped fibrovascular scar around the macula, which causes long-term deterioration of the central vision . Apart from the collection of fluid in the subretinal or intraretinal space and subretinal haemorrhage, a few other clinical indications of neovascular AMD are fat deposits, grey or greenish-yellow discolouration and detachment and rupture of the retinal pigment epithelium . Haemorrhage, serous fluid collection or drusen accumulation under the retinal pigment epithelium can all result in a retinal pigment detachment (PED). A dome-shaped detachment of RPE, along with robust and diffuse hyperfluorescence and progressive pooling in a specific area, indicates serous PED. Haemorrhagic PED causes the RPE to darken because there is underlying blood, and all angiography phases show blocked fluorescence . Association of AMD with Alzheimer's disease Several traits are shared between AMD-associated retinal degeneration and AD, such as extracellular Ab deposits and oxidative stress, primarily mediated by iron accumulation. Apart from Ab, the cerebral plaques seen in AD also consist of numerous lipid and protein components of drusen, such as vitronectin, apolipoprotein E, clusterin and components of complement activation, including C3 and C5b9. Additionally, the lesions of AMD, as well as AD, also show the presence of several metallic elements, including zinc, copper, iron and ubiquitin. Interestingly, in addition to the classical cerebral plaques found in the brains of AD patients, amyloid deposits have also been found within the inner layers of their retina . Impairment of the functions of lysosomes and mitochondria plays a pivotal role in the development of AD and AMD. This results in a reduced capacity of the ageing cells of the brain and retina to clear the damaged cellular proteins leading to the formation of extracellular deposits. Uncontrolled activation of the complement system has also been implicated in the development of both diseases. It is believed that amyloid-b blocks the inactivation of C3b, resulting in uncontrolled activation of the complement system, which is responsible for the formation of drusen. This is proved by identifying various complement proteins in the drusen and the cerebral plaques in AMD and AD, respectively . Mechanism of Retinal and Neuronal Degeneration The retinal cells and a few other cells in the eye contain the type I transmembrane glycoprotein known as the amyloid precursor protein (APP) and other proteins implicated in AD. Two distinct post-translational processing pathways, amyloidogenic and non-amyloidogenic, are used in the brain to metabolize APP. The amyloidogenic pathway culminates in the generation of Ab fragments following the breakdown of APP by the action of b-secretase and g-secretase. The most harmful of them all, Ab1-42, accumulates within the brains of Alzheimer's patients as extracellular plaques. Ab aggregates bind reactive oxygen species such as metals, including iron and copper, resulting in mitochondrial damage and neurotoxic effects . APP is metabolized similarly in the retina and other types of eye cells. Similar to the cerebrospinal fluid (CSF), pathogenic Ab, soluble APPa and APPb are all present in varying amounts dissolved within the aqueous as well as vitreous humour, and pathological Ab deposits predominate in drusen in AMD. These findings are more pervasive and evident in AD mice models, which have proved to be essential in comprehending the contribution of Ab in AD-related retinal degeneration. Several animal models of AD have demonstrated the presence of Ab deposits and apoptotic RGCs . It is not precisely known how the amyloidogenic pathway of APP breakdown in the retinal pigment epithelial (RPE) cells surpasses the non-amyloidogenic pathway. It is thought that when people age naturally, their RPE cells make and release more Ab1-42, which collects within the intersection of these cells and the external part of the photoreceptor tips as well as in the area beneath the retina, followed by its microglial consumption . This causes an inflammatory response that leads to the typical AMD drusen deposition. The role of Ab in the pathogenesis of AMD is further supported by a recently conducted meta-analysis comprising 21 studies, which suggested a strong correlation between AD and AMD . Nerve Growth Factor (NGF) as a Therapeutic Approach in AMD and AD Nerve growth factor (NGF) is essential for the growth and survival of the neuronal cells of the peripheral and central nervous systems. The administration of NGF as a therapeutic agent in neurodegenerative disorders, especially AMD and AD, has shown promising results owing to its neuroprotective action on cerebral as well as extracerebral tissues such as the retina. When administered via the ocular route, NGF exerts a protective action on the RGCs and the photoreceptors and prevents their degeneration. It inhibits the degeneration of RGCs by decreasing the intracellular levels of pro-NGF and promoting the phosphorylation of tropomyosin receptor kinase A (TrkA). Various clinical trials have employed this anti-apoptotic effect of NGF to stop or prevent the further progression of visual loss. Following topical or intraocular administration of NGF, an increase in its systemic bioavailability is observed. This enhances the neuroprotective action of NGF on the eye-brain projections as well as on the nucleus basalis. Therefore, this approach can be employed to prevent neurodegenerative changes in the brain and the retina and slow down the progression of AD as well as AMD . Diagnosis Individuals above the age of 55 are advised to go for a routine fundus examination for early detection of macular degeneration. The presence of typical drusen, exudates, haemorrhage or geographic atrophy on fundus examination indicates AMD. Although the examination may account for most of the disease staging, using various imaging methods is now crucial for correlating examination findings and directing therapy. Fluorescein Angiography In the past, the gold standard for determining choroidal neovascularization in AMD had been fluorescein angiography (FA). Herein, fluorescein dye is introduced into the patient's vein, after which pictures of the chorioretinal circulation are recorded over several minutes. This invasive method may identify any exudation from various neovascular lesions . Indocyanine Green Angiography Patients with AMD were diagnosed and given treatment recommendations using indocyanine green angiography (ICG). This kind of angiography could distinguish the choroidal circulation more clearly than fluorescein angiography because of the properties of the dye. In individuals with dry AMD, indocyanine green angiography may detect plaques indicative of asymptomatic choroidal neovascularization, watershed zones indicative of potential future exudative transformation or regions of undetected CNV. Optical Coherence Tomography Optical coherence tomography (OCT) is a widely used technique that allows us to visualize the various layers of the retina in great detail. OCT may be compared to ultrasound, except that it uses light waves instead of sound waves to provide a complete cross-sectional picture showing all the layers of the retina along with the choroid. This makes it possible to recognize the specific layers of the retina that have been affected by AMD . Optical coherence tomography angiography (OCT-A), a novel imaging technique, is based on optical coherence tomography, which improves the visibility of the complex choroid vascular network. This approach helps us understand the changes in neovascular AMD at the microvascular level when CNV lesions are present. This technique has largely taken the place of FA and ICG in these situations . Treatment modalities Laser Therapy Until 2000, thermal laser therapy remained the basis of wet AMD treatment. By applying heat energy directly to the neovascular lesions, argon-laser photocoagulation causes CNV to regress with scar formation. It can induce CNV lesions to close when treated with a longer-wavelength infrared laser. Photodynamic treatment (PDT) was first introduced in 2000. In PDT, a photosensitive dye (verteporfin) is infused intravenously into the body. The body absorbs verteporfin, which builds up in CNV . Intravitreal Injections and Anti-VEGF Agents AMD treatment has been entirely changed by introducing localized intravitreal therapy combined with anti-VEGF therapy. At the level of pars plana, which is located 3 to 4 mm beyond the limbus, a tiny, 30-gauge needle can be used to safely and directly administer the required agent into the vitreous cavity. The manufacturer or compounding pharmacy dispenses the drug in a prefilled syringe, with the medication volume typically 0.05 mL . Anti-VEGF medications effectively focus on CNV lesions and protect eyesight in wet AMD. Advanced AMD develops due to overexpression of VEGF, which causes leakage and neovascularization. One of the first mediators connected to the emergence of CNV was VEGF-A, which was also the initial focus of anti-VEGF therapy. Numerous VEGF-A isoforms exist, in addition to other angiogenic VEGFs such as placental-like growth factor (PLGF). The three commonly used intravitreal treatments for wet AMD are bevacizumab, ranibizumab and aflibercept . Surgery In the past, excision of neovascular lesions by surgery was considered a therapeutic choice; however; it has now mostly been abandoned in favour of more effective, minimally invasive alternative treatment options. The Sub-macular Surgery Trials, conducted in the 1990s, looked at how individuals with neovascular AMD fared after having sub-macular surgery for bleeding caused by CNV lesions. The study's findings indicated no advantage for those who received surgery, and the surgery arm saw a higher risk of problems. Conclusions Age-related macular degeneration (AMD) is a major cause of blindness which primarily affects the older population. It induces detrimental changes within the deeper layers of the retina, along with the macula and the adjacent vasculature, thereby causing impairment of macular vision. Drusen, or retinal deposits, are a distinctive clinical trait of AMD. Based on certain specific characteristics, AMD can be classified into two broad types, neovascular (wet) and non-neovascular (dry). Dry or non-neovascular AMD is relatively more common than neovascular AMD. Neovascular AMD is characterized by the development of central choroidal neovascular membranes (CNVs) owing to aberrant vascular proliferation triggered by the action of vascular endothelial growth factor (VEGF). Therefore, intravitreally injected anti-VEGF is the chosen treatment for the neovascular type of AMD. AMD significantly impacts the quality of life of the senior population. The capacity to read, drive, identify people and carry out primary daily duties is affected by central vision loss. The phenotypic expression of the illness varies substantially. In the early form of the disease, the patient may experience little to no symptoms. On the contrary, in the later stages, the patient may complain of distortion of vision or even total loss of central vision. AMD is frequently linked to Alzheimer's disease (AD), which is considered to be the most common type of dementia among older people. In AD, there is an accumulation of amyloid-b (Ab) in the extracellular space and hyperphosphorylated tau (p-tau) deposits within the cells, accompanied by neuroinflammation and brain iron dyshomeostasis. These changes collectively cause progressive neuronal death and dementia. Similarly, the build-up of Ab and iron within the drusen in AMD suggests an overlapping pathogenic mechanism between the two diseases. The authors have declared that no competing interests exist.
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BMC Med BMC Med BMC Medicine 1741-7015 BioMed Central London 36918901 2803 10.1186/s12916-023-02803-z Commentary 'Willpower' is not enough: time for a new approach to public health policy to prevent obesity Jebb Susan A. [email protected] Aveyard Paul [email protected] grid.4991.5 0000 0004 1936 8948 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK 15 3 2023 15 3 2023 2023 21 8921 2 2023 21 2 2023 (c) The Author(s) 2023 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Keywords Obesity Food Environment Policy issue-copyright-statement(c) The Author(s) 2023 pmcBackground In most high-income countries, we eat too much. Looking around the world, it seems that obesity parallels economic development. Within countries, there is a more mixed picture, but there are few people who actively choose to become overweight. Indeed, weight gain has occurred against a strong cultural pressure to be slim, widespread knowledge of the harms of being overweight, and many people spending time and money actively trying to control their weight. The Health Survey for England suggests almost half the adult population are trying to lose weight at any one time . Yet, despite this, there is a persistent belief among the public and policymakers that the solution is more education and urging people to make the right choices. Public health prevention policies should not be confused with interventions to support meaningful weight loss treatment for people living with obesity. The latter is best achieved with individual support and specific weight loss programmes. But successful prevention of weight primary weight gain or secondary regain will also be supported by an environment which does not encourage overconsumption. Creating a supportive food environment How can we do this? Research shows clearly that we overvalue individual decision-making and underestimate the impact of our environment on our behaviour. Consider our study where a supermarket removed chocolate from the most prominent places in selected shops in the run-up to Easter, though the products were still available for sale elsewhere in the store . Prior to the experiment, sales of chocolate in these stores and matched controls, where chocolate was promoted as usual, were similar. In the stores with less prominent positioning, people bought 12% more chocolate in the period before Easter than during the preceding period, while in the stores with (typical) layouts, they bought 31% more. In intervention stores, people put fewer calories in their baskets than control stores. Modern food purchasing environments are set up to maximise profit and not health. Perhaps we could learn to be hyper-vigilant when shopping, but this requires a level of executive functioning ('willpower') that is more that we can reasonably be expected to mobilise at every moment of the day, especially when we are stressed or distracted. Food cues are embedded throughout our environment. Moreover, they prime our behaviour in ways far more subtle than we consciously recognise. In another experiment, children watched food or toy advertisements prior to a cartoon. Later, they were offered a choice of foods to eat. Compared with children who had watched TV without food adverts, children who had seen food advertisements ate more . The same was true when children saw a celebrity on TV who was associated with advertisements for crisps, even though no food was shown . It is unlikely that people perceive that their 'choice' in these and other similar experiments had been shaped by the environment. So why does this happen? The UK Government Foresight report on obesity in 2007 described a reinforcing loop where biological hunger signals dominate over the much weaker satiety cues . What evolved as a survival strategy now leaves us vulnerable to an environment where food is palatable, available, and heavily marketed. Weight gain is an almost inevitable consequence in economically advantaged countries, yet we berate ourselves for lack of willpower. More importantly, our society, expressed through the action of our policymakers, continues to believe that individuals have more control over their choices than is actually the case. This thinking shapes the policy discourse and presents a challenge to the introduction of policies seen as curbing the 'free market'. Accepting the need to change our food environment is crucial to making progress towards societies with a healthier weight. This is not something individuals can do alone. In the mid-twentieth century, the food industry worked to provide more food to more people more cheaply following a period when the main threat was undernutrition, but the market needs a reset if it is to deliver for today's health needs. That probably requires government intervention to encourage and support progressive businesses through a time of change. The soft drink industry levy in the UK provides a good example of what can be achieved. By incentivising reformulation of soft drinks, sugar intake from drinks fell by 30% without decreasing sales . This small change to the environment is predicted to decrease the prevalence of obesity by 0.2-0.9% and the incidence of type 2 diabetes by 0.8-4.4/1000 person-years . Just as no single change in the environment created the high prevalence of obesity, so no one policy can reverse that change. We need to accumulate policies, as we have done in tobacco control, to reverse the environmental changes that have led to overconsumption. This requires sustained action, outlasting the usual political cycles. But at present, standing between us and a healthier environment is policy inertia. We posit that our strong belief, arising from our daily experience of our self-conscious selves, leads us to consider that our behaviour is consciously governed because we do not perceive the myriad times a day when the environment changes what we do. While we can accept the intellectual argument that advertising works, we tend to view the effects of advertising as much greater on others rather than ourselves , and thus, our belief about the conscious drivers of our own behaviour remains intact. Moreover, as citizens or as policymakers, we have a strong moral belief that behaviour change should come from within and that external factors are somehow second-rate ways to change behaviour . Conclusions We have strong evidence that fiscal policies, advertising restrictions, and curtailing the availability of unhealthy products changes behaviour and no shortage of policy documents recommending specific interventions to prevent obesity. Yet, only a few are enacted anywhere in the world. Explaining the neurobiological basis of behaviour does not seem to change our view that we are masters of our own destiny but highlighting the everyday experiences when our food 'choices' are shaped by the environment may be more persuasive in explaining why the 'willpower' model is flawed and, accordingly, open the door to more effective policy action. Authors' contributions Both authors contributed equally. The author(s) read and approved the final manuscript. Funding SAJ is funded by the National Institute of Health Research (NIHR) Oxford University Hospitals Biomedical Research Centre and PA by the NIHR Oxford Health Biomedical Research Centre. Both are funded by the Oxford and Thames Valley Applied Research Collaboration. PA is an NIHR Senior Investigator. Availability of data and materials Not applicable. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests SAJ is a member of BMC Medicine's Editorial Board. The authors declare that they have no other competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Piernas C Aveyard P Jebb SA Recent trends in weight loss attempts: repeated cross-sectional analyses from the health survey for England Int J Obes 2016 40 11 1754 1759 10.1038/ijo.2016.141 2. Piernas C Harmer G Jebb SA Removing seasonal confectionery from prominent store locations and purchasing behaviour within a major UK supermarket: evaluation of a nonrandomised controlled intervention study PLoS Med 2022 19 3 e1003951 10.1371/journal.pmed.1003951 35324903 3. Halford JCG Gillespie J Brown V Pontin EE Dovey TM Effect of television advertisements for foods on food consumption in children Appetite 2004 42 2 221 225 10.1016/j.appet.2003.11.006 15010186 4. Boyland EJ Harrold JA Dovey TM Allison M Dobson S Jacobs M-C Halford JCG Food choice and overconsumption: effect of a premium sports celebrity endorser J Pediatr 2013 163 2 339 343 10.1016/j.jpeds.2013.01.059 23490037 5. Butland B, Jebb S, Kopelman P, McPherson K, Thomas S, Mardell J, et al. Tackling obesities: future choices. Project report. London: Government Office for Science; 2007. 6. Bandy LK Scarborough P Harrington RA Rayner M Jebb SA Reductions in sugar sales from soft drinks in the UK from 2015 to 2018 BMC Med 2020 18 1 20 10.1186/s12916-019-1477-4 31931800 7. Pell D Mytton O Penney TL Briggs A Cummins S Penn-Jones C Rayner M Rutter H Scarborough P Sharp SJ Changes in soft drinks purchased by British households associated with the UK soft drinks industry levy: controlled interrupted time series analysis BMJ 2021 372 n254 10.1136/bmj.n254 33692200 8. Eisend M The third-person effect in advertising: a meta-analysis J Advert 2017 46 3 377 394 10.1080/00913367.2017.1292481 9. Morphett K Partridge B Gartner C Carter A Hall W Why don't smokers want help to quit? A qualitative study of smokers' attitudes towards assisted vs. unassisted quitting Int J Environ Res Public Health 2015 12 6 6591 6607 10.3390/ijerph120606591 26068089 10. Marteau TM White M Rutter H Petticrew M Mytton OT McGowan JG Aldridge RW Increasing healthy life expectancy equitably in England by 5 years by 2035: could it be achieved? Lancet 2019 393 10191 2571 2573 10.1016/S0140-6736(19)31510-7 31258113
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J Orthop Surg Res J Orthop Surg Res Journal of Orthopaedic Surgery and Research 1749-799X BioMed Central London 3631 10.1186/s13018-023-03631-w Research Article The use of a 30-degree radiolucent triangle during surgery in distal avulsion fractures of the patella Ragot Lea [email protected] Gerber Filippo Lannes Xavier Moerenhout Kevin grid.8515.9 0000 0001 0423 4662 Department of Orthopaedics and Traumatology Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland 15 3 2023 15 3 2023 2023 18 20413 12 2022 21 2 2023 (c) The Author(s) 2023 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Background Avoiding patella baja or alta after the Krackow suture technique for distal avulsion fractures of the patella can be challenging. We aim to introduce a simple and reproducible technique using a 30-degree radiolucent triangle involving the contralateral knee to ensure the correct positioning of the patella intraoperatively. Method The radiolucent triangle is positioned under the contralateral knee before operating the injured knee. A strict lateral view is obtained using fluoroscopy as a reference before a Krackow technique is performed on the avulsion fracture of the patella. Results The triangle technique is straightforward and easily reproducible by surgeons of all levels. It allows the surgeon to correctly position the patella intraoperatively in avulsion fracture repair and modify tension on the patellar tendon. Conclusion This method avoids millimetric mispositioning of the operated patella, thus improving the management intraoperatively and could decrease postoperative complications. Keywords Patella baja Patella alta Fluoroscopy Contralateral knee Krackow technique University of LausanneOpen access funding provided by University of Lausanne issue-copyright-statement(c) The Author(s) 2023 pmcBackground Extraarticular distal avulsion fractures of the patella generally occur in young patients (20-50-year-olds), are more frequent in males, and occur by direct trauma or with a rapid hyperflexion mechanism. They represent 5-22.4% of all patellar fractures whereas patellar fractures represent approximatively 1% of all skeletal fractures . Distal avulsion fractures of the patella are biomechanically equivalent to patellar tendon ruptures, which are rare, affecting < 1 per 100,000 people annually. Repairing the patellar tendon with correct positioning is crucial to avoid a severe limitation of knee flexion, early femoropatellar arthritis, and non-union . Patella baja or alta is diagnosed using standard orthogonal radiography before and after surgery by calculating the Insall-Salvati Ratio. A mean ratio of 1 is considered normal, a ratio of > 1.2 is diagnostic of patella alta and < 0.8 is diagnostic of patella baja (Fig. 1).Fig. 1 Insall-Salvati ratio = A/B However, judging the exact length of the patellar tendon intraoperatively with a Krackow technique assuring the correct positioning of the patella can be challenging. Patient positioning is an essential factor, as varying degrees of knee flexion can affect the accuracy of patellar height ratio measurement . We describe a simple and reproducible technique using conventional perioperative fluoroscopy involving the contralateral knee, which to our knowledge, has not yet been described in the literature. Knee fluoroscopy is conducted on the healthy knee using a 30-degree radiolucent non sterile triangle placed under the knee to evaluate the correct position of the patella. The same radiolucent triangle, this time sterile, is used intraoperatively, allowing the operator to ensure the correct positioning and length before suturing the patella tendon. Method The radiolucent triangle at our institution, designed by INNOMED, 30/75deg, 36 cm, is a convenient tool that helps position the knee with 30 degrees of flexion. The patient is supine without a bolster under the ipsilateral buttock. A general or locoregional anesthetic is administered. The radiolucent triangle is positioned under the contralateral knee, and a strict lateral view is obtained with fluoroscopy (Fig. 2a, b). Images of the lateral contralateral knee view are saved. The patient is then draped and prepped for surgery (Fig. 3).Fig. 2 a patient positioning during profile fluoroscopy of the contralateral knee. b Lateral view of the healthy knee to reference the patella's correct position with the 30deg radiolucent triangle Fig. 3 Patient positioning during final lateral view fluoroscopy of the operative knee Once satisfactory images have been captured, we begin the open repair of the distal avulsion of the patella on the operative knee. The Krackow technique is frequently used at our institution and involves a continuous locking loop suture. The classic Krackow stitch involves three or more locking loops placed along each side of the ligament or tendon. Before securing the sutures, a sterile 30-degree radiolucent triangle is placed under the operative knee, thus allowing tension and positioning of the patella to be estimated on fluoroscopy and compared to the contralateral image. Suture and patellar height modifications can then be made intraoperatively (Figs. 3 and 4). Test repair stability after tying sutures is made at 90 degrees of flexion. When satisfactory patellar height and adequate contact between tendon and patella are obtained, the sutures that were previously held by clamps until satisfying height achievement can be tied, and the wound is rinsed and closed.Fig. 4 Satisfactory patellar height marked by Kelly clamps on fluoroscopy at the end of the surgical procedure Case presentation A 78-year-old woman, known for a peripheral arterial obstructive disease treated by Aspirine Cardio 100 mg/day, consulted the Emergency department at our institution after direct trauma to her flexed right knee. The radiographs performed showed a multifragmentary distal avulsion fracture of the patella. Surgical treatment was decided, aspirin was not stopped before the surgery, and the patient underwent the operative technique described above. In our case, we used three patellar tunnels for passing our braided nonabsorbable threads (Ethibond(r) 6) and we put our suture knot on the superior pole of patella. We added one Ethibond(r) 6 in a circumferential manner to reinforce the stability. The preoperative radiographs can be seen in Fig. 5.Fig. 5 a, b Distal avulsion fracture of the right patella, x-rays before surgery The patient could mobilize the operated limb from day one with a hinged brace to gradually recover the knee's range of motion using the following protocol: 0-30deg for two weeks, then 0-60deg from weeks three to four, then 0-90deg for a final two weeks, with closed chain strengthening implying static isometric quadriceps exercises during this period, followed by free movement. Total weight bearing was authorized as of post operative day 1. Patients can usually restart competitive sport at 4 months. The radiography control at day one is shown in Fig. 6.Fig. 6 a, b, c: Day one post operative control x-ray Insall-Salvati ratio = 0,92 Both clinical and radiography results at six weeks and six months postoperative controls were satisfactory (Fig. 7).Fig. 7 a, b, c: Month 6 post operative control x-ray Insall Salvati ratio = 0,94 Discussion The present technical note has introduced a simple technique to complement the fixation of avulsion fractures of the patella. The intraoperative 30-degree radiolucent triangle aids the surgical approach and permits correct patellar positioning. Ultimately the technique described above allows the operator to avoid patellar asymmetry via malpositioning. Further benefits include intraoperative modifications and avoiding tension problems as intraoperative feeling, as height estimations based on clinical feeling may be misleading. Currently, priced at 390 Swiss Francs (roughly 405 Euros and 412 US dollars) and considering its aids in avoiding potentially costly complications, this technique using a resterilizable triangle is potentially very cost-effective. Additionally, it avoids waiting for multiple conventional radiographs of the contralateral knee. These are not always available in an emergency setting and comparatively are more expensive and irradiating than one lateral fluoroscopy intraoperatively. Our institution encourages this technique in the operative treatment of extraarticular avulsion fractures of the patella. One significant limitation is that this technique is not applicable when the contralateral knee is injured or has a pathological Insall-Salvati ratio due to previous surgery or trauma (Table 1). To avoid a misuse of our proposed technique, we present our pearls and pitfalls below (Table 2).Table 1 Pros and cons of our technique using the 30-degree radiolucent triangle during surgery in distal avulsion fractures of the patella PROS CONS Easy to use Reproducible Avoid patellar asymmetry via malpositioning Cost effective Less irradiating than multiple conventional radiographs Not applicable if contralateral knee: Is injured too Has pathological Insall-Salvati ratio due to previous surgery or trauma Has previous knee arthroplasty Table 2 Pearls and pitfalls of our technique PEARLS Strict profile fluoroscopy of the contralateral knee at 30deg of flexion Contralateral knee positioning flush on radiotranslucent triangle Don't forget to save the fluoroscopy image for later use Patella height analysis should be conducted before tightening sutures PITFALLS Images not conform with the requirements mentioned in the text should not be considered and may result in mal positioning of the patella Conclusion Performing preoperative fluoroscopy of non-injured knees with 30 degrees of flexion using a radiolucent triangle prior to tendon repair in extraarticular avulsion fractures of the patella avoids millimetric malpositioning of the operated patella. We believe it improves intraoperative management during procedures in patella surgery and decreases postoperative complications. Further comparative studies comparing different technical procedures would be needed to confirm if this technical novelty is equivalent or better for reconstructing a comparable Insall-Salvati ratio. Acknowledgements We thank Filippo Gerber for English language editing. Author contributions KM discovered the technique mentioned above. LR and KM wrote the article. All authors read and approved the final manuscript. Funding Open access funding provided by University of Lausanne. The authors did not receive support from any organization for the submitted work. Availability of data and materials These are available according to the reader's request. Declarations Ethics approval and consent to participate The patient gave her written consent for publishing this manuscript. Consent for publication Not available. Competing interests The authors declare that they have no competing interest. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Chang CH Chuang HC Su WR Fracture of the inferior pole of the patella: tension band wiring versus transosseous reattachment J Orthop Surg Res 2021 16 365 10.1186/s13018-021-02519-x 34103048 2. Sayum Filho J Lenza M Tamaoki MJ Matsunaga FT Belloti JC Interventions for treating fractures of the patella in adults Cochrane Database Syst Rev 2021 2 2 CD009651 10.1002/14651858.CD009651.pub3 33625743 3. Volk WR Yagnik GP Uribe JW Complications in brief: quadriceps and patellar tendon tears Clin Orthop Relat Res 2014 472 3 1050 1057 10.1007/s11999-013-3396-6 24338040 4. Ward SR Powers CM The influence of patella alta on patellofemoral joint stress during normal and fast walking Clin Biomech (Bristol, Avon) 2004 19 10 1040 1047 10.1016/j.clinbiomech.2004.07.009 15531054 5. Insall J Salvati E Patella position in the normal knee joint Radiology 1971 101 101 104 10.1148/101.1.101 5111961 6. Narkbunnam R Chareancholvanich K Effect of patient position on measurement of patellar height ratio Arch Orthop Trauma Surg 2015 135 1151 1156 10.1007/s00402-015-2268-9 26138208
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First Day. Evening Session. Wednesday, June 26th, 8.30 P. M. PSORA SOME FEATURES OF ITS TREATMENT. Frank W. Patch, M. D., South Framingham, Mass. It was once said of Ruskin that when he wanted to work out a subject he wrote a book on it. It was an earnest desire to better understand the above that led me to prepare this paper, and not on account of any new light or extended knowledge on my own part. It is possible, however, that a close survey of one of the most profound of Hahnemann's doctrines, and an attempt to put in concise form his classic recommendations on the treatment of psora, may not be out of place among the efforts of our society. If we are to accept the broadest application of the meaning of the term psora, we shall understand the treatment of this form of dynamic disturbance to cover nearly the whole field of chronic non-venereal disease, as, indeed, was distinctly taught by . And, furthermore, as primary uncomplicated psoric disease when treated by strictly homoeopathic methods does not result in an unconquerable chronic miasm, it will be understood here that the term psora refers to the secondary or chronic form. This may or may not remain as a distinct result of the suppression of some primary attack, but in any case manifests itself by a long train of symptoms well known to all who examine cases according to the methods of Hahnemann, and having possible ramifications in all parts of the organism. Recent itch, " with the eruption still existing on the skin," Hahnemann says, may occasionally be cured by one dose of in the space of from two to four weeks. But " whether the violent suppression of the eruption has forced the internal psora to manifest itself in the form of secondary chronic , or whether it be still slumbering in the system, alone is never sufficient to effect the cure of such a psoric disturbance." After the external eruption has existed for a long time, or after suppression or other cause whereby the internal organism has become infected to any considerable extent with the disease, neither Sulphur or any other single antipsoric remedy will prove sufficient to effect a cure, but several antipsorics will invariably be found necessary. Before approaching the true heart of our subject, let us inquire first what is curable in psoric diseases, or rather what are the greatest obstacles to cure with which we are compelled to deal. It is here at the very threshold that we are called upon to decide one of the most momentous questions regarding our own standing, as well as the scope and reputation of Homoeopathy. Happy is that physician whose powers of discernment enable him at the outset of a difficult psoric case to prognosticate, with even approximate correctness, the probabilities of cure or of the time needed. Hahnemann recognizes the power of the mind as one of the strongest elements in arousing latent psora which has hitherto been but imperfectly manifested, and warns us against the pernicious influences of permanent "grief and vexation" as a condition from which we must free our patients if we would expect adventitious results. He says: "If the patient is assailed by grief and vexation without the physician being able to ward off those pernicious influences, then it is better that the patient should be left to his fate; for even the wisest, most skillful, and most conscientious physician will find it impossible to procure the patient relief under these circumstances." Again there is the .class of chronic patients coming from a course of crude drugging or mineral baths, or, worse, from a crusade among the long list of proprietary applications, external and internal, whose name is legion. A large of these cases are, strange as it may seem, amenable to homoeopathic prescribing, A few are utterly hopeless. It is truly wonderful, however, to see what may often be in the very teeth of crude drugs by the application of the higher homoeopathic potencies. Of these cases, Hahnemann says that they " are often so complicated that the physician is obliged to abandon them at once. But were they ever so , he ought never to promise more than relief after a long lapse of time." " The first thing to be done is, that the various medicinal influences which undermine the system in all should be removed from the organism." For this of clarification Hahnemann advocates rest, a strict diet, and a regular life, affirming also that " medicine can do almost nothing against these chaotic devastations of crude drugs." A statement that might be challenged to-day by those who have found, in the antidotal power of the highest potencies, an of seeming magnitude in combating drug effects. But, says Hahnemann : " Woe to the homoeopathic physician who means to make his reputation by the cure of such wofully diseases! He will fail in spite of all his care." With the probably curable case of psoric disease before us we must proceed to the taking of the symptoms in the manner laid down in The Organon where Hahnemann says, " in the investigation of a case of disease, demands, on the part of the physician, principally unbiassed judgment and sound senses, attentive observation, and fidelity in noting down the image of the disease." He says, further, in the Chronic Diseases: il There are three mistakes which the physician cannot too avoid;" the first is the fear of administering too small a dose of the medicine found to be indicated ; the second is " the improper use of a remedy;" the third is "not letting the remedy act a sufficient length of time." Hahnemann us that "The doses can scarcely be too much reduced, provided the effects of the remedy are not disturbed by food." " The advantage of giving the smallest doses is that it is an easy matter to neutralize their effects in case the medicine should not have been chosen with the necessary ." There is no doubt among us to-day of the value of these words upon the size of the dose: the accumulation of experience with the highest potencies since they were written has proven their value beyond further discussion. But how many of the practitioners of to-day so closely observe the drug effects after the administration of a remedy that they are able to give the correct antidote, provided it proves to have been incorrectly chosen ? Indeed, it seems to me that with the use of the highest potencies, we have less need than formerly for the drug so carefully mentioned by our pioneers. The shock to the vital force after the administration of one of those highly drugs is seldom sufficient to cause disturbance enough to call for other antidote than that of rest, and the total of all medicine for greater or less time. Indeed, the great advantage of these potencies is seen in the quiet and natural response of the vital force to the curative power, and the absence of all shock even under the influence of a mistaken choice; we simply fail, after waiting what experience has taught to be a sufficient time, to observe the proper curative response to the remedy, and we then know that further study and a new choice must be made. Of Hahnemann's second warning the " use of the improper remedy," but little can be said. His placing of the blame on "carelessness, laziness, and levity " is no doubt frequently just; yet even after what seems to us the utmost care and long study, we all fail, most frequently, to make correct selections in given cases. While many times we fail from a knowledge of just what is curative in chronic disease, as before said, it is probable that much more often we fail from improper selection of the remedy. Perhaps because we have not given sufficient care to the taking of the case or to the study of the materia medica; perhaps because we have failed to grasp the essential or vital element in the nature of the dynamic disturbance itself, which another mind might discern at once. At any rate, let us have great charity. We all earnestly desire success; we all fail at one or another time. In the third warning of Hahnemann, " the too hasty of the dose," we may take a vital interest to-day. We hear a great deal of discussion in our ranks on the length of time which remedies should be allowed to act before repetition. That there can be no absolute rule even with regard to the same remedy in different cases, is evident enough, and it would seem that Hahnemann was sufficiently explicit when he said that " The duration of the action of antipsoric remedies is proportionate to the chronic character of the disease," and, " vice versa, even such remedies as Belladonna, Sulphur, Arsenic, etc., which act for a considerable length of time in the healthy organism, have the duration of their action diminished in proportion as the disease is acute and runs speedily through its course." " The fundamental rule in treating chronic diseases is, to let the carefully selected homoeopathic antipsoric act as long as it is capable of exercising a curative influence, and there is a visible improvement going on in the system. This rule is opposed to the hasty selection of a new or the immediate repetition of the same remedy?' The case taken, our remedy selected, we must now await with all the patience at our command. The methods of Hahnemann in the treatment of psora were careful, , and sure, strongly opposed to those of certain sections of modern medicine which aim at extinction by suppression after the manner that sovereigns have taken so often in a vain attempt to crush revolt by similar tactics. The disease and the subjects each return with added strength at one or another point, eager for the fray. Many of us have learned from sad experience to look with great distrust on any sudden and marked improvement, out of proportion to the character of the disease, after the of an antipsoric remedy, finding such result, almost , to be fleeting and untrustworthy. It is the gradual and persistent, though slow change, that we have learned leads toward health. This ground also was covered by the master mind of , who says, " Even should a remedy produce a sudden great improvement in the condition of the patient, there is danger that the remedy may have acted as a mere palliative; in this case it never should be exhibited a second time, not even after other intermediate remedies" Hahnemann claims, however, that " there are exceptions to this rule, in that a second dose of the same remedy may be given immediately after the first, when the remedy had been chosen with strict regard to its homoeopathic character, and had produced a good effect but had not acted long enough to cure the disease." This occurs more seldom in chronic than acute disease. Some question as to the discrimination between these different manifestations of might seem to arise, though, practically, among those accustomed to the observation of the action of remedies such would seldom be the case. Again, Hahnemann says that " The same remedy may be given a second time when the improvement which the first dose had produced by causing the morbid gradually to become less frequent and less intense, ceases to continue after the lapse of fourteen, ten, or seven days, when it becomes, therefore, evident that the medicine has ceased to act, the condition of the mind is the same as before, and no new or troublesome symptoms have made their appearance?' Under these exceptions Hahnemann advises the remedy to be used a second time in a lower potency than at first, and says further that " Sulphur, Hepar-sulphur, and Sepia excepted, the other antipsorics seldom admit of repetition." " One antipsoric having fulfilled its object, the modified series of symptoms generally requires a different remedy." Hahnemann reminds us that cases which come from serious drugging may need an occasional dose of Sulphur or Hepar-sulphur before the indicated remedy will act, or if much crude Sulphur had been taken, a dose of Mercury should precede that of potentiated Sulphur. Hahnemann recognized the occasional need of interrupting antipsoric treatment on account of extraneous attacks of other forms of disease, and the consequent use at such a time of other non-psoric remedies. Strange as it may seem, however, such condition may exert not more than a slight retarding effect upon the action of the antipsoric as has been recently in two cases of psora attended by the writer of this paper. One, a sycotic tumor, was complicated during treatment by an attack of sciatic rheumatism for which several different remedies were required, the cure of the tumor progressing afterward under further repetition of the previously indicated remedy, Thuja. The second case, one of chronic psoric ulceration of the nose, for which Nit-acid was the indicated remedy, suffered an attack of la grippe, for which non-antipsoric were used. The cure of the nasal condition went on to the end, seemingly in an uninterrupted manner, and without further repetition of the Nit-ac. Hahnemann claims, however, that by these " intermediate diseases " the antipsoric treatment is "not only disturbed, but positively interrupted, usually necessitating an entirely new picture of the case." As to the true space of time needed for the cure of an inveterate case of psora, we may be sure that Hahnemann is not overestimating when he places it ordinarily at from " one to two years, provided the case has not been mismanaged to the extent of having become incurable." During this time the strength of the patient ought to increase continually. The antipsoric remedy should be " taken in the morning;" at least an hour before breakfast, either dry upon the tongue or dissolved in a small amount of water. " It should neither be taken immediately before nor during the period of the menses." The system of the female during pregnancy being in so active a state renders this a favorable time for antipsoric treatment. The only adjuvant to the remedies in the treatment of psora, sanctioned by Hahnemann, is the occasional use of warm-water injections for the relief of constipation at the beginning of treatment. He advised against the use of woollen underwear, a matter which we should more often bring to the notice of our patients in these days of overheating and overdressing. Patients, also, should abstain from all extraneous medicinal or semi-medicinal articles from hot baths and from electrical . At the present day the latter adjuvant is enjoying quite a period of popularity in the hands of a great many physicians who claim to sail under the banner of Homoeopathy, though it is certain that its use is distinctly condemned by the founder of this art, hence their authority must come from other source. In regard to diet, Hahnemann enjoins general rules only, cautioning against the use of whatever may be found injurious to the patient or to the action of the remedy, allowing ample latitude to the needs or idiosyncrasies of the case. He does, however, strongly advise against the use of coffee, tea, and hard liquors, not only on account of their interference with the best action of remedies, but also from their pernicious influence upon the body and soul of human beings. Adjourned to 9 A. m.
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Sao Paulo Med J Sao Paulo Med J Sao Paulo Med J Sao Paulo Medical Journal 1516-3180 1806-9460 Associacao Paulista de Medicina - APM 28562735 10.1590/1516-3180.2016.0258191116 Case Report Dieulafoy's disease of the bronchial tree: a case report Doenca de Dieulafoy da arvore bronquica: relato de caso Wadji Massoud Baghai I Farahzadi Athena II I MD. Associate Professor of Surgery, Firuzgar Hospital, Iran University of Medical Sciences, Tehran, Iran. II MD. Resident of General Surgery, Iran University of Medical Sciences, Rasool Akram Hospital, Shahrara, Tehran, Iran. Address for correspondence: Massoud Baghai-Wadji. Iran University of Medical Sciences, Firuzgar Hospital. Karimkhan St. Beh Afarin Str. Tehran, Iran. Tel. 989131415262. E-mail: [email protected] Conflict of interest: None 29 5 2017 2017 135 4 396400 30 9 2016 11 11 2016 19 11 2016 (c) 2022 by Associacao Paulista de Medicina 2022 Associacao Paulista de Medicina This is an open access article distributed under the terms of the Creative Commons license. ABSTRACT CONTEXT: Dieulafoy's disease of the bronchial tree is a very rare condition. Few cases have been reported in the literature. It can be asymptomatic or manifest with massive hemoptysis. This disease should be considered among heavy smokers when recurrent massive hemoptysis is present amid otherwise normal findings. The treatment can be arterial embolization or surgical intervention. CASE REPORT: A 16-year-old girl was admitted to the emergency department due to hemoptysis with an unknown lesion in the bronchi. She had suffered massive hemoptysis and respiratory failure one week before admission. Fiberoptic bronchoscopy revealed a lesion in the bronchus of the right lower lobe, which was suspected to be a Dieulafoy lesion. Segmentectomy of the right lower lobe and excision of the lesion was carried out. The outcome for this patient was excellent. CONCLUSION: Dieulafoy's disease is a rare vascular anomaly and it is extremely rare in the bronchial tree. In bronchial Dieulafoy's disease, selective embolization has been suggested as a method for cessation of bleeding. Nevertheless, standard anatomical lung resection is a safe and curative alternative. RESUMO CONTEXTO: A doenca de Dieulafoy da arvore bronquica e uma condicao muito rara, poucos casos foram descritos na literatura. Pode ser assintomatica ou manifestar-se com hemoptise macica. Esta doenca deve ser considerada em fumadores pesados quando eles tem recorrentes hemoptises macicas sem outros achados anormais. O tratamento pode ser tanto embolizacao arterial como intervencao cirurgica. RELATO DE CASO: Uma menina de 16 anos foi admitida no Servico de Urgencias devido a hemoptise com uma lesao nos bronquios de origem desconhecida. Havia sofrido hemoptise macica e insuficiencia respiratoria uma semana antes da admissao. A broncoscopia de fibra optica relevou lesao no bronquio do lobo inferior direito, com suspeita de ser lesao de Dieulafoy. Foi realizada uma segmentectomia do lobo inferior direito com excisao da lesao. O resultado da paciente foi excelente. CONCLUSAO: A doenca de Dieulafoy e uma anomalia vascular rara, sendo extremamente rara na arvore bronquica. Na doenca de Dieulafoy bronquial, embolizacao seletiva tem sido sugerida como metodo para cessacao do sangramento; no entanto, a habitual ressecao anatomica do pulmao e uma alternativa segura e curativa. KEY WORDS: Dieulafoy disease Bronchi Hemoptysis Pulmonary artery Lung lobectomy pmcINTRODUCTION Dieulafoy's disease of the bronchial tree is a very rare disease. Few cases have been reported in the literature. It can be asymptomatic or can manifest with massive hemoptysis. This disease should be considered among heavy smokers with recurrent massive hemoptysis.1 The diagnosis can be confirmed by means of bronchoscopy, which shows aberrant arterial bleeding in the bronchial tree. Imaging, consisting of either normal chest X-ray or chest computed tomography (CT) scan, can be helpful in making the diagnosis, through ruling out other causes of hemoptysis. The treatment usually comprises arterial embolization. If this method is unavailable or unsuccessful, surgery can be another option for achieving a definitive cure. Here, we report a case of Dieulafoy's disease in a girl who presented with massive hemoptysis, which was diagnosed by means of bronchoscopy and treated through segmentectomy. CASE REPORT A 16-year-old nonsmoking girl was referred to our hospital because of an episode of massive hemoptysis. She had been admitted to a local hospital one week earlier because of this symptom and had developed respiratory failure, requiring mechanical ventilation for two days. After extubation and cessation of bleeding, she was referred to our hospital for further evaluation. On admission to the thoracic surgery department, she was conscious and extubated, without respiratory distress, but mildly anxious. Her vital signs were stable and she was afebrile. Physical examination on the head and neck, chest, abdomen and extremities showed that these were normal. Oxygen saturation in the ambient air was 98%. There was no longer any hemoptysis. Laboratory data including white blood cell (WBC) and platelet counts, hemoglobin and hematocrit, prothrombin time, partial thromboplastin time (PTT) and international normalized ratio (INR) were within normal limits. A chest X-ray was normal, while chest CT scans showed some patchy haziness in the right lower lobe and a very small lesion in the distal bronchus intermedius . The imaging did not show any atelectasis, honeycomb appearance, cavitation, consolidation or tumoral lesion. Common causes of massive bleeding like bronchiectasis, carcinoid tumor, tuberculosis, arteriovenous (AV) malformations and other conditions were less likely to be the reason for the bleeding in this girl. Figure 1. Chest X-ray showing nearly normal lung field. Figure 2. Computed tomography scan of the chest (pulmonary window), depicting patchy alveolar hemorrhage in right lower lobe. On the next day, fiberoptic bronchoscopy was performed and this showed a lesion at the beginning of the bronchus of the basal segments of the right lower lobe, without evidence of active bleeding. The lesion originated from the mucosal surface, with a small clot over it. The mucosa surrounding the lesion was absolutely normal . No biopsy was taken, because of the suspicion of Dieulafoy's disease and the risk of bleeding. Given the lack of expertise in bronchial angiography and embolization at our center, we preferred surgical treatment. Therefore, within an elective setting and after hemorrhaging had ceased, basal segmentectomy of the right lower lobe was carried out in a planned manner, by means of right lateral thoracotomy. The superior segment of the right lower lobe remained intact . There was no intraoperative finding except for consolidation of the parenchyma of the diseased lobe, most probably due to hemorrhage. The operation was performed without any difficulty because of normal anatomical integrity. Figure 3. Bronchoscopy showing a small lesion in the bronchus of basal segments of right lower lobe (arrow). Figure 4. Right thoracic cavity after basal segmentectomy on the right lower lobe. The arrow shows upper segment of right lower lobe. An intraoperative frozen section study was negative for any malignant condition. The patient had a very smooth and uneventful postoperative course, in which she only presented pain, which could be controlled with ordinary analgesics. She was discharged on the sixth postoperative day. At an outpatient visit one week later, she did not have any serious complaint. Moreover, in the third, sixth and eighteenth months of follow-up, she was still asymptomatic without recurrence of any kind of hemoptysis. Although the diagnosis of this disease was clinical, further pathological studies showed few dilated vessels in the submucosa. This was compatible with a diagnosis of Dieulafoy's disease . Figure 5. Histological section through bronchial Dieulafoy lesion (arrow: dilated hypertrophic submucosal artery; 2.5 X magnification, hematoxylin and eosin staining). DISCUSSION Dieulafoy's disease is a rare vascular anomaly consisting of a dysplastic artery in the submucosa. It is mostly seen in the gastrointestinal tract and is extremely rare in the bronchial tree. To the best of our knowledge, there are only a few reports of Dieulafoy's disease of the bronchial tree in the English-language literature (Tables 1 and 2 1,2,3,4,5,6,7,8). Accordingly, the natural history of this disease and the preferred treatment are not known well. On the other hand, the mortality rate in the absence of any treatment rises to more than 50%.1 Table 1. Articles relating to Dieulafoy's disease that were found through searching the medical literature databases (November 22, 2016) Table 2. A review of Dieulafoy's disease reported in the medical literature The pathogenesis of this disease is also unclear, but most reports state that it occurs in heavy smokers and presents with massive and recurrent hemoptysis. Dieulafoy's disease of the bronchus may have a congenital origin, arising from either the systemic or the pulmonary circulation.2 Spontaneous bleeding has been described in these cases, but bleeding in such cases often occurs after a biopsy on a lesion that has not been diagnosed as a vascular anomaly. Age and tobacco use have an influence on occurrences of this disease.1,3 Dieulafoy's disease can be suspected when there is severe or massive hemoptysis in the absence of any significant abnormality on either chest X-ray or chest CT scan and in the absence of any medical or surgical history, as in our patient's case. Bronchoscopy, preferably using a fiberoptic when the bleeding is not severe, may be diagnostic. It will usually make it possible to find both the source and the cause of the bleeding.3 The characteristics of the lesion are nonspecific, but it can be suspected when a small (usually less than 1 cm) sessile non-pulsatile nodular lesion with a white cap and apparently normal mucosa is seen.2 It has been suggested that, after the diagnosis has been made, angiography and embolization can be the preferred treatment5,6 and that surgical resection would only be needed in a few cases.4 However, the failure rate of embolization is not negligible, whereas surgery alone or after failure of embolization has had a success rate of nearly 100% in all reports.7 Nevertheless, angioembolization is less invasive than surgery, and both physicians and patients prefer it as the first attempt to halt the bleeding. In the event of surgical intervention, since the lesion is usually located in a lobar or segmental bronchus, the surgery should be carried out as an anatomical segmentectomy or lobectomy. Alternatively, bronchoplastic procedures can be performed if the lesion is located in a major bronchus. There is a lack of long-term follow-up in the reports on patients who have undergone embolization alone.7 Although the bleeding recurrence rate in patients whose hemorrhaging has stopped spontaneously is not known, physicians cannot take the risk of not initiating any interventions. If selective embolization is unavailable or if it fails, surgery can be lifesaving. Even in patients whose bleeding stops spontaneously, surgery can have a role in prevention of life-threatening hemoptysis. CONCLUSION Dieulafoy's disease is a rare vascular anomaly and is extremely rare in the bronchial tree. It should be considered as a diagnosis when there is severe or massive hemoptysis in an otherwise normal patient who has nearly normal chest imaging. Bronchoscopy is diagnostic. In bronchial Dieulafoy's disease, selective embolization has been suggested as a method for cessation of bleeding. When angioembolization fails or is unavailable, surgical resection consisting of either segmentectomy or lobectomy can be lifesaving for these patients. Acknowledgement: We would like to thank Dr. Shakira Ghaffoor for editing the manuscript and Dr. Francisco Ferreira e Silva for translating the title, abstract and keywords into Portuguese Firuzgar Hospital, Iran University of Medical Sciences, Tehran, Iran Sources of funding: None REFERENCES 1 Barisione EE Ferretti GG Ravera SS Salio MM Dieulafoy's disease of the bronchus: a possible mistake Multidiscip Respir Med 2012 7 1 40 40 23137343 2 Fang Y Wu Q Wang B Dieulafoy's disease of the bronchus: report of a case and review of the literature J Cardiothorac Surg 2014 9 191 191 25438694 3 Smith B Hart D Alam N Dieulafoy's disease of the bronchus: a rare cause of massive hemoptysis Respirol Case Rep 2014 2 2 55 56 25473566 4 Savale L Parrot A Khalil A Cryptogenetic hemoptysis: from a benign to a life-threatening pathological vascular condition Am J Respir Crit Care Med 2007 175 11 1181 1185 17332480 5 Bhatia P Hendy MS Li-Kam-Wa E Bowyer PK Recurrent embolotherapy in Dieulafoy's disease of the bronchus Can Respir J 2003 10 6 331 333 14530826 6 Hope-Gill B Prathibha BV Bronchoscopic and angiographic findings in Dieulafoy's disease of the bronchus Hosp Med 2002 63 3 178 179 11933825 7 Ganganah O Guo S Chiniah M Sah SK Wu J Endobronchial ultrasound and bronchial artery embolization for Dieulafoy's disease of the bronchus in a teenager: A case report Respir Med Case Rep 2015 16 20 23 26744645 8 van der Werf TS Timmer A Zijlstra JG Fatal haemorrhage from Dieulafoy's disease of the bronchus Thorax 1999 54 2 184 185 10325926
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Sao Paulo Med J Sao Paulo Med J Sao Paulo Med J Sao Paulo Medical Journal 1516-3180 1806-9460 Associacao Paulista de Medicina - APM 29236935 10.1590/1516-3180.2017.0183030817 Original Article Translation and cultural adaptation of the revised foot function index for the Portuguese language: FFI-R Brazil Yi Liu Chiao I Cabral Ana Carolina Camacho II Kamonseki Danilo Harudy III Budiman-Mak Elly IV Vidotto Milena Carlos I I PhD. Professor, Department of Human Movement Sciences, Universidade Federal de Sao Paulo (UNIFESP), Campus Baixada Santista, Santos (SP), Brazil. II Undergraduate Student, Physiotherapy Course, Universidade Federal de Sao Paulo (UNIFESP), Campus Baixada Santista, Santos (SP), Brazil. III Postgraduate Student, Universidade Federal de Sao Paulo (UNIFESP), Campus Baixada Santista, Santos (SP), Brazil. IV PhD. Professor, Medicine Department, Loyola University of Chicago, Chicago, United States. Address for correspondence: Liu Chiao Yi. Departamento de Ciencia do Movimento Humano, Universidade Federal de Sao Paulo (UNIFESP), Campus Baixada Santista. Avenida Dona Ana Costa, 96, Santos (SP) - Brasil. CEP 11060-001. E-mail: [email protected] Conflict of interest: None 07 12 2017 2017 135 6 573577 12 6 2017 17 7 2017 03 8 2017 (c) 2022 by Associacao Paulista de Medicina 2022 Associacao Paulista de Medicina This is an open access article distributed under the terms of the Creative Commons license. ABSTRACT BACKGROUND: The revised foot function index (FFI-R) is used to evaluate the functionality of patients with conditions that affect the feet. The objective here was to produce the Brazilian Portuguese version of this index. DESIGN AND SETTING: Translation and validation study conducted at the Federal University of Sao Paulo, Brazil. METHODS: The translation and cultural adaptation process involved translation by two independent translators, analysis by an expert committee, back translation into the original language, analysis by the expert committee again and a pretest. The Portuguese-language version was administered to 35 individuals with plantar fasciitis and metatarsalgia to determine their level of understanding of the assessment tool. RESULTS: Changes were made to the terms and expressions of some original items to achieve cultural equivalence. Terms not understood by more than 10% of the sample were altered based on the suggestions of the patients themselves. CONCLUSION: The translation and cultural adaptation of the FFI-R for the Portuguese language were completed and the Brazilian version was obtained. KEY WORDS: Foot Translations Surveys and questionnaires Outcome assessment (health care) pmcINTRODUCTION Musculoskeletal injuries in the ankle and foot cause functional limitations that have a negative impact on quality of life.1 Classification of the degree of dysfunction is fundamental for characterization of patients' status and enables quantification of the effect of treatment.2 The main assessment tools used to evaluate the functionality of the feet, such as the foot function index (FFI), foot and ankle outcome score (FAOS), foot health status questionnaire (FHSQ) and Manchester foot pain and disability index (MFPDI), were developed in the English language.3,4 For these assessment tools to be used in different countries with different languages, it is necessary to perform translation and cultural adaption and to test the psychometric properties of the adapted tools.5 The FFI is considered to be one of the main assessment tools for evaluation of the functionality of the ankle and foot, because all its psychometric properties have been validated.1,6,7 Subsequently, adjustments and new domains were added to broaden its scope, thereby creating the revised foot function index (FFI-R).8 In this version, the visual analogue scale (VAS) was replaced with a Likert scale. The domains and items of the original questionnaire were maintained and others regarding psychosocial characteristics were added. The FFI-R has five domains containing 68 items, with questions relating to pain (11 items), stiffness (8 items), problems (20 items), activity limitation (10 items) and social issues (19 items).8 Because of the importance of standardization when using evaluation measurements, questionnaires developed in foreign languages need to be translated and their psychometric properties evaluated, to create equivalence between studies. This process makes it possible for physicians and other professionals working in a given field to obtain a reliable tool for patient evaluations. Thus, the FFI-R can become available for assessing patients with foot and ankle musculoskeletal disorders. The FFI has been translated and validated for use in several countries, such as Germany, Spain, France, China and Brazil.9,10,11,12,13,14 However, the revised version has not yet been translated and culturally adapted to any foreign language based on its original version. OBJECTIVE The aim of the present study was to translate and culturally adapt the revised foot function index to the Brazilian Portuguese language. METHODS Thirty-five patients participated in this study: the first phase involved 20 volunteers and the second phase involved 15 other volunteers with plantar fasciitis and metatarsalgia. The participants were recruited through announcements in the printed and digital media and through verbal invitation. Their mean age was 25.2 years (range: 18 to 57 years) and females accounted for 57% of the sample. With regard to schooling, 12% had completed higher education and 80% were still studying. This investigation received approval from the human research ethics committee of the institution in which it was conducted (ethics committee no. 327.129) and all the participants signed a free and informed consent statement. The authorization for the use of the FFI-R was obtained from the original authors through electronic mail . Figure 1. Flowchart of the study. The translation and cultural adaption of the FFI-R followed the method described by Beaton et al.15 and the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) were used:16 Translation; Analysis by an expert committee; Backtranslation into the original language; Analysis by the expert committee again; and Pretest. The FFI-R was translated into Portuguese by two Brazilian professional translators who were fluent in English. The translators were informed regarding the objective of the study and the two versions of the translation thus produced (V1 and V2) were developed independently. The two translations and the original questionnaire were compared and discussed by the members of the expert committee, in order to reach a consensual version in Portuguese that maintained the fundamental characteristics of the original questionnaire, thus forming V3. In the backtranslation phase, V3 was translated back into English by two translators whose native language was English and who had no access to the original questionnaire. These versions (V4 and V5) were shown to the expert committee. The committee discussed the differences between all the versions created and the original questionnaire. Inadequate or ambiguous items were altered, changes were suggested and equivalences were determined, regarding the meanings of words, idiomatic equivalence (interpretation of colloquialisms), cultural equivalence (to ensure that the practices mentioned in the questionnaire were common to the new culture to which it would be administered) and conceptual equivalence (to determine the cultural importance of the situations presented in the questionnaire). Sentences were rewritten as necessary until a consensual version of the index in Portuguese had been obtained. This version was then used in the pretest, which was divided into two parts: V6-1 and V6-2. V6-1 was administered to 20 patients to determine the understanding of the questions. The researcher read aloud the content of the questionnaire to each participant, who then made suggestions if any items required a change (Table 1). Table 1. Translation phase. Changes in "V1" and "V2" to obtain "V3" V1 = translator 1 version; V2 = translator 2 version; V3 = consensual version in Portuguese after translation phase. Items that did not achieve a level of understanding that exceeded 90% of the volunteers were rewritten, which thus created V6-2. This new version was administered to another 15 patients, who underwent the same procedures as were used for V6-1, until all items in the questionnaire were understood by more than 90% of the patients, which led to the final V7 version. This version was sent to the author of the original FFI-R, who did not suggest any changes. RESULTS In the translation phase, the two versions of the translated questionnaire (V1 and V2) were compared and were used to create the first consensual version (V3) (Table 1). In the backtranslation phase, V3 and the backtranslated versions (V4 and V5) were analyzed and compared with the original questionnaire in English in order to develop V6. This stage involved grammatical, semantic and idiomatic changes for cultural adaptation of the questionnaire while maintaining the objective of each item (Table 2). Table 2. Back translation phase. Changes in "V4" e "V5" to obtain "V6 V3 = consensual Portuguese version of V1 and V2; V6 = final Portuguese version, after analyzing the original version, V3, V4 and V5. In the pretest phase, items that were not understood were altered based on suggestions provided by the patients, thus leading to the final version of the questionnaire in Portuguese (Table 3). Table 3. Modifications to the pretest phase that were made DISCUSSION The translation and cultural adaptation process on the revised foot function index, for use in Portuguese was performed and the Portuguese language version for use in Brazil was achieved. The cultural adaption process for the FFI-R8 followed the method proposed by Beaton et al.15 Several other questionnaires that have been translated and validated for the Portuguese language have followed this model, such as the FFI,9 WOMAC (Western Ontario and McMaster Universities)17 and FAOS.18 The questionnaire was administered to a greater number of young, physically active women, which was similar to the method that had been used for the original questionnaire.8 In the initial phase of translation into the Portuguese language, the term "five pounds" was replaced with 2 kg by the expert committee, since this is the measurement unit for mass that is used in Brazil, thereby allowing patients to correlate the measurement unit with the mass of common objects used in everyday life. In the back translation, question 35 was discussed during the analysis by the committee because it had been translated in a literal fashion. The expression "keeping your foot clean" in English is quite precise and specific, but when translated into Portuguese, this resulted in "mantendo o pe limpo", which caused a lack of understanding. Nevertheless, the committee suggested that this question should be kept in the same format for the pretest phase, to test its clarity in practice. In the first phase of the pretest, approximately 50% of the interviewees had doubts about the meaning and the expression "mantendo a higiene do pe" [maintaining the hygiene of the foot] was suggested. After this change, there were no longer any doubts in the second phase of the pretest. In the backtranslated version of item 62, the committee thought that the original word "burden" did not have the same meaning as the backtranslated word (obligation, from "obrigacao"). Therefore, the word in the Portuguese version was replaced with "incomodo" [inconvenience], to maintain the same idea as in the original word. With regard to the term "rigidez" [stiffness], the interviewees defined it as passive resistance of muscles, tendons, ligaments and fascia, since rigidity is a mechanical property relating to resistance of these tissues to deformation in the absence of muscle contraction.19 In the original questionnaire, the Likert scale has a fifth option ("does not apply") for some items. In the second phase of the pretest, this option 5 was added to more items, as shown in Table 3, since these items did not apply to the majority of the individuals interviewed. In the sample, 80% of the participants were students at a public university and 12% had completed their university education. Thus, there was no considerable difference with regard to the level of understanding of the questionnaire among the interviewees. Original questionnaires in English that have been validated for use in Brazil are generally submitted to a pretest process to obtain the final version in Portuguese, as well as to evaluate the psychometric properties, such as reliability and validity, which are applied in interview form. This type of application has been used in Brazil because of the profile of the populations evaluated during the process, most of whom are recruited from public clinics and hospital services. Although the use of two pretest phases is not commonly found in the literature, important questionnaires that have frequently been cited, such as the SF-36,20 FHSQ4 and WORC,19 have also used this model. Pretesting is an important phase in the cultural adaptation process, since it demonstrates patients' interpretation of the items in a questionnaire. Thus, two pretest phases were used for the FFI-R to ensure that the final version would be understood by more than 90% of the patients21,22 and that the questionnaire would be culturally adapted to the Brazilian population. The psychometric properties of the FFI-R are currently in the test phase to validate the questionnaire for use in Brazil. CONCLUSION The translation and cultural adaptation of the FFI-R for the Portuguese language were completed and the Brazilian version was obtained. Universidade Federal de Sao Paulo (UNIFESP), Campus Baixada Santista, Santos (SP), Brazil Sources of funding: Scientific Initiation bursary from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, CAPES REFERENCES 1 Martin RL Davenport TE Reischl SF Heel pain-plantar fasciitis: revision 2014 J Orthop Sports Phys Ther 2014 44 11 A1 33 2 McColl E Jacoby A Thomas L Design and use of questionnaires: a review of best practice applicable to surveys of health service staff and patients Health Technol Assess 2001 5 31 1 256 3 Riskowski JL Hagedorn TJ Hannan MT Measures of foot function, foot health, and foot pain: American Academy of Orthopedic Surgeons Lower Limb Outcomes Assessment: Foot and Ankle Module (AAOS-FAM), Bristol Foot Score (BFS), Revised Foot Function Index (FFI-R), Foot Health Status Questionnaire (FHSQ), Manchester Foot Pain and Disability Index (MFPDI), Podiatric Health Questionnaire (PHQ), and Rowan Foot Pain Assessment (ROFPAQ) Arthritis Care Res (Hoboken) 2011 63 Suppl 11 S229 S239 22588747 4 Ferreira AF Laurindo IM Rodrigues PT Brazilian version of the foot health status questionnaire (FHSQ-Br): cross-cultural adaptation and evaluation of measurement properties Clinics (Sao Paulo) 2008 63 5 595 600 18925317 5 Lopes AD Ciconelli RM Reis FB Medidas de avaliacao de qualidade de vida e estados de saude em ortopedia [Quality of life and health status evaluation measurements] Rev Bras Ortop 2007 42 11/12 355 359 6 Budiman-Mak E Conrad KJ Roach KE The Foot Function Index: a measure of foot pain and disability J Clin Epidemiol 1991 44 6 561 570 2037861 7 Budiman-Mak E Conrad KJ Mazza J Stuck RM A review of the foot function index and the foot function index - revised J Foot Ankle Res 2013 6 1 5 5 23369667 8 Budiman-Mak E Conrad K Stuck R Matters M Theoretical model and Rasch analysis to develop a revised Foot Function Index Foot Ankle Int 2006 27 7 519 527 16842719 9 Yi LC Staboli IM Kamonseki DH Budiman-Mak E Arie EK Traducao e adaptacao cultural do Foot Function Index para a lingua portuguesa: FFI - Brasil [Translation and cross-cultural adaptation of FFI to Brazilian Portuguese version: FFI - Brazil] Rev Bras Reumatol 2015 55 5 398 405 25772657 10 Martinez BR Staboli IM Kamonseki DH Budiman-Mak E Yi LC Validity and reliability of the Foot Function Index (FFI) questionnaire Brazilian-Portuguese version Springerplus 2016 5 1 1810 1810 27812449 11 Wu S Liang HW Hou WH Reliability and validity of the Taiwan Chinese version of the Foot Function Index J Formos Med Assoc 2008 107 2 111 118 18285243 12 Poutier-Piotte C Pereira B Soubrier M French validation of the Foot Function Index (FFI) Ann Phys Rehabil Med 2015 58 5 276 282 26343763 13 Paez-Moguer J Budiman-Mak E Cuesta-Vargas AI Cross-cultural adaptation and validation of the Foot Functional Index to Spanish Foot Ankle Surg 2014 20 1 34 39 24480497 14 Naal FD Impellizzeri FM Huber M Rippstein PF Cross-cultural adaptation and validation of the Foot Function Index for use in German-speaking patients with foot complaints Foot Ankle Int 2008 29 12 1222 1228 19138487 15 Beaton DE Bombardier C Guillemin F Ferraz MB Guidelines for the process of cross-cultural adaptation of self-report measures Spine (Phila Pa 1976) 2000 25 24 3186 3191 11124735 16 Kottner J Audige L Brorson S Guidelines for Reporting Reliability and Agreement Studies (GRRAS) were proposed J Clin Epidemiol 2011 64 1 96 106 21130355 17 Fernandes MI Traducao e validacao do questionario de qualidade de vida especifico para osteoartrose WOMAC (Western Ontario McMaster Universities) para a lingua portuguesa [dissertation] Sao Paulo Universidade Federal de Sao Paulo, Escola Paulista de Medicina 2002 18 Imoto AM Peccin MS Rodrigues R Mizusaki JM Traducao e validacao do questionario FAOS - FOOT and ankle outcome score para lingua portuguesa [Translation, cultural adaptation and validation of FOOT and ankle outcome score (FAOS) questionnaire into Portuguese] Acta Ortop Bras 2009 17 4 232 235 19 Latash ML Zatsiorsky VM Joint stiffness: myth or reality? Human Movement Science 1993 12 6 653 692 Accessed in: 2017 (Sep 5) 20 Ciconelli RM Ferraz MB Santos W Meinao I Quaresma MR Traducao para a lingua portuguesa e validacao do questionario generico de avaliacao de qualidade de vida SF-36 (Brasil SF-36) [Brazilian-Portuguese version of the SF-36. A reliable and valid quality of life outcome measure] Rev Bras Reumatol 1999 39 3 143 150 21 Lopes AD Ciconelli RM Carrera EF Traducao e adaptacao cultural do WORC: um questionario de qualidade de vida para alteracoes do manguito rotador [Translation and cultural adaptation of WORC: a quality-of-life questionnaire for rotator cuff disorders] Rev Bras Fisioter 2006 10 3 309 315 22 Guillemin F Bombardier C Beaton D Cross-cultural adaptation of healthy-related quality of life measures: literature review and proposed guidelines J Clin Epidemiol 1993 46 12 1417 1432 8263569
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Sao Paulo Med J Sao Paulo Med J Sao Paulo Med J Sao Paulo Medical Journal 1516-3180 1806-9460 Associacao Paulista de Medicina - APM 29166434 10.1590/1516-3180.2017.0146260617 Original Article Evidence hierarchies relating to hand surgery: current status and improvement. A bibliometric analysis study Barroso Thais Silva I Cavalcante Marcelo Cortes II dos Santos Joao Baptista Gomes III Belloti Joao Carlos III Faloppa Flavio IV de Moraes Vinicius Ynoe V I MD. Hand Surgery Resident, Department of Orthopedics and Traumatology, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPM-UNIFESP), Sao Paulo (SP), Brazil. II MD. Resident in Orthopedic Surgery, Department of Orthopedics and Traumatology, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPM-UNIFESP), Sao Paulo (SP), Brazil. III MD, PhD. Adjunct Professor, Department of Orthopedics and Traumatology, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPM-UNIFESP), Sao Paulo (SP), Brazil. IV MD, PhD. Full Professor, Department of Orthopedics and Traumatology, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPM-UNIFESP), Sao Paulo (SP), Brazil. V MD, PhD. Orthopedic Surgeon, Department of Orthopedics and Traumatology, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPM-UNIFESP), Sao Paulo (SP), Brazil. Address for correspondence: Vinicius Ynoe de Moraes. Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPM-UNIFESP), Departamento de Ortopedia e Traumatologia, Disciplina de Cirurgia da Mao. Rua Borges Lagoa, 778, Vila Clementino - Sao Paulo (SP) - Brasil. CEP 04041050. Cel. (+55 11) 99973-8622. E-mail: [email protected] Conflict of interest: None 17 11 2017 2017 135 6 556560 09 5 2017 19 6 2017 26 6 2017 (c) 2022 by Associacao Paulista de Medicina 2022 Associacao Paulista de Medicina This is an open access article distributed under the terms of the Creative Commons license. ABSTRACT BACKGROUND: Hierarchy of evidence is an important measurement for assessing quality of literature. Information regarding quality of evidence within the Brazilian hand surgery setting is sparse, especially regarding whether research has improved in either quality or quantity. This study aimed to identify and classify hand surgery studies published in the two most important Brazilian orthopedics journals based on hierarchy of evidence, with comparisons with previously published data. DESIGN AND SETTING: Bibliometric analysis study performed in a federal university. METHODS: Two independent researchers conducted an electronic database search for hand surgery studies published between 2010 and 2016 in Acta Ortopedica Brasileira and Revista Brasileira de Ortopedia. Eligible studies were subsequently classified according to methodological design, based on the Haynes pyramid model (HP) and the JBJS/AAOS levels of evidence and grades of recommendations (LOR). Qualitative and quantitative data were gathered regarding all studies. Previous data were considered to assess whether the proportion of high-quality studies had improved over time (2000-2009 versus 2010-2016). RESULTS: The final analysis included 123 studies, mostly originating from the southeastern region (78.8%) and private institutions (65%), with self-funding (91.8%). Methodological assessment showed that 15.4% were classified as level I/II using HP and 16.4% using LOR. No significant difference in proportions of high-quality studies was found between the two periods of time assessed (5% versus 12%; P = 0.13). CONCLUSION: Approximately 15% of hand surgery studies published in two major Brazilian journals were likely to be classified as high-quality through two different systems. Moreover, no trend towards quality-of-evidence improvement was found over the last 15 years. KEY WORDS: Hand Orthopedics Evidence-based medicine pmcINTRODUCTION The systematic approach of evidence-based medicine involves critical appraisal and stratification into levels of evidence1,2,3 as a first step. Classification of research considering its internal validity is important in translating research results into clinical practice.1,2 In this regard, stratification of evidence is the key to distinguishing robust high-quality research from biased or low-quality research. Stratification is demanded, given that the number of published studies in the literature is increasing year by year.4 Poolman indicated that higher quality research is linked to better reporting, which relates to trustworthiness and applicability.5 As a basic principle, researchers and practitioners should consider the best evidence available, in making health-related decisions. However, it is often not easy to distinguish good from poorly performed research. Thus, systematic reviews (SRs) are an important tool for combining and summarizing relevant previously published studies.2,4 Most SRs only consider level I and sometimes level II studies as eligible for data synthesis. Therefore, only highly unbiased studies are eligible for inclusion and final analysis. In the setting of hand surgery, although there has been an absolute increase in research production, little is known about the quality of the evidence generated. A previous study suggested that higher levels of evidence are related to higher applicability within clinical, academic and educational scenarios.6 One Brazilian study from the early 2000s assessed hand surgery studies and demonstrated that only a low proportion provided level I and II evidence, accounting for less than 10% of all the studies analyzed.7 These data7 are in accordance with other findings in other settings.8 Bibliometric analyses, as performed in these two studies,7,8 are important because they can potentially have an impact on research policies and academic actions and can pinpoint unnecessary or unethical studies.7,9 Hypothesis The hypothesis for the present investigation was that recent studies have improved in terms of scientific methodology, thus moving towards a proportional increase in the numbers of level I and II studies produced. OBJECTIVES This study aimed to: Identify hand surgery studies published over the last five years (2010-2016) in the two main Brazilian orthopedics journals: Acta Ortopedica Brasileira (AOB) and Revista Brasileira de Ortopedia (RBO). Classify the types of study and levels of evidence according to evidence-based medicine hierarchies. Compare findings from two different periods (2000-2009 versus 2010-2016) within the same journal using the same methodology. METHODS This study was approved by the local ethics committee of our institution (Universidade Federal de Sao Paulo, UNIFESP) under the number CAAE 60911016.8.0000.5505. The methodology used for this study was similar to that used in the senior author's previous publication.7 Search strategy Using the specific web databases of the two journals (AOB and RBO), two researchers (M.C. and T.B.) independently evaluated all studies published between January 1, 2010, and December 31, 2016. These two prominent journals were chosen since they are national-level journals in Brazil that have an orthopedics scope and are indexed in international research databases (SciELO and MEDLINE). Studies were initially screened based on their titles and were classified as eligible, potentially eligible or not eligible. The initial inclusion criteria included the presence of the following themes in the titles/abstracts: hand and wrist fractures, peripheral nerve lesions and vascular lesions in the upper limbs, nail bed lesions, brachial plexus lesions, muscle tendon lesions, upper-limb skin coverage, microsurgery, upper-limb pain syndromes, upper-limb congenital malformations, and anatomical and experimental studies. From the methodological perspective, narrative reviews, economic appraisal studies and experimental studies in vitro or on animals were excluded. After this initial screening, eligible and potentially eligible studies were assessed: first using the abstracts and then the full-text articles. These studies were evaluated by the two examiners, who subsequently categorized them according to study type and level10 of evidence, using two different approaches: the Haynes pyramid of evidence (HP) and the JBJS/AAOS Evidence-Based Practice Committee guideline - levels of evidence and grades of recommendations (LOR).11 Stratification was conducted after reading the full text of all eligible studies. Any disagreements were resolved by a third evaluator (V.Y.M.). Haynes pyramid of evidence We considered that systematic reviews of randomized clinical trials provided evidence at level I; randomized clinical trials, level II; cohort and case-control studies, level III; case series, level IV; and case reports, level V. JBJS/AAOS Evidence-Based Practice Committee guideline This guideline, produced jointly by the Journal of Bone and Joint Surgery (JBJS) and the American Academy of Orthopaedic Surgeons (AAOS), is an improved, robust and detailed version of the previous HP stratification. Its levels of evidence are classified as follows: Level I Randomized controlled trial (RCT): a study in which patients are randomly assigned to the treatment or control group and are followed prospectively; or a meta-analysis on randomized trials with homogeneous results. Level II Poorly designed RCT: follow up data on less than 80% of patients. Prospective cohort study (therapeutic): a study in which patient groups are separated non-randomly according to exposure or treatment, with exposure occurring after the study started. Meta-analysis on Level II studies. Level III Retrospective cohort study: a study in which patient groups are separated non-randomly according to exposure or treatment, with exposure occurring before the study started. Case-control study: a study in which patient groups are separated according to the current presence or absence of disease and examined for the prior exposure of interest. Meta-analysis on Level III studies. Level IV Case series: a report on multiple patients with the same treatment, but no control group or comparison group. Level V Case report (a report on a single case), expert opinion or personal observation. For all the studies ultimately included, we obtained information regarding the journal (AOB or RBO); geographic location of the study (south, southeast or north plus northeast plus center-west of Brazil); number of authors; and funding. Case reports were excluded from the analysis. Statistical analysis Descriptive statistics consisting of the mean (following by standard deviation) and proportions were produced. Fisher's F test was used to evaluate the proportions between the two periods of assessment. We considered P-values < 0.05 to be statistically significant. RESULTS Study characteristics A total of 1200 papers in the journals' databases were screened. From these, 123 (10.2%) were eligible for the current study. Sixty-three were retrieved from Acta Ortopedica Brasileira (51.2%) and 60 (48.8%) from Revista Brasileira de Ortopedia. The agreement between the observers for inclusion of the studies was 98.8%. Table 1 depicts the results from the data retrieved covering the period 2010-2016 and historical data from the previous study (2000-2009) on the same subject and journals.7 The data distribution in the two periods did not show any differences in the assessed outcomes between these periods (2000-2009 versus 2010-2016), since the confidence intervals overlapped for all relevant data. Table 1. Study characteristics - qualitative and quantitative data SD = standard deviation; AOB = Acta Ortopedica Brasileira; RBO = Revista Brasileira de Ortopedia. Most studies were from private institutions (65%), were self-funded (91.8%) and were conducted in Brazil's southeastern region (78.8%). The distribution of the studies conducted in other countries (12 studies) was: Turkey (4 studies), Portugal (3 studies) and others (5 studies; one each from China, Colombia, Uruguay, Italy and a multicenter study). Evidence hierarchy assessment Haynes pyramid of evidence Considering the standard classification as published by Haynes, most of the studies were considered to present evidence at level IV/V. No systematic reviews of randomized trials (RCTs) on hand surgery were recognized. However, we found 7 RCTs and 12 case-control/cohort studies, which encompassed 15.4% of the total number of studies considered, as shown in Graph 1. Graph 1. Distribution of studies as proposed using the Haynes model. JBJS/AAOS Evidence-Based Practice Committee Guideline The more comprehensive criteria proposed by the Journal of Bone and Joint Surgery showed a similar trend. Level I, II and III studies encompassed 16.4% of the total number of studies assessed. As occurred with the HP assessment, the majority of the studies were level IV and V. Graph 2 shows the distribution of the studies according to this classification. Graph 2. Distribution of studies according to the JBJS/AAOS Evidence-Based Practice Committee Guideline. Comparison with historical data from previous study:2000-2009 versus 2010-2016 In our previous report (2000-2009), we recognized 83 studies and only four were considered as presenting level I or II according to HP. There were no statistical differences (Fisher's F test, P = 0.13) in the proportion of published studies with level I or II evidence between 2000-2009 (4/83) and 2010-2016 (14/123). DISCUSSION Our study characterized the current panorama of hand surgery research published in Brazilian journals. Two different criteria were used to classify these studies. We first used the extended pyramid model proposed by Haynes in 2006. Each of these levels should build systematically from lower levels and provide substantially more useful information for guiding clinical decision-making.10 Secondly, the JBJS/AAOS Evidence-Based Practice Committee Guideline.11 This was created by a task force of representatives from the AAOS Evidence-Based Practice Committee and the Journal of Bone and Joint Surgery, with the aim of providing the best answers to questions about interventions, in a timely manner. As far as we know, this was the first study to include both evidence hierarchy criteria in the same investigation. We demonstrated that approximately 15% of the available research may be considered to present high quality-evidence (level I or II). In comparison with our previous analysis (2000 to 2009), a trend towards improvement of evidence was identified, although this was not statistically significant. Our findings reflect the challenge of conducting high-quality studies relating to hand surgery, such as blinded RCTs. Classifying studies within the hierarchy of evidence is important as a first step. However, some published data have proven that RCTs may be prone to a great variety of systematic errors, which means that analysis on the internal validity of each study is an essential measurement for assessing its quality.12 Bias assessment is another means of rating research and may be standardized using specific tools. However, to our knowledge, there is no consensus in the literature regarding the application of such assessments.13 Recent research conducted on papers published in other journals, such as Plastic and Reconstruction Surgery, Journal of Plastic, Reconstructive and Aesthetic Surgery, Journal of Hand Surgery - European Volume, Journal of Hand Surgery - American Volume, Journal of Bone & Joint Surgery and Bone & Joint Journal, has demonstrated similar low rates of high-quality studies (11.2%). This shows that the data regarding hand surgery are in line with data from other specialties.14 Another study reviewed all online articles published in 2010 in The Spine Journal (TSJ), Spine, European Spine Journal (ESJ), Journal of Neurosurgery: Spine (JNS) and Journal of Spinal Disorders and Techniques (JSDT). It found that 27.9% of the articles were of high quality and that spinal surgery journals with higher impact factors contained higher proportions of studies of better quality.15 Research on the neurosurgical literature from 2009 to 2010 demonstrated that only 10.3% of the studies were of high quality. Only 1 in 10 of the studies was classified as presenting a high level of evidence.16 Research in the palliative medicine literature has shown that there was an increase in the proportion of studies presenting a high level of evidence among all published articles, from 0.08% in 1970 to 0.38% in 2005. However, it does not show the quality of the studies, only the quantity.17 Finally, our findings may not reflect the current status of Brazilian hand surgery research. We believe that the quantity of RCTs may have been underestimated, given that relevant high-quality research tends to be published in high-impact journals, with greater visibility and academic impact. Broader analysis on this subject might explore these phenomena in the future. CONCLUSIONS Approximately 15% of hand surgery studies published in two major Brazilian journals are likely to be classified as high quality through two different classification systems. In addition, no trend towards improvement of the quality of evidence over the last 15 years was found. Division of Hand and Upper Limb Surgery, Department of Orthopedics and Traumatology, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPM-UNIFESP), Sao Paulo (SP), Brazil Sources of funding: None REFERENCES 1 Bhandari M Evidence-based medicine: why bother? Arthroscopy 2009 25 3 296 297 19245993 2 Guyatt GH Rennie D Users' guides to the medical literature: A manual for evidence-based clinical practice Chicago American Medical Association Press 2001 3 Sackett DL Richardson WS Rosenberg WM Haynes RB Evidence-based medicine: How to practice and teach EBM New York Churchill Livingstone 1997 4 Poolman RW Kerkhoffs GM Struijs PA Bhandari M International Evidence-Based Orthopedic Surgery Working Group Don't be misled by the orthopedic literature: tips for critical appraisal Acta Orthop 2007 78 2 162 171 17464602 5 Poolman RW Struijs PA Krips R Does a "Level I Evidence" rating imply high quality of reporting in orthopaedic randomised controlled trials? BMC Med Res Methodol 2006 6 44 44 16965628 6 Eberlin KR Labow BI Upton J 3rd Taghinia AH High-impact articles in hand surgery Hand (N Y) 2012 7 2 157 162 23730234 7 Moraes VY Belloti JC Moraes FY Hierarchy of evidence relating to hand surgery in Brazilian orthopedic journals Sao Paulo Med J 2011 129 2 94 98 21603786 8 Rosales RS Reboso-Morales L Martin-Hidalgo Y Diez de la Lastra-Bosch I Level of evidence in hand surgery BMC Res Notes 2012 5 665 665 23199054 9 Grandizio LC Huston JC Shim SS Graham J Klena JC Levels of Evidence for Hand Questions on the Orthopaedic In-Training Examination Hand (N Y) 2016 11 4 484 488 28149219 10 Haynes RB Of studies, syntheses, synopses, summaries, and systems: the "5S" evolution of information services for evidence-based health care decisions ACP J Club 2006 145 3 A8 A8 11 Wright JG Swiontkowski MF Heckman JD Introducing levels of evidence to the journal J Bone Joint Surg Am 2003 85-A 1 1 3 12 Burns PB Rohrich RJ Chung KC The levels of evidence and their role in evidence-based medicine Plast Reconstr Surg 2011 128 1 305 310 21701348 13 Juni P Witschi A Bloch R Egger M The hazards of scoring the quality of clinical trials for meta-analysis JAMA 1999 282 11 1054 1060 10493204 14 Sugrue CM Joyce CW Sugrue RM Carroll SM Trends in the Level of Evidence in Clinical Hand Surgery Research Hand (N Y) 2016 11 2 211 215 27390565 15 Amiri AR Kanesalingam K Cro S Casey AT Level of evidence of clinical spinal research and its correlation with journal impact factor Spine J 2013 13 9 1148 1153 23806347 16 Tieman J Sladek R Currow D Changes in the quantity and level of evidence of palliative and hospice care literature: the last century J Clin Oncol 2008 26 35 5679 5683 19001326 17 Yarascavitch BA Chuback JE Almenawer SA Reddy K Bhandari M Levels of evidence in the neurosurgical literature: more tribulations than trials Neurosurgery 2012 71 6 1131 1137 discussion 1137-8 22986592
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34926 Family/General Practice Obstetrics/Gynecology Nutrition A Case of Late Dumping Syndrome in a Post-bariatric Pregnant Lady Seen in a Primary Care Clinic Muacevic Alexander Adler John R Voon Son Wong 1 Ganason Anu Suria 2 Kang Waye Hann 3 1 Department of Population Medicine, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, MYS 2 Department of Primary Healthcare, Universiti Sains Islam Malaysia, Nilai, MYS 3 Department of Medicine, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, MYS Anu Suria Ganason [email protected] 13 2 2023 2 2023 15 2 e3492613 2 2023 Copyright (c) 2023, Voon Son et al. 2023 Voon Son et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Dumping syndrome is a common complication of bariatric surgery. A high clinical suspicion of hypoglycaemic events is required as the symptoms mimic early pregnancy complaints. Diagnosis and treatment of dumping syndrome remain a challenge in pregnancy. Thus, diet modification remains a mainstay of management. This case report discusses dumping syndrome in a post-bariatric surgery mother who presented hypoglycaemia symptoms in the primary care clinic. nutritional deficiency hypoglycaemia pregnancy bariatric surgery dumping syndrome The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction As the number of bariatric surgeries among women of childbearing age increases, dumping syndrome is not infrequently seen in pregnancy . Bariatric surgeries improve anovulation and lead to spontaneous pregnancy . Studies revealed that post-bariatric surgery, women have lower incidences of gestational diabetes and pregnancy-induced hypertension, and better fetal outcomes . However, pregnancy following bariatric surgery poses surgical, medical, and obstetric challenges, which require multidisciplinary team management . Thus, pre-pregnancy care is critical to ensure mother and fetal wellbeing. A pregnant mother with dumping syndrome may present with abdominal pain, nausea, palpitation, or tremor, which can be a physiological manifestation of pregnancy . Primary care physicians should be aware of possible symptoms of dumping syndrome and assess nutritional deficiencies in pregnant mothers following bariatric surgery . Case presentation A 37-year-old lady (gravida 2 para 0+1) had a booking visit at her local maternal health clinic during her first trimester. She has had a history of bariatric surgery, given morbid obesity with a body mass index (BMI) of 40, and subfertility with polycystic ovarian syndrome. She underwent bariatric surgery in 2020 but defaulted on her subsequent follow-up. She successfully lost 41 kg and eventually conceived spontaneously 18 months post-surgery. During her booking visit, she was screened for diabetes mellitus at nine weeks of gestation because of her advanced maternal age and her strong family history of diabetes mellitus. Her oral glucose tolerance test result was 4.2 (fasting) and 10.8 mmol/L (two hours post 75 g of glucose in 200 ml of water). She was then on medical nutrition therapy, with her home self-blood sugar monitoring ranging between 3.7 and 4.8 mmol/L. She reported a few episodes of hypoglycaemic symptoms such as sweating, hunger, and hand tremor, especially at two to three hours postprandial during her second trimester. Her capillary glucose reading documented during these hypoglycaemic events was within 2.5-2.8 mmol/L. She was subsequently diagnosed with late dumping syndrome and referred to the antenatal clinic for combined care. She was advised to reduce carbohydrate loads and space carbohydrate intake with a high protein diet and vegetables. With diet adjustment, hypoglycaemic events resolved. Her investigation revealed an iron deficiency anaemia with a haemoglobin of 9.8 g/dL. Following booking, the haemoglobin level was 11 g/dl. However, it slowly dropped to 10.2 g/dl and then 9.8 g/dL with hypochromic microcytic features (Table 1). She had a low serum iron, ferritin, and calcium level (Table 2). She was then started on a tablet of calcium carbonate 1 g twice daily, Iberet tablet once daily, and multivitamins. She was later diagnosed as a group B Streptococcus carrier at 10 weeks gestation when she presented with per vaginal discharge. Furthermore, at 24 weeks of gestation, she presented with chorioamnionitis symptoms and delivered a baby boy prematurely with a birth weight of 710 g. The baby was admitted to the neonatal intensive care unit and passed away on day four of life due to severe prematurity. Her post-partum period was uneventful, and no hypoglycaemia episodes were noted. Table 1 Serial readings of full blood count Full blood count Gestation age 9 weeks 15 weeks 20 weeks Normal reading Haemoglobin (g/dl) 11 |10.2 |9.8 13-17 Mean corpuscular haemoglobin (MCH) (pg) 31 29 |25 27.5-33.2 Mean corpuscular volume (MCV) (fl) 92 91 |78 80-100 Platelets (PLT) (x109/L) 289 299 215 150-450 Table 2 List of blood investigations and results Blood investigation Reading Normal reading Oral glucose tolerance test Fasting blood sugar (mmol/L) 4.2 4-5.1 Two hours postprandial glucose (mmol/L) |10.8 4-7.8 Blood sugar monitoring at home Fasting capillary glucose (mmol/L) 4.0-4.9 4-5.3 One hour postprandial glucose (mmol/L) 3.7-4.8 4-7.8 Capillary blood sugar during hypoglycaemia event (mmol/L) |2.5-2.8 4-7.8 Iron studies Iron (umol/L) |6.7 10.74-30.43 Ferritin (umol/mL) |5.8 18-160 Total iron-binding capacity (umol/L) |83.9 42-80.5 Renal profile Urea (mg/dl) 1.8 6-24 Sodium (mmol/L) 138 135-145 Potassium (mmol/L) 4.2 3.5-5 Creatinine (mmol/L) 39 95-105 Other blood tests Corrected Ca (mmol/L) |2.15 2.25-2.65 Phosphate (mg/dl) 1.26 0.85-1.1 Magnesium (mmol/L) 0.75 0.85-1.58 Vitamin D (ng/ml) 31.5 30-100 Folate (nmol/L) 10.48 3-18 Vitamin B12 (pmol/L) 182.8 180-914 Discussion Obesity is a worldwide health issue impacting about 650 million individuals, particularly during the reproductive years . In Malaysia, one in two adults is overweight or obese, according to the National Health Morbidity Survey 2019. Obesity was higher in females (up to 54.4%), and one in five mothers was obese when conceived . There is an increase in bariatric surgeries among women of childbearing age to achieve sustained weight loss. Thus, family physicians should be aware of the complications of bariatric surgery and its impact on pregnancies . All active reproductive women who underwent bariatric surgery should be provided pre-pregnancy counselling. The conventional type of contraception should be considered as the efficacy of hormonal contraception may be affected due to malabsorption post-bariatric surgery. Pregnancy should be postponed for 12 to 24 months post-bariatric surgery until weight is stabilized . There is a higher risk of miscarriage, fetal malnutrition, and intrauterine growth retardation if conceived in the post-bariatric period . There is some indication, nevertheless, that pregnancy within the first year after surgery may have a negative outcome . The typical nutritional deficiencies found after bariatric surgery are iron, folate, vitamin B1, B12, and D, and calcium. These micronutrients are essential for maternal health and fetal growth. Severe deficiency of micronutrients can cause adverse effects of pregnancy, such as anaemia and congenital abnormality. A multidisciplinary team should therefore be involved in pre-pregnancy care. Mineral supplements and multivitamins should be prescribed before and during pregnancy . Dumping syndrome is a common complication of post-bariatric surgery. It has a higher risk of maternal hypoglycaemia and subsequent fetal hypoglycaemia resulting in intrauterine growth restriction and small gestation-age infants . There are few postulated mechanisms towards dumping syndrome. The pathophysiology of dumping syndrome can be multifocal and not well understood. It can be either early dumping or late dumping . During the early gestational period, there is a physiological increase in insulin secretion and insulin hypersensitivity. These subsequently increase the risk of hypoglycaemia in pregnant ladies post-bariatric surgery. In post-bariatric surgery, rapid gastric emptying and glucose absorption following smaller stomach capacity can cause hyperinsulinemia and reactive hypoglycaemia . Early dumping syndrome usually happens 15 minutes to one-hour post-meal. It is due to the rapid transit of gastric content causing osmotic shifts in the proximal small intestine. Vasomotor symptoms develop as a consequence of a decrease in blood pressure . Patients are advised to have smaller meals up to six times per day and avoid fluid intake within 30 minutes after the meal. They should be supine for 30 minutes to reduce vasomotor symptoms by prolonging gastric emptying . Late dumping syndrome usually happens one to three hours postprandial. It is further explained in this patient as she has a recurrent episode of hypoglycaemic effects two to three hours postprandial . Dietary modifications include advice on low glycaemic index foods, elimination of simple carbohydrates, and daily protein of 60 g . The oral glucose tolerance test (OGTT) is frequently poorly tolerated and less accurate in women post-bariatric surgery. OGTT should be substituted with home capillary blood sugar measurement over one week in 24 to 28 weeks . The patient's symptoms improved significantly following guided dietary advice. However, in view of nutritional deficiency and group B Streptococcus infection, there is a possibility of complications in pregnancy leading to premature delivery. Women following Roux-en-Y gastric bypass are at higher risk of developing internal hernia during pregnancy . They may present with abdominal pain and vomiting, easily mistaken for pregnancy-related complaints. Immediate surgical intervention must be considered in abdominal pain, regardless of pregnancy. Other surgical complication includes adhesion, band slippage, and small intestine ischemia. The course of labour and delivery should not be affected by a patient's prior history of bariatric surgery . Conclusions Women are prone to clinical challenges in subsequent pregnancies following bariatric surgery. A physician should provide pre-pregnancy counselling and regular assessment of nutritional status prior to conception. Clinical difficulties can arise following bariatric surgery in pregnant women of reproductive age. Thus, pregnancies that follow bariatric surgery require extensive team involvement due to the high risk of complications. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Pregnancy following bariatric surgery medical complications and management Obes Surg Narayanan RP Syed AA 2523 2529 26 2016 27488114 2 Bariatric surgery and its impact on fertility, pregnancy and its outcome: a narrative review Ann Med Surg (Lond) Pg Baharuddin DM Payus AO Abdel Malek Fahmy EH 103038 72 2021 34849219 3 Maternal and neonatal outcomes in women undergoing bariatric surgery: a systematic review and meta-analysis Eur J Obstet Gynecol Reprod Biol Galazis N Docheva N Simillis C Nicolaides KH 45 53 181 2014 25126981 4 Pregnancy after bariatric surgery: consensus recommendations for periconception, antenatal and postnatal care Obes Rev Shawe J Ceulemans D Akhter Z 1507 1522 20 2019 31419378 5 Pregnancy after bariatric surgery: a narrative literature review and discussion of impact on pregnancy management and outcome BMC Pregnancy Childbirth Falcone V Stopp T Feichtinger M 507 18 2018 30587161 6 World Health Organization. Obesity and overweight 2019 7 National Health and Morbidity Survey (NHMS) 2019 Malaysia. Non-communicable diseases, healthcare demand, and health literacy 2019 8 Preparing for and managing a pregnancy after bariatric surgery Semin Perinatol Kominiarek MA 356 361 35 2011 22108087 9 A matter of timing pregnancy after bariatric surgery Obes Surg Heusschen L Krabbendam I van der Velde JM 2072 2079 31 2021 33432482 10 The effects of bariatric surgery on periconception maternal health: a systematic review and meta-analysis Hum Reprod Update Snoek KM Steegers-Theunissen RP Hazebroek EJ Willemsen SP Galjaard S Laven JS Schoenmakers S 1030 1055 27 2021 34387675 11 Pregnancy outcome of patients who conceive during or after the first year following bariatric surgery Am J Obstet Gynecol Sheiner E Edri A Balaban E Levi I Aricha-Tamir B 50 56 204 2011 12 Pathophysiology, diagnosis and management of postoperative dumping syndrome Nat Rev Gastroenterol Hepatol Tack J Arts J Caenepeel P De Wulf D Bisschops R 583 590 6 2009 19724252 13 Internal hernias in pregnant females with Roux-en-Y gastric bypass: a systematic review Surg Obes Relat Dis Dave DM Clarke KO Manicone JA Kopelan AM Saber AA 1633 1640 15 2019 31378635
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Front Oncol Front Oncol Front. Oncol. Frontiers in Oncology 2234-943X Frontiers Media S.A. 10.3389/fonc.2023.1054978 Oncology Case Report Sigmoido-vesical fistula secondary to sigmoid colon cancer presenting as urinary tract infection with Lactococcus lactis: A case report An Yanhua 1 Cao Qiumei 1 * Liu Yixin 2 Lei Luping 1 Wang Dawei 1 Yang Yanjie 2 Kong Weijie 3 An Dali 3 Liu Dan 4 1 Department of General Practice, Beijing Tongren Hospital, Capital Medical University, Beijing, China 2 Emergency Department, Beijing Tongren Hospital, Capital Medical University, Beijing, China 3 Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China 4 Department of Urologic Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China Edited by: Narimantas Samalavicius, Vilnius University, Lithuania Reviewed by: Babak Haghshenas, Kermanshah University of Medical Sciences, Iran; Bahareh Hajikhani, Shahid Beheshti University of Medical Sciences, Iran *Correspondence: Qiumei Cao, [email protected] This article was submitted to Gastrointestinal Cancers: Colorectal Cancer, a section of the journal Frontiers in Oncology 01 3 2023 2023 13 105497827 9 2022 13 2 2023 Copyright (c) 2023 An, Cao, Liu, Lei, Wang, Yang, Kong, An and Liu 2023 An, Cao, Liu, Lei, Wang, Yang, Kong, An and Liu This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. A colovesical fistula is a pathological communication between the colon and bladder. The symptoms include pneumaturia, fecaluria, and a lower urinary tract infection. The diagnosis is based on clinical symptoms, but the symptoms are not specific. Therefore, confirming the diagnosis is challenging. Urine cultures performed in patients with colovesical fistulas usually show growth of Escherichia coli or mixed growth of bowel organisms. Urinary tract infections caused by Lactococcus lactis are very rare, as it is rarely considered pathogenic in humans. We report the case of a 70-year-old woman who presented with symptoms of a recurrent urinary tract infection. Urine cultures were positive for L. lactis. Abdominopelvic computed tomography (CT) revealed focal thickening of the bladder wall and gas in the bladder. Cystoscopic examination and colonoscopy revealed sigmoid colon cancer and a sigmoido-vesical fistula. Laparoscopic surgical treatment was done. The patient recovered and was discharged 3 weeks later without chemoradiotherapy. On follow-up after 6 months, the patient was asymptomatic and stable. To our knowledge, this is the second reported case of L. lactis infection of the urinary tract and the first reported case in adults. L. lactis infection usually indicates the presence of serious underlying diseases such as malignancies, uncontrolled diabetes, and organ failure. sigmoid colon cancer sigmoido-vesical fistula urinary tract infection Lactococcus lactis diabetes mellitus pmcIntroduction Colovesical fistula is a rare complication of various diseases, particularly diverticulitis and neoplasms of the colon and bladder. It is difficult to diagnose because of the atypical symptoms. Lactococcus lactis infection is very rare since it is considered nonpathogenic in humans. Here, we present the case of a 70-year-old woman with a recurrent urinary tract infection. Urine cultures revealed L. lactis. She was diagnosed with a sigmoido-vesical fistula secondary to sigmoid colon cancer, underwent surgical treatment, and recovered. To our knowledge, this is the first reported case of L. lactis infection of the urinary tract in adults. Case presentation A 70-year-old woman was admitted to our hospital due to urinary frequency, urgency, and hematuria of 1 month duration. She also complained of lower abdominal pain and 3 kg weight loss. She presented with a fever for 3 days during this period, with a peak body temperature of 38.3degC. Approximately 10 days prior to admission, she consulted the urology outpatient department and received anti-microbial treatment. Thereafter, only a slight resolution of symptoms was observed. The patient had a history of type 2 diabetes mellitus for 10 years and was maintained with oral hypoglycemic drugs. Upon physical evaluation, her vital signs were stable. Enlarged superficial lymph nodes were not palpable. Mild tenderness was observed in the lower abdominal region, without rebound tenderness. No costovertebral angle tenderness was noted. Routine blood tests revealed a normal white blood cell count, hematocrit, and platelet count. Serum C-reactive protein level was increased to 78.38 mg/L (normal range: <10 mg/L). Routine urinalysis showed positive results for red cells (39/high power field), white cells (47/high power field), urine protein, and urine sugar. The fecal occult blood test results were positive. Serum tumor marker analysis revealed that carcinoembryonic antigen (CEA) was mildly elevated to 6.0 ng/ml (normal range: <5 ng/ml). Fasting plasma glucose was 13.6 mmol/L, and glycated hemoglobin A1c (HBA1C) was 8.9%. Urine culture was done thrice, which detected L. lactis in two readings. Ultrasound examination showed that the right bladder wall was thickened and revealed a 3.6 cm x 1.5 cm lesion, which was considered likely inflammatory tissue . Figure 1 Imaging examinations. (A): Ultrasound examination. The right bladder wall was thickened, and a 3.6 cm x 1.5 cm lesion was revealed; (B): Abdominopelvic computed tomography (CT). Focal thickening of the bladder wall and gas in the bladder were noted; (C): Computed tomography urography (CTU). Gas between the bladder dome and adjacent sigmoid colon, and a thickened bladder and sigmoid colon wall were revealed. On day 10 of admission, the temperature suddenly increased to 39.3degC with worsening lower urinary tract symptoms and lower abdominal pain. Also, foreign bodies were observed in the urine, described as similar to watermelon seeds and tea stems. Abdominopelvic computed tomography (CT) revealed focal thickening of the bladder wall and gas in the bladder . The CT scan also showed thickening of the peritoneum in front of the bladder; however, no significant abnormalities were found in the small intestine or colon. Then computed tomography urography (CTU) was performed, which showed gas between the bladder dome and the adjacent sigmoid colon. These findings were consistent with a sigmoido-vesical fistula . The urologic surgeon performed a cystoscopic examination, which showed turbid urine and a rough bladder wall , but no fistula was found. Colonoscopy was then performed, which revealed sigmoid colon cancer that occupied nearly the entire colon . Figure 2 (A): Cystoscopic examination. Changes in the mucosa of the bladder were noted; (B): Colonoscopy. Sigmoid colon cancer was revealed which occupied nearly the entire colon. The patient was transferred to the general surgery department and underwent laparoscopic surgical treatment. The tumor was visualized to be in the sigmoid colon, where it was observed that the tumor had invaded the entire wall of the colon to the bladder. The colonic wall outside the tumor was adhered to the bladder wall. Enlarged lymph nodes were identified at the root of the mesenterium. No ascites or peritoneal neoplastic dissemination was found during intraoperative exploration. A postoperative pathological examination confirmed persistent, highly differentiated tubular adenocarcinoma (about 7.0 x 4.0 x 4.5 cm in size) accumulating almost the entire colonic wall. The tumor invaded through the muscularis propria into the subserosal adipose tissue. No metastasis was found in 15 peri-colonic lymph nodes. The pathological report also revealed fistulous tract formation between the sigmoid colon and the bladder with severe acute and chronic inflammation in the bladder wall. No tumor invasion was found in the bladder. The tumor was staged as T3N0M0 according to the TNM classification. Figure 3 Postoperative pathological outcomes. Highly differentiated tubular adenocarcinoma. (A) x40; (B) x100; (C) x200. The patient recovered and was discharged 3 weeks later without chemo-radiotherapy. Six months after surgery, the patient exhibited normal eating and bowel habits and experienced a weight increase of 1 kg. The blood glucose level was normal and there were no symptoms of a urinary tract infection. The case timeline is shown in Figure 4 . Figure 4 Case timeline. Discussion and conclusions Colovesical fistulas are pathological communications between the colon and bladder (1). Among these, sigmoido-vesical fistulas are the most common (2). Etiological factors include inflammatory diseases, neoplasms of the colon and bladder, pelvic radiation therapy, and traumatic and iatrogenic injuries (3). Diverticulitis is the most common cause, accounting for approximately 65%-79% of cases. The second leading etiology is cancer, contributing 10%-20% of cases, with colonic adenocarcinoma being the most frequent type. Crohn's disease accounts for 5%-7% of cases (4). Patients with colovesical fistulas usually present with pneumaturia (50%-85% of cases), fecaluria (51%-68% of cases), and symptoms of lower urinary tract infection (57%-71%), which include frequency, urgency, suprapubic pain, and hematuria (1, 3-5). Our patient presented with urinary frequency, urgency, hematuria, lower abdominal pain, and weight loss. The diagnosis is based on clinical symptoms; however, the symptoms and signs are not specific. It is challenging to confirm the diagnosis of a colovesical fistula, and it may take months before the condition is recognized. The patient in this case was monitored for almost a month before the diagnosis was confirmed. After admission, poor glycemic control was considered the probable cause of the urinary tract infection; however, the symptoms resolved partly after administration of insulin glargine and intravenous ceftazidime. Further work-up was performed when a sudden worsening of symptoms was observed despite ongoing treatment. A classical presentation of colovesical fistulas is Gouverneur syndrome, characterized by suprapubic pain, frequency, dysuria, and tenesmus (6), which were consistent with the patient. In this case, the fistula was caused by the tumor and repeated inflammatory reactions around it. Another relevant concern is investigating the specific pathogen. Bacteria that commonly cause urinary tract infections include Escherichia coli, Klebsiella, and Enterobacter, which travel from the gastrointestinal tract and perineal area into the urinary tract. Previous studies reported that urine cultures performed in patients with colovesical fistulas showed growth of E. coli in approximately 33% of cases and mixed growth of bowel organisms or enterococci in approximately 65% of cases (1, 4). In this case, urine culture was performed three times, which revealed L. lactis twice. Lactococcus is a genus of facultative anaerobic catalase-negative gram-positive intestinal cocci (7). This genus of bacteria is commonly used in manufacturing dairy products and has been investigated for use in the biotechnology industry as a delivery system for vaccines and other therapies (8). Urinary tract infections caused by L. lactis are very rare, as it is not considered pathogenic in humans. To our knowledge, this is the second reported case of L. lactis infection of the urinary tract and the first reported case in adults (7, 9). A preterm neonate was reported to experience a urinary tract infection caused by L. lactis from the gastrointestinal tract after ingestion of the mother's breast milk (9). L. lactis infection occurs more frequently in immunocompromised patients or those with significant underlying conditions such as malignancies, uncontrolled diabetes, and organ failure (10, 11). In our case, the patient had uncontrolled diabetes and sigmoid colon cancer; hence, she was more at risk for opportunistic infections. CT showed free gas in the bladder, which was initially considered to be produced by bacteria. However, laboratory examinations showed mildly elevated CEA levels and a positive fecal occult blood test, which suggested a possible underlying lesion that should be further investigated. Hence, a clinical history and physical examination, supplemented by appropriate laboratory work-up and imaging, are required to prevent delay in diagnosis. In conclusion, it is recommended to determine the specific etiology of recurrent urinary tract infections, and colovesical fistulas must be included as a differential diagnosis. If L. lactis infection is present, it is essential to identify the underlying diseases, such as malignancies, uncontrolled diabetes, and organ failure. Data availability statement The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author. Ethics statement Written informed consent was obtained from the participant/patient(s) for the publication of this case report. Author contributions YA, QC, and YL were the physicians-in-charge of the patient, reviewed the literature, and contributed to manuscript drafting. LL, DW, and YY reviewed the literature and contributed to manuscript drafting. WK and DA were the patient's surgeons, analyzed and interpreted the imaging findings. DL performed the cystoscopy and was responsible for the interpretation of the findings. All authors contributed to the article and approved the submitted version. Acknowledgments We would like to express our gratitude to the doctors from the Department of Clinical Medical Laboratory for interpretation of urine cultures. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. References 1 Pollard SG Macfarlane R Greatorex R Everett WG Hartfall WG . Colovesical fistula. Ann R Coll Surg Engl (1987) 69 :163-5. 2 Fujii Y Moriguchi Y Taniguchi N . Vesicosigmoidal fistula: Sonographic findings. J Ultrasound Med (2010) 29 :993-996. doi: 10.7863/jum.2010.29.6.993 20498474 3 Granieri S Sessa F Bonomi A Paleino S Bruno F Chierici A . Indications and outcomes of enterovesical and colovesical fistulas: Systematic review of the literature and meta-analysis of prevalence. BMC Surg (2021) 21 :265. doi: 10.1186/s12893-021-01272-6 34044862 4 Golabek T Szymanska A Szopinski T Bukowczan J Furmanek M Powroznik J . Enterovesical fistulae: Aetiology, imaging, and management. Gastroenterol Res Pract (2013) 2013 :617967. doi: 10.1155/2013/617967 24348538 5 Daniels IR Bekdash B Scott HJ Marks CG Donaldson DR . Diagnostic lessons learnt from a series of enterovesical fistulae. Colorectal Dis (2002) 4 :459-62. doi: 10.1046/j.1463-1318.2002.00370.x 6 Vidal Sans J Pradell Teigell J Palou Redorta J Villagrasa Serrano M Banus Gassol JM . Review of 31 vesicointestinal fistulas: Diagnosis and management. Eur Urol (1986) 12 :21-7. doi: 10.1159/000472571 7 Slaoui A Benmouna I Zeraidi N Lakhdar A Kharbach A Baydada A . Lactococcus lactis cremoris intra-uterine infection: About an uncommon case report. Int J Surg Case Rep (2022) 94 :107077. doi: 10.1016/j.ijscr.2022.107077 35461182 8 Bahey-El-Din M Gahan CG . Lactococcus lactis: From the dairy industry to antigen and therapeutic protein delivery. Discovery Med (2010) 9 :455-61. 9 Newby B Ramesh KK . Urinary tract infection in a preterm neonate caused by lactococcus lactis. Can J Hosp Pharm (2014) 67 :453-4. doi: 10.4212/cjhp.v67i6.1409 10 Lee MR Huang YT Lee PI Liao CH Lai CC Lee LN . Healthcare-associated bacteraemia caused by leuconostoc species at a university hospital in Taiwan between 1995 and 2008. J Hosp Infect (2011) 78 :45-9. doi: 10.1016/j.jhin.2010.11.014 11 Shimizu A Hase R Suzuki D Toguchi A Otsuka Y Hirata N . Lactococcus lactis cholangitis and bacteremia identified by MALDI-TOF mass spectrometry: A case report and review of the literature on lactococcus lactis infection. J Infect Chemother (2019) 25 :141-6. doi: 10.1016/j.jiac.2018.07.010
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34929 Allergy/Immunology General Surgery Diagnosis and Management of a Hypersensitivity Reaction to Titanium-Containing Surgical Clips: A Case Report Muacevic Alexander Adler John R Ramcharan Darren N 1 Alaimo Kayla L 1 Tiesenga Frederick 2 1 Medicine, Saint James School of Medicine, Park Ridge, USA 2 General Surgery, West Suburban Medical Center, Chicago, USA Darren N. Ramcharan [email protected] 13 2 2023 2 2023 15 2 e3492912 2 2023 Copyright (c) 2023, Ramcharan et al. 2023 Ramcharan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Although titanium allergies are not commonly diagnosed, they can present with a variety of conditions years after the implantation of titanium-containing medical devices. Furthermore, there are few options to effectively manage the long-term outcomes of these conditions. We present the case of a 41-year-old female who experienced neck swelling, pain, and difficulty swallowing 16 years after a right thyroid lobectomy for benign follicular adenoma, requiring the implantation of titanium-containing surgical clips in her neck. This was accompanied by an extensive symptomatic history, and the patient showed mild reactivity to nickel and titanium on a metal lymphocyte transformation test analysis. X-ray and computed tomography of the neck later confirmed the location of 18 surgical clips. The patient was diagnosed with a chronic immune disease including immune complex disease and mast cell activation-related symptoms. Symptoms were managed with low-dose naltrexone until the surgical clips were removed. Further research is needed to identify more accurate testing methods to diagnose titanium hypersensitivity. Alternative treatment methods should be explored to reduce disease burden and complications related to titanium-containing implants. metal-ltt melisa case report low-dose naltrexone patch testing titanium allergy hypersensitivity The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Nickel, cobalt, chromium, and titanium are just some of the many metallic elements used widely in dental and surgical implants. While nickel has a well-documented history of causing hypersensitivity reactions, with an estimated prevalence of 17% in women and 3% in men in some studies, titanium allergies are less frequently diagnosed . Titanium alloys are desirable for implantable devices due to their biocompatibility and resistance to corrosion within body tissues. Implantation of titanium-containing devices increases the metal concentration and exposure to bodily fluids or tissues. This increases the likelihood of allergic or hypersensitivity reactions . Metallic ions and particles released into the surrounding environment may generate molecules capable of triggering immune reactions. There are multiple mechanisms by which metallic ions are believed to cause hypersensitivity reactions to metal alloys. Proposed mechanisms include sensitization of T cells to hapten-like molecules or phagocytosis and activation of macrophages. The activation of immune cells may lead to the release of pro-inflammatory cytokines and stimulation of B cells to produce IgE and IgG antibodies to metal-containing molecules . Reactions to metallic ions tend to have systemic effects and manifest as a broad range of signs and symptoms between individual cases, making it difficult to diagnose cases purely on clinical presentation. Prior notable cases of suspected metal reactions encountered include a 61-year-old female who had complaints of nonspecific symptoms following surgical clip placement during cholecystectomy. This patient had a history of a localized allergic reaction to titanium plates after ankle surgery. A review of medical records showed her memory lymphocyte immunostimulation assay (MELISA) had equivocal results for titanium allergy . Also encountered was a 28-year-old female who presented in 2016 with a variety of symptoms 11 months after cholecystectomy with surgical clip placement. This patient had a history of delayed hypersensitivity to nickel and other metal allergies with documented positive titanium skin patch test but equivocal MELISA results. Laparoscopic removal of the clips led to the resolution of symptoms in one month . Although surgical removal of metallic foreign bodies is the typical intervention for these conditions, novel drug therapies such as low-dose naltrexone (LDN) may provide the benefit of symptomatic relief until surgical intervention due to their immunomodulatory effects . In this report, we present a case of a suspected titanium hypersensitivity reaction managed with LDN and the removal of surgical clips. Case presentation Chief complaint A 41-year-old female presented to her primary care physician (PCP) in August 2021 complaining of worsening neck pain, swelling, and difficulty swallowing at the site of a previous partial thyroidectomy . She also reported having associated intermittent nausea and tenesmus, episodes of presyncope, and full-body tremors triggered by crouching, leaning, sitting, or standing upright for extended periods at the time of presentation. Figure 1 Swelling and rash visualized on the anterior neck. History of present illness The patient contacted the surgery clinic after her PCP referred her for an X-ray and a three-dimensional computed tomography (3D CT) scan in October 2021 due to suspicion of delayed hypersensitivity reaction to surgical clip implantation in her neck. Imaging revealed 18 surgical clips that were implanted in her neck during a right thyroid lobectomy for the removal of a benign follicular adenoma in 2005. The patient reported a majority of her symptoms occurred in 2015 or later that were described by her PCP as a "mono-like" syndrome, although she had negative mononucleosis antibody titers when evaluated. She first experienced extreme fatigue and general malaise associated with difficulty ambulating and speaking, as well as general left-sided abdominal pain. Additional symptoms experienced by the patient over the last 10 years include but are not limited to memory loss, difficulty concentrating, severe shortness of breath, hot and cold flashes, metallic taste in the mouth, halitosis, change in body odor, abdominal bloating, decreased libido, joint and body aches, muscle pain and tightness, bruxism, insomnia, dizziness, sudden-onset nausea, diarrhea, constipation, blurred vision, hair loss, skin rash, dermatitis, tachycardia, palpitations, weight gain, mood swings, coarse facial hair growth, increasing frequency of asthma exacerbations, paresthesia of extremities, migraines, acne, anovulation, lymphadenopathy with associated pain, swelling of hands and feet, mild fevers, sore throat, cough, laryngitis without a sore throat, thyroid swelling, tinnitus, and fecal incontinence. She reported an episode of syncope in 2019 and described brain fog and episodic fasciculations throughout 2020. At the time of the encounter, the patient reported her current symptomatology consistent with her chief complaint while awaiting surgical removal of the implanted clips. Past medical history The patient's past medical history consisted of type 2 diabetes, mixed hyperlipidemia, nonalcoholic steatohepatitis, pancreatitis, splenomegaly, and autonomic neuropathy. The patient was also diagnosed with atypical depression and was prescribed mirtazapine which temporarily relieved her insomnia. However, when the depression symptoms returned, mirtazapine was discontinued. The patient was currently on 15 mg of melatonin to aid with sleep. The patient's past surgical history included bilateral tubal ligation with Filshie clip placement in 2010 as well as laparoscopic cholecystectomy with surgical clip placement in 2005. The patient's social history was insignificant, with no smoking and occasional alcohol consumption. The patient had no known history of allergic reactions or allergies to metals or other substances. Investigations Laboratory Investigations The patient had positive laboratory results for inflammation between 2016 and 2021 (Table 1). Further testing revealed negative results for markers of autoimmune disease and inflammation between 2016 and 2019. Metal lymphocyte transformation test (metal-LTT) performed in 2021 revealed mild reactivity to nickel and titanium metals. Repeat examination for markers of autoimmune disease and inflammation remained within normal limits and not significant in 2022. Table 1 Significant laboratory findings. SBP = systolic blood pressure; DBP = diastolic blood pressure; CRP = C-reactive protein; LSI = lymphocyte stimulation index Patient value Normal range CRP 0.5 mg/dL <0.3 mg/dL Eosinophils 4.4% 1-4% Blood pressure (SBP) 78-133 mmHg <120 mmHg Blood pressure (DBP) 53-114 mmHg <80 mmHg LSI (titanium alloy) 2.1 <2.0 LSI (nickel) 2.0 <2.0 Imaging CT scan of the abdomen and pelvis performed with oral contrast in 2011 confirmed metal surgical clips in the gallbladder fossa and bilateral tubal ligation with Filshie clips. Cervical X-rays and a CT scan of the neck performed in October 2021 showed 18 surgical clips in the midline with mild-to-moderate degenerative changes of the cervical spine. Figure 2 Cervical X-ray with frontal (A) and lateral (B) views of the neck showing surgical clips (yellow arrows). Figure 3 3D CT scan of the neck with frontal (A), posterolateral (B), and lateral (C) views showing surgical clips (yellow arrows). Preoperative diagnosis Metallic surgical clips (foreign bodies) implanted in the right thyroid bed/parapharyngeal space causing a hypersensitivity reaction resulting in immune complex disease and mast cell activation-related symptoms. Treatment The patient was prescribed 0.1 mg fludrocortisone after being diagnosed with autonomic neuropathy in 2021 which helped regulate her blood pressure and decreased thyroid pain. After consultation with a rheumatologist in July 2022, the patient was started on LDN therapy of 1.5 mg twice daily to minimize immune activation prior to surgery. This led to an improvement of most autonomic symptoms (dizziness, paresthesia, presyncope, etc.), as well as neck swelling. Removal of 18 surgical clips from the previous right thyroid bed/paratracheal space was performed in December 2022 with one clip remaining due to the inability to properly identify it on X-ray/CT scan prior to the procedure . Figure 4 Intraoperative X-ray with lateral (A) and frontal (B) views showing empty right parapharyngeal space. Figure 5 X-ray of 18 surgical clips removed during the procedure. Postoperative diagnosis Hypersensitivity reaction to surgical clips causing suspected immune-related disease inclusive of immune complex disease and mast cell activation-related symptoms. Outcome/Progress The patient reported resolution of most symptoms within one week of surgical clip removal, complicated by a self-resolving seroma at the incisional site . At the two-month follow-up, the patient reported the appearance of pruritic rashes at the surgical site, which were easily managed with over-the-counter antihistamines. The patient has resumed LDN therapy taking 3 mg daily to minimize hypersensitivity reactions to future metal exposure (diet, environmental). Figure 6 Incisional site with seroma (yellow arrow). Discussion The challenges presented in patients with complex presentations of hypersensitivity reactions to metallic ions include a lack of availability of validated tools for a reliable diagnosis of these diseases and management of symptoms prior to definitive surgical intervention. A possible reason for the inaccuracy of current testing methods may be the impurity or variability in the composition of surgically implanted metal devices. Different metallic ions can provide a multitude of immunogenic molecules that induce allergic reactions . Currently, patch testing is the most common method for diagnosing metal allergies, especially in orthopedic procedures, whereby a series of small amounts of metallic compounds are placed in patches on the skin and observed for inflammatory changes. In patients with known metal allergies who have metal-containing implants, nickel has been documented to show strong reactions to patch testing while other metals such as titanium and aluminum powder show no reaction to testing. These inconsistencies may be due to differences in metal salt used in patches, concentrations of compounds, and timings of readings . Prior studies report a sensitivity of about 75% using traditional patch testing for type IV hypersensitivity reactions which may lead us to consider using alternative metal solutions such as titanium sulfate or titanium chloride. These solutions may produce more reliable reagents than titanium oxide, although further studies would need to be conducted. Metal-LTT, as used in this patient's case, may produce false-positive results by detecting non-relevant lymphocyte proliferation in nonsensitized patients. Therefore, it does not provide reliable, specific, or sensitive results compared to MELISA when diagnosing metal allergies . This suggests that MELISA is the most favorable diagnostic test to use in patients with or without suspected metal allergies or those being considered for metal-containing implants. Interleukin-17 (IL-17) and interleukin-22 (IL-22) may provide a novel diagnostic testing method for metal hypersensitivities as IL-17 has been found to be increased in patients with positive patch testing and IL-22 is implicated in inflammatory reaction of dermatitis to other metals such as nickel. Further studies are needed to determine the reliability and accuracy of these biomarkers in patients with undiagnosed metal allergies . Nonsurgical management of symptoms in patients experiencing metal hypersensitivity reactions has traditionally been with the use of corticosteroids to reduce inflammation but LDN is emerging as an alternative to reduce inflammation without as much concern for harmful side effects. LDN is thought to reduce inflammation by antagonizing mu-opioid receptors paradoxically increasing endogenous endorphin production. Endorphins modulate the function of T-regulatory cells which reduces the production of proinflammatory cytokines and immunoglobulins by T and B cells, respectively. This therapy has been shown to be an effective long-term alternative to surgery or traditional medications in a variety of autoimmune and inflammatory diseases related to immune cell activation, which may allow improved function for patients . Conclusions Our approach to patients with suspected metal allergies should consider both the patient's exposure to metal implants and their history of symptoms. This, however, proves to be challenging when considering the variability of clinical presentations of metal hypersensitivity reactions. Clinical suspicion of these conditions should be able to further guide when to utilize available diagnostic tools. The need to develop more reliable and accurate testing for diagnosis is an important concern in clinical practice with the increasing prevalence of metal allergies, specifically in the fields of dentistry and surgery. When managing symptoms of patients with confirmed or suspected metal hypersensitivity reactions and related conditions, physicians should consider a multidisciplinary approach utilizing both medical and surgical interventions when appropriate to improve the overall health and outcome for these patients. We would like to acknowledge our mentor Dr. Frederick M. Tiesenga, MD, FACS, for his supervision, support, and valuable recommendations without which this report would not have been possible. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Exploring the incidence, implications, and relevance of metal allergy to orthopaedic surgeons J Am Acad Orthop Surg Glob Res Rev Haddad SF Helm MM Meath B Adams C Packianathan N Uhl R 0 3 2019 2 Titanium allergy: a literature review Indian J Dermatol Goutam M Giriyapura C Mishra SK Gupta S 630 59 2014 3 Titanium: a review on exposure, release, penetration, allergy, epidemiology, and clinical reactivity Contact Dermatitis Fage SW Muris J Jakobsen SS Thyssen JP 323 345 74 2016 27027398 4 Adverse reactions to titanium surgical staples in a patient after cholecystectomy CRSLS Tiesenga F Wang J Crews C 1 2 18 2014 5 Delayed titanium hypersensitivity and retained foreign body causing late abdominal complications Case Rep Surg Jain MS Lingarajah S Luvsannyam E 5515401 2021 2021 33763279 6 Low-dose naltrexone (LDN): a promising treatment in immune-related diseases and cancer therapy Int Immunopharmacol Li Z You Y Griffin N Feng J Shan F 178 184 61 2018 29885638 7 Titanium allergy or not? "Impurity" of titanium implant materials Health Harloff T Honle W Holzwarth U Bader R Thomas P Schuh A 306 310 2 2010 8 Patch testing with a large series of metal allergens: findings from more than 1,000 patients in one decade at Mayo Clinic Dermatitis Davis MD Wang MZ Yiannias JA Keeling JH Connolly SM Richardson DM Farmer SA 256 271 22 2011 22652903 9 Validity of MELISA for metal sensitivity testing Neuro Endocrinol Lett Valentine-Thon E Schiwara HW 57 64 24 2003 12743534 10 Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment BMJ Case Rep Weinstock LB Brook JB Myers TL Goodman B 0 2018 2018
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Eur Bus Org Law Rev European Business Organization Law Review 1566-7529 1741-6205 Springer International Publishing Cham 279 10.1007/s40804-023-00279-1 Article Covid-19 Measures in Switzerland Considerations from a Practice Perspective Jagmetti Luca [email protected] Attorney-at-law, partner with Bar & Karrer AG, Zurich, Switzerland, Dr. iur. LL.M., Co-Head of the Practice Group Turnaround, Reorganization and Insolvency of Bar & Karrer AG, Brandschenkestrasse 90, 8002 Zurich, Switzerland 15 3 2023 15 3 2023 2023 24 2 277285 23 2 2023 (c) The Author(s) 2023 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit This paper offers some observations from a practitioner perspective on Swiss measures to support businesses during the Covid-19 pandemic, as a complement to the paper 'Governmental measures in Switzerland against mass bankruptcies during the Covid-19 pandemic' by Rodriguez and Ulli in this volume. A brief overview of the main fiscal and non-fiscal measures is followed by analysis of the reasons for non-use of a major non-fiscal measure (a new moratorium), and some suggestions as to the lessons that can be learned from this for the design of analogous relief policies in future crises. Keywords Covid-19 Fiscal measures Short-time work Covid loans Restructuring issue-copyright-statement(c) T.M.C. Asser Press 2023 pmcIntroduction As from March 2020, the Swiss federal government implemented an array of Covid-19 measures based on emergency competences in the Constitution. Some measures were specifically designed for certain industries (e.g., the travel sector, or support for sports/cultural institutions), but the majority were of a general nature, applying across industries. In this paper, I focus on the latter type of intervention, i.e., non-sector specific measures, and seek to address the following questions in this regard: Why were some of these measures widely used and measured in terms of popularity successful, while others were hardly applied? What are the lessons that we can learn from experiences with these measures for the design and implementation of analogous measures in a future crisis? I do not consider the political and debatable question of whether the goals pursued by the implemented measures were sensible in all instances. The article begins with a brief overview of the main fiscal and non-fiscal measures for supporting distressed businesses in Switzerland (Sect. 2), before turning to the evidence of (non-)use of these measures (Sect. 3), and the lessons that can be learned from this (Sect. 4). Overview of Swiss Covid-19 Measures In the following, a condensed overview is provided of the main fiscal measures (Sect. 2.1) and the restructuring law-specific measures (Sect. 2.2) implemented in Switzerland during the Covid-19 pandemic. Fiscal Measures Short-Time Work (Kurzarbeit) From a practical perspective, the so-called short-time work (Kurzarbeit) was probably the most important governmental support measure in Switzerland. It was not a Covid-specific tool, but already existed as part of the Swiss unemployment insurance legislation1 and can generally be applied by enterprises in distress situations. Its goal is to avoid layoffs in situations where the reduction in work is expected to be of limited duration. Enterprises can with the consent of the affected employees temporarily reduce the working hours of their employees with a corresponding reduction in wages. Provided the respective conditions are met, the Swiss Unemployment Insurance scheme will cover up to 80% of the loss of income attributable to the reduction in working hours. In other words, the employees agree to reduce working time, but continue to receive 80% of the salary for the time they are not working, which is borne by the Swiss Unemployment Insurance scheme. So, the employer only incurs the cost of the time that employees are actually working. During the pandemic, the Swiss Federal Council lowered, by its Covid-19 Ordinance on Unemployment Insurance,2 the hurdles for access to short-time work compensation and simplified the application processes for enterprises, thereby expediting the handling and payout by the unemployment insurance. Covid Loans As in many other jurisdictions, Switzerland also implemented a Covid loan programme to provide rapid and non-bureaucratic access to liquidity for enterprises with a turnover of no more than CHF 500 million in 2019, in an amount of up to 10% of their pre-pandemic turnover. Under the widely used programme, commercial banks granted two types of bridge loans to enterprises, which were backed by the Swiss government:3 'Regular Covid-19-Credit': banks granted loans of up to CHF 500,000 at no interest and on uniform standard terms and conditions for such loans, fully guaranteed by the Swiss Confederation; In addition to the Regular Covid-19-Credit, enterprises could take out a 'Covid-19-Credit Plus' loan of up to CHF 19.5 million. 85% of such loans carried an interest of 0.5% p.a. and were guaranteed by the Swiss Confederation; the remaining 15% were not state-backed and the interest rate was left to be negotiated between the parties. These Covid-loans are repayable within 8 years, which can be extended by another 2 years in case of hardship and if the extension is likely to lower the financial risk of the Swiss Confederation.4 Restructuring Law Measures General Stay of Proceedings The Swiss Debt Enforcement and Bankruptcy Act ('DEBA')5 gives the federal government the possibility to decree a general stay of debt enforcement proceedings for a certain period of time. At the outset of the pandemic in Switzerland in March 2020, the Federal Council made use of this instrument and ordered a suspension of all debt enforcement acts for almost 3 weeks which produced a grace period of in total almost 5 weeks (combined with the regular enforcement pause during Easter holidays).6 Covid Moratorium The Swiss insolvency regime includes a procedure called composition proceedings (Nachlassverfahren; Art. 293 et seq. DEBA), which is similar to but at the same time has some important differences with in-court restructuring proceedings of other jurisdictions. Composition proceedings are relatively seldom used in Switzerland7 and of less practical significance than, for example, Chap. 11 proceedings under the US Bankruptcy Code. During the Covid pandemic, the federal government temporarily introduced an additional, new form of composition proceedings for small and medium-sized enterprises through its Covid-19 Ordinance on Insolvency Law.8 Upon application to the competent court, companies were granted a payment moratorium of 3 months, which could be extended by another 3 months.9 During such period, creditors could not continue debt enforcement steps against the debtor for claims that had arisen prior to the opening of the proceedings, and the debtor was prohibited from (voluntarily) settling such stayed claims (except salaries). The debtor was further prohibited from performing legal acts that (i) impaired the legitimate interests of creditors, or (ii) favoured individual creditors to the detriment of others.10 After the lapse of the moratorium, the stayed claims had to be settled. Claims newly arising after opening of the proceedings were not stayed and could be enforced. Such moratorium 'light' thus only granted a temporary relief to make payments and could hence be considered useful only in cases where a 'V-shaped' business recovery was expected. Suspension of Duty to File for Bankruptcy Under Swiss law, if a company is over-indebted (liabilities are no longer covered by assets Uberschuldung), the board of directors is obliged to file for bankruptcy, unless creditors subordinate claims at a level sufficient to cover the over-indebtedness (or if the company files for composition proceedings) (Art. 725, para. 2, Swiss Code of Obligations 'CO'). Also, the board may delay a filing for a maximum of 4-6 weeks if it immediately implements restructuring measures and there is a realistic prospect of financial recovery.11 While the directors' obligation to file for bankruptcy is, at first glance, triggered by the balance sheet situation only, bankruptcies are often opened because of illiquidity: under general Swiss accounting law, if continuation of the business activities during the next 12 months is likely not possible (i.e., no longer a going concern; in particular due to lack of liquidity), financial accounting must switch to usually substantially lower liquidation values (Art. 958a, para. 2 CO). Therefore, illiquidity often leads to over-indebtedness, which in turn triggers the duty of the board to file for bankruptcy. In the pandemic, the duty of the board to file for bankruptcy was alleviated in two respects: first, government guaranteed Covid loans of up to CHF 500,000 do (still today) not count as liabilities for purposes of assessing whether a company is over-indebted within the meaning of Art. 725, para. 2 CO.12 Secondly, the board was relieved from its duty to file for bankruptcy despite over-indebtedness, if the company only incurred the indebtedness in 2020 (i.e., had not yet been over-indebted at 31 December 2019) and there was a prospect (Aussicht) that the over-indebtedness could be eliminated by 31 December 2020. The board had to document its decision to abstain from filing for bankruptcy based on the Covid relief, including, e.g., preparing an interim balance sheet and liquidity plans.13 Observations Covid Moratorium Hardly Used Contrary to general expectations, the newly introduced Covid moratorium (Sect. 2.2.2 above) was hardly used in practice.14 Regarding the alleviations of the duty of the board of directors to file for bankruptcy (Sect. 2.2.3 above), no data is available on how many companies applied this grace period, given that the associated board resolutions are not publicly available. The fact that the number of bankruptcies did not increase once the Ordinance with the alleviations lapsed15 may suggest that no significant number of companies delayed bankruptcy filings based thereon. The obvious question that arises is why in particular the Covid moratorium was so rarely used. Lacking full data, I offer some conjectures below. No Need for Insolvency Measures in View of Fiscal Measures The first and quite surely most relevant factor for the non-use of the Covid moratorium is that the financial Covid measures described in Sect. 2.1 above rendered the former superfluous: with the short-time work relief, employers could rid themselves of a major source of cash drainage, as they only had to pay for those employees who actually worked. If no work was to be done, no costs were incurred. Remaining liquidity needs of businesses could largely be covered with the Covid loans described in Sect. 2.1.2 above. While the taking out of such loans entailed certain restrictions, e.g., a prohibition on paying out dividends, basically no restrictions applied on an operational level and after the abandonment of the initial prohibition to use the funds received for new investments16 they could be used for the business as desired. Put in somewhat blunter terms, given that the economy was flooded with government money, there was arguably simply no need for further, restructuring-law-specific measures. The situation might have been quite different if financial aid had been less readily available. With respect to lease agreements typically another significant source of fixed costs for most small and many medium-sized enterprises further factors contributed to a reduced liquidity need. First, there was (and is) an ongoing legal debate as to whether an obligation to pay rent subsists at all during the time that the rental object cannot be used due to government-mandated lockdowns. In many instances, landlords and tenants negotiated compromise solutions leading to temporary rent reductions or deferrals. Moreover, during almost 3 months at the beginning of the pandemic, the statutory time period during which a tenant may be in payment default before the landlord can extraordinarily terminate the lease was extended from 30 to 90 days.17 Parliament debated a mandatory reduction of rent, but in the end this was not enacted. The threat of this legislation may, however, have fostered agreement for the more amicable solutions between landlords and tenants mentioned above. Simplicity of Fiscal Measures The fiscal measures described above had one thing in common: they were relatively clear to grasp and simple to apply. To obtain short-time work benefits, companies basically just had to complete a short form. The position was similar for Covid loans, which were available on companies filling in a standard application form to obtain credit. This simplicity no doubt facilitated take-up of both schemes. Shortcomings of the Covid Moratorium In contrast to the simplicity of the fiscal measures, understanding the Covid moratorium, its advantages and disadvantages was by its nature more complex, and a typical SME would have had to involve an external lawyer for a proper assessment thereof. Further, the moratorium required the involvement of the court. Both of these factors imply a need for upfront cash in a situation where liquidity is scarce by definition. The Covid moratorium provisions also had disadvantages in their design. The granting of the moratorium had to be published and the debtor had an obligation to actively inform its creditors in writing or by email,18 which would have been expected to lead to suppliers demanding pre-payment, thereby increasing liquidity needs even more. More fundamentally, the moratorium only granted relief for existing but not for ongoing obligations, and after at the latest 6 months all claims would become payable again. In the spring/summer of 2020, this was likely too short given the general uncertainty about how the pandemic would develop. Weighing these downsides against the rather limited benefit of a short stay for existing debt probably, in many cases, resulted in not pursuing the possibility of the Covid moratorium; even more so as bridging a 3-6 months liquidity shortfall was possible in a much easier way through the financial aids. No Safe Haven As a further important point, the Covid moratorium as well as the alleviations regarding bankruptcy filing which were both intended and labelled as relief to debtors left important uncertainties that undermined their goals to some extent. As mentioned in Sect. 2.2.2, the Ordinance regarding the Covid moratorium contained a provision according to which the debtor was prohibited from performing legal acts that impaired the legitimate interests of creditors or favoured individual creditors to the detriment of others. It remained vague what such acts, legitimate interests and favouring would have been. If certain creditors are paid during a stay while others are not and ultimately the company goes bankrupt, it can always be argued that the interests of some creditors are impaired. Does this hence mean that during the stay all new obligations must strictly be settled according to their rank and equally within a rank? And once the stay lapses, do all prior claims have to be settled according to rank and pro rata within the last rank? Both seem difficult in practice, would create an administrative burden and a need for outside legal support (creating additional costs), and could thus threaten to imperil the goal of helping debtors. The clause potentially created a route for creditors to later bring personal liability claims against the directors and officers for breach of their (fiduciary) duties (Art. 754 CO) if a restructuring failed. A similar critique can be levelled at the provision for temporary relief from the obligation to file for bankruptcy. As described in Sect. 2.2.3, abstaining from a bankruptcy filing despite over-indebtedness was only allowed if there was a prospect that the over-indebtedness could be eliminated by 31 December 2020. If the company ultimately went bankrupt nevertheless, it would have been plausible to expect that certain creditors could, with the benefit of hindsight, bring liability claims against the directors, arguing that there was no prospect of eliminating the over-indebtedness by the end of 2020 and the board thus illicitly delayed bankruptcy filing. Remembering the situation in spring/summer 2020, with all uncertainties regarding even short-term developments, next Covid wave(s) and virus variations, it seems extremely difficult for a board of directors at that time to realistically make a prognosis for the period until 31 December 2020. Applying the two restructuring law measures hence left a risk for personal liability of the acting directors and managers, which of course reduced their attractivity in practice. Conclusion Based on the above observations, the following lessons can be learned from the Covid pandemic with respect to the design of future emergency measures in comparable crisis situations: In a first step, the desired goals and effects of a measure should be clearly defined. What such goals are remains ultimately a political question and must depending on the circumstances be agreed upon. It is, for instance, debatable whether keeping in business each and every SME by flooding billions of Swiss francs into the economy is sensible under all circumstances; in particular as it appears that the numbers of bankruptcies now start increasing, which nourishes the suspicion that a large number of bankruptcies have simply been postponed at enormous cost to the public. Secondly, once the aim of a measure is defined, its design needs to be structured so as to enable achievement of the defined goal. In order to be effective, measures should be simple and easy to apply by their addressees. Thirdly, measures that seek to grant relief must actually do so: they need to provide a true safe haven to the acting directors and officers of the company. If a measure is only labelled as relief, but leaves a 'back door' open for creditors to later bring personal liability claims, such a measure will likely not be widely used. In summary, in a crisis situation it is, in my view, preferable to have simple and clear measures with true relief for a short time period rather than compromise measures of longer duration. A good example of such a measure that fulfilled the above criteria were the general stay of debt enforcement actions at the outset of the pandemic. While a longer application would probably have led to severely detrimental effects (as in World War I),19 granting a short, but truly comprehensive and simple pause for companies and their managements to regroup and adapt to a completely changed world was probably an important element for the Swiss economy to overcome the crisis. While the above observations and considerations are neither groundbreaking nor new and apply in other areas as well, it is to be hoped that they are considered by governments and that the experience made during the Covid-19 pandemic so far will improve the handling of future crisis situations. 1 Art. 31 et seq., Unemployment Insurance Act, (accessed on 13 February 2023). 2 See Covid-19 Unemployment Insurance Ordinance, (accessed on 13 February 2023). 3 Art. 3 et seq., Covid-19 Solidarity Guarantee Ordinance, (accessed on 13 February 2023). 4 Art. 3, para. 2 Covid-19 Solidarity Guarantee Act, (accessed on 13 February 2023). 5 Resolved upon on 11 April 1889 with the current version effective as of 1 August 2021, (accessed on 13 February 2023). 6 See Eichel and Turtschi (2020), p 1011 et seqq. for more details. 7 Staehelin and Bopp (2020), n. 37. 8 See (accessed on 13 February 2023). 9 Art. 6, para. 1 and Art. 7, para. 1 Covid-19 Ordinance on Insolvency Law. 10 Art. 13, para. 1 Covid-19 Ordinance on Insolvency Law. 11 Wustiner (2016), Art. 725, n. 40a. 12 Art. 24 Covid-19 Solidarity Guarantee Act, (accessed on 13 February 2023). 13 Affolter (2020), p 3; Diem and Ehrsam (2020), n. 40 et seq. 14 Swiss Official Gazette of Commerce, (accessed on 13 February 2023); see also Rodriguez and Ulli (2023). 15 See Rodriguez and Ulli (2023). 16 Art. 6, para. 2, let. B Covid-19 Solidarity Guarantee Ordinance, (accessed on 13 February 2023). 17 Art. 2, Covid-19 Leases Ordinance, (accessed on 13 February 2023). 18 Art. 10, para. 2 Covid-19 Ordinance on Insolvency Law. 19 See Rodriguez and Ulli (2023). Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References Affolter MA (2020) Insolvenzrecht in der COVID-19-Krise: Notrecht und Ausblick. In: RR-VR 5/2020, p 2 et seqq Diem HJ, Ehrsam S (2020) Gesellschaftsrecht. In: COVID 19. Ein Panorama der Rechtsfragen zur Corona-Krise. Helbing Lichtenhahn Verlag, Basel, p 377 et seqq Eichel F, Turtschi S (2020) Der Rechtsstillstand nach Art. 62 SchKG. In: AJP 8/2020, p 1008 et seqq Rodriguez R, Ulli J (2023) Measures taken by the Swiss Confederation against mass bankruptcies due to the Covid-19 pandemic. In: European Business Organization Law Review (this volume) Staehelin D, Bopp L (2020) Insolvenzrechtliche Massnahmen zur Bewaltigung der Coronakrise. In: COVID 19. Ein Panorama der Rechtsfragen zur Corona-Krise. Helbing Lichtenhahn Verlag, Basel, p 513 et seqq Wustiner H Honsell H Vogt NP Watter R Art. 725 OR Basler Kommentar Obligationenrecht II 2016 Basel Helbing Lichtenhahn Verlag
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Ochsner J Ochsner J TOJ ochjnl The Ochsner Journal 1524-5012 2831-4107 Academic Division of Ochsner Clinic Foundation 10.31486/toj.22.0109 toj.22.0109 Editorial Physician Well-Being and the Promise of Positive Psychology Shahid, M Practical Interventions for Physician Well-Being Shahid Mahum MD Director of Program Diversity and Early Career Development for Women in Internal Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD Spring 2023 Spring 2023 23 1 24 (c)2023 by the author(s); Creative Commons Attribution License (CC BY) 2023 (c)2023 by the author(s); licensee Ochsner Journal, Ochsner Clinic Foundation, New Orleans, LA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (creativecommons.org/licenses/by/4.0/legalcode) that permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. pmcPhysician well-being has been gaining more attention across all circuits of physician advocacy given the current state of our health care systems. Physician wellness (well-being), per a systematic review of 78 studies, is defined by quality of life, which includes the absence of ill-being and the presence of positive physical, mental, social, and integrated well-being experienced in connection with activities and environments that allow physicians to develop their full potentials across personal and work-life domains.1 Physician burnout has a clear and consistent definition. The World Health Organization International Classification of Diseases-11 defines burnout as an "occupational syndrome," cementing the Maslach Burnout Inventory triad of emotional exhaustion, depersonalization, and cynicism or feelings of diminished personal accomplishment as the classic definition of physician burnout.2 Mental illness in physicians and burnout, although closely related, are acknowledged as separate entities. Physician suicide rates historically have been higher compared to the general population, with a 2004 meta-analysis reporting rates 1.41 times higher in male physicians and 2.27 times higher in female physicians.3 Yet data from the National Violent Death Reporting System showed that physicians who died by suicide were less likely to be under treatment for a mental illness and more likely to have antipsychotics, barbiturates, and benzodiazepines rather than antidepressants in their systems compared to nonphysicians.4 Stress, a common occupational hazard in many professions, is a known risk factor of burnout and mental illness. Stress can induce neuroinflammation affecting the brain's hippocampal centers of memory, emotional processing, and cognition.5 Resilience, the ability to bounce back in the face of adversity, is a protective factor against both burnout and mental illness.6,7 Resilience training interventions have been shown to decrease depression, stress, and stress perception in health care workers.7 So even if physician burnout is not the result of a resilience deficit but is instead a health system-related issue, resilience training can help reduce some of the impact of chronic workplace stress. The Dr. Lorna Breen Health Care Provider Protection Act that was signed into law on March 18, 2022, promotes physician wellness and resilience.8 This legislation was designed not only to increase awareness but also to establish grants to support mental health and resilience in physicians. As an adjunct to this legislation, physicians and health systems can adopt self-help measures to improve well-being. POSITIVE PSYCHOLOGY-BASED INTERVENTIONS Since 2000, positive psychology-based interventions have emerged as a promising technique to manage stress and to increase psychological resilience and engagement.9,10 Positive emotions, purpose, and a sense of achievement can drive the process of flourishing and contribute to individual success.11 Most of these interventions are low-cost and time-efficient, with yields comparable to or even better than pharmacologic therapies.12 These interventions can be introduced into work routines without the burden of extensive training. Some interventions are targeted toward certain domains of burnout (emotional exhaustion, depersonalization), yet when used at the institutional level, positive psychology-based interventions can support overall physician well-being. COST-EFFICIENT EVIDENCE-BASED INTERVENTIONS Imposter phenomenon self-doubt and the inability to internalize success is more prevalent in US physicians than in the US working population according to a 2022 study that compared responses to an item from the Clance Imposter Phenomenon Scale between the 2 populations: "I'm disappointed at times in my present accomplishments and think I should have accomplished much more."13 Imposter phenomenon was associated with increased burnout,13 suicidal ideation,13 decreased professional fullfillment,13 and lower problem-solving confidence.13,14 Positive psychology-based coaching, per a 2020 literature review, involves identification, development, and utilization of strengths to turn a vision into reality.15 This style of coaching can help overcome imposter phenomenon which is a driver of physician burnout, mental illness, and negative self-perception.15,16 Professional development coaching, a form of peer coaching in which faculty from a different specialty coaches a resident using basic principles of positive psychology, has shown promise in fostering resident wellness without the use of significant resources.17 Appreciative inquiry, an asset-based approach to organizational changes, is another example of a positive psychology intervention for managing the stress associated with transition and change in health care systems. The 4-D model (discovery, dream, design, and destiny) of appreciative inquiry involves achieving goals by dreaming together as a team, focusing on strengths, and using those strengths to design strategies to achieve goals. This positive outlook at challenges can enhance meaning in work18 and augment professionalism and problem-solving capabilities of health care teams.19 Appreciative inquiry-centered narrative storytelling can also be used as a team-building exercise to cultivate reflective group learning, peer support, and meaningful professional relationships.20 Three Good Things is a simple journal activity in which participants log 3 good things that went well in a day. This well-being intervention was tested in health care workers for 15 days, and significant improvements from baseline were found in the emotional exhaustion, depression symptoms, and happiness metrics, with effect sizes of 0.55 to 1.57.12 In comparison, a Kirsch et al meta-analysis studying the effects of antidepressants found a difference between improvement in the drug and the placebo groups of only 0.32.21 Further, the results of the Three Good Things exercise were sustained at 6-month and 1-year intervals.12 Using this intervention qualitatively can also identify areas that provide meaning and joy to health care workers and give direction to leadership. This activity can also be conducted through cellular phone applications, making it more time-efficient than manual recording. Mindfulness is the nonjudgmental observance of thoughts during overwhelming and stressful situations. Mindfulness-based interventions have shown promise for physicians in individual studies and meta-analyses.22 They are being used at several centers in the form of video modules, weekly activities, and group exercises, especially with resident physicians, and data suggest significant improvement in overall well-being.22 Given the alarming rise in physician burnout, with a 2015 study reporting that more than 50% of US physicians experience at least one symptom of burnout,23 action at the national, institutional, and personal levels is needed because physician burnout is directly related to substance abuse,24 suicidal ideation,25 self-reported medical errors,26 and overall poor quality of patient care.26 Although burnout is largely driven by work-related factors, including the clerical burden of electronic health records,27 long work hours,28 and work-home conflict,29 some of the interventions discussed here could be adopted by institutions and physician groups as a self-help measure to mitigate chronic workplace stress and improve overall mental health. ACKNOWLEDGMENTS The author has no financial or proprietary interest in the subject matter of this article. REFERENCES 1. Brady KJS , Trockel MT , Khan CT , What do we mean by physician wellness? A systematic review of its definition and measurement. Acad Psychiatry. 2018;42 (1 ):94-108. doi: 10.1007/s40596-017-0781-6 28913621 2. Department of News. Burn-out an "occupational phenomenon": International Classification of Diseases. World Health Organization. Published May 28, 2019. Accessed December 20, 2022. who.int/news/item/28-05-2019-burn-out-an-occupational-phenomenon-international-classification-of-diseases 3. Schernhammer ES , Colditz GA . Suicide rates among physicians: a quantitative and gender assessment (meta-analysis). Am J Psychiatry. 2004;161 (12 ):2295-2302. doi: 10.1176/appi.ajp.161.12.2295 15569903 4. Gold KJ , Sen A , Schwenk TL . Details on suicide among US physicians: data from the National Violent Death Reporting System. Gen Hosp Psychiatry. 2013;35 (1 ):45-49. doi: 10.1016/j.genhosppsych.2012.08.005 23123101 5. Wu Z , Xiao L , Wang H , Wang G . Neurogenic hypothesis of positive psychology in stress-induced depression: adult hippocampal neurogenesis, neuroinflammation, and stress resilience. Int Immunopharmacol. 2021;97 :107653. doi: 10.1016/j.intimp.2021.107653 33915495 6. Nituica C , Bota OA , Blebea J . Specialty differences in resident resilience and burnout-a national survey. Am J Surg. 2021;222 (2 ):319-328. doi: 10.1016/j.amjsurg.2020.12.039 33431168 7. Kunzler AM , Helmreich I , Chmitorz A , Psychological interventions to foster resilience in healthcare professionals. Cochrane Database Syst Rev. 2020;7 (7 ):CD012527. doi: 10.1002/14651858.CD012527.pub2 32627860 8. The Lorna Breen bill, in memory of front-line worker, passes Congress. Ment Health Wkly. 2022;32 (9 ):8. doi: 10.1002/mhw.33134 9. Ciarrochi J , Hayes SC , Oades LG , Hofmann SG . Toward a unified framework for positive psychology interventions: evidence-based processes of change in coaching, prevention, and training. Front Psychol. 2022;12 :809362. doi: 10.3389/fpsyg.2021.809362 35222161 10. Smith JL , Hanni AA . Effects of a savoring intervention on resilience and well-being of older adults. J Appl Gerontol. 2019;38 (1 ):137-152. doi: 10.1177/0733464817693375 28380722 11. Seligman M . PERMA and the building blocks of well-being. J Posit Psychol. 2018;13 (4 ):333-335. doi: 10.1080/17439760.2018.1437466 12. Sexton JB , Adair KC . Forty-five good things: a prospective pilot study of the Three Good Things well-being intervention in the USA for healthcare worker emotional exhaustion, depression, work-life balance and happiness. BMJ Open. 2019;9 (3 ):e022695. doi: 10.1136/bmjopen-2018-022695 13. Shanafelt TD , Dyrbye LN , Sinsky C , Imposter phenomenon in US physicians relative to the US working population. Mayo Clin Proc. 2022;97 (11 ):1981-1993. doi: 10.1016/j.mayocp.2022.06.021 36116974 14. Lin E , Crijns TJ , Ring D , Jayakumar P ; The Science of Variation Group. Imposter syndrome among surgeons is associated with intolerance of uncertainty and lower confidence in problem solving [published online ahead of print, 2022 Sep 6]. Clin Orthop Relat Res. 2022;10.1097/CORR.0000000000002390. doi: 10.1097/CORR.0000000000002390 15. van Zyl LE , Roll LC , Stander MW , Richter S . Positive psychological coaching definitions and models: a systematic literature review. Front Psychol. 2020;11 :793. doi: 10.3389/fpsyg.2020.00793 32435218 16. McGonagle AK , Schwab L , Yahanda N , Coaching for primary care physician well-being: a randomized trial and follow-up analysis. J Occup Health Psychol. 2020;25 (5 ):297-314. doi: 10.1037/ocp0000180 32297776 17. Palamara K , Kauffman C , Chang Y , Professional development coaching for residents: results of a 3-year positive psychology coaching intervention. J Gen Intern Med. 2018;33 (11 ):1842-1844. doi: 10.1007/s11606-018-4589-1 30039493 18. Hipp DM , Rialon KL , Nevel K , Kothari AN , Jardine LDA . "Back to bedside": residents' and fellows' perspectives on finding meaning in work. J Grad Med Educ. 2017;9 (2 ):269-273. doi: 10.4300/JGME-D-17-00136.1 28439376 19. Hung L , Phinney A , Chaudhury H , Rodney P , Tabamo J , Bohl D . Appreciative inquiry: bridging research and practice in a hospital setting. Int J Qual Methods. 2018;17 (1 ). doi: 10.1177/1609406918769444 20. Taylor A , Karnieli-Miller O , Inui T , Ivy S , Frankel R . Appreciating the power of narratives in healthcare: a tool for understanding organizational complexity and values. In Candlin CN , Sarangi S , eds. Handbook of Communication in Organisations and Professions. De Gruyter Mouton; 2011:457-480. doi: 10.1515/9783110214222.457 21. Kirsch I , Deacon BJ , Huedo-Medina TB , Scoboria A , Moore TJ , Johnson BT . Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008;5 (2 ):e45. doi: 10.1371/journal.pmed.0050045 18303940 22. Fendel JC , Burkle JJ , Goritz AS . Mindfulness-based interventions to reduce burnout and stress in physicians: a systematic review and meta-analysis. Acad Med. 2021;96 (5 ):751-764. doi: 10.1097/ACM.0000000000003936 33496433 23. Shanafelt TD , Hasan O , Dyrbye LN , Changes in burnout and satisfaction with work-life balance in physicians and the general US working population between 2011 and 2014 [published correction appears in Mayo Clin Proc. 2016 Feb;91(2):276]. Mayo Clin Proc. 2015;90 (12 ):1600-1613. doi: 10.1016/j.mayocp.2015.08.023 26653297 24. Oreskovich MR , Kaups KL , Balch CM , Prevalence of alcohol use disorders among American surgeons. Arch Surg. 2012;147 (2 ):168-174. doi: 10.1001/archsurg.2011.1481 22351913 25. Shanafelt TD , Balch CM , Dyrbye L , Special report: suicidal ideation among American surgeons. Arch Surg. 2011;146 (1 ):54-62. doi: 10.1001/archsurg.2010.292 21242446 26. Williams ES , Manwell LB , Konrad TR , Linzer M . The relationship of organizational culture, stress, satisfaction, and burnout with physician-reported error and suboptimal patient care: results from the MEMO study. Health Care Manage Rev. 2007;32 (3 ):203-212. doi: 10.1097/01.HMR.0000281626.28363.59 27. Shanafelt TD , Dyrbye LN , Sinsky C , Relationship between clerical burden and characteristics of the electronic environment with physician burnout and professional satisfaction. Mayo Clin Proc. 2016;91 (7 ):836-848. doi: 10.1016/j.mayocp.2016.05.007 27313121 28. Lin RT , Lin YT , Hsia YF , Kuo CC . Long working hours and burnout in health care workers: non-linear dose-response relationship and the effect mediated by sleeping hours-a cross-sectional study. J Occup Health. 2021;63 (1 ):e12228. doi: 10.1002/1348-9585.12228 33957007 29. Dyrbye LN , Shanafelt TD , Balch CM , Satele D , Sloan J , Freischlag J . Relationship between work-home conflicts and burnout among American surgeons: a comparison by sex. Arch Surg. 2011;146 (2 ):211-217. doi: 10.1001/archsurg.2010.310 21339435
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Ochsner J Ochsner J TOJ ochjnl The Ochsner Journal 1524-5012 2831-4107 Academic Division of Ochsner Clinic Foundation 10.31486/toj.22.0052 toj.22.0052 Case Reports and Clinical Observations Bilateral Internal Carotid Artery Agenesis in a Patient With a Family History of Intracranial Pathology Liau, YMJ Bilateral Internal Carotid Artery Agenesis Liau Yi-Ming J. BS 1 * Jabbour Austin J. MD 1 2 * + Yerdon Heather MD 1 ++ Chonillo Carlos Cevallos MD 3 Amjed Saira MD 4 SS Hong Andrew MD 4 || Khan Behram MBBS 5 P 1 The University of Queensland Medical School, Ochsner Clinical School, New Orleans, LA 2 Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 3 Department of Neurology, Ochsner Clinic Foundation, New Orleans, LA 4 Department of Internal Medicine, Ochsner Clinic Foundation, New Orleans, LA 5 Department of Hospital Medicine, Ochsner Clinic Foundation, New Orleans, LA *Mr Liau and Dr Jabbour contributed equally to this report. +Dr Jabbour is now affiliated with the Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY. ++Dr Yerdon is now affiliated with the Department of Internal Medicine, University of New Mexico, Albuquerque, NM. SSDr Amjed is now affiliated with Ochsner Health Center - Lake Terrace, New Orleans, LA. ||Dr Hong is now affiliated with the Department of Occupational Medicine, Yale University, New Haven, CT. PDr Khan is now affiliated with the Department of Pulmonary Disease and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA. Address correspondence to Behram Khan, MBBS, Department of Pulmonary Disease and Critical Care Medicine, Virginia Commonwealth University, 1101 E. Marshall St., Sanger Hall Ste. 1-030, Richmond, VA 23298. Tel: (401) 516-5790. Email: [email protected] Spring 2023 Spring 2023 23 1 8891 (c)2023 by the author(s); Creative Commons Attribution License (CC BY) 2023 (c)2023 by the author(s); licensee Ochsner Journal, Ochsner Clinic Foundation, New Orleans, LA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (creativecommons.org/licenses/by/4.0/legalcode) that permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Background: Agenesis of the internal carotid artery (ICA) is a rare congenital malformation that is often asymptomatic until the fourth or fifth decade. ICA agenesis is associated with several intracranial pathologies, the most reported being intracranial aneurysms, thought to be attributable to the increased flow in the collateral vessels supplying the anterior circulation. The cause of ICA agenesis is largely unknown and has not been consistently associated with any genetic mutations or syndromes. Case Report: We present the case of a 37-year-old female who was incidentally found to have bilateral agenesis of the ICA system. Patient history revealed that the patient's father and 12 of his 14 siblings died from either ruptured brain aneurysms or cerebrovascular accidents before the age of 50 years. Presenting symptoms included right eye pain radiating to her right posterior neck, a 2-month history of diplopia, and associated nausea and vomiting. Differential diagnoses included immunoglobulin G4-related disease, sarcoidosis, lymphoma, and vasculitis. Absent internal carotids were attributed to congenital agenesis vs hypoplasia. The patient was seen by neurology and initiated on prednisone 80 mg by mouth once daily with a 2-week taper to treat systemic inflammation. The patient was deemed stable for discharge after a 2-day hospital admission and was scheduled for follow-up appointments with genetics, neurology, rheumatology, and ophthalmology. Conclusion: Bilateral ICA agenesis is a rare occurrence, with only 33 cases documented in a case report and literature review published in 2016. Because of the otherwise normal anatomy of the patient and the pervasive intracranial pathology seen in late adulthood in her family, we propose the likelihood of an inheritable form of bilateral ICA agenesis vs vascular disease or familial aneurysms. Keywords: Carotid artery diseases intracranial arterial diseases neuroanatomy vertebrobasilar insufficiency pmcINTRODUCTION Agenesis of the internal carotid artery (ICA) is a very rare event, occurring in 0.01% of the population. Bilateral cases are even rarer. In a case report and literature review published in 2016, Alexandre et al reported a total of 33 documented cases of bilateral agenesis of the ICA.1 The cause of ICA agenesis, unilateral and bilateral, is largely unknown and has not been linked with any genetic abnormalities. ICA agenesis has been observed conjointly with rare genetic disorders, but these reports have been anecdotal, with no hypotheses proposed to explain the association.2-4 We describe a case of bilateral agenesis of the ICA system in a class III obese African American adult who had no known genetic disorders. CASE REPORT A 37-year-old African American female with a body mass index of 62 kg/m2 and a history of hypertension, type 2 diabetes, and alcohol abuse presented to the emergency department (ED) for evaluation of sudden onset, throbbing, right eye pain radiating to her right posterior neck and a 2-month history of diplopia. Full review of systems revealed associated nausea and vomiting. Family history revealed the patient's father and 12 of her father's 14 siblings died from either ruptured brain aneurysms or cerebrovascular accidents before the age of 50 years. Vital signs were remarkable for a blood pressure of 156/92 mm Hg. Examination of the right eye revealed a complete deficit in abduction, partial deficit in upward gaze, and partial deficit in adduction, suggestive of a cranial nerve VI palsy with partial, pupil-sparing cranial nerve III palsy. Computed tomography angiography (CTA) and magnetic resonance imaging (MRI) of the brain were performed to rule out vascular etiologies. Notable CTA incidental findings included the absence of the bilateral carotid canals, intracranial internal carotid arteries, and cavernous sinuses . MRI revealed vertebrobasilar dolichoectasia that was notably adjacent to the origin of the sixth cranial nerve in the region of the pons with resultant compression . Ill-defined enhancement surrounded the right optic nerve with resultant asymmetric proptosis, thought to be idiopathic orbital inflammation. Brain parenchyma was normal, and no hydrocephalus or aneurysms were identified. Computed tomography (CT) of the chest, abdomen, and pelvis was unremarkable for acute pathology. Figure 1. (A) Axial computed tomography angiography (CTA) image of the skull base shows the absence of petrous carotid canals. (B) Axial CTA image of the brain demonstrates absent intracranial carotid flow above the cavernous sinuses. Figure 2. T2 weighted magnetic resonance imaging with contrast shows absent internal carotid artery flow voids through the cavernous segments (apparent absence of the bilateral internal carotid arteries). A tortuous and enlarged basilar artery passes adjacent to the origin of the sixth cranial nerve in the pons. Complete blood count and comprehensive metabolic panel were grossly unremarkable. Inflammatory markers were significantly elevated, with erythrocyte sedimentation rate of 96 mm/h (reference range, 0-36 mm/h) and C-reactive protein of 59.2 mg/L (reference range, 0-8.2 mg/L). Rheumatologic testing revealed negative antinuclear antibody and elevated C3 at 199 mg/dL (reference range, 50-180 mg/dL). Cerebrospinal fluid analysis was significant for an elevated opening pressure in the seated position at 36 mm Hg (reference range, 5.1-13.2 mm Hg in the lateral recumbent position). Differential diagnoses included immunoglobulin G4-related disease, sarcoidosis, lymphoma, and vasculitis. Absent internal carotids were attributed to congenital agenesis vs hypoplasia. The patient was seen by neurology and initiated on prednisone 80 mg by mouth once daily with a 2-week taper to treat systemic inflammation. The patient was deemed stable for discharge after a 2-day hospital admission and was scheduled to receive close follow-up appointments with genetics, neurology, rheumatology, and ophthalmology. The patient presented to the genetics department 3 weeks later for workup of potential heritable causes of her neurovascular abnormalities. However, her visit ended prematurely because of vomiting and shortness of breath, for which she was taken to the ED. She was found to be dehydrated secondary to decreased oral intake and increased alcohol use because of the recent death of her mother. She was given fluids and discharged after 1 day in observation. At the time of this report, the patient had not scheduled another appointment with genetics and had not followed up with neurology or rheumatology. However, she did report for the ophthalmology appointment 2 months later, and her eye-related symptoms had resolved. DISCUSSION Agenesis, hypoplasia, and aplasia of the ICA are often used interchangeably in the literature. However, ICA agenesis is defined as the complete absence of the vessel and branches. It is differentiated from aplasia or hypoplasia by the absence of all segments and by an underdeveloped carotid canal on imaging.5 In a fetus, the ICA is formed 2 weeks before the skull base and is thus required as a scaffold for proper skull base development. Agenesis of the ICA is thought to take place during the third and fifth week of embryologic development during simultaneous regression of the first and third aortic arches.6 Imaging in this patient revealed the absence of the bilateral ICAs and carotid canals, thus supporting ICA agenesis vs postbirth hypoplasia, aplasia, or occlusion. ICA agenesis, aplasia, and hypoplasia have been reported to be associated with numerous intracranial pathologies that appear in later years such as headaches, seizures, tinnitus, strokes, transient ischemic attacks, and Horner syndrome.7 However, the most prevalent pathology associated with ICA agenesis in the literature has been intracranial aneurysms and consequent subarachnoid hemorrhages8 resulting from increased volume and abnormal flow dynamics in the collateral vasculature caused by deficient anterior circulation.9 Over time, the vessels dilate and become torturous, as seen in the vertebrobasilar circulation in our patient, and eventually lead to weakening of the vessel walls and aneurysms. Therefore, many patients are asymptomatic until the fourth or fifth decade.10 Zink et al reported a prevalence of intracranial aneurysm in patients with congenital hypoplasia or aplasia of the ICA in up to 14.6% in patients <30 years of age and 36.6% in patients >30 years.10 According to Zink et al, the increased prevalence of aneurysms in the older group suggests that the pathogenesis of the aneurysms in their study population was more likely secondary to chronic stress on the vessels rather than intrinsic vascular disease. Nevertheless, some authors have proposed that ICA agenesis is merely a symptom of a congenital vascular disease.11 Several well-known hereditary conditions have been known to affect the vasculature and cause intracranial aneurysms. Polycystic kidney disease (PKD), caused by alterations in the PKD1/2 gene, is associated with berry aneurysms and vertebral dissection. Ehlers-Danlos syndrome (EDS) can lead to cerebral aneurysm secondary to a COL3A1 mutation.11 Other conditions that can affect the vasculature and cause cerebral aneurysms include neurofibromatosis type 1 (NF1), multiple endocrine neoplasia type 1 (MEN1), and hereditary hemorrhagic telangiectasia (HHT).12 These inherited conditions are unlikely in our patient, as her CT scans of the chest, abdomen, and pelvis were without typical findings of thoracic artery aneurysm or bilateral polycystic kidneys. She had no signs of telangiectasias or of neurofibromas. The patient also lacked findings characteristic of EDS, such as a marfanoid body habitus or hyperextensibility of joints and ligaments. In addition, cerebral aneurysms occur in a small percentage of patients with the above-mentioned genetic diseases. Therefore, given the fact that 12 of the patient's father's 14 siblings died from brain complications, these familial disorders are not likely to have caused the high prevalence of aneurysms seen in the patient's family. Many cases of familial occurrence of intracranial aneurysms have been reported without a known heritable condition.12 Familial aneurysms are largely idiopathic, with reported mutations spanning many different chromosomes and loci, and in addition, having equally variable inheritance patterns.12,13 The patient's family possibly could have had a severe form of familial aneurysms in the absence of a known genetic mutation; however, aneurysms tend to occur at younger ages, in multiples, and with a predilection for the middle cerebral artery.12-14 Our patient had no visible aneurysms on CT or MRI. Based on our patient's imaging and history, we believe the intracranial aneurysms and cerebrovascular pathology in her family were likely attributable to hereditary ICA agenesis and consequent high-volume flow in the collateral circulation. Our patient did not have physical examination findings consistent with the genetic diseases that cause intracranial aneurysms (PKD, EDS, NF1, MEN1, HHT). Also, unlike patients with familial aneurysms, who often have multiple aneurysms at a young age, our patient's imaging was grossly normal other than the ICA agenesis and vertebrobasilar dolichoectasia. In addition, while the incidence of familial aneurysms can be as high as 19.1% in siblings,12 the prevalence of aneurysms with single ICA agenesis is estimated to be much higher at 36.6%.10 In fact, if the mechanism of the aneurysms is chronically stressed collaterals as we propose, bilateral agenesis could yield an even higher prevalence of aneurysms than unilateral agenesis and explain the permeating intracranial pathology in the patient's family. Without a detailed genetic workup of the patient and her family and only subjective reporting of the patient's family history, we acknowledge that the conclusions we can make are limited. The patient also had significantly elevated inflammatory markers; therefore, a rheumatology workup would be needed to rule out autoimmune or inflammatory disease. However, if the cause of the patient's family history is inherited ICA agenesis, to our knowledge, this case is the first report of such a phenomenon. CONCLUSION While ICA agenesis can be asymptomatic for most of adulthood, it should be taken seriously as a strong risk factor for cerebral aneurysms and other cerebrovascular accidents. When ICA agenesis is found incidentally, as most cases are, physicians should understand the importance of surveillance and identifying collateral pathways supplying the brain that may eventually succumb to disease. The literature offers few explanations for patients with no obvious genetic abnormalities and a strong familial history of brain aneurysms. For these patients, abnormalities in the main vessels supplying their brain should be investigated. ACKNOWLEDGMENTS The authors have no financial or proprietary interest in the subject matter of this article. This article meets the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties Maintenance of Certification competencies for Patient Care and Medical Knowledge. REFERENCES 1. Alexandre AM , Visconti E , Schiarelli C , Frassanito P , Pedicelli A . Bilateral internal carotid artery segmental agenesis: embryology, common collateral pathways, clinical presentation, and clinical importance of a rare condition. World Neurosurg. 2016;95 :620.e9-620.e15. doi: 10.1016/j.wneu.2016.08.012 2. Ruzic-Barsic A , Kovacic S , Mijatovic D , Miletic D , Antulov R . Coexistence of left internal carotid agenesis, Klippel-Feil syndrome and postaxial polydactyly. Pol J Radiol. 2015;80 :128-130.25806098 3. Kraus J , Jahngir MU , Singh B , Qureshi AI . Internal carotid artery aplasia in a patient with nail-patella syndrome. Vasc Endovascular Surg. 2020;54 (2 ):175-181. doi: 10.1177/1538574419888345 31746280 4. MacDonald A , Alvaro A . CADASIL in a patient with bilateral internal carotid artery agenesis. J Clin Neurosci. 2021;83 :128-130. doi: 10.1016/j.jocn.2020.11.009 33317884 5. Lie TA , Hage J . Congenital anomalies of the carotid arteries. Plast Reconstr Surg . 1968;42 (3 ):283. doi: 10.1097/00006534-196809000-00046 6. Padget DH . The cranial venous system in man in reference to development, adult configuration, and relation to the arteries. Am J Anat. 1956;98 (3 ):307-355. doi: 10.1002/aja.1000980302 13362118 7. Cohen JE , Gomori JM , Leker RR . Internal carotid artery agenesis: diagnosis, clinical spectrum, associated conditions and its importance in the era of stroke interventions. Neurol Res. 2010;32 (10 ):1027-1032. doi: 10.1179/016164110X12767786356273 20712923 8. Kunishio K , Yamamoto Y , Sunami N , Asari S . Agenesis of the left internal carotid artery, common carotid artery, and main trunk of the external carotid artery associated with multiple cerebral aneurysms. Surg Neurol. 1987;27 (2 ):177-181. doi: 10.1016/0090-3019(87)90292-8 3810447 9. Uchino A , Sawada A , Hirakawa N , Totoki T , Kudo S . Congenital absence of the internal carotid artery diagnosed during investigation of trigeminal neuralgia. Eur Radiol. 2002;12 (9 ):2339-2342. doi: 10.1007/s00330-001-1262-5 12195492 10. Zink WE , Komotar RJ , Meyers PM . Internal carotid aplasia/hypoplasia and intracranial saccular aneurysms: series of three new cases and systematic review of the literature. J Neuroimaging. 2007;17 (2 ):141-147. doi: 10.1111/j.1552-6569.2007.00092.x 17441835 11. Tangchai P , Khaoborisut V . Agenesis of internal carotid artery associated with aneurysm of contralateral middle cerebral artery. Neurology. 1970;20 (8 ):809-812. doi: 10.1212/wnl.20.8.809 5465849 12. Caranci F , Briganti F , Cirillo L , Leonardi M , Muto M . Epidemiology and genetics of intracranial aneurysms. Eur J Radiol. 2013;82 (10 ):1598-1605. doi: 10.1016/j.ejrad.2012.12.026 23399038 13. Bromberg JE , Rinkel GJ , Algra A , Familial subarachnoid hemorrhage: distinctive features and patterns of inheritance. Ann Neurol. 1995;38 (6 ):929-934. doi: 10.1002/ana.410380614 8526466 14. Brown RD Jr , Huston J , Hornung R , Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection. J Neurosurg. 2008;108 (6 ):1132-1138. doi: 10.3171/JNS/2008/108/6/1132 18518716
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Ochsner J Ochsner J TOJ ochjnl The Ochsner Journal 1524-5012 2831-4107 Academic Division of Ochsner Clinic Foundation 10.31486/toj.22.0033 toj.22.0033 Case Reports and Clinical Observations Trigger Wrist Caused by a Rheumatoid Nodule on the Flexor Pollicis Longus Tendon Higginbotham, D Trigger Wrist Caused by Rheumatoid Nodule Higginbotham Devan MD Fleifel Dominik MD Tsai Andrew MD Department of Orthopedic Surgery, Detroit Medical Center, Detroit MI Address correspondence to Andrew Tsai, MD, Department of Orthopedic Surgery, Detroit Medical Center, 4201 St. Antoine, UHC 9-B, Detroit, MI 48201. Tel: (313) 832-0500. Email: [email protected] Spring 2023 Spring 2023 23 1 6466 (c)2023 by the author(s); Creative Commons Attribution License (CC BY) 2023 (c)2023 by the author(s); licensee Ochsner Journal, Ochsner Clinic Foundation, New Orleans, LA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (creativecommons.org/licenses/by/4.0/legalcode) that permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Background: Trigger wrist is a rare condition. Previously reported cases have involved nodules or ganglion cysts affecting flexor digitorum profundus tendons; however, we found no reported cases of trigger wrist caused by a rheumatoid nodule on the flexor pollicis longus tendon. Case Report: A 57-year-old female presented with the complaint of chronic triggering of the right thumb and numbness in her fingers consistent with carpal tunnel syndrome. Corticosteroid injection did not provide symptom relief, so the patient was scheduled for surgery. A 3 x 1.5-cm lesion was removed from the flexor pollicis longus tendon distal to the carpal tunnel. Histopathologic examination demonstrated that the lesion was a rheumatoid nodule. Conclusion: Patients with rheumatoid arthritis who present with trigger finger symptoms of the thumb with concomitant carpal tunnel symptoms require careful evaluation to rule out trigger wrist before the condition progresses to Mannerfelt lesion. Keywords: Arthritis-rheumatoid hand trigger finger disorder trigger wrist pmcINTRODUCTION Trigger finger is one of the most common disorders of the hand.1 Compared to trigger finger, trigger wrist is a relatively rare condition, and triggering of the fingers secondary to a lesion at the wrist is an uncommon phenomenon. Multiple causes of trigger wrist have been described, with lesions reported as lipomas, fibromas, anomalous skeletal muscles, tophi, synovitis of the carpal tunnel, pigmented villonodular synovitis, and rheumatoid nodules.2-9 Most commonly, trigger wrist has been described as occurring on the flexor tendons.10 To our knowledge, trigger wrist caused by a rheumatoid nodule on the flexor pollicis longus tendon has yet to be described. Rheumatoid nodules of the upper extremity are relatively common in patients with rheumatoid arthritis, seen in up to 25% of those patients.11 Research suggests that the etiology of rheumatoid nodules is related to immune-complex-mediated small vessel vasculitis in areas of high use or trauma.11 These lesions can lead to pain, nerve compression, mechanical block from tendon or joint involvement, and infection.12 CASE REPORT A 57-year-old right-hand-dominant female with history of rheumatoid arthritis presented to the clinic with complaints consistent with carpal tunnel syndrome of the right wrist, synovitis of the flexor tendons, trigger thumb that did not present as a normal trigger thumb, and pain in her hand and wrist. On examination, the patient had noticeable swelling and persistent thumb triggering with numbness in her index, middle, and ring fingers. The triggering of the thumb appeared to be coming from the carpal tunnel because no palpable lesion surrounded the A1 pulley as seen in a typical trigger thumb. Radiographs of the right thumb revealed mild osteoarthritic changes over the interphalangeal joint but no scaphoid-trapezium-trapezoid joint degenerative changes. Electrodiagnostic studies demonstrated severe median neuropathy on the right with evidence of ongoing denervation of the right abductor pollicis brevis muscle. Figure 1. (A) Posteroanterior and (B) lateral radiographs show mild degenerative joint disease of the interphalangeal and carpometacarpal joints of the thumb. The patient received a corticosteroid injection for her right trigger thumb over the A1 pulley, but the injection did not provide any symptom relief. The working diagnosis was locked trigger thumb or wrist, and the patient was scheduled for surgical release of the cause of the triggering, carpal tunnel release, and excision of synovitis around the flexor tendons caused by swelling and poorly controlled rheumatoid arthritis. The carpal tunnel release was performed, and the median nerve was noted to be extremely compressed, assuming an hourglass-type shape underneath the carpal tunnel. Inflamed synovium covered all the tendons, both the deep and superficial flexor tendons. Attempts were made to remove all of the synovium. The thumb tendons were explored. Intraoperatively, the patient was asked to flex and extend her thumb, with no further triggering of the digit. Exploration of the flexor pollicis longus tendon demonstrated a 3 x 1.5-cm lesion affixed to the flexor pollicis longus tendon just distal to the carpal tunnel. The lesion did not appear to be a ganglion cyst or giant cell tumor. The lesion was bluntly dissected, excised, and sent to pathology. Further examination of the flexor pollicis longus tendon demonstrated a large area of tendon disruption along the lesion that measured approximately 3 to 4 cm in length and encompassed approximately one-third to one-half of the tendon. The tendon was much thinner in this region compared to the areas proximal and distal to the lesion. The lesion was concerning for an early Mannerfelt lesion because of repetitive rubbing of the tendon on the lesion. The base of the carpal tunnel was palpated, and no protruding osteophytes or other obvious abnormality could be found in the carpal tunnel or carpometacarpal region to explain her lesion. The tendon was repaired directly with a running 5-0 dissolvable suture to minimize any stray fragments. Pathology report described the lesion as a rheumatoid nodule with reactive hyaline changes and synovial tissue with hyperplastic changes . Figure 2. Rheumatoid nodule removed from the flexor pollicis longus tendon has a central area of necrotic tissue with a thick border of fibroblasts ([A] magnification x 2 and [B] magnification x 10). At 3-month follow-up, the patient reported improvements with sensation in the median nerve distribution of her hand, complete resolution of the mechanical locking symptoms of her thumb, and no postoperative complications. DISCUSSION Marti first described trigger wrist in 1960,13 and in 2016, Park et al suggested the following 3 cardinal symptoms: (1) finger triggering at the wrist during finger motion, often with more than 2 digits involved; (2) mild to moderate paresthesia of the hand presenting as carpal tunnel syndrome; and (3) crepitus with a swelling or palpable moving mass over the wrist.9 Arumugam et al described evaluating for an absence of tenderness over the A1 pulley in patients with trigger finger to suggest possible trigger wrist.14 As case reports of trigger wrist have been published, attempts have been made to create a classification system. In 1985, Suematsu et al reported on three types of triggering of the wrist: (1) type A, a mass occurring on the flexor tendon or flexor tendon sheath as it enters and leaves the carpal tunnel; (2) type B, an anomalous muscle belly entering and leaving the carpal tunnel (including an abnormal lumbrical muscle or abnormal muscle belly of the flexor digitorum superficialis); and (3) type C, a combination of tumor and anomalous muscle.10 The lesion causing trigger wrist in our patient was located on the flexor pollicis longus tendon. While Suematsu et al provided a good overall classification of trigger wrist types, more recent case reports demonstrate the need for an updated system, as prior classification systems do not contain comprehensive etiologies.2 In our patient, daily use of the flexor pollicis longus with the rheumatoid nodule in the carpal tunnel induced hypertrophic tenosynovitis. Similar mechanisms have been described with hypertrophied lumbrical muscles.15 Rheumatoid nodules located on extensor carpi radialis longus and flexor digitorum superficialis tendons have been documented to cause trigger wrist.5 Additionally, Giannikas et al described a case in which the combination of a rheumatoid nodule on the flexor digitorum profundus tendon and extensive synovitis caused ruptures of the superficial flexor tendons and trigger wrist.16 If allowed to progress, our patient's lesion likely would have resulted in a Mannerfelt lesion, which occurs when the flexor pollicis longus tendon ruptures from wear against an osteophyte in the carpal tunnel. These lesions are more common in patients with rheumatoid arthritis, and the flexor pollicis longus is the most widely known flexor tendon to rupture.17 The scaphoid was evaluated intraoperatively in our patient and was not noted to contain osteophytes. Given time for her rheumatoid arthritis to progress, the patient likely could have developed a Mannerfelt lesion because of tendon irritation from the rheumatoid nodule. CONCLUSION While rheumatoid nodules located on the extensor carpi radialis longus, flexor digitorum superficialis, and flexor digitorum profundus tendon have been documented to cause trigger wrist, a rheumatoid nodule located on the flexor pollicis longus tendon causing trigger wrist is an uncommon entity that to our knowledge has not been reported in the literature. In patients with rheumatoid arthritis who present with trigger finger locking symptoms of the thumb with concomitant carpal tunnel symptoms, clinicians must evaluate for possible rheumatoid nodules on the flexor pollicis longus tendon. ACKNOWLEDGMENTS The authors have no financial or proprietary interest in the subject matter of this article. This article meets the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties Maintenance of Certification competencies for Patient Care and Medical Knowledge. REFERENCES 1. Matthews A , Smith K , Read L , Nicholas J , Schmidt E . Trigger finger: an overview of the treatment options. JAAPA. 2019;32 (1 ):17-21. doi: 10.1097/01.JAA.0000550281.42592.97 2. Matsui Y , Kawamura D , Kida H , Hatanaka KC , Iwasaki N . Trigger wrist caused by avascular necrosis of the capitate: a case report. BMC Musculoskelet Disord. 2018;19 (1 ):90. doi: 10.1186/s12891-018-2010-1 29587785 3. Aghasi MK , Rzetelny V , Axer A . The flexor digitorum superficialis as a cause of bilateral carpal-tunnel syndrome and trigger wrist. A case report. J Bone Joint Surg Am. 1980;62 (1 ):134-135.7351405 4. Minami A , Ogino T . Trigger wrist caused by a partial laceration of the flexor superficialis tendon of the ring finger. J Hand Surg Br. 1986;11 (3 ):457-459.3794499 5. Lemon RA , Engber WD . Trigger wrist: a case report. J Hand Surg Am. 1985;10 (1 ):61-63. doi: 10.1016/s0363-5023(85)80248-3 3968405 6. Minetti G , Bartolini B , Garlaschi G , Silvestri E , Cimmino MA . Rheumatoid trigger wrist. Reumatismo. 2015;67 (3 ):123-124. doi: 10.4081/reumatismo.2015.852 26876192 7. Park IJ , Lee YM , Rhee SK , Song SW , Kim HM , Choi KB . Trigger wrist. Clin Orthop Surg. 2015;7 (4 ):523-526. doi: 10.4055/cios.2015.7.4.523 26640639 8. Rand B , McBride TJ , Dias RG . Combined triggering at the wrist and severe carpal tunnel syndrome caused by gouty infiltration of a flexor tendon. J Hand Surg Eur Vol. 2010;35 (3 ):240-242. doi: 10.1177/1753193409357374 20200080 9. Park IJ , Lee YM , Kim HM , Multiple etiologies of trigger wrist. J Plast Reconstr Aesthet Surg. 2016;69 (3 ):335-340. doi: 10.1016/j.bjps.2015.10.030 26644083 10. Suematsu N , Hirayama T , Takemitsu Y . Trigger wrist caused by a giant cell tumour of tendon sheath. J Hand Surg Br. 1985;10 (1 ):121-123. doi: 10.1016/s0266-7681(85)80038-3 3998591 11. Shapiro PS , Seitz WH Jr. Non-neoplastic tumors of the hand and upper extremity. Hand Clin. 1995;11 (2 ):133-160. doi: 10.1016/S0749-0712(21)00039-1 7635878 12. McGrath MH , Fleischer A . The subcutaneous rheumatoid nodule. Hand Clin. 1989;5 (2 ):127-135.2661569 13. Marti T . Snapping wrist and carpal tunnel syndrome. Article in German. Schweiz Med Wochenschr. 1960;90 :986-988.15445455 14. Arumugam M , Sallehuddin H , Rashdeen FMN . A clinical approach to diagnosing trigger wrist [published correction appears in Indian J Orthop. 2020 Dec 7;55(2):498]. Indian J Orthop. 2020;55 (2 ):492-497. doi: 10.1007/s43465-020-00248-7 33927830 15. Shimizu A , Ikeda M , Kobayashi Y , Saito I , Mochida J . Carpal tunnel syndrome with wrist trigger caused by hypertrophied lumbrical muscle and tenosynovitis. Case Rep Orthop. 2015;2015 :705237. doi: 10.1155/2015/705237 16. Giannikas D , Karabasi A , Dimakopoulos P . Trigger wrist. J Hand Surg Eur Vol. 2007;32 (2 ):214-216. doi: 10.1016/J.JHSB.2006.10.016 17196718 17. Miranda BH , Cerovac S . Spontaneous flexor tendon rupture due to atraumatic chronic carpal instability. J Wrist Surg. 2014;3 (2 ):143-145. doi: 10.1055/s-0034-1373840 25032080
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Ochsner J Ochsner J TOJ ochjnl The Ochsner Journal 1524-5012 2831-4107 Academic Division of Ochsner Clinic Foundation 10.31486/toj.23.5033 toj.23.5033 Quarterly Column The Era of Climate Change Medicine Challenges to Health Care Systems Conrad, K Health, Medicine, and Society Conrad Kevin MD Department of Internal Medicine, Ochsner Clinic Foundation, New Orleans, LA Spring 2023 Spring 2023 23 1 78 (c)2023 by the author(s); Creative Commons Attribution License (CC BY) 2023 (c)2023 by the author(s); licensee Ochsner Journal, Ochsner Clinic Foundation, New Orleans, LA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (creativecommons.org/licenses/by/4.0/legalcode) that permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. pmc Editor's Note: With the Spring 2023 issue, we introduce a new recurring quarterly column in the Ochsner Journal. The column will focus on health care delivery and its impact on society. A particular emphasis will be placed on the role the environment, health equity, and social determinants play in health care delivery. A specific focus will be placed on the challenges of providing care to underserved populations and how health care systems are evolving to meet those needs. -R.A. An unprecedented joint editorial published simultaneously in 2021 in The Lancet, New England Journal of Medicine, and The BMJ stated that climate change will cause catastrophic harm to health that will be impossible to remediate unless action is taken.1 The editorial reported that the science is unequivocal: a 1.5 degC expected rise in temperature above the preindustrial average will cause catastrophic harm to health.1 A new era of climate change medicine is emerging. New diseases are being identified, existing ones are being exacerbated, and traditional health care delivery is being challenged. Climate, which has always been associated with health, is now one of the primary forces disrupting health care delivery. Climate change is impacting health in a myriad of ways, including the health impacts of increasingly frequent extreme weather events, such as heat waves, hurricanes, and floods. These events have led to the disruption of the food supply chain, increases in zoonoses, changing patterns of vector-borne diseases, and rising mental health issues. Without intervention, the crisis threatens to undo much of the progress made in global health and poverty reduction. Mesoamerican nephropathy, commonly called chronic kidney disease of unknown cause (CKDu), is a sentinel disease that has emerged and is directly related to exposure to increasing temperatures among field workers in Central America.2,3 Hot spots for CKDu are in areas most impacted by rising temperatures. In Central America, CKD driven in part by CKDu has now become a significant cause of hospitalization and death. CKD is now the second leading cause of death in both Nicaragua and El Salvador.4 The emergence of CKDu also demonstrates that marginalized populations, such as field workers, are the ones most impacted by climate change.3,4 Infectious diseases are also evolving as a result of climate change. The 2022 Intergovernmental Panel on Climate Change reports that the prevalence of vector-borne diseases has increased in recent decades.5 Warmer summers and milder temperatures have allowed pathogens to gain footholds in regions where populations have little immunity and warning systems are poorly developed.5,6 Rising sea temperatures also present unique problems. Harmful algal blooms, the rapid growth of algae or cyanobacteria in lakes, rivers, oceans, and bays, are increasing, potentially exposing marine life, wildlife, and humans to potent neurotoxins.7,8 If we are entering the era of climate change medicine, how should health care systems adapt? First, each health care system must address its impact on climate change and its primary driver carbon emissions. The US health care industry produces 8% of the nation's carbon emissions.9 A more worrisome statistic is that 10% of all smog and 9% of all particulate-related respiratory diseases can be attributed to the carbon emissions of the health care industry.10 One possible solution is to encourage health care systems to begin the process of becoming carbon neutral. In 2020, Kaiser Permanente became the first health care system in the United States to achieve carbon-neutral status.11 Gundersen Health System, a nonprofit hospital network operating in 19 counties across three Midwest states, reports that it sustainably produces more energy than it uses.12 Slowly, health care systems within the United States have made specific sustainability and carbon neutrality goals. Such efforts have advanced at a faster rate abroad. The United Kingdom became the first country to make a carbon neutrality pledge for its entire health care system by 2040.13 To assist these efforts in the United States, the Office of Climate Change and Health Equity was established in 2021 within the US Department of Health and Human Services. The aim of the office is to provide health care systems with clear metrics for assessing greenhouse gas emissions and other health care-related sustainability goals.14 Second, health care systems must integrate environmental information into clinical and public health practice. Robust early-warning systems that correlate climate events with disease occurrence should be developed. Examples include heat waves that may trigger heat-related nephropathy, worsening air quality that may worsen respiratory conditions, and severe weather events that cause disruption of medical services. Health systems can identify the populations most impacted by climate events and work with municipalities to reduce the impact through programs such as increased tree canopy, industrial pollution reduction, and traffic diversion. Mental first aid, a rapid post-event intervention, is also needed in response to severe weather events. Warning systems must also monitor, in real time, the downstream effects of climate change. Such monitoring should include climate-sensitive infectious diseases such as Vibrio vulnificus in our waterways and vector-borne diseases such as Zika virus and dengue fever. For the first time, we are seeing climate refugees who are stressing the capacity of existing health care systems. Health care capacity should be developed to accommodate the expected increase in migration caused by land loss, crop failure, and economic pressures resulting from climate change. Third, a health care workforce that is knowledgeable and prepared for both the physical and mental effects of extreme weather should be developed. Coronavirus disease 2019 was a global event that profoundly impacted the health care workforce.15 Climate change will cause similar worldwide disruptions. Health care systems are in the position to increase awareness of the impact of climate change on health within their communities, starting by educating their large workforces. Climate health literacy is an understanding of your influence on climate and climate's influence on you and society. It is essential that climate health literacy be instituted in medical schools, nursing schools, and allied health training programs. We must all speak a common language when addressing these issues. The next generation of clinicians is certainly engaged, but they need tools to handle the dynamic challenges of climate health. Despite this multifaceted challenge, I am optimistic. Despite what may seem a futile effort, collective action is taking place. Health care is one of the few industries that has the economic clout, the scientific basis, community engagement, and, perhaps most important, the motivation to "first do no harm" to evolve quickly. Our trusted voices are certainly needed to lead in these polarized times. The issues of climate change are significant here in Louisiana. Since the founding of Louisiana, the climate has profoundly impacted our health. The combination of a coastal population that is susceptible to rising sea levels and extreme weather events has made Louisiana vulnerable to the effects of climate change on health and health care delivery. Our response may be seen as a laboratory and example for the rest of the country. In Louisiana, we see the casualties of climate change firsthand and realize that time is not on our side. At a local level, coastal erosion displaces our citizens, amplifies extreme weather events, and threatens the infrastructure of our health care system. Heat waves, hurricanes, floods, and climate-driven yellow fever epidemics have defined our history. Through the years, Louisiana communities have acquired a proud resiliency, and our health care systems have always found ways to meet new challenges. Perhaps climate's impact on health is approaching a tipping point where recovery is not inevitable unless a united effort is made. Planetary health and human health have always been connected. Let's ensure our future health care systems are designed and implemented around that fact. REFERENCES 1. Atwoli L , Baqui AH , Benfield T , Call for emergency action to limit global temperature increases, restore biodiversity, and protect health. N Engl J Med. 2021;385 (12 ):1134-1137. doi: 10.1056/NEJMe2113200 34491006 2. Priyadarshani WVD , de Namor AFD , Silva SRP . Rising of a global silent killer: critical analysis of chronic kidney disease of uncertain aetiology (CKDu) worldwide and mitigation steps. Environ Geochem Health. 2022;10.1007/s10653-022-01373-y. doi: 10.1007/s10653-022-01373-y 3. De Broe ME , Vervaet BA . Is an environmental nephrotoxin the primary cause of CKDu (Mesoamerican nephropathy)? PRO. Kidney360. 2020;1 (7 ):591-595 doi: 10.34067/KID.0003172020 35372944 4. Sorensen C , Garcia-Trabanino R . A new era of climate medicine addressing heat-triggered renal disease. N Engl J Med. 2019;381 (8 ):693-696. doi: 10.1056/NEJMp1907859 31433914 5. IPCC Sixth Assessment Report. Climate change 2022: impacts, adaptations and vulnerability. Intergovernmental Panel on Climate Change. Accessed February 13, 2023. ipcc.ch/report/ar6/wg2/about/how-to-cite-this-report 6. Caminade C , McIntyre KM , Jones AE . Impact of recent and future climate change on vector-borne diseases. Ann N Y Acad Sci. 2019;1436 (1 ):157-173. doi: 10.1111/nyas.13950 30120891 7. Hallegraeff G , Enevoldsen H , Zingone A . Global harmful algal bloom status reporting. Harmful Algae. 2021;102 :101992. doi: 10.1016/j.hal.2021.101992 33875180 8. Patel SS , Lovko VJ , Lockey RF . Red tide: overview and clinical manifestations. J Allergy Clin Immunol Pract. 2020;8 (4 ):1219-1223. doi: 10.1016/j.jaip.2019.10.030 31761688 9. Richie C . Can United States healthcare become environmentally sustainable? Towards green healthcare reform. J Law Med Ethics. 2020;48 (4 ):643-652. doi: 10.1177/1073110520979371 33404336 10. Eckelman MJ , Sherman J . Environmental impacts of the U.S. health care system and effects on public health. PLoS One. 2016;11 (6 ):e0157014. doi: 10.1371/journal.pone.0157014 27280706 11. Reed T . Kaiser Permanente's health system reaches carbon-neutral status. Fierce Healthcare. Published September 15, 2020. Accessed February 14, 2023. fiercehealthcare.com/hospitals/kaiser-permanente-s-heath-system-reaches-carbon-neutral-status 12. Fabris P . Gundersen Health System says it is nation's first net-zero healthcare network. Building Design+Construction. Published January 8, 2015. Accessed February 14, 2023. bdcnetwork.com/gundersen-health-system-says-it-nations-first-net-zero-healthcare-network 13. Jennings N , Rao M . Towards a carbon neutral NHS. BMJ. 2020;371 :m3884. doi: 10.1136/bmj.m3884 33032985 14. Balbus JM , McCannon CJ , Mataka A , Levine RL . After COP26 putting health and equity at the center of the climate movement. N Engl J Med. 2022;386 (14 ):1295-1297. doi: 10.1056/NEJMp2118259 35363451 15. Smallwood N , Harrex W , Rees M , Willis K , Bennett CM . COVID-19 infection and the broader impacts of the pandemic on healthcare workers. Respirology. 2022;27 (6 ):411-426. doi: 10.1111/resp.14208 35048469
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Ochsner J Ochsner J TOJ ochjnl The Ochsner Journal 1524-5012 2831-4107 Academic Division of Ochsner Clinic Foundation 10.31486/toj.22.0039 toj.22.0039 Case Reports and Clinical Observations Renal Squamous Cell Carcinoma Presenting With Renohepatic Fistula: A Rare Amalgam Varshney, B Squamous Cell Carcinoma With Renohepatic Fistula Varshney Bharti MD 1 Nalwa Aasma MD 1 Yadav Taruna MD 2 Choudhary Gautam MCh 3 1 Department of Pathology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India 2 Department of Diagnostic and Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India 3 Department of Urology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India Address correspondence to Taruna Yadav, MD, Department of Diagnostic and Interventional Radiology, All India Institute of Medical Sciences, Basni Phase II, Jodhpur 342005, Rajasthan, India. Tel: +91 0291 283 1961. Email: [email protected] Spring 2023 Spring 2023 23 1 7276 (c)2023 by the author(s); Creative Commons Attribution License (CC BY) 2023 (c)2023 by the author(s); licensee Ochsner Journal, Ochsner Clinic Foundation, New Orleans, LA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (creativecommons.org/licenses/by/4.0/legalcode) that permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Background: Primary squamous cell carcinoma (SCC) of the kidney, a rare malignancy that accounts for less than 1% of all urinary tract malignancies, is usually diagnosed in late stages because of the lack of characteristic clinical and imaging features and aggressive behavior. Case Report: A 66-year-old male presented with complaints of right flank pain. Imaging suggested the differential diagnoses of xanthogranulomatous pyelonephritis or renal malignancy extending into segment VI of the liver. Right subcapsular nephrectomy was performed, and nonbilious fluid from the liver cavitary lesions was drained. Histopathologic examination showed that the lesion was a renal SCC with contiguous malignant infiltration of the liver that led to a renohepatic fistula. Conclusion: Renal SCC is a rare high-grade neoplasm and can present in an unusual form with a poor prognosis. Keywords: Carcinoma-squamous cell kidney neoplasms nephrolithiasis pyelonephritis-xanthogranulomatous pmcINTRODUCTION Primary squamous cell carcinoma (SCC) of the kidney, a rare malignancy that accounts for less than 1% of urinary tract malignancies,1 is usually associated with nephrolithiasis and hydronephrosis. Calculi in the kidney are a cause of chronic irritation causing squamous metaplasia that can become malignant.2,3 SCC of the kidney, in contrast to other renal tumors, is usually diagnosed late because of nonspecific clinical and radiologic findings. We present a case of kidney SCC that led to a renohepatic fistula diagnosed after nephrectomy for suspected xanthogranulomatous pyelonephritis. CASE REPORT A 66-year-old male presented with complaints of right flank pain for 20 days that he described as mild to moderate in intensity; nonradiating; and not associated with fever, vomiting, hematuria, or pyuria. The patient had no history of smoking but did have a history of right-sided pyelolithotomy for renal calculi 35 years prior. On examination, he had right flank tenderness without any palpable mass. His leukocyte count was 15,800 cells/mm3 (reference range, 4,000-11,000 cells/mm3), predominantly neutrophilic. He had elevated C-reactive protein of 105.7 mg/L (reference range, 8-10 mg/L) and elevated erythrocyte sedimentation rate of 91 mm/h (reference range, 0-20 mm/h). The patient's kidney, liver function, and other biochemical tests were within normal limits. On the day of admission, he was started on a 3 times daily intravenous (IV) infusion of cefoperazone-sulbactam 1.5 g because of the suspicion of urinary tract infection. Abdominal ultrasound showed an ill-defined heterogeneous mass in the upper pole of the right kidney, extending into segment VI of the liver with no significant vascularity. The liver component showed central necrotic areas . On further evaluation with contrast-enhanced computed tomography, a 3.5-cm staghorn calculus was visualized in the right renal pelvis with other small calculi in the pelvicalyceal system, leading to moderate hydronephrosis . The right kidney was nonfunctioning with an absence of contrast excretion in the delayed phase . Multiple necrotic lymph nodes were seen in the right renal hilar and retroperitoneal (para-aortic, aortocaval) region. The right renal vein and inferior vena cava showed normal contrast opacification with no evidence of thrombus. The left kidney was normal. Figure 1. (A) Sagittal ultrasound image shows a heterogeneous mass in the upper pole of the right kidney with contiguous extension in segment VI of the liver and a central necrotic component (arrows on the left). Renal calculus with distal acoustic shadowing (arrow on the right) and hydronephrosis are also present. (B) Sagittal and (C) coronal reformats of contrast-enhanced computed tomography show multiple right staghorn renal calculi with hydronephrosis. A heterogeneously enhancing mass in the upper pole of the right kidney infiltrates the adjacent liver (arrows). (D) Excretory phase volume-rendered image shows right staghorn calculus with nonfunctioning right kidney. The left renal pelvis, ureter (arrows), and urinary bladder are delineated due to normal contrast excretion. UB, urinary bladder. Three samples of the patient's urine were negative for malignant cytology, and culture was negative for the growth of any microorganisms. On day 4 of admission, the patient's total leukocyte count increased to 18,600 cells/mm3 despite IV antibiotics. Given the patient's nephrolithiasis, preoperative differential diagnoses were xanthogranulomatous pyelonephritis with an extension of infection to the liver or renal malignancy. The patient underwent a right open subcapsular nephrectomy through an extraperitoneal incision on day 6 of admission. The kidney was adherent to the parietal wall. The 2 cavitary lesions in the liver were filled with turbid nonbilious fluid and were drained . The peritoneal cavity was thoroughly washed with saline, and a small peritoneal opening at the inferior margin of the liver was repaired. The postoperative period was uneventful, and the patient was discharged on postoperative day 6 with oral cefixime 200 mg twice daily for 5 days. Figure 2. (A) Intraoperative image shows cavitary lesion in the inferior part of the liver (arrow). (B) Cut section of the kidney displays hydronephrosis, renal cortical atrophy, yellowish discoloration of pelvicalyceal lining, multiple calculi, thickening of intercalyceal septa, and renal pelvis. On gross examination of the nephrectomy specimen , the kidney was mildly enlarged. The cut section of the kidney showed multiple variable-sized calculi. The wall of the kidney was diffusely thickened, and no definite intraluminal growth was identified. On microscopy , the renal parenchyma was infiltrated with nests and sheets of epithelial cells, polygonal in shape and with a central hyperchromatic nucleus and dense eosinophilic keratinized cytoplasm. Between the tumor nests, entrapped renal parenchyma in the form of a few cystically dilated and predominantly atrophic tubules and sclerosed glomeruli were seen. Perineural invasion was present. The renal sinus and perinephric fat were uninvolved. Foci of foamy histiocytic cell collections, lymphocytes, and plasma cells were in the surrounding renal parenchyma. On immunohistochemistry, the tumor cells were immunopositive for p40. Fine needle aspiration cytology of the liver lesion revealed atypical squamous cells in a necrotic background. The tumor was diagnosed as a renal SCC with focal areas of xanthogranulomatous pyelonephritis. The renohepatic fistula was formed by the contiguous malignant invasion of the adjacent liver. Figure 3. (A) Photomicrograph shows a tumor arranged in nests and islands with adjacent renal parenchyma in the lower left corner displaying atrophied interstitium and tubules (hematoxylin and eosin stain [H&E], magnification x40). (B) Photomicrograph demonstrates the focal replacement of renal parenchyma with foamy histiocytes and lymphoplasmacytic inflammation (H&E, magnification x100). (C) High-power view displays prominent histiocytes with the adjacent focus of the tumor (H&E, magnification x400). (D) Photomicrograph shows tumor cells immunopositive for p40 (magnification x100). The patient refused adjuvant therapy. His fever had resolved and his general well-being had improved at 2-month follow-up, but the patient died from acute myocardial infarction 6 months after surgery. DISCUSSION Renal SCC is a rare high-grade neoplasm that is generally in an advanced stage at presentation, thus having a poor prognosis. The usual reported age of presentation of renal SCC is the fifth to the seventh decade, similar to the more common renal cell carcinoma (RCC), which has a better prognosis. The associated causative factors for SCC are recurrent urinary tract infections with chronic pyelonephritis, long-standing staghorn-type calculi, smoking, schistosomiasis, hormonal imbalance, analgesic abuse, and previous surgery for renal calculi.4,5 Most renal SCCs are associated with nephrolithiasis, but renal SCCs have no specific radiologic features.1 Because of the rarity of this malignancy, the literature is scarce. Renal SCC can have varied presentations such as diffusely enlarged nonfunctioning kidney with renal calculi, diffuse wall thickening with the absence of a distinct mass, hydronephrosis, and low echogenicity in the renal parenchyma or solid-cystic mass.1,3,4 On imaging, enhancing lesions with the exophytic or intraluminal components in the kidney can be a helpful feature for indicating the presence of renal SCC.1 The unpredictable imaging appearance often delays clinical/radiologic diagnosis. Histopathology generally clinches the final diagnosis. This situation is in contrast to RCC, in which patients may have classic symptoms of hematuria, flank mass, and flank pain, and typical radiologic features such as a solitary solid enhancing mass with decreased attenuation suggestive of necrosis are often present. Renal SCCs originate more often from the renal pelvis than the renal parenchyma. Primary renal SCC needs to be differentiated from squamous differentiation in urothelial carcinoma and metastatic SCC.2,5 The closest differential diagnosis of SCC of renal origin is xanthogranulomatous pyelonephritis, an uncommon type of chronic pyelonephritis resulting from chronic obstruction, usually from renal stones and formation of an inflammatory mass destroying renal parenchyma and masquerading as malignancy.6 Xanthogranulomatous pyelonephritis can infiltrate adjacent organs, thus making it even more challenging to distinguish from malignancy.6,7 Renohepatic fistulas are rare and can result from trauma, infection (eg, tuberculosis, pyonephrosis, renal abscess rupture, liver abscess rupture into renal parenchyma), or, rarely, malignancy.8 Chung et al described a case of renal SCC leading to the development of a pyelo-colo-duodenal fistula.8 Chung et al also reported a pyelo-hepatic fistula that developed from the spread of infection from the kidney to the liver.9 A high index of suspicion on imaging and preoperative biopsy can aid in distinguishing between infection and malignancy.10,11 Our case clinically and radiologically appeared as xanthogranulomatous pyelonephritis; however, the histopathologic examination revealed an SCC of the kidney in a background of xanthogranulomatous pyelonephritis with metastases to the liver. Although primary renal SCC is rare, our case had contiguous liver invasion by renal SCC leading to a renohepatic fistula which, to our knowledge, has not been previously reported.2,4,5,8-10,12-16 This case highlights the highly variable presentations of renal SCC. The primary treatment for renal SCC is nephrectomy, and the role of adjuvant chemotherapy or radiotherapy is uncertain.3,13 No standard guideline is available because of the rarity of this tumor. Our patient did not consent to adjuvant therapy. Further studies are essential to determine if chemotherapy or radiotherapy may improve survival, especially anti-epidermal growth factor receptor (EGFR) therapy in EGFR receptor-positive cases.15 CONCLUSION Renal SCC should be a differential diagnosis for any renal mass presenting as xanthogranulomatous pyelonephritis with renal calculi, long-term hydronephrosis, or thickened renal parenchyma. Extensive sampling of the specimen is essential to detect the presence of tiny unobvious foci of malignancy, especially in patients with xanthogranulomatous pyelonephritis or nephrolithiasis. Also, patients with nephrolithiasis should be regularly monitored for the development of malignancy. ACKNOWLEDGMENTS The authors have no financial or proprietary interest in the subject matter of this article. This article meets the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties Maintenance of Certification competencies for Patient Care and Medical Knowledge. REFERENCES 1. Kalayci OT , Bozdag Z , Sonmezgoz F , Sahin N . Squamous cell carcinoma of the renal pelvis associated with kidney stones: radiologic imaging features with gross and histopathological correlation. J Clin Imaging Sci. 2013;3 :14. doi: 10.4103/2156-7514.109741 23814686 2. Ghosh P , Saha K . Primary intraparenchymal squamous cell carcinoma of the kidney: a rare and unique entity. Case Rep Pathol. 2014;2014 :256813. doi: 10.1155/2014/256813 3. Holmang S , Lele SM , Johansson SL . Squamous cell carcinoma of the renal pelvis and ureter: incidence, symptoms, treatment and outcome. J Urol. 2007;178 (1 ):51-56. doi: 10.1016/j.juro.2007.03.033 17574059 4. Jiang P , Wang C , Chen S , Li J , Xiang J , Xie L . Primary renal squamous cell carcinoma mimicking the renal cyst: a case report and review of the recent literature. BMC Urol. 2015;15 :69. doi: 10.1186/s12894-015-0064-z 26201315 5. Kulshreshtha P , Kannan N , Bhardwaj R , Batra S . Primary squamous cell carcinoma of the renal parenchyma. Indian J Pathol Microbiol. 2012;55 (3 ):370-371. doi: 10.4103/0377-4929.101747 23032834 6. Khalid S , Zaheer S , Zaheer S , Ahmad I , Khalid M . Xanthogranulomatous pyelonephritis: rare presentation of a rare disease. South Asian J Cancer. 2013;2 (1 ):4. doi: 10.4103/2278-330X.105863 7. Al-Ghazo MA , Ghalayini IF , Matalka II , Al-Kaisi NS , Khader YS . Xanthogranulomatous pyelonephritis: analysis of 18 cases. Asian J Surg. 2006;29 (4 ):257-261. doi: 10.1016/S1015-9584(09)60099-3 17098659 8. Chung SD , Sun HD , Hung SF , Chiu B , Chen Y , Wu JM . Renal stone-associated squamous cell carcinoma and pyelo-colo-duodenal fistula. Urology. 2008;72 (5 ):1013. doi: 10.1016/j.urology.2008.06.020 18684495 9. Chung SD , Chen KH , Chang HC . Pyelo-hepatic fistula. Urology. 2008;72 (3 ):524. doi: 10.1016/j.urology.2008.02.075 18649927 10. Mardi K , Kaushal V , Sharma V . Rare coexistence of keratinizing squamous cell carcinoma with xanthogranulomatous pyelonephritis in the same kidney: report of two cases. J Cancer Res Ther. 2010;6 (3 ):339-341. doi: 10.4103/0973-1482.73351 21119270 11. Lee TY , Ko SF , Wan YL , Renal squamous cell carcinoma: CT findings and clinical significance. Abdom Imaging. 1998;23 (2 ):203-208. doi: 10.1007/s002619900324 9516518 12. Fotovat A , Gheitasvand M , Amini E , Ayati M , Nowroozi MR , Sharifi L . Primary squamous cell carcinoma of renal parenchyma: case report and review of literature. Urol Case Rep. 2021;37 :101627. doi: 10.1016/j.eucr.2021.101627 33747792 13. Zhang X , Zhang Y , Ge C , Zhang J , Liang P . Squamous cell carcinoma of the renal parenchyma presenting as hydronephrosis: a case report and review of the recent literature. BMC Urol. 2020;20 (1 ):107. doi: 10.1186/s12894-020-00676-5 32689976 14. Wang Z , Yan B , Wei YB , Primary kidney parenchyma squamous cell carcinoma mimicking xanthogranulomatous pyelonephritis: a case report. Oncol Lett. 2016;11 (3 ):2179-2181. doi: 10.3892/ol.2016.4200 26998145 15. Sahoo TK , Das SK , Mishra C , Squamous cell carcinoma of kidney and its prognosis: a case report and review of the literature. Case Rep Urol. 2015;2015 :469327. doi: 10.1155/2015/469327 16. Terada T . Synchronous squamous cell carcinoma of the kidney, squamous cell carcinoma of the ureter, and sarcomatoid carcinoma of the urinary bladder: a case report. Pathol Res Pract. 2010;206 (6 ):379-383. doi: 10.1016/j.prp.2009.07.021 19766408
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Front Plant Sci Front Plant Sci Front. Plant Sci. Frontiers in Plant Science 1664-462X Frontiers Media S.A. 10.3389/fpls.2023.1157296 Plant Science Editorial Editorial: Beneficial microbes and the interconnection between crop mineral nutrition and induced systemic resistance, volume II Lucena Carlos 1 * Aroca Ricardo 2 * Wang Jianfei 3 * Zimmermann Sabine Dagmar 4 * 1 Departamento de Agronomia (DAUCO-Maria de Maeztu Unit of Excellence), Campus de Rabanales CeiA3, Universidad de Cordoba, Cordoba, Spain 2 Departamento de Microbiologia del Suelo y Sistemas Simbioticos, Estacion Experimental del Zaidin (CSIC), Granada, Spain 3 Anhui University of Science and Technology, Huainan, China 4 IPSiM, Univ Montpellier, CNRS, INRAE, Institut Agro, Montpellier, France Edited and Reviewed by: Andrea Genre, University of Turin, Italy *Correspondence: Carlos Lucena, [email protected]; Ricardo Aroca, [email protected]; Jianfei Wang, [email protected]; Sabine Dagmar Zimmermann, [email protected] This article was submitted to Plant Symbiotic Interactions, a section of the journal Frontiers in Plant Science 24 2 2023 2023 14 115729602 2 2023 14 2 2023 Copyright (c) 2023 Lucena, Aroca, Wang and Zimmermann 2023 Lucena, Aroca, Wang and Zimmermann This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial on the Research Topic Beneficial microbes and the interconnection between crop mineral nutrition and induced systemic resistance, volume II nutrient deficiency ISR eliciting microbes crops soil microbial consortia pmcSimilarly to responses to biotic stresses, provoked by biological agents, like pathogens or insects (Verbon et al., 2017), plants respond to abiotic stresses, such as mineral nutrient deficiencies. Some of these responses are located at the effector site but others are systemic, inducing defense responses in the entire plant (Pieterse et al., 2014). Among the systemic responses is reported the Induced Systemic Resistance (ISR) (Romera et al., 2019). ISR is induced by beneficial rhizobacteria or by rhizofungi (Pii et al., 2016). The ways beneficial rhizosphere microorganisms elicit ISR is not totally understood but several substances produced by these microorganisms, like volatile organic compounds or siderophores that interact with the plants, have been proposed as elicitors (Martinez-Medina et al., 2017; Romera et al., 2019). Hormones and signaling molecules, either produced by the microorganisms or generated by the plants upon interaction with them, are also implicated in the ISR and mineral nutrient deficiency responses. Among them, jasmonic acid, ethylene, auxin and nitric oxide play a key role (Romera et al., 2019; Pescador et al., 2022). Some years ago, it was found that the MYB72 gene, encoding a transcription factor (TF), was greatly induced in Arabidopsis thaliana roots upon treatment with Pseudomonas simiae (Van der Ent, 2008). A. thaliana myb72 mutant plants can not develop ISR. This suggests that this TF plays a key role in the transduction pathway leading to ISR (Van der Ent, 2008; Zamioudis et al., 2015). Elucidating the main nodes of interconnection between the pathways regulating microbe-elicited ISR and mineral uptake is critical for optimizing the use of plant mutualistic microbes in agriculture. The Research Topic updates latest findings related to the roles of ISR eliciting microbes in crops. The Research Topic was launched in late 2021 in the section "Plant Symbiotic Interactions" of Frontiers in Plant Science to continue further this thematic series (Lucena et al., 2021a). This second call includes 5 additional articles, three original research articles (Liu et al.; Qian et al.; Shan et al.) and two review papers (Qin et al.; Zhu et al.) by 34 authors. Interplay between beneficial plant-microbe interactions and biotic and abiotic stress conditions has been observed and intensively studied (Romera et al., 2019; Usman et al., 2021). In fact, in addition to plant tolerance and plasticity for adaptation to harmful environements, beneficial miroorganisms will allow a kind of fortification of the plant physiology. The study by Liu et al. is dealing with an abiotic stress tightly linked to ongoing climate change, namely with heat stress. Authors, compared the effect of mild or high heat stress over several physiological indexes of Rhododendron simsii and on the posible changes of bacterial and fungal soil communities. The results showed that R. simsii may cooperate with soil microbial communities to obtain nutrients from the soil to help them resist heat stress when this stress is mild. The role of the endophyte Pseudomonas sp. MCS15 through the production of a glucuronic acid and its interaction with ethylene inhibiting heavy metal uptake in rice was studied by Qian et al.. The Authors aimed at increasing evidence that endophytic bacteria can regulate plant hormone levels to help their hosts counteract adverse effects imposed by abiotic and biotic stresses. They showed that inoculation with MCS15 significantly inhibited the expression of ethylene biosynthetic genes and thus reduced the content of ethylene in rice roots. Using both precursors and inhibitors of ethylene biosynthesis, the author s results revealed that the endophytic bacteria MCS15-secreted glucuronic acid inhibited the biosynthesis of ethylene and thus weakened iron uptake-related systems in rice roots, which contributed to preventing the Cd accumulation. Abiotic stress is also connected to a lack of nutrients occuring in poor or affected environments. Implication of beneficial plant root associations with soil microbes becomes dissected at the molecular level revealing a symbiotic transportome. A broad interest has been developed for this topic during the last years (e.g. Garcia et al., 2016; Guerrero-Galan et al., 2018; Garcia et al., 2020; Lucena et al., 2021b). In this context, the study by Shan et al. dealing with the beneficial effects of mycorrhizal fungi for orchid growth is clearly demonstrating an improvement in nitrogen uptake. Previous studies had reported orchid growth promotion by such fungi. Here, the authors analyzed growth, transcriptomic and metabolic parameters of the medicinal important orchid Dendrobium officinale in interaction with the fungus Mycena sp., called MF23. Several plant genes involved in N transport and assimiation have been found to become upregulated upon symbiotic interaction. In addition to mitigation of abiotic stress, beneficial interactions are playing also an important role in defense stimulation limiting pathogenic attacks (Pieterse et al., 2014). Better understanding of such interactions will surely become more important with respect to their applications in challenging agroecosystems. The review by Qin et al. aims at a systematic analysis of published data concerning the interplay between arbuscular mycorrhizal fungi (AMF) and pathogenic microbes from 36 studies including 650 observations. This meta-analysis revealed a tight link between AMF-stimulated plant growth and reduced pathogenic harm levels. AMF root length colonization was taken as best parameter for this analysis. More generally, the review by Zhu et al. is related to the mechanisms underlying how plants recognize beneficial rhizobacteria which are generally called as plant growth-promoting rhizobacteria (PGPR). These PGPRs can be recognized as microbial associated molecular patterns (MAMPs), commonly called as pathogen associated molecular patterns (PAMPs), by diverse plant pattern recognition receptors (PRRs) further triggering host defense responses. The authors described that for establishing mutual benefits with the hosts, PGPRs have developed strategies to weaken the activation of host defense systems. Moreover, the process of the PGPR-induced ISR in plants can be regulated by root hair-specific syntaxins and non-coding RNAs. However, it remains elusive how plants balance between microbial recognition and defense activation. Moreover, the transferring mechanisms of small RNAs from roots to shoots for provoking ISR need to be deeply explored. In conclusion, this second part of the Research Topic, bringing together 5 more articles dealing with plant-microbe associations in the context of plant defense and systemic resistence, reflects well the ongoing research in this area. In the light of agricultural demands to improve plant tolerance and growth, questions linked to this Research Topic remain challenging. Author contributions CL and SDZ wrote the manuscript. All Editors contributed and approved this editorial. Acknowledgments We are grateful to all Authors who contributed to this Research Topic, to the Reviewers who evaluated their work and to the Frontiers editorial staff for their assistance. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. References Garcia K. Bucking H. Zimmermann S. D. (2020). Editorial: Importance of root symbiomes for plant nutrition: New insights, perspectives, and future challenges. Front. Plant Sci. 11 . doi: 10.3389/fpls.2020.00594 Garcia K. Doidy J. Zimmermann S. D. Wipf D. Courty P. E. (2016). Take a trip through the plant and fungal transportome of mycorrhiza. Trends Plant Sci. 21 (11 ), 937-950. doi: 10.1016/j.tplants.2016.07.010 27514454 Guerrero-Galan C. Houdinet G. Calvo-Polanco M. Bonaldi K. E. Garcia K. Zimmermann S. D. (2018). The role of plant transporters in mycorrhizal symbioses. Adv. Bot. Res. 87 , 303-342. doi: 10.1016/bs.abr.2018.09.012 Lucena C. Alcala-Jimenez M. T. Romera F. J. Ramos J. (2021b). Several yeast species induce iron deficiency responses in cucumber plants (Cucumis sativus l.). Microorganisms 9 , 2603. doi: 10.3390/microorganisms9122603 34946203 Lucena C. Zimmermann S. D. Wang J. Aroca R. (2021a). Editorial: Beneficial microbes and the interconnection between crop mineral nutrition and induced systemic resistance. Front. Plant Sci. 12 . doi: 10.3389/fpls.2021.790616 Martinez-Medina A. Van Wees S. C. M. Pieterse C. M. J. (2017). Airborne signals from Trichoderma fungi stimulate iron uptake responses in roots resulting in priming of jasmonic acid dependent defences in shoots of Arabidopsis thaliana and Solanum lycopersicum . Plant Cell Environ. 40 , 2691-2705. doi: 10.1111/pce.13016 28667819 Pescador L. Fernandez I. Pozo M. J. Romero-Puertas M. C. Pieterse C. M. J. Martinez-Medina A. (2022). Nitric oxide signalling in roots is required for MYB72-dependent systemic resistance induced by Trichoderma volatile compounds in Arabidopsis . J. Exp. Bot. 73 , 584-595. doi: 10.1093/jxb/erab294 34131708 Pieterse C. M. J. Zamioudis C. Berendsen R. L. Weller D. M. Van Wees S. C. M. Bakker P. A. H. M. (2014). Induced systemic resistance by beneficial microbes. Annu. Rev. Phytopathol. 52 , 347-375. doi: 10.1146/annurev-phyto-082712-102340 24906124 Pii Y. Borruso L. Brusetti L. Crecchio C. Cesco S. Mimmo T. (2016). The interaction between iron nutrition, plant species and soil type shapes the rhizosphere microbiome. Plant Physiol. Biochem. 99 , 39-48. doi: 10.1016/j.plaphy.2015.12.002 26713550 Romera F. J. Garcia M. J. Lucena C. Martinez-Medina A. Aparicio M. A. Ramos J. . (2019). Induced systemic resistance (ISR) and fe deficiency responses in dicot plants. Front. Plant Sci. 10 . doi: 10.3389/fpls.2019.00287 Usman M. Ho-Plagaro T. Frank H. E. R. Calvo-Polanco M. Gaillard I. Garcia K. . (2021). Mycorrhizal symbiosis for better adaptation of trees to abiotic stress caused by climate change in temperate and boreal forests. Front. For. Glob. Change 4 . doi: 10.3389/ffgc.2021.742392 Van der Ent S. (2008). Transcriptional regulators of rhizobacteria induced systemic resistance (Utrecht: Utrecht University Repository). Ph.D. Thesis. Verbon E. H. Trapet P. L. Stringlis I. A. Kruijs S. Bakker P. A. H. M. Pieterse C. M. J. (2017). Iron and immunity. Annu. Rev. Phytopathol. 55 , 355-375. doi: 10.1146/annurev-phyto-080516-035537 28598721 Zamioudis C. Korteland J. Van Pelt J. A. Van Hamersveld M. Dombrowski N. Bai Y. . (2015). Rhizobacterial volatiles and photosynthesis-related signals coordinate MYB 72 expression in Arabidopsis roots during onset of induced systemic resistance and iron-deficiency responses. Plant J. 84 , 309-322. doi: 10.1111/tpj.12995 26307542
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34933 Genetics Ophthalmology Pseudodominant Inheritance of Retinitis Pigmentosa Due to Mutations in the Phosphodiesterase 6B Gene: A Case Report Muacevic Alexander Adler John R Robles Bocanegra Andrea 1 Tato Javier 2 Molina Thurin Leonardo J 1 Izquierdo Natalio 3 Oliver Armando L 4 1 Ophthalmology, San Juan Bautista School of Medicine, Caguas, PRI 2 Ophthalmology, Ponce Health Sciences University, Ponce, PRI 3 Surgery, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PRI 4 Ophthalmology, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, USA Andrea Robles Bocanegra [email protected] 13 2 2023 2 2023 15 2 e3493313 2 2023 Copyright (c) 2023, Robles Bocanegra et al. 2023 Robles Bocanegra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Mutations in the phosphodiesterase 6B (PDE6B) gene are a rare cause of autosomal recessive retinitis pigmentosa (arRP). We report on a non-consanguineous family with a pseudodominant inheritance of RP due to PDE6B mutations. We conducted a chart review of four members of a Puerto Rican family who underwent a comprehensive ophthalmic evaluation by at least one of the authors. The mutational screening was done using a genotyping microarray provided by Invitae Corporation, using next-generation sequencing (NGS) technology. Genomic DNA obtained from saliva samples is enriched for targeted regions using a hybridization-based protocol and sequenced using Illumina technology. A descriptive analysis was done. Patient 1A had a normal ophthalmic examination and a heterozygous pathogenic variant in the PDE6B gene c.1540del PLeu514Trpfs*61. Patients 1B, 2A, and 2B had mid-peripheral retinitis pigmentosa, concentric visual field ring scotomata in both eyes (OU), extinguished electroretinogram (ERG), and homozygous pathogenic variants in the PDE6B gene c.1540del PLeu514Trpfs*61. Even though mutations in the PDE6B gene usually lead to arRP, they may be inherited in a pseudodominant pattern in geographically isolated populations. Genotyping studies in patients with RP are warranted to classify inheritance mode correctly. retinitis pigmentosa retinal dystrophies inherited retinal disease case report bony spicules pde6b variant autosomal recessive retinitis pigmentosa The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Previous studies have reported that retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases (IRD) characterized by the loss of photoreceptor activity and retinal pigment epithelium function . It affects 1 in 3,000 to 7,000 people, and their symptoms develop from childhood to early adolescence. RP is the most common form of IRD . Although RP is associated with high genetic and clinical heterogeneity, nyctalopia is the most common clinical manifestation. Subsequently, patients may develop progressive loss of their central and peripheral vision . To date, there are 89 causative genes associated with RP . Reports of the phenotypic presentation classically seen in RP were initially found in rodless mice in 1928 . The phosphodiesterase 6B (PDE6B) gene is inherited as an autosomal recessive trait and accounts for approximately 8% of all diagnosed autosomal recessive RP (arRP) patients . Khramtsov NV et al. reported that the PDE6B gene is located on chromosome 4p16.3. It comprises 22 coding exons and encodes 854 amino acid residues . This gene codes for the beta-subunit of rod-specific cyclic guanosine monophosphate (cGMP) phosphodiesterase 6 (PDE6) and is an essential component of the visual phototransduction cascade . To date, 28 mutations in the human PDE6B gene have been reported in the literature and classified as leading to the progression of RP . We report non-consanguineous patients with pseudodominant inheritance of RP associated with mutations in the PDE6B gene. Case presentation Gene sequencing and deletion/duplication analysis using next-generation sequencing (NGS) were utilized to assess the inherited pattern of RP within a non-consanguineous family from a geographically isolated location. Genetic studies were initially done on a child that presented with nyctalopia and his mother, who had a previous diagnosis of RP. The mutational screening was done using a genotyping microarray provided by Invitae Corporation, using NGS technology. Genomic DNA obtained from saliva samples was enriched for targeted regions using a hybridization-based protocol and sequenced using Illumina technology. Following the results, genetic analysis was done on the other two members of the family due to the autosomal recessive inheritance of the disease. The analyses showed a pathogenic homozygous mutation in the PDE6B gene in both children. The mutation is a c.1540del of the variant p.Leu514Trpfs*61. Figure 1 shows this family's pedigree. The mother presented with the same homozygous mutation as the children, whereas the father had a heterozygous pathogenic mutation in the PDE6B gene. This suggests that, within this family, a variant of this autosomal recessive retinal disease was inherited in a pseudodominant pattern. Each member of this family underwent a comprehensive ophthalmic evaluation. Figure 1 Two-generation pedigree of arRP with PDE6B gene mutation. Pedigree depicts the arRP phenotypes associated with this family's PDE6B genetic mutation. It shows the individual mutations in each family member and their corresponding macular optical coherence tomography. arRP: Autosomal recessive retinitis pigmentosa. Patient 1A A 43-year-old male underwent genetic testing, and analysis showed a heterozygous pathogenic mutation in the PDE6B gene. He had a best-corrected visual acuity of 20/40 and 20/30 +2 in the right eye (OD) and left eye (OS), respectively. Refraction was plano in both eyes (OU). Upon fundus examination, he had normal optic nerves, vessels, and retinal findings. There was no macular edema or mid-peripheral bony spicules OU. Upon macular optical coherence tomography (OCT), the patient had an average macular thickness of 279 mm and 287 mm in OD and OS, respectively. Total macular volume was 10 mm3 and 10.3 mm3 OD and OS, respectively. No visual field was obtained from this patient. Patient 1B A 45-year-old female underwent genetic testing, and the analysis showed a pathogenic homozygous mutation in the PDE6B gene. She had been diagnosed with RP at age 26. She has a best-corrected visual acuity of 20/40 +2 and 20/40 +2 in OD and OS, respectively. Refraction was -2.00 +1.50 x 5 and -1.50 +2.50 x 175 in OD and OS, respectively. Upon fundus examination, she had pale optic nerves, attenuated vessels, macular edema , and mid-peripheral bony spicules OU. Upon macular OCT, the patient had an average macular thickness of 266 mm and 258 mm in OD and OS, respectively. Total macular volume was 9.5 mm3 and 9.3 mm3 OD and OS, respectively. Visual field testing revealed a mean deviation of -25.96 dB (p <0.5%) OD and -26.77 dB (p <0.5%) OS. The patient had mild red-green deficiency upon homologous recombination repair (HRR) testing. Patient 2A A 15-year-old boy underwent genetic testing and was subsequently diagnosed with RP. He had presented with progressive worsening visual symptoms (i.e., nyctalopia) and displayed a best-corrected visual acuity of 20/50 +2 and 20/50 +1 in OD and OS, respectively. Refraction was +0.50 DS +2.00 DC x 110 and +0.75 DS +2.00 DC x 95 in OD and OS, respectively. Upon fundus examination, he had pale optic nerves, attenuated vessels, macular edema , and mid-peripheral bony spicules OU. Upon macular OCT, the patient had an average macular thickness of 325 mm and 312 mm in OD and OS, respectively. Total macular volume was 11.7 mm3 and 11.2 mm3 OD and OS, respectively. Visual field testing revealed a mean deviation of -22.28 dB (p <0.5%) OD and -21.03 dB (p < 0.5%) OS. The patient had mild red-green deficiency upon HRR testing. Patient 2B A 13-year-old boy underwent genetic testing and was subsequently diagnosed with RP. His uncorrected visual acuity was 20/80 +1 OD and 20/50 +1 OS. Refraction was +2.00 +1.00 x 90 and +3.00 +1.50 DC x 90 in OD and OS, respectively. Upon fundus examination, he had pale optic nerves, attenuated vessels, macular edema , and mid-peripheral bony spicules OU. Upon macular OCT, the patient had an average macular thickness of 352 mm and 355 mm in OD and OS, respectively. Total macular volume was 12.7 mm3 and 12.8 mm3 in OD and OS, respectively. Visual field testing revealed a mean deviation of -19.56 dB (p <0.5%) OD and -16.77 dB (p < 0.5%) OS. The patient had mild red-green deficiency upon HRR testing. Discussion RP is the most common subtype of inherited retinal disease (IRD) . The disease manifests with early-onset nyctalopia followed by visual field defects. Literature suggests that RP is inherited in either an autosomal recessive, autosomal dominant, or X-linked pattern in 30%, 20%, and 10% of families, respectively . Nevertheless, mutational screening of the cases we reported on shows a pseudodominant inheritance pattern for the pathogenic variant in the PDE6B gene. Pseudodominance typically occurs when a patient with a known recessive disorder and a clinically unaffected partner have offspring that are affected with the same recessive disorder as the affected parent . It is usually associated with high mutant frequency in isolated populations. In our family, the affected mother (A2) was homozygous for a pathogenic p.Leu514Trpfs*61 variant on the PDE6B gene, whereas the unaffected father (A1) was a heterozygous carrier of the same pathogenic variant. For this reason, they had two affected offspring (B1 and B2) that inherited one variant from each parent. This resulted in patients with the classic arRP phenotype. Possibilities for pseudodominance were considered. Habibi I et al. showed that autosomal recessive retinal dystrophies could be transmitted in a pseudodominant pattern in consanguineous families . Parents in this family denied consanguinity. However, this family was from the central mountainous region of Puerto Rico, where a high prevalence of this gene mutation may exist. We thus concluded that the presence of this inheritance pattern was a result of geographic isolation. Conclusions Inheritance patterns in patients with RP remain challenging, especially in patients from geographically isolated populations. Genotyping studies in patients with RP are warranted to classify inheritance patterns correctly. If there is more than one affected member of a nuclear family, pseudodominance should be considered. Limitations in this study include the small number of patients. RP is a rare disease as it is, and the frequency of this mutation leading to RP makes it even rarer. Future studies are warranted to find the origin of this gene variant on the island. The focus of such studies should be placed on patients with a clinical diagnosis of RP in the central mountainous regions of Puerto Rico, where consanguinity leads to an increased incidence of autosomal recessive diseases. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Retinitis pigmentosa Surv Ophthalmol Pagon RA 137 177 33 1988 3068820 2 Genes and mutations causing retinitis pigmentosa Clin Genet Daiger SP Sullivan LS Bowne SJ 132 141 84 2013 23701314 3 Novel variants in PDE6A and PDE6B genes and its phenotypes in patients with retinitis pigmentosa in Chinese families BMC Ophthalmol Li Y Li R Dai H Li G 27 22 2022 35033039 4 The geotropic reaction of rodless mice in light and darkness J Gen Physiol Keeler CE 361 368 11 1928 19872404 5 Structural disease progression in PDE6-associated autosomal recessive retinitis pigmentosa Ophthalmic Genet Takahashi VK Takiuti JT Jauregui R Lima LH Tsang SH 610 614 39 2018 30153077 6 The human rod photoreceptor cGMP phosphodiesterase beta-subunit. Structural studies of its cDNA and gene FEBS Lett Khramtsov NV Feshchenko EA Suslova VA 275 278 327 1993 8394243 7 Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa Nat Genet McLaughlin ME Sandberg MA Berson EL Dryja TP 130 134 4 1993 8394174 8 Novel mutations in PDE6B causing human retinitis pigmentosa Int J Ophthalmol Cheng LL Han RY Yang FY 1094 1099 9 2016 27588261 9 Genomic landscape of sporadic retinitis pigmentosa: findings from 877 Spanish cases Ophthalmology Martin-Merida I Avila-Fernandez A Del Pozo-Valero M 1181 1188 126 2019 30902645 10 Different phenotypes in pseudodominant inherited retinal dystrophies Front Cell Dev Biol Habibi I Falfoul Y Tran HV El Matri K Chebil A El Matri L Schorderet DF 625560 9 2021 33634125
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Schizophr Bull Schizophr Bull schbul Schizophrenia Bulletin 0586-7614 1745-1701 Oxford University Press US 36257668 10.1093/schbul/sbac156 sbac156 Editorials AcademicSubjects/MED00810 COP27 Climate Change Conference: Urgent Action Needed for Africa and the World Wealthy nations must step up support for Africa and vulnerable countries in addressing past, present and future impacts of climate change++ Atwoli Lukoye Editor-in-Chief, East African Medical Journal Erhabor Gregory E Editor-in-Chief, West African Journal of Medicine Gbakima Aiah A Editor-in-Chief, Sierra Leone Journal of Biomedical Research Haileamlak Abraham Editor-in-Chief, Ethiopian Journal of Health Sciences Kayembe Ntumba Jean-Marie Chief Editor, Annales Africaines de Medecine Kigera James Editor-in-Chief, Annals of African Surgery Laybourn-Langton Laurie University of Exeter, UK Mash Bob Editor-in-Chief, African Journal of Primary Health Care & Family Medicine Muhia Joy London School of Medicine and Tropical Hygiene Mavis Mulaudzi Fhumulani Editor-in-Chief, Curationis Ofori-Adjei David Editor-in-Chief, Ghana Medical Journal Okonofua Friday Editor-in-Chief, African Journal of Reproductive Health Rashidian Arash Executive Editor, Eastern Mediterranean Health Journal El-Adawy Maha Director of Health Promotion, Eastern Mediterranean Health Journal Sidibe Siaka Director of Publication, Mali Medical Snouber Abdelmadjid Managing Editor, Journal de la Faculte de Medecine d'Oran Tumwine James Editor-in-Chief, African Health Sciences Sahar Yassien Mohammad Editor-in-Chief, Evidence-Based Nursing Research Yonga Paul Managing Editor, East African Medical Journal Zakhama Lilia Editor-in-Chief, La Tunisie Medicale Zielinski Chris University of Winchester, UK To whom correspondence should be addressed; e-mail: [email protected] 3 2023 19 10 2022 19 10 2022 49 2 231233 (c) The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. 2022 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. pmcThe 2022 report of the Intergovernmental Panel on Climate Change (IPCC) paints a dark picture of the future of life on earth, characterised by ecosystem collapse, species extinction, and climate hazards such as heatwaves and floods.1 These are all linked to physical and mental health problems, with direct and indirect consequences of increased morbidity and mortality. To avoid these catastrophic health effects across all regions of the globe, there is broad agreement as 231 health journals argued together in 2021 that the rise in global temperature must be limited to less than 1.5degC compared with pre-industrial levels. While the Paris Agreement of 2015 outlines a global action framework that incorporates providing climate finance to developing countries, this support has yet to materialise.2 COP27 is the fifth Conference of the Parties (COP) to be organised in Africa since its inception in 1995. Ahead of this meeting, we as health journal editors from across the continent call for urgent action to ensure it is the COP that finally delivers climate justice for Africa and vulnerable countries. This is essential not just for the health of those countries, but for the health of the whole world. Africa has Suffered Disproportionately Although It has Done Little to Cause the Crisis The climate crisis has had an impact on the environmental and social determinants of health across Africa, leading to devastating health effects.3 Impacts on health can result directly from environmental shocks and indirectly through socially mediated effects..4 Climate change-related risks in Africa include flooding, drought, heatwaves, reduced food production, and reduced labour productivity.5 Droughts in sub-Saharan Africa have tripled between 1970-1979 and 2010-2019.6 In 2018, devastating cyclones impacted 2.2 million people in Malawi, Mozambique, and Zimbabwe.6 In west and central Africa, severe flooding resulted in mortality and forced migration from loss of shelter, cultivated land, and livestock.7 Changes in vector ecology brought about by floods and damage to environmental hygiene have led to increases in diseases across sub-Saharan Africa, with rises in malaria, dengue fever, Lassa fever, Rift Valley fever, Lyme disease, Ebola virus, West Nile virus, and other infections.8,9 Rising sea levels reduce water quality, leading to water-borne diseases, including diarrhoeal diseases, a leading cause of mortality in Africa.8 Extreme weather damages water and food supply, increasing food insecurity and malnutrition, which causes 1.7 million deaths annually in Africa.10 According to the Food and Agriculture Organization of the United Nations, malnutrition has increased by almost 50% since 2012, owing to the central role agriculture plays in African economies.11 Environmental shocks and their knock-on effects also cause severe harm to mental health.12 In all, it is estimated that the climate crisis has destroyed a fifth of the gross domestic product (GDP) of the countries most vulnerable to climate shocks.13 The damage to Africa should be of supreme concern to all nations. This is partly for moral reasons. It is highly unjust that the most impacted nations have contributed the least to global cumulative emissions, which are driving the climate crisis and its increasingly severe effects. North America and Europe have contributed 62% of carbon dioxide emissions since the Industrial Revolution, whereas Africa has contributed only 3%.14 The Fight Against the Climate Crisis Needs All Hands on Deck Yet it is not just for moral reasons that all nations should be concerned for Africa. The acute and chronic impacts of the climate crisis create problems like poverty, infectious disease, forced migration, and conflict that spread through globalised systems.6,15 These knock-on impacts affect all nations. COVID-19 served as a wake-up call to these global dynamics and it is no coincidence that health professionals have been active in identifying and responding to the consequences of growing systemic risks to health. But the lessons of the COVID-19 pandemic should not be limited to pandemic risk.16,17 Instead, it is imperative that the suffering of frontline nations, including those in Africa, be the core consideration at COP27: in an interconnected world, leaving countries to the mercy of environmental shocks creates instability that has severe consequences for all nations. The primary focus of climate summits remains to rapidly reduce emissions so that global temperature rises are kept to below 1.5degC. This will limit the harm. But, for Africa and other vulnerable regions, this harm is already severe. Achieving the promised target of providing $100bn of climate finance a year is now globally critical if we are to forestall the systemic risks of leaving societies in crisis. This can be done by ensuring these resources focus on increasing resilience to the existing and inevitable future impacts of the climate crisis, as well as on supporting vulnerable nations to reduce their greenhouse gas emissions: a parity of esteem between adaptation and mitigation. These resources should come through grants not loans, and be urgently scaled up before the current review period of 2025. They must put health system resilience at the forefront, as the compounding crises caused by the climate crisis often manifest in acute health problems. Financing adaptation will be more cost effective than relying on disaster relief. Some progress has been made on adaptation in Africa and around the world, including early warning systems and infrastructure to defend against extremes. But frontline nations are not compensated for impacts from a crisis they did not cause. This is not only unfair, but also drives the spiral of global destabilisation, as nations pour money into responding to disasters, but can no longer afford to pay for greater resilience or to reduce the root problem through emissions reductions. A financing facility for loss and damage must now be introduced, providing additional resources beyond those given for mitigation and adaptation. This must go beyond the failures of COP26 where the suggestion of such a facility was downgraded to "a dialogue."18 The climate crisis is a product of global inaction and comes at great cost, not only to disproportionately impacted African countries, but to the whole world. Africa is united with other frontline regions in urging wealthy nations to finally step up, if for no other reason than that the crises in Africa will sooner rather than later spread and engulf all corners of the globe, by which time it may be too late to effectively respond. If so far, they have failed to be persuaded by moral arguments, then hopefully their self-interest will now prevail. Acknowledgments In the interest of transparency the authors wish to declare the following roles and relationships: James Kigera is the Ex-Officio, President and Secretary of the Kenya Orthopedic Association; Paul Yonga been paid to speak or participate at events by Novartis, bioMerieux and Pfizer; Chris Zielinski is a paid consultant for the UK Health Alliance on Climate Change; Joy Muhia is an unpaid board member of the International Working Group for Health systems strengthening; David Ofori-Adjei has a relationship with GLICO Healthcare Ltd. The authors declare no further conflicts of interest beyond those inherent in the editorial roles listed. Footnotes Provenance and peer review Commissioned; not externally peer reviewed. ++ This Editorial is being published simultaneously in multiple journals. For the full list of journals see: References 1. IPCC. Climate Change 2022: Impacts, Adaptation and Vulnerability. Working Group II Contribution to the IPCC Sixth Assessment Report. IPCC; 2022. 2. UN. The Paris Agreement: United Nations. UN; 2022. Accessed September 12, 2022. 3. Kaddu JB , GebruB, KibayaP, MunabiIG. Climate change and health in sub-Saharan Africa: The case of Uganda. Climate Investment Funds; 2020. 4. WHO. Strengthening Health Resilience to Climate Change. WHO; 2016. 5. Trisos CH , AdelekanIO, TotinE, et al . Africa. In: Climate Change 2022: Impacts, Adaptation, and Vulnerability. Working Group II Contribution to the IPCC Sixth Assessment Report. IPCC; 2022. Accessed September 26, 2022. 6. World Bank. Climate Change Adaptation and Economic Transformation in Sub-Saharan Africa. World Bank; 2021. 7. Opoku SK , Leal FilhoW, HubertF, AdejumoO. Climate change and health preparedness in Africa: Analysing trends in six African countries. Int J Environ Res Public Health. 2021; 18 (9 ):4672.33925753 8. Evans M , MunslowB. Climate change, health, and conflict in Africa's arc of instability. Perspect Public Health. 2021; 141 (6 ):338-341.34787038 9. Stawicki SP , PapadimosTJ, GalwankarSC, MillerAC, FirstenbergMS. Reflections on climate change and public health in Africa in an era of global pandemic. In: Contemporary Developments and Perspectives in International Health Security. Vol. 2 : Intechopen; 2021. 10. Climate Change and Health in Africa: Issues and Options. African Climate Policy Centre; 2013. Accessed September 12, 2022. 11. Climate change is an increasing threat to Africa 2020. Accessed September 12, 2022. 12. Atwoli L , MuhiaJ, MeraliZ. Mental health and climate change in Africa. BJPsych Int. 2022:1-4. Accessed September 26, 2022. 13. Vulnerable Twenty Group. Climate Vulnerable Economies Loss Report. Vulnerable Twenty Group; 2020. 14. Ritchie H. Who has contributed most to global CO2 emissions? Our World in Data. Accessed September 12, 2022. 15. Bilotta N , BottiF. Paving the Way for Greener Central Banks. Current Trends and Future Developments Around the Globe. Edizioni Nuova Cultura for Istituto Affari Internazionali (IAI); 2022. 16. WHO. COP26 Special Report on Climate Change and Health: The Health Argument for Climate Action. WHO; 2021. 17. Al-Mandhari A , Al-YousfiA, MalkawiM, El-AdawyM. "Our planet, our health": saving lives, promoting health and attaining well-being by protecting the planet - the Eastern Mediterranean perspectives. East Mediterr Health J. 2022; 28 (4 ):247-248. 10.26719/2022.28.4.247. Accessed September 26, 2022.35545904 18. Evans S , GabbatissJ, McSweeneyR, et al . COP26: key outcomes agreed at the UN climate talks in Glasgow. Carbon Brief [Internet]. 2021. Accessed September 12, 2022.
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PREVENTION AND TREATMENT OF TIIE DISEASES OF INFANTS. REMARKS MADE BEFORE THE OBSTETRICAL SECTION OF TIIE NEW YORK ACADEMY OF MEDICINE, MAY 17TH, 1869. By STEPHEN ROGERS, M.D., New York. Mr. Chairman: Asa text for the few following remarks, I present a sentence from the address of Sir Thomas Watson, on the occasion of his retiring from the presidency of the Society of London, because it expresses accurately my own sentiments in reference to the subject before us, and, no doubt, those of many of the Fellows also. "What I deprecate," says Dr. Watson, "what I would fain see altered, what it is one great end of this Society to do away with, is the vagueness of aim, the uncertainty of result, the merely tentative nature of too many of our prescriptions." In no department of medicine is vagueness of aim, of result, and consequently tentative practice, more , and, I may add, more disastrous, than in diseases of infants, and especially diarrhoeal diseases. We lose our aim, first, by forgetting, or by never knowing, the anatomy and physiology of the infant; and we are forthwith environed by complications and inexplicable phenomena which befog every effort we make. The*digestive apparatus of the infant is, in some respects, like that of the carnivorous animals, arranged for highly and easily assimilable food. This alone should teach us that the pharinaceous and vegetable substances should not enter the diet of young infants. Infants, like animals and like adults, require water; and while their proper food, milk, all the water usually demanded, any accident or disease which cuts off the accustomed supply of milk, as well as any circumstance which greatly increases perspiration, such as warm weather, is certain to induce thirst, for which water is the true remedy. The infant intestines, like the adult, are provided with a reservoir for the reception, detention, and absorption of the assimilable fluids. This organ is the large intestine, or colon and ccecum and the rectum included, and has not like the , and a considerable part of the small intestine, any function. No part of it, therefore, can perform digestion, from the anus to the caput coli it can only absorb; and which are simply in suspension, not in solution, are not appropriated when introduced into this portion of the intestine. Substances, in short, which are not transmitted through by osmosis, are not utilized by the rectum or colon. As an absorbing organ, however, the large intestine is very active. There can be no doubt. I think, that the digestive portions of the intestinal tube of the infant, as well as the absorbing , are liable to the same diseases that affect them in the adult; and as diarrhoea is one of the results of disease in both portions, in both adults and infants, we will make our upon this understanding. Commencing with the stomach, I will say that diarrhoea from indigestion is, perhaps, quite as frequent, if not much more so, in infancy as in adult age. It is very liable to occur in warm weather, to infants both breast and bottle-fed, on account of their taking more milk than the stomach can dispose of, and more than the system requires, the child taking it for thirst instead of for hunger. It is also liable to occur in children bottle-fed on milk too much diluted; the digestive action of the gastric fluids suffering embarrassment by the very great amount of fluid,"to say nothing of the grave of the digestive organs, which are produced by of nutritive material given in such habitually dilute food. The slow starvation produced by insufficient diet, and by diet which, though sufficient as to quantity, is unsuited as to quality, has many symptoms in common with much of the fatal infantine diarrhoea. This diarrhoea of indigestion is usually ushered in by more or less sudden anorexia, vomiting, thirst, nervous disturbance, and heat of skin, followed in a few hours by diarrhoeal discharges, containing more or less undigested food. Unless the cause is repeated, the attack generally with the expulsion of the offending material. It is an exceedingly easy disorder to treat in both the young and old. The treatment, as a rule, need be nothing else than physiological and physical rest. This is attained by food a practice readily followed, for the patient does not desire food quieting thirst by cold water without stint or ,* keeping the patient still, and, finally, when desire for food may return, to allow it in moderate amounts, and, if it be milk, undiluted. * I am ready to stake my reputation as an observer, student of nature, and practitioner, upon the declaration that there is no support in physiology, nor in pathology, nor in practice, for the popular and extensive professional idea that water, to satisfy thirst, can do any infant harm. The idea that it distends the stomach, that it weakens the organ, and prevents digestion, no matter when given, is all clap-trap, without a shadow of foundation in truth. This is a very mild term to use relating to these fostered ideas, if we take into account the misery, and even mortality, they annually produce in the diseases of the prima via of infants. In bottle-fed babies, whose milk has been diluted in the usua manner, from one-half to three-fourths water, nothing can b< more striking than the change to undiluted milkman's milk, ex cept, perhaps, when the dilution has been with barley, or othei farinaceous decoction. Of all the compounds fruitful of infan tile diarrhoea, in our city especially, those by farinaceous de coctions with milk rank first. Children over six months often desire, and are benefited ap parently, by farinaceous food occasionally; but the child shoult be allowed its choice to take it or not. This cannot be done U mixing it with its milk. All such articles should be given b; themselves. The observation of these fewr plain rules for tin treatment of the diarrhoea of indigestion, will be quite sufficien for most cases, medicinal aid being generally unnecessary. T( avoid these attacks of diarrhoea of indigestion during our sum mers, every mother or nurse should be instructed to offer cok water to the infant, whether breast or bottle-fed, before offering it its food, for by so doing, the infant has the opportunity t( quench its thirst with water, preserving the unembarrassed en ergies of the stomach for the digestion of the food.f f Much favorable testimony has been furnished the profession, relating to the employment of pepsin in the diarrhoea of indigestion of children and . I have not met with cases in which a resort to this agent became , and can therefore offer no experience with it. But as the principle upon which its use is based has a well-known physiological foundation, I am disposed to adopt it in cases which are not promptly controlled by proper physiological feeding. Following the intestinal disturbance produced by an attack of diarrhoea of indigestion, the annexed train of symptoms are very often met with: Frequent alvine dejections of greenish, very fluid, and foetid character, frequently containing portions of undigested casein coagulum if its diet include milk irritable stomach, and appetite, and almost continual thirst. Its discharges may be yellowish, foetid, and watery, when voided, but become green after a little exposure, generally containing mucus; and there is usually some tenesmus. The child does not have very marked fever, except at varying intervals; emaciation progresses more or less rapidly, and the tongue, as well as the anus, indicate by their redness, enlarged papillae, and excoriation, a profound disturbance of the alimentary canal. The case is one of chronic colitis, the usual diarrhoea of . The colon, as a receiving and absorbing cavity for the excrementitious and alimentary matter poured into it by the small intestine, and by its own excretory glands, refuses to its functions; consequently, as fast as material is lodged in it from above, it is hurried on through to the rectum and discharged, not only adding to its own irritability, but not the absorption of much of the alimentary matter for it in the canal higher up. During the transit of a fresh supply of such material through the diseased colon, the child often has an intense febrile heat of skin, and not convulsions, which terminate life. Both the fact that the morbid changes found after death from diarrhoea in infancy are chiefly in the large intestine, and the phenomena of the show conclusively that it is a colitis almost exclusively. When we add to these evidences the results of the treatment of colitis, I see no room for a doubt that the usual diarrhoea of infancy, of which so many children die among us annually, is simply colitis. The treatment is clearly to avoid the causes which set up this inflammation, and to lessen the already inflammation and irritability. This is accomplished by food as much as possible, keeping the desire for drink satisfied with water, and thus securing physiological rest for the colon. This rest may be more completely effected by calming its pain and irritability by means of anodynes thrown over part of its surface, viz.: the rectum. But in this use of anodynes we should never forget that neither the rectum, nor any other part of the large intestine, can digest; that its function is to absorb, and, therefore, nothing should be introduced into it, except , or substances easily soluble in water, and therefore in the moisture of the mucous membrane. Nothing but evil can come from introducing the time-honored starch, gum-water, mucilage of various kinds, oil, albumen, etc., into a diseased and irritable colon or rectum. The watery portions of these preparations are alone absorbed, if retained long enough, and the solid residue is left behind, doing much more harm than good, and often more harm than the combined anodyne does good. The idea that in some forms of inflammatory disease of the large intestine, its usual lubricating covering of mucus , and any of the gummy or mucilaginous substances may in such case be with advantage as a simple protection of the denuded tissue of the mucous membrane, is,'to my mind, totally destitute of the support, not only of demonstration, but of probability ; and so far as my individual experience may permit me to judge, has not practical support either. Poultices applied to the membrane of the rectum, no matter of what bland substance they be composed, are foreign and excrementitious, and give no rest to the bowel. Alcoholic solutions, unless largly diluted with water, are liable to irritate, and therefore objectionable. Watery solutions, which leave no solid residum, are clearly the most preferable, and of all preparations, the morphine salts in solution I think best. Where there is not very great irritability of the rectum, the much-used cocoa-butter suppository is a convenient and useful form of introducing the morphine, or other very soluble . The warmth of the bowel slowly melts down the mass, allowing the salt to come in contact with the bowel whose dissolves it, and it is then absorbed, while the butter remains as excrement. But the simple watery solution of sulphate of morphine is the least irritating as well as the most active form of anodyne enema. Its dose by the rectum when thus introduced is rather less than by the mouth, and its action is more prompt and more effective to relieve tenesmus and irritability of the large bowel. I have often seen a single injection prevent all movement of the bowels for ten to twelve hours, in cases where the movements before it were almost incessant. Many adjuncts to this treatment will suggest themselves to any educated , and I therefore need not mention them here. I will add, however, that I rarely employ any other medication for the diarrhoea of infancy of this degree: and, so far as my enables me to judge, much of the favorable results claimed by our practitioners for their favorite prescriptions, such as doses of calomel, Dover's powder, ipecac, the sulphite salts, the bromine salts, and the various astringents, alkalies, and and disinfectants, is due to the concident modification of the diet and care of the child. A diarrhoea, like that just , of no great severity, having existed for some days, , suddenly suffers a great increase in the frequency of the movements of the bowels, nausea and vomiting come on, the skin becomes hot, the thirst is urgent, there is more or less extreme restlessness and actual or threatened convulsions. The are, if possible, still more foetid, watery, and of various colors from black to yellow; they are often streaked or dotted with blood, and the fluid portions sometimes stain reddish the clothes upon which they fall; there is sooner or later mucus with them, the tenesmus becomes tormenting, the anus red excoriated, and the tumefied mucous membrane of the rectum shows a tendency to descend. This has now become. acute colitis, inflammatory diarrhoea of some authors, or of others. Its treatment does not differ from that already mentioned for colitis, except that it must be conducted with greater energy and watchfulness. Withhold food as strictly as possible, give cold water ad , arrest the pain ami irritability of colon by morphine , and keep the patient as quiet and cool as practicable, for this is a disease of hot weather. The use of pure cold water in the irritable stomach of diarrhoea, is theoretically opposed by many practitioners, on the ground that it keeps up the vomiting, as they allege, and furnishes indefinite quantities of fluid to protract the diarrhoeal discharges. Practically, I have never seen this theory . unless the water were combined with some alimentary . It is surprising, however, to see how little milk, or arrowroot, or barley, or any similar substance combined with water, will keep the vomiting and diarrhoea going on to a fatal issue. Pure cold water, on the contrary, will soon arrest , will give physiological rest to the stomach and intestines, will furnish the much needed fluid to the blood, and thereby calm nervous agitation and afford physical rest and restoration. As to the treatment of the prolapsus of the mucous membrane of the rectum which we occasionally see follow one of these of colitis, I will add that I have found nothiug of any which does not arrest the irritability of the part, and the frequent movements of the bowels which attend it. Any agent which secures prolonged repose of the colon and rectum, will cure this condition. The most certain means which I have is an injection of the solution of morphine, thrown up immediately after reducing the prolapsed membrane by a compress and putting the patient to bed. The bowels do not move for tw'elve to forty eight hours, and recovery of tone and natural condition progresses rapidly. A single application of this kind is generally sufficient, and I have seen very few resist more than two or three. There is still another form of most fatal diarrhoeal disease of infancy, presenting the train of symptons: A mild form of diarrhoea having existed for a few days, there suddenly come on vomiting and purging of a copious watery substance, at first containing feculent material, but subsequently an almost pure, opalescent, and nearly odorless fluid, without apparent pain or tenesmus. There is total loss of appetite, great thirst, the surface of the body rapidly becomes cold, the skin shrivelled and moist; in short, a more or less rapid collapse ensues which, as a rule, terminates in fatal convulsions, or anaemic coma, and does so generally within twenty-four hours after the attack. This is the form of diarrhoea, and the only form, in my opinion, to which we should apply the name Cholera infantum, and when with all the cases of diarrhoeal diseases we see, I think the Fellow's of the Academy will agree with me in saying, that it composes a small minority of them. I have no suggestions for its treatment that would not occur to the mind of any physician. Unquestionably the wisest plan in this, as well as in all the diarrhoeal diseases of infancy, is to prevent them if possible. This we may do much to achieve by management of the food. While there is too much evidence to permit us to doubt that, if not a cause, dentition at least attends a period of development of the digestive apparatus of the infant, during which it is liable to diarrhoeal disease, we cannot close our eyes to the fact that very large numbers of our infants die before dentition or any such development commences, before six months, and die of diarrhoeal disease. Any extended remarks upon the subject of the diet of infants here I deem uncalled for, and I therefore shall say but little. We, however, all accept the proposition as self-evident, that the best food for the infant is-good breast-milk. We are all quite as thoroughly convinced that this is very often not obtainable. Now comes the question as to what is the best substitute for breast-milk. That the milk of some animal should compose the basis of the substitute all, with few insane , agree. Great numbers of modifications of the milk of the cow the only available one in this part of the world have been advocated, chiefly in the degree of its dilution, and the addition of various farinacious substances. But my observations have most thoroughly convinced me that the theoretical dilution of cow's milk, with the view of rendering it similar to the milk of the human female, is an unscientific delusion. It is founded, in the first place, upon the false premises, that our Croton, or other water, is a similar fluid to the watery portions of human milk. Its till further supports itself upon the unfounded , that dilated milk of the cow is more easily digested than the original fluid, on account of the excessive proportion of casein. There is no means of demonstrating the theory that the of water to the milk of the cow renders it more digestible in the infant stomach. But, on the contrary, any one can almost any day during our summers, that the labor of the infant's stomach is much easier in the digestion of the best milkman's milk we can obtain here, than it is in the of the usual dilute form, and still less than when diluted with farinacious decoctions. Providence has wisely arranged this matter so that if the milk the food intended for the infant be variable as to its constituents, the stomach has the power to digest and more or less completely appropriate them. Hence the milk of the human female, which is often richer in all of its constitutents than many samples of the milk of the cow, is , and the child flourishes; and on the contrary, the milk of the cow, which posesses many per cent, more of oil and casein than the average human milk, is easily digested, and the child thrives satisfactorily. The essential points in the whole matter being that the milk given contain nutrient material within a reasonable bulk, sufficient for the nutrition of the child, and that it be given soon enough after leaving the breast or udder to be sweet and good. I avail myself of this opportunity, as I uniformly do of any which presents itself, to denounce the doctrine of dilute cow's milk as infant food, as one destitute of reason and extremely dangerous. If this be true of milk simply diluted, what must be the state of the case when diluted with vegetable and substances? For about ten years of my professional life, I have watched this subject closely, having had several children of my own to raise on the milk of the cow. I have yet seen no reason for diluting the milk sold in this city, to make it fit food for the infant at any age. On the contrary, I have often found a necessity for richer milk than could well be obtained here. My experience has satisfied me, that a great part of the and danger attending the raising of children by hand, as it is called, proceeds from this tinkering of the milk used. I regard the raising of a child with a tolerably good organization as about as easy on the milk of the cow as on the breast. The essential points for the mother or nurse to observe are, that the milk be sweet, that is to say, not soured, that it be warmed to about 100deg, that it be taken from the bottle through finely nipples, that the bottle and nipple be kept clean, and finally, that the child have all it will take. And here I would repeat the precaution before alluded to, not to give the child milk during the very warm wreather of our summers, till water has first been offered to it, else it will often take milk in quantities simply because it is thirsty, and will thus be overfed and injured. Children at the breast are often injured by this neglect. To those who may possibly regard these views of infant feeding as radical and perhaps dangerous I feel bound to say that I am supported by unquestionably competent . While writing these pages, I had the exteme of receiving the pamphlet paper on "Food for Infants," lately read before the Medical Society of the State of , by Dr. Iliram Corson, of that State. The Dr. has his observations through more than thirty years, and they have obviously been well and carefully conducted. He says, " I feel quite certain that it is almost as easy to raise children by hand, if they have an abundant supply of good cow's milk, as it is by the breast." And he repeats this expression of belief, adding, with great propriety and force as his observations are conducted in the country and villages where good milk is easily obtainable "if, then, in the country, where the milk is good, the child should have all it will take undiluted, how very important that no water should be added to the milk brought to cities by milkmen. It is not too much to say that before it reaches the citizen's door it is only two-thirds milk." He details the symptoms he has often seen presented by infants fed, but only half nourished, on dilute milk, and those accurately apply to great numbers of the diarrhoeal disease we see here. Ilis experience leads him to conclude that of infants who die annually of these diseases, really "die from want of food." "They are starved to death," says he, speaking to the profession, "and wre are not blameless." Again he says: "Little children not only need plenty of good food, but, even those who are fed at a full breast, also need a little cool water as drink." This sentiment I am delighted to see as thus generally stated, but in the warm weather of our summers it is especially . Dr. Corson very justly "wonders that these facts have not more generally impressed themselves upon physicians, and that as a consequence the public teachers with few exceptions, and the text-book of to-day, are promulgating the same doctrine and giving the same rules that they have for the last hundred years, changing, if at all, for the worse, for higher dilutions, and in the face of the frightful fact that infant mortality is rather than diminishing. He very properly suggests that we try a change, which can hardly be for the worse. This is very grateful support to the sentiments I uttered many months ago, in the pages of the Reeord of Oct. 1st, 1868, p. 341. With this care to properly feed infants, much, very much, can be done to prevent their diarrhoeal diseases, especially diarrhoeas from indigestion; and with these simple measures for the treatment of chronic and acute colitis, vastly better results, I am , may be obtained. The comparative experience of many physicians, male and female, in the city and in the country, confirms me in this belief, which I formed from an extensive public practice, added to that on my own family, and in private. N. Y. Med. Record.
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ARTICLE XXXIV. MERCY HOSPITAL. X LAYING OF THE CORNER STONE. Address by Dr. N. S. DAVIS. The ceremonies and impressive exercises connected with the laying of the corner-stone of the Mercy Hospital, took place on the afternoon of July 25, 1869, on the corner of Twenty-sixth Street and Calumet Avenue. A large crowd were in , and, notwithstanding the intense heat, remained and with wrapt attention to the addresses, and throughout the whole of the interesting services. While the audience was gathering, and during the time of the laying of the stone, the Immaculate Conception Band, of Father Waldron's church, and Father Conway's Band, of St. James' church, were upon the stand, and added much to the interest of the exercises by their excellent music. The Society of the Immaculate Conception were on the main stand in full uniform. At 7 o'clock, the procession was formed in the old hospital and marched to the stand, the band meanwhile playing a solemn march. The procession was preceded by six acolytes, each bearing in his hand some holy symbol connected with the . Following was the Very Rev. T. Halligan, , who was escorted, with the orator of the day, Dr. N. S. Davis, by the Reverend Fathers McDermott, Conway, Lyon, Scott, Cushman, Leyden, and Waldron, to the platform. The Very Rev. T. Halligan then proceeded to read in Latin the service usual in the Catholic Church on such occasions. In this part of the ceremony he was assisted by the Reverend Fathers already named. At the conclusion of the opening , architect Boyington placed in the receptacle prepared for it, the box containing the relics and curiosities, after which the stone was lowered to its place. The concluding ceremonies, consisting of blessing the stone and sprinkling it with holy water, were then accomplished, after which the procession and marched back to the hospital. Dr. Davis was then introduced, and spoke as follows: Fellow Citizens: Until my arrival here, I expected you would be addressed by another, before I was called upon, and lest I should weary your patience, I have prepared to occupy you but a few minutes. Nineteen years since, the City of Chicago contained less than 30,000 inhabitants; was supplied with only a limited amount of water, by an engine and pump at the foot of Lake Street, and was entirely destitute alike of sewers and public hospitals. The ground on which we now stand was covered with the coarse grass of the unoccupied prairie. The summer previous (1849) that dreaded pestilence, the epidemic cholera, had severely scourged our citizens, and was prevailing more moderately at the time to which I more particularly allude (the summer of 1850). The need of a permanent public hospital had been so far felt that a charter for one had been procured from the State Legislature at a previous session; and the city authorities were making their first attempt at the construction of sewers, by down a three-cornered or triangular plank sewer in Clark Street, from the river to Lake Street. It was for the double purpose of protesting against the squandering of public money on such temporary and imperfect structures, and awakening the public attention to the whole subject of the sanitary in our city, that your speaker announced a course of six public lectures on the sanitary condition of the city and the means for its improvement, the proceeds of which were to be used in opening a public hospital under the charter already to. These lectures were given in the old State Street Market Hall, which has long since disappeared, and netted the trifling sum of $100, to which was added some contributions of $5 and $10, from four or five of the more prominent citizens, at the head of whom stood R. K. Swift, then a prosperous banker. With this limited sum of money, twelve beds were and put into rooms on the third floor of the south part of the old Lake House, then occupied by a lady as a private boarding-house; and she was engaged to feed and nurse the at a specified sum per week. The beds were ready for the reception of patients by the first week of October, 1850, and were soon filled with patients, attended by the late Daniel Brainard as surgeon, and myself as physician. In the spring of 1851, the Trustees named in the charter, consisting of Judges Skinner and Dickey, and Dr. John Evans, finding it not easy to obtain sufficient subscriptions from our citizens to sustain and endow the hospital, were induced to accept an offer made by the Sisters of Mercy, to take charge of it, and meet all the expenses of its management, except the rent of the necessary building. They immediately began to increase the number of beds, and soon occupied one-half of the old Lake House building, the rent of which was paid during the first three years by the contributions of a few citizens, aided by the Faculty of the Rush Medical College. From that time the passed entirely into the hands of the Sisters of Mercy, where it has remained till the present time. From the old Lake House, it was removed to a building on Kinzie Street, where it remained only a few months. Then it occupied a building constructed for an orphan asylum, on Wabash Avenue, near Van Buren Street, several years, and from thence it was moved into the building originally constructed for a seminary for young ladies, on the grounds we now occupy. Its growth has been steady and uniform, until, from the small beginning just mentioned, it now lays the foundation of the magnificent structure whose corner-stone you have just placed in its proper position; a structure which will not only remain for ages an ornament to our city, but, what is far better, it will stand as a perpetual monument to the liberality and Christian charity of its founders, and an asylum for the suffering and afflicted of many generations. During its past brief history, without the aid of public appropriations or private endowments, and embarrassed by the temporary structures it has , it has accommodated and kindly treated more than 6000 human beings, suffering from serious diseases, at least of whom have been cared for gratuitously. Its doors have been open alike to the afflicted of every class and creed. It has received the professional services, always gratuitous, of the most eminent members of the medical profession, among whom have been Daniel Brainard, Wm. B. Herrick, J. V. Z. Blaney, L. D. Boone, J. E. McGirr, H. A. Johnson, E. Andrews, W. H. Byford, D. T. Nelson, and your speaker. In regard to the ability and faithfulness of the Sisters of Mercy, in the of the hospital, I can speak in terms of the fullest commendation. Having visited the institution, professionally, almost constantly, from its incipient organization to the present hour, I must say that in cleanliness, good order, kindly , and Christian liberality I have not seen them equaled in any other public hospital in this country. With the building now in process of erection, each department of the hospital will be amply provided for. Besides the public wards, there will be many rooms affording every comfort and convenience for the accommodation of such patients as are able to provide with the comforts, as well as the necessaries, of life, and yet need the advantages for special treatment that the hospital affords. Among its inmates heretofore have been patients from all the North-western States, as well as from the City of . To sustain such an institution, however, requires, in to the faithfulness and skill of its immediate attendants, the active aid and sympathy of the whole community. The untiring labors of the Sisters may be bestowed without money and without price; the Medical Faculty may give it the benefit of their highest skill without a fee; but to furnish it with food, fuel, light, water, and medicines requires money, and that, too, in larger quantity than can be derived for the payment of board by the patients. There are many of both sexes having no homes of their own, who, when taken sick, are not proper to be made a county charge, and to whom the well- public hospital affords the only safe resort. If their proves severe, the little money on hand at the beginning is exhausted long before they are well, and they must remain gratuitously or be turned helpless away. There are others whose education, social relations, prejudices, perhaps, are such that they could not be induced to go into the public wards of a hospital for the city or county poor, and yet who are of the means with which to pay for either board or the services of a physician or surgeon, and, yet, who would gladly avail themselves of the advantages of an institution like this, if a way was provided by which they could be admitted. Hence, when this noble structure shall have been finished; when the self sacrificing Sisters of Mercy shall have completed and every room, from basement to attic, with themselves in readiness to care for the sick, and the board of physicians and surgeons ready to aid them, there will yet lack one thing to render its means of usefulness complete. To supply this one thing, and make the Mercy Hospital of Chicago not only one of the best hospitals, but also one of the noblest charities in the world, it should receive such a pecuniary endowment as would make, at least, twenty of its beds free for the occupancy of those who are destitute as well as sick. Ticenty beds thus free would accommodate an average o 150 patients per annum. Who can estimate the benefits that would result or the amount of human suffering that would be relieved in the lifetime of a single generation? And are there not twenty men within hearing of my voice who could each donate $1000, to be invested* and held in trust, the interest of which would secure twenty free beds for suffering humanity? Is there any other way in which a like sum could be invested with a certainty of securing an equal amount of good? To clothe the naked, to feed the hungry, to provide for and heal the sick are among the highest and most sacred injunctions of the Divine Author of Christianity. However much the world of mankind may be divided in to religious creeds and ceremonies, there can be but one sentiment in regard to the universally binding character of these injunctions. They are broad in their scope as the brotherhood of man, and as binding as the divine impress can make them. Then, let every thoughtful man who has an abundance of this world's goods, reflect that for every dollar he will be called to render an account. Not as to whether he obtained it honestly or by fraud; not whether he expended it for the gratification of his pride or passions, or hoarded it in his safe, but in that great day of fina judgment, we are told the question will come, did ye clothe the naked; did ye feed the hungry; did ye visit the prisoner; did ye minister to the sick? Christianity demands of its votaries not negative virtues merely, but positive acts of charity and human kindness. Then, fellow-citizens, while this noble structure is advancing to completion, let me entreat you to make such provisions, , as will secure to it the highest possible degree of , and you will thereby secure to yourselves, also, the reward of the Christian, namely, the consciousness of having added to the sum of human life and happiness. After the public exercises the distinguished guests present were invited to an elegant collation, prepared by the Sisters, in the parlors of the old hospital. There were present beside the Very Rev. Father Halligan and the Reverend Fathers already mentioned, the orator of the day, Dr. Davis, the architect, Mr. Boyington, Dr. Byford, Dr. Andrews, Dr. Johnson, and a of others who, during the past years, have connected prominently, by their charitable acts, with the institution. After doing justice to the viands prepared, the pleasant company enjoyed a social hour, and were invited to inspect the building and the proposed improvements. The plans for the new hospital were made from suggestions that were offered by Dr. Edmun Andrews, who has spent much time abroad studying the construction and architecture of the most noted European hospitals. This hospital will contain every improvement, and be one of the most complete and in this country. The following is a description of the hospital as it will be when completed: The principal front of the building is on Calumet Avenue, occupying 200 feet, and the average depth of the main building is 35 feet. On 26th Street, the frontage is 86 feet, which forms the south wing of the building. The north wing is formed by the old hospital, which has been greatly enlarged and remodeled throughout, to make it with the other portions of the structure. There is a third wing immediately in the rear of the centre of the main building which extends back 86 feet, thus making the three wings of an equal size and depth. The building is to be constructed in the Byzantine style of architecture, and will be three stories high, with a basement which is partly above the ground, and, therefore, might be another story, as it is nine feet in the clear. Beneath the whole is a deep cellar, and over all a large, roomy attic, which may be used in case of need for rooms. The front of the building is divided into five sections, two of which recede in order to give place to the towers which are placed at each of the corners. These towers have a canopy top, and as they will be used as ventilators, the whole building will be furnished with pure air in abundance. In the centre of the building is the main entrance to the basement, which opens into a hall that leads back to the . This corridor passes along the rear wall of the building, on each of the three stories and basement. This a new method of constructing the interior of a hospital, it hitherto having been the plan to place the corridor in the centre of the building, with the rooms on either side opening into it. After a careful study of many plans, it is believed, however, that the present one is much more suitable for the purposes for which the is being erected, as the air is thus allowed to circulate freely through the rooms from the front and rear. Thus a continuous circulation of pure air is secured, while the foul air escapes through the rear windows, instead of passing through the rooms on the opposite side of the corridor. By this plan of , infection from contagious disease is rendered almost . As you enter the main hall in the basement, on one side is the visitors' room, while upon the other side, directly opposite, is the reception room for patients. In the rear of these, on the south side of the main entrance, is a pleasant roomy dining-hall, 24 by 37 feet; back of this is the kitchen, 25 by 25J feet, while still back of these rooms are the and pantry, six cells for uncontrollable or quarrelsome patients, and a ward 28 feet wide by 38 feet long. On the north side, the whole of this floor is divided up into rooms, 15 by 20 feet, which are to be used by the patients who are sent to the hospital for treatment. The laundry department is also on this floor, in the centre wing, and is to be fitted up with every convenience, and provided with all the modern inventions for the washing, drying, and ironing of clothes. There are three entrances, which lead up by three flights of steps to the main floor. As in the basement, the hall runs back to the corridor in the rear, while one side is a room for those who come to visit the institution; while on the opposite side is the room where the patients are to be . A large hall, 30 feet wide by 45 long, in which and other lectures are to be delivered, is on this floor, the chapel. Seats are arranged in the hall that will comfortably accommodate 300 people. In the rear of the hall is an octagonal recess for the lecturer, and above is a large window, or skylight, that throws a flood of light down upon the lecture-desk. The hall in front is finished with a row of cases, in which the medicines are to be kept. The north wing of this main floor is used wholly for patients' rooms. Wards, 25 feet wide by 37 feet long, are situated north and south of the main hall, on the corridor. In the south wing there is likewise a large ward 25 by 80 feet, while between the corridor and the south wing is the nurses' room, 12 by 16 feet. Adjoining are water-closets, a large bath-room, which all the patients are allowed to use, a dumb waiter which carries the food up to all the floors, and all the other conveniences that are needed to care properly for the patients. The height of the ceiling on this floor is 18 feet, giving the room an airy, light appearance. In the second story the halls and corridors are the same as those below, and the ceiling is 13 feet high. In the south wing of this floor a number of pleasant parlors, 21 feet long by 11 wide, are arranged, in which the convalescent patient may and enjoy social intercourse. In addition to these is a ward 25 by 30 feet. There are likewise water-closets one in each section of the building and a bath-room. There are also two suits of rooms, into each of which passes the dumb waiter. The remainder of this floor is divided up into separate , of the same size as these below, for the accommodation <of the patients. The ceiling on the third story is also 13 feet high, and the whole floor is laid out in about the same mapper as the floor below, with the exception of the chapel. This is finished in a neat and tasteful style, being plain but convenient in its . A small gallery is erected in the front end of the chapel, while a large chancel, with all the accessory furniture, is situated in the rear. The seating capacity of this chapel is about 300, and is comfortable. The building is covered by a large attic, which is both well ventilated and lighted, and may be used for various purposes, should the accommodations below at any time prove insufficient. In the large cellar underneath the building is placed the furnace, fuel-room, and all the necessary appliances for heating the building, which is done by steam. Beside the steam apparatus, nearly all the rooms are furnished with grates for coal fires, to be used in cases of emergency. In addition to all these conveniences, the hospital is provided with a large elevator, which runs from the basement to the story. This has been constructed so that patients may be removed from one part of the building to another, without them from their cots; the elevator having been made large enough to carry a full-sized cot. A spiral staircase the elevator and connects all the floors of the building. There is also, in addition to this and the main stairway, an one in each wing of the building. The hospital is throughout in pine, grained to resemble oak. The roof has a steep pitch, and is covered with slate, with three pediments, one in front of each wing. The building will cost, when completed, about $60,000.
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THE CHICAGO MEDICAL EXAMINER. N. S. DAVIS, M.D., Editor. VOL. X. MAY, 1869. NO. 5 ) r fl na i v o lit ri u u 11u ns ARTICLE XVII. DR. MERRIMAN'S ADDRESS. / DELIVERED TO THE ALUMNI OF THE CHICAGO MED. COLLEGE. Brother Alumni: The constitution of our Society says, its first object shall be "to keep alive and perpetuate that kind* and cordial feeling which binds us together by reason of our common Ain.a Mater " which I understand to mean that we shall assemble here to have a good time; that we shall lay aside our pills, powders, and prescriptions, our saws, splints, and scalpels, our grave faces, and wise looks, and feel that we have so far success, that we can afford for to-day to look around us and see what work we have done, not only individually, but collectively; that we can grasp each other's hands with hearty friendliness and congratulations upon the many successes the Alumni have had. It is very pleasant to meet together as we are doing to-day to see that Alma Mater is growing, as we perceive from the accession to our ranks of so fine a class as will to-morrow their diplomas to meet many of our old associates, and to hear from others how some of them are across the great waters, and some about to go, to pursue the same studies they commenced here so thoroughly how others are winning for themselves greenbacks, or laurels, or, better still, the love and gratitude of whole communities; so that to lose their doctor, or have any evil befall him, would be looked upon not only as a public, but, to each individual, a private loss. Thus, the sons of our Alma Mater are growing in numbers, wisdom, and pow'er; and the dear old Mother herself is not standing still. Within the last two years, foui* of her original faculty have added the value of an European experience to their previous thorough acquisitions, while three more have come to us fresh from those time-honored schools: and, not content with her previous requirements, Alma Mater is the first of American colleges to demand of her students three courses of lectures, and six months in each course, instead of the customary two courses, four months each, of sister . With her progressive system, giving an entirely new course each year of the three, bur college goes over nearly twice the ground of any similar institution in the country. The system adopted here is attracting great attention in cities. Professor Bumstead, in the "Introductory Lecture," at the College of Physicians and Surgeons, last fall, advised the students to choose from the course there given anatomy, , chemistry, and materia medica, and to pay their chiefly to those studies the first year, and to the others the second year. Seeing, then, what she has done, and is doing, how proud wTe are of Alma Mater to-day; and I feel that each year as we assemble here we shall have new and greater cause for so pardonable a pride. While we thus meet to revive old friendships and , and to enjoy the social hour together, we ought not to forget to take home with us new determinations to work for the exhaltation of our noble profession, and to increase its . The success of one is an honor to all of us. Each new truth developed or old one made clear adds to the power of every physician, and gives the profession a stronger claim to the love and respect of the human race. Science has a claim upon each one of her votaries; and, as Sparta demanded that each subject should be a brick in her strong wall of defence, so the great Genius of Medicine may say to each one of us, "You must give me strength, or I shall become feeble." Though some men have gone forth from our Alma Mater who are already wielding an influence, not only in their own locality, but upon science everywhere still, our college is not old few can look back to famous deeds; but the future opens to us, and " As drops of rain fall into some dark well, And from below comes the scarce audible sound, So fall our thoughts into the dark hereafter; And the mysterious echo reaches us." But those delightful echos from the unseen future, those dreams of high achievements, fame, and happiness, are not separated from us merely by a space of time; we cannot sit down at ease with any prospect of their being realized, nor will accident give them to any of us. Accident sowtefzwies gives men a discovery which benefits the world; but, as a rule, the accident is merely the suggestion of a most thoughtful mind. The discovery of the pendulum and of the steam-engine required minds that could work out a great principle from events so common as to be scarcely noticed by ordinary men. Apples had fallen human eyes for thousands of years before a mind like Newton's seized the suggestion, and deduced from it that law which binds the planets to the sun, and the great systems all in one. We may safely lay it down, as a rule, that no man will anything to-morrow who does not accomplish to-day. The surgeon who, in the future, will most perform the great capital operations is he who, in the present, is most diligently preparing himself. In such an , the important moment to the surgeon is not when he takes his knife in hand, with the anaesthetized patient before him, but, rather, when in previous study he has gone over, again and again, every step of the operation, till he is as sure of it as the penman of his power to form a letter. If, then, we look for the causes of success, we shall find them in the early lives of successful men. Let us take a few examples of such men, and see if we cannot draw from their early lives a lesson which, if applied to our own, will help us on toward the career we all desire. Demosthenes, the orator, inherited a most constitution; but he overcame the defect by the most rigid temperance in food and drink, conjoined with a thorough of exercise. lie was troubled with a stammering speech and shortness of breath, which he overcame by the most labor and perseverance. He shut himself up, for months at a time, to practice his beloved art, and copied the lengthy works of a noted author, whose style he admired, no fewer than eight times. What American is not proud of the career of Benjamin Franklin, the printer boy, who became the eminent statesman? His father frequently repeated to him in boyhood: "Seest thou a man diligent in his business, he shall stand before kings." He said he was reminded of this when at the court of France. His diligence in making opportunities, and in them when made, are too well known to you to need . The man who could live upon saw-dust pudding and water did not need any man's patronage. Sir Astley Cooper, though a wild and ungovernable boy, , at the age of sixteen, a most indefatigable student of medicine. His diligence in anatomy was so great that he stood at the head of the class in the beginning of his second year; and, before he was eighteen, he was admitted to membership in the Physical Society the oldest medical society in London. Entirely reversing his former habits, he spent his vacations in the closest study. He early became a teacher, and such was his professional zeal that, even on the day of his marriage, he gave his lecture in the evening, as usual. What result but could follow such devoted labors? Space permits me to cull merely a suggestion from these noted examples; but, through all the thousands that history records, we find this same precept enforced "The hand of the diligent maketh rich." I cannot resist the desire to mention one more example that of one whom we have all learned to love for his , and revere for his intellectual power and great of medical knowledge. It is unnecessary for me to mention a name; you will all recognize the man. In early life poor, having 'hardly what is now considered a common school education, without influential friends, without opportunities, except such as he made himself, with, absolutely, no advantages, save a soul endowed with a determination to do, he began his career. Soon after, he graduated, the Society, of New York, offered a prize for the best essay on " Diseases of the Spinal Column." lie knew no more of the than the most recent graduate, but at once began to study it up; wrote the essay, and gained the prize. The next year, he gained another, upon "Discoveries in the Physiology of the Nervous System, since the time of Sir Charles Bell," in which were first mentioned many of the points that have since become generally accepted. Thus, he went on investigating new , and writing new articles every year, always keeping on hand a list of obscure points for investigation. On removing to New York, he at once became Assistant to the Demonstrator of Anatomy, in the College of Physicians and Surgeons; and, while there, passed through the cholera epidemic of 1849. lie remained but a> short time in that city, and then came here. His history since, you all know how from early morn till late at night, in storm and sunshine, in season, and out of season, he toiled and succeeded. Although ray description has been of only one man, he is but a type of our faculty. To their assiduous labors and , no less than to their intellect, do they owe their high standing in the profession. Just here, the thought comes to me, "Who are are to take the places of the illustrious men of the present day, when they pass from the stage of active life?" Let each one of us ask himself "May I not be among the number?" for each are offered the same prizes for the same endeavor. The reason of most failures is, that men want a practice earning it, and success without deserving it. He who is #willing to pay the price of these things in labor and self-denial will surely gain them. Work, then, first, to make yourself all you can be. else you do, don't neglect to grow. Remember that when you graduated, the close of the course was called "," and not "completion." You were turned loose upon humanity as doctors; but with some little doubt as to whether you would prove destructive or not. "A little knowledge is a dangerous thing," you know; and those who rely upon what they gained at lectures only as sufficient will really prove . Our weapons are powerful for good or ill, according to the way they are used; and in an unskilful hand are always to be dreaded. I had rather trust a friend to the infinitessimals of true homoeopathy than to the half-informed practitioner of the regular school; especially if he be heroic. Continue your medical studies; keep always on hand subjects for , and study them; be an active member of medical ; write for medical journals; always have a medical , and be sure you instruct him, for the surest way to learn a thing is to teach it. Work, secondly, for influence, and then to use it aright. Physicians are becoming every year more and more men of weight in the community; and this will continue to be so as the profession becomes more advanced, and culture has more sway. Bring your influence to bear upon the prominent mon, and the Legislators, that they may give correct votes on bills for dissections, and providing materiel therefor, also to pass laws restraining quackery, regulating practice and druggist's duties, and the sale of poisons; and urge your Medical Society to use its influence in the same direction. Don't be discouraged at failure. The man who never failed is a myth; and, frequently, the men who have failed the most have become the most successful in the end. It was a beautiful idea of the ancient Greeks that classic people to make Apollo God of medicine. Apollo, you , was God of the Sun that symbol of life and peace and happiness. He was also God of music, which, among them, included all kinds of culture. TEsculapius was a kind of saint of physicians; but the real God of medicine was he who united in himself manly grace and beauty with genial ways and the highest culture, of all the heathen divinities, the one who would to-day be called the truest gentleman. Let us from him, too, draw our lesson; and, with all medical knowledge, mingle the kind disposition, the agreeable manners, and the general culture of the gentleman: but let us lift higher than to be merely disciples of JEsculapius or ; and, as Christianity is higher than heathenism, let us rather be followers of Him who is the grandest model of all virtues, and who alone is called the "Great Physician."
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o n a i<< a i r a i s a n << n s THE PHYSIOLOGICAL ACTION OF THE SULPHATES OF POTASS, SODA, AND MAGNESIA WHEN INJECTED IN THE BLOOD. By MM. F. JOLYET AND CAHOURS. Translated for the Medical Examiner. We propose in this article to demonstrate 1st. That the neutral salts (sulphate of soda and sulphate of magnesia) which are daily employed as purgatives in the do not produce purgation, when injected in the veins. 2d. That these same injections enable us to distinguish the sulphates of potass, soda, and magnesia by their poisonous properties, and their physiological effects. Physiologists frequently have injected the different salts of potassium and sodium in the blood, for the more special of distinguishing these two alkaline metals by their properties. The most delicate experiments on this have been made by M. Grandeau. ( Vide Journal de et de la Physiologie, etc., by M. Ch. Bobin, 1864: upon the Physiological Action of the Salts of , of Sodium, and of Bubidium.) They show 1st. That the salts of soda can be introduced in the without producing accident, and that very large doses do not lead to fatal results. 2d. That the salts of potass, injected in the blood, are poisonous, and that very minute portions suffice to a frightful death. The experiments of M. Cl. Bernard have taught that the salts of potass direct their action upon the muscular tissue, and that death, caused by the injection of these salts in the blood, is due to the sudden arrest of the heart, before the cessation of the respiratory movements. In his investigations upon the physiological action of the salts of potassium, and of sodium, P. Guttman (Berliner Klinische IVochenschrift, 1865, Numbers 3435 and 3436,) examined more closely than any one had before him the mode of action of these compounds. According to his observations, all the salts of potassium (with the of bromide and iodide, and some salts, the acid of which is poisonous in itself) have an equally toxical property, and all act directly upon the heart. They diminish, at first, the force and frequency of its pulsations, and they effect its arrest by of the muscular action of the organ, which, once at rest, does not react under electrical excitement. The greatest between the physiological action of the salts of and the salts of sodium is, that the latter exercise no influence upon the heart as Blake has already observed { Medical Journal, 1839). Upon these two points poisonous properties, and intimate action of the salts of potass our experiments with the sulphate of potass, alone, confirm the data already given. What the action of the salts of magnesium, and, particularly, of the sulphate of magnesia, may be, has not been investigated very thoroughly, at least to our knowledge; and we should hesitate to accept the opinion of M. Rabuteau {Etude sur les effets physiologiques des fluorures et composes metalliques en general; These de Paris: 1867), who, after one experiment with the chloride of magnesium, concluded that this metal is as entirely harmless as sodium. SULPHATE OF POTASS. The experiments we are about to report are designed to show the action which the sulphate of potass exercises upon the heart and the muscles. To evince clearly the action upon the heart, it is necessary to experiment upon an animal, withdrawn from all causes that can modify the rythm, and the frequency of the pulsations of this organ. To accomplish that, we have employed the method of double poisoning. We have made our experiments upon dogs subjected to the influence of curare, the excitability of the motive organs by electricity is destroyed. By this procedure, and maintaining an respiration, w'e can expose the heart to view, and observe, directly, the troubles arising from the introduction of a foreign substance in the circulation. Example I. July 8th, 1868. Poisoned a small-sized bitch, by injecting under the skin some centigrammes of curare, in solution. After a short time, signs of poisoning manifested themselves. Artificial respiration was maintained for an hour. At that time, the sciatic nerve laid bare was no longer . The heart was exposed; the pulsations were very ,' but sufficiently frequent. (The two pneumogastrics were severed.) At 9 h. 55 m., two cubic centimetres of a solution of sulphate of potass of lOe (that is, 20 centigrammes of sulphate of potass) were injected carefully in the left crural vein. The phenomenon which suddenly manifested itself in the of the heart was a diminution, a kind of hesitancy, in the pulsations. This diminution, which -was only transient, was succeeded, almost immediately, by a greatly accelerated action; there were, as far as one could judge, a-third -or a-half more strokes than before the injection. Then came a time when the pulsations were disturbed. They presented an accelerated series, separated by moments of a series of vigorous throbbing, followed by feeble . Then, the pulsations became less and less frequent, and were replaced by the partial and, as it were, vermicular of the ventricle, -which became distended, in a , by the blood, which it could no longer expel. 10 h. 1 m. Complete cessation of the heart in diastole. The blood of the heart, collected in a saucer, coagulated with great rapidity. This experiment has been repeated three times with identical results. With dogs of small size it was sufficient to introduce two and three cubic centimetres of the solution of sulphate of potass to produce the trouble of the heart, and its complete , in some minutes. In another series of experiments, we have practiced injecting sulphate of potass in the blood of frogs. The following is the process at which we have arrived: We make the injection in the arterial system. In order to do that, we expose the terminal part of the aorta and its into the two iliac arteries; and it is in one of these arteries that we introduce a fine canula and make the injection. The canula of the syringe is introduced in the artery, very near the aorta, in such a manner that when the liquid is injected, by the eighth of a drop, from the syringe of Parvas, that which passes immediately into the artery of the opposite side diffuses itself throughout the corresponding posterior member, and is returned immediately to the heart by the venous system. This method has the advantage, at the same time, of one of the members of the animal (the posterior member, in the artery of which the injection is made) from the action of the substance. Example II. 2h. 26 m. 15 centigrammes of the solution of sulphate of potass, of lOe, are injected in the left iliac of a green frog, 5vhose heart beats 70 times in a minute. While the injection is made very carefully, slight fibrile are observed in the muscles of the thigh, then in those of the calf, and some trembling of the toes of the right side. These contractions, which impart a little rigidity to the member, cease in about two minutes. The limb, released and extended, does not retract. 2h. 30m. The heart is observed; 20 pulsations a minute. The ventricle remains a comparatively long time in diastole. Its contraction is unequal; some parts of the ventricle close, while others do not empty themselves. The auricle contracts with difficulty and irregularity. The frog, being.released, executes some energetic movements of the right hind foot; the left remains extended and paralyzed. Feebleness of the anterior parts, which are somewhat depressed, sensibility preserved throughout. 2h. 38m. 50 pulsations of the heart; more regular; the auricle contracts with more power; repose of the heart more or less prolonged from time to time. Motion begins to return in the right posterior member; and the thigh flexes itself gently upon the body. 2h. 50 m. 60 beats of the heart; full and regular. 4h. 10m. Normal condition of the frog: right posterior member very active; left posterior member (vessels ligated) grows paralyzed. Example III. The arteries and lumbar nerves of a large frog are severed; and, at 12 h. 52 m., 20 centigrammes of the solution of sulphate of potass are injected in the left iliac artery. During the process of injection, the fibrile contractions, which, at that time, usually manifest themselves in the right foot, are not apparent. 1 h. The lumbar nerves of the right side are excited by the forceps of Pulvermacher. No contractions in the muscles of the foot. The same excitant directed against the muscles of the foot fails equally to provoke any contraction. On the contrary, contractions are plainly evident when the forceps are applied to the muscles of the left foot (vessels ). Besides, the animal executes some energetic movements with this foot. 1 h. 5 m. and 1 h. 10 m. Same results non-excitability of the muscles on the right; excitability on the left. 1 h. 20 m. The muscles of the right thigh begin to contract. This is shown likewise by electricizing the lumbar nerves. The part is nevertheless paralyzed. 1 h. 35 m. Spontaneous movements in the right hind foot, which has regained its energy, in a great measure. Among the frogs, the difficulties arising in the heart's action are only transient, and have never occasioned the arrest of that organ. The reason is, the doses of sulphate of potass (1 to 2 centigrammes) are too small. The same hesitation, the same irregularities in the cardiac , are observed, either when the frogs are well or previously poisoned by curare. Only one phenomenon is lacking, in every instance, among the frogs under the influence of curare, that is, the muscular fibrile contraction, that, in the healthy frog, invariably manifests itself in the posterior member, where the liquid of the injection passes immediately. SULPHATE OF SODA. The almost absolute harmlessness of injecting the salts of soda in the blood enables us to determine whether the sulphate of soda, injected in the veins, purges, as when given by the . A priori, and, by analogy, it seems to be thus. It appears perfectly natural that the same as an emetic injected in the veins produces vomiting, Glauber salts should purge. It is undoubtedly upon these data, only, that cathartic properties have been attributed to the sulphate of soda injected in the blood. Example IV. July 27th, 1868: 11 A.M. 12 grammes of sulphate of soda dissolved in 40 grammes of water were injected in the crural veins of a dog weighing 10 kilogrammes. after the injection, and even before it was terminated, the respiration of the animal growing embarrassed became and wheezing. This trouble continued a little time, and, presently, respiration was natural. The animal released and placed on the ground went about the laboratory, appearing a little more feeble in the posterior region, and after a time laid down. He was seized with a slight trembling or shivering, which continued nearly five hours. At six o'clock in the evening, that is, after a period of seven hours, the animal was observed and had no evacuation, neither solid nor liquid. He had remained all this time lying in the same position. The next day (July 28th), at 8 A.M., the animal appeared quite recovered from the injection: from the depression which at first ensued, he has become sportive and fawning. There was in the kennel only one scanty evacuation, half liquid, half solid, bilious, of recent date. July 29th. Solid evacuations. July 31st. The animal has had quite profuse hemorrhage in the night. The wound in the thigh still bleeds easily. No reunion by first intention of the wound, the edges of which are gaping and scarcely swollen. This experiment repeated several times shows: 1st. That the sulphate of soda, when injected in the veins, does not purge. 2d. That by the diminution of the coagulability and which it occasions in the blood, the salt of soda disposes to hemorrhages, and retards the work of cicatrization. SULPIIATE OF MAGNESIA. Example V. September 17, 1868. 15 cubic centimetres of a solution, 20 parts sulphate magnesia to 100 parts water, were injected in the right crural vein of a vigorous dog, weighing 8 kilogrammes. At 2 h. 16 m., during the injection, the was restive, its respiration accelerated, then became feeble, and, presently, was carried on by short and abrupt contractions of the diaphragm. 2 h. 22 m. New injection of 15 cubic centimetres of the . Complete arrest of respiration. Artificial respiration maintained by means of bellows. No reflex action of the eyes, upon touching the cornea. No movements of the foot or tail, when pinched severely. The heart beats very regularly. 2 h. 30 m. The left sciatic nerve was galvanized by means of the apparatus of Legendre and Morin: very feeble contraction of the muscles of the member. The muscles under direct contracted well. No reflex movements of the eyes. 2 h. 35 m. Galvanization of the sciatic nerve ; no movement of the foot. Muscles excitable; no reflex action; pupils largely dilated. 2 h. 40 m. Spontaneous respiration commenced in the ; but weak and insufficient. 2 h. 45. Sciatic nerve became slightly excitable. respiration stronger and more regular (artificial respiration discontinued.) No reflex action of the eyes or feet, when pinched hard. 2h. 55 m. Feeble effort to close the eyelids, upon irritation of the cornea. 3h. Galvanization of the sciatic nerve; decided motion in the foot. Strong and full respiration, which indicated that the animal perceived the uncomfortable sensation, caused by of the nerve. 3h. 20 m. Voluntary movement of the head and . Reflex action of the eyes partially returned. Pupils-. 3 h. 30 m. General tremor commenced in the anterior parts, and extended itself to the hind feet, in proportion as motion there. It ceased about 4 o'clock: at that time the had regained all its movements, but its gait was still feeble and uncertain. September 18th. Two bilious liquid evacuations in the night. September 22d. The animal had recovered partially. There was no immediate reunion of the wounds in the neck and thigh; the edges were gaping, and nearly free from tumefaction. On pressure of the wound, a bloody serum exuded. September 25th. The wounds commenced to suppurate, that of the neck, which was in a more advanced state of cicatrization. Example VI. Frog. 25 centigrammes of a solution, one part sulphate of magnesia to three parts water, wras injected in the left iliac artery, at 6 h. 55 m. Injection finished at 7 h. 5 m. 7 h. 15 m. Complete paralysis of voluntary and reflex action, save in the left posterior member, preserved by the ligation of its vessels. Lumbar nerves of the right side not excited by the forceps of Pulvermacher. Muscles excited directly. Regular action of the heart. The next day, the frog has regained full power of motion. One fact results from our experiments with the sulphate of magnesia, it is: that injections of this salt in the blood are poisonous. We cannot admit, then, with M. Rabuteau, that the salts of magnesium are as harmless as the salts of sodium. In our experiments with the sulphate of soda, we have injected, always, from 10 to 15 grammes, and sometimes 20 grammes of this salt, without producing death. On the contrary, 2 to 6 grammes of sulphate of magnesia, according to the size of the animals, have invariably sufficed to occasion an almost frightful death. This first point established, let us seek to ascertain the mode of intimate action of the sulphate of magnesia. In of these facts, only, paralysis of voluntary and reflex , bordering upon loss of the excitability of the motive nerves, with preservation of the action of the muscles, which follow the introduction of the substance in the blood, among dogs; the same effects, with greater preservation of the sensibility and movements of the isolated member, among frogs. One cannot refrain from comparing the action of sulphate of magnesia with the characteristic action of curare, and the poisons of the nerves. Without doubt, the alteration that the sulphate of magnesia originates in the blood should be taken into ; but this alteration would not give an explanation of the phenomena which immediately follow the injection. The of the coagulability and plasticity of the blood can only, as with sulphate of soda, account for the later phenomena, that is, the consecutive hemorrhages and delay occasioned in the cicatrization of the wounds. Experiment V. shows, finally, that if the sulphate of magnesia injected in the blood sometimes produces liquid and bilious evacuations, properly speaking, it does not purge, as when <nven in the intestine.* * Since this article was sent to the press, we have learned that M. Rabuteau and M. A. Moreau have each arrived at the same result as ourselves, relative to the non-carthartic action of sulnhate of soda iniected in the blood. In the course of experiments made in April, 1867, to study the toxical action of different metalic salts, I introduced a very small quantity of crystallized sulphate of magnesia under the skin of a frog's back. The animal became gradually enfeebled: at the end of an hour, there was no movement, either spontaneous or reflex, in the different parts of the body. It was the same when sulphate of potass was introduced, hypodermically; but sulphate of soda had no analogous effect. The chlorhydrate of ammonia, on the contrary, occasions, also, an abolition of spontaneous and reflex action, excepting that of the heart, but after having produced a more or less transient tetanic condition. In many cases, the effects of these salts have been dissipated completely at the expiration of a few hours. fA. Vulpian.
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0' ( 11 fl r i a 1 Explanation. On the 28th of April, when we left home to attend the meeting of the American Medical Association, the present numbei' of the Examiner was so far printed, and the matter all furnished for its completion, that we supposed it would be sent to the subscribers promptly, as usual, during the first week in the month. Returning on of May, we were much surprised to find it still in the printer's hands. The delay had been occasioned solely by some misunderstanding in relation to the cuts with which the number is illustrated. Homeopathy. We have received a pamphlet of 100 pages, embracing four lectures on this subject, by A. B. Palmer, A.M., M.D., Professor of Pathology, Practice of Medicine, etc., in the Medical Department of the University of Michigan. These lectures embrace a very interesting and valuable exposition of the doctrines of homoeopathy, as it was and is, and would be very useful for reference in the library of the physician, or even for general circulation among the people. Copies may be had at S. C. Griggs & Co., of this city. Price, 30c. Illinois State Medical Society. We are informed by the Committee of Arrangements that the members of the State Medical Society will commence in the Common Council Room, in the City Hall building, at 10 o'clock A.M., of Tuesday, May 18th, 1869. This is an excellent and place in which to meet, and every arrangement will be made to promote the interests of the Society. Correspondence. Just after the last pages of our April number had gone to pres3, we received, in the form of advanced sheets, a copy of very interesting letters, written by Wm. 0. Baldwin, M.D., President of the American Medical Association, and by G. C. Nott, M.D., formerly of South Carolina. The letters were written in excellent spirit, but related to matters bearing on the meeting of the Association this Spring, and, hence, could be of little use at this date. Chicago Medical Society. At the recent annual meeting of this Society, the following officers were elected, and appointed for the ensuing year: President, R. G. Bogue; Vice-President, Ernst Smidt; Secretary and Treasurer, Hiram Wanzer. Sanitary Committee, Drs. Quales, Fenn, and Hutchinson. Censors, Drs. Fitch, McDonnell, and Holmes. Committee on JEthics, Drs. Davis, Trimble, and Margueret. Committee on Microscopy, Drs. Mitchell, II. M. Lyman, and Danforth. Committee on Questions for Discussion, Drs. Paoli, Hildreth, and Adolphus. Adams County Medical Society. The Adams County Medical Society, at its November meeting, adopted a revised Fee Bill, together with the following: In cases where consultations have been had, or where two or more physicians have been in attendance, the physician having the case in charge shall embody in his bill the fees of the or assistants, and account therefor to the same, paying the full amount or such proportion of the whole bill as may be . I. Resolved, That the foregoing table of fees be adopted as the Fee Bill of this Society. II. Resolved, That the virtuous and industrious poor shall be attended by the members of this Society as cheerfully as the rich, and for such compensation as they are able to make. III. Resolved, That every member of this Society shall keep a record of all patrons who are able, but who neglect or refuse to pay for medical services, and report the name and residence of the same at every meeting; and that all such persons be afterwards required, by all the members, to pay for services in advance. IV. Resolved, That our fees are due as soon as the services are'rendered, and that all members of the Society shall make prompt collections, and give the community to understand that we are entitled to the same consideration in this respect that is claimed by merchants, artisans, and laborers. V. Resolved, That this Fee Bill, and these Resolutions, with the names of all the members of the Society appended thereto, be printed in a suitable form, and that every member be required to have a copy of the same conspicuously placed in his office, that our patrons may be fully apprised of its contents and conditions. VI. Resolved, That members wTho disregard this Fee Bill and these Resolutions shall be liable to the same penalties that are attached to a violation of the Code of Ethics. Money Receipts to April 26. Dra. J. F. Kelsey, $3; D. A Sheffield, 3; S. J. Starr, 1; Daniel Gard, 3; John D. Wood, 3; D. S. Jenks, 3; Wm. Dougall, 3; A. G. Jones, 3; D. LaCount, 1.50; Harrison Rodbaugh, 3; J. B. Cloud, 3; R. Winton, 3; V. L. Hurlburt, 3; Theodore Hoffman, 3; Jessie H. Foster, 3; W. M. Chambers, 3; C. S. Hamilton, 3; J. FI. Reynolds, 3; L. Brookhart, 3; Murphy and Wharton, 6. The Discovery of a Minute Fossil Horse. Professor Marsh, of Yale College, has discovered in the tertiary deposits of Nebraska, the minutest fossil horse yet obtained. It is only two feet high, although full grown. This makes the seventeenth species of fossil horse discovered on this continent. Boston Medical and Surgical Journal. Mortality for the Month of March, 1869: The sanitary superintendent submitted the following report of mortality for the month of March, 1869: The number of deaths during the month of March was 353, with 41 premature and still births. COMPARISON. Deaths in March, 1869,_353 j Deaths in March, 1868,_380 | Decrease,_27 Deaths in Feb., 1869_______382 I Decrease.__________________________20 Males,_____________207 Single, 267 | White,______________349 I Females,____________146 Married_______________86 Colored,_____________ 4 Total,____________353 Total,__________,_353 Total,____________353 NATIVITIES. Bohemia,_____________ 3 Canada,______________ 8 Native Chicago,____ 76 Foreign " 95 U. S., other parts,_ 70 England,_____________ 5 France, 3 Germany, 33 Holland, 2 Ireland,____________ 37 Italy,_______________ 1 Norway, 5 Switzerland,_________ 2 Sweden,______________ 8 Scotland,____________ 3 Unknown,_____________ 2 Total,_____________353 MORTALITY BY WARDS FOR THE MONTH. Ward. Mortality. Pop. in 1868. One death in Ward. Mortality. Pop. in 1868. One death in 1 6 9,094 2,2734 2 12 13,074 769 3 22 15,076 793$ 4 18 17,796 936; 5 19 16,033 943* 6 18 13,083 769 1-10 7 28 25,492 772$ 8 14 15,813 790 4-7 9 27 19,297 689$ 10 20 12,925 1,435 7-9 11 17 14,340 1,024 1-5 12 24 17,485 603 13 15 11,164 507$ 14 24 14,839 742 15 28 21,078 958 1-10 16 21 15,465 736 3-7 County hos. 13 Accidents, 11 Mercy Hosp. 5 Suicides, 1 St. Jo. Orph. Asylum 1 Poisoning, 9 Marine hosp. 1 Woman's home, 1 Home for the Hosp, for Women & TH *__31__O -1.1_ 1 Total,_____________________________ 374 REPORT OF SANITARY SUPERINTENDENT. The sanitary superintendent also submitted his yearly , of which the following is a brief synopsis: The total number of deaths was 5,807. The sexes were, males, 3,191; females, 2,616. The condition was, married, 1,222; single, 4,585. Color, white, 5,742; colored, 65. In the way of nativities, Chicago suffers to the extent of 3,144. The greatest number of foreigners were from Germany, 671; the next greatest number, 510, being natives of Ireland. The mortality by wards shows the largest number to have been in the Seventh Ward, and the smallest in the First Ward. The total number of births was about 8,000. The number of femalesjborn during the year was much less than males. At the last annual meeting of the Medical Society of the State of New York, Dr. March read a paper entitled " Lithotomy" giving an account of a case in which a large-sized vesical calculus was discharged through an in the perinteum. Medical Record. A Singular Disease. Before the London Obstetrical , Mr. Heckford recently exhibited the generative organs of a child aged ten months, in which the vagina was enormously dilated, and occupied by villous growths of a medullary . The rectum, bladder, and urethra were normal. The os uteri opened into the upper wall of the vaginal sac. The disease had lasted for about four months; and the child died shortly after its admission into the East London Children's Hospital. Medical Record. The Half-Yearly Compendium. The number of this for January has now appeared. It is full of the choicest selections on all branches of medical science, and should be in the hands of every physician. No synopsis of professional works, or articles, at all compare with it, either in the diversity of sources consulted, or the number of valuable facts . The annoying delay in the publication of this number will be avoided in future. The next number may be confidently looked for by July 10th. Med. and Sarg. Reporter. A Valuable Collection for Sale. A large and superior collection of original illustrations, by the late Prof. Turck, of Vienna, comprising 777 water-color paintings of life size, and illustrating the diseases of the larynx and pharynx, as seen with the laryngoscope or from pathological specimens, is for sale by the family of the Professor. The paintings were by Drs. Elfinger and Ileitzmann in the first style of the art. A history of each case is annexed. Will not some of the profession so far render himself a benefactor of his brethren as to purchase the collection, that we may have it among us. F. H. b. Boston Med. and Surg. Journal. Catarrhus Vesicle. This disagreeable chronic complaint is often very obstinate; it may therefore, be stated that M. Mallez has found the following solution injected into the very efficacious: Water ten ounces; tincture of iodine, -five drops; iodide of pottassium, fifteen grains. When the pain is very annoying, add fifteen grains of the extract of to the above. He has also employed carbolic acid, nitrate of silver, and hyposulphite of soda with advantage. Lancet, Jan. 2, 1869. Medical News and Library. A Superior Liquid Glue. A liquid glue, far superior to mucilage, may be made by dissolving glue in an equal quantity of strong hot vinegar, adding a fourth of alcohol and a little alum. This will keep any length of timci when placed in closed bottles, and will glue together horn, wood, and mother of pearl. Scientific American. Diabetes Cured by Peroxide of Hydrogen. Mr. J. J. Bayfield (British Medical Journal') reports a case of diabetes cured by peroxide of hydrogen. He commenced with doses of the ethereal essence of the peroxide, and increased it to three drachms a day. The Med. Record. A Surgical Prize. The Surgical Society of Paris has just announced the subject of the Laborie prize (<PS48), to be awarded in January, 1870: "Point out, by the aid of clinical facts, the actual value of supramalleolar amputation from the following points of view: 1. The mortality consequent upon the operation. 2. On the different ways of performing it. 3. The usefulness of stumps in the act of walking. 4. The limbs best calculated for these stumps." Med. Record. Treatment of Diseased Gums. A writer in the London Lancet recommends the following treatment of diseased gums: The teeth should be washed night and morning writh a small and soft brush; after the morning ablution, pour on a second toothbrush, slightly damped, a little of the lotion, and apply it to the affected parts: Carbolic acid, one scruple; rectified spirits of wine, two drachms; distilled #water, six ounces. By the use of this preparation, suppurative action is kept under, and the gums get firmer and less tender. The Medical Record. The Last Wonder of the Spectroscope. The , which, since its invention eight years since, by Bunsen and Kirchoff, has contributed so much to the progress of , was used with signal success in observations of the recent total eclipse of the sun, by English and French parties, in parts of Asia. By this means, the nature of the on the rim of the solar disc, observed in former eclipses, has been satisfactorily explained. They are found to be of incandescent gas, possibly containing hydrogen. The Medical Record. C/iLCiFiCATiON of Tootii Pulp. Recently Miss L., aged 21, of nervous, sanguine temperament and general good health, called for consultation in reference to her two superior central incisors. About four years before, they had received a blow which partially loosened them ; they were quite sore and for a few weeks, and then recovered so far as to be used with a tolerable degree of comfort. The left tooth soon changed somewhat in color; and the presumption was that the pulps of both were devitalized. Two years and a half after the , the teeth began to change position, the cutting edges thrown forward against the upper lip, disfiguring the mouth very much. . i In consequence of this, together with constant soreness, which had existed for several months, it was decided to remove them, which being done nothing particular was observable, than had been shown before extraction, the left tooth some change of color, but the right, none from that of a healthy tooth. Through inadvertence, the crown of the latter, a day or two after extraction, was broken into three or four pieces, breaking off at the neck of the tooth; the pulp was found to be calcified, entirely filling the pulp chamber; it did not break; the fragments of the crown parted from it, leaving it standing perfect, tightly imbedded in the canal of the root so firmly that it can not be drawn out with the fingers. This is the only case of the kind we have ever seen, and is a very marked illustration of a process upon which very little has been bestowed, and about which not much is known. We were recently presented by Dr. Cushing, of Chicago, with a section of tooth in which the calcification of the pulp was complete; but it was perfectly united to and continuous with the dentine all round the walls of the pulp chamber, which was obliterated thereby. This is clearly a calcification of the pulp, and not a merely of calcific matter upon the walls of the chamber, for the structure of the pulp is clearly seen in the tissue. We shall have sections of each mounted for microscopic , when we shall perhaps have something further to say in reference to them. History of Vaccination. The Pall Mall Gazette states that the Russian Government has offered a prize of 3000 roubles (,PS400) for the best history of vaccination, by way of the hundredth anniversary of the introduction of that into Russia by the Empress Catharine II. The prize is open to all European competitors, and the history may be in any modern European language. Boston Med. and Surg. Journal. Webster's Unabridged Illustrated. In all the points of a good dictionary, in the amplitude anti selectness of its vocabulary, in the fullness and perspicacity of its , in its orthoepy and {cum grano sails) orthography, in its new and trustworthy etymologies, in its elaborate, but not too learned, treatises, of its introduction, in its carefully prepared and valuable appendices, briefly, in its general accuracy, , and practical utility, the work is one which none who read or write can henceforth afford to dispense with. Monthly.
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CHICAGO MEDICAL SOCIETY. Friday Evening, March 5, 1869. The Society was called to order, and in the absence of Marguerat, Dr. W. Kersham was appointed to fill the chair pro tem. The Secretary read the minutes of last meeting, which were duly approved. Drs. Groesbeck and Wickersham recommended Dr. J. R. Groesbeck for membership. Referred to Board of Censors. The Board of Censors reported favorably in the case of Dr. Lyman Ware. Society proceeded to ballot, Dr. Ware being unanimously elected a member of the Society. Dr. Paoli asked permission to read a letter from a member of the Legislature in relation to the Medical Bill, to the effect that the bill would not pass this session for want of time, as it had at that time not been reported on. Dr. Groesbeck remarked that he was sorry the Society had taken any action to promote the passage of the bill, and hoped they would cease all further action in the matter. Under call for report of cases, Dr. Paoli reported case of a lady on Erie St., who supposed herself suffering from of the bowels. Dr. found no inflammation, but of the uterus. The woman had some accident five years ago. Lately she has suffered a great deal from leucorrhoea, which the Doctor thinks is the great cause of the retroversion. Under the use of tonics, iron, etc., the patient is doing well. Dr. Paoli asked of the Society what diseases were most in the city. Dr. Davis reported the cases of two girls, aged respectively 10 and 15 years, who had suffered from scarlatina in a mild form. In one week, the youngest complained of pain in the back. There was general anasarca, continuing four days. Urine scanty and high colored. She took bitartrate, nitrate, and acetate of potassa* and digatalis. Notwithstanding only one passage of urine was effected for 24 hours, which was half blood. This was soon followed by symptoms of giddiness, of the pupils, and quick, successive convulsions, for 18 hours. Everything taken into the stomach was rejected. Bromide and iodide of potassium was given without effect, together with vapor baths aud fomentations. Still convulsions continued. I ordered nitrate of potassa and calomel, each 5 grs., to be given every hour until two doses were taken, then the interval to every two hours, alternated with a mixture of and tinct. cannabis Indica. Four powders were given before the bowels were moved, evacuation being copious. Then withdrew the calomel and gave nitrate potassa and pulv. Doveri aa gr. ij., every four hours, continuing the chloroform and Indica. Child is now well. In the other case, the girl of 15 years, I could get nothing to act on the bowels until I finally prescribed three gtts. oleum tiglii, part of which was rejected. It, however, produced a evacuation, which relieved her. For one week she seemed quite well, when she was again seized with violent convulsions, which continued for 24 hours. Dr. Byford saw her and ordered a vapor bath and some other remedies. It is now one week since she has had a convulsion. These are the only cases of scarlet fever that have been followed by anasarca and that I have met with for a considerable period of time. As regards the prevalence of disease, the Doctor stated that there is a great deal of pertussis, but not sufficient scarlet fever to be called an epidemic. Has noticed some cases, , which assumed a diphtheritic form. Dr. Groesbeck reported fatal cases of scarlet fever, the first a little boy of 3| years. At an early stage of the disease there appeared on both tonsils white patches which extended to the mouth. The patches, however, soon cleared off, and I looked for convalescence. After one week had elapsed, the tonsils began to swell, and in due time I opened one tonsil, pus escaping. In a day or two later there , was severe hemorrhage from the sloughing surface of the tonsil, and the child died. The other case, a boy of 4| years, was taken with the same symptoms, the same exudation appearing on the tonsils and in the mouth. When convalescence was expected in this case they became swollen and edema of the lungs supervened. Dr. Paoli thinks that when you find blood present in the urine in acute Bright's disease following scarlatina, that it is a favorable symptom. The Doctor wished to know if any had used cannibis Indica alone as an antispasmodic. Dr. Davis says there was no effects of antispasmodics in the cases referred to until after free elimination had been produced, but thinks the cannibis Indica would have acted favorably alone. Dr. Davis says he saw Dr. A. A. Dunn four days before his death, and that Dr. Andrews had seen him several days , as lie was attending him. Says that Dr. Dunn seemed to think he was buffering from neuralgia in the cicatris, on his forehead, although the pain was somewhat diffused. The Doctor seemed wearied and tired, and had been taking morphine and quinine while going about. Nearly a week before his death, he said he felt as though his end was coming. I visited patient that day. He grew rapidly worse. Pulse not accelerated. Very moderate increased heat of head. Went steadily, although quite rapidly, into a dull, drowsy condition, but if roused would talk. Pupils a little dilated. When I was again called I could not rouse him sufficient to converse, although he seemed to me. Pulse soft and compressible. Pupils contracted and but little affected by light. Bowels inactive. Gave an enema. Red and congested condition of the nases and fauces, but throat was not swollen. He continued to sink into a stupor, and the third day after I saw him he died. There is no doubt in my mind but what there was disease of the anterior lobes of the brain, as we could not get him to swallow, the second day after I saw him. At the time of death there seemed to be edematous infiltration about the glottis. Dr. Davis also spoke highly of the deceased, and recommended that a committee of three be to adopt resolutions and send a copy to the family of the deceased and copies to the city papers. Dr. Fitch said that he has been acquainted with Dr. Dunn for twenty years, and all that Dr. Davis has said is true. that the Doctor did not serve in the army as a surgeon but as a Captain in the line. During the service he received a shell wound of the forehead, which continued to discharge for two years and only healed about one year ago. Dr. F. was also inclined to think the wound was the predisposing cause of his sickness, as there was a fracture of the cranium. Dr. Holmes said Dr. Dunn gave a long report of his own case to the Society some time ago, and stated that spicula of bone had been discharged from the nostril. Dr. Fitch said that he thought Dr. Dunn had seemed and dull ever since he received the wound, not appearing like the same man to him. On motion, a committee was appointed, consisting of Drs. Davis, Fitch and Groesbeck, to report resolutions in the case of Dr. Dunn at the next meeting of the Society. After transaction of some miscellaneous business the Society adjourned. Chicago, Friday Evening, March 12, 1869. Society was called to order, President Marguerat in the chair. Secretary Macdonald read the minutes of last meeting, which were duly approved. Board of Censors reported favorably in the case of Dr. J. R. Groesbeck. Society proceeded to ballot, Dr Groesbeck being unanimously elected a member of the Society. The Secretary read the resignation of Dr. J. E. Ray, which after some discussion was duly accepted by the Society. Then proceeded to the discussion of the "Hypodermic of Medicinal Substances." The discussion was opened by Dr. Ingalls, who gave an history concerning its discovery. Dr. Wood, of Scotland, in 1850, introduced this method of applying medicines, but it has been proven that Dr. Brainard, of Chicago, used a syringe constructed on the same principle, and manufactured for him by Tieman, as early as 1845, and used it in the treatment of spina bifida, hydrocephalus, ascites, etc., and that he wrote several articles on the subject about that time. Hence we can justly say that the system of the hypodermic application of medicines originated in Chicago. The Doctor also considered the different complaints in which it was most applicable. Dr. Marguerat said that he was glad to hear Chicago had a claim to such a valuable discovery, but did not think it would supercede the administration of drugs by the old way. Says he noticed a case of death from erysipelas, following a large injection of quinine, but thinks there is no doubt but what it is of great service in the treatment of neuralgia, dysmenorrhoea, etc., and believes its effects more permanent than when administered. Said he was called in the case of a woman who was suffering from hysterical insanity, the result of ill treatment by her husband. She had been a raving maniac for three weeks; could not give her medicine, as it took three or four to hold her in bed. He injected morphine, and in five minutes the patient passed into a quiet sleep. Dr. Paoli remarked that he had no doubt but what the time will come when the hypodermic application of medicine will be approved by the profession generally. In cholera time, sab* he derived more benefit from the administration of morphine in this way than by any other. Has had no experience with other alkaloids. Dr. Foster asked what proportion of morphine was most for hypodermic action. Dr. Fitch said he had but little experience in this mode of treatment, except as recommended by Dr. Brainard in the treatment of varicose veins and hydrocele. Generally 15 or 20 drops of the liquid, first pinching up a fold of the skin before inserting the point of the instrument. Says Dr. Anstie, in Braithwaite s Retrospect, considers atropine of great value when the disease is located in the pelvis or , and strychnia in gastralgia. Dr. F. reported a case of abortion which occurred two months a*go, when the patient was in great pain, restless and uneasy, and could take no food. Gave gr. atropine with great success; after second dose was introduced there was dilatation of the pupil. Dr. Davis remarked that he had not much experience in the use of the hypodermic injection. Used it in one case of facial neuralgia with permanent benefit. Patient has had no attack for a year. Used it in several other cases with temporary . Thinks when the solution contains too much acid then it is apt to be followed by ulceration or abcess. Dr. Ingalls thinks that what Dr. Davis has said is true, and is of the opinion that all acids should be discarded from , always using distilled water. (Magendie's solution morph, gr. xvj.; aqua gj.) Dr. Bogue thinks there is great benefit from the addition of from 1-40 to 1-80 of a gr. of atropine to about a-half of a dose of morphine, as it extends the effects of the anodyne from 12 to 16 hours. Thinks this method very useful given in the cramps of cholera. Society passed to miscellaneous business. The committee appointed to report resolutions in the case of Dr. Dunn submitted the following, which was duly accepted by the Society: (See Resolutions in April number.) Society adjourned. Friday Evening, April 16th, 1869. Society called to order by the President, Dr. R. G. Bogue. Reports of cases being the order of the evening, Dr. N. T. Quales reported the following interesting case4 of rupture of uterus: March 9th, 1869, at two o'clock P.M., I was called to tend Mrs. L., a strong, healthy Irishwoman, aged 28, in her third confinement two previous having been instrumental deliveries told me she had been sick since five o'clock in the morning; pains having been strong and regular; membranes ruptured half an hour before my arrival, and about 15 or 20 minutes later (the pains having continued with increased severity) she felt "give way," and the pains almost instantly ceased. On examination, I found the os uteri fully dilated, the cord down, but no parts presenting. By introducing the hand, I found the promantory of the sacrum unusually prominent, and by carrying the hand farther, it came in contact with the , and I made out the position as transverse, the abdomen presenting the head to the right, and the feet to the left, side of the mother. In passing my hand (right) round in order to. get hold of the feet, I found a longitudinal rupture of the wall of the uterus, above the promontory of the sacrum, about 2| 3 inches in length, with intestines protruding. My feelings at this discovery can better be imagined than described. I despatched a messenger for my friend Dr. Paoli. With the conviction that immediate action offered her the best chance, I decided to turn and deliver at once. I brought down the left foot, and, by gentle traction, succeeded in her, in course of 15 or 20 minutes, of a fullborn, healthy male child apparently stillborn, yet, after some patient effort, I had the satisfaction of seeing vitality restored. By gentle traction on the cord, the placenta was expelled in about three inches. There was now some considerable . I at once gave the fl. extract of ergot (Duffield's), introduced my hand and replaced the protruding intestines, and, by friction and pressure over the abdomen, caused firm of the uterus before I withdrew my hand. In course of 15 minutes, I repeated the ergot, in order to obtain contraction; and having succeeded in this, I applied a moderately tight bind and napkin to the ulva waited another half hour the contraction of the uterus continued. I gave gr. ij. of opium, and left orders to call me if anything unusual should occur. At eight o'clock in the evening, I called and found the uterus somewhat dilated, the patient otherwise . Ordered gr. ij. of opium at once, and to be followed with gr. j. doses of opium every two or three hours, if she was awake. March 10th, at eight o'clock A.M., I found her feverish and uneasy. She had slept about three hours during the night, and passed urine twice. Pulse 112 per minute; respiration somewhat labored; tongue dry; considerable tympanites and tenderness about the uterine region; lochial discharges . Ordered tinct. verat. vird., gtt. 4, every three hours, and pulvis opium and dydrorg. submureas, of each, gr. j., every two hours, with turpentine stupes over the abdomen: saw her at noon, when she was more comfortable. At eight o'clock in 'the evening, the pulse was 108 per minute; the tenderness about the abdomen subsided. Ordered gr. ij. of opiuip, at . March 11th, at eight o'clock A.M., pulse 106 per minute; no great pain; had slept several hours during the night, and taken some nourishmeut. Treatment continued, with longer intervals between the doses. Also, injection into the uterus of solution of acid carbol., gtt. vj. to the warm water, three times a day. March 12th. Symptoms much aggravated; pulse 120 per minute; tongue dry; lympanites and tenderness increased; had passed a restless night. Ordered blister, 12X12, over the , to be left on for six hours. Internally, I ordered quinia sulph., gr. j.; pulvis opium, gr. ss., every four hours, to alternate with tinct ferrsh, gtt. xx. On removing the blister, a large, warm flax-seed poultice was applied to the abdomen, and a full anodyne at night. March 13th. Much improved; little pain besides the from the blister; lympanites greatly subsided; pulse 112 per minute; tongue moist; bowels moved for the first time since confinement; locheal discharges reestablished; took nourishment during the day. March 14th. Improving; pulse 90 per minute; tongue moist; no pains, and but little lympanites: treatment continued. March 27th. Sits up, and can walk across the floor. of milk liberal. At the present writing, April 14th, 1869, both mother and child are doing well; the mother performs her ordinary duties, yet complains of occasional soreness over the . Dr. G. C. Paoli, in remarking on the foregoing case, gave the following statistics of ruptures of the uterus: In the Kingdom of Wurtenburg, in 219,535 births was six ruptures of the uterus, being only one in 36,539. Madam La Chapel observed in Paris Hospital only one in 20,000 births. Professor Jocery Elipse observed two ruptures in 20,056. Dr. Erringman, of Prague, from 1827 to 1833, observed seven ruptures in 18,085 cases. Dr. Cedershold, of Sweden, from 1830 to 1831, observed two ruptures in 2334. Churchill, of England, in 42,768 there was 75 cases, making 1 in every 657 which occurred in Dublin. Verbal reports of cases were made by Drs. Groesbeck, Paoli, Mitchell, and others. Dr. T. D. Fitch, one of the surgeons to the Cook County Hospital, reported a case of death from the inhalation of , which occurred that day at the Hospital. The patient was an adult, native of Sweden, and a laborer. Several months since he suffered a severe injury of his foot and ankle, by a waggon-wheel passing over it. The injury had in extensive destruction of soft parts by suppuration, and caries of the bones of the ankle. He was admitted to the Hospital only a few days since; and a consultation of the surgeons of the institution resulted in the decision that amputation was necessary. The patient had been kept on good diet and tonics during the short time he had been in the Hospital, and had taken a glass of wine immediately entering the operating room. No disease had been detected in the organs of respiration or circulation; and the patient was himself anxious to have the operation performed. The was administered on a napkin, held over the nose and mouth, not so close as to prevent the free access of atmospheric air. When the inhalation had progressed from one to two , and ten or twelve inspirations had been taken, an sound was noticed, and the napkin immediately removed. A slight tremor of rigidity or spasm passed over the muscular system; three or four slight efforts at inspiration took place at long intervals, and then ceased entirely with .complete muscular relaxation. The heart, however, continued to beat feebly for more than half an hour after the respiration ceased. The most strenuous efforts were made to revive the patient by artificial respiration, and otherwise, for more than one hour. The of Dr. Fitch was corroborated by Drs. Bevan and Bogue, who were present and assisted in the efforts to restore the . A minute and careful post mortem was made the following day, but no disease of the organs of circulation or respiration were found, and no congestion or even fulness of the vessels of the brain. After the transaction of some miscellaneous business the adjourned.
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t' r o 1PSPS ( i n a s o t wu us CHICAGO MEDICAL SOCIETY. Friday Evening, January 29, 1869. The Society was called to order, President Marguerat in the chair. Secretary Macdonald read the minutes of the last meeting, which were duly approved, after slight modification by Dr. Davis. The name of Dr. Bosley was proposed for membership by Drs. Seely and Clarke; also, Dr. W. M. Jackson, by Dr. . Referred to Board of Censors. Dr. Seely opened the discussion on the "Pathology and Treatment of Saccharine Diabetes.'' Is of the opinion that the term Glucohemia would be the best to signify the presence of sugar in the blood. Stated that it has been shown that the sugar formed in the liver is consumed by the lungs. Thinks sugar is also formed in the stomach; and the collection of sugar in the urine is due to its not being consumed by the lungs. Is of the opinion that the alkaline treatment is the best that has been advocated to diminish the amount of sugar in the urine. Has read some statements published by Mr. Day, in which he recommends the use of the peroxide of hydrogen. Cited one case which recovered in seventeen days. Dr. Schmidt says, according to late experiments, it has been shown that there is no sugar to be found in the liver, nor veins, during life; or, at least, it cannot be detected upon immediate examination after life has become extinct. Other experiments showed, that if the femoral arteries were , that sugar was formed; and hence they came to the conclusion that diabetes was due to paralysis of the nerves the arteries, and a ferment in the blood. Has heard of cases treated successfully by the application of streams of water down the spinal column. Is of the opinion that arsenic is a valuable remedy in this disease. Dr. Loverin asks if diabetes may not occur from nervous ? If so, the treatment most appropriate would be tonics. Dr. Davis remarked, that he had been very much interested by what had been said, and that he had never been satisfied with Bernard's experiments; and thinks that the more recent experimenters have failed to show or prove the source of the sugar, although they have thrown some light on the subject. He has noticed that punctures of the brain, or particularly of the medulla oblongata, have been followed by saccharine . Also, that strychnia and chloroform, used internally, have been followed by the same results. Says there was a doctor called on him that evening, who has been suffering from saccharine diabetes for some months, and who attributes the cause to the excessive use of strychnia. Dr. Davis says, he does not think that nervous debility, nor even paralysis, can produce this disease, as we have a great many examples of great exhaustion from masturbation; also, paralysiZand hemiplegia; and but very seldom any increase of urine. Hence, thinks it will not do for us to attribute the cause to debility of the nervous system. Thinks that the of the production of sugar is due to deficient action in some of the systemic and pulmonary capillaries. Says his confidence has been shaken in all remedies except such as assimilation. Hence, recommends the acetated tincture of calves' rennet, two drachms of which may be taken at each meal. Cited the case of a little girl who had saccharine some five years since, and who was successfully treated by "Haughton's Pepsin;" the patient not having shown any signs of the disease since. Has been in the habit of using liquid rennet, 5j-, dose before each meal, and ty. Pulv. Opii, gr. ss., Cupri Sulphus, gr. after each meal, with good diet, avoiding starchy vegetables. Cited case of woman on West Side who was treated this way; and in two months hardly a trace of sugar could be found in urine, and has been entirely well for ssveral months. Noticed an article in the New Orleans Medical Journal, where bran bread and meat diet were highly spoken of, avoiding all starchy vegetables. Thinks we have yet to trace out the source of the sugar. Says if strychnine is capable of producing diabetes, it may still be beneficial in the treatment, if administered in doses. Cited cases where atrophy of the limbs was by an overdose of strychnine. Dr. Paoli highly favors the vapor-baths in treatment of . Cited case of a woman who seemed to be benefited by the baths, but who, after a protracted illness, died. Dr. Seely says that the pepsin has been used in France, but it is not considered a very efficient remedy. Thinks, with Dr. Davis, that nervous debility is not productive of the disease. Is of the opinion that the peroxide of hydrogen is worthy of trial. Society next proceeded to Deports of Cases. Dr. Paoli reported case of Swedish woman whom he was called to see at 10 P. M. last Saturday. The woman had been in care of a midwife, and was delivered of a small child at 3 A. M. Hemorrhage continuing from time of delivery until he was called. Found patient lying on her side; head high; pulse feeble, and greatly prostrated. Placed a pillow under her hips, and gave a teaspoonful of turpentine, and produced friction over abdomen. Pulse soon began to improve, and all ceased. Passed to Miscellaneous Business. Dr. Davis proposed next subject for discussion: "What is the active agent that produces convulsions in uraemic poisoning, and the most reliable treatment?" Drs. Schmidt and Paoli were appointed to open the , two weeks hence. Dr. Davis thinks it in the power of those present to make these meetings interesting, and suggests that every member read upon the subjects proposed for discussion, and be prepared to give their experience; thus benefiting each other. Members present: Drs. Marguerat, Macdonald, Davis, Paoli, Loverin, Grosbeck, Guerin, Fredigke, Schmidt, Seely, Wickersham. Society adjourned. Friday Evening, February 5,1869. The Society was called to order by the President, Dr. . Secretary Macdonald read the minutes of last meeting, which were duly approved. The President remarked that there were two members to be elected to-night. Dr. Paoli recommended that the election be postponed until next meeting. The name of Dr. William T. Johnson was proposed for by Dr. Fisher. Under call for Pathological Specimens, Dr. Holmes presented an ossified crystalline lens, which had been shaking around loosely in the anterior chamber of the 's eye for a period of five years. It was removed at the patiems request, as he had suffered considerable pain. The sight of the eye was lost, as it was the result of a blow. Dr. Bogue asked if the anterior chamber was filled after the extraction ? Dr. H. says it was, preserving the rotundity of the eye. Drs. Paoli, Quales, and Marguerat participated in the . Dr. Bogue presented a specimen, the result of conception. During the hemorrhage, the mass was partly held by the of the os uteri. The sac was ruptured on his hand, and he says that he does not think there was anything but fluid escaped. Between the amnion and chorion found quite a large blood-clot. The question is, What has become of the foetus? There was no appearance on either side of the attachment of the cord. Judges the patient to have been in about the sixth week of pregnancy. Dr. Paoli asked if the foetus did not pass off with the ? Dr. Bogue was of the opinion that it was absorbed. Dr. Fisher says he has seen a similar case, although rather larger, where there was no foetus. Dr. Marguerat also reported having removed a sac size of a pigeon's egg, containing a clear fluid, at the third month of pregnancy. Dr. Bogue presented, for Dr. Hutchinson, a portion of a tape-worm, containing the head. Does not know what the used to cause its expulsion. Dr. Paoli remarked, it was rare to see the head, but the tail is often seen. Dr. Holmes asked if there were more tape-worms in this country now than common? Dr. Trimble says that he has not seen many cases of late years. Dr. Wanzer spoke of their being more common in warm California. Said he lately expelled one from a man on the West Side, which the patient thinks was 200 feet long. The successful remedy was the ethl. oil of male fern, in doses. Says he employed other remedies without benefit. Dr. Bogue reported the case of a woman who had taken | of a grain of atropia in solution, by mistake, supposing it was . As soon as swallowed, there was a severe burning in the stomach. Saw her in twenty minutes after, and gave an emetic, which operated immediately; in the mean time, there wTas considerable twitching of arms and legs, which began to pass away, together with the pain, in the course of half an hour. Next morning, the patient had some difficulty in seeing. The question is, Was it a poisonous dose? Dr. Paoli thinks that a quarter of a grain would usually prove fatal, as the dose is from to g1^ of a grain. Dr. Holmes also concurs in the opinion of Dr. Paoli. case of a lady who took | grain, but vomited immediately after. He usually gives about Tgg grain at dose, internally. Thinks morphine and strong coffee the best antidotes. Dr. Macdonald says that he gave a little boy of two years, who was suffering from incontinence of urine, Jj, increased to | gr. ext. belladonna, for two weeks and a half, without of its toxic effect. Dr. Bogue thinks, when a small portion of atropia is with morphia, adds very much to its anodyne influence, the effects continuing much longer than when the morphia is given alone. As an antidote, he prefers strong coffee to either whiskey or opium. Dr. Bogue asked if | g. ext. belladonna was not a pretty large dose for a child? Dr. Marguerat says that Brown-Sdquard records cases where he has given it in grain-doses in pertussis of children, having the effect to temporarily paralyze the fauces. Dr. Paoli thinks it was commenced in |-grain doses, increased to one gr. Dr. Adolphus thinks it very dangerous to give one gr. at a dose. Drs. Tucker and Wanzer participated. Dr. Paoli spoke of having used the chloride of quinia in |-gr. doses in the treatment of five cases of malignant scarlet fever, with very beneficial results, reducing the pulse very rapidly. Asked the experience of the Society in its use. Dr. Quales said he had heard it recommended in membranous croup. Dr. Quales reported case of miscarriage. Patient was in hands of a midwife, and when he was called the hemorrhage was severe. The placenta was very large, and indurated. Foetus some two months old. Dr. Trimble reported a rare case of fracture of 5th bone, from a sudden fall of the patient while skating. The sensation imparted to the young man at the time of was that of an acute pain. Dr. Bogue remarked, that fracture of the Sth metatarsal bone is of exceedingly rare occurrence, especially by turning of the foot. Dr. Wanzer says he has rather a lengthy report on of the shoulder-joint, but prefers to read it at the next meeting. Society then proceeded to Miscellaneous Business. Dr. Paoli presented copies of the Ohio and Illinois Laws governing the practising of physicians, which the Secretary read. Dr. P. then moved that a Committee of three be to report on these laws at next meeting. The appointed Dr. Davis Chairman, and Drs. Paoli and Trimble Associates. Members present: Drs. Knox, Marguerat, Macdonald, Davis, Bogue, Trimble, Paoli, Quales, Wanzer, Fisher, Tucker, , Holmes. Society adjourned. Friday Evening, February 12, 1869. The Society was called to order, President Marguerat in the chair. Secretary Macdonald read the minutes of the last meeting, which were duly approved. The Board of Censors reported favorably in the cases of Drs. Bosley and Johnson. Society then proceeded to ballot, Drs. Bosley and Johnson being duly elected as members of the Society. Under call for pathological specimens, Dr. Fenn presented a salivary calculus extracted from Wharton's duct. Society next proceeded to the discussion of the .subject chosen at last meeting, w'z. ,,* "What is the active agent that produces convulsions in uremic poisoning, and the best ? " Dr. Schmidt opened the discussion, by saying that he had gone through a great deal of literature on the subject, and has found that most European authors refer to American authority, especially Dr. W. A. Hammond's work; but says that have shown that not a single substance of the urine would produce uremia except urea, which had to be injected in very large quantities in order to produce the symptoms. Says he has a patient under treatment at present at the Jewish Hospital, who has some fifteen fistulas, the urine from all. He opened the fistula and introduced a catheter. Patient had chills and headache, which symptoms were for several days by the administration of hydrochloric acid. Dr. Paoli says that uremia exists in albuminuria, and is by the blocking of the ureters. Asked Dr. Schmidt if he tested the urine for albumen? Dr. S. replied that he had not. Thinks albumen is present in the urine of nearly every woman at the 7th or 8th month. Dr. Paoli says he now has a case presenting symptoms of uremic poisoning. The patient is an old lady, and her bladder does not contain more than a tablespoonful of urine. Specific gravity, however, is about normal. Has been giving acid, which seems to give some relief. Cited a case in cholera-time of a young man who did not pass any urine for four days, still there were no symptoms of uremia. Dr. Trimble saw the same case. Patient died in a comatose state. Thinks it is evident that urea is found in the kidney, and not in the blood. Dr. Schmidt says he was called some ten years since in consultation with two other doctors. Patient was a man of 35, and had been suffering from amaurosis. When he arrived, found the patient in a dying condition. Had been gradually losing his sight for three weeks, but had continued to work up to within two days. Pulse was weak, but all the functions seemed to be normal. Found a large tumor on the right side. Asked his wife in regard to the voiding of his urine. She said when he became excited, he would pass urine a half an hour at a time. Patient died that night. Found the right kidney to consist of a sac as large as my hat, while the left was very much enlarged, and fatty. Dr. Gray reported the case of a young man who injured his hand. Three weeks after, tetanus set in. Applied turpentine and belladonna to spine by means of a cloth being saturated, over which he placed a warm flat-iron. Gave internally gtt. x. every fifteen minutes, during the time of which there was no spasm. Then resorted to bromide of potassium, in 20-grain doses, every two hours, without effect, as the spasms again recurred. Patient died in three days; and, although he had not passed water or anything from his bowels for 24 hours, upon the introduction of the catheter his bladder was found perfectly empty. Dr. Fredigke says he has noticed an account of five cases of tetanus in the London Lancet, four of which recovered under the use of Calabar bean. Dr. Foster remarked, that there is a horse-doctor in the city who gives hydrocyanic acid, in from one to two drachm doses, in the treatment of tetanus in horses. Also, tincture of , in 20-drop doses, with very good success. The Secretary then read the report on the Medical Bill, and it was moved and seconded that the bill be accepted. Dr. Wickersham said that the bill presented was free from the objections of the one he opposed. Thinks it will start for the protection of the people, and moves it be , although it is borrowed from the Ohio bill. Dr. Paoli says that he is sorry that the Society did not Dr. Wickersham Chairman of the Committee to report on the bill, and says that the reason for adopting the Ohio bill is because it is more practical than the one originally proposed. Dr. Reid thinks it necessary to appoint a Board to examine those who desire to practise, and recommends the appointment of separate Boards, Homoeopathic, etc., to examine those of their own school. Dr. Trimble says he thinks the remarks of Dr. Reid very appropriate, in order to make the bill more practicable. Dr. Wickersham says he does not favor any such project. Dr. Davis says that what ought to be done is the from the profession of a Board whose duty it would be to examine every person desiring to practise medicine, diploma or no diploma; and says there was a period when two-thirds of all the States of the Union had such organized Boards. Thinks, however, if we ask for a Board, appointed by competent , the Legislature would not pass any such laws. If the Board were appointed by the Governor, it would be nothing but a football in politics, and the Board would be made up of anything but what we want; and it would amount to about the same if the judges of courts had the appointment of Boards. Hence, does not believe there is any use in going outside of the profession for a Board. Not being able to do this, we next aim to have educated men in the profession. Thinks that if the Society do anything, they would do well to adopt the law, and recommends that a Committee of three be appointed to get the bill put in print, and send it to the , with the request that they accept this bill in place of the one proposed, as the opinion of this Society. Dr. Davis recommended subject for discussion two weeks from to-night "Pathology and Treatment of Scarlet Fever." Drs. Tucker and Guerin appointed as disputants. Members present Drs. Marguerat, Macdonald, Davis, Paoli, Bogue, Wickersham, Schmidt, Trimble, Reid, Tucker, Ray, Fisher, Loverin, Quales, Hutchinson, Baxter, Gray, Bridge, Foster, Guerin, and Fredigke. Society adjourned.
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OHlUtnO FROM THE SERVICE OF PROF. N. S. DAVIS, IN THE MEDICAL WARDS OF MERCY HOSPITAL, February 18, 1869. Reported by W. A. BARSTOW. Gentlemen : This man tells us that, some six months ago, while engaged in sinking a shaft in the vicinity of Morris, in this State, he was attacked W'ith pain in the anterior portion of the thigh, stopping short above the knee. The pain, however, soon extended to the iliac and lumbar regions, and subsequently I across to the epigastrium, which has continued since the last of July, with but little relief. He has been under treatment for rheumatism. I first saw him at my office one or two weeks since. I find, on examining the spine at the lower, or next to the lower, lumbar vertebra, there is a little prominence. There is but little tenderness over the spinous processes, but directly along the right side of the vertebra, for several inches, it is extremely sensitive, and seems to be almost exclusively limited to the right side. There seems to be a very little swelling, but wffiich may be due to dry cups which were applied two days since. He will allow any degree of flexion of his thigh, but if you extend the leg and carry it back of its fellow, the pain is reflected along the margin of crest of the ilium and . If he sits down, or stoops to pick up anything, instead of bending forward as a well person would, he squats down, to keep his spine as straight as possible. This symptom is of great value in forming a diagnosis, and raises the question as to what the disease is, and what has it? To the experienced observer, his symptoms suggest one of the three following diseases: 1. of the psoas muscle, or adjacent areolar tissue, tending to the formation of an abscess. 2. Disease of the vertebra. 3. Inflammation of the right half of the spinal cord. Any one of these three diseases would be brought to mind in the . First, we will take up affections involving the psoas muscle. Pain in the front part of the thigh and abdomen would first lead us to suspect that this muscle was involved. The first effect of inflammation in contact with a muscle is to render it rigid. The tendency, if the psoas muscle is inflamed, is to relax the abdomen by flexing the thigh on the pelvis. If he puts his leg down straight, or stands square on his feet, he will lean his body forward, so as to still relax the muscle on the anterior part of the spine; and, if in bed, he will be found to have the thigh drawn up. The pain accompanying psoas is dull and deep-seated, extending from the abdomen to the junction of the lumbar vertebra, and across by the crest of the ilium. The most diagnostic signs being, pain down the thigh, and in one side of the abdomen, and the flexion of the thigh. If asked to flex the thigh strongly, he cannot, the pain being much increased. If you examine the patient while on his back, you will generally find, on pressure, a degree of along the inside of the anterior part of the crest of the ilium, or a sense|of fulness and tenderness, which does not correspond to the opposite side. In the present case, none of these symptoms are present, except the pain in the anterior part of the thigh, and pain in extending the leg backward. Is the disease in the vertebra? One symptom exactly corresponds with the early stage of spinal disease, viz.: the mode of stooping down, which may be noticed in children who have spinal disease, coming on even before they complain much. Instead of stooping over, they will likewise squat; and if they can reach anything to support them in rising, they will do so. This symptom, however, is not restricted to disease of the bones of the spine, but may be present in any affection that renders the spine sore. Six months have elapsed, and there is no perceptible , except in the one spinous process previously mentioned; hence, we are not justified in saying that he has disease of the vertebra from the manner of stooping alone. The tenderness along the sides of the vertebrae is severe, while in disease of the bone there is rarely any muscular or neuralgic pains, until the disease has progressed to such an extent as to make some degree of deformity perceptible; then you have severe paroxysms of pain in the epigastric region, in the intercostal spaces, or horizontally around the abdomen. There is seldom any evidence, in the early stage, of with muscular action. But in this case, pain in the was one of the first symptoms; and, taking this together with the facts that it is of six months' duration, and no ; while the pain follows certain nerves, with acute and severe tenderness along right side of the spine; increased by exercise, and occasional cramps in the abdominal muscles; all of which point to the right half of the spinal cord, with the lower half of the dorsal vertebra, as the seat of disease. Both sets of nerves are involved namely, those of sensation and motion. From a close investigation of his case, my is, that he has chronic inflammation of the membranes of the spinal cord, along the lower third of the dorsal vertebrae. If that is the case, has it produced any disorganization of structure? We answer no, or it would have left him^ith ; and, if there was effusion, this would have certainly produced paralysis in some degree. If it be simple chronic inflammation, involving the roots of nerves, what is the treatment? We answer, dry cupping, followed by plasters or hypodermic injections of atropine; and, , we will first put him on the following treatment: ly. Tinct. Cimmicifuga, gij. Tinct. Stramonii, gss. Iodide Potassa, 5iiss. Simple Syrup, SSiss. Mix. Of which, we will give a teaspoonful every four hours; and, three times a day, a powder, consisting of Bj. Potassa Nitras, 1 __ Pulv. Doveri, j aa' &1' V11J' Hyd. Chlor. Mite, gr. ij. The calomel to be discontinued as soon as its alterative effects are perceptible in the breath or gums. These means, with rest in the horizontal position, will be likely to remove the disease in from four to six months. Common tumblers form good cups for broad surfaces like the back, as was shown by their application in this case before the Class. Gentlemen : The next case to which I propose to call your attention to-day is one of partial hemiplegia. The patient is a carpenter, and says that, for two or three months before the attack, he was at times light-headed and dizzy, and was afraid to venture upon the scaffolding, and went to work in the shop. It seems that, the night of the attack, the patient was out later than usual with some friends, and during the evening had indulged in a glass or two of stimulants, but not enough to feel the effects to such an extent that he did not know all that . After parting with his friends, he started for home. Before he proceeded far, however, he says that he was gradually taken blind and dizzy, and finally fell on the sidewalk, and became partially unconscious. When he recovered himself, he found he had no power in his right arm nor leg, but succeeded in dragging himself to a doorway. Until within the past week, he has been under treatment at Madison, Wis., where he was living at the time of the attack. At present, you would hardly know that his leg was affected in walking; but, on closer observation, you would notice that he raised it with difficulty when attempting to step over anything. His face has improved equally with his leg, but his arm is still nearly useless. Can shut his hand quite tight, and has a good degree of power in the flexor muscles; but the action of the extensors is much impaired, and supination is also rendered imperfect. This shows us that the whole set of extensors, from he shoulder down, are more feeble than the flexors. The first item we wish to investigate is the seat of the . The paralysis of the arm and leg are but symptoms, and may arise from three sources: 1. The muscles themselves, as in lead palsy. 2. The spinal cord. 3. The brain itself. The symptoms of giddiness and the paralysis, extending to the face, must necessarily involve the nerves within the cranium; hence, we refer it to the brain. If there had been no paralysis of the face and tongue, we might have presumed it was in the spinal canal. The patient's mind being clear, while there is giddiness and dimness of vision at times, we refer the seat of disease to the base and central portions of the brain. In determining the nature of a disease like this, it is to get as accurate a history of the case as possible. First, we may have paralysis come on suddenly, with severe pain, as in the case of the patient up-stairs, to which your was a few days since directed, indicating a pathological chancre of an anoolectic character. In this case, it has come on gradually, and became fully when under the effects of stimulants. Rest improves his muscular power, while exercise uniformly exhausts it. This would indicate the existence of some gradual change at the base of the brain, like syphilitic thickening of the dura mater, the growth of a tumor, or gradual softening of brain substance. We will endeavor to draw the line of distinction between these pathological conditions. The symptoms of white atrophy or softening do not to those of the case before us. That disease comes on insidiously, by simple impairment of the muscular power, the legs or arms requiring an extra exertion on the part of the to use them. It is a gradual weakening, which, when once begun, continues on worse and worse, and involves loss of coordinating power and strength, without complete paralysis, until the last stage of disease. Now this man was not progressively losing the strength and coordinate power of his muscles, but merely giddiness and headache. And, instead of steady increase of his disease, under treatment he has been decidedly improving, and now only complains of paralysis of the right arm, with pain in the shoulder of the affected side, and occasional darting of pain up the back part of the head. It seems that, several years ago, this patient contracted ; and he now has maculae on the skin, and what he calls disease in the nostrils. And it is highly probable that his giddiness and paralysis arise from thickening of the dura mater over the sphenoid bone. It is of the utmost importance to ascertain the cause, in such cases as this, in order to know how to treat the disease . He has been taking iodide of potassium and strychnia; and I think, had the iodide been combined with minute doses of the bichloride of mercury, it would have benefited him still more. The question is, had the disease involved the bones either the ethmoid and palate, or any portion of the sphenoid? If it has, the prognosis would be considered unfavorable, not terminating for three or four years. If it is to the soft parts, we would expect a recovery. Viewing the case in this light, we will put him on the treatment, with an occasional intermission of a week: 1^. Iodide Potassium, . Hydr., gr. j. Syr. and Aquae, SSiv. M. Of which, we will give a teaspoonful four times a day. We will also use a weak solution of carbolic acid as an injection, which may be applied by means of a curved syringe through the posterior nares. We may derive some benefit from tonics when the muscles are flaccid; but strychnia and should never be used to any extent, if there is rigidity of the muscular fibres. Under the foregoing treatment, we may expect the patient to recover a good degree of health, and the use of his arm, in from four to six weeks. It will depend, however, upon whether the bones at the base of the brain are affected or not.
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ARTICLE XVI. A SINGULAR CASE OF PURPURA AND TETANUS. Extract from an Inaugural Thesis presented to the Faculty of Chicago Medical College for Session of 1868-69. By EDWARD R. KITTOE. As you will see by the heading, I intend to proffer as my thesis a report of a singular case of purpura and tetanus, which I had the good fortune to see and watch from the first attack to the final recovery, during the first year of my study with my preceptor, which happened to be my father, and I made it a part of my study to visit with him some of the most important cases which came under his care. The one I now intend to give a report of, struck me at the time as being one of peculiar interest, and I wanted him to keep a record of it and make a report to some of the medical journals, but he neglected to do so, and I now take it up to lay before you, as I it, with the few notes I have been able to collect from the patient's father, as well as those of my preceptor. It was as follows: Philip Bolinger, aged 9 years, had what to be a small pimple on the lower eyelid of the left eye, his father punctured it, and there escaped a small drop of pus; a few hours after it commenced to bleed very freely. Having tried in vain to arrest the hemorrhage, by all the means they had at hand, my preceptor (Dr. E. D. Kittoe) was called in. He found a clot of blood about the size of an ounce ball, which, on being touched, blood appeared all over it in drops like dew. He removed the clot and applied some Monsel's styptic on cotton, but with no effect. He applied successively, tannin, alum, kino, agaric, nitrate of silver, etc., etc., with no benefit. It being impossible to apply pressure with any direct force upon the wound, a bandage was passed around the head, with a , over the temporal artery. This appeared to answer the desired purpose for about twenty-four hours, at the end of which time, there being much tumefaction of the face and scalp of the affected side, with an erysipelatous blush, it was deemed to continue pressure any longer. Upon removing the bandage and dressings, blood immediately began to ooze out around the coagulum, which had gradually increased until now it was the size of a hen's egg, flattened out by the pressure. Upraising carefully the edge, blood streamed out rapidly, and he found that there was a slough involving nearly two-thirds of the eyelid. He then removed the entire clot, and endeavored to staunch the blood by styptics once more, but with very poor success. He then tried the application of ice water, by the way of irrigation, by means of a fruit can, with a minute hole in the bottom, suspended so as constantly to drop on the part affected. In the meantime the boy was put upon tonic . There had appeared on various parts of his body, . He was directed to take quinia sulph. gr. ss.; tr. ferri chlo. min. xx.; vini rubri SSss., every three hours, with beef essence, chicken soup, etc., ad libitum. After about twelve hours the ice-water treatment failing to arrest the bleeding, and the slough appearing to increase, recourse was had to bark, and powdered charcoal mixed quite stiff with yeast, and applied to the wound. On the removal of the fourth the entire slough came away, leaving a clean granulating surface, with a very minute arterial jet near the centre. This was grasped with a pair of Liston's artery forceps, and pretty effectually twisted, after which no further hemorrhage occurred, and the boy recovered rapidly. In about six weeks from the first attack of hemorrhage, he got a slight scratch on the temple on the same side, the bleeding from which was almost as unmanageable as at the first, but was controlled mainly by large doses of tinct. ferri chloridi, 25 drops every four hours, with port wine. Styptics, and pressure were again tried, but but with no avail. The bleeding was evidently controlled by the tinct. ferri. There was at the time profuse hemorrhage from the gums, but no appearance of petechia on any part of the body. The iron and wine together, with nutritious food, was continued for several weeks, w'hen the boy appeared to perfectly his color and health. About the 9th of December following this, (the first attack being in July,) he fell down stairs and cut his hand across the ball of the thumb, with a piece of glass. It was tied up, and gave no inconvenience until the third or fourth day, when it became painful and commenced bleeding very profusely. My preceptor was at once called on, and again tried the use of styptics, but with no success. He also placed a compress of cork over the radial artery, which did partially control the bleeding, but immediately a large slough began to form about the cut, and a very considerable coagulum, about the size of a hen's egg, formed over the first incision. This clot had very much the appearance of fungus haematodes, the blood oozing from it at innumerable points. lie removed this once or twice and applied dry lint, which would appear to keep it in check for a time, for several hours. However, this was soon for the bark, charcoal and yeast, with the tinct. ferri, 25 drops every three hours, which again had the effect to check the sloughing, and eventually the hemorrhage. (I should also mention that he tried at this time the use of bromine and also carbolic acid, but without benefit.) Now came on another phase of the case. My preceptor was called in the night to see his patient, the father stating that the boy was in a -'fit." On arriving at the house, he found that he had a regular attack of tetanus. The jaws were tightly clenched, and the spasms, which came on in paroxysms, were terribly severe. Perspiration poured from every pore, and the whole appearance of the child was distressing in the extreme. lie at once gave him the sixth of a grain of morphine, and directed the same quantity to be given at intervals of an hour, until relief was afforded; to the wine, with a teaspoonful of tinct. cinchona comp., every three hours. After a lapse of twenty-four hours, no benefit appearing to arise from these means, and the spasms being perfectly terrific, the dose of morphine was increased to one-fourth of a grain, in combination with valerianate of , 5i, repeated every hour; porter or lager beer ad libitum. The spasms continued with great severity for sixteen days, and the dose of morphine was eventually increased to half a grain every two hours. The bowels were kept open by enemas of mutton or chicken broth, administered every second day. At A one time he tried bromide of ammonia, with no effect; also the bromide of potassa, with similar results. The spasms, after the sixteenth day, began gradually to subside, and after a lapse of twenty-six days left him entirely. The hand healed kindly during the first three or four days of the attack of tetanus, and the boy recovered rapidly. There appeared to be a peculiar hemorrhagic tendency about this case. He is of a leucophlegmatic temperment, rather large, and somewhat fatter than usual for boys of his age. His mother died of phthisis pulmonalis. He had had an attack of scarlatina auginosa, about three months previous to the first attack of hemorrhage, but there was none of the sequelae common in such cases, although he was much enfeebled by the. disease, and continued peevish and fretful. The scarlatina, I am inclined to believe, acted as a predisposing cause to the . Wood mentions it as one of the causes that sometimes produce the disease, and in this case it seems very plausible to consider it so, as previous to the attack of scarlatina there was none of the tendency to hemorrhage, but immediately after, the father noticed a tendency to ecchymosis upon the child's the least bruise, so that I am led to believe that the really followed immediately after, but was not discovered until the hemorrhage took place. The pimple, as the father supposed it to be, I believe was one of the petechial spots in the form of a bloody blister, and that he was mistaken in regard to the escape of pus from it when he punctured it, as he was not aware that there was any upon the body of the child until my preceptor showed them to him. There was but one crop of them, for as soon as the hemorrhage appeared they ceased to show themselves. At the time of the second attack, the child appeared to be in good health, with the one exception that there still remained a slight tendency to eccymosis, but upon his receiving the scratch upon the temple, the tendency to hemorrhage of the same severe form again showed itself. Of course, as would be naturally supposed, after the child recovered from two severe hemorrhages of fourteen days each, he was very much debilitated, and almost bloodless, for I have seen him loose almost a pint of blood at one dressing of the wound, the hemorrhage was so severe. He was, I think, the whitest piece of humanity I have ever seen. The third attack, which was only about two months after the second, hardly time for him to regain his strength, was, as I have said, caused by a slight cut from a piece of glass. The same hemorrhagic tendency still remained, and was equally as unmanagable, and, like its predecessors, lasted just fourteen days. Then came the attack of tetanus as soon as the was stopped and the hand began to heal. The cause of which was, without a doubt, the debility arising from the hemorrhage. In the paroxysms he ground out two of the back teeth of the left side and bit his tongue fearfully, the blood from which formed in a pretty firm clot, so that it had to be removed by a pair of forceps, for fear of its suffocating the child, and I am sure that any one would have thought just as all who saw him, that he could not possibly live through these spasms, now that he was so reduced, and yet they continued in their most severe form for sixteen, and in all twenty-six days, when, as I have said, the child recovered, and is now as healthy a looking boy as one might wish to see. There is one or two things in the treatment of this case worth notice. First. I have neglected to say that the wounded hand and arm were put in a bowl of warm water as soon as a spasm came on, and it afforded great relief. Second. The cessation of the hemorrhage, upon the application of the bark, charcoal and yeast poultice, after having resisted all other known means; and Third. The benefit derived from the very large doses of tinct. ferri chloridi, which seemed to be the only means of checking the hemorrhage. He took as much as 25 drops every three hours; besides this the enormous quantities of wine and whiskey, as well as quinia and morphine, all having the desired effect. The recovery of the patient seems to me almost a miracle, and is at least very remarkable. It is one of those cases that go to show us how much our patients will go through and still recover, and that while life still remains, wTe may yet hope to afford relief, or even better, see our patient recover his health entirely, a pleasure which to the medical man is so great that none but those who have experienced it can realize the joy it affords him. lie feels, in such a case, that he has gained the great object that prompted him to study medicine, that of his fellow-creature from suffering, or, as it were, him from the grave. A man who gains such triumphs as this over the greedy hand of death, has in my mind the most noble calling God has given to any of his creatures.
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p 11 r t a. The Opium Habit, with Suggestions as to the Remedy. : Harper & Brothers, Franklin Square. 1868. This is a neatly-published volume of 334 pages. Its are as follows: Introduction; A Successful Attempt to abandon Opium; De Quincey's "Confessions of an English Opium-Eater"; Opium Reminiscences of Coleridge; William Blair; Opium and Alcohol Compared; Insanity and Suicide from an Attempt to abandon Morphine; A Morphine Habit overcome; Robert Hall John Randolph William ; What shall they do to be Saved? Outlines of the Opium Cure. From these headings, every reader will be able to judge concerning the contents of the book. It is well calculated to interest and instruct both non-professional and professional readers. For sale by S. C. Griggs & Co., Chicago. Price, $1.50. A Treatise on Physiology and Hygiene; for Schools, Families, and Colleges. By J. C. Dalton, M.D., Professor of in the College of Physicians and Surgeons of New York. With Illustrations. New York: Harper & Brothers, Publishers. 1868. This is a small octavo volume of near 400 pages, printed on good type and paper, with many cuts as illustrations. The author has succeeded well in presenting the leading facts of physiology and hygiene, in a small compass, well arranged for study in schools and academies, and for reference by the reader. For sale by S. C. Griggs & Co., Chicago. Price, $1.75. Lectures on the Study of Fever. By Alfred Hudson, M.D., M.R.C.A., Physician to the Meath Hospital. Philadelphia: Henry C. Lea. 1869. For sale by W. B. Keen & Co., Chicago. This is a full-sized octavo volume of 316 pages. The have done their part of the work well; and the author has given a very interesting discussion of the whole subject of fevers. Annual Report of the Surgeon-General of u. S. Army for 1868. We have received a copy of the Surgeon-General's Annual Report, and read it with interest and pleasure. Below, we copy the greater part of the report: At the date of my last Annual Report, epidemic cholera and yellow fever prevailed among the troops in various sections of the country, a very full and exhaustive report of which was published for the information of medical officers of the army, in Circular No. 1, War Department, Surgeon-General's Office, June 10, 1868. To this date, there has been no well- case of epidemic cholera or yellow fever reported as occurring among troops in the present year. * The Monthly Reports of sick and wounded, for the fiscal year terminating June 30, 1868, received in the Division of Records of this Office to this date, represent an average mean strength of forty-five thousand two hundred and fifty-seven (45,257) white, and four thousand seven hundred and (4,774) colored, troops. For the white troops, the total number of cases of all kinds reported under treatment was one hundred and thirty-one five hundred and eighty-one (131,581), or two thousand nine hundred and eight (2,908) per thousand (1,000) of strength nearly three entries on the sick report, during the year, for each man. Of this number of cases, one hundred and eighteen thousand nine hundred and twenty-five (118,925) were for alone, and twelve thousand six hundred and fifty-six (12,656) for wounds, accidents, and injuries; being two six hundred and twenty-eight (2,62b) per thousand (1,000) of strength for disease, and two hundred and eighty (280) per thousand (1,000) of strength for wounds, accidents, and . The average number constantly on sick report was two thousand eight hundred and fifty-two (2,852), of whom two thousand five hundred and ten (2,510) were sick and three and forty-two (342) wounded, or fifty-five (55) per (1,000) constantly under treatment for disease, and eight (8) per thousand (1,000) for wounds and injuries. The total number of deaths from all causes reported, was one thousand three hundred and fifty-three (1,353); of which, one thousand one hundred and seventy-five (1.175) were from disease, and one hundred and seventy-eight (178) for wounds, accidents, and injuries; being at the rate of twenty-six (26) deaths from and four (4) from wounds, to each thousand (1,000) of' strength. Of the deaths from disease, four hundred and twenty-seven (427) were from yellow fever, one hundred and thirty-nine (139) from cholera, and six hundred and nine (609), or thirteen (13) deaths per thousand (1,000) of strength, from all other diseases. The proportion of deaths from all causes to cases treated, was one (1) death to ninety-seven (97) cases. Nine hundred and eighty-four (984) white soldiers, or (22) per thousand (1,000) of strength, were discharged upon Surgeon's certificate of disability. For the colored troops, the whole number of cases, of all kinds, treated, was fourteen thousand six hundred and sixteen (14,616); being at the rate of three thousand and sixty-one (3,061) per thousand (1,000) of strength, or three (3) cases of sickness for each man. Of this number, thirteen thousand five hundred and fifty (13,550) were for disease; being two eight hundred and thirty-eight (2,838) per thousand (l^OO) of strength; one thousand and sixty-six (1,066) were for wounds, accidents, and injuries; being two hundred and twenty-three (223) per thousand (1,000). The average number constantly on sick report was two hundred and eighty-three (283); of whom two hundred and forty-eight (248) were sick, and (35) wounded; being at the rate of fifty-two (52) per (1,000) constantly under treatment for disease, and seven (7) per thousand (1,000) for wounds, accidents, and injuries.' The total number of deaths reported was two hundred and sixty-eight (268); of which, two hundred and forty-two (242) were from disease, twenty-six (26) from wounds and injuries; being at the rate of fifty-one (51) deaths per thousand (1,000) of strength from disease, and five (5) per thousand (1,000) from wounds. Of the deaths from disease, twenty-five (25) were from yellow fever, eighty-nine (89) from cholera; leaving one hundred and twenty-eight (128), or twenty-seven (27) per (1,000) of strength, from all other diseases. The of deaths from all causes to cases treated, was one (1) death to fifty-five (55) cases. Ninety (90) colored soldiers, or nineteen (19) per thousand (1,000) of strength, were discharged on Surgeon's certificate of disability. During the year, the records filed in the Record and Pension Division of this Office have been searched, and such official relative to deaths, discharges, and treatment as they contain has been furnished, in reply to the inquiries of the Pension Bureau, in 16,786 cases; Adjutant-General, U.S.A., in 15,582 cases; Paymaster-General, U.S.A., in 473 cases; and in 1,929 cases to other authorized inquirers; making a total of 34,770. In the Division of Surgical Records, the histories of 74,954 cases of wounds and injuries have been transcribed, chiefly from field reports, hospital case-books, and registers of 1861 and 1862, and the earlier part of 1863. The records of the Office, in regard to injuries of the head, face, neck, thorax, abdomen, spine, and pelvis, have been and studied. Illustrative cases have been selected and written out in minute detail, while numerical tables have been prepared, exhibiting the progress arid results of the different classes of injuries to which these individual examples belong. To illustrate these injuries, for future publication, there have been completed, during the year, 8 chromo-lithographs, 8 , and 3 diagrams. There have also been prepared, the year, 122 woodcuts, to be intercalated in the text, descriptive of the various classes of injuries and operations. 500 pages of manuscript are in readiness for the printer, and a large amount of the statistical material is in such a state of forwardness that it can be made ready for the press at a few weeks' notice. To make the publications of this Office as as possible, in relation to the results of the major injuries and operations, and especially in regard to the excisions of the larger joints, and other operations embraced under the general designation of conservative surgery, much time and labor have been expended in tracing the ultimate of patients who have undergone such mutilations. This has been accomplished to a very satisfactory degree, through' the cooperation of the examining surgeons of the Pension , of the Surgeons-General and Adjutants-General of the several States, of retired volunteer medical officers, and of physicians. Besides the digestion and tabulation of the surgical data pertaining to the late war, there have been and consolidated, 699 quarterly reports of post-hospitals, 34 reports of the examination of men, who, having been wounded, presented themselves for reenlistment at recruiting stations, and 32 special reports of surgical operations. The Army Medical Museum continues to increase in value and usefulness. During the year, 673 specimens have been added to the surgical section, 121 to the medical section, 202 to the section of comparative anatomy, 687 specimens and 114 photographic negatives of microscopical specimens to the section. An anatomical section, of 163 specimens, has been formed, and is rendered of especial interest by the large proportion of typical crania of the North American which it contains. A collection of 187 specimens of Indian weapons and utensils has also been added. 266 specimens, the histories of which could not be found at the period of publication of the catalogue of the surgical , have been identified and restored to the collection. For purposes of exchange with other museums, or with learned , either for specimens or publications, 4,472 photographs, illustrative of injuries and operations, have been printed. There were, during the year, 14,448 visitors to the Museum, many military surgeons of eminence. On the 30th of September, there were 289 garrisoned posts in the various Military Departments, besides an almost equal number of detachments on temporary duty, throughout the South, and on expeditions, or protecting the lines of travel on the plains, requiring medical attendance. The number of and assistant-surgeons being altogether inadequate to meet this demand, it has been necessary to employ , especially at the South, where but few of the physicians could take the oath necessary to their payment, and the fees for attendance in individual cases would be far in excess of the contract rates. The number of physicians so employed upon the 30th of September was 282, at rates of varying from $45.00 to $125.00 per month; but a large proportion of these will be dispensed with so soon as the troops are concentrated in winter-quarters, and the condition of public affairs will admit of the discontinuance of the small garrisons throughout the States recently in rebellion. Since the date of my last Annual Report, 3 surgeons and 2 assistant-surgeons have died, 8 assistant-surgeons have , 2 assistant-surgeons have been dismissed, and 1 -surgeon cashiered total, 16. A medical board, for the examination of candidates for as assistant-surgeons, U.S. Army, and of for promotion, is now in session in New York City. There are now 49 vacancies in the grade of Assistant-. Most respectfully, your obedient servant, J. K. BARNES, Surgeon-General, U.S. Army.
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Or (Minifliu. CLINICAL CASES OF CONTINUED FEVER. THERAPEUTICAL ITEMS. THE VALUE OF STRYCHNINE IN CERTAIN PATHOLOGICAL . By N. S. DAVIS, M.D., Professor of Principles and Practice of Medicine in Chicago Medical College, and of Clinical Medicine in Mercy Hospital. Case I. A. B., aged about 22 years, was admitted to the medical wards of Mercy Hospital, October 17th, 1868. He was reported to have been sick in bed one week, but we could learn nothing reliable, concerning either his symptoms or , during that time. At the time of admission, his of countenance was dull; the surface, especially of the face, hands, and neck, was suffused with a dark, dingy , dry, and temperature moderately increased; pulse 120 per minute, quick, and weak; lips and mouth dry; tongue with a thick coat, dry and brown along the middle of the dorsal surface; abdomen moderately distended, tympanitic, and presenting a few small, red papules on its surface. He was reported to have had five or six thin intestinal evacuations per day, for two or three days past. The chest was resonant and natural, except dry bronchial rales over both sides. The faculties dull, drowsy, and wandering, so much so as to him incapable of giving any reliable intelligence. His muscular movements were unsteady and tremulous. He was directed to have two or three tablespoonsful of and wheat-flour porridge every two hours for nourishment, with whey, bread-water, or milk and water for drink; and a teaspoonful of the following emulsion every three hours: I^a. 01. Terebinth., . Opii, diij. Pulv. G. Arabic, 1 __ t... White Sugar, J aa' 51,J' Rub together, and add Mint Water, SSiij. Mix. He continued this treatment two days, during which time his bowels remained quiet; but his urine passed involuntarily, and he continued to exhibit all the symptoms of a strongly-marked typhus condition. The abdomen was full and tense, the pulse very soft and frequent, and the mind somnolent and . On the evening of the 19th, an enema of warm water was administered, which was followed by a moderate evacuation of faecal matter and some flatus. During the latter part of the night he had another large evacuation in bed, which was thin and freely intermixed with blood, and the urine continued to pass without his notice. At the clinic hour on the 20th, the whole cutaneous surface was dingy, with slowness of capillary circulation; the mouth and tongue very dry, with constant to gather dark sordes on the lips and teeth; mind very somnolent and muttering; respiration slow and irregular, with sharp, dry, bronchial rales; pulse 128 per minute, and weak; but less distention of the abdomen than previously. It was evident that the depression of the excito-motory nervous , as indicated by the slow and irregular respiration, feeble circulation, and relaxation of the sphincters, was directly threatening the life of the patient; while the copious intestinal discharge, largely intermixed with dark blood, indicated a of the mucous membranes scarcely less critical. To counteract, as far as possible, the first of these conditions, the patient was directed to have a teaspoonful of the following formula every four hours: 1^. Strychnine, 1 gr. Nitric Acid, . Opii, 5uj. Simple Syrup, 1 __ Water, faa' 5iss' Mix. To aid the mineral acid and opium in restraining the further intestinal discharges, the emulsion of oil turpentine and of opium was continued, in doses of a teaspoonful each of the doses of the solution containing the . For nourishment, he was fed regularly two or three tablespoonsful of sweet-milk and wheat-flour porridge every hour, sometimes exchanging it for the same quantity of , well salted. No further intestinal evacuations occurred, and after about 36 hours he ceased to dribble his urine in bed, and voided it regularly. After he had followed this treatment punctually for three days, he became less somnolent, and exhibited less muttering and subsultus, but his skin remained dry; pulse soft, frequent, and weak; tongue dry, with dark sordes on the lips and teeth; bronchial rhonchi over both sides of the chest, with dulness over the lower and posterior parts; and abdomen tympanitic. The same treatment was continued, with the addition of a warm-water enema, which procured a slight movement of the bowels, until the 27th of October. During the 25th, 26th, and 27th, the patient gradually passed from his state of somnolency and muttering to that of morbid vigilance or constant , with less subsultus, and a slight improvement in the of the mouth and tongue, but the mind still wandering; pulse soft, weak, and frequent; and commencing bed-sores over the sacrum and trochanters. Thinking that the change from mental drowsiness to constant wakefulness might be the result of the continued action of the strychnine on the nervous , directions were given to have the interval between the doses extended to six hours, and fifteen grains of bromide of ammonium to be given at bedtime; all other directions the same as before. On the 28th, it was found that the bromide had failed to sleep, although the dose was repeated a second time, and the patient appeared in all respects more exhausted and than on the day previous. The emulsion and the solution were again given, at intervals of four hours, or two hours apart; and instead of trying further the bromide to overcome the morbid vigilance, fifteen drops of chloroform were' added to each dose of the emulsion. The nourishment to be continued as before. This treatment was continued until November 1st, with a very gradual but marked improvement in the condition of the patient. The febrile heat had diminished; the skin was better color; sordes gathered less rapidly on his lips and teeth; the edges of the tongue were moist, though the middle was still dry and ; the mind less wandering, with intervals of quiet sleep. The bowels had not moved except by means of a warm-water enema, which had been given about once in three or four days. The last enema was followed by an evacuation of firmly-, healthy-looking faeces. The strychnine solution was still continued every four hours, but six grains of Dover's and four of pulverized gum camphor were given instead of the emulsion of turpentine, etc. Two days later, November 3d, it was found that the of convalescence had vacillated, being much more every alternate day, and two grains of sulphate of quinine were given between the doses of strychnine solution, while the Dover's powder and camphor were limited to a single dose at night. This treatment was continued until May 9th, when was fully established. The bed-sores over the sacrum and trochanters had been treated by an application of the tincture of the chloride of iron, daily, and were improving; but the patient was very feeble. The solution containing strychnine and nitric acid was every six hours, with the quinine between. On the 11th, the solution was restricted to a teaspoonful three times a day, and the quinine to twice a day. From this time the patient gained rapidly, until his recovery was . Case II. Mr. R., aged 25 years, was admitted into the in the early part of November. About six days , he had been attacked with a chill, so decided as to make him think he had the commencement of an intermittent. He had felt unwell during the preceding three or four days. When the chill occurred, he called a physician, who gave some powders, and followed them by a cathartic. The latter operated freely, and during the succeeding three days he had from twelve to fifteen intestinal discharges per day. It was at the end of these three days that he was brought to the hospital. On examination, it was found he was laboring under all the symptoms of continued fever, with great . He was first given the emulsion of oil of turpentine and tincture of opium, in doses of a teaspoonful every three hours, until the intestinal discharges should be stopped; with milk and flour porridge for nourishment. The next day his bowels had become quiet, but he presented every symptom of profound typhus: countenance dull; color of skin brown or dingy; capillary circulation feeble; pulse 124 per minute, soft and weak; abdomen slightly tympanitic, and bowels quiet; some subsultus, and constant delirium; and once hemorrhage from nose. A slight papular eruption was discernible over his chest and abdomen. He continued the emulsion three times a day, and in addition took a teaspoonful of the solution of , nitric acid, and tincture of opium every four hours, same proportions as already stated in the preceding case; and the same strict attention to the giving of bland nourishment. The further increase of prostration was arrested in hours, but the same treatment was continued, without change, for one week; during which time, a slow but steady improvement took place. The emulsion was then discontinued; the strychnine solution continued every six hours, with two grains of quinine alternated with it, and convalescence was fully established at the end of the second week after admission into the hospital. Case III. Mr. II., native of Ireland, aged 27 years; ; had been sick four weeks before admission into the . At present, countenance dull; skin dry, congested, above the natural temperature; lips thin, retracted, and teeth covered with dark sordes; tongue covered with a dark-brown, dry coat, fissured; mouth dry; mind dull and wandering; much , the hands trembling constantly, and the tongue so that he could neither run it out nor speak plainly. His urine dribbled in bed, and a somewhat extensive superficial bed-sore existed over the sacrum. The abdomen was neither distended nor tympanitic, but he had from one to three thin faecal evacuations daily. Pulse 130 per minute, soft and weak; respiration accelerated, but no thoracic dulness or bronchial rales. In this case, impairment of the functions of the nervous and the general exhaustion were so prominent, that the patient was given at once the same strychnine and acid used in the other cases, in doses of a teaspoonful every four hours; five grains each of pulv. Doveri and pulv. g. camph. at night; and the prompt attention to nourishment, of sweet-milk and wheat-flour porridge, and beef-tea salted with chlorate potassa, given in small but frequently doses. On the third day, he had so much improved that he could speak plain, protrude his tongue readily, and there was but little tremor of the extremities. The strychnine solution was then given only once in six hours, and a powder consisting of sulph. quinine 2 grs., pulv. Doveri 5 grs., pulv. g. camph. 3 grs., was given alternately with it; with same attention to diet as before. He continued steadily to improve, and in eight days after his admission into the hospital (five weeks from the of his fever), his convalescence was fully . These cases strikingly illustrate a most important stage in the progress of the more severe cases of continued fever. It is a stage in which, in addition to the ordinary deterioration of the blood, and more or less local changes in the abdomen and chest, we have great depression or failure in the functions of the nervous centres; as indicated by the soft, weak pulse, the muscular tremors, the relaxation of the sphincters, etc. To counteract this condition, we have found no remedy equal in value to strychnine in solution with nitric acid, as given in the preceding cases. Tincture of opium is added, whenever the intestinal discharges are thin, or too frequent.
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UTILIZATION AND CONTAGION. Dr. Wm. T. Thomas, of New York, has furnished a very and thoughtful article in the Transactions of the New York Medical Society. In 1863 there were 15,369 tenement houses in New York, with a population of about 500,000. There are only two in which the mortality in New York and London are nearly equal, viz., Small-Pox and Remittent Fever. Of the former disease, 1 in 1384 of the population die in London; and 1 in 1303 in New York. Of remittent fever, 1 in 32,954 of the population in London, and 1 in 34,615 in New York. New York has a less mortality than London, in measles, scarlet fever, quinsy, whooping-cough, erysipelas, carbuncle, influenza, rheumatism, zymotic diseases generally. Thus, 1 in 1772 of population die of measles in London, and only 1 in 4186 in New York. As many as 1 in 585 of population die of scarlet fever in London, and only 1 in 4186 in New York. 1 in 35,802 of quinsy, to 1 in 81,818; 1 in 1333 of , to 1 in 7887; 1 in 6561 of erysipelas, to 1 in 7258; 1 in 51,786 of carbuncle, to 1 in 250,000; 1 in 70,773 of , to 1 in 81,818; 1 in 6666 of rheumatics, to 1 in 18,544. New York has a greater mortality than London in diphtheria, croup, typhus and typhoid and puerperal fever, dysentery, , cholera, and ague. Thus, only 1 in 3755 of population die of diphtheria in London, while as many as 1 in 918 die in New York; 1 in 3111 of croup, to 1 in 901; 1 in 1032 of typhus and typhoid fevers, to 1 in 854; 1 in 13,181 of puerperal fever, to one in 10,742; only 1 in 26,851 of dysentery in London, to 1 in 3146 of population in New York; 1 in 1212 of , to 1 in 380; 1 in 18,230 of cholera, and 1 in 7429; 1 in 152,681 of ague, to 1 in 56,259. Of all other zymotic , 1 in 116,000 of population die in London, 1 in 150,000 in New York. In the tenement houses of New York every 6-story building averages 24 families, of five or more persons each. Each person has a little over 15 square feet of ground area, and 480 cubic feet of air space in the whole house. In the apartments the allowance of air space is only 317 cubic feet, and in the but 89 feet to each person. A full 1000 cubic feet of air space are required. The air (if pure) which an adult healthy man breathes in contains only 0.4 per 1000 volumes of carbonic acid; while that he breathes out contains 40 volumes per 1000, in addition to fetid organic maker and water-vapor to saturation. It requires at least 2000 cubic feet per hour, of pure air, to keep the carbonic acid at 0.5 or 0.6 per 1000 volumes, and to entirely the fetid smell of organic matter exposed, to say nothing of the filth and smell of persons, clothes, cooking and food-utensils, remains of food and offal generally. The carbonic acid of respiration is equally diffused through the air of a room, and is very rapidly got rid of by opening windows. But neither the fetid or organic matter, nor the watery vapor, diffuse rapidly nor thoroughly. At least 30 grains, and perhaps 240 grains, of organic matter are given off from the lungs and skin, and from 25 to 40 ounces of water in 24 hours. The organic matter is made up of small particles of epithelium and fatty matter detached from the skin, and partly of an organic vapor given off from the lungs and mouth. It has a fetid smell, and is retained in a room for a long time, sometimes for 4 hours, even when there is free , showing that it is oxidized very slowly. It is absorbed most by wool, feathers, damphrally and moist paper; and least by straw and horse-hair. It is molecular, and floats in clouds in the air, when the odor of it is not always equally diffused through a room. A large quantity of carbonic acid, derived from respiration, always indicates a large quantity of organic matter, the smell of which generally becomes perceptible when the carbonic acid reaches 0.7 per 1000 volumes; and is very strong when it amounts to 1 per 1000. Besides the gaseous products strictly derived from the lungs, the air of most dwelling-houses, when examined by the aeroscope, is found to contain many epithelium cells; most of which are evidently derived from the skin. They are rubbed off and then float through the air, and often become the carriers of the of scarlet fever and measles, as they are saturated with poison when these diseases prevail. The epithelium of the mouth, throat, and nostrils, are foliated, and in diphtheria, typhus and typhoid fevers, and thus load the air with poisonous particles. In all tainted atmospheres of this kind, it seems that the germs of infusoria abound to a much greater extent than in pure air. The possibility of a direct transference from body to body of cells (or epithelium) undergoing special changes, is thus placed beyond doubt, and the doctrine of contagion receives an additional elucidation. It remains to be seen whether pus or epithelium cells, becoming dried in the atmosphere, can again, on exposure, become revivified. Some protophytes, like the prolococcus pluvialis, may be dried, and yet retain their vitality for years, and may be flown about in atmospheric currents. The effect of the fetid air containing organic matter, except of carbonic acid and water, is very marked on many people, causing heaviness, headache, inertness, nausea, or even decided symptoms, such as heat of skin, quick pulse, furred tongue, loss of appetite, and thirst, lasting for 24 or over 48 hours. Usually, the persons who are compelled to breathe such an atmosphere are, at the same time, sedentary, and remain in a constrained position for many hours, are also underfed, and intemperate. They soon become pale, lose their appetite, decline in muscular strength and spirits. They are very apt to become scrofulous and consumptive. Baudelocque long ago asserted that impure air is the great cause of scrofula, and that hereditary predisposition, syphilis, uncleanliness, want of , bad food, and humid air, are, by themselves, non-effective. In the Dublin House of Industry, where consumption was so common as to be thought contagious, there wtere in one wtard, 60 feet long and 18 broad, 38 beds, each containing four children; the atmosphere was so bad that, in the morning, the air of the ward was unendurable. The food was excellent, and the only causes for the excessive prevalency of consumption were foul air and want of exercise. In the prison of Leopoldstadt of Vienna, which was very badly ventilated, 378 prisoners died out of 4280, or one in twelve; and of these, no less than 220, or nearly two-thirds, died of consumption. There were no less than 42 cases of acute military tuberculosis. In the well-ventilated houses of correction, in Vienna, only 43 died out of 3037, or 1 in 7.1; and of these only 24, or 1 in 126, died of phthisis. (But consumption is only a personal and family affection ; it is not handed from mouth to mouth, or from person to person, and thus made to invade the whole community.) The most important class of diseases produced by impurities in the atmosphere are certainly caused by the presence of organic matter floating in the air; and thence come all specific and contagious diseases. This organic matter may be present in the form of impalpable particles, or of moist or dried epithelium and pus-cells. It may be contained in the substances discharged or thrown off from the body, as in the discharges from the nose, throat, and lungs, of measles, scarlet fever, diphtheria, and whooping-cough patients; or in the epidermic scales of measles or scarlet fever or , or in the crusty scabs and pus of small-pox; or in the changes in the discharges of typhus fever, cholera, dysentery, etc. And from the ease with which, in many cases, organic matters are absorbed by hydroscopic substances, it would appear that they may often be combined with, or in, the water of the atmosphere. The specific poisons differ greatly in the ease with which they are oxidized and destroyed. Thus, the poison of typhus is very easily got rid of by free ventilation, by means of which it is diluted and oxidized, so that it becomes innocuous at the distance of a few feet. (But if the streets, gutters, and sewers of houses in which typhus prevails are loaded with filth, and the scanty back yards are defiled by offensive cesspools and privies, free ventilation with pure air is impossible; then the volatile poison of typhus fever may unite itself with the impurities of the atmosphere, and perhaps convert the whole into a virulent miasma.) This is also the case with the poison of Oriental plague. But the poisons of small-pox and scarlet fever will spread in spite of very free ventilation, and they retain their power of causing the same disease for a long time, and, in the case of scarlet fever, for months. (Then the scabs and epidermic scales are doubtless the active agents of . In the one case, the poison may be a mere cloud of ; in the other it may be contained in the epithelium and pus-cells, thrown off from the skin in both cases, and from the throat also in one, which adhere to walls, clothing, or carpets, become partially dry; but then, becoming dislodged by , dusting, etc., are blown up into the air and inhaled into the lungs of some one, where they again become active by means of warmth and moisture. Thus scarlet fever, measles, small-pox, diphtheria, whooping-cough, typhus fever, etc., come up from the tenement houses and filthy parts of the cities, and are to the well-to-do and wealthy. Convalescent small-pox and varioloid patients return to their work with their hair filled with crusts and scabs, and their clothes defiled with dried pus. Scarlet fever and measles convalescents visit the houses of their patrons and friends with their unwashed heads filled with the scurf of measles and scarlet fever scales, and scatter it broadcast into the air, from whence it is inhaled into the , throat, or lungs, of some unsuspecting creature. They come also with their clothes contaminated with the dried of their children suffering with diphtheria and , and shake the dust of these poisons in the houses of the rich and philanthropic. Weavers, lace and ribbon makers, just recovering from small-pox, contaminate the new goods they manufacture, and dirty bank bills are often smeared with the same dangerous elements. Ed. New York Med. Gazette.
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$if Iff tifl pg. THE HYGIENE OF INFANCY: ABSTRACTS OF LECTURES DELIVERED AT THE BELLEVUE HOSPITAL MEDICAL COLLEGE, By GEORGE T. ELLIOT, Jr., M.D., Prof, of Obstetrics and the Diseases of Women and Children. Gentlemen: The subject to which I shall call your , in the four lectures of this preliminary course, is of the first importance to the rational study and treatment of the of infancy; for many of these owe their existence to of the laws of hygiene. To diminish the terrible though to a certain extent mortality of infancy, to avert evil influences, to develop the good, to diminish the necessity for drugs, and so to carry these helpless little ones through the perils of infancy that they may reach the less dangerous years of childhood with well- constitutions, are tasks which demand both the and the application of the best hygienic laws. While it will be impossible for me to attempt to exhaust the subject, I shall avoid at least useless details, and endeavor to fix your minds only on what may be direct and practical; nor shall I hesitate to set the hygienic indications in a clearer light by illustrating pathological conditions which may follow their neglect, as well as those which may forbid success. If time would permit our thorough study of the subject, we should commence with those hereditary predispositions and which affect for good or ill the foetus and the man, and those conditions of the mother's health and hygiene which are liable to affect gestation; but, passing over these interesting questions, we come at once to a broad division of the subject. I. DUTIES OF THE PHYSICIAN TO THE NEW-BORN CHILD. Establishment of Respiration. Hitherto, in the womb, it has drawn its supply of oxygen from the mother, through the circulation; now it is obliged to obtain this vitalizing agent from the outer world, through organs whose functions have rested in abeyance. Hence our first duty is to see that the function of respiration is fully established. Fully, I say, because it not unfrequently happens that unless this be done, portions of the lungs are left unexpanded, as they were in the womb before respiration was ; and thus, sufficient machinery not being set in action, after a while oxygenation is not thoroughly accomplished; the respiration labors; the vital power fails; more lung tissue ceases to work, perhaps collapses; the surface becomes blue, the nerve tissue poisoned by black blood, the senses benumbed, the vital warmth displayed by the advancing coldness of death. This unexpanded condition of the air-cells, which may obtain from the failure to establish respiration, and to which the lungs of infants are liable to revert in conditions of debility and catarrh, is knowm under the name of atelectasis. Prevent these dangers by insuring such full and continued respirations as may make you morally certain that all the cells have been distended. Hearty and continued cries from the child generally attest this result. Now children are often born in natural labor, and in labors attended by special dangers, in a condition of apparent death. A broad distinction is drawn by authors between those dead or apparently dying, with a congested or a pallid surface of the body. Treatment has been formulated in with these obvious signs. I do not dwell upon them. No greater congestion of the internal organs has ever come under my observation, in the autopsy of these children, than in cases where the surface has been pallid. Congestion of the skin does not kill; it is congestion and extravasation within that we dread. Skin congestion accompanies internal congestions, but these latter may exist without the former. Signs of strength and vigor may permit treatment contraindicated in premature and puny children. Do not believe that the liver and brain must be pallid, because the skin is white. Do not assume that, because a child is born and shortly dies with a thoroughly congested and blue surface, it died from "the blue disease," or cyanosis. Cyanosis to constitute a disease, must be recurrent; or if believed to have caused the death under the circumstances we are considering, something more than a patent foramen ovale must be shown by the autopsy. The foramen ovale would be patulous, as a matter of course. How could it have closed in so short a time, even if its patency were assigned as the cause of cyanosis? When, therefore, children are born and do not respire, is blood to be let? Is the indication to be based on the color of the skin? What method is to be preferred? Shall we allow blood to flow from the cord, or take it by leeches? I mention the latter only for condemnation. If you allow the blood to flow from the cord, hold it well, as you would a cut axillary artery, so that you can control it at once. A teaspoonful is a limit beyond which I would very rarely go. But I very seldom allow any blood to flow, and still more rarely until I have rapidly tried the measures to which I now invite your attention. respiration thoroughly, and the sluggish circulation becomes active, the ruddy glow of health colors the skin. Free the mouth and nose from mucous and vaginal discharges. Note that there be no malformation. It has been noticed that a simple band of skin over both nostrils, easily divided with a bistoury, has powerfully affected the respiration of a new-born child. Women relatively breathe more with the thorax, men with the abdomen; perhaps the new-born child, destined in to rely so much on the nostrils, may physiologically need them more than we. Free the nostrils and the mouth , both in order to admit air, and because in the first inspirations these materials may be drawn into the air-passages and occlude the bronchi. Such conditions may have obtained in utero from premature inspiratory efforts. Liquor amnii and meconium may be demonstrated in the air-passages by the microscope. The child yet contained within the unbroken pouch, compelled to respire prematurely by reflex , or by that respiratory need awakened by interference with the placental circulation, may thus be drowned in the womb of its mother, and the cause of death demonstrated at the autopsy. Try to prevent this accident to the respiratory when the child is born, and in your hands. When the child is separated from the placenta, if the of the respiratory need, and the transition to the cool air of the room are not sufficient, spank it over the buttocks with the tips of your fingers, and rapidly use Marshall Hall's or 's method for the resuscitation of those who have been drawn from the water. If not promptly successful, plunge the body of the child in warm water (which should be ready in advance), and then into cold water. You thus keep up the warmth, draw blood to the surface, and increase the shock of the cold . Spur the diaphragm and intercostals by brisk of water; a lump of ice or a column of water to the ; then back again to the warm water, so as to diminish internal congestion and the benumbing influence of continued cold. From the warm water place the child on a blanket, on the floor or bed, and thoroughly try Hall's or Sylvester's method. I prefer Hall's but use both, and have seen children saved exclusively by each. It is not necessary to draw the tongue forward. It is important to keep the chin in a line with the sternum, and to keep the trachea somewhat prominent. to prevent the child from getting too cold. Hot and cold water again. Slap, sprinkle, blow on the surface of the body, aid the slow and struggling expiration by gentle pressure on the chest. Have a battery on hand. Place the poles on the sides of the neck (third and fourth cervical), and over the . The theory is to stimulate the phrenic nerve. The battery, however, under my observation, has proved less than the other methods detailed, and I therefore only the most important application. During this time of blood will have been considered. Do not let the water be too hot; you may scald the insensible child. Too hot water has been asserted to have caused trismus. Shall you inflate the lungs with your own breath? If so, be sure that the air enters the larynx. With skilful manipulation a catheter makes this . Generally the stomach is blown up, unless precautions be taken. Do not blow into the lungs so as to produce emphysema. I have seen emphysema, however, in new-born children, whose lungs had not been thus inflated. If you inflate the lungs, do not blow when the child is making a respiratory effort. In one word, my personal experience makes me rank this method of inflation as secondary to alternations of heat and cold, stimuli, and the methods of Hall and Sylvester. Persist in these trials as long as the heart can be felt or heard, and a little longer than it can be heard. The quickest way to feel the heart is to put the pulp of your finger under the ribs and lift up the diaphragm. Pulsation can be felt thus when it cannot be touched through the thorax. Persist a while after the heart has apparently ceased to beat. A life for which you are responsible hangs upon the effort. There is more surprising than the tenacity with which some infants cling to life, except the facility with which others lose it. But, gentlemen, all your endeavors will often fail. For your satisfaction, and for the satisfaction of the family, obtain an autopsy. 3Tie pathology of foetal life and of the still-born yields to none other in interest or value. It is a microcosm but too little explored. It is melancholy to see the neglect of the subject in practice and in the records of great hospitals. A still-born child one would suppose to be a child still-born from some unexplained and sufficient general cause. Start clear from such apathy, such delusions. The autopsy may show that you struggled against hope, that the establishment of was hopeless, or its continuance impossible. Gather this consolation when you can. Search at least for truth. The respiratory passages may be proved by the autopsy to be absent in whole or in part. Trachea or bronchi may be replaced by impervious cords. Cysts, peritoneal effusions, pleuritic effusions, may have developed themselves in foetal life, may not have killed the child, but may prevent air from reaching the lungs, the diaphragm from descending, the lungs from expanding. The pulmonary artery may be absent or barely pervious. The heart may be in front of the neck, within the abdomen, outside of the thorax; it may be unfitted for the strain of the altered circulation from malformation and from intra-uterine disease. The diaphragm may be open, and the intestines have crowded into the thorax and stopped the lungs from expanding. on the brain and into its tissue may have caused the death. These extravasations may have occurred before the labor commenced. I have said enough to show that you may have the consolation of knowing and proving that your has been discharged, that the cause of death bore no relation to your management of the labor, or to your choice and use of means to establish respiration, when respiration was impossible. Ligation of the Cord. In ligating the cord, always examine the umbilicus thoroughly for hernial protrusion. Cut far enough away from the body to leave space for a second ligature, in case it becomes necessary to apply it after the occurrence of hemorrhage. The gelatinous material composing the envelope of the cord is very apt to make the first ligature slip. Knots in the cord may be found, but they rarely produce death. Their occurrence has been explained by supposing that the head of the child passed down through a loop in the cord. The cord is often twisted about the neck; and it is sometimes necessary to use forceps to effect delivery in these cases; I have never, however, had to cut the cord before delivery. A cord shortened from this or other reasons may produce delayed labor; and, if the forceps be used, the resistance due to the cord may be felt upon attempting traction in increasing ratio to the advance. It is difficult or impossible to diagnosticate these cases, until the head is well down in the vagina, or until the head is delivered. Warmth and Ventilation. After having secured the of respiration, it is of the first importance to see that the infant be kept warm. Of all the young mammals, the human probably requires the most care in this respect. Yet instances may be cited indicative of the opposite . Children exposed in the streets and taken to foundling hospitals often die from cold. The competent motherly nurse takes the greatest care of the warmth of the child. Sleeping with its mother is the natural means for warming the child, a species of incubation, but is attended with liability to accidents; the child may be smothered beneath the bedclothes, by the mother or nurse, either accidentally or intentionally, overlaying it. The mother or nurse is also very apt to nurse the child too often at night, and thus institute a bad habit both for herself and for the infant. Moreover, the air of the mother's bed is more or less impure from the lochia. I now wish to advise you particularly to see that there is in the nursery a sufficient supply of fresh air. No illustrate my remark better than those made in the Dublin Lying-in Asylum, where for twenty-five years the was 1 in 6. On the introduction of proper ventilation, the mortality fell to 1 in 19|, and subsequently to 1 in 58|. A thousand cubic feet of space are ordinarily regarded as for an adult; a young child requires no less than an adult. Apart from the respiratory troubles overcrowding produces, it increases the liability to epidemics, to ophthalmia, and depraved nutrition. Residence. Very frequently it will be found that a change of residence will prove of decided benefit to the infant, when some depressing or contagious atmospheric influence exists in the neighborhood where the child is residing. A change from one part of the city to another may be sufficient. Often, however, the sea-side or the mountain may offer special claims, especially for escape from heat. Urination. It is of great consequence to see that the infant passes its water. Urine is secreted and passed in utero, and may be passed during and just after birth. In some children the urine has been retained, and the distention of the bladder has been so great as to prove a cause of delayed labor. Cystic kidneys have done the same. In one case the bladder was found capable of containing two quarts of urine; in other cases it has ruptured before birth. After birth, almost before the child draws its first breath, it often passes its urine. Should it not do so within the first twenty-four hours, we should learn why not. It may happen that the bladder was emptied immediately after or during labor. It may be that so little milk has been taken that the kidneys have not been called upon to act freely. Babies urinate in direct proportion to the amount of milk or liquid nourishment they receive, in a ratio five or six times as great in proportion to bulk as in the case of the adult. Hence, whenever we learn that the infant is passing but a scanty amount of urine daily, it is always safe to ask whether it is receiving milk enough from its mother or the lvet-nurse. Obstruction to the passage of urine may occur from , or the partial or total absence of the organs necessary to the function of urination; such as partial or complete absence of the urethra, absence of the bladder, with compensatory openings, or of the kidneys, or impervious ureters. Perhaps the bladder may be very capacious or atonic. A cause of obstruction to the flow of urine shortly after birth, in boys, is dependent upon simple agglutination of the urethral walls. (I have more found urine in the bladders of still-born boys than in those of still-born girls. It is natural that it should be so.) This condition is easily remedied by the introduction of a silver prob.e, curved into the form of a catheter; the urine generally trickles out along its sides, and then flows freely. The reflex irritation thus produced is often all that is necessary. you are told that the water does not pass by the natural outlet, always examine thoroughly for some abnormal opening through which it may be passing unperceived, especially for vesico-vaginal fistula, cloacae, and hermaphroditism. , but not very frequently, a condition occurs, known as hydronephrosis, in which the bladder and ureters may be dilated, so as to resemble the foetal intestines, and the kidneys affected by the pressure of the retained urine. In one case under my observation, in which this condition was found, my explanation was that, owing to the shallowness of the pelvis and the obliquity of its brim, the bladder had fallen forwards, after dilation had commenced, thus producing an angular flexure of the urethra or neck of the bladder, preventing the discharge of the urine, for the urethra was normal in size; accumulation had then occurred, and, by the "back-water" action, produced the changes in the urinary tract, distending the ureters, calices, pelves, and causing absorption of the cortical structure. of urine may also occur from pressure upon the ureter, as by the passage across it of a supernumerary branch of the renal artery. I have never seen a case in which puncture of the bladder was demanded, in the new-born child, for retention; but, if necessary, I should prefer the supra-pubic method. Cleanliness. The education of the infant should begin with the first days of its extra-uterine life, and a point of no little importance is to see that it does not lie in wet or soiled diapers. Let these be removed immediately after it has soiled them, and soon it will learn to indicate by its cries its disapproval of damp diapers. See that the napkins are not dried in crowded rooms before the registers. Moreover, if a child is allowed to lie almost constantly in its own excretions collected in the napkins, erythematous eruptions, or even ulcerations, will be formed upon its nates, and these may sometimes have a very suspicious appearance. Now, gentlemen, do not be in a hurry to all ulcerations you find upon the buttocks of an infant as necessarily syphilitic in character. Appearances should not always be interpreted against the infant. Uncleanliness, and neglect to apply other clean, dry napkins as soon as the first are soiled, is a very common source of sores about the infant's buttocks, simulating syphilitic cachectic ulcers. By removing the cause of the trouble, applying a mild lead wash or other lotion, and seeing that the child is well nourished, we can heal up these ulcerations without difficulty, and dissipate 'the mistaken diagnosis. In diarrhoea, redouble precautions: cleanliness, lead water, calamine powder, disinfectants. Passage of Faeces. The liquor amnii does not, as a rule, contain meconium. When the finger, introduced into the , encounters this, its presence is commonly supposed to indicate the death of the foetus, or a breech presentation. But even when there is no breech presentation, we should not lay too much stress upon this symptom when making our prognosis, except in so far as it is indicative of great danger to the foetus. There are very few positive signs of death of the foetus. to recognize the foetal heart-beat is not sufficient evidence that the child is dead. There are few very strong evidences of its death. No pulsation distinguishable, after a long lapse of time, in the cord; second, the perception by the finger that the parietal and occipital bones collapse and move about on , while the skin peels off on friction. If you do not by the touch that the child is putrid, try to deliver promptly, and revive it if possible. Always inquire, the first day after birth, if the infant has had a passage from its bowels. If it has not, examine it carefully. An examination of the external orifice, alone, is not sufficient. Introduce a probe into the rectum, and see whether it does not end in a cul-de-sac. It may be that parts of the intestines, which you cannot reach, consist only of fibrous bands, and in these various contingencies the question will arise as to the of an artificial anus. Obstruction of the intestinal canal may occur from infarction by an accumulation of epithelial scales. In children born without an anus, there may be a connection of the rectum with the vagina or the bladder. In the former case, we should make an incision in the median line, establish an anus in its usual situation, and, later in life, heal the fistula by the usual procedures. In the latter wait developments, or, if possible, follow the same course. Simple closure of the raphe or lower part of the rectum is the easiest malformation to detect and treat. When the arises as to the advisability of groping one's way with bistoury, scissors, and fingers, where the rectum ought to have been, and then of plunging a trocar into something above that we believe to be intestine, or when we select the alternative of an artificial anus, our duty is clear, to represent fully the and dangers to the family, with the limited chance of success in the last contingency. If the parents refuse, a painful and unsatisfactory operation need not be performed. If they assent, or saddle you with the whole responsibility of the decision, you must even make the artificial anus, for it has saved life in the history of the operation, though you will fail. The alacrity to be felt in the operation is in direct ratio to the expectation of speedily reaching the intestine from below. Before performing it, wait for the intestine to be , if you cannot feel it, but not too long. 2V. K Medical Record.
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THE CHICAGO MEDICAL EXAMINER. - # N. S. DAVIS, M.D., Editor. VOL. X. JANUARY, 1869. NO. 1. (Original GHutnbntUo. ARTICLE I. AN INTRA-MURAL FIBROUS TUMOR REMOVED FROM THE ANTERIOR WALL OF THE UTERUS. By WILLIAM H. BYFORD, A.M., M.D., Professor of Obstetrics, etc., Chicago Medical College. Mrs. McC., of Terre Haute, Indiana, is thirty-nine years of age; has been married twenty-one years; has four children, the first nineteen years old, the last eight, and had one miscarriage, twenty years since. Her health has been in every respect good until the last five years. Five years ago, she had severe pain in her left side, extending to the hip and down the leg of the same side; from the history, most likely in the nerve and its branches; for about one month the limb was partially paralyzed. She has since then almost continually been the subject of indigestion, constipation, etc. Eighteen months since, she commenced having profuse discharges of blood from the vagina. These discharges had continued to increase up to the time when Dr. J. B. Buchtel was called to see her, on 22d, 1868; when, according to the description given by Dr. Buchtel, she was anaemic to an extreme degree, with face and extremities, and effusion in the peritoneal cavity. She was almost constantly confined to her bed; had pain in the left iliac region, and dowtn the left leg; was constipated, and vomited a part of her food, and was also much distressed witl the digestion of what she retained. Her menses were regular but profuse; besides this, she had profuse floodings betweer times, which were controlled only by the most active treatment sometimes it was necessary to use the tampon. Between tin hemorrhages she had profuse leucorrhoea. An examination made by Dr. Buchtel was followed by alarming hemorrhage. By this examination he discovered the presence of a larg fibroid growth in the anterior wall of the uterus. After a skilful and diligent course of treatment, consisting, for the most part, of tonics and alteratives, with good diet, for about four weeks, Dr. Buchtel found his patient able to be brought to Chicago for advice and surgical . October 24th, Mrs. McC.'s health very much improved, but still so feeble that she passed much of the time in bed. She expressed great fear of another paroxysm of hemorrhage. A careful examination confirmed Dr. Buchtel's diagnosis. There was a large, hard tumor imbedded in the anterior wall of the uterus. When the probe was passed into the cavity of that organ, and a catheter in the bladder, their lower extremities crossed each other, while the wide separation of their upper ends showed an substance of about five inches. The lower end of the tumor was about on a level with the arch of the symphisis , and had greatly developed and the anterior wall of the cervical part of the uterus, while the upper could be felt high up towards the , a little more to the right than to the left of the linea alba. The os uteri was soft and dilated, so that one finger would easily enter it. A good idea of the tumor in situ is given in Fig. 1. The bladder is crowded up to the symphisis, and the cavity of the uterus may be seen very greatly elongated behind the tumor. I hoped to be able to destroy the vitality of the tumor by coring it after the method practised by Mr. Baker Brown, of London. With a view to an attempt of this kind, I placed the patient on the operating-table, on her left side, with her left arm behind her, so that she would lie well over on her breast, with the knees drawn up, the right bent the most, and drawn forward and over the left on the table. This is Sims's position for the operation for vesico-vaginal fistula. The of a large-sized Sims speculum brought the lower end of the tumor full in view. After having anaesthetized the patient, in presence of the students of Chicago Medical College, at Mercy Hospital, assisted by Dr. Buchtel and some of the senior students, I commenced the operation. An incision was first made in the most dependent part of the tumor, in the anterior lip of the uterus, which extended from one side of the pelvis to the other, and must have been over three inches long; another, commencing in the centre of this, was extended up the posterior surface of the tumor, in the cavity of the uterus, as far as I could guide the scissors by the finger, with the hand partly introduced into the vagina. This last incision must have been more than three inches long also. The substance cut through was at least a quarter of an inch thick. The two incisions formed a 1-shaped opening into the cyst containing the tumor. The freedom with which I could separate the walls of the cyst from the tumor encouraged me to attempt the removal of the whole mass, instead of a part of it. For this purpose, I introduced my left hand into the vagina, and my fingers high up into the cyst; and after some exertion, had the satisfaction to break up the adhesions of the tumor to its envelope over much of its circumference, and well up towards the upper end. I then seized the mass with a strong vulsel forceps, and made traction upon it in various directions, twisting, with a view to loosen it from its bed, and changing the bearing of the instrument in numerous ways, with apparently but little effect. After much effort, I passed the up the surface of the tumor, in the manner by Fig. 2, and made with great force, giving the instrument a swaying motion from side to side. Soon it became evident that the whole tumor was approaching the external orifice of the vagina. Thus I continued passing the forceps higher up from time to time, untif, to my great delight, the whole mass engaged in the lower strait of the pelvis, through which it passed, after some resistance. The fingers were then passed up into the cavity of the cyst, in order to ascertain whether there was anything to be removed. The uterus contracted very decidedly, and became firmer to the touch. I could not detect any other growth by the most careful examination. Not more than two ounces of blood was lost, and the woman exhibited no signs of exhaustion. No more than forty minutes elapsed from the time the patient was placed completely under the influence of ether until she was carried to her bed. No treatment but rest, and opiates enough to allay pain, was directed. Twenty drops of tincture of opium is all the medicines she required or took. There was no symptom requiring attention, but the patient seemed comfortable and cheerful from the time of the , and on the 10th of November she made the journey home. December 1st I received a letter from Dr. Buchtel, saying that his patient was "quite well." The tumor was fibroid, oval in shape, the small end down. It weighed twenty ounces avoirdupois, was five inches and a half long, four inches and three-quarters broad, and four and a quarter thick. It was so firm in structure, that the forcible efforts at removal did not mutilate it scarcely at all. Remarks. The profession is anxiously collecting facts, and comparing the results, in the treatment of fibroid growths of the uterus, with a view to the formation of rules of practice. Heretofore, and at present, there is very little on the subject of management in reference to them definitively settled. Yet, when we look back for only a felv years, we will find there has been progress enough to warrant the expectation that the future treatment of fibroids will be made better than the past. It is with a view to assist in collecting material upon which to base rational methods of cure in the formidable conditions connected with them, that I record this case, and venture upon these remarks in connection with it. The successful enucleation of intra-mural fibroid tumors of the uterus is acknowledged to be the best mode of treatment, especially when their removal can be done at once; yet most instances are attended with many difficulties and dangers. The principal dangers are 1st, Serious damage to the uterus; 2d, Injury to other viscera, as the bladder, bowel, and peritoneal cavity; 3d, Hemorrhage' 4th, Subsequent inflammation; 5th, Toxaemia. The most important difficulties 1st, The remote situation of the tumor; 2d, Contracted and undeveloped condition of the os and cervix uteri; 3d, Too great size of the growth to pass through the pelvis and cervix, after the latter is well . I am aware that these are not all the dangers and difficulties met with; for every case will present its own peculiar ; to be surmounted, at the time, by the ingenuity of the operator alone; but I think we have in those above mentioned such as are to be feared in the majority, if not the whole, of the cases operated upon. One of the most important, in fact , items preparatory to treatment, and which will enable us to avoid much of the dangers, and overcome many of the difficulties, is to definitely determine the relations of the tumor to the different parts of the uterus, the pelvic viscera, and the peritoneal sac. A few very simple means of exploration are necessary, and, ordinarily, sufficient, for this purpose. The tumor should, in the first place, be pressed down as low in the pelvis as possible; the finger, in the second place, should be introduced as far up into the rectum as practicable; 3d, the probe passed up the of the uterus; and 4th, a catheter introduced into the . If the tumor is in the posterior wall of the organ, the finger and probe will be separated as widely as the thickness of the fibroid intervening. The finger may further determine something of the shape and consistence of the tumor, as also whether it occupies the median or lateral parts of the wall. If the growth is in the anterior wall, then the distance between the probe and catheter determines its size. The hand pressed down from above in the abdominal cavity, while the probe is in the uterus, will enable us to judge pretty accurately the vertical dimensions. By this sort of we definitely determine the position of the bladder and rectum, and may thus have the knowledge that will guide us clear of them, and point out the places where the peritoneal cavity approaches nearest the field of operation. With this knowledge, a careful operator would not be likely to inflict damage upon any of these organs. The part of the uterus most in danger is that above the attachment, as it would seem that the segment ordinarily included in or pressed down into the vagina and developed by the tumor, will suffer almost any practicable mutilation, and recover from it without danger to life. It may be extensively excised and largely distended without serious hemorrhage, or other detriment resulting, as this and many other cases on prove. If the vaginal portion is opened by incision or , so that the operator has free access to the cavity in which the tumor is imbedded, the uterine walls will bear great freedom of manipulation, on account of both their great elasticity and strength; for they are generally much hypertrophied. The most distended portion of uterine tissue, in the case , was one-fourth of an inch thick; and it is reasonable to suppose that this part was not thicker than elsewhere. I think it may now be considered as true, that in very few cases is the danger from hemorrhage great; yet we should ever be watchful against the possibility of the contrary. The free use of iron, pulverized rhatany, cold, and, if need be, the tampon, are the resources available and effective. Nor does there seem to be just grounds for suspecting that the operation for and avulsion of these tumors will be followed by more violent or dangerous inflammation than amputations or other capital operations. The means of avoiding it are, to establish the best possible condition of health, by the administration of iron, nourishing diet, and cod-liver oil, before the operation, keep the bowels quiet and suppress pain by the moderate use of opium after it. Toxaemia will not be likely to occur if the cavity of the uterus, vagina, and sac of the tumor be kept clear of blood, or the debris and sloughs of the injured structures, by the free use of tepid water, and, if necessary, solutions of antiseptics. When the tumor is high up, it may be impossible to reach it so as to attack it successfully; yet in many instances we may do much by pressing the tumor down from above. The state of the cervix and closed condition of the mouth of the uterus may often be remedied in a short time by the admirable means we now possess for dilating them; but I the bruised and excited state of the tissues thus dilated is not as favorable for speedy recovery from damage as the left after simple incision, and should rather favor free division of the parts at the time of the operation. It will be seen that much of the incision made in my case was outside the cavity of the cervix, and that the os was not dilated, except by dragging the tumor through it. The plan practised by Dr. Scott, in a case recently reported by him in the California Medical Gazette, of dividing the tumor when too large to be delivered otherwise, with the ecrasseur or scissors, until small enough to pass easily, is to be commended as a measure that will enable us to avoid the damage that might from too great distention or pressure in forcing it through the external parts, and indispensable when too large to be otherwise. The only symptom that I think justifies an effort for the of intra-mural fibroids, where the operation is likely to be successful, is an exhausting or dangerous drain of blood; and even then the milder, though somewhat uncertain, measure recommended by Mr. Brown, of London, of incising the cervix, ought to be tried first, with the hope that nothing further will be necessary. Although these tumors of the uterus are very common, they comparatively seldom grow large enough to prove fatal by their size. Their presence alone, for the most part, is merely an inconvenience; but hemorrhage, when excessive, does great damage to the system often directly, and oftener , bring about fatal results. We should not, therefore, operate because our patient has a tumor, but because the tumor is attended with damaging or dangerous hemorrhage.
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WISCONSIN STATE MEDICAL SOCIETY. The meeting of the State Medical Society convened at the State Agricultural Rooms at 4 P.M., June 10th, 1868. Dr. H. Van Dusen, President, in the chair. Dr. II. P. Strong, Secretary, not being present, Dr. A. J. Ward, of Madison, was appointed temporary Secretary. On motion of Dr. Brown, Drs. Carr and Dalton were , pro tem., to act as Censors, in place of those absent. CREDENTIALS OF APPLICANTS EXAMINED. Those presented wtere: Isaac E. Thayer, Brandon, Fond du Lac Co., graduate of Rush Medical College, also of University of Illinois; Antinous A. Rowley, Middleton, Dane Co., Rush Medical College; A. II. Salisbury, Mazo, Maine, graduate of Bellevue Hospital Medical College; I. J. Whitney, Prairie du Chien, graduate of Buffalo Medical University; vouched for by Drs. Mason and Favill. L. G. Armstrong, Boscobel, of Rush Medical College; vouched for by Drs. Mason and Corey. D. M. Bond, Johnstown, Rock Co., graduate of Medical College; James Cody, Watertown, Jefferson Co., graduate of Harvard, Mass.; Henry M. Lilley, Fond du Lac, Wis., graduate of Medical Department of the University of Michigan; vouched for by Dr. Isaac E. Thayer, Brandon. On motion of Dr. Taggart, of Beloit, the above-mentioned gentlemen were duly elected members of the Society. On motion of Dr. Favill, the new members were allowed all the privileges of the Society in the discussions that may arise before the arrival of the Secretary and Treasurer. There was some discussion as to whether the Society would grant diplomas, and, if so, on what basis. On motion of Dr. Marks, adjourned to 7| o'clock. 7| P.M. Reports of Standing Committees were passed over until morning. Dr. Marks moved to adjourn, which was lost. Dr. Taggart moved that miscellaneous business be taken up. Carried. He also suggested that some action should be taken with regard to examinations for life insurance. Dr. Cody suggested that something should be done, in the Legislature, with regard to services as experts in medical testimony. 01:n motion of Dr. Marks, it was resolved that a committee of three be appointed by the President, to ask such legislation as they may think proper on the subject. Carried. Dr. Marks moved that Dr. Strong receive from the Society $25, to pay his clerk-hire, which was carried. Drs. Cody, Carr, and Barrett were appointed by the Chair, to ask some legislation for pay as experts, in giving medical testimony. Dr. Whiting moved that another Cotnrriittee be added to* our list which comes under the head of Mental and Nervous . Carried. Drs. Van Nostrand, Stoddard, and Corey were appointed on that committee. Dr. Cody reported a case of fracture of the ribs. The part of the case was, the extensive emphysema that ensued it having extended over the whole body. There was ,also extensive hemorrhage of the lung. Dr. Whiting spoke of thp danger of fracture of the ribs; did not believe that in half of the cases reported there was any fracture. Dr. Taggart thought the danger depended upon the of the bone. Dr. Barrett said he had known of 10 or 12 cases, that had been reported in his town, and he did not know of but two of the cases that were really fractured. The Censors then made the following report: " Your Censors, having examined Dr. Mayham, concur in recommending him for membership, as much upon the of his neighboring practitioners as upon the result of the examination. We would further state, we cannot recommend him for a diploma. [Signed,] "N. Dalton, "Jas. Brown, Adopted. "Censors." On motion, adjourned until 8 o'clock to-morrow morning. A. P. WARD, Secy, pro tem. June 11, 1868, 8 o'clock A.M. Meeting called to order by President Van Dusen. Present Drs. Van Dusen, Strong, Ferrin, Brown, Favill, Ward,- Thayer, Carr, Taggart, Dickson, Mason, Marks, Dalton, , Stoddard, Whiting, Barrett, Ellsworth, Benson, Linde, Coolidge, Cody, Armstrong, Whitney, Bond, McKennan, Lil. ly, Mayham, Millard, N. C. Rowley, A. A. Rowley, Jones, and President Chadbourne. Gov. Fairchild presented an invitation to the gentlemen of the Medical Society to spend the hour of 7 to 8 o'clock at his house, this evening. Accepted. Minutes of last meeting read and approved. Report of accepted. Dr. Brown offered the following resolution, viz.: Resolved, That the Board of Censors having examinod the qualifications of Dr. T. F. Mayham, and reported favorably thereon, he be admitted to membership in this Society. Dr. Favill moved that the Censors have leave to withdraw' their report on the case of Dr. Mayham, made last evening. Adopted. On motion of Dr. Favill, the resolution offered by Dr. Brown was then accepted as a report of the Censors. Moved, by Dr. Taggart, that Dr. Mayham be elected a of this Society. Motion lost. Moved, by Dr. Strong, that the rules and regulations to the admission of members be suspended during action on the case of Dr. Mayham, and that hereafter the Censors are instructed not to entertain any application for membership, unless the applicant shall conform to the rules then existing as to admission to membership in this Society. Adopted. On motion of Dr. Ward, the motion rejecting Dr. Mayham was reconsidered. On motion of Dr. Ward, he wtas then elected a member. Dr. Brown then offered the following resolution, which was adopted: Resolved, That in explanation of the action of the Society heretofore upon the subject of admission to membership, the following conditions are required: The applicant shall present to the Board of Censors a diploma from a regular school of medicine, of good repute; or a certificate or diploma of in a county or district society, accompanied with a of six years' practice, and of good moral and character; or he shall submit to such an examination as the Censors may impose. Censors reported in favor of admitting Dr. F. R. Millard, of Beetown, graduate of Rush Medical College, to membership. Report adopted, and he was elected a member. Dr. Ward asked leave to present a patient to the Society for opinion as to the nature of the disease, which was granted, and an examination made by the members of the Association . The patient was a lady of about 30 years of age. After confinement some time since, she left her bed rather too early, and was attacked with roaring in the right side of the head. This is constant, and very annoying. Instant relief is obtained by pressure upon the common carotid artery, and remains so long as the pressure continues. This is the only means by which relief is afforded. There was a diversity of opinion as to the nature of the difficulty, and no definite conclusion . Dr. Marks, Chairman of the Committee on Surgery, made a report at length on treatment of fractures of the thigh. The report goes on to prove, by the best authority, that oblique fractures of the femur in adults nearly always results in more or less shortening. He also proved that the majority of prefer the straight position in treatment of these ; and goes on to say, that, "when there is displacement of the fragments, the points of bone must be in contact with the soft parts, and that any unnecessary handling or twisting of the limb inflicts injury upon the muscles, and other tissues, which taxes nature to repair. Gentleness is not incompatible with good surgery, although there are men who, judging from their method of manipulation, would differ with me. Those claiming to be good surgeons, often inflict an amount of injury to the soft parts, in their examination, that takes nature weeks, I might say, months, to repair." The treatment he has adopted and prefers is to use extension by means of adhesive plaster applied to the leg, terminating below the foot, to which is attached a weight running over a pulley, varying in size from 8 to 20 pounds in adult cases. A is placed on each side of the limb, and the foot of the elevated 3 or 4 inches, the weight of the body being the counter-extension. When the fracture occurs below the lesser trochanter, he pasteboard splints the whole length of the limb, upon either side using the extension as before indicated. "The advantages claimed for this method are: First, ease and comfort to the patient. Second, the dressing does not in the least with the circulation in the limb. Third, the limb can be seen at all times; and, in case of compound , the wound can be dressed as often as desirable. Fourth, the limb can be dressed and placed in position in one-fourth the time required to apply the splint and roller. Fifth, I claim better results from this method than from any other I have ever seen tried, though I do not pretend that it will always shortening." In fractures within the capsule, or partly within, he uses only sand-bags, with the weight and pulley, as before alluded to. Dr. Marks gave several cases treated in this manner; and the result warrants a general trial. Dr. Mason, of Prairie du Chien, was called upon to give the result of his experience in the treatment of fractures without splints. He made a statement, that he had treated fractures of the femur and tibia by the use of sand-bags and the weight, with good success; and had also used the same treatment for , with good results. Dr. Marks reported at the previous meeting a case of of the subclavian artery, then under treatment, and for which he had amputated at the shoulder-joint. The patient died, and he presented a full written report of the case, with a statement of the appearance of the tumor after death. Dr. McKennan, of Sauk City, presented a written report of a case of .'boulder presentation, where the uterus was ruptured during the act of version. The child was immediately , and the mother recovered. He also presented the written report of another case, where the woman was very short of stature, but stout and robust, and had a deformity of the pelvis, from an undue prominence of the promontory of the sacrum. Antero-posterior diameter less than three inches. She had borne twelve children, nine of which had been delivered with instruments, and were dead. The 10th, 11th, and 12th were very small, and were born instrumental aid. He was called to her in her 13th , and found the pains strong, and the head presenting, and pressing strongly against, and partially engaged in, the brim of the pelvis; and so it remained for 12 hours. The Doctor 'hen turned the child, and delivered it by the feet # considerable force being required to extricate the head. The child was alive, and weighed some ounces over 13 pounds. The report of this case gave rise to some discussion as to the practicability of turning in such cases some apprehending that in most cases the head could not be extricated. Dr. Dalton, of Mineral Point, made an extended report of a case of aneurism of the axillary artery, which terminated in death. The patient presented himself "with a large pulsating tumor in the left axilla, a small part presenting above and within the acromial articulation of the clavicle, the scapula considerably elevated, a pain, at times, in the left arm, with considerable swelling, and at all times a numbness, or, as he expressed it, a 'dead-feeling, extending to the ends of his fingers.'" He goes on to give a history of the case from the first appearance of the tumor. Told the patient the only remedy was ligation, and that the result would probably be fatal under any method of treatment. He decided to have the operation performed, and Dr. Dalton tied the left subclavian artery, at the outer margin of the external scalenus muscle, following the form of incision introduced by J. Kearney Rodgers. The operation was followed by sensible diminution in the size of the tumor, and coldness of the whole surface of the arm. Case did well up to the 24th day, when the ligature came away, followed by slight hemorrhage. Incision had entirely healed, except that portion about the ligature warmth nearly restored, and tumefaction almost disappeared. The case went on until the incision entirely healed, and in six days he was discharged as cured. The operation was performed in November, and on the 7th day of March following, he felt pain in the back and right shoulder, and on the night of the 10th he suddenly expired. Dr. Dalton closes his report, which is given in detail, as : "I requested a post mortem, but could not prevail upon them to grant it. Therefore, of what he died I am wholly ignorant, but, from their description, came to the conclusion that it might have been angina pectoris. They stated he had been suffering, as usual, with his pain, when he suddenly threw his right hand to his left side, and screamed with pain; turning himself partially over, he became some easier, but his ease was of short . In from three to five minutes he acted in the same , and expired. "Whether this could in any way be connected with the or operation, is a question I leave to the profession to ." Adjourned to 1| o'clock. 1| o'clock. The Committee on Practical Medicine was not ready to , and was continued, with the exception of the Chairman. Dr. C. J. Taggart, of Beloit, was appointed Chairman. Dr. Ferrin, of the Committee on Practical Medicine, made a verbal report of an anomalous case of pain and irritability of the urethra. The subject of puerperal convulsions having been brought up, a very general and animated discussion upon the pathology and treatment followed. President Van Dusen left the chair and participated, in his usual pointed and style; he was full of the subject. Being an elderly , of large experience and close powers of observation, he was pretty good authority upon this subject. His opinion was, that it usually occurred in persons of plethoric or full habit, and bleeding was the remedy. Such had been his practice, and he bad never lost a case. He had but little faith in without bleeding, and such appeared to be the general opinion. Most of the afternoon was consumed in the report of cases and general discussion. President Chadbourne, of the State University, appeared, and was introduced by President Van Dusen. He gave some remarks upon the duties and requirements of the medical profession. He introduced the subject of establishing a school within the State under the law creating the , and sai.., as one of the members of the committee appointed by the Regents to take into consideration the practicability of a school to be established at Milwaukee or elsewhere, he felt to advance the project, but he felt that the initiative should be taken by the State Medical Society, as it must in a great measure depend upon it for its support and direction, and he hoped that the Society would take action upon this when it seems to be desirable to organize such a school. The subject of treatment of rheumatism was under discussion for some time, and the majority seemed to favor alkalies as the most efficacious remedies. On motion of Dr. Marks, of Milwaukee, Dr. Taggart, of , was requested to furnish a written report of a case of spontaneous rupture of the sphincter ani; also, that Dr. , of Sauk City, be requested to furnish a written of his treatment of fracture of the malar 'bone; and Dr. Cody, of Watertown, of a case of emphysema. Dr. Van Dusen announced the death of Dr. J. B. Dousman, and moved that a committee be appointed to give a biographical sketch of Dr. Dousman at the next meeting. Adopted. Dr. Whiting, Vice-President, in the chair, appointed Dr. II. Van Dusen. On motion, Drs. Jesse Moore, of Beloit, and Azariah , of Milwaukee, were elected honorary members. On motion, a standing committee of three was appointed to report on new remedies. Chair appointed Drs. Cody, Corey, and Mason. On motion of Dr. Whitney, of Prairie du Chien, a committee on diseases of the eye and ear was appointed. Chair'appointed Dr. Whitney. Dr. Mason presented a biographical sketch of Dr. B. F. White, deceased, and a report was presented by Dr. Treat on the life of Dr. C. S. Farr, deceased. A communication from Dr. Storrs Hall, of Rosendale, was presented, regretting his inability to attend. On motion of Dr. Marks, the Secretary was instructed to furnish the Chicago medical journals with a synopsis of the . Moved, by Dr. Marks, that the Constitution, By-Laws, and Code of Ethics, with the Proceedings, be published in pamphlet form, and distributed to the physicians generally in this State. Adopted. Dr. Whiting presented the following resolution, which was ado'pted: Resolved, That whenever any member shall have neglected to pay his annual dues to this Society for the period of three years, his name shall be stricken from the rolls of the Society, in ; provided, however, that the Secretary shall previously send him a copy of this resolution. * Dr. Dalton offered the following: Resolved, That when we adjourn we adjourn to meet on the 3d Wednesday of June next, at the city of Madison. Adopted. Dr. Barrett offered the following: Resolved, That in view of the increasing population of and other Northwestern States, a larger number of well and thoroughly educated medical men are demanded to meet the wants of the community, the time has come for the of a medical school in this State, under the auspices of the State Medical Society. Resolved, That a committee of three be appointed to confer with a similar committee recently appointed by the regents of the State University, in regard to the immediate establishment of such a school. Laid over to next meeting. A committee of one from each Congressional District to the Secretary the names of physicians in the State, was appointed, as follows: First District Dr. Marks, Milwaukee. Second District Dr. Favill, Madison. Third District Dr. Dalton, Mineral Point. Fourth District Dr. Lilley, Fond du Lac. Fifth District Dr. Russell, Oshkosh. Sixth District Dr. Thayer, Brandon. Moved by Dr. Strong, that a committee on Pathology and a committee on medical education be appointed. Adopted, The Chair announced the standing committees for the year as follows: Arrangements Drs. Brown, Favill, and Ward. Surgery Drs. Marks, Dalton, Palmer. Obstetrics Drs. McKennan, Barrett, Thayer. Pathology Drs. Stoddard, Bond, Armstrong. Practice Drs. Taggart, Vivian, Ferrin. New Remedies Drs. Cody, Corey, Mason. Executive Committee Drs. Carr, Dickson, Salisbury. Medical Education Dr. Carr. The thanks of the Society were tendered to Gov. Fairchild for the hospitality of this evening. Adjourned. Id. P. STRONG, Secretary.
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Oitr> r iaI. Nothing New. In the clinical reports in the Medical Record of New York, we find on page 463 the following: "Case IV. Renal Dropsy. Treatment by the Bichloride of Mercury. In the case of a man with general dropsy of four months' standing, dependent on renal disease, Dr. Flint called attention to a new method of treatment by the use of the of mercury in small doses. On admission, his urine contained albumen and waxy casts. Corrosive sublimate was given, in doses of -3'2 part of a grain with compound tincture of cinchona. The dropsy had now nearly disappeared." What is here spoken of as a "new method'' of treatment for renal dropsy, was proposed arid practised in New York City more than twenty years since. It was adopted in the of several cases in the New York Hospital, with reported benefit. We heard it spoken of in one of the College clinics, we think, by Prof. Willard Parker. We were at that time residing in New York City, and kept a male patient, who had been disabled by general dropsy with highly albuminous urine for six months, on the following during nearly eight months, with interruptions of only a few days at a time: I|z. Tinct. Cinchona, SSiij. Bichlorid. Hydrarg., 1 gr. Mix. Give one fluid drachm, in sweetened water, before each meal and at bedtime. After he had been under treatment one month, the dropsical infiltrations had diminished so much that he' could take exercise, and the medicine was limited to three doses per day. At the end of eight months, there was still a little about the eyes in the morning, and in the feet and ankles at night. There were also slight traces of albumen in the urine. But he was able to do a moderate amount of manual labor every day. Ever since that time we have continued to use small doses of the bichloride of mercury in some cases of renal dropsy, with benefit. We have generally given it in tincture of cinchona bark. Given in this manner, and in doses of of a grain or less, we have seldom known it to affect the gums of the patient, even after several weeks' . Dr. Arthur E. Peticolas, Superintendent of the Eastern Lunatic Asylum at Williamsburg, committed suicide there on the morning of Nov. 28th, by leaping from a window of the building, and dashing out his brains. He was a distinguished physician, and formerly a professor in the medical college at Richmond. Ilis mind had been unsettled for some time past. Medical and Surgical Reporter. It is proposed by the New York Medical College for Women to educate a body of professional nurses to attend freely or for a moderate charge, persons living in boarding-houses and like places, who are not able to secure regular attendance. Medical and Surgical Reporter. Money Receipts to December 23. Drs. W. A. Gordon, $5; E. L. Holmes, 3; J. S. Sherman, 3; N. W. Abbott, 1; W. A. Knox, 3. J. H. Rauch, 9; M. Parker, 3; R. N. Isham, 6. M. 0. Heydock, 6; J. P Ross, 3; W.C. Lyman, 3; John M. Woodworth, 2; A. Groesbeck, 3; J. W. Mill, .75; John Macalister, 6; J. M. Hutchinson, 3; M. F. DeWitt, 6; D, C. Roundy, 3; W. II. Byford, 3; G. C. Paoli, 5; J. N. McLane, 6; Latta & Sparklee, 6; A. Fisher, 6; , 3; D. B. Bobb, 3; J. B. Buchtel, 6; Hosme A. Johnson, 10; M. F. Bassett, 3; J. S. Hildreth, 6; R. C. Hamill, 6; Daniel Gard 1.50; J. C. , 3; W. W. Allport, 6; A. Hager, 3; D. H. Spickler, 6; S. S. Terry, 6; . Wilcox, 5; D. E. Woodward, 6; John Conant, 6; G. Wheeler Jones, 3.25; E. Ballard, 6; D. V. Cole, 6; S. Wickersha >, 3; C. H. Quinlan, 9; Wolcott & Markes, 6; Wm. J. Wheelan, 3; D. M. Creed, 7.50; Geo. Fredigke, 3; Henry Sweet, 6; II. A. Allen, 6; Cleveland, 3; J. B. Walker, 3; Daniel Duckett, 6; Theron Nichols, 2.50; R. J. Patterson, 6; G. L. Henderson, 1.50; R. , 6; Ira Hatch, 6; J. McLaughlin, 3; Edwin M. Park, 3. BELLEVUE PLACE, For the care and treatment of Nervous and Insane Inva'ids. Address R. J. PATTERSON, M. D., Jan. 1, 1869. Batavia, Ill. Reliable vaccine matter can be had of dr s. a. McWilliams, 166 STATE STREET, CHICAGO. Mortality for the Month of November, 1868: CAUSES OF DEATH. Accident, drowned____ 6 " fall,_______ 2 " run over by wagon______ 1 " railroad,___ 4 Angina,_______________ 2 " scarlet fever & exhaustion, __ 1 Anaemia,_______________ 1 Apoplexy,_____________ 1 Aphthae,_______________ 1 Births, premature,___11 " still___________48 " tedious_________ 2 Bronchitis,___________ 5 and dropsy 1 Bowels, inflammation, 2 Brain, apoplexy of___ 1 " dropsy of,______ 1 " congestion of,_ 6 " and convulsions 1 " " from injury, 1 " inflammation,. 1 " softening of___ 1 Cancer, 1 " of breadegt,_____ 1 Carbuncle and , _______________ 1 Cholera infantum,____' 2 " morbus,_________ 1 Convulsions,__________44 puerperal 1 " from of drugs,_____ 1 Croup, 8 " diptheretic,____ 1 " membranous______ 1 Cyanosis,_____________ 1 Debility______________ 3 " general,________ 4 Delirium tremens,____ 1 Deficient vitality,__ 1 Diphtheria,___________10 Diarrhoea,____________ 3 " chronic,_______ 9 Dropsy,______________ 5. " peritonitis and gangrene,__________ 1 Dysentery_____________ 5 " chronic________ 3 Epilepsy_____________ 1 Enteritis, chronic, 1 " and -cough, 1 Erysipelas,____________ 6 Fever, congestive,____ 3 " puerperal, 2 " remittent______ 2 " and , ______ 1 " " pneumonia 1 " scarlet, 23 " " malignant,. 2 " " and dropsy, 2 " " and , _____ 1 " " and e n e of tonsils,__ 1 " " and ,____________ " " and , 1 " " pericarditis 1 " typhoid,_________20 " 11 and , 1 Gastro-enteritis,_____ 1 Gangrene, traumatic,- 1 Glottis, spasms of,___ 1 Heart, dropsy of,_____ 1 " disease of,______ 5 " following parturition,___ 1 " valvulalar of, 1 " mitral valve, disease of,________ 1 Hernia strangulated _ 1 " incarcerated, _ 1 Hydrothorax & dropsy 1 Hydropericardium and paralysis,_____________ 1 Hip disease___________ 1 Hydrocephalus,________ 5 acute,- 1 Injuries, 1 Inanition,_____________ 8 Intemperance and , 1 Impaired nutrition,___1 Kidneys, Bright's of,______________ 3 Laryngitis,___________ 2 Liver, inflammation of 1 Lungs, congestion of_ 3 " and ,________________ 1 " effusion of,____ 1 " emphysema of, 2 " hemorrhage of, 2 " paralysis of,____ 1 " 1 and old age,______ 1 Measles,______________ 2 Meningitis____________ 2 " cerebro-,______ 3 " tubercular, 5 Mitral, insufficiency of, and albuminuria, 1 (Edema pulmonium, 2 Old age,_____________ 9 " and fever , ________ 1 Paratitis & fever , 1 Paralysis,____________ 1 Peritonitis,__________ 5 " acute_________ 1 puerperal, 1 Pyaemia, 1 " and compound fracture of leg,___ 1 Phthisis pulmonalis, _ 34 Pneumonia,___________20 and _____ 1 " typhoid,_______ 1 Scrofula, 1 Stomach, cancer of,__4 Suicide, poisoning, 1 Tabes mesenterica,___10 longue, cancer of, 1 Teething, 5 " and scarlet fever, 1 Urethra, stricture of,_ 1 Uterus, cancer of, 1 " tumor of,_______ 1 Whooping-cough, 7 " and convulsions, 1 Unknown 5 Total,_____________401 COMPARISON. Deaths in Nov., 1868, 401 | Deaths in Nov., 1867,_370 | Increase,_31 Deaths in Oct., 1868, _______ 448 | Decrease,____________________ 47 AGES. Under 1____________ 116 30 to 40_________ 42 90 to 100________ 1 1 to 3______________ 57 40 to 50_________ 32 100 to 105_______ 1 3 to 5 32 50 to 60 18 Unknown__________ 2 5 to 10____________ 34 60 to 70__________ 10 10 to 20___________ 15 70 to 80__________ 10 Total__________401 20 to 30 __________ 27 80 to 90__________ 4 Males,_________221 | Females, 180 | Total, ___________401 Single, 293 | Married, 108 | Total,_________401 White,__________ 399 | Colored, 2 | Total, 401 NATIVITY. Foreign Chicago 118 Chicago____________ 73 Other parts U. S. 61 Poland,_____________ 1 Bohemia_____________ 5 Canada______________ 4 France 2 England 13 Germany___________ 45 Holland____________ 3 Ireland___________ 47 Norway 10 Scotland 4 Italy,_____________ 1 Denmark,__________ 1 Sweden___________ 12 Unknown___________ 1 Total,______ 401 MORTALITY BY WARDS FOR THE MONTH. Ward. Mortality. Pop. in 1868. One death in Ward. Mortality. Pop. in 1868. One death in 1___ 8 9,094 1,137 2 14 13,074 934 3 26 15.Q76 580 4 16 17,796 1,112 5 32 16,033 501 6 25 13,083 523 7 42 25,492 607 8 33 15,813 479 9 18 19,297 1,072 10 13 12,925 994 11 14 14,340 1,024 12 25 17,485 699 13 21 11,164 531 14 27 14,839 549 15 33 21,078 639 16 18 15,465 859 Bridewell, 1 County hosp.lO Chi. River, 4 Mercy Hosp. 4 St.Luke's H's.l Immigrants 10 St.Jo. Orph. Asyl. 1 Hosp, of . Orph. Asylum 1 ian Bros., 1 Hosp, for Women and Children, 1 HomeforFriendless, 2 Total,__________________________________________ 401 A Clerical Surgeon. Father Ileylen, a catholic priest of Boom in Belgium, performed the Caesarian operation on a young woman in order to baptize the infant before it died. The mother appears to have been living when the operation was , but both mother and child succumbed. In his defence the priest said that he performed the operation in obedience to the direct instructions of the archbishop. These instructions are now to be cancelled, and the clerical surgeon tried for . Medical and Surgical Reporter.
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or m Lima nt CLINICAL CASES IN MEDICAL WARDS OF MERCY HOSPITAL TYPHOID FEVER, CARCINOMA, WITH EXTRAORDINARY SYMPTOMS. By N. S. DAVIS, M.D., Professor of Clinical Medicine. Case I. September 89th, 1869. The case before you, gentlemen, is that of a laboring man, aged about 28 years, naturally spare in flesh and of nervous temperament. He came to me about four weeks since, in my office, complaining of the usual initial symptoms of an attack of typhoid fever. I directed him some medicine, and proper hygienic management, and saw or heard nothing more from him until he was brought into this ward of the hospital, about one week since. At the time of admission his case presented all the symptoms of a grave form of typhoid fever, in the advanced stage of its . His skin was dingy; countenance dull; lips retracted and dry, leaving the upper teeth covered with sordes; mouth and tongue dry; mind somnolent and sometimes wandering; skin dry and rough, and above the natural temperature; movements unsteady and awkward; abdomen tympanitic and full; bowels moving five or six times per day, the discharges being dark-brown and thin; respirations 20 per minute and short, with dry bronchial rhonchi over both sides of the chest, and some dulness on percussion over the lower and posterior parts. The pulse was soft, quick, and varying from 120 to 130 per minute. If we suppose that at the time he called at my office, he was in the forming stage of the fever, it will be seen, that when admitted into the hospital, he was at the end of the third week of the disease, and the symptoms such as to render the prognosis doubtful. The soft, frequent pulse, the mental dulness, the muscular unsteadiness, the dark hue of the lips and skin all indicate that profound typhoid condition, when the qualities of the blood and the properties of the tissues are both impaired, causing all the resulting actions in the economy, such as capillary circulation, secretion, nutrition, inervation, etc., to be performed feebly. In the more malignant cases of typhus and typhoid fevers, these alterations in the qualities of the blood and the properties of the tissues arc sufficient to suspend the organic changes, and, consequently, to prove the direct cause of death. In addition to the general pathological conditions, there are important local changes in the viscera of the chest and abdomen. The dry, bronchial rhonchi over the whole anterior part of the chest, with dulness on percussion over the lower and posterior part, and the short inspirations, show that the bronchial mucous membrane is in a state of congestion, and the parenchyma of the lower lobes so occupied with hypostatic or passive , as to materially diminish the capacity of the lungs for air. The condition of the lungs, of course, lessens the and decarbonization of the blood, and thus indirectly increases the general impairment of function throughout all the organs. The tympanitic abdomen, with the frequent, thin, redish-bro^Tn, and copious discharges from the bowels, indicate, in this stage of the disease, extensive softening, and, perhaps, ulceration of the aggregated glands of the ilium and mesentery. These local pathological conditions in the chest and abdomen are frequently the most dangerous developments, during the progress of this variety of fever; sometimes determining a fatal result in cases presenting only moderate primary changes in the blood and properties of the tissues. In the patient before us, at the time of his admission, the symptoms, as we have already described, indicate much general depression, with lesions, both in the chest and abdomen. Hence, the special indications for treatment 'were, to sustain the general properties and functions, by plenty of good air and judiciously selected nourishment, and to administer such as would relieve the congested condition of the bronchial mucous membrane, on the one hand; and on the other such as would arrest the process of softening and disintegration in the glands of the ileum and colon. The first object was secured by the size of the ward, its free ventilation, and the limited of patients in it, and the feeding of the patient, animal broths, well salted, alternately with thin, sweet milk and wheat flour porridge. These articles of nourishment, given in small quantities, and at short intervals, are capable of being taken up by the absorbants and lacteals of the stomach and , leaving the smallest amount of fecal residue to pass over the diseased surface of the ilium and colon. To accomplish the second purpose, we gave one fluid drachm of the following , every four hours : I^. Hydrochlorate Ammonia, 5iij. Tart. Ant. et Pot., 2 grs. Sulph. Morph., 3 grs. Syrup Glycirrhiza, giv. Mix. To secure the third object we give one fluid drachm of the following emulsion, every four hours, alternately, with the prescription: 01. Terebinth., 5iij. Tinct. Opii, 5iij. Pulv. G. Acaccia, 1 __ White Sugar, yaa, Oiv. Rub together, and add Mint Water, giij. Mix. After these remedies had been used three days, the dry, bronchial rhonchi diminished, and were partially replaced by moist mucous rattles; the skin became less hot and dry; but the pulse remained weak and frequent, and the mind more wandering. The emulsion was continued every four hours, and 10 drops of chloroform added to each dose. The use of the solution of hydrochlorate of ammonia, etc., was diminished to one dose, morning, noon, and evening. The same nourishment was as before. Four days have elapsed since any alteration was made in his treatment. If you now examine the patient carefully, you will find the skin but little above the natural temperature, and more soft; the countenance more pale; the lips thin, and still somewhat retracted, but the sordes mostly gone from the teeth; the of the tongue dry and red, but moist and white along the margins; the respirations shorter and more frequent than , with a moderate development of mucous rhonchus over the anterior part of the chest, and some dulness on percussion over the lower and posterior part. (Here the class were required, individually, to auscultate the patient.) The pulse is 110 per minute, small and soft. The abdomen is only slightly , but the intestinal discharges continue thin and light-brown, and average from three to five discharges in the 24 hours. You will readily perceive that some of the symptoms to which your attention has been called indicate improvement, while others point to a more doubtful prognosis. For instance, the nearer approach to a natural condition of the skin, the less appearance of sordes on the edges of the lips and teeth, the moist condition of the margins of the tongue, and the lessening of morbid sounds in the chest all indicate the commencement of convalescence. But the continued weakness and frequency of the pulse, with the quality and number of the intestinal discharges, indicate the continuance of a serious amount of disease in the ilio-csecal portion of the alimentary canal. It happens not very unfrequently in the severer cases of enteric or typhoid fever, that all the general symptoms of fever subside, and convalescence ensues, while these patches of aggregated glands in the ilium, which had become softened or ulcerated during the progress of the fever, are still not or much improved in texture. Your attention is called to the fact as one of much practical importance. If it be , and as soon as the patient appears otherwise , all remedies designed to exert a soothing influence on this part of the mucous membrane are withdrawn, and a liberal diet allowed, it will sometimes happen that the intestinal evacuations will gradually increase in frequency; and after a week of convalescence, the abdomen will again become tympanitic, the mouth dry, the pulse frequent and feeble, with rapid loss of strength, until a fatal result is reached. In a smaller number of cases, the general appearances of convalescence continue, but the patient does not improve in strength. The bowels do not become regular, sometimes moving three or four times in succession, and then quiet 24 or 36 hours. After a time, varying from one to three weeks, they are attacked with acute pain, in some part of the abdomen, followed rapidly by abdominal distension, tenderness, and . The pulse becomes very rapid and feeble; the hippocratic; the skin covered with cold perspiration; and death follows in from 24 to 48 hours. These are cases in which some one of the patches of Peyer's glands remained unhealed, after the convalescence of the general fever; and instead of subsequent cicatrization, it slowly extended, until the coats of the intestine were perforated, inducing, suddenly, peritonitis and death. Many years since, a marked instance of this kind occurred in the person of a medical student in this city. After an apparently mild course of typhoid fever he , continued to be up a part of each day, for a week, and began to go to the table for his meals, -with other boarders, when he was attacked suddenly 'with fatal peritonitis, from a perforating ulcer in the intestine. In a much larger number of cases, however, patients convalesce from typhoid fever, while numerous places in the mucous membrane are in a state of or complete ulceration. They regain a fair degree of flesh and strength, and often attempt to resume attention to their ordinary work. But the intestinal evacuations never become regular. In some, there will occur from one to three or four thin, fecal discharges per day, constituting what might be styled a slight, chronic diarrhoea. This state of the system will continue, in some cases, many months; and, finally, the patients begin to lose flesh and strength, and slowly reach a stage of fatal exhaustion. In other cases, the uncicatrized patches appear to be limited to the colon. The patients recover a fair degree of flesh, and resume attention to business, but their intestinal evacuations remain very irregular, usually going from two to four days without any discharge, and then have six or eight in a single day. It would seem that the peristaltic motion of the small intestines was impaired, and the fecal contents were carried forward only slowly; but so soon as they begin to accumulate in the colon, and come in contact with the patches of diseased membrane, an exaggerated motion is started, which does not stop until the whole canal is emptied, when it returns to its dormant state as before. Patients have come to me often with this state of the bowels, and on carefully inquiring into their history, I have traced them directly back to an attack of typhoid fever, which had occurred, sometimes, four or five years previously. I am thus particular in calling your to this point, because it is one of direct practical . Careful attention to the state of the bowels, during the from typhoid fever, will save many patients from troublesome sequelae. The patient before us gives plain of commencing convalescence, but his bowels remain actively loose, and his pulse quick and feeble. We shall, therefore, continue to give him the emulsion of turpentine and laudanum, every four hours, and feed him on sweet milk and wheat-flour porridge, until the intestinal become more natural. Case II. Mrs. , aged 40 years, native of Ireland, was brought to the hospital several weeks since, from Kansas, where she had been living with her husband for some time past. I do not call your attention to this case for the purpose of discussing either the pathology or treatment of the disease under which she is laboring, but simply to point out some that are of rare occurrence. You perceive that the right side of the face and neck are much swollen, and the right arm and hand still more swollen, distending the skin until it is and tense to the ends of the fingers. As I remove the covering you see the same swelling occupying the whole of the right anterior half of the chest, from below the breast to the top of the shoulder and neck, and from the middle of the sternum to the right laterally to the anterior edge of the scapula. This swelling, embracing the right anterior and lateral half of the chest, right arm, shoulder, and corresponding side of the neck and face, is simply oedementous, pitting, as you see, on pressure, and accompanied by no discoloration, except along the right side of the trachea where it is purplish, as though the extravasation of serum or water had been accompanied by some of the red corpuscles. The cedematous infiltation in the neck and over the upper end of the sternum is so great as to render both respiration and deglutition somewhat difficult, and her to remain in an upright or inclined position nearly all the time. On examining further, you find the right breast little more than its natural size, the skin looking corrugated, and the nipple drawn in, while to the touch it is hard as a stick, and immovably fixed to the ribs, presenting a good sample of schirrhus, or hard cancer, involving the whole breast, mammary gland, areolar tissue, and all. The left breast is larger, but moveable on the ribs, with hard lumps or nodules of schirrhus limited to the mammary gland. There are no of the lymphatic glands in either axilla, or along the clavicles externally. The^patient is of a sanguino- temperament, not emaciated, and the general functions of the system very well performed. The chief peculiarity of this case, which distinguishes it from ordinary cases of cancer in the breast, is the extent and of the oedema. Schirrhus of the breast is often accompanied by enlargement and induration of the Lymphatic glands in the axilla and along the border of the pectoral muscle. And these glands press upon the nerves and bloodvessels to such an extent as to make the arm both painful and oedematous. But in this case there are no tumors in the axilla, and none to be felt externally along the clavicle. Neither is the oedema limited to the arm, as is usual in such cases: but it extends to all that part of the right side of the chest, shoulder, neck and face, from which the blood is returned through the right vein. This would indicate the formation of some growth behind the first rib or its junction with the sternum, in such position as to obstruct that vessel. The caused by the oedema, however, is such as to prevent any satisfactory examination of that region, either by or auscultation. That the oedema is the result of direct obstruction of bloodvessels, either by pressure or emboli, is from its strictly circumscribed character. When dropsical effusions take place from spanaemia or impoverishment of the blood, they are general, and are always influenced by gravity, and hence appear most prominent in the feet and legs first. But here the lower extremities are entirely free. The apparent obstruction of the subclavian vessels, in this case, and the increasing oedema in the neck, will probably cause life to terminate early, by complete suspension of and deglutition. As the hour has expired, I will not detain you for any comments on the subject of treatment; for, in this case, medicine and surgery are alike powerless.
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ARTIFICIAL MINERAL WATERS Kissingen. By R. ROTHER. The numerous inquiries concerning methods for preparing artificial mineral waters, and the recent attempt of some to furnish the necessary information, together with the demand for this luxury, all concur that a commentary upon this interesting subject would not be out of place. As a type of this class of preparations, Kissingen Water was chosen, since the apparent difficulty attending its production, and the high esteem in which it is held, but especially as constituting the topic of an anonymous chemist of the Druggists Circular, make it a point of some interest to the writer.* * Druggists' Circular, July, 1869. That contributor s elaborate and practically impossible leads to the supposition of being a manufacturer's device, to divert attention from, and further monopolize, the industry of mineral waters; but the indescribable syntax, and worse chemistry, in fact, the total process is so awkwardly exhibited as to betray nothing of the necessary shrewdness usually so of such an enterprise. The flattering enconium upon the "celebrated Liebig" is cast into ridiculous contrast, when viewed in connection with the author's formula, which, as he states, is to represent Liebig's analysis of the Rakoezy Spring. If it was the design of the author, prompted by a generous impulse, to benefit unassuming enquirers, he should have that few can comprehend the abstruse chemical he lays before them, and that whoever could complete his dubious process would certainly possess the requisite to devise a working formula from the original data of the analyst, without soliciting his intervention. At the present time, the great bulk of artificial mineral waters consumed is furnished by a class of manufacturers who make its fabrication a specialty; each producer claiming for his preparation merits peculiar of its own, representing it as identical with the natural article, but manufactured by entirely original methods, only known to themselves. The retail vender thus obtains his mineral waters in concentrated solution, which, according to manufacturer's direction, is mixed with more water, and the dilute solution impregnated with carbonic acid, under pressure. This is, evidently, a great convenience to those who are not aware of a more economical, but, above all, reliable source. What guarantee exists for the correctness of the manufacturer's statement, whose selfishness prompts him to conceal his process? Does the confiding retailer know that the manufacturer's solutions, No. 1 and No. 2, contain all the necessary constituents of the mineral water they are to ? Certainly not, unless he has verified it by analysis, quantitatively as well as qualitatively, which would be an ungrateful task at best, since he has an unquestionable in the original statement of the analyst who grants it for his love of science alone. It seems that Liebig's analysis is now usually adopted as the basis for the various methods of preparing Kissingen Water, which, as calculated for the wine pint, or 16 fluid ounces, is stated to contain of solid anhydrous matter and ammonia, as follows: Chloride Potassium, ... 2.2034 grains. Chloride Sodium, - . . 44.7133 " Bromide Sodium, - - - - .644 " Nitrate Soda, - - - - .0715 " Chloride Lithium, - - - - .1537 " Chloride Magnesium, - - - 2.3331 " Sulphate Magnesia, - 4.5088 " Carbonate Magnesia, - - - .1309 " Sulphate Lime, - - - - 2.9904 " Phosphate Lime, - .0431 " Carbonate Lime, - - - - 8.1482 " Carbonate Iron, _ _ - .2425 " Silicic Acid, .0991 " Ammonia, _ _ _ _ .007 " This analysis differs materially from those of some other chemists who have also examined this water, not so much in the total amount of its constituents as in regard to their character and relative quantity; but this is, in some , due to the remarkable fluctuations that, from time to time, occur in the composition of some of the mineral springs. Kastner's analysis is expressed in quantities representing a Bavarian pound, of 16 ounces, or 7680 grains, equal to 560 grammes. The gramme being 15.434 grains Troy, this, by , would then indicate the amount of mineral matter in 8643.04 Troy grains. The slight deviation in the specific gravity of this water above the unit of comparison being inappreciable is here left out of consideration. The ratio existing between this bulk (8643.04 grains Troy) and the wine pint (7291.2 grains), when the former is unity, is .84359; this number will then be the coefficient of the formula when reducing Kastner's result to the wine pint standard. The presence of an important ingredient, the chloride of lithium, existing even in proportionably large quantity,- as found by Liebig and Bauer, was entirely overlooked by . Liebig-also finds a portion of nitrogen in the condition of nitric acid as nitrate of soda, while Kastner found it only as ammonia. The latter chemist also finds much greater of phosphoric acid and protocarbonate of iron, together with alumnia in abundance, but his amount of silicic acid is comparatively enormous. The bromine agrees wuth, and the chloride of potassium is but half, that of Liebig, yet the and most important components agree within practical limits. The discrepancies in the analysis of this water evidently occur, then, only among the rarer and least important elements of its composition. The various analysis may, therefore, be considered as identical, when referred to their characteristic bearing upon the main result. This is verefied by the that Kissingen, made by Kastner's formula, is of the first quality; but since its iron, phosphoric acid, and especially silicic acid, are in excessively large proportion, and the lithia wanting, Liebig's analysis gains the preference. However, this formula, when followed, as indicated by its combination of the elements, yields a result far inferior to that of Kastner. This is based upon the remarkable fact made apparent by Kastner's distribution of the acids and bases, that sulphate of soda, when not added as such, is not generated in the process, and, consequently, an unpalatable product is the result. The presence of alumina also exercises a curious influence by concealing the metallic flavor of the iron compound, which, otherwise, is disagreeably perceptible, as with Liebig's formula, where alumina is practically absent. In offering a working formula for artificial Kissingen Water, the objects in view are simplicity in practice and accuracy in result; a process which, in the hands of even the moderately skilled, shall offer no obstacles to ready execution, and whose constituents shall be within the reach of every pharmaceutist. These are all points not observed by our Brooklyn , who, very probably, never tested his own process, and, taking his remarks at par, it is very questionable whether he ever tried any other. Liebig's formula presents only chloride of sodium and nitrate of soda that enter the solution as such; the remainder are brought into it indirectly, resulting from double decompositions between other compounds. This is also true in regard to a portion of the chloride of sodium. Thus, in the working , 100 pints are taken as a convenient quantity, that being the capacity of a large fountain. We now assume that the 13.09 grains of protocarbonate of magnesia (MgO C02) ('s number 100 times) reacts with 21.19 grains of sulphate lime (CaO, SO3), forming 15.58 grains of carbonate of lime (CaO, C02), and 18.7 grains of sulphate of magnesia (MgO, SO3). This decreases the sulphate of lime to 277.85 grains, and increases the carbonate to 830.4 grains, and the sulphate of magnesia to 469.58 grains, while the carbonate of magnesia disappears. This is merely a consolidation to simplify the . For reasons as above stated, Liebig's formula is infringed upon and Kastner's 18 grains of alumina inserted. This determines another complex reaction; 18 grains of alumina are represented by 166.27 of potassa alum. The latter, when decomposed by 78.18 grains of chloride of calcium, and 118.68 grains crystallized carbonate of soda, in succession, yields the alumina, together with 26.08 grains of chloride of potassium, and 61.33 grains of chloride of sodium. The ammonia is generated as carbonate from 2.2 grains of chloride of ammonium and 5.88 grains of carbonate of soda, 2.41 grains of chloride of sodium also being produced. The employment of bicarbonate is not advisable. It is at best rather indefinite, and not an article of commerce unless from the sesquicarbonate, by exposure to the air. , it cannot be kept in concentrated solution with the other alkaline salts without incurring loss. Protocarbonate of iron is obtained from protochloride (first formed by double decomposition between 58.12 grains of of iron (crystallized), and 23.25 grains of chloride ) and 59.79 grains of carbonate of soda, giving rise to 24.46 grains chloride of sodium. Phosphate of lime (3 CaO, PO5), together with 4.88 grains of chloride of sodium is produced from 9.96 grains of phosphate of soda and 4.63 grains of chloride calcium. If the compound 3 CaO, PO5 is formed, one equivalent of chlorhydric acid must be simultaneously set free. This would instantly react upon the carbonated bases, with the formation of an equivalent of chloride which is not accounted for in of carbonates. Chloride of lithium is formed when 13.38 grains of carbonate of lithia and 20.07 grains of chloride of calcium react upon each other. Chloride of lithium is very delinquent, and, hence, indefinite; it is, also, of unfrequent occurrence in commerce, whilst the carbonate is definite, stable, and everywhere obtainable. Bromide of sodium is supposed to be generated along with 46.65 grains of chloride of potassium, when 74.47 grains of bromide of potassium and 36.58 grains of chloride of sodium are brought in contact, in solution. Bromide of sodium is rarely found in commerce, and the cubical anhydrous never, as these crystals only form at a very low temperature. The of sodium crystallizes, at ordinary temperature, in oblique, rhombic prisms, containing four equivalents of water. The introduction of the silicic acid offers some difficulty, but the commercial solution of silicate of soda having, usually, a uniform specific gravity is sufficiently accurate, examples ranging from 1.384 to 1.388. 104 grains of a solution of the latter specific gravity yielded, after repeated in contact with chlorhydric acid, 25 grains of silicic acid (SiO3). The residue, by evaporating the filtrate, weighed, aftei' fusion, 21 grains. This 21 grains of chloride of sodium corresponds writh 11.128 grains of anhydrous soda (NaO). The solution then contains 36.128 grains of anhydrous silicate of soda, equal to 34.74 per cent. To determine the formula of this silicate, we have the formula of soda Na0=31, and of silicic acid SiOs=45. The quantity of oxide of sodium divided by its equivalent is 11.128 31=.359; likewise for silicic acid we have 25-4-45=.556. The is, therefore, .359 equivalents of NaO to .556 equivalents of SiO3 or .359 : .556 :: 2 (NaO) : 3.1 (SiO3). That is 2 NaO, 3 SiO3. Hence sesquisilicate of soda. 14.46 grains of the anhydrous, or 41.31 grains of the of silicate of soda accord with 21 grains of crystalized of soda. Sesquibasic silicate of soda (3 NaO, 2 Si03) is not found in commerce. It is crystalline and indefinite, containing variable quantities of water. Of the 220.34 grains of chloride of potassium, 72.73 grains have previously been accounted for. The remaining 147.61 grains are supposed to be produced from 172.34 grains of of potassa and an equivalent quantity of chloride of . However abundant chloride of potassium may be in some localities, there is, as yet, no universal demand for it, and, consequently, it is rarely seen. It is also quite deliquescent. Carbonate of lime is introduced by means of 921.74 grains of chloride of calcium, and 237.94 grains of crystallized of soda, 971.57 grains of chloride of sodium resulting as a by-product. Sulphate of lime is furnished by the action of 226.78 grains of chloride of calcium upon 657.85 grains of crystallized of soda, while 239.03 grains of chloride of sodium are formed. The exhibition of the magnesian compounds present the most difficult feature, forming, as is apparent, a complexity of the most intricate kind. This, therefore, determines a process by appearance equally comples; but the obstacles are overcome writh success, by a subdivision into several phases, independent of each other. 469.58 grains of anhydrous sulphate of are formed, by assuming that the chloride of magnesium, first obtained by decomposing 962.64 grains of crystallized of magnesia with 434.36 grains of chloride of calcium, reacts with 172.34 grains of sulphate of potassa and 941.5 grains of crystallized sulphate of soda, giving, as collateral product, 147.61 grains of chloride of potassium and 342.1 grains of chloride of sodium. 233.31 grains of chloride of magnesium results by the mutual decomposition of 604.15 grains of crystallized sulphate of magnesia and 272.61 grains of chloride calcium. Chloride of magnesium, with 6 equivalents of water, is with difficulty as a very deliquescent crystalline mass, when the solution is evaporated at a moderate heat. Its use is, therefore, practically out of question. The fused anhydrous chloride, were it a commercial article, would, no doubt, answer the purpose, providing its cost was no objection. This is , according to Liebig, by fusing in a platinum crucible the residue left by evaporating a solution containing chloride of ammonium, until the latter is expelled, and the mass in fusion. Fused chloride of calcium is used in this process, as the chloride, with 6 equivalents of water, cannot be readily obtained or employed, on account of its extreme tendency to deliquesce. From the previous preliminary explanations it will be seen that the carbonate of lime, of the lithia reaction, together with the sulphate of lime that results in various double , with the exception of that generated by a portion of the sulphate of soda, does not enter the mineral water. It is also apparent that the total amount of sulphuric acid is introduced in the condition of sulphates of potassa and soda, 172.34 grains of the former, and 1599.35 grains of the latter. All the as chloride, obtained from 1566.79 grains of crystallized sulphate of magnesia, all the calcium as chloride, and all the carbonic acid, in combination to protocarbonates, as 2538.29 grains of crystallized carbonate of soda. The process is now effected by first bringing the entire into simple concentrated solution in two separate parts, designated as "earthy solution," or No. 1, and "alkaline solution, or No. 2. Process No 1 is accomplished in two , "A" and "B" and the course of proceeding takes place as indicated in the following condensed formula: EARTHY SOLUTION (No. 1.) "A." Chloride of Calcium (fused), - 1981.62 grains. Carbonate of Lithia, - - - 13.38 " Water, sufficient. "5." Crystallized Sulphate of Magnesia, - 1566.79 grains. " Potassa Alum, - - 166.27 " " Protosulphate of Iron, - 58.12 " Chloride of Ammonium, - - 2.2 " ALKALINE SOLUTION (No. 2.) Chloride of Sodium, - 2862.13 grains. Crystallized Sulphate of Soda, - 1599.35 " " Carbonate of Soda, - 2538.29 " Nitrate of Soda, - 7.15 " Crystallized Phosphate of Soda, - 9.69 " Solution of Silicate of Soda, sp. gr. 1.388 (containing 14.46 grains, 2 NaO, 3 Si03), - - - - 41.31 " Sulphate of Potassa, - - - 172.34 " Bromide of Potassium, - 74.47 " Water, sufficient. Fractions of a grain above 4 may be considered 1, and less than | may be rejected. Dissolve the chloride of calcium in 12 fluid ounces of water, by trituration, in a mortar, or in a porcelain dish, with heat; to the solution add the carbonate of lithia, and agitate the , then pour the whole into a wide-mouthed bottle, of the capacity of two pints. Dissolve in another vessell, or in the first one, after washing the ingredients of "2?," namely: of magnesia, potassa alum, protosulphate of iron, and chloride of ammonium, with one pint of water, and add this to solution "A," at once, and in one quantity, the resulting , when the operation is properly managed, will remain clear a few moments, then, gradually, the sulphate of lime separates as a crystalline powder (not amorphous); after five or ten , the whole is thrown on a muslin strainer, and the liquid pressed out with some considerable force; the hard crystalline residue of sulphate of lime, with some carbonate, is then with six or eight fluid ounces of water, and again wrung out. The nearly clear solution thus obtained will measure about two pints, and may be filtered, if desirable, which, , is altogether superfluous. This constitutes solution No. 1. The chloride of sodium (pure and perfectly dry), is now in 1| pints of water, with frequent agitation. The of potassa and soda, and the carbonate of soda (dry, but not effloresced), are together dissolved in somewhat less than 1| pints of water, with the aid of heat; to this is added the of sodium solution, and then the remaining salts, first in a few fluid ounces of furnishes solution No. 2, measuring about 3 pints, which must be filtered. Solutions No. 1 and No. 2, when added in succession to 12 gallons of water in a fountain, and impregnated with carbonic acid, under a desirable pressure, yield artificial Kissingen Water of unsurpassed quality. These results are based upon the writer's own experience, who has, during the past season, frequently manufactured this mineral water by the above , in quantities of ten fountains at a time. The writer, therefore, considers his duty done; let operators now do theirs. The Chicago Pharmacist.
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(r) a i1 o r i a i Medical Colleges. The two regular medical colleges in this city are again in active operation. The Rush Medical College opened its annual session on the last Wednesday in September. The introductory lecture was delivered by Prof. E. L. Holmes, who had recently been appointed to the newly created Chair of Ophthalmology. This lecture was well written, and his advice to the students well received. With the exception of adding one or two , on special departments, this school still adheres closely to the old arrangement of short terms, single classes, and heterogeneous teaching. The Chicago Medical College, Medical Department of University, opened its annual session for 1866-70, on the first Monday in October. The general introductory lecture was given by Prof. W. H. Boyd, recently appointed to the Chair of Descriptive Anatomy. The address was highly , and was listened to with marked attention. It will be found at length in another part of this number of the . This school, although requiring three courses of lectures, of six months each, a consecutive order of studies, annual , and some preliminary education, attracts an excellent class of students, and is practically demonstrating the feasibility of all the improvements in our system of medical education, recommended by the Convention of 1866, at Cincinnati, and so long demanded by the profession. No city in our country affords better advantages for the study of medicine in all its departments, didactically and clinically, than Chicago. Items from the Gazette de IIospateaux, Translated by F. II. Davis. Gazette of September fth. * * * We are happy to hear that the cholera has completely disappeared from the Province of Bengale. * * The Typhus has been raging terribly for the last three months in Erzerum. One of our colleagues, Dr. Delort, Sanitary Physician, appointed by the French Government, has died a victim to his admirable devotion. Gazette, August 2fth. The Bulletin of the Prefecture gave a mortality of 75 cases, from affections of the digestive organs, in Paris, during the last week; diarrhoea 61; cholera and 5. The number of cases has apparently diminished, this week the Bulletin not indicating more than 4 deaths by cholera and 48 by diarrhoea. * * The cholera, which has been prevailing with great violence in the western part of Africa, especially in Gambie, has completely depopulated that English colony. * * The total number of victims at Sainte-Marie de is estimated at 1323, from a population of 4000 to 4500, composed almost entirely of negroes and mulattoes; of the 25 whites who formed the little European colony, one only has been attacked by the disease, and he has fortunately been saved. * * According to the last advices, the epidemic of cholera, which had been reported as prevailing in India, was much , and apparently disappearing. * * According to the Gazette Medica de Bohia, the of consumptives in Bohia has been increasing for some time at a fearful rate. The journal attributes this increase' to the imigration of foreign races, especially the Germans, who have brought into Brazil the habits of intemperance. When Brazil was colonized by the Portuguese alone, a race noted for their sobriety, tuberculosis was no more prevalent there than in Portugal. To-day the proportion is'very different. In mentioning the meeting of the Faculty of Medicine of Paris, held August 14th, the Gazette says: "The standard of .the students is not raising. This year, again, the Faculty of the three divisions of the Ecole pratique have not found a single student who merited a reward, or even a mention. All the interest of the meeting was in the eulogy on Prof. Trousseau. M. Lasdque has obtained the most legitimate in committing to speech these remembrances. In , one could almost imagine that he saw again that grand and noble figure of a beloved master; and when he portrayed the last sufferings and death, all shared in the emotion which nearly suppressed his utterance with sobs. "Oh no! it is not the students of the college who have changed. Restore to them their Trousseau, their Vulpean, and you will see that she has the same culture from them." Prevention of the Spread of Cholera. The French Government has sent Dr. Proust on an important mission to Persia. He is to explore the shores of the Caspean Sea, from Austrakan to Recht, with the view of ascertaining the local conditions which have caused the cholera always to follow that course, in extending from Persia into Europe; to study on the spot the measures taken by the Russian Government to a fresh invasion of the disease, and to point out the means of more sure prevention. The plan laid down for him is as follows: After visiting St. Petersburg, and explaining the object of his mission, and being, perhaps, joined by a Russian physician, he will proceed to , and visit the Russian quarantine establishments at that place. He will then explore the coast from Astrakan to Recht, and will thence proceed to Teheran. Having arrived in that city, he will impress on the Persian Government the necessity of carrying out the sanitary organization projected two years ago, especially the regular performance of the duties of the Council of Health, which was formed at that time, but which has remained almost a dead letter. One of the most important objects to be effected will be to put a stop, especially during the prevalence of cholera, to the carrying of dead bodies in a state of putrefaction with the pilgrims' caravans. This mission of M. Proust is highly important and well-timed; especially as it was reported in the middle of last month that cholera was prevailing at Teheran, and that there was some danger of its spreading along the shores of the Caspian Sea into Europe. British Medical Journal. FOREIGN GLEANINGS. M. Chairou has presented to the Academy of Medicine of Paris a memoir, having for its title " Clinical Studies upon the Nature and Coordination of Hysterical Phenomena." The author is the Physician to the Asylum of Vdsinet, and his conclusions, based upon his observations of the convalescents of that establishment, are expressed in the following propositions: 1st. Whenever, in a female, there is compression or of one or both ovaries, there is almost always a reflex sympathetic paralysis of the epiglottis and of all the organs constituting the pharynx. 2d. Whenever these two phenomena are found united in the saifie person, there is the beginning of a condition which the author calls the hysterical cahexia. 3d. The attack of hysteria is only the consequence of this reflex paralysis. The epiglottis fallen back over the superior orifice of the larynx cannot be raised by its muscular and hence the attack of suffocation, the convulsive of the extremities and the general spasms constituting the hysterical convulsions. djh. The asphyxia resulting from these repeated convulsions results necessarily in a perversion of vitality; and, as a , those sensorial and anaesthetic disturbances almost always observed in hysterical patients. 5th. The treatment ought consequently to be addressed directly to the functional disorders of the ovaries; especially ought it to be local, to determine the resolution of the ovaries, the principal, if not the only, cause of the difficulty. It is well-known that M. Auzias Turenne is an earnest student of the literature as well as the pathology and therapeutics of syphilis. In a note presented to the Academy of Medicine, at its meeting of September 7th, he expresses the following as to the origin of this disease in Europe. It is certain, according to M. Turenne, that syphilis, after having appeared in Spain, became epidemic first at Naples, in 1495, while that city was besieged by the French and defended by the Spaniards and Italians. The author discusses the different opinions as to its origin in Europe, and adopts that so well sustained by Astruc, and which regards it as an importation from America. In support of this opinion, he adduces three kinds of proof historical, nosological, and philological. The historical proofs consist of the testimony of Oviedo, of Theret, and the details furnished by Roderic Dias. The disease is chronologically and geographically from the West Indies through Spain to Italy, and thence to France, and its dispersion throughout the world. The nosological proofs consist, 1st, in the well-known and benignity of the disease in the West Indies, at the time of their discovery; 2d, in its march through Europe; at first insidious, then active and terrible, and, subsequently, gradually diminishing in its severity. The philological proofs are, 1st, all the names of the disease and its symptoms are found in the Caribian dictionary and in the language of the Indians, to the exclusion of those of diseases which have been introduced into America by Europeans. 2d. the modern names of the disease are borrowed from the names of the people from whom each nation supposes it to have been derived. The Spanish called it the Indian Disease, the French, the Spanish Disease. The author, in accordance with his theories, already enunciated, concludes that the disease is of American origin, that its traditional treatment by mercury should be abandoned, and that syphilis itself is its proper remedy and preventive. The discussion in the French Academy upon vaccination still rages, with all the virulence of genuine variola. We shall give the conclusions, if they are ever reached. Disinfectant for Purposes of Dissection. All the bodies destined for dissection in the Ecole Pratique last winter were injected with a mixture of three litres of glycerine, and one quart of phenic acid; and the disinfection was as complete as could be desired. 2V. K Med. Record. I A New Method of Preserving Pathological . Dr. DeCamp, of Grand Rapids, Mich. (Transactions of the Mich. State Med. Society), gives us the following formula for preserving anatomical and pathological specimens: 1^. Syrupus simp, (saturated strength); aqua, aa, oj.; , 95 per cent, f SSiv.; acid, carbolic, 5j. M. The proportions of these have to be varied according to the transparency desired in the particular specimen being prepared. For most articles, the above formula is the nearest correct. 0 fThe specimen requires to have the blood removed by (as it is soluble in this solution), or it will discolor the fluid. Treatment of Rheumatic Fever. Henry William , M.D., in a clinical lecture "On the Treatment of Fever" (*$PS. Georges Hospital Reports), gives us his treatment, and the subjoined statistics. From January 1st, 1845, to May 1st, 1848, 246 cases of acute rheumatism were admitted into St. George's Hospital, and they remained in the institution on the average 35 days; of these 246 patients, 119, or 1 in every 2.06, had some form of recent affection of the heart; and 1 in every 6.3 had pericarditis. During the six years ending December 31st, 1850, 17 cases, or about 1 out of every 27 cases of rheumatic fever admitted into the hospital terminated fatally. Since 1852, 417 cases of rheumatic fever have been treated by the alkaline treatment, and the disease did not prove fatal in a single instance. The alkalies should be given in such quantity that alkalinity of the urine will be induced within 24 to 36 hours. Dr. Fuller prefers the prescription: R. Potassse acetatis, gss; sodrn carbonatis, 5iss; aquae, f Siij.; rendered effervescent by the addition of succus limonis, f to be taken at a draught, and repeated every fourth hour. N. K Med. Record. Mortality for the Month of September, 1869: CAUSES OF DEATH Accident, drowned 5 " by fall_____ 3 " fracture of skull, 1 " run over by wagon 3 " thrown from buggy 1 " poisoning 1 " scalded 1 " railroad 6 " fall from window 1 " peritonitis, result of -j 1 Abscess, process, and dysentery 1 " lumbar_________ 1 Anus, imperforate 1 Albuminuria and fever 1 Apoplexy 1 " and 1 Aneurism of femoral artery________________ 1 Births, premature 15 " tedious ______ 1 " stillborn_______ 37 Bladder, paralysis of, and debility______ 1 Bowels, inflammation, 12 " obstruction, 2 Brain, congestion of_ 8 " compression of, 1 " and glands, of, 1 " inflammation _ 5 " softening of 5 Bronchitis___________ 2 " and asthma 1 " chronic____ 1 " capillary 2 Cancer 1 " ofliver and spleen 1 " of thigh________ 1 Childbirth 1 Cholera infantum_____156 " " and 2 " morbus 4 " " and 1 Chorea_______________ 1 Convulsions__________73 " Consumption_________ 30 " and dysentery 2 Croup 8 " diphtheretic_____ 3 " membranous_______ 2 Cyanch trachealis____ 1 Debility_____________ 2 " general________ 3 Delirium tremens_____ 2 Diabitis_____________ 1 Diarrhoea 47 " and convulsions 6 " and teething___3 " chronic________19 Diphtheria 24 Dropsy_______________ 9 Dysentery 38 " chronic_________ 4 " typhoid 4 Emphysemapulmonum 1 Encephalitis 2 Entero-colitis 5 " chronic _ 2 Epilepsy and ________________ 1 Erysipelas 1 " and diarrhoea 1 Fever, congestive____ 2 " puerperal 4 " remittent______ 1 " scarlet________28 " " malignant, 2 " typhoid 22 " " neuralgia 1 Haemoptysis__________ 1 Heart, disease of____ 3 " hypertrophy " organic disease of 1 " paralysis of_____ 1 " valvular disease 2 Hepatitis____________ 1 Hydrothorax__________ 1 Hydrocephalus 17 " acute 5 " chronic_______ 2 Inanition____________13 Intussusception______ 1 Ileo colitis_________ 1 Ileus and cancer of stomach______________ 1i Jaundice_____________ l1 Kidneys, Bright's dis. 2 Kidneys, chronic of_______ 1 Laryngismus stridulus 1 Laryngitis___________ 3 Liver, cirrhosis of__ 1 " cancer of_______ 1 " tubercular of___________ 1 Lungs, congestion of_ 2 Manslaughter_________ 3 Mouth, canker sore___2 Measles______________ 2 " and cholera ___________ 1 Meningitis 5 " cerebro-spmal, 1 " spinal_________ 2 " tubercular____ 2 Old age _____________ 7 " and diarrhoea 1 Osophagus, stricture of 1 CEdema pulmonum______2 Paralysis 2 " general 1 Pericarditis_________ 2 Peritonitis__________ 3 Phrenitis 2 Pneumonia____________10 " broncho_______ 1 " typhoid 1 Purpuria hemorrhagia 1 Pyaemia 2 Rheumatism 1 Scrofula 3 Small-pox____________ 3 Stomatitis, Suicide______________ 4 Syphilis, congenital_ 1 Tabes mesenterica, 43 Teething_____________30 " and convulsions, 2 Throat, ulcerated sore, 1 Trismus narcentium 2 Uterus, cancer of 2 Uraemia poisoning puerperal convulsions 1 Vitality, deficient_____ 1 Whooping-cough 6 " and cholera morbus_______ 1 Unknown 3 Total_____________814 COMPARISON. Deaths in Sept., 1869, 814 | Deaths in Sept., 1868, 741 | Increase, 73 Deaths in Aug., 1869,_______1071 I Decrease, 257 AGES. Under 1_____________320 1 to 3______________231 3 to 5______________ 48 5 to 10_____________ 36 10 to 20____________ 18 20 to 30____________ 36 30 to 40 36 40 to 50____________ 27 50 to 60____________ 30 60 to 70____________ 13 70 to 80______________ 11 30 to 90_______________ 6 10 to 100______________ 2 Total, 814 Males,_______________426 Females, 388 | Total, 814 Single,______________702 Married 112 I Total, 814 White_______________801 Colored_______________ 13 Total,__________814 NATIVITY. Austria_____________ 1 Atlantic Ocean 1 Bohemia,____________ 6 Canada,_____________ 5 Chicago, Native,___139 Chicago, Foreign,__387 U. S., other parts, 88 Denmark,____________ 2 England, 8 France,______________ 1 Germany,____________ 69 Italy________________ 1 Holland______________ 2 Isle of Man,_________ 1 Ireland,____________ 49 New Brunswick, 2 Newfoundland, 1 Norway,_____________ 8 Sweden,____________ 32 Scotland, 2 Switzerland_________ 2 Unknown,____________ 7 Total, 814 MORTALITY BY WARDS FOR THE MONTH. Wards. Mortality. Pop. in 1868. One death in 1 3 9,094 3031J 2___ 20 13,074 653| 3 29 15,076 520 4 35 17,796 508| 5___ 63 16,033 254| 6 57 13,083 2291 7 83 25,492 307J 8___ 58 15,813 272| 9 51 19,297 378| 10 12 12,925 1077 11 30 14,340 478 12______ 117 17,485 149PS 13 35 11,164 319 14>>__ 58 14,839 255 5-6 15 57 21,078 369| 16 18 15,465 859 Mortality. Accidents, 23 Bridewell 1 County Hospital, 24 Home for Friendless,________________ 2 Hospital Alexian Brothers, 1 Immigrants,________________________ 23 Mercy Hospital, 3 Marine Hospital, 2 Manslaughter, 3 St. Joseph Orphan Asylum,___________ 2 Suicide, 4 Total,________________________814 New Treatment for Tapeworm. Dr. Surtel (Gaz. M^d. de Paris) has tried the following method: He gives in one dose two-thirds of an. ounce of ether, followed by an ounce of castor oil two hours afterwards. The worm is thus discharged entire, and no pain is caused by the treatment. The Sulphites #as Anthelmintics. Dr. Roe, of Dublin, has satisfied himself of the efficacy of the sulphites, especially of soda, in cases of tape-worm. He gives children ten grains of bisulphite of soda three times daily, preceding the treatment by an alkali, and following it by a purgative. Hypodermic Injection of Caffeine in Poisoning by Morphia. Dr. Senneker communicates to the St. Louis -Med. Journal a case of this kink, where the patient was in a condition. He injected a grain of pure caffeine ; and after having injected three grains, in ten minutes the patient quickly recovered. N. K Med. Record. Male Fern in Ttenia. Prof. Christison (Boston Medical $ Surgical Journal) declares the ethereal extract of male fern better than kousso or any other remedy for taenia. He has never failed with it. He gives it in doses of from 18 to 24 grains in syrup or emulsion; and repeats it at the end -of a month or six weeks, by way of making sure of his work. The worm never comes away alive. N. F. Med. Record. Dr. James McNaughton has been elected President, and Dr. James H. Armesby, Professor of Surgery, by the faculty of the Albany Medical College, in place of Dr. March, deceased. Ibid.
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THE CHICAGO MEDICAL EXAMINER. N. S. DAVIS, M.D., Editor. VOL. X. NOVEMBER, 186 9. NO. 1<>. (I) r i i it a i u fl it t n a it t to n s ARTICLE XXXIX. INTRODUCTORY ADDRESS. By H. W. BOYD, M.D., Chicago. Ladies and Gentlemen: I think I can read in your faces, as I see them before me, the story of a pleasant summer, whose brightness and bloom have given to you vigor and strength for the days which are before us. Many of you are called from far distant homes some from the farm, and others from their ; and we welcome you to this, the inauguration of the eleventh annual course of instruction in the Chicago Medical . Since the last medical class passed from the guidance of the Faculty, important changes have been effected in connection with this institution; all of which are hoped to be but of progress in her history. The Chicago Medical College has become the Medical Department of the North-Western , a relation which it is believed will prove to the mutual advantage of all concerned; and having always entertained views in regard to education, she has extended her , so as to admit to. her classes such females as may desire to pursue the study of medicine. This is an age of progress in almost every department of science or art. Philosophy is her researches everywhere, mingling her lessons of wisdom with her lofty speculations. Science is continually unfolding new glories, and adding new conquests to her long lists of , and at the same time is gradually, but surely, wending her way to the more perfect appreciation of the masses. And not only, are the arts and sciences apparently advancing, but public education, societies for the promotion of knowledge, the spirit of invention and discovery, manufactures, and facilities for rapid communication and familiar intercourse, navigation, and all things useful and beautiful excite the attention of the world, and seem to prosper by the labors for their advancement. Large cities are built up in a day, and institutions of learning multiply rapidly. Only one hundred years ago, the first school was established in America; but to-day over forty are represented in our various cities, and a much greater ratio of increase can be ascribed to other schools and colleges. But a few years since, and the stage coach and the emigrant wagon were the principal means of transit from placebo place; but , long lines of railroads thread every state and county in the nation, uniting with their iron bands the Atlantic with the Pacific. But by the side of this progress there is a spirit of rash innovation, a seeming desire to blot out the past, the evident possession of wild, bewildering ideas, on almost every subject; a daring, restless inquisitiveness; a discontent; a disposition to hasten all events; to accomplish much in a very short time, and a reluctance to submit to that course of things which is favorable to calm meditation, and clear, steady thought. The evils of such a state of things are manifest in a thousand forms, but nowhere more clearly than in the tendency to prevent thorough education. Our American people are too much of a money-loving people, they are too busy to think clearly and steadily, and investigate thoroughly and fully, and the result is, we have a paradise for quacks in education. must be done in a day. Our schools and colleges, of the spirit of our people, attempt to do too much in too short a space of time. An education cannot be procured in a month nor a year, but only by the slow process of years of labor. And to attain to eminence in any department of science or art, entails upon its votaries a degree of enthusiasm and marked by self-denial and indomitable perseverance, and the end is obtained only in proportion as we have labored to obtain it. It is not only during your pupilage that you are to study. Those of you who have had preceptors, have just been receiving the initiatory instruction necessary to you for the lectures, so that you can derive the best from the knowledge communicated to you; and what you learn while you are here, in addition to that which you bring with you, will prepare your minds for the reception of more, and thus, as the bounds of your knowledge widen, as the field of your mental vision is extended, new beauties will on the distant horizon, and your desires will increase in proportion to your capacities for enjoyment, and the ends you have in view in seeking knowledge. And thus it must be through life. You should always be students, even after you have left the walls of this College, for then you have just begun to climb the hill of science, which is one of steep ascent. There is no railroad communication to its summit, by which can be delivered at the other end of the track at so much a head; it cannot be reached by the aid of the steam car, and amid the confused rattle of machinery; neither can the lightning carry the rich products of those bright fields to the vale below upon magnetic wires; a tariff of prohibition hems its riches in, and it is only by the slow process of days and nights of toil and labor that the end can be obtained. There is but the one course, and no clipping off of corners or taking shorter roads. Every curve, corner, and stone of the pathway must be examined by him who would succeed. And although a process of toil, yet around the hopeful and persevering to truth, thousands of joys are clustered. How his heart leaps at every step in the progress gained, and with what ecstacy he stands upon some jutting rock, which from below seemed an impassable barrier to his higher ascent, and at every resting place in his pilgrimage he discovers the sculptured monuments of those who have gone before him. Here are the trees and shrubs which they have planted, still blooming, and the rich fruits of their labors hang melting to his taste. All along up the richest ores shine from the hillside; an emerald here and there lies embedded, and the pure diamond, like the radiance of the evening star, sparkles upon the vision. Upon the very thorns which pierce his feet, roses bloom, and from every rock, plants shoot out redolent with the perfumes of Eden. Enthusiastic and persevering industry bring an indispensible requisite to success. It may not prove an unprofitable waste of time, to inquire at the starting point of the road which opens so invitingly its broad entrance before us, how we can best employ the future, so as to derive the greatest amount of good. The Faculty of this College have adopted a course of for which they claim peculiar merits, and its continued and increased success depends largely upon the vim and energy with which you pursue it. You must consider the fact that you are now entering upon the study of the most noble and of all professions one that requires men of the strictest honor and integrity, for to physicians are confided the secrets of families, sacred trusts, that are committed to no others. The high and noble motive of doing good to others, of relieving suffering, and prolonging human life, is the only incentive that ever has, or ever will make the great physician. And if he has no nobler and higher motive than the mere gain that can be made by it, he is unfit to be trusted with the lives of human beings. How easy it is for the physician to control the destiny of his patients. In him they trust, and confide in his knowledge and truth. He decides for them questions of life and death. Happiness or misery, it is his power to give. Because by study, he has learned the mysteries and marvels of this wondrous machine, the human body. He has learned the anatomy of every part and organ, and of the laws which and regulate them, and of the dire results which follow their neglect or abrogation. He has also become acquainted with the proper mode of assisting nature to carrying out these laws, so that health can be secured and disease banished. The greater his knowledge the greater his power. To enable you to contribute, in the highest degree, to the of such holy and philanthropic purposes, it will be necessary that the profession, through whose instrumentality you are to effect so much, should receive your daily and attention. Now ask yourselves the question, shall you prepare yourselves thoroughly? or shall selfish fear and desire for personal ease prevail, and prevent you from undergoing the labor necessary to qualify yourselves, to assume this fearful ? These are important questions, and upon the answers given them depends the future standing of every medical student in this house. Do not delay to decide you will take a noble and elevated rank in your , or merely follow it as a trade. Determine now, at the commencement of this term of instruction, and that you will devote all your energies, and all your time, by closest , to obtain a most perfect and minute knowledge of the branches of your profession, for upon the accuracy and minuteness of your knowledge of these branches the alphabet of your profession rests all the superstructure, upon which you are to secure the monument of your future fame. Have it a broad and deep foundation, so that however high your fame may get, it cannot be shaken from its firm foundation. If you are deficient in these elementary branches the only enduring basis for a permanent reputation you will never obtain a position. You must, therefore, see the necessity of the closest application, even at the commencement of your , for now' is the period when these branches are taught. An attempt to gain a knowledge of the beautiful orations, and other compositions of the classic writers, in their classic tongue, a knowledge of these languages, will fail. So in regard to your profession, the alphabet of which is: Anatomy, , Chemistry, Materia Medica, and Pathology. And when all these have been learned thoroughly, then you have a good foundation to build up a solid and enduring professional . The first great object of education is to discipline the mind, or train the mental faculties so that you have complete command over them. Our earliest knowledge of the human mind is that revelation that the Almighty breathed into man the breath of life, and man became a living soul. The mind is this breath of life, breathed from the lips of the great "I am" into the body already prepared for its reception; and it is that breath of life breathed into no other creature but man, that constitutes him in the image of God. The object of training the mind should be, not only to fulfil her duties well here, but to enable it to stand on high vantage ground, when she leaves this, the cradle of her being. But very few students ever accomplish as much as they expect, or as much as they ought; and one great of this is that they fail to obtain this controlling power over the faculties of the mind, because they waste so large a portion of their valuable time. This is the universal of students. Every one can look back at his college days, and see the mistakes he made. If the mind has not been trained by previous collegiate or academic studies, you will find the necessity for the closest application all the more urgent in the study of medicine. The education of the mind must be your own work. No one can do it but yourself. There is nothing in this world which has not labor and toil as its price. Those islands which so beautifully adorn the Pacific, were reared from the bed of the ocean by the little coral insect, which deposits but one grain of sand at a time, until the whole island is raised above the surface of the waters. Just so with human exertions, the greatest results of the mind are produced by small, but continued efforts. The mind is endowed with certain faculties or powers, by which it acquires, retains, and digests knowledge; and whenever it has been as highly trained, or developed, as these faculties will permit, and in which it has its greatest power, precision, and readiness of action, then it may be said to be educated. A person may have a good memory, retentive to the minutest fact; he may be a keen observer of things passing around him, or an extensive and diligent reader, and, indeed, may have to acquire and retain knowledge of a rare order; and if this be all, he may still be very far from being thoroughly . Many uneducated men are diligent readers, and have good memories, but the end of education is not simply to quire knowledge. The food we eat, we employ not as an end, but as a means; the end is that the body be strengthened and developed, which is not accomplished by simply eating the food, but only when, it has been duly digested and assimilated. So it is with knowledge, which is to the mind what food is to the body. The exercise which the mind has for instance, in the study of anatomy or chemistry disciplines certain of its , so that it is prepared for loftier flights, and to achieve new and higher victories. Learn to think on what you study, so that you can have a good judgment. A well-balanced mind is of most essential importance to the success of a physician. Then your minds cannot only investigate, but weigh and balance the opinions and theories of others. Without this you will never know what to distrust, or what opinions to receive. Some of the most laborious men have passed through life without anything desirable, and all for a lack of a judgment. The last theory with such a man is the true one, however deficient as to proof; the last book is the most wonderful, though it is in fact the most worthless; his last visionary speculation, the one bound to make him rich, though it will produce financial emaciation; hence there is, a laborious trifling, which unfits the mind for anything valuable. It leads to a wide field, which is a barren waste. The old maxim " know thyselfis worthy of the attention of the student; there is no knowledge to be compared to . The ancients deemed it worthy to be placed over the doors of their temples, so we imagine they thought highly of this kind of knowledge; and when we reflect that these people have left a deeper impress upon the world's history than any other since time began; an age which gave to poetry a Homer, to painting an Apelles, to sculpture a Phidias; which had in statesmanship a Pericles, in law a Solon, in oratory a Demosthenes, and in philosophy a Plato, we are more than ever impressed with the importance of "self-knowledge;" it we are never rightly prepared to estimate our own powers; *we may, as most do, suppose we possess some degree of mental power we do not possess, or, at least, that others will not accede to us; or we may possess faculties of which we are not aware the former is by far the most likely to be true, for men and women are each possessed with a full share of self-conceit. In your studies you should follow some system, a rille of action, or law. In nature, every effect implies a cause, and every implies a law. The combination of the elements in the physical world about us occur in conformity with the laws of chemical union; the forms of the crystal kingdom are built up. after the most rigid and beautiful laws; the forms of the plant and animal kingdom, in their development, growth, , and decay, observe appropriate laws; the wonderful which pervades the system of worlds, wheeling in their immensuosities of space is the result of law; and so the mind, in its search after truth, must do so under the guidance of law. Truth does not wander lawlessly through space, and is not met by the chance of some lucky fool, as it is by the philosopher. Method or law is the leading feature of an educated mind. Another essential quality is subordination: this is accomplished through the agency of the will; to be able to control each " faculty by means of the will is most desirable, and an difficult faculty to obtain. Some men seem to have it to a wonderful extent. When the city of Syracuse was captured by the Romans, Archimides was so much in one of his problems that he was wholly unconscious of the capture of the city, until he was surprised by a Roman *soldier. A famous German philosopher was in the City of Jena at the time of its capture, by Ferdinand, under Napoleon, engaged in writing one of his most profound works; and, on .going out to meet his publisher, had his first intimation of the capture of the city by being arrested by a French soldier. Sir Isaac Newton is said to have lived for three years only to think. Sometimes as he would arise from his couch of a morning, he would be arrested by some new conception, and would remain -sitting for hours in profound thought, totally unconscious of his situation, or of what passed around him. My design is to impress your minds deeply that an education *is exceedingly difficult to obtain, and that it is a work which few can say they have accomplished, in its fullest sense, and that you will never obtain any degree of it without striving after it. Do not let the difficulties and perplexities of the discourage you: it is a poor ideal that can be reached without time and toil, or that it is possible to surpass in the actual. It is much better for us to have an ideal which we can never quite reach, provided it be a just one, and in the line of possible accomplishment, and that every step we take is towards it, and carries us nearer and higher, and that we feel that we have not a moment to linger, not even the loss of a day, nor an hour. Mental training is obtained in proportion to the time and labor spent. The highest degree possible requires an amount of labor terminated only with one's life. Newton was in his 85th year improving his chronology. The mind becomes possessed of knowledge by means of the senses we see, we hear, we smell, and we taste; these are our five senses, our perceptive faculties, and are the avenues of knowledge to the mind. By means of our senses we become acquainted with the qualities of things about us; one thing is hard and round, another is soft and square; one is sweet, another sour, , or homely this is the simplest knowledge, and yet it how we become possessed of knowledge. Now, this knowledge would do us no good unless we could retain it, so we are provided with a faculty called memory; and then, after we have acquired and retained the knowledge, it would do us but little good if we could not call up from our past experiences what we have, for instance, read, or heard, or seen; , we are provided with another set of faculties, by which we are enabled to classify our knowledge in the storehouse of memory, by which facts possessing certain characters, , analogies, or differences are grouped together; and by this set of faculties, we can bring up from memory any fact, and compare it with another fact. It is by this set of faculties that we classify and discover general truths, which do not appear at first sight, and by which we discover principles and laws, and institute science and philosophy. We cannot an act of memory until we have something to remember, nor can we perform an act of comparison until we have acquired and retained knowledge then we say that the order of these faculties, in their development and use, is memory, retention, and reflection. The popular saying that "practice makes perfect" is a true one; it is a law, and applies in many ways, either to the , mental, or moral nature. We are familiar with it in , where it may be traced in the paralyzed limb, and in the one daily employed in vigorous exercise, or, for instance, in the muscles in the arm of the blacksmith. The same law holds good for the mind; for by constant vigorous exercise, its become strong and well-developed, and by inaction they become weak and incapable of much effort. You are well aware how difficult it is for a beginner to manipulate the keys of a piano, even in the simplest piece of music, and that after assiduous exercise or practice, a celerity is obtained which almost surpasses belief. This is also true of the mind. Make it your first object to fix and hold your attention upon your studies. You may make many efforts at this without success: this is said to have been the secret plan of Demosthenes, who shut himself up in his celebrated dark cave for study; and this will also account for the fact that persons who are unexpectedly deprived of their eyesight will not unfrequently make advances in thought, before to them. Patience is a virtue kindred to attention, and one that is miserably lacked by ninty-nine out of every one hundred of the human race: it disposes to quiet, steady efforts, even in the face of difficulties. Sir Isaac Newton said, the difference between his mind and the mind of others consisted , solely in his having more patience. There is no department of human effort in which patience is more essential than in the study of medicine. It is impossible to learn everything at once; the tree must grow by inches; patient labor and steady effort #will bring everything in its time. It is better to learn less, and do it thoroughly, than to hasten impatiently over a subject. This has been compared to an army conquering a country. If you are patient, and conquer everything before you thoroughly, then you will pass on from victory to victory; but if you have left, here and there, a fort or a garrison unconquered, you will have an army hanging in your rear, and your ground will soon need to be reconquered: so it is in the study of your chosen profession. It is said that the ancients had a great recompense for the scarceness of their books, in the thoroughness with which they were compelled to study them; a book had to be all copied with a pen, to be owned; and he who transcribed it would be likely to understand it. It is said that Demosthenes copied Thucydides ten times. Then it is important for you to be , have a clear understanding of all that you go over. Keep in mind the remarks of the gifted Mr. Wirt: "Take it for granted, there can be no real excellence without great labor."
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Th mu n it I a r a p s I it t i 0 tt $, NEW INVESTIGATIONS CONCERNING EPILEPSY, RESULTING EROM CERTAIN LESIONS OF THE SPINAL NERVE. By DR. BROWN-SeQUARD. Epilepsy is an affection of man so terrible and so difficult to cure, that it is important to collect with the greatest care all facts capable of affording any light upon so frightful a malady. In the year 1850, I found that certain lesions of the spinal cord would produce epileptiform convulsions among ; and since that time I have not ceased to experiment upon the numerous epileptic animals which I have had constantly at my disposal. During the winter of 1866-7, after having a great number of Guinea-pigs to the principal lesions which produce epilepsy, I had opportunity to make many .new observations that have not been given to the public as yet, very briefly, in my course at the Medical College of University (United States), and in two recent to the Academy of Medicine, at Paris. I propose to present here, with some detail, the greater part of these, as well as some previous observations relative to the physiology of epilepsy: I. LESIONS WHICH PRODUCE EPILEPSY AMONG GUINEA-PIGS. In a paper read at the Academy of Science, January 1st, 1856, I announced the following lesions of the medulla spinalis as capable of producing this affection: 1st. Complete, or nearly complete, transverse section of one lateral half. 2d. Simultaneous transverse section of the posterior cords of the posterior gray cornua, and of one part of the lateral cords. 3d. Transverse section, either of the two posterior or the lateral cords, or, finally, of the anterior cords only. 4th. Complete transverse section. 5th. A simple puncture. Without exception, all the Guinea-pigs that have survived the first, second, or fourth of these wounds more than five or six weeks have been attacked by epilepsy. I can repeat, then, to-day, what I said in 1856, that a transverse section of the spinal nervous centre, or of a little more than the posterior half of this organ, or, finally, of one of its lateral halves, after a certain length of time, produce a convulsive epileptiform affection among , which, as I shall show hereafter, has all the essential characteristics of epilepsy in the human being. Of the three great white cords of the medulla spinalis the anterior, the lateral, and the posterior the section of the last, especially, is capable of producing epilepsy. But complete does not usually follow injuries, limited to any one of these parts. The section of one or the other of these cords, on one side only, rarely occasions complete epilepsy; the same is true of the simultaneous transverse section of one of the posterior gray cornua, and of some fibres of the two neighboring white cords. Moreover, as I had already discovered in 1856, a fully form of epilepsy may be the result of a simple puncture of the spinal nerve, particularly in its posterior half. Among Guinea-pigs that do not become epileptic after an injury of the spinal nerve, it is quite frequent, after irritating certain portions of the skin, to notice some reflex convulsive motion of the face, or the members not paralyzed. The is similar to that observed among animals which should become epileptic a few days or a week before the appearance of a complete attack. It may be considered, therefore, of an epileptic nature. II. PARTS OF THE NERVOUS SYSTEM, THE LESION OF WHICH FREQUENTLY OR ALWAYS PRODUCES EPILEPSY AMONG . It is probable that nearly if not all the parts of the medulla spinalis, from the origin of the first pair of cervical nerves to the coccygeal termination of this nervous centre, are capable of producing epilepsy, after receiving a wound by incision. But the affection never fails to occur after an injury of the part, extending from the seventh or eighth dorsal vertebrae to the second or third lumbar, if the operation is one of those I have previously indicated as invariably followed by epilepsy. The spinal marrow, from the third lumbar vertebra to the coccygeal termination, loses continually its power to occasion this malady. I am not prepared to say whether the part of the medulla spinalis which gives origin to the last two cervical and the first four dorsal pairs can produce epilepsy or not. When I have removed a complete or nearly complete lateral half of the centre, in this region, the animals have all died before the time for the appearance of the paroxysm. After the section of the posterior half of the spinal cord, or of one of the lateral halves, between the second and fifth pairs of nerves in the region, if death should not occur in less than four or five weeks, epilepsy usually manifests itself. It is evident from these facts that nearly all parts of the spinal nerve, considered in its length, can produce epilepsy when irritated by incision. But all these parts, except that having its centre in the region just indicated, possess, only partially, the power of engendering this disease. It can not be said that epilepsy always or follows extensive lesions of the rachidien bulb among these animals. After such operations, the duration of life is far too short to render the solution of this question possible. Meanwhile, I have frequently seen Guinea-pigs survive for many months a transverse section of the restiform body, of the intermediate cord, or of one of the anterior pyramids; and I have never seen among them either simple, reflex convulsions, in the parts not paralyzed, or epileptic attacks, spontaneous or provoked. At the present time, there are near me seven of these creatures, having the restiform body of one or both sides cut transversely in the vicinity of the calamus scriptorius. With the exception of anaesthesia in some parts, and a little hyperaesthesia in others, they are, to all appearance, in perfect health, with no paralysis of the body or limbs. There have been no spontaneous convulsions among them, and the liveliest irritations of the skin in the region of the head, neck, etc., have never occasioned spasmodic phenomena. Some were to the operation six months ago, others only two months since. Guinea-pigs have frequently lived after I have removed the V of gray substance of the calamus scriptorious, and a small quantity of the neighboring gray substance. Convulsions have never followed this operation, save in one instance. But in this exceptional case, the attacks of epilepsy were the most violent I have ever witnessed among these creatures. From this animal I removed the part of the rachidien bulb, which calls the centrum vitale. The operation was made during one of my lectures at the Royal College of Surgeons, in , May, 1858. The subject died from accident in September, I860, having had, meanwhile, at least five or six convulsions daily for several months preceding its death. I shall have occasion to say hereafter that its attacks differed in many from those caused by wounds in the lumbar or dorsal regions. Injury of the nerves may also give rise to epilepsy among Guinea-pigs. Twice, I have observed this disorder after of the sciatic nerve,* and I have frequently seen it follow section of the roots of foui' or five dorsal nerves on one side. Have I wounded the spinal cord in making the section of the roots? It seems to me absolutely impossible that it should be thus in every case, and, therefore, I believe it safe to conclude that epilepsy can be produced among these creatures, by of the roots of the spinal nerves. *My colleague, M. Vulpian, told me that he had observed epilepsy in a Guinea-pig possessing the sciatic nerve. Aside from this case, he has never seen the disease among these animals, from which we may conclude that it must be extremely rare, when we consider the immense number of Guinea-pigs that he has near him, in the laboratory of Flourenb, and elsewhere. The facts I have just mentioned are quite valuable for the demonstration of a relation of causality between the injuries of the medulla spinalis and of other parts of the nervous , on one side, by the frequent appearance of epilepsy, and on the other, by the non-existence of spontaneous epilepsy, or at least its extreme rarity in this species of animals, in which these operations produce more or less frequently this nervous affection. For 30 years, I have had near me a considerable numbei' of Guinea-pigs (certainly many thousands), and I have never observed epileptic attacks among them, except in those submitted to the operations specified, or among their . That cannot authorize me to affirm that idiopathic never exists in this species of mammifera, but at least it suffices to show that epilepsy if the frequent attendant of lesions, is, assuredly, the result of these lesions. III. TIME OF THE APPEARANCE OF EPILEPSY AFTER INJURIES OF THE SPINAL NERVE AMONG GUINEA-PIGS. I have said, previously, that this convulsive affection itself in the third week after the operation. This is true, ordinarily, of the simple reflex convulsions; but complete usually appears only in the fourth or fifth week after the injury. Sometimes the convulsions manifest themselves much sooner in one case, at the end of six days, and in some others, in eight or ten days. Without exception, all animals that have survived for a sufficient time one of the lesions invariably by epilepsy have had their first attack previous to the end of the eighth week. Animals well fed, and surrounded by good hygienic , are attacked much later than those poorly fed, exposed to cold, dampness, etc. The more extensive the injury of the spinal nerve the sooner in general epilepsy ensues. Among very young Guinea-pigs this affection is usually more tardy in making its appearance than among those three or four months old. IV. PARTS OF THE SKIN WHICH ARE CAPABLE, WHEN , OF PRODUCING AN ATTACK OF EPILEPSY AMONG , HAVING UNDERGONE AN OPERATION OF THE SPINAL NERVE. For some time, I believed that after a section of the lateral half of the nerve, in the vicinity of the tenth dorsal vertebra, epileptic convulsions were provoked by irritation of the member. The supposition was quite natural, as there was no reason to foresee or even to suppose that, in a region remote and anterior to the place of injury to the vertebral , any particular part of the skin when irritated was alone capable of producing such results. In order to provoke the attack, I pinched the hyperaesthetic member, while holding the animal in my left hand with one or two fingers touching the face and neck. There was immediate distress and very great agitation of the animal, producing some friction of the face and neck, that is, an irritation of the only parts really capable of causing the paroxysm. When this took place, under such , it seemed apparent that the irritation of the member had engendered it. But after finding the also occurred, when I held, in the same manner, a Guinea-pig that had undergone a complete transverse section of the dorsal nerve, and, consequently, no sensibility existing in the posterior region, the irritation of which only produced reflex motion, it became evident that my first opinion was false. I was then led to inquire what were the parts of the anterior region the irritation of which would cause the attack ? and I was not long in, deciding that the face was one of these parts. I immediately extended my investigations in this subject, and I ascertained: 1st. That it is only on the side of a unilateral lesion of the spinal nerve that certain portions of the skin the faculty of occasioning an attack of epilepsy when irritated. 2d. That these portions of the skin are those of one part of the face and neck. 3d. That the nerves which are to these portions of the skin originate from the and the second and third pairs of rachidian nerves. My latest investigations in this subject confirm what I had already briefly announced in 1856, at the Academy of Medicine, that the irritation of a certain zone of the skin would produce epileptic paroxysms, in cases where epilepsy had followed the section of one lateral half of the spinal cord. The limits of this zone, as I have discovered them, are represented by the dotted lines in Figure 1. These limits, as it appears, are slightly curved lines which circumscribe an ovular space, which, in the adult Guinea-pigs, is about five centimetres long, and three and a-half or three and three-fourths centimetres in width. If we should draw, as in the figure just mentioned, a line from the anterior to the projection of the superior maxillary bone, which forms the lower limit of the suborbitar fossa, from there to the middle of the lower jaw, from this point, passing below the angle of the jaw to the scapulo humeral articulation, thence reascending along the anterior edge of the shoulder-blade, until the middle point of its length is reached, from this last point into the attachment of the lobe of the ear, and, finally, from there to the point of departure, the anterior palpebral angle, passing below and very near the edge of the lower eyelid, we the excitable region. All other parts of the body, the hyperaesthetic portions of the skin, back of the seat of hemisection of the spinal nervous centre, without producing any spasmodic action, without even any convulsive movements of the face, head, and eyes, which are frequently manifested after very slight irritation of the zone capable of producing an attack. On the head and neck, we can, without exciting convulsions, irritate severely the skin or membrane of the nose, lips, tongue, conjunctiva, upper eyelid, edge of the lower eyelid, space between the eyes, ears, shoulders, and head, and also between the lower jaws (except in a very short space along the inferior maxillary). I repeat, then, there is only the zone of skin on the head and neck, that may be capable under the influence of severe or trivial irritation of occasioning epileptic spasms, among Guinea-pigs that have been submitted to the operation designated. It is not always thus in cases where there has been a or nearly complete transverse section of the spinal cord. On the contrary, it is most common to find that besides the zone described above, and which in these cases, on both sides, has power to cause convulsions, other parts of the skin possess the same faculty. The skin between the right and left zones, which extends over the last four cervical vertebra, and, , that portion comprised between the scapulae, has also power to cause attacks of complete epilepsy, or spasmodic action of some muscles of the face, neck, and anterior members. This zone, intermediate to the other two, sometimes extends back even to the region of the cicatrix, where the incision was made, and the vertebral canal was opened to allow the section of the nerve. Sometimes I have even seen a paroxysm occur after irritation of the cicatrix; but, as in the very same where I have observed this phenomena, I have not been able to reproduce it in numerous experiments, it is possible that the local disturbance may have affected the parts of the skin anterior to the cicatrix, and thus have caused the attack by irritation of those portions possessing undue excitability. When the lesion, consisting of a transverse section of the posterior half of the spinal nerve, on both sides, is more extensive on one side than the other, it is found, very frequently, that only one side of the face or neck is capable of producing convulsions. In these cases, the zone of the skin which acquires this morbid property is always found on the side where the nerve has been more severely wounded. Then, sometimes, portions of the skin beyond the zone limited to one side of the neck and face, and pertaining to the intermediate zone just alluded to, have also the power to bring on the spasms. The portion comprised the scapulae especially possesses this faculty. Now and then, too, a lesion of the two posterior thirds of the spinal cord, on both sides, renders both sides of the face and neck capable of producing the convulsions, the same as occurs after a complete transverse section of this nervous centre. But there is this difference in the two cases, that in the first, the intermediate zone of which I have spoken, does not acquire, usually, the power of causing an attack, while, in the second case, on the contrary, this almost invariably takes place. In the zone of skin on the face and neck, the points seeming most excitable are found at the angle of the jaw, below the eye, and at the middle of the lower edge of the scapula. V. NERVES WHICH ARE DISTRIBUTED IN THE ZONE OF SKIN CAPABLE OF CAUSING AN EPILEPTIC ATTACK. Among Guinea-pigs having undergone a transverse section of one lateral half of the spinal cord, this sensitive zone of skin receives ramifications from one cranial nerve, the trigeminal, and some of the cervical pairs. Of the three great branches of the trigeminal, the ophthalmic does not furnish ramifications to this zone; the other two supply it, particularly by the and the auricular temporal. The posterior branches of the second, third, and fourth pairs of cervical nerves are distributed in this space. As I have already said, when there is a complete or nearly complete transverse section of the spinal cord, beyond the zone, on both sides of the head and neck, there is an zone over the last cervical vertibrae, and a part of the dorsal vertibrae, also capable of causing spasms when irritated. The branches of nerves which distribute themselves in this new zone of skin originate nearly, if not entirely, from the posterior branches of the spinal nerves, in a part of the cervical and dorsal regions. (To be continued.}
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O i h r i a 1. Illinois State Medical Society. The proceedings of the recent annual meeting of this Society must be deferred until the July number of the Examiner. Meeting of the American Medical Association at New Orleans. The record of proceedings of the recent meeting of this great national organization occupies so much space in the present number that our clinical matter and book notices are both crowded out. And, yet, our readers will get but a very imperfect idea of the work done by the during its recent session. Nearly all the scientific part of the work was done in the Sections, where many papers and reports were read and discussed, very much to the pleasure and profit of those in attendance. But of all these, nothing appears in the record of proceedings as published. We notice, also, that many of our cotemporary journals are publishing the record literally as it was reported in the New Orleans daily papers, and are consequently giving currency to some errors, especially in regard to committees. For instance, in several, the President, Dr. W. 0. Baldwin, is represented as appointing himself at the head of the Committee on the establishment of "a National Medical College," while, the truth was, that after he had announced the committee, his own name was added by a special vote of the Association. Again, in another part of the record, they represent the President as adding to the on Correspondence tvith Medical Societies, Drs. Davis, Wetherly, and Toner; while the true reading should be, that the gentlemen named were appointed a committee, charged with the special duty of presenting to the several State medical a series of resolutions that had been already adopted by the Association. The recent meeting was one of the most pleasant and profitable that we have attended. Dr. Baldwin presided with ability, and all the business of the Association was transacted with unusual harmony and . The hospitalities received were abundant, and of the most appropriate character. The week of our sojourn in the Crescent City will ever bring to mind only the most pleasant memories. Association of American Medical Editors. In the present number of the Examiner, we publish the proceedings taken in the formation of a permanent organization of those connected with the medical press of oui' country. The objects of the organization as set forth in the are important, and, if judiciously pursued, will lead to the most important results. That mutually advantageous arrangements can be made by associated action, in reference to foreign exchanges, there can be no doubt. That annual meetings will be productive of more unity of action, and, consequently, greater influence, and far greater attention to some topics of permanent importance to the profession, is equally evident. The medical periodical press should be, not merely a medium for the dissemination of in the various departments of medical science, but it is preeminently the proper and only efficient medium through which to reach and influence the general sentiment of the , on all questions relating to medical education and medical ethics. It has often been said that many of the periodicals are published by and constitute simply the organs of the faculties of particular medical colleges, and lienee they canhot be relied on to expose abuses or to efficiently independent measures of improvement. This may be true in some instances, but association and consort of action will do much to obviate that evil, and develop much more fully editorial responsibility and influence. Hence, we hope to meet, next May, in Washington, representatives from every regular medical periodical in our country. In the meantime, let our editorial brethren commence the work at once of candidly, courteously, and thoroughly the all-important topic of medical education, in all its relations. If the honor and usefulness of the profession, as well as the nature of the medical sciences, require a fair degree of preliminary education and mental discipline, on the part of those who commence the study of medicine, let us not only say so, but let us continue to discuss the subject until some practicable method for the'object is actually adopted. What shall be the standard required? Shall its enforcement be required by the medical colleges, or by the private preceptor, through boards of censors, appointed by the local medical associations? These are the questions. If the lecture terms in our colleges, , are too short to permit an adequate course of instruction? if the system of giving heterogeneous instruction on all the branches of medical science and practise, to students in all stages of study in one class, is contrary to the dictates of -sense, and productive of many evils? and if the making of the college diploma a license to practise and a full admission into the profession tends directly and strongly to keep the and rivalry among the schools, on the basis of the shortest terms and smallest possible requirements for the ? let the facts be kept constantly before the whole reading portion of the profession, until a united and enlightened devises and enforces the proper remedies. That the social status and usefulness of a great profession, embodying the highest attainments in science and the most humane objects, should be injured, year after year, and generation after , by manifest and acknowledged defects in its system of education, is simply puerile. For us to continue listening to annual addresses of presiding officers of social organizations, whether state or national, and the reports of committees, reciting in glowing colors the , absurdities, and practical evils of such system, as we have been doing for twenty years past, -without agreeing upon some practical measure of improvement and setting ourselves about the work of executing them, is to make ourselves the laughing-stock of all intelligent men. The only medium through which the great mass of the profession in all parts of the country can be reached is the medical periodical press. Let those having the editorial management of that press realise their responsibility and act accordingly. Illinois State Microscopical Society. A society with this title has been recently organized in this city, under a charter granted by the Legislature of the State. Its meetings thus far have given promise of great usefulness. Dr. W. W. Allport is the President, and James Hankey, Esq., is -Secretary. We shall notice some of the doings of this Society more at length hereafter. MEDICAL LAW. The State of Minnesota has shown a very commendable to many of her older sisters in passing a law to protect her people from empiricism and imposition in the practice of medicine and surgery. The bill is so much to the point, and so commendable in its provisions as regards protection of the rights of legitimate medicine, that we give it entire, taking the occasion to commend it to the special attention of all parties concerned: Section 1. That it shall be unlawful for any person within the limits of said State, who has not attended at least tw'o full courses of instruction, and graduated at some school of within the United States, oi' of some foreign country, or who cannot produce a certificate of qualification from some State, district, or county medical society, and is not a person of a good moral character, to practise medicine in any of its departments, or perform any surgical operations for reward or compensation, or attempt to practise medicine, or prescribe medicines, or perform any surgical operation for reward or compensation, within the said State of Minnesota. Sec. 2. Any person living in the State of Minnesota, or any person coming into said State, who shall practise medicine, or attempt to practise medicine, in any of its departments, or perform, or attempt to perform, any surgical operation upon any person within the limits of said State, in violation of Sec. 1, of this Act, shall, upon conviction thereof, be fined not less than fifty dollars, nor more than one hundred dollars for such offence; and upon conviction for a second violation of this Act, shall, in addition to the above fine, be imprisoned in the County jail of the County in which such offence shall have been , for the term of thirty days; and in no case wherein this Act shall have been violated, shall any person so violating, a compensation for services rendered: Provided, nothing herein contained shall, in any way, be construed to apply to any person practising dentistry exclusively. Sec. 3. No person who fails or neglects, on or before the first day of October, 1869, to file, in the office of the Clerk of the District Court of the County in which he resides or keeps his office, a sworn copy of the certificate or diploma of some school or college of medicine, that he has attended at least two full courses and graduated at such school, or a sworn copy of a certificate of qualification of some State, District, or County medical society, shall be permitted in any court of this State to sue for or recover any compensation for his services, advice, or attendance as a physician or surgeon; and the failure to file a sworn copy of such diploma or certificate, as above provided, shall be prima facie evidence that he has not attended or at any school of medicine, or received a-certificate of from any State, District, or County medical society. Sec. 4. Any person studying medicine with a preceptor, qualified as in this Act above provided, shall have three years from the commencement of his term of study to comply with the provisions of this Act. Sec. 5. This Act shall take effect and be in force from and after the first day of October, 1869. We are indebted to Dr. Samuel Wiley, of St. Paul, Minn., for the above copy of the bill. It was passed March 4th, 1869. The Medical Record. Note on tpe Cure of Acute Orchitis in twenty-four, hours. By Furneax Jordan, F.R.S., Surgeon to the Queen's Hospital, Professor of Surgery at the Queen's College. It is gratifying to me to know that Mr. Noble Smith has found "most satisfactory" results (British Medical Journal, Jan. 30th) from the treatment of acute orchitis which I described at Oxford. May I suggest that still better results may be by using a solution of nitrate of silver and applying it immediately the cases present themselves? In very acute cases, I add a little vesication over the femoral artery of the same side. This is the treatment, as seen in a severe double orchitis treated in my absence, and reported to me by a correct observer, our house-surgeon, Dr. Jolly. A man, aged 30, had intense pain, intolerable tenderness, and great swelling and induration in both testicles, and could not stand upright. The scrotum was covered with a solution of nitrate of silver (two drachms to an ounce); a stripe of was established over the upper halves of both femoral by means of linamentum iodidi; and the testicles supported with cotton-wool. lie was well in 24 hours. The treatment of orchitis is of more than ordinary , from the discovery by Dr. Marion Sims that closure of the vas deferens from acute orchitis is a common cause of often where the blame is laid to the wife. The return of some urethral discharge is best removed, often in a few days, by maintaining, with iodine, a disc of milder counter irritation, the centre of the disk being the genital organs. On this principle I treat all inflammations of the genito-urinary organs, male and female; adding in the acute form a little vesication on the sheltered position of the femoral arteries. The above treatment of orchitis is simply an illustration of a new ^ystem of treating all inflammatory diseases, and which I constantly adopt in all, with a success proportionately as great as in-acute orchitis. A brief sketch of the system appears in the February Practitioner. British Med. Jour., and New Jour, of Medicine. N. K. Medical Gazette. Creasote in Typhoid Fever. M. Pecholier, of , has recently been conducting a series of interesting on the action of creasote in typhoid fever. the disease to be one, totius substantiae, depending on changes in the blood, caused by the action of an organized ferment, which draws from the blood the materials necessary for its nutrition, and exhales those thrown off by its , M. Pecholier has been led to employ creasote as an agent. Sixty patients at the Hdpital St. Eloi were chosen as the subjects of the experiment. Every day a draught containing three drops of creasote, two of essence of lime, ninety grammes of water, and thirty grammes of orange-flower water was administered to the patients. At the same time, enemata were given, containing from three to five drops of creasote. M. Pecholier states, as the result of his experiments, that creasote employed in weak doses, either in draughts, , or in the form of vapor, at the outset of typhoid fever, acts powerfully in diminishing the intensity of the disease, and shortening its duration. M. Pecholier adds that the of the remedy as a prophylactic agent in schools, , hospitals, etc., during epidemics, would be of extreme . Lancet. N. Y. Med. Gazette. Subcutaneous Medication for Syphilis. Dr. Max has reported in the Brussels Academy five cases of syphilis, with indurated chancres, treated by the injection of calomel. Three of the cases received two or three injections each (quantity not stated), at intervals of about 12 days. At the time of writing, these were nearly or quite cured, after the lapse of 37, 20, 19 days respectively; and the remaining two cases, which had each received one , only eight days previously, were notably improved. If this discovery is verified, it will prove one of the most ever made in regard to the treatment of syphilis. Wiener Med. Wochenschrift. No. 24. D. f. l. Med. and Surg. Jour. Death of Dr. Alexander H. Stevens. At a special meeting of the New York Academy of Medicine, held April 2d, 1869, for the purpose of paying a tribute to the memory of the late Alexander II. Stevens, M.D., a series of resolutions were unanimously passed, expressive of the high estimation in which he was held by the members of the Academy, and of their deep sorrow at his departure. Boston Med. and Surg. Journal.
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TREATMENT OF ANEURISM BY IODIDE OF POTASSIUM. In Vol. 1, p. 253, of the Gazette, we reported 12 cases treated. In the Edinburgh Medical Journal, for July, 1369, Dr. Balfour, of the Edinburgh Royal Infirmary, adds 11 additional cases, and says, that in all of them, there has been such a measure of success, as justifies him in saying this treatment holds out an excellent prospect of relief, and even of cure. He knows that spontaneous abatement takes place without any real improvement : but in all his cases, not only relief, but positive improvement was obtained in every instance. And he thinks that there are many facts which tend to prove that iodide of potash is not only curative in aneurism already developed, but that it also acts remedially and prophylactically in the aneurismal . ANEURISM OF THE AORTA. Case I. Had been under observation for twelve months; the aneurism wtas reduced under treatment to a dull thud, in the second intercostal space, but no pain or uneasiness was complained of. The patient was able to tend shop. Case II. Aneurism of the abdominal aorta had remained quite well for more than a year after treatment. Case III. Aneurism of the innominata, implicating the carotid and subclavian arteries. There was also an aneurism of the abdominal aorta, and a general aneurismal condition of the arteries. He remained comfortable for many months after treatment. His abdominal aneurism could be felt as a hard, firm knot, much diminished in size; his innominate aneurism now never troubles him, but it is not absolutely consolidated, neither is it any longer a true aneurism; for it is restored to the condition of an elastic artery, enlarged fusiformly, of course, but no longer bulging as it formerly did, as a pulsating globular tumor stretching across the trachea. Case IV. Was an aneurism of the aorta, in a man aged 46. There was a large pulsating tumor to the right of the sternum, extending from the third to the seventh rib, and projecting fully one inch and a-half above the level of the ribs. Part of the tumor was solid; but all below the centre was soft and pulsated fluidly. The dullness extended fully five inches all around the centre of the tumor. He had intense dyspnoea, amounting to orthopnoea, violent, harassing, dry cough. His food and drink were restricted in quantity; a belladonna plaster was put over tumor; 15 minims of chlorodyne were given every half hour to quiet his cough, and one tablespoonful of a solution of one-half ounce of iodide of potash in six ounces of infusion of chiratae, was given in tablespoonful doses, three times a day. The patient was relieved in 48 hours and much improved in two months; the cough became very troublesome from time to time, but was relieved by the following : K. Morphiae Hydrochlor, gr. j. Acid Hydrochlor, dilut., m. v. Acid Hydrocyan, 3ss. Syrupi Scillae, oj. Aquae Font, 5j. Given in teaspoonful doses every two or three hours. Paralysis and loss of pulse in the left arm occurred and passed away. A violent serous diarrhoea was relieved by of lead and opium, in small doses, without stopping the use of the iodide. After five months treatment, the improvement was quite remarkable. The pulsation was very much lessened; the tumor was perfectly solid in every part and visibly decreased in size. The patient was still kept in bed, and the iodide of potash treatment still continued, in the hope of seeing the disappearance of this large tumor. But the patient obtained liquor on the sly, and relapsed; still, at the end of nine months, the tumor was considerably reduced in size, the cough was all gone, and the patient, although emaciated to a skeleton, was able to walk out daily. Case V. Was one of aneurismal dilatation of the aorta. The patient (aged) had suffered for 16 months with severe pain across upper part of sternum, and breathlessness. There was dulness on percussion across the whole of the upper part of the breast-bone. There was a pulsating tumor deep in the tracheal fossa, and a double bruit, extending up into the left carotid. Six drachms of iodide of potash were dissolved in six ounces of infusion of chiratae, and a tablespoonful given three times a day. The patient was kept in bed, and his food and drink restricted. He was quickly relieved; and in a fortnight the rasping bruit wras softened, and the pulsation much lessened. Case VI. Was one of aneurism of the aorta, which, taken singly, would attract much attention, but is remarkable as one of a series. The patient, aged 40, had suffered for twelve months with a severe and constant aching pain in the chest. His breath was short and wheezing; cough troublesome, choking feeling on stooping, difficulty in swallowing solid food, pulse at left wrist almost imperceptible. There was a distinct bulging on the upper part of the left side cf the chest, most marked over the second rib, and second intercostal space, also decided impulse, and dulness from the clavicle to within two inches of the , over which a double blowing murmur was to be heard. There was also enlargement of the heart and valvular disease. Pain and sense of choking prevented the patient from sleeping. Two drachms of iodide of potash were dissolved in six ounces of water, and two tablespoonfuls given three times day, with chlorodyne, ether, and morphine injections, etc., to relieve the cough. In the course of six months, after much suffering from pain and cough, he was materially better, the breathing was easier, cough and expectoration almost gone; but slight fatigue or exposure to cold would bring them back again, and, at one time, there was complete loss of pulse in the left arm, with coldness and excruciating pain, the expectoration became , purulent, and bloody. He recovered from this, and during the whole of the next nine months continued to take two drachms of the iodide daily, with the exception of twice, when it caused pain, vomiting, and gastric irritation. It was not till the end of 18 months that the tumor seemed sufficiently consolidated to allow the patient to get out of bed; and then, although he looked well and healthy, one drachm of iodide of iron was added to his medicine. There was great dulness on percussion of the chest, the sternal ends of both clavicles were dislocated, there was considerable puffiness and enlargement of the veins of the chest, a solid mass could be felt in the tracheal fossa, behind the sternum, over the left there was a solid tumor, pulsating not very forcibly, and only with a movement of elevation, but more of dilatation, over which no bruit could be heard, but only a dull thud. The patient had no difficulty of breathing or swallowing, could go up and down stairs and walk about, no cough, and aneurism evidently consolidated or consolidating. Dr. Bennett was also satisfied with the reality of the improvement. Case VII. Aneurism of the aorta in a man aged 22, had lasted nine months, attended with harassing cough and copious purulent expectoration, severe pains in left side of chest and neck, and in the left arm. Pulse 110; heart normal; between second and third left ribs, there was a conical elevation, one inch and a-half long, rising half an inch above the level of the ribs, pulsating fluidly, with thin walls and distensile action. Dulness on percussion, extending from the first rib down toward the sternum, and over this space a pulsatile wave passed from right to left, attended with a tolerably loud and well-marked bruit. The belladonna plaster, morphine mixture, and iodide of potash, one drachm to the ounce of water, was used in one-half ounce doses, z.e., 30 grains per dose, three times a day. The pain ceased in a few days, in a month the cough was all gone, his breathing easy, and he comfortable. In a month more, the cough and expectoration had entirely ceased, and the patient thought himself cured. But the pulsating tumor, although lessened in size, had not thickened in its walls, and the bruit was as loud as ever. He left the hospital arid relapsed; in a month, cough became harassing and he expectorated 15 ounces of purulent matter in one night. He required ten minims of chlorodyne to keep him from vomiting the iodide; but in six weeks more his cough and expectoration was all gone, he was looking well and gaining flesh, and the pulsations were quieter. At the end of four months the pulsations were so quiet, and the walls felt so solid and dense, that he was able to leave the hospital. Case VIII. >> Was rather a case of disease of the aortic valves, attended with violent palpitation, severe pain over the heart, difficulty of breathing, with feeling of suffocation, on walking or going up stairs, all of which was relieved in a month by one-half drachm doses of the iodide, three times a day. Case IX. Was an aneurism of the innominata, in a patient aged 37, sick for three months with beating in the throat, pains shooting down from there into the right shoulder and arm, and especially up the right side of neck and head. On the right of the tracheal fossa there was a tolerably firm, but distinctly expanding, pulsatile tumor, rising up out of the chest, and nearly two inches in diameter. There was dulness on , a dull thud, but no bruit on auscultation, propagated up the carotids, but not along the subclavians. Pulse 120. He took one-half drachm of the iodide three times a day, for three months, when the tumor was quite firm and solid, no longer dilating, but not materially lessened in size; and nine months after he was able to work, the tumor having almost , although there was still excessive pulsation. Case X. Was an aneurism of the aorta in a man aged 47, with cough, pain in the chest and down left arm, followed by great swelling of it; large pulsating tumor of right side. The patient had pain in the head and coryza, from the use of the iodide, but tolerance was soon established. Case is still under treatment. Case XI. Was one of the aorta, which had been kept in abeyance for six years, with the iodide, taken of his own accord, while following his business as a peddler. He was then treated in hospital, by recumbent posture, restriction of . food and drink, and drachm doses of the iodide, three times a day. In two months, he was much relieved, pulsations were no longer perceptible. Finally, while sinking from dropsy, he suddenly died of hemorrhage from the mouth. The heart and kidneys were sound, the aneurism did not press upon the trachea, bronchi, or gullet, the whole ascending aorta was atheromatous and calcareous; the middle coat greatly thinned; the mouth of the aneurism was three inches vertically and two inches across; the aneurism itself was four and a-half inches in breadth, and five inches long. A second aneurism of the size of a walnut rose from the right side of the aorta and pressed on the right auricle so as to occasion the dropsy. The larger aneurism contained firmly adherent fawn-colored clots, and some large, softer, and dark clots. The aneurism had not ruptured, and Balfour thinks it affords an apt illustration, not only of the mode of cure of an aneurism, but of one of those uncommon occurrences (the pressure of the right auricle), which rendered a well-devised and successful mode of cure abortive. J. C. P. N. Y. Med. Gazette.
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ARTICLE XLVI. THE SUM AND SUBSTANCE OF ANTISEPTIC surgerae. By E. ANDREWS, M.D., Prof, of Principles and Practice of Surgery, Chicago Medical College. There are many practitioners whose time and opportunities have not enabled them to give carbolic acid, and its kindred agents either a careful trial or full investigation by reading, and who, consequently, do not know how much is truth, and how much is error in what is said on the subject. This article is intended to supply a want by making a condensed statement of this part of surgery. First, then, WHAT WILL CARBOLIC ACID ACCOMPLISH? Carbolic acid, creasote, sulphurous acid, permanganate of potash, and all the other poisons, which destroy animalcular life without too much irritation to human tissues, act in the same manner, and produce similar results. Carbolic acid being most used, is, however, here taken as the type. 1. In compound fractures of the most aggravated character, it prevents almost absolutely all suppuration, and most of the soreness and swelling, causing large lacerated openings to go through their process of healing, without any unpleasant smell, and often without the formation of a spoonful of pus. 2. Lacerations and compound fractures laying open large joints, such as the knee, are often healed by it without , and without exhaustion. Lacerated flesh wounds follow the same law. 3. Lumbar abscesses, and other largo collections of pus, opened under a carbolic acid covering, close again by first , and after the pus is evacuated, the cavity ceases to produce any more, secreting only a clear bland serum. , the patient, instead of falling into hectic in the usual manner, grows fat and strong, and ultimately recovers. 4. Fistulas communicating with carious bone, may be often healed permanently, without operation, the suppuration ceasing, and the granulations first firmly enclosing the dead bony spicula, and then effecting their removal by absorption. This is, , the most surprising of the effects of carbolic acid. 5. In surgical operations it may be used to promote union by - first intention, and to prevant erysipelas, pyaemia, and other septic forms of disease. WHAT IT is. Carbolic acid (formerly called phenic acid) is a hydrocarbon obtained from coal tar. It can scarcely be termed a true acid, its acid properties being almost nothing. It more properly to the class of alcohols. When pure it crystalizes. It coagulates albumen, and acts as a slight caustic on the tissues, being in that respect rather feebler than nitrate of silver. DIFFERENT FORMS. When the crystals are mixed with 5 per cent, of water, they deliquesce and form a permanent fluid. If more water be added it will not mix, but floats on the top, taking up into only about 6 per cent, of the acid. If the two solutions are shaken together, they soon Separate again, the lower one containing 95 per cent, of the crystalized acid, and the upper about 5 per cent. The upper solution is the one generally to be used for injecting abscesses, etc., the lower one being too strong. There are no officinal names for distinguishing these three forms of the medicine, and hence the manufacturers give them all sorts of titles. The only reliable way is to buy the crystals, and prepare the solutions by adding water. THE THEORY OF ITS ACTION. The atmospheric air always contains, floating as dust in it, a great number of vegetable and animalcular germs, which light upon exposed organic fluids, and multiplying by millions hourly, convert the organic material into a putrifying mass. If the germs be wholly excluded, it is found that putrifaction does not occur, even though warmth and moisture both are present. Prof. Lister maintains that these putrefacient animalcules are the cause of putridity and irritation, and that the irritation causes the suppuration, and hence, that when no other strong cause of irritation is present, the effusion of pus from any raw tissue may be wholly prevented by simply applying carbolic acid, and killing all the animalcules, and preventing the access of any new ones. HOW TO USE IT. Prof. Lister uses rather complex methods, which can, by no means, be carried out easily by American surgeons, outside of the large cities. During the past year, I have devised various ways of simplifying the applications, with excellent success; and I am glad to see by late European advices that he himself is now resorting to some of the identical modes which I had planned independently. I have found the following three preparations the most : First, take about one ounce of the crystals, or of the 95 per cent, solution, which is nearly as strong, and agitate it in a bottle, with 10 or 15 ounces of water; allow it to settle a few minutes, and the clear 5 per cent, solution will appear at the top, and the surplus of acid will settle to the bottom, in the form of the 95 per cent, solution. Also, take about one ounce of the crystals, or of the 95 per cent, solution, and dissolve it in any oil. The best is a pure quality of castor oil, both because it has more viscidity, and is, therefore, better for , and because it will dissolve the 95 per cent, solution of the acid completely, making a perfectly bright, clear compound, which is elegant in its appearance. Other oils precipitate the 5 per cent, of water, in the form of an emulsion, which gives them a dull look. Finally, take eight parts of collodion, and mix them with one part of carbolic acid. We are now armed with three preparations, via.: the carbolated water (5 per cent, solution), the carbolated oil, and the carbolated collodion, and are prepared for action. TREATMENT OF COMPOUND FRACTURES. The fracture being adjusted and splints applied, the wound should be washed to its remotest corner, with the 5 per cent, solution, using a syringe, if necessary, to throw it fully into deep parts. This will kill all the animalcular germs present in the wound. The next step is to prevent the admission of any more. For this purpose, take a pledget of lint or cotton , large enough to fill the wound, if it is open, or to more than cover the orifice if closed, and lay it in or on, as the case may be. If elegance is sought after, a piece of tinfoil or oiled silk may be placed over the lint, to prevent the oil from soiling the outside dressings. Finally, confine the whole in place with a roller, or with a Mayor's handkerchief. The next day, the injection and dressing must be gently repeated. It should be observed, that new wounds and freshly opened abscesses, whose raw nerves are not yet covered with granulations, often feel the smart of the first wash severely. If so, the second wash may be reduced to one-third strength, gradually increasing again to 5 per cent., or 20 grs. to the ounce. Under this treatment, frequently there is not an ounce of pus secreted during the whole cure, and the bone often unites as promptly as in a simple fracture, an important gain, as all know how prone fractures are to slow union. LUMBAR AND OTHER LARGE ABSCESSES. These large collections of pus, which often destroy the patient soon after they are opened, may generally be rendered surprisingly harmless in the following manner: Dip a trochar in carbolated water, and thrust it obliquely into the abscess, so as to make a valvular opening. Let the pus flow as long as it will, or press it gently out, but do not allow a particle of air to regurgitate through the canula, as that would introduce germs. When the pus ceases to flow, dip a few fibers of cotton batting into the carbolated collodion, lay them over the point of entrance to the trochar, then placing the thumb on the end of the canula, or a cork in it, to prevent any of air, draw it out from under the collodionized cotton pressing, the latter, instantly, upon the orifice, to prevent the admission of living germs. In this way, the orifice will be sealed, and a union, by first intention, usually obtained. After a week or more, the abscess will generally be found filled again, when it should be again tapped in the same way. The pus #will now be found thinner and more serous. After a longer interval, a third tapping will find the pus almost transparent, and the fourth one often will draw absolutely transparent serum. In this way, the intervals will lengthen, and the , at least, in many instances, be gradually made to wither away and disappear, the patient all the while growing fat and rosy, and presenting a total contrast to the usual results of a lumbar abscess. Sometimes the abscess is clogged with masses of dead areolar tissue, so that it is impossible to evacuate it through the canula. In this case, it may be still possible to draw them out through the tube by slender forceps, dipped before each insertion in carbolated water, or oil; but if this fails, or if the collodion does not produce a union by first , or if it has been already opened before coming under treatment, a different method is necessary. We must now by injections. For this purpose, use a 1 or 2 per cent, solution, the first few days, gradually increasing to five per cent., or 20 grs. to the ounce, as the patient becomes used to it. This must be thrown in once a day, filling the abscess completely. Then allowing the solution to run out, a large pledget of cotton, dipped in carbolated oil, must be placed over the fistula, and confined by a bandage. It will be the neater and better if a piece of druggist's tin-foil is placed between the cotton and the bandage. This dressing must be repeated daily. Frequently the flow of pus will continue, gradually diminishing for one, two, or three weeks under this 'treatment; but it will be almost always brought under control, and the abscess at length discharge only a little transparent serum, without any odor. This may continue many months, but the patient is saved from hectic, grows fat and vigorous, and his life is saved. CARIOUS JOINTS. Prof. Lister claims that carbolic acid will heal up a fistula over necrosed bone, and cause its absorption. In my own , I have been able to do this, where the sequestrum was of cancellar tissue, or a fragment of compact tissue, of small size; but large fragments of compact bone, two or three inches long, have, in my hands, resisted the treatment, and required . The principle appears to be this: Cancellar bone, if suppuration be suppressed by the injections, becomes with the granulations which hug close to all the little , and being in absolute contact, effect their absorption; but large compact fragments cannot be thus interpenetrated with living granulations, and hence their absorption, if accomplished ' at all, would, probably, be too slow to be waited for. At any rate, such is my experience up to the present time. The smaller joints do admirably under the daily carbolated injections and dressings. I have repeatedly healed them up in a complete and permanent manner, after the probe showed the articular surfaces of the hopes to be thoroughly carious. Anchylosis, of course, occurs. Finger-joints may be often healed in two weeks, but larger ones require much more time. I have an elbow whose articular surfaces were perfectly carious, six months ago; the limb was swollen and red, discharging large quantities of pus, and the patient was emaciated, cadaverous, and hectic. Under the antiseptic dressings, he has grown plump and , the swelling has all disappeared, and the skin resumed its natural whiteness. For three months, I have been unable to find any dead bone with the probe, and there is no discharge of pus, yet the fistulas are still permeable to the probe, and will not close under several months more. Wounded and carious knee-joints can often be treated with splendid success in the same way, compared with the disasters which used to follow these conditions. I have one now on hand which does not discharge a teaspoonful of pus in a week, and the patient will save both his life and his limb. I have seen one compound fracture, penetrating the knee, thus treated, where the joint did not even inflame, and was not anchylosed. Some carious knees, however, are too extensively diseased to admit of final cure, and the antiseptic treatment is only useful to arrest exhaustion, and enable the surgeon to get them up to a condition vigorous enough to bear an operation. The of hip-disease often respond admirably to the same . INCISED WOUNDS. Wash the wound thoroughly to its remotest recesses with the carbolated water, then close it with sutures, and add adhesive straps or carbolated collodion. If the straps are used, a of lint, dipped in carbolated oil, should be laid over the wound and covered with tin-foil and bandages. In this way, union by first intention is greatly promoted, and the risk of erysipelas almost absolutely annihilated. If any one, however, supposes that carbolic acid is infallible, he will be disappointed. Many particular cases occur where it partly fails of its end. In these instances, it w'ill often be found that a solution of one part of the officinal sulphurious acid to two parts of water does better. Solutions of of potash, two grains to the ounce, sometimes do well; and, in the same manner, other antiseptic solutions, if used in sufficient strength, occasionally succeed. Many persons miss entirely the effects of the antiseptic treatment, because they are inefficient in its application. If they do not effectually destroy every animalcule in the abscess or wound, and absolutely bar out the access of every new germ in the living state, they accomplish nothing. The washing and injection must be , and the carbolated outside dressings must cover the whole orifice and its vicinity. When these principles are observed, the success is wonderful. Ou the whole, it must be acknowledged that the use of acid has revolutionized certain branches of surgery, and enables us to save many limbs and lives which would formerly have been lost. I would advise no one to make a hobby of it, but that it is a remarkable addition to the resources of our art is a fixed and undeniable fact.
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PSHcrtion$. PHYSIOLOGICAL ACTION OF THE HYDRATE OF CHLORAL. Dr. B. W. Richardson made an extremely interesting report on this subject to the Biological Section of the British for the advancement of Science, at its recent meeting, from which we make the following extract: The hydrate of chloral, for the introduction of which into medical practice we are indebted to Liebreick (known for his researches on ), is a white, crystalline body, soluble in water, and a solution not very disagreeable to the taste. It is made up by the addition of water to the substance chloral. Chloral, the composition of which is C2HC13O, is the final product of the action of dry chlorine on ethylic alcohol. It is an oily fluid, thin, colorless, volatile. The specific gravity is 1.502 at 64deg Fahr., and it boils at 202deg Fahr. It has a vapor density of 73, taking hydrogen as unity. The odor is pungent. When chloral is treated with a little water, heat is evolved, and small stellate white crystals are formed as the fluid solidifies. The solid substance is the hydrate of chloral, C2HCl30H20. The hydrate is slowly volatilized if it be exposed to the air, and the odor of it, were it not pungent, is so like melon as to be hardly distinguishable from melon. When heat is applied to the hydrate, it distils over without undergoing decomposition. When to a watery solution of hydrate of chloral caustic soda or potassa is added, the hydrate is decomposed, chloroform (CHClg) is set free, and a formate of sodium or potassium, according to the alkali used, is formed. It was on a knowledge of this decomposition by an alkali that Liebreich was led to test the action of the substance physiologically. He conceived the idea that in the living blood the same change could be effected, and that the chloroform would be liberated so SSlowly that anaesthesia of a prolonged kind would result. To try this, he subjected animals to the action of chloral, and even man, and proved that sleep could be rapidly induced without the second stage of excitement common to the action of chloroform, when it is given by inhalation. Liebreich produced in a , by a dose of 0.5 gramme of the hydrate of chloral, a sleep which lasted nine hours. This dose was equivalent to 0.35 of chloral, and to 0.29 of chloroform. The symptoms, he found, were like those produced by chloroform. In some cases, he gave the hydrate to the human subject. The first case was that of a lunatic, to whom he administered 1.35 gramme. No irritation was set up, and five hours of sleep was obtained. . In a second case, he gave internally a dose of 3.5 grammes to a man suffering from melancholia, by which he produced a sleep of 16 hours. Such, said Dr. Richardson, was an epitome of the facts placed before him at the time when he commenced to make his experiments. In setting out on his own account, he first a standard solution of the hydrate. He found that 30 grains dissolved in 40 grains of water, and formed a saturated solution, the whole making up exactly the fluid drachm. The standard solution prepared in this way was very convenient. He next proceeded to enquire whether, by the addition of hydrate to fresh blood, chloroform was liberated. This was proved to be the fact; the odor of chloroform was very distinct from the blood, and chloroform was itself distilled over from the blood, and condensed by cold into a receiver. The narcotic power of the hydrate was then tried on pigeons, rabbits, and frogs. The standard solution named above was employed, and was administered either by the mouth or by hypodermic injection. The action was equally effective by both methods. The general results was confirmatory of 's own experience to a very considerable extent. They areas follows: In pigeons, weighing from 8| to 11 ounces, narcotism was produced readily by the administration of from to 2| grains of the hydrate. In these animals, the dose of 2^ grains was the extreme that could be borne with safety, and a dose of 1| grain was sufficient to produce sleep and . The full dose of 2| grains produced drowsiness in a few minutes, and deep sleep, with entire insensibility, in twenty minutes. Before going to sleep, there was, in every case, the dose was large or small, vomiting. As the sleep and the insensibility came on, there was, in every instance, a fall of animal temperature; and even in cases where recovery , this decrease was often to the extent of five degrees. I he respirations also fell in proportion, declining, in one case, from 34 to 19 in the minute, during the stage of insensibility. Fcom the full dose that could be borne by the pigeon, the sleep which followed lasted from three and a-half to four hours. Six hours at least was required for perfect recovery. During the first stages of narcotism in pigeons, the evolution of chloroform by the breath was most distinctly marked. In rabbits weighing from 83 to 88 ounces, 30 grains of the hydrate were required in order to produce deep sleep and insensibility. A small dose caused drowsiness and want of power in the hinder extremities, but no distinct insensibility. When the full effect is produced in rabbits from the adminis,- tration of the large dose, the drowsiness comes on in a few minutes: it is followed by want of power in the hinder limbs, and, in fifteen minutes, by deep sleep and complete . The pupil dilates and becomes irregular; the falls (in one case, from GO to 36 in the minute), and the temperature declines 6deg Fahr.; sensibility returns with the rise in number of respiratory movements, but, in some cases, falls again during the process of recovery. The drowsiness, or, if the animal is left alone, what may be called sleep, lasts from five and a-half to six hours. But it was observed that the period of actual anaesthesia was very short, lasting not longer than half an hour, after which the skin seemed rather more than naturally sensitive to touch. During recovery, there are tremors of muscles, almost like the rigors from cold; they are due, probably, to great failure of animal temperature. In frogs, a grain of the hydrate causes almost instant , coma, and death. In further prosecution of his research, the author tested, on similar subjects, the effect of chloroform, bichloride of , tetrachloride of carbon, and chloride of amyl. In all the observations with these substances, the narcotizing agent was used by hypodermic injection. It was found, as a result of these inquiries, that seven grains of chloroform, five of of carbon, and seven of chloride of amyl produced the same physiological effect as two grains of the hydrate. Seven grains of bichloride of methylene induced a shorter . A rabbit subjected to 30 grains of chloroform slept 4 hours and 25 minutes; and a pigeon subjected to 7 grains slept 3 hours and 25 minutes. All these agents caused vomiting in birds, before the insensibility was pronounced, the same as did the hydrate; but in no animal was there any sign of the stage of excitement which is seen when the same agents are by inhalation. This fact is most important, as indicating the difference of action of the same remedy, by difference in the mode of administration. The temperature of the body was reduced by the agents named above, but not so determinately as by the hydrate. Two animals, pigeons, made to go into profound sleep, the one by the hydrate, the other by chloroform (each substance administered subcutaneously), were placed together, and the symptoms were compared. The sleep from the chloroform was calmer; there was freedom from convulsive tremors, which were present in the animal under the hydrate, and recovery was, it was thought, steadier. It was observed, and the fact is well worthy of note, that no irritation was caused in the skin, or subjacent parts, by the injection of the chloroform and other chlorides. The neutralizing action of the hydrate on strychnia was tried, and it was determined that the substance 'arrests the development of the tetanic action of the poison, for a short period, and maintains life a little longer afterwards, but does not avert death. This subject deserves further elucidation. When the hydrate of chloral is given in an excessive dose it kills; there are continuance of sleep, convulsion, and a fall of temperature, of full eight degrees, before death. The post mortem appearances were noticed after a poisonous dose. The vessels of the brain are found turgid with blood. The blood is fluid, and coagulation is delayed (in a bird, to a period of three minutes), but afterwards a loose coagulum is formed. The color of the brain substance is darkish-pink. The muscles generally contain a large quantity of blood, which exudes from them, on incision, freely. This blood with moderate firmness. Immediately after death, all motion of the heart is found to be arrested. The organ is left with blood on both sides, but with more in the right than in the left side. The color of the blood on the two sides is natural, and the coagulation of the blood is moderately firm. The other organs of the body are natural. Other observations were made on the changes which the blood undergoes when the hydrate of chloral is added to it. The corpuscles undergo shrinking, and are crenate; and when excess of hydrate is added, the blood is decomposed in the same way as when treated with formic acid. The summary of the author's work may be put as follows: Hydrate of chloral, administered by the mouth or by injection, produces, as Liebreich states, prolonged sleep. The sleep it induces, as Liebreich also shows, is not preceded by the stage of excitement so well known when chloroform is administered by inhalation. The narcotic condition is due to the chloroform liberated from the hydrate in the organism, and all the narcotic effects are identical with those caused by chloroform. In birds, the hydrate produces vomiting in the same manner, and to as full a degree as does chloroform itself. The sleep produced by hydrate of chloral is prolonged, and during the sleep there is a period of perfect anaesthesia; but this stage is comparatively of short duration. The action of the hydrate is (as Liebreich assumes) first on the volitional centres of the cerebrum; next on the cord; and, lastly, on the heart. Practical Applications. Whether hydrate of chloral will replace opium and the other narcotics is a point on which the author was not prepared to speak. It is not probable that it will supercede the volatile anaesthetics, for the purpose of removing pain during the performance of surgical operations, but it might be employed to obtain and keep up the sleep in cases of painful disease. This research had, however, led to the fact that chloroform, when injected subcutaneously, in efficient doses, leads to as perfect and as prolonged a narcotism as the hydrate, with an absence of other symptoms caused by the hydrate, and which are unfavorable to its action. This was a new truth in regard to chloroform, and might place it favorably by the side of the hydrate for hypodermic use. Lastly, as the hydrate acts by causing a decomposition of the blood, ?'.e., by undergoing decomposition itself and seizing the natural alkali of the blood, it adds to the blood the formate of sodium. How far this is useful or injurious remains to be discovered. But while putting these views as to practical application at once and fairly forward, Dr. Richardson said, it was due to Liebreich to add that his (Liebreich's) theory and his experiments have done fine service in a physiological point of view. They have shown in one decisive instance that a given chemical substance is decomposed in the living body, by virtue of pure chemical change, and that the symptoms are caused by one of the products of that decomposition. The knowledge thus definitely obtained admits of being applied over and over again in the course of therapeutical inquiry. Med. Times and Gazette. Am. Jour, of Dental Science.
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ARTICLE XLIII. DR. BREED'S REPLY TO DR. McELROY. Since my report on Ileitis, in the October number of the Chicago Medical Examiner, I have received several letters from medical men living in different parts of the country, in regard to the case. While all seem to agree in commending the report in a way, each has some suggestion to make in reference to some minor point, where he thinks the paper might have been improved. In comparing these letters I find that what one criticises, another praises, and vice versa no two agreeing in condemning the same thing; so that I find it impossible to please all, and, indeed, have not quite satisfied myself. Dr. Holton, an intelligent physician, of Buda, Ill., thinks I should have given more prominence to the peritoneal inflammation, by the extensive adhesions, as, to his mind, that was the principal lesion to be considered. Dr. W. II. Nance, a successful and experienced physician of Vermont, Fulton County, Ill., writes me as follows: "I will say, Doctor, that I am much pleased with the "" and the conclusions drawn from it, and presume that they are correct, in the main, and that you are right in your conclusions respecting the results emanating from inflammation of the muscular coat of the small intestines. I am not sure, however, that in your concluding paragraphs, where you are summing up the fatal results of such a condition, that you have made the happiest selection of a word to represent that , where you speak of a portion of the alimentary canal being paralyzed. "That all normal function is suspended, is admitted; but is not that suspension the result of a condition the very reverse of paralysis? Paralysis is a loosening, relaxing, or letting go, from want of nervous force, or energy. But this intestinal condition is the result of a hyper exaltation of the nervous and muscular powers, of the part, blown into the intense heat of inflammation, represented as being seized and held as with the hand of some etherial Titan." Dr. Z. C. McElroy, a medical philosopher of Zanesville, 0., in a carefully written " Memoir," on "The forces of organic life," reviews this report from a different stand-point, and, in the light of certain philosophical, physiological, and principles laid down by him, reaches a conclusion that it was simply a case of lead-poisoning. Now, as all these suggestions are made in a courteous and friendly way, and intended to enure to my benefit, and promote the science of medicine, I am exceedingly thankful for them, and will try to profit by them. That this report should have thus called out this discussion, upon the interesting questions involved, is neither surprising nor displeasing to me. Indeed, I have no doubt that, in the end, I shall not receive the least of the benefits from it. In offering a few additional remarks upon the same subject, it may as well be admitted, that, while workiftg up the report from the symptoms, history, and autopsy, my mind was, for a time, undecided as to how best to interpret the phenomena. The leading symptoms, during the illness, were those of . The autopsy, however, revealed the effects of and severe inflammation, involving all the coats of the small intestines, together with such signs as led to the belief that the cerebro-spinal and ganglionic masses were seriously implicated in the disease. While my mind was thus , halting, as it were, between two opinions, viz.: Whether I should go back of the inflammation, which was an undoubted element in the disease, and interrogate the nerve centres for the prime cause of the difficulty, or, on the contrary, confine my speculations to the former, and hold inflammation for the trouble; the question of lead-poisoning came up for consideration. The occupation, habits, and several striking peculiarities of the case, conspired to direct my attention to this particular point. I was told that the patient was much in the habit of holding type in his mouth while at work. This was a leader. The symptoms that led me to suspect the integrity of the nerve centres were, a decided and unmistakable absence of arterial tensions, and the partial paralysis of the abdominal muscles, so as not to exhibit the usual reflex movements in emesis and defecation; and the post mortem displayed, an atonic condition of the muscular fiber of the intestinal walls, indicated by a distended condition of the empty intestines, where we usually find them collapsed. I first directed my attention to this question. In lead-, are the intestines, at the seat of the disease, distended, dilated, or are they, on the contrary, collapsed, or contracted? After a careful investigation of this subject, I came to the that there was a vast preponderance of testimony in favor of the opinion that, where there was any pathological appearance at all, a contracted and collapsed condition were those generally found at the seat of the disease. The arteries were also, in lead disease, smaller than natural, from the same general contractile condition, affecting the arterial coats, and, moreover, the tissues affected were found generally pale, , and more or less wasted. The disease, "tabes ," is supposed to be due to this constringing influence of the bloodvessels. While Dellaen, Merat, Eberly, Wood, and Letherby, in the belief that the contracted or collapsed state of the empty bowel, at the seat of the disease, is the pathological condition to be looked for, Sir Gr. Baker, Andral, Townsen, West, and Louis have often found no alterations whatever in the intestines. In a case which terminated with the symptoms of saturnine encephalopathia, viz.: delirium insensibility, and convulsions, Empis and Robinet found no anatomical of any importance. Lead was discovered by in the brain and liver. In Letherby's case, lead was freely discovered in the stomach, in the brain, muscles, liver, intestines, blood, and in the serum of the cerebral ventricles. The stomach and intestines were pale, and the latter were contracted, and in some places . Pereira says, in regard to the constitutional effects of .small doses of lead, that the arteries become reduced in size and activity, and that the pulse becomes slower and smaller, from which I infer that the preparations of lead give rise to a contracted state of the bloodvessels. How did these symptoms correspond with my case? Why, the muscular coat of the small intestines, besides showing such signs of inflammation as thickening, a deep red, or purple color, the muscular fibers w'ere evidently in an atonic, inactive, or paralyzed condition, so that they were quite unable to propel the contents of the tube onward. They had lost their contractile power. This was a prominent feature in the case, and one that I believed was the key to the explanation of the unusual phenomena in the symptoms, and I desired, therefore, particularly to it. This want of contractile power in these mucular fibers was the cause of the symptoms of obstruction. There was no other apparent cause to be found. Was this suspended due to some lesion in the nerve centres, or was it a result of the inflammation of the muscular coat itself? This was the question. I acknowledged that I was not quite satisfied on this point; but, in either case, the symptoms of obstruction would be the same, and, as the former hypothesis involved a somewhat speculative question, and the latter would fully account for all the symptoms, and, moreover, not finding the symptoms to correspond with those of lead-poisoning, I to adopt the simpler explanation, and not go behind the inflammation in the structures for the proximate cause. While my mind was perplexed on this subject, I was assisted, perhaps, by Prof. Gross' definition of disease, quoted by Dr. McElroy, in reply to Dr. Hendrick, in the July number of the Chicago Medical Examiner, for 1868. Dr. McElroy says: "First. What is disease? Disease is not, as it was formerly supposed to be, a special entity, a particular essence, a some thing vague, intangible, mysterious, but simply a departure from the normal standard, a change in, or of a part, brought about by the perverted action of its circulation, innervation, and nutrition; and modified by function and structure. Nearly every disease, whatever its nature or site, is essentially an . Even in what are called the neuroses, or nervous affections, generally plays a conspicuous part.' * By carefully scanning this definition, it will be s(fen that is simply an abnormal condition, an obvious change, in a part, brought about by a perverted action of the circulation, , or nutrition. Dr. McElroy seems to endorse this definition, and hence, he will be likely to excuse me for not being ready to call the disease by some name that would aim to ignore the inflammation, and fix the trouble upon the lesion of innervation. Let it be remarked that the perverted action here is not the disease, but the proximate cause of the disease. Now, * Prof. Gross, "Now and Then," published address. 1867. suppose Dr. McElroy does succeed in establishing a fact in this case that the trouble could be traced remotely to the gray of the "nervous masses," it can only be called a perverted action (the cause), resulting in inflammation (the result, or ,) according to his own definition. If all diseases are, moreover, essentially an inflammation, I could not have been very far wrong when I denominated the disease an of a particular structure. But I do not desire to split hairs with the Doctor, for I am too well pleased with his paper for that. That the reader may have a fuller view of the matter, and enable him the better to understand my reasons for not the disease to lead, I here submit the principal symptoms of the two diseases, in parallel columns. The symptoms of in the first, and those reported in my case of ileitis, in the second: POST MORTEM APPEARANCES IN BOTH. Symptoms of Lead-Poisoning. Intestines generally contracted. Inflammation not characteristic. Muscular fiber pale, exsanguined, and wasted. Skin generally hot and dry. Muchj>ain and colic. Signs of spasms. Convulsions. Gums, pale bluish line. Tongue flabby, and tremulous. Mouth dry. Urine scanty, and high colored. Face pale, dingy, and sallow. Motor power impaired. Weakness of wrists and joints. Extremities cramped. Pressure gives relief to pain. Muscles of chest spasmodically . Pulse slow, and artery small. Symptoms of Ileitis. Intestines dilated. Inflammation severe. Muscular fiber red, purple, atonic, and thickened. Skin cool and moist. Very little pain. No spasms. No convulsions. Tongue covered with dark, slimy coating. Mouth moist. Urine free, not particularly high . Face flushed and livid. Sensory power more injured. Normal. Normal. Pressure not well borne. Muscles of abdomen paralyzed. Pulse slow, and soft, undulating, and artery large. Loss of sensorial function. Palsy of extremities. Vomiting bilious matters. Hardened feces in passages Normal. Normal. Vomiting bilious and stercoraceous matters. Feces thin and aqueous. Such are the most prominent symptoms, and anatomical changes found in lead disease, as contrasted with those reported in the case denominated ileitis. After as full and careful an examination of the symptoms, morbid anatomy, and general history of lead-poisoning, as I was able to make, and comparing them with the case in hand, pro and con, I determined on the name "Ileitis," as the best term I could think of, to indicate the nature and of the affection, I concluded, therefore, to make no mention of lead, as cutting any figure in the disease; but I aimed, nevertheless, to employ such phraseology as would convey to the mind all the important features of the case. I expected every physician who read the report carefully would form his own opinion of the diagnosis, and, therefore, I to send it forth to meet its fate, while I anxiously waited the denouement, whatever it might be. Whether I was right or not, I do not now know. Those who, with myself, looked upon inflammation of the coats of the as the essential and most important element in the disease, will now see, and understand why I used the term "paralysis,'' as I did; while those who, from the symptoms and autopsy, were led to infer some serious lesion of the nerve centres, will, at least, allow the fidelity of the description. It may be in this connection, however, that while studying Dr. Abercrombie's observations on ileus (see diseases of the viscera) I found that he declared, in opposition to all the above authors, that the collapsed portion of the empty intestine, is the natural condition, while the distended portion is the seat of the disease; the distention arising from a paralytic condition of the muscular fiber, whereby it is unable to and propel the contents of the tube onwards through it. Now this view seems very probably the correct one, if we the same hypothesis to lead colic, since the action of lead upon the muscular fibers of the intestines is doubtless of the same kind as that exerted upon the fibers of the voluntary . This hypothesis, moreover, is greatly strengthened when we consider the therapeutic action of alum in curing lead colic. In most, if not all, of our works on therapeutics, there is a striking analogy between the recorded symptoms of lead, and alum, when administered internally in small doses. , alum is represented as the best remedy in lead colic. This looks unphilosophical, and should be looked into. We do not cure diseases on the Homoeopathic theory of " similia similibus curant^r," but on that of " contraria contrariis curanter" . Now, Dr. Copeland has actually ascribed the curative effect of alum in lead colic, to its power of exciting the of the partially paralyzed muscular coat of the small intestines in this disease. If he is correct in thus regarding these two remedies as antagonistic, and antidotal, in their effects on the system that, while one has a tendency to relax, and paralyze the intestinal, arterial, and voluntary muscular fiber, the other has a directly opposite tendency; then will the be explained, and the philosophy of our medication be . I feel under deep obligation to Dr. McElroy, and the other medical gentlemen, for raising these questions in the manner they have, and thus stimulating inquiry on this subject. With my eyes half open to these facts, I felt sure that there was a condition in the case justifying the term paralysis, yet I felt unwilling to launch out into unknown seas, and indulge in fruitless speculations upon the mysteries of innervation. That there was some fault, some abnornal condition in these nerve centres, interfering with their acknowledged function in keeping up that tireless state of muscular tension throughout the body, I felt quite confident. The atonic condition of the muscular fiber in the alimentary canal, in the coats of the arteries in the abdominal and respiratory muscles, all clearly indicated this want of nervous power. This striking peculiarity first awakened my suspicion that there was some toxic agent in the blood, and thus weakening the secret springs of life. Had the symptoms of lead-poisoning corresponded with these notable facts, I should have attributed the difficulty to that cause.* * That inflammation in a muscle is quite competent to arrest its power of contraction, many familiar examples might be given, aphonia in laryngitis is one good illustration. I am, by no means, unobservant of the fact that these nerve centres are, especially in this climate, frequently at fault, and seem to constitute one of the first, and most important links in the chain of morbid actions in very many diseases. In a , as Chairman of the Committee on Practical Medicine, read before the "Military Tract Medical Association," and published in the April number of the Chicago Medical , for 1868, I devoted considerable attention to the of the cerebro-spinal and ganglionic systems of nerves in the diseases of Northern Illinois. In this report will be found enunciated views, which seem peculiarly applicable in this connection. The importance of the subject must be my excuse for repeating them here. When the nerve centres presiding over nutrition, digestion, and the intestinal secretions generally, from any cause (and they are subject to be sympathetically modified in their actions by the slightest and most varied impressions upon any portion of the body) become too much depressed, irritated, or in any way so modified in the delicacy of their normal as to unfit them for furnishing the stated necessary supply, disordered digestion is the result, either diarrhoea or constipation." Again, I quote from the same report: "When the nature and modus operandi of these delicate structures are better understood in maintaining the solidarity of the whole human economy, the part they play in the delicate processes of innervation, sensation, digestion, secretion, elaboration, , calorification, growth, extension, and repair, respiration, disintegration, excretion, locomotion, and ratiocination, we may begin to conceive something of the importance and magnitude of this intricate subject." Again: "When it is borne in mind that, in this climate, , the onus of disease is often thrown upon these , and that it is in these nerve centres that the nerve force is correlated into cell action cellulation: (the primal and process of all organized structures,) secretion, etc., that it is here, indeed, that the nerve force seems to be , and that the nerve centres altogether preside over every physical phenomena in the body, it will not seem so strange that even slight molecular changes in these delicate tissues should crop out in grave and formidable symptoms of disease; and, more especially still, when it is remembered that these nerve centres first feel the noxious or depressing effects of any toxic agent in the circulation, that they, more than any other organ of the body, therefore demand for their normal action pure, oxygenated blood, and healthy food, free from any agents, we shall be able to understand why they are so frequently at fault." Hence it will be seen, I hope, that there is no inconsistency in the hypothesis of a perverted action of these nerve centres, even though we may not be able always to designate the precise cause of the perversion. Should it be decided, however, after all, that Dr. McElroy is correct in his opinion of the principal agency of lead in the case reported, then will it appear still more probable, in the light of all the phenomena in this case, that Dr. Abercrombie is right in his view of the pathology, and Dr. Copeland, in the modus medendi of alum in the cure of lead colic; and that all the other eminent pathologists cited are mistaken. However this question may be viewed, it is an interesting subject of inquiry; and with the ultimate decision I shall be content.
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$ e u r 11 o n s. MEDICAL SOCIETY OF COUNTY OF NEW YORK. Stated Meeting, March 1st, 1869. Dr. GEO. T. ELLIOT, Jr., President, in the Chair. After transaction of the usual preliminary business, and the reading of the reports of committees, a paper was presented by Dr. F. D. Weisse, entitled "Lister's Antiseptic Treatment in Surgery." This paper is published in full in the Medical Record, and we therefore present only a summary thereof. After stating the object of the paper, the author gave an historical sketch of the introduction of the antiseptic treatment of wounds, accrediting Mr. Lister, of Glasgow, with the chief merit of originating and perfecting this system of treatment although he had been anticipated by many in the use of acid, for its antiseptic qualities. The mortality of surgical cases is generally due to one of four general causes: 1. Shock from injury or operation. 2. Consecutive inflammation, with sequelte of injuries and operations (profuse suppuration, pyaemia, etc.) 3. Heterologous formations (cancer, etc.) 4. Degenerations of tissue which destroy the integrity of organs, such as calcification and atheroma of the coats of , leading to gangrene, aneurism, etc. The second of these general causes is the most prolific source of mortality in practice. The cause of all these disturbances in surgical cases is , in the opinion of Mr. Lister, the irritating and poisoning influence of decomposing blood or sloughs. The essential cause of suppuration in wounds is decomposition, brought about by the influence of the atmosphere upon blood or serum retained within them; and, in the case of contused wounds, upon of tissue destroyed by the violence of the injury. Proof of this is obtained from the fact that, within 24 hours after the accident, the colored serum which oozes from wounds is already distinctly tainted with the odor of decomposition; and during the next two or three days, before suppuration has set in, the smell of the effused fluids becomes more and more . These putrid fluids may be absorbed, and so give rise to irritation the term so generally employed to the infection of the system from the absorption of materials. Microscopical examination of the atmosphere shows that it contains innumerable germs of living bodies, and the varied experiments, by Pasteur and others, prove that to the presence of these germs in fluids decomposition is due. Prevent these germs absolutely from entering fluids, and no such thing as fermentation or decomposition can take place. Thus the old idea that putrefaction was effected by the oxygen of the atmosphere is exploded. Prom this we know that the unhealthiness of crowded wards is due principally to the presence of these germs in the atmosphere. The claims of antiseptics in surgery are based upon the fact that they have the power of destroying these germs, and thus rendering the air free from septic influence upon wounds. The power of sulphurous acid in preventing and arresting fermentation and decomposition has long been an established fact. To Polli, of Milan, we owe its therapeutical application. The virtues of choloride of zinc have been advanced by Mr. Campbell de Morgan, of the Middlesex Hospital, London. The sulpho-carbolates of soda, etc., have, of late, been brought as more efficient than sulphurous acid preparations, by Mr. Arthur E. Sansom. Carbolic acid outrivals them all, , as a general local application in surgical practice. The advantages which Mr. Lister finds that carbolic acid possesses are: "1. It is a most potent poison to the low forms of life which determine putrefaction, and it retains this power, even though diluted to such a degree as to be almost entirely unirritating to the tissues of the human body. "2. It is volatile, and its vapor is quite efficacious as an upon the air in the vicinity (of wounds). "3. It is a local anaesthetic, and exercises a most soothing influence upon a painful wound. "4. It is soluble in a variety of liquids of very different and each of these solutions has its own special value in practice." The preparations of carbolic acid which have been employed by Mr. Lister have been of various strengths, ranging from the pure acid (liquefied crystals) to a dilution in the proportion of one part of the acid to forty parts of a suitable solvent or vehicle. The glacial or crystalline form is used in all his preparations. (It is solid at ordinary temperatures, but melts readily when heated, or when a little water is added to the crystals.) In his earlier cases of compound fractures, etc., Mr. Lister used the pure acid (deliquesced crystals); but he renounced it, because it induced too much unnecessary irritation, increasing discharge, and thus retarding cicatrization. The materials used in the present system of treatment are liquid and solid preparations of carbolic acid, and pieces of , tin-foil, etc. Liquid solutions: 1. In water; 2. In oils or glycerin; 3. Alcohol. Solid preparations: Paste or putty; 2. Plasters; 3. . LIQUID SOLUTIONS. 1. In water: "Water dissolves but a small portion of the acid, only l-20th part of the pure crystals, and holds that small quantity very loosely, so as to permit it to act with energy on any substance for which it has stronger attractions, and also to become dissipated by exposure." It is applicable as a wash to the interior of recent wounds, whether the result of accident or operation. 2. Oily solutions. (Linseed and olive oil, glycerin.) "The fixed oils have so strong an affinity for the acid, that they will mix in any proportions with it, and hold it so firmly as not to permit it to act with much energy on the tissues, or to become dissipated into the atmosphere." 3. An alcoholic solution of one to four has been used. readily dissolves the acid crystals, almost equal to the oils: but, like the watery solution, it holds it but loosely. For this latter reason it is applicable to the surface of wounds, etc., especially those that have been exposed for several hours after injury. SOLID PREPARATIONS. 1. Paste or putty. This is an oily application made to assume a solid form. Linseed-oil, four parts, carbolic acid (crystals), one part, enough common whitening to form a paste of the consistence of glazier's putty. 2. Plasters. These are made with olive-oil, litharge, beeswax, and acid, one to ten, one to twenty, and one to forty. They are reliable, retaining their virtues for many hours. As an external dressing or guard, they shed the discharges freely, and keep all underneath antiseptic. They possess some , and have more recently been superseded by what Mr. Lister calls the antiseptic lac. It consists of shell-lac with which carbolic acid will mix in any amount by aid of heat; when mixed in right proportions it may be spread, when cool on calico. In this manner a large of the antiseptic is stored up. It is not softened by the . By brushing over the surface with a weak solution of gutta-percha in bisulphide of carbon, it is rendered . We have in this a durable and perfectly reliable antiseptic external dressing or guard, and at the same time a light and neat one. 3. Antiseptic Ligature. This is prepared by steeping the silk thread for two hours in strong fluid carbolic acid, prepared by adding a small proportion of water to the crystals. This ligature is applicable to the deligation of main arteries in their continuity, or arteries on the face of a stump or wound. The antiseptic curtain is a piece of muslin saturated with oily solution of carbolic acid, under which cavities are punctured, to prevent regurgitation of any air except that which has been deprived of its germs by being filtered through a carbolic acid vapor. The antiseptic guard is the external antiseptic , which is a reservoir of the acid, to be replenished from time to time, preventing the introduction of septic germs to the wound, and yet allowing the discharge to flow out under it. In the manipulations required in carrying out the antiseptic system of treatment, we must ever bear in mind the existence of septic atmospheric germs, and be particularly careful in not allowing the air to have access to the surface of a solution of continuity or cavity before it has been filtered through an dressing. The watery solution should be freely applied to all wounds of whatever character. In compound fractures, care should be taken to have the solution penetrate to all the recesses of the wound; during and after the performance of all surgical operations, the cut surfaces should be washed with it. , The alcoholic solution is to be used in the same cases when some hours have elapsed between the solution of continuity and the application of the antiseptic. In the performance of operations, all the instruments, probes, knives, etc., should be dipped into a solution one to four of olive-oil before being used. If the operation involves the of a joint or serous cavity, drop a one to four solution in the track of your incisions. In external wounds opening into the pleura or peritonaeum, a solution one to four may be introduced by strips of lint into the cavity. Dr. Weisse closed his paper by a summary of the of our pathological views, which in his estimation were forced upon us as the results of the antiseptic method of wounds, and he also gave a resume of the various of this method. Dr. E. R. Squibb was called upon by the President, and remarked: I have some knowledge of carbolic acid which I may add to that given in the very interesting paper we have just heard. I confess to a strong prejudice, since first reading Mr. Lister's articles, against what I have regarded as a complication of a simple method already well known. , Mr. Lister's honesty and earnestness grew into fanaticism, and led him to exaggerate and over-dose. At first he was to use the undiluted acid in wounds; but he has now got down to two per cent, in water, and finds this strong enough. We have been misled a little in the use of the crystallized substance known as carbolic acid. The term has ordinarily been applied to three associated substances, phenyl-alcohol, cresyl-alcohol, and xylic-alcohol, belonging to a series which most of the aromatic oils. They have all been pretty well proven to be alcohols, and they are not acids by any of this word. Of late, however, it has been disputed by Kekule and others that these substances are alcohols, and this opinion would seem to be gaining ground. Of these three , the phenyl is crystallizable, and has the lowest boiling point. As these became an object of commercial manufacture, the matter was taken up by a Fellow of the Royal Society, a pupil of Laurence, Mr. F. Crace Calvert. Seeing that there was one of the group which required much chemical knowledge and skill to produce it nicely, and knowing that, should he the manufacture of the others, he would be subject to much competition, he turned all his attention to the production of the most difficult, the crystallized phenyl-alcohol, without knowing that it was the least effective of the three. He had no competition. Up to the time of the investigation of the cattle-plague, the other tar-alcohols were supposed not to be antiseptic at all. When Mr. Crookes, and Dr. Smith, and others, took the matter in hand, they had no desire to damage Mr. Calvert's commercial prospects; but were finally compelled to admit that the phenyl-alcohol had no exclusive virtues. In his first report, Mr. Crookes says that the cresyl-alcohol has been supposed to have no antiseptic properties whatever, but that it seems to be nearly if not quite equal to the crystallized preparation. This remark led me to look into the subject; and some experiments convinced me that the cresyl-alcohol is far more efficient than the phenyl. Mr Parkes says that the acid, that is, the whole group together, is better for all purposes to which he has applied it, than are the crystals. , the whole group as found combined in the old-fashioned creasote, the ordinary creasote of the market, is the thing after all. Its efficiency has never been excelled by any of the " acids," and the result of their separation is merely to enhance the cost. As I before remarked, this whole matter of the antiseptic treatment of wounds has been too much . Simple watery solutions would probably produce quite as good an effect as these putties, plasters, lac, etc. With regard to burns, I can claim to speak from experience. A watery solution of creasote, of the strength of about one-half of one per cent., or the creasote-water of the pharmacopoeia diluted about one-half, applied on a single thickness of old pocket-, will allay the pain of a burn sooner than any thing else. Thus diluted it is a most valuable local anaesthetic. Under this dressing, a burn of the first degree will usually heal suppuration. One of the second or the third degree will not; nor will it under Mr. Lister's applications. The septic-germ theory of Pasteur, though now commonly accepted in a general way, cannot be made responsible for all the evils of suppuration without grave mistake. Dr. Jacobi wished to inquire of Dr. Squibb what was the chemical or physical effect of the creasote, undiluted or in strong solution, on healthy tissue? Dr Squibb: Its prominent characteristic is to coagulate . A strong solution applied to the surface turns the white, by virtue of this property. The whiteness after a time, and the epithelium becomes again . But this transparency indicates no return to its normal condition. The albumen once coagulated, it is dead, and must peel off. Another curious effect is noticeable: if too strong a solution is applied to a burn, it does not appear to relieve the pain; I have repeatedly seen a one or two per cent, solution fail to give relief. The character of the pain produced by a strong solution is exactly like that of a burn; but in the of the two there is this difference: If the part rendered painful by such an application be held up so as to drain it of blood, the pain is increased till it may become almost ; if held down so as to allow the influx of blood, the pain is diminished; herein the pain is like that from chloroform, and is exactly opposed to that from a burn. I might add that the reason why anatomical specimens are so often rendered opaque and unfit for microscopic examination, by being preserved in carbolic acid, is doubtless the too great strength of the solution employed. I suppose an aqueous of one-fourth of one per cent, of the cheap impure acid ought not to injure a delicate specimen. I have now in a series of experiments to determine this point, using solutions varying from one-tenth of one to one per cent., which last, I am convinced, is quite too strong. The best test of the proper strength of your solution is its application to the tongue. If it coagulates the albumen, producing an effect like that of hot tea or coffee, it is too strong. Dr. Jacobi: I am glad to see, Mr. President, that the agrees perfectly with what many of us have repeatedly seen. I have made the same observation with regard to the pain, and the effect of position upon it. I have felt, too, that, if the antiseptic treatment is to be of any use, it must be simpler than Mr. Lister has made it, for by his plan each patient requires five or ten times as much attendance as usual. I have myself used carbolic acid in a great number of instances, both upon living and upon dead tissue. A solution of one-tenth applied to croupous membrane will cause it to shrivel up in a very short time; and the very beneficial effect of the acid upon membranes is due to its coagulating power. But this very property leads me to think that solutions of one-fifth to applied to wounds, etc., as in Mr. Lister's practice, will have an effect just the reverse of what he intends. He wishes to preserve healthy tissue; I think I have often it by using a solution too strong. I know that a number of years ago, when I knew less about the subject than I do now, I very speedily destroyed the cornea in a case of diphtheritic conjunctivitis. I applied a very thin layer of a dilution of one part to eight or ten of glycerine and water to the conjunctiva; the cornea thus became slightly touched by it, and the result was that it was perforated much earlier than in the normal course of the 'disease. The diphtheritic affection might have caused perforation in thirty-six hours, while I had done it in five or six. I have seen the shrinking and destruction of healthy tissue immediately follow the use of strong solutions; and I agree with Dr. Squibb, that we have not yet reached the minimum of strength desirable. I now commonly employ a dilution of three or four grains to the ounce. I have used it to wash out the uterus in puerperal endometritis; and I am that in many cases of this kind, which have lately come under my hands, the patients have owed their lives to this . In very bad cases, I have used intra-uterine injections of twenty grains to the ounce; but then I am careful to use very little of the injection, to throw it directly into the uterus, and immediately to wash out the vagina with a milder solution, to avoid the unpleasant effect which the stronger one would produce upon it. In cases of common catarrh of the external ear, which are often as obstinate as they are uncomfortable, I have employed a three or four-grain solution, and found them yield more speedily than to any thing else. Dr. Chadsey had made use of carbolic acid from its first introduction, always in weak solutions, never stronger than one part to forty. A severe burn of the second degree had healed without suppuration under a dressing of the acid covered with oiled silk. He had gained happy results in gunshot wounds, putrid sores, disease of the ear, leucorrhoea, and gonorrhoea. For the latter cases, glycerine rather than oil should be used as a solvent, to avoid staining the linen. Dr. Smith wished to know whether tissue, whose albumen has been coagulated by any means whatever, could possibly retain its vitality; and if not, how such devitalized tissue was gotten rid in wounds subjected to Lister's treatment? Dr. Weisse thought it was carried away by absorption, and that the results proved this. Dr. Jacobi doubted whether albumen so coagulated would find any solvent in the fluids of the wound; and if not, then its absorption was impossible, for absorption could take place only after solution or fatty degeneration. Dr. Griscom had given inhalations of carbolic-acid vapor in a case of abscess of the lung, with a happy effect. Dr. Weisse, referring to the statement that Mr. Lister had come down from the use of the pure alcohol to that of a -cent. solution, said that he would doubtles come lower yet, only he wished to feel his way carefully, without incurring in any case what he woud deem a risk to the patient. Mr. Lister by no means claimed that all suppuration was due to septic germs. He simply said that experience had taught him that you will limit suppuration in a wound if you prevent of its fluids. Dr. Stein had made considerable use of the agent. He tin-foil to protect the dressings, as it could be most nicely adapted to the surface. He had assisted in the removal of nearly the entire frontal bone, for necrosis supposed to be , the soft parts having previously sloughed. The , which was excessive, was checked under the application of carbolic acid, and the wound healed very well. Iodide of was freely given. Dr. Chamberlain, attempting on one occasion to use what he believed to be the impure acid, had found it quite unmanageable, of about the thickness and color of dark molasses, nearly in water, and indelibly staining the vessel. lie wished to know if he had obtained the right article. Dr. Squibb: "That, sir, is not the 'impure' but the 'crude' carbolic acid. Nothing should ever be used for medical or surgical purposes which is not transparent, though it may be dark. The impure acid is made by redistilling the crude; it is a combination of the three alcohols, and would much better be called creasote, for it is identical with the old-fashioned coal-tar creasote. A mistake often made is that of prescribing a , and getting this; and fearful accidents have occurred from its application pure to burns, etc. The safest mode is to the crystals by measure. The impure acid is never wholly soluble in water, but it should leave merely a slight scum. The tar and oils are rendered more soluble by the addition of alkalies, an occasional adulteration." "Having answered Dr. Chamberlain, I would say that Mr. Lister began at the wrong end, with the heroic style of . I think it a very interesting question what did become of the coagulated albumen sealed up by him in his early ; for he used a large amount of the acid, dipped his finger into it, and smeared it all around inside the wound. If we could suppose pepsine to be introduced there, and a process of digestion to be set up, one might look for absorption. I think it most probable that the coagulated material, in such cases, becomes encysted, like other foreign bodies, for it is, to all intents, a foreign body. Mr. Lister's system illustrates what seems to be a strong tendency in human nature to seek . I am constantly finding persons leave the simple solution I have recommended for burns, and go to ointments, etc., which are not only useless but hurtful." The President: "I may say that, two years ago last , I commenced to direct that the wood-work of all the wards of Bellevue Hospital should be daily dampened with a solution of the crystals, two grains to the ounce. I afterward replaced this by a cheaper preparation of about the same strength. We have since a great diminution in the mortality there; but I would not ascribe this to carbolic acid alone, for we are very careful in our hygiene. In addition, I always direct that every woman in the lying-in ward shall have her vagina thoroughly disinfected. I make it the duty of the to see that no woman has any smell of the lochia about her; and for that purpose we have used carbolic acid, 's solution, and the permanganate of potassa. The last I have now discarded, because the specimens furnished were found irritating, perhaps from some admixture of caustic potash. I am not prepared to say that the carbolic acid is preferable to the Labarraque. Moreover, whenever a woman's vagina is found difficult to disinfect and we meet with such cases now and then it is made the nurse's duty to have a large piece of rag, saturated in a solution of the acid, laid near the vagina. We do not rely upon these means alone; when the floors are washed, a bottle of Labarraque's solution is added to the bucket of water; pans of chloride of lime are placed in the wards, and also shallow dishes of carbolic acid; the windows are kept open day and night, and the doors nearly all the time. It is certain that, by one or all of these means, we are getting clear of fever in that hospital. "As to the manner in which carbolic acid checks , it at this moment occurs to me, as a matter worth , whether it may not possibly so affect the capillaries of the part to which it is applied, as to prevent the lymph globules from escaping." The Society then adjourned. New York Medical Journal.
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(r) u 11 n r 1 a i Female Students and Physicians. A recent letter from a correspondent in Europe closes with the following report from the Gazette de Hospiteau: "Decidedly, the medical profession in France can no longer be considered the exclusive property of the male sex. Among the students who have passed the most brilliantly their examinations to the Faculty of Medicine are included three ladies one French, one Russian, and one American. The latter has proved herself to possess a solid knowledge of anatomy, and dissections, pathology, and surgery." It thus appears, that female students have not only gained admittance to the best hospitals and medical schools of Europe, for instruction, but they have finally been admitted to regular examinations and graduation, by the highest medical tribunal in France. Is it not time that the position of female medical students should be more definitely settled in this country? At present, they are admitted freely to clinical instruction in the hospitals of most of our large cities, but are denied admission into the colleges, or to become regular candidates for graduation. If, in despite of the latter obstacle, one of them persists, until she finally gets a degree, from some school in this country or Europe, she is freely recognized in practice, and consulted with by members of the profession of the highest standing; and if she can get a hospital or infirmary for the treatment of women and children started, any number of respectable physicians are ready to lend their names to make up the usual list of physicians, surgeons, obstetricians, etc. Now, if it is right thus to admit them to clinical instruction, in hospitals, consult with them in private practice, and associate our names with theirs, as attendants on public institutions, where is the or propriety of shutting them out of the colleges ? , there is no more indelicacy in mingling the sexes in the lecture room of a college than around the operating table of a public hospital. We are not disposed to encourage women to study medicine, simply because its practice is not a business suited to her nature, or which she can follow successfully, ignoring some of the most important objects of her own creation. To do the work of a general practitioner, she must be ready in the darkness of night, as well as at noonday; in storm as well as sunshine at all hours, to ride over the country, or traverse the streets or alleys of cities, all of which she do without stultifying her own social instincts, and the performing of some of the highest duties required of her by her Creator. And, yet, it is doubtless true, that there is now, and always will be, a very few females who are so , mentally and physically, that they will exhibit a disposition to study and practise medicine. These, if well educated, could be made very useful members of the profession, and find honorable and remunerative employment in the of special departments of the profession, in our more cities. Hence, we think, it would be much better, if the medical colleges should open their doors to them, and give them the same opportunities, and hold them to the same full as the other sex. Chicago Medical College Medical Department of the North-Western University. The next annual course of instruction in this institution commences on Monday, the 4th day of October. The general introductory lecture will be given in the College Hall, on Monday evening, by II. W. Boyd, M.D., Professor of Descriptive Anatomy. We feel no hesitation in saying, that the student of medicine, who is earnestly desirous of thoroughly educating himself in all the departments of medical science and practise, can find no college in this country more complete in its arrangements, more comprehensive in its curriculum, or more reliable in the faithful execution of what it promises, than this. There is already a good class attending the clinical instruction in Mercy Hospital, the new building for which is rapidly approaching completion. Archives de Physiologie Normale et Pathologique. Publiees par MM. Brown-Sequard, Ciiarcot, Vulpian. The number of this very valuable French journal for September and October is promptly on table. Its contents are varied and highly interesting. Pharmacist. We h^ve received the September number of the Pharmacist and Chemical Record of this city, containing the proceedings of the recent National Pharmaceutical , but too late Vo enable us to notice its contents in this number. We were absent from the city during the sessions of the Convention, or we should have been happy to have witnessed its proceedings. Canadian Medical Association. The second annual of this Association was recently held in Toronto. We enjoyed the pleasure of attending its sessions, and forming the personal acquaintance of many of its members. We had an abstract of such part of its proceedings as would our readers, but want of space will compel us to postpone its insertion until our next number. Mortality for the Month of August, 1869: Accident, drowned____14 " burns, 4 " by fall____ 4 " railroad 3 " run over by wagon 2 Anasarca 1 " and fever scarlet 1 Apoplexy 4 Ascitis and of liver________ 1 Asthma , 2 " and consumption 1 Births, premature____26 " " tedious_______ 2 Bowels, inflammation, 4 Brain, congestion of_ 8 " compression of, 1 -l disease of____ 3 " inflammation _ 6 " malformation _ 1 " softening of 1 Cachexia, Cancer of superior maxillary bone 1 Childbirth__________ 1 Cholera infantum___328 Cholera morbus 7 Convulsions__________86 Consumption 40 Convulsions, puerperal 5 Croup 8 " diphtheretic____ 1 " membranous______ 2 Cyanosis 1 Debility 3 " general 1 Delirium tremens 1 Diarrhoea___________81 " chronic_________ 4 " whooping-cough 2 Diphtheria 12 Dropsy 3 Dysentery_____________38 " chronic_________ 1 " typhoid 2 Encephalitis__________ 5 Endo-carditis_________ 1 Entero-colitis 5 Enteritis_____________12 Epilepsy______________ 1 Exhaustion____________ 1 Erysipelas 1 Fever, congestive____ 1 " puerperal 7 " scarlet 53 " " malignant, 3 " typhoid 19 " typhus__________ 2 Gastritis_____________ 3 Gastro-enteritis 4 Hemorrhage, internal, 1 Heart, disease of_____ 3 " organic disease of 1 " valvular " 2 " fatty of_____________ 1 Hemipligia____________ 2 Hepatitis, acute_____ 2 Hernia, umbilical____ 1 Hydrocephalus________17 " acute 7 Inanition_____________10 " and diarrhoea___1 Intestinal obstructions 1 Jaundice______________ 1 Kidneys, Bright's dis. 1 Liver, atrophy of____ 1 " disease of_______ 1 " abscess of 1 " inflammation of, 1 Lungs, con estion Mouth, canker sore___1 Measles_______________15 " and diarrhoea____ 1 " and teething_____ 2 Meningitis 12 " cerebro-spinal, 7 Meningitis, tubercular, 2 Manslaughter_________ 3 Neuralgia 1 Old age______________ 6 Otitis_______________ 1 Paralysis____________ 4 Peritonitis__________ 3 " puerperal 3 Phrenitis____________ 1 Pleurisy 3 Pneumonia 9 " typhoid 1 Poisoned, unknown 1 Pyaemia 1 " from complicat'd fracture of leg 1 Rheumatism, Scrofula 3 " of hip joint and gastritis 1 " of intestines 1 Small-pox____________ 1 Septaemia 1 Spine, fracture of 1 Syphilis 1 Stomach, cancer of 2 " hemorrhage of 1 " scirrhosis of 1 Sun-stroke 3 Suicide______________ 7 Tabes mesenterica, 39 Teething_____________26 " and convulsions, 6 Throat, ulcerated sore, 1 " putrid sore 1 Uremia_______________ 1 Vitality, deficient 1 Whooping-cough 24 " and teething 1 Womb, contraction of, 1 " inflammation of, 1 Wound to foot from fall_________________ 1 Total____________1070 COMPARISON. Deaths in Aug., 1869, 1070 | Deaths in Aug., 1868, 945 | Increase, 125 Deaths in July, 1869,_________815 | Increase, 255 AGES. Under 1 488 1 to 3_____________313 3 to 5______________ 44 5 to 10____________ 25 10 to 20___________ 24 20 to 30____________ 53 30 to 40____________ 45 40 to 50____________ 31 50 to 50____________ 21 60 to 70____________ 14 70 to 80_____________ 8 30 to 90____________ 2 10 to 100___________ 1 Unknown 1 Total,__________1070 Males, 548 Females, 522 | Total,_________1070 Single, 950 Married______________120 | Total,_________1070 White, 1062 Colored,_______________ 8 | Total, 1070 NATIVITY. Austria 1 Atlantic Ocean______ 3 Bohemia,_____________ 7 Bavaria______________ 1 Canada,_____________ 10 Chicago, Native,____197 Chicago, Foreign,___549 U. S., other parts,_109 Denmark,____________ 2 England,____________ 8 France,_____________ 1 Germany,___________ 75 Ireland,___________ 41 Italy_______________ 1 Norway,____________ 18 Poland 1 Scotland, 5 Sweden,____________ 29 Wales_______________ 3 Unknown, 4 Total,__________1070 MORTALITY BY WARDS FOR TIIE MONTH. Wards. Mortality. Pop. in 1868. One death in 1 16 9,094 568^ 2 18 13,074 726| 3 39 15,076 384 4___ 62 17,796 287 5 95 16,033 168 7-9 6 64 13,083 204J ' 7 104 25,492 245 1-9 8 103 15,813 153j 9 53 19,297 364 1-10 10 24 12,925 538| 11 29 14,340 494| 12 135 17,485 129i 13 55 11,164 203" 14 62 14,839 239J 15 58 21,078 363 3-7 16 42 15,465 368 1-5 Mortality. Accidents,_________________________ 27 Bridewell 1 County Hospital,___________________ 21 Home for Friendless, 6 Immigrants,________________________ 32 Jewish Hospital,____________________ 1 Mercy Hospital,_____________________ 1 Marine Hospital, 2 Manslaughter, 3 Protestant Orphan Asylum, 1 St. Joseph Orphan Asylum, 7 Poisoned, unknown___________________ 1 Convent of Good Shepards 1 Suicide,____________________________ 7 Total,________________________1070 Resolutions of Respect upon the Death of Dr. F. O. Earle. Whereas, the Chicago Medical Society has been of one of its members, by the death of Dr. F. O. Earle. Resolved, that we lament his loss. Although he had been with us but a brief time, we had learned to respect him for his gentlemanly deportment and professional ability. Although quite young in the profession, he had given promise of more than ordinary ability, and could look forward to a noble and useful future in the profession of his choice. We cannot but feel that the close application and devotion to the labor of the profession, during his stay among us, had much to do in his early death, which seemed too soon. The profession has lost an earnest worker. To bis family and relatives we may be permitted to express our sincere sympathy. Resolved, that a copy of these be sent to the family, and that they be published in the medical journals of this city, and in the Medical Record of New York. R. G. Bogue, M.D. T. D. Fitch, M.D. A. H. Foster, M.D.
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MEDICAL SOCIETY OF COUNTY OF NEW YORK. Stated Meeting, June 7, 1869. Dr. GEO. T. ELLIOT, Jr., President, in the Chair. The President announced the election of Dr Robert McNeil to membership. Dr. Salvatore Caro read a paper upon the Treatment of Summer Complaints by the Bromide of Potassium J * This paper is published in full in the Medical Record of July 1, 1869. Although the title of this paper comprises the entire range of diarrhoeal diseases both of adult and infantile life, special reference was had to the diarrhoeal diseases of infancy, standing prominent in the list. The causes, , progress, and termination of this complaint were described at length, as well as, in a general way, the treatment which is usually considered orthodox in these cases. Then stating that an accidental success in the treatment of several cases, wherein he had administered the bromide for other purposes than to control the diarrhoea, had led him to more fully test the value of this remedy, the speaker narrated twenty cases which might be taken as types of the cases usually met with in practice, and which were selected from 163 recorded cases occurring under his own observation. We present herewith, from the Record, five of the cases in full: III. John Sinott, 28 months old. I took charge of him on the 1st of August. For several days he had been suffering from vomiting and purulent discharges from the bowels. I prescribed aromatic syrup of rhubarb with laudanum, but without effect. On the 2d, I gave twenty drops every hour, of a mixture of ten grains of bromide of potassium, in an ounce of mucilage, with twenty minims of krameria. After a few doses the child slept, and upon awakening asked for bread and butter. Vomiting ceased. The flux of the bowels changed from purulent to ; and the 24 to 30 passages, every 24 hours, diminished to six. He became convalescent, and on the 8th was discharged. IV. J. A. Criger, 20 months old; has twelve teeth. to his mother's statement, he has never given trouble, and drinking whatever was offered him. On the 3d of August he fell from a chair, striking his buttock, apparently receiving no injury. During the night his bowels became loose, accompanied by a dirty-water-like substance. In the morning he had convulsions. During the afternoon I found him very comatose; pulse froui 95 to 100; pupils dilated; hemiplegia of the right side; alvine discharges, from twelve to fourteen, every 24 hours, of a thin fetid matter. About every six hours, of ten minutes' duration, accompanied by vomiting. I prescribed revulsives to the lower extremities and arms; and, every two hours, twenty drops of a mixture of one drachm of bromide of potassium, in an ounce of mucilage. The motion of the bowels and vomiting ceased. After a few days, as the comatose and hemiplegic condition continued, iodide of potassium brought matters right. On the 1st of November he had another fall, merely affecting his bowels by free motion; the bromide of potassium immediately stopped it. V. John Balheimer, 13 months old; has six teeth; is fed by the bottle. On the 15th of August I saw the child for the first time. He had been suffering for 14 days from inflammatory dysentery, having passages of a purulent and bloody nature, from 20 to 24, every 24 hours. His thirst was intense; he vomited every fluid offered him. The eyes were sunken, pupils dilated, skin corrugated and spotted blue, body cold, tongue red and dry, pulse imperceptible; no urine. In addition to this, he had bronchitis, with severe cough. I prescribed 1 scruple of bromide of potassium, in an ounce of mucilage, with J drachm of tincture of krameria, 20 drops every two hours. The passages decreasd. On the 16th day of his sickness, and the second under my care, he was able to eat and sleep. His passages were only 4 in 24 hours, and of a healthy appearance. In order to allay the bronchial cough, I prescribed 10 drops of fluid extract of poppy, to be taken every two hours. On the 1st of September, he was discharged. A few days later he had a relapse, and on account of distance was placed under the care of a homoeopathist, and died. On the 15th, an elder brother was brought to me suffering in a similar manner from dysentery. The disease was immediately checked by the bromide of potassium. X. J. McEvoy, 12| years old: a healthy boy, attending school. August 13th, having eaten a bellyful of green apples, he was seized with cramps in the belly and legs, colic pains, vomiting, and loose bowels. For 48 hours his parents doctored him with castor-oil, paregoric, cholera drops, mustard baths, etc., etc., but without giving relief. I was sent for on the 15th, the third day of his sickness. I found him with eyes sunken, skin cold and corrugated, extremeties bluish, which upon being touched would leave the white impress of the fingers for more than 25 seconds. The abdomen was almost struck to the column; breath hurried and hot; tongue pale; voice scarcely audible. The boy was shivering with cold, although covered with mustard plasters, blankets, etc., and in an hot, low-ceilinged room on the top floor. His thirst was intense. The drinks given him were, rice-water, beef-tea, brandy-and-water, ice-water, milk-whey, etc. No sooner taken than ejected indiscriminately, both up and down, almost in their natural state. I thought this case almost hopeless, but, trusting to the efficacy of the bromide of potassium, I prescribed J drachm in an ounce of water a teaspoonful every two hours; also a flaxseed meal poultice over the abdomen. The second dose caused great reaction, stopping the vomiting and flux of the bowels, and the boy fell asleep. The next morning I Tound him in his hot unhealthy room, laughing and well. I have had 25 similar cases, ranging from 12 to 46 years of age. XIV. J. Higgins, a healthy infant, deprived of the breast from his mother's dying seven days after confinement. When only three days old he began to suffer from retention or . All nourishment was ejected with great force, even the breast milk of a woman confined five days before his birth. The stomach, from the irritating action of the meconium, could not retain either medicine or food, nor could the bowels be mo/ed. Ten grains of the bromide of potassium in an ounce of orange-flower water, ten drops every hour, put a stop to all symptoms; the baby slept, its bowels moved, and, after the discharge of the meconium, it commenced to nourish from the bottle without any further disagreeable results. I had three similar cases, not owing to the mothers' death, but the infants being deprived of the maternal nourishment from other causes. The paper concluded as follows: Now let us speak on the merits of the drug. Taking for granted that, in matters of fact, in medicine particularly, we can judge better a posteriori than a priori, I submit my cases and conclusions to this enlightened body. Not accepting the doctrine of some of the modern writers, that the intestinal flux is a symptom of some inflammatory affection, but adopting the opinion of the celebrated Capuron, that infancy being naturally the age of nervous sensitiveness, susceptible to internal and external impressions, easily irritated or calmed, and judging from several other cases besides those just read, I think that, in its beginning, summer-complaint arises from an over- of the nervous and vascular systems, and that therefore the bromide of potassium affects it, and acts as a sure cure. I cannot better explain the action of the bromide of potassium on the system, than by quoting the words of Headland, found on page 272 of his work, " On the Action of Medicines,' "The bromide of potassium, a medicine of the mineral kingdom, has been much recommended lately for its power of producing sleep ; it is, however not a true soporific, but rather a general sedative. As far as my experience goes, it acts by allaying irritability of the brain, spinal cord, and sexual system, and thus may cause sleep." And on page 283, "The bromide of potassium, a remedy of recent introduction, is exceptional among nerve medicines as, belonging to the mineral instead of the vegetable kingdom. It quiets the nervous system generally, allays pain, promotes sleep, and subdues a morbid irritability of cutaneous or mucous surfaces, by its influence over functional disorders of the nervous centres. It is only indirectly soporific, as far at least as I have been able to judge." Mr. Gubler the bromide of potassium a general sedative to the system, allaying irritability of the mucous membranes, and at the fauces and genital passages especially. He thinks it hypnotic, causing sleep by its sedative action on the whole nervous system. M. Vigouroux thinks it acts by diminishing vascularity of the great nervous centre. It is therefore the remedy, par excellence, for the nervous complaints that are common in large cities. (Z' Union Medicale, 1864.) I have never discovered any unpleasant effects produced by the use of the bromide of potassium, and have always found it to answer my purposes. If locally applied, it reduces the excessive heat found in the mouth of the baby, caused by the inflamed condition of the gums. On introducing the into the mouth or anus of the baby, I have seen the fall four or five degrees. The drug is an anaesthetic to the nerves of the mucous membrane of the alimentary canal from the mouth to the rectum, of the urethra, the conjunctiva, and the nares. It is also a diuretic. In cases where the urine has not been voided for 24 hours, after the first dose of the it is freely passed; the skin commences to feel warm, and becomes covered with a gentle perspiration, removing uraemic symptoms, causing general reaction, and invariably the decrease of the intestinal flux, and an absolute cessation of vomiting. The medicine being almost tasteless, and of no bulk, it is easily taken by the most fastidious and troublesome child. I generally prescribe from 10 to 30 grains in an ounce of vehicle, either mucilage or orange-flower water, for their pleasant taste; the dose being 10 to 30 drops every hour or two, varying to the age of the patient, and the acuteness of the case. I seldom use astringents with it; but, if required, I select the tincture of krameria, as less disgusting than kino and others. For local application, I mix the salt with mel rosarum, generally using one scruple of the first to an ounce of the latter, the mother to rub it on the gums with her finger ad libitum. When used in large doses, I have not found very satisfactory results from the bromide of potassium; but I always succeeded with minute doses. You will observe that, of the cases I have just reported, only three died, and the fatal result in these was due not to the bowel complaint, but to other causes. I had also four cases which I purposely and obstinately treated according to the -adopted system. To my regret I must confess, that but one, after a severe and hard struggle, recovered; the other three died. Dr. Calkins deemed hot-water and hot-vapor baths auxiliaries in the treatment of the bowel complaints of children, and related a fatal case, which he thought had from their omission. Dr. Garrish had found the bromide fail to control the nausea and vomiting of pregnancy, and asked Dr. Caro's experience. Dr. Caro had not used the drug in pregnancy, as he had gained the impression, from something in his reading, that it was emmenagogue, and might do harm. He had found it arrest the vomiting in the case of a woman with Bright's disease, who had, for three or four weeks, been unable to retain food. It had stopped the nausea and vomiting in a case of typhoid double pneumonia. Dr. Chadsey had been using the bromide quite freely, for the last three months, in affections of the stomach and bowels. It had happily relieved the only case of cholera-infantum he had chanced to have in at that time. In a case of vomiting, in the commencement of pregnancy, which nothing else would check, it had been promptly effective, and no bad results had followed indeed, none had been anticipated. A druggist, having a very large prescription business, had said that the consumption of the bromide had quadrupled within a short time, and that it was now greater than that of the iodide, which it was replacing in many instances. The President was asked whether he considered the bromide an emmenagogue. He replied that he had used it in many cases of pregnancy, as well to control the nausea and vomiting as for other indications, and his experience was that it had no emmenagogue action whatever. He was in the habit of it freely, and in large doses, in dysmenorrhoea, to gain its sedative effect, and he had never seen it increase the flow. He could not, therefore, think we were justified in refraining from its use on account of the pregnant condition. He had not found it so satisfactory a remedy in the nausea and of pregnancy as to lead him to give it the first rank; but neither did he know any other remedy to which this could be assigned. In the treatment of such a symptomatic disorder we must expect failure. It was trying to remove the effects of the thorn in the flesh, without removing the thorn. Among the articles that had lately appeared, commending the bromide in the various forms of nausea, was one by Dr. Storer, of Bos ton, showing that it counteracted the nauseating effects of ether. With regard to the class of cases related by Dr. Caro, Dr. Elliot yielded entirely to him in experience, and could speak, from personal knowledge, of his accuracy of observation and record. His testimony was of such value that it would more or less shape the practice of his hearers this summer. In the case of a rachitic little child, suffering from and bronchial catarrh, with a good deal of diarrhoea, refusing nourishment, and lying on the bed, with hot skin, restless and fretful, Dr. E. had given the bromide alone, and its effect was delightful. It had produced like results in one or two other cases equally unpromising. As to the extended use of the salt, Dr. Chadsey was right. Probably every druggist was now selling much more than four times as much of it as a few years ago. For his own part, while prescribing it much more frequently than before, it was not so lately that Dr. E. had been awakened to its value. Fourteen years ago it was his favorite remedy in spasmodic croup, and bronchial catarrh, with irritation of the respiratory passages. Having about that time a troublesome case of croup, he had at last given the mother the prescription, labelled "Preventive for croup," to be used whenever she saw an attack coming on. On her return from Europe, the lady said it had worked so well that she had given the prescription to some sixty families. The hypnotic action of the bromide was so well known as to need no comment. The danger was, now, that too many of the public would acquire the habit of taking it, as a regular thing, to procure a quiet night's sleep. Dr. E. believed that a of this city had lost his life from its excessive and use. A prescription given to secure sleep, this man had kept and had renewed, again, and again, until he used to lie half the day in a state of languor. Coming under the speaker's care, his habit was discovered, and finally given up ; but not before it had produced the prostration which was probably the cause of his death. Dr. Caro, in response to questions, said that he had given the small doses | of a grain to 3 grains mentioned in his record of cases; and that he had never, save in a single instance, given a dose larger than 8 grains. He had seen no eruption follow, except in one case, and there he thought it not attributable to the bromide. Dr. Kennedy thought the dose of the drug might be very indefinite. He had himself taken a large amount of it last winter, for an obscure trouble in the head and pain in the shoulders the doctors were undecided about the diagnosis, but agreed in recommending the bromide. He had begun with a solution of 2 drachms of the salt to 4 ounces of water, a every three or four hours. This dose he increased till he was taking 2 and 4 drachms of the salt daily. Then he bought | a pound of it and made a saturated solution, of which he took at first a teaspoonful, and afterward a tablespoonful, four times a day; and he might have taken more without injury. It gave a very pleasant night's rest, and a delightful feeling of languor and lassitude, which was continued for days and weeks. He had observed the eruption; also that the medicine disturbed the bowels and stimulated the kidneys; but, in his own case, it did not at all disturb the stomach, simply producing an sense of warmth. He believed that, where the nervous system is irritated, from whatever cause, and it becomes to soothe either body or mind, the bromide is an excellent remedy. He would recommend it to be taken freely in such cases, and especially by rum-drinkers. The President stated that a saturated solution in water was one part to four. Dr. Farnham referred to the cases reported by Dr. , where the bromide, in large doses, had produced - The President had once given J an ounce in the course of one night, in a bad case of delirium tremens. The morning came, and it had produced no perceptible effect; but a shower-bath on the head and neck put the patient to sleep in a couple of hours. He would hardly give such a dose again; for, although some persons might bear it well, there was undoubted testimony to its evil effects on others. We should remember the fate of Fountain, who to prove his views of the harmlessness of chlorate of potassa, took the dose which killed him. Dr. Howard had used 10 grain doses, every two hours, with great benefit, in cases of sick headache. W. Y. Med. Jour.
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s> PS 11 r i in li s CONCERNING THE ACTION OF OPIUM UPON TIIE UTERUS, AND PARTICULARLY AS A PARTURIENT AGENT. By P. C. BARKER, M.D., Morristown, N. J. "Parturition consists in the expulsion of the foetus and its appendages from the cavity of the uterus, and ends in the of the child and the mother" (Churchill). It is by means of non-striated contractile fibres, which are practically muscular, and constitute what is generally termed "the muscular coat of the uterus." These fibres are arranged in longitudinal, oblique, and (circular) transverse directions. The two first predominate in the body, and the latter in the cervix, and particularly in the "os uteri externum." Before the expulsive contractions commence, which terminate the process, these circular fibres should relax, and the "os" become widely dilated; but irregular contractions of the sets of fibres, or contractions of the circular alone ( false pains), or rigidity of the "os uteri," due to tonic of its circular fibres, often prevent this physiological dilatation, and prove the source of great distress to the patient and annoyance to the obstetrician. It -was in cases of this character that I discovered in opium a valuable parturient agent. I will narrate a few cases w'hich will illustrate how it became manifest to me: Case I. Mrs H., about 25, a strong and healthy woman, primipara, was taken in labor, 2 P.M., July 15th, 1862. Saw her soon after. Pains frequent, and of moderate severity; os dilated sufficiently to admit the point of the index-finger. Head presenting in first position. Left her for half an hour, and upon returning found her condition unchanged. Visited her at intervals until late in the evening, when, no progress having been made, ordered antimon, et potass.-tart., gr. |, every half hour. Went home, leaving directions that I should be sent for if any change occurredt Messenger came to me about 2 A.M., 16th. No further dilatation. She complained very much of the severity of the pains. Tartar emetic, gr. |, every half hour. No improvement resulting, and nausea being constant, it was discontinued in the morning; and a stream of warm -water was thrown upon the os, by means of a Davidson's syringe, for half an hour. This was repeated three times during the morning. c2 P.M. Still no dilatation. Patient a little feverish, and complaining of being very tired and sleepy. Ordered morph, sulph., |th, and left her to get a little sleep, while I went to to other engagements. Returning about an hour after, I found mother and child comfortably asleep side by side. About half an hour after taking the morphine she had a hard expulsive pain; and before any one could leave the.house the child was born. The pains had not changed in character until just before the termination of the labor, nor had she been asleep. Case II. Mrs. 0., 35, multipara. Previous confinement easy. Taken in labor with her fourth child, November, 1863. Pains of same character as in Case I., for 16 hours producing little dilatation. At 1 A.M., gave morph, sulph., gr. J, hoping to quiet the pains. Left for home, a short distance away, and retired at once. Just as I was getting asleep, a messenger came for me in hot haste, stating that the child was born. Hastily dressing, I returned in time to remove the placenta. Less than three-fourths of an hour had elapsed since I quitted the house. She had but one pain, of different character from those which had tormented her so long unavailingly, previous to taking the morphine. Case III. Mrs. W., about 24, primipara, sent for me early in the evening. Being absent from home, my former partner, Dr. F. D. Leute, of Cold Spring, N. Y-, answered the summons. Upon my return I went to relieve the Doctor. There was no dilatation, although the pains had been recurring for some time. We gave her morph, sulph., gr. |. and went home, giving to send for me should any change occur. On the following day, I learned that about half an hour after our departure she was seized with severe expulsive pains, which terminated the labor before a messenger could be dispatched after me. It is obvious that morphine was given in these cases, as it is usually given by the profession, if at all, with the intention of obtaining a respite from the pains, in the hope that when they returned they would be more efficient. I was surprised in each case at the result; although in the first I attributed it to the repeated use of the warm douche, from its recognized power in certain cases of this character. In the succeeding cases I was obliged to look for a different explanation, and at length concluded that the morphine increased the expulsive power of the body of the uterus to a degree sufficient to overcome the circular fibres and connecting tissue of the "os uteri." Further light was thrown upon the subject by the following case: Case IV. Mrs. G., 28, multipara. In labor a number of hours. Os uteri remaining about half dilated, and rigid. Gave morph, sulph., gr. |. About half an hour after, while making an examination during a pain, my first and second fingers being applied to opposite sides of the os, in order that I might observe the effect of the pain upon its hitherto unyielding tissues, I was surprised to feel it easily dilating:.* *1 will add, for the benefit of those interested in the discussion which some time since appeared in the columns of one of our medical journals, concerning the propriety of making forcible attempts to dilate the os with the fingers, that I have for several years practised it, and think that I have shortened the first stage of labor many times thereby. In cases where the anterior lip has not been fully dilated after expulsive pains began, I have also shortened trie second stage, by persistently pressing upon it until it receded beyond the presenting portion of the head, even after it had become oedematous. The rationale is quite simple: the tissues being subjected to increased pressure, relax sooner than they otherwise would. In this case, I suspected that while opium stimulated the fibres of the body of the uterus (longitudinal and oblique), it also relaxed the circular fibres of the os. Further observation, in a large number of cases of varied character, has convinced me that opium, instead of having a general anodyne effect upon the uterus, possesses this special power as a parturient agent. I say general anodyne effect, for while it sometimes quites contractions (witness its universal use for this purpose), yet it is in those cases in which the circular fibres are called into action alone, or where the longitudinal and oblique fibres irregularly in short, in false pains. I am fully persuaded that opium never did or can arrest a physiological labor. I have many times been called to cases in which the pains have returned regularly and with increasing intensity for a number of hours, without producing dilatation to any extent; and, after giving a full opiate, have had the satisfaction of a marked improvement, after sufficient time had elapsed for its absorption, the patient having even harder contractions, with less distress than before, and the os uteri being speedily dilated. During the first stage of a physiological labor, I believe that the circular fibres of the os are passively relaxed, and that the active, usually gentle, contraction of the fibres of the body of the uterus serves to overcome the resistance which the tissues of the cervix and os present to dilatation. Now, if the circular fibres of the os retain their tonicity, or if they contract with those of the body during a pain (and I have felt them contracting in a number of cases), no dilatation can be effected; or, at any rate, it will be with great difficulty, and the resulting distress will be greater than w'hen they offer only the minimum amount of resistance. The cases above narrated and referred to have taught me that opium possesses the power of relaxing the circular fibres, at least of the os, and of stimulating the longitudinal and oblique fibres into active contraction. It is upon these principles that opium is exhibited in dysmenorrhoea, when it is dependent upon spasmodic contractions of the circular fibres; or where it is owing to the presence of "menstrual decidua," clots, etc. In abortions it is an invaluable remedy, facilitating dilatation, diminishing hemorrhage, promoting the expulsion of the , and lessening suffering. Ergot, on the other hand, by causing contraction of the fibres, retains the placenta, and, therefore, should rarely be given (in abortion) until after the foetus and secundines have been expelled. Placenta Prcevia. I have used opium in three cases of praevia, one at the sixth month, and two at term, saving the mother in each instance. In another case, I attempted to turn, but, having made an erroneous diagnosis as to position, the placenta being planted directly over the os uteri, I the wrong hand, and, failing to get hold of the feet , so as to bring them down, I detached the (entire) placenta, rather than lose time by changing hands. I mistook a R. Occip. Post, for a L. 0. Anter, position. The haemorrhage ceased at once, and the mother subsequently did well. I think that opium meets two important indications in prcevia: 1. It facilitates dilatation, thus shortening the period of greatest danger. 2. It promotes the expulsive power of the uterus. It also serves to lessen hemorrhage by a special haemostatic action. It is an interesting fact, that in one of these cases, when the respiration was reduced to four in the minute by cumulative of the opium, which had been too frequently repeated by mistake, the uterus expelled the child with one pain, thus my statement that opium does not possess the power of arresting normal uterine contractions. IIour-G-lass, Contractions, etc. While hour-glass, cylindrical, or other irregular tonic contractions of the uterus (particularly those which occur after the expulsion of the foetus) may be (and doubtless are sometimes) spontaneous; still, in my experience, they have always seemed to be due to ergot. Since I have learned the special power of opium, as set forth in this paper, I have used it in these cases with invariable success, although some of the most approved obstetric authorities say such use "is objectionable." I will give the following cases in point: Case V. December, 186//.. Mrs. McD., aged about 38. Primipara. Labor progressed steadily until the head had fully distended the perinaeum. Retrocession followed every pain; and, as they were neither strong nor long no progress was made. The vulva, too, was well dilated, and I gave f 5jss. Squibb's fl. ext. ergot to complete the delivery. Fifteen minutes afterward the peculiar contractions produced by ergot commenced, and the child was soon born. Placing my hand upon the fundus of the uterus (it having been pressed upon by the hand of an while the child was being delivered, and the funis tied and severed), I discovered it to be much elongated, reaching above the umbilicus; and, making a vaginal examination, found the placenta to be beyond the reach of my fingers, and, the hand, discovered it so tightly grasped by an contraction that I could not remove it. Gave morph, sulph. gr. J, noting the time. A little less than half an hour afterward, I was awakened (having fallen asleep from great fatigue) by a contraction of the uterus under my hand. The placenta was expelled with considerable impulse, and the uterus contracted down almost entirely below the os pubis (which, by the way, judging by my experience, it seldom does, teachers and text-books to the contrary notwithstanding). Case VI. Mrs. S., multipara. A delayed labor dependent upon inefficient pains. Gave f. 3jss. ergot. The child being born, I delivered the placenta at once (as I now invariably do after giving ergot). A cylindrical contraction immediately , the fundus rising considerably above the umbilicus, in fact almost as high as the ensiform cartilage. The cylinder was about three inches in diameter, firmly and uniformly . An opiate was given, and in due time a permanent, globular contraction followed. Dr. J. D. Trask, in his essay upon "Rupture of the Uterus," published in the American Journal of Medical Sciences, and April, 1848, gives four cases of rupture of the uterus due to ergot. Malgaigne and others have reported similar cases. The following case is given to show how this accident might be produced in a diseased or even very powerful uterus, as well as to illustrate the apparently antagonistic effects of ergot and opium upon the gravid uterus. Case VII. Mrs. M., multipara, about 35. Previous easy. Present labor not worthy of note until the os was nearly obliterated, a ring only being left, when dilatation was for some unknown reason arrested, and no progress made for an hour. The uterine contractions then becoming inefficient, gave ojss. ergot. As soon as the pains peculiar to ergot began, I made an examination, and found the os less dilated than , and its fibres contracting with those of the body. Gave gr. |, morph, sulph. Within half an hour the pains had become more like those of a "physiological labor," the os uteri relaxed and became dilated, and the expulsion of the child speedily . I gave opium in this case, with the expectation that it would produce a relaxation of the circular fibres of the os. It seems to have exerted this power in opposition to ergot as effectually as in the "hour-glass" and other irregular contractions above mentioned. It may readily be seen that the simultaneous action of the ergot upon the os and body might have caused a rupture of the uterus. The contractions produced by ergot are continuous. I have often observed, however, that they have not been , but have occurred in different sets of fibres successively. Herein lies one great danger of its use. In these, as well as all other irregular contractions of the uterus, I find opium a prompt and reliable remedy. In fact, I now use it in those cases of delayed labor dependent on inefficient uterine , instead of ergot. This property being established, the administration of opium admits of wide application in uterine therapeutics. In , abortion, irregular contractions of the uterus of all kinds, previous, during, and subsequent to labor, and in placenta praevia as an adjuvant to Barnes' dilator, it will be found to be a valuable remedy; more certain in desired action (when given under proper indications) than any other remedy in our . Such at least it has been in my hands in quite an obstetric experience. In dysmenorrhoea, opium is given to quiet the contractions of the circular fibres (when this variety is present). In abortion, it is administered in the hope that the pains are caused by contractions; and, if there is no dilatation (producing a partial separation of the membranes), it will often prove . If, on the contrary, the process has progressed so far as to render abortion inevitable, opium promotes it by relaxing the circular fibres of the os. It may appeal* at first strange to hear such apparently opposite properties ascribed to a remedy; but there is no inconsistency in the statement. The irregular (colicky) contractions do not constitute abortion, but they may produce it; and there is much less risk in a temporarily relaxed os uteri without pain, than in a normal condition of the os, with contractions of any kind in the body. In the "irregular " at term (as in Cases V., VI., and VII.), it acts promptly, I will state that cases might have been multiplied to a large number illustrating this subject; but the practical value of my paper would not have been enhanced at all, as the cases selected are as well or better-marked instances, each of its kind, than any others recorded by me since I commenced my observations seven years ago. (I had previously observed its powerlessness in quieting physiological uterine contractions, in the lying-in wards of Bellevue Hospital, while an interne.) With respect to the mode of administration, I am not aware that it makes any difference what preparation of opium is used. I have generally employed solid opium pills, grs. 1 to 3, or morph, sulph., gr. to | (the latter given dry on the tongue if nausea is present) at term. In abortion, if seen early, I give enemas of corresponding strength, usually employing from 3ss. to 3j. doses of opii. tinct., in a tablespoonful of warm water, to be repeated after three hours if the pains continue, or later, if they return after being quieted. If abortion can not be , the hypodermic syringe and Barnes' dilator of tampon are preferable. I have not used the hypodermic method at term, having been satisfied with the more gradual effects of by mouth; and, besides, I have thought that its rapid absorption inio the maternal circulation might be injurious to the child. I have never observed any such effects following the administration by mouth. And, what is very singular, it seldom induces somnolency in the mother. There are cases in which the os uteri (from previous ) is almost, and sometimes entirely, undilatable, over which opium (in common with all other known therapeutic agents) exercises no control, and for which the knife is the remedy. In conclusion, it will be seen that the theory set forth in this paper explains phenomena in the action of opium upon the gravid uterus, which have hitherto, from the time of Denman to the present, been regarded as exceptional, and that it the value of this remedy as a parturient agent. My object in calling the attention of the profession to these peculiar and very useful properties of opium has been the of a wider knowledge, and a more general application of them in practice; and I feel assured, that if opium is in the conditions and doses above indicated, it would not disappoint the obstetric practitioner. Nero York Med. Journal.
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PLACENTA PR2EVIA, AND OTHER CASES. Reported by B. H. CHENEY, M.D., of Joliet, Ill. Three cases of placenta praevia have recently occurred in my practice; a much larger number proportionally than is usual. The eases present nothing remarkable either in their pathology <or treatment; still, the nature of this dangerous complication -of labor is always of such interest and importance that they will perhaps bear a brief rehearsal. PLACENTA PRJEVIA LATERALIS. Case I. Mrs. B., aged 34 years, multipara, American, temperament leucophlegmatic; no hemorrhage in previous . A midwife attended her in her present confinement. I subsequently learned that there was considerable hemorrhage at the commencement of the labor, but that it soon ceased; the pains being frequent and strong, and the delivery rapid. As soon, however, as the child was born, alarming hemorrhage again set in, and a physician was sent for in great haste. The child had been born some 15 minutes when I reached the house. Found the patient bloodless; lips as pale as her cheek; extremely faint and scarcely perceptible; pulse at wrist, faintly perceptible over heart; flooding profusely. On examination, found umbilical cord had been torn off at its placental insertion by the midwife's traction upon it. About one-fourth or one-third of the placenta was lying unattached over the os; the remainder firmly adherent to the left wall of the cervix. I at once detached it, as is usual in such cases, by passing the fingers under it, being careful to secure and remove the whole organ. Then dashing ice-water, at once, upon the abdomen, the uterus promptly contracted, and hemorrhage ceased. Brandy and ammonia were given at short intervals, to the first dose of which a portion of ergot was added, as a measure. At the end of two hours, patient showed signs of returning consciousness, and from that time continued to improve. Recovered; child living. The history of this labor is what would have been expected under the existing conditions. There was some flooding when the dilating pains detached that portion of the placenta immediately over and around the os; but the presentation was, fortunately, natural, the uterine contractions frequent and strong, and the labor quick: the child's head, by its pressure, assisted in the incipient hemorrhage, which, however, of course, at once on the birth of the child and the cessation of uterine contraction. I neglected to ascertain if any hemorrhage had occurred in this patient during the latter part of her . If so, it must have been so slight as to excite no alarm, as no physician was consulted. PLACENTA PICEVIA CENTRALIS. Case II. Mrs. G., aged 37 years, Irish, robust and stout, temperament bilious, multipara. Previous labors natural. August 18th. Was called to stop an attack of flooding; not expecting her confinement for two weeks or more. Some four weeks ago, had an attack of hemorrhage, which has recurred from time to time since. Present condition pulse regular; respiration good; loss of blood considerable, but not alarming; no sign of commencing labor; os uteri so closed that I could not diagnose whether this was a case of placenta preevia or of detached placenta. The clinical history, however, led me to presume the former. Prescribed rest in recumbent posture, cool drinks, acid, sulph., etc. August 21st. Was called at 7.30 P.M. Waters had broken at 4 P.M. Os uteri dilated to size of a quarter dollar piece, extremely rigid. Found the placenta attached directly over it; the pains very irregular, undecided, and inefficient, but the hemorrhage alarming, and patient prostrated. Used ice locally, and gave ammonia and whiskey. Dr. A. W. Heise in . The os being still rigid, with no contractile pains, and flooding continuing, we decided to remove the placenta, at once, if possible. Found it to be central; os so rigid that only pieces broken up could be removed at a time. Removed as much as possible, and inserted tampon. One and a-half hour later flooding. Removed tampon, and more of placenta. Os still rigid: no contractile pains. Presentation left shoulder, with elbow down, back of child anterior. On further consultation, determined to administer chloroform to relax the os, and enable us to turn. Patient has been whiskey constantly; to the last two doses of which was added fl. ext. secal. cornut. Administered chloroform at 2 A.M. Dr. Heise turned, bringing down feet. Allowed patient to come out from anaesthesia, and repeated whiskey and ergot. Beginning traction, slight labor pains came on, and labor was completed with no difficulty. Removed remaining pieces of placenta and blood-clots from uterus, and applied ice-water to abdomen. Contraction took place, and all hemorrhage ceased. Child, of course, stillborn. Mother, although exhausted by fearful loss of bload, recovered, with no untoward symptom. The prominent features of the above case the rigidity of the os, the total absence of contractile pains, etc. render the for attempting to detach and remove the placenta, as the first procedure, so evident, that it is not necessary to state them in detail. My limited experience and my judgment would not lead me to adopt, as a general rule, the plan so strongly by its able and distinguished proposer, Prof. Simpson, of Edinburgh, viz., that of artificial detachment and delivery of the placenta before the child. Still, I am aware that the does not recommend this as a method applicable to all cases; and there may be some in which it will be found feasible, if not advisable. Believing that the hemorrhage proceeds from the bloodvessels of the uterus (the utero-placental), and not, unless secondarily, from those of the placenta, the indications above all others seem to be 1st. To empty the cavity of the womb; and 2d. To secure its permanent contraction. The test of clinical experience, and not theorizing, is to decide by what method these results can be quickest and safest attained. PLACENTA PRJEVIA CENTRALIS. Case III. Mrs. D., aged 22 years, multipara, German, , actress. Was called at 10 A.M. Found patient at beginning of labor; pains weak and inefficient; flooding with each one. On vaginal examination, found os nearly dilated, soft, and yielding; placenta attached directly over mouth of womb; presentation, cephalic. Pains had begun only about an hour previous. The hemorrhage was increasing, and the rapidly losing strength. Accordingly, in the presence of Dr. Harwood, who was called in counsel, I introduced the hand; and, finding it would be difficult and occasion loss of time to get around the placenta, as is usually recommended, I passed directly through it, turned, and delivered at once by the feet, removing the placenta immediately afterwards. Cold water to the abdomen at once induced contraction of the uterus, and the hemorrhage did not recur. The whole delivery did not occupy five minutes, but the child was in articulo mortis, gasping but a few times. Persistent efforts and trial of eyery means for its restoration, for three-quarters of an hour, were wholly . Mother recovered well and rapidly. Placenta prsevia is variously estimated by different to occur from 1 in 500 to 1 in 1000 cases. The average of o statistics, from various sources, give as the result 1 in 3 of the mothers, and over | of the children lost. The resort, in these cases, to premature delivery, as a prophylactic measure, as by Prof. Thomas (vide American Journal of , for May, 1868), would, doubtless, materially diminish this mortality. As Dr. Thomas says: "By resorting to this , we should be dealing with a woman who is not exhausted by repeated hemorrhages, the obstetrician would be in at the commencement of the labor; and he would be able, by hydrostatic pressure, to control flooding, while the same pressure accomplished rapidly and certainly the first part of the labor." The case of Mrs. G., No. II., is one in point. Premature delivery, by the use of Barnes' dilators, would very probably have prevented the occurrence of such profuse hemorrhage, and its attendant dangers. Dr. Thomas, in the article referred to, gives as the reasons for the great mortality in placenta praevia 1st. Hemorrhage, occasioned by dilatation of cervix; 2d. Repeated hemorrhages, occurring during ninth month; 3d. Profuse flooding at of labor. To these, it seems to me, should be added the unusually large proportion of unnatural presentations which occur in this complication of labor, rendering the introduction of the hand and turning necessary, aside from the malposition of the placenta and the hemorrhage. LATENT METRITIS. (?) Mrs. 11., aged 38 years, multipara, Irish, bilious habit. This patient lived five miles in the country; and I was not called until she had been in labor 14 hours. On arriving at the house, found delivery completed, and patient in very favorable . Left her with a few general directions. On the fourth day thereafter, the husband came to town, and informed me that his wife was " not doing well;" lochia were suppressed; had fever, etc. Prescribed a poultice of flax-seed and camphor to vulva, warm applications, etc., laxatives, and spts. mindereri. Fifth day, no better; was asked to visit her. Found her with no fever, pulse regular and soft, skin moist and natural. had moved; urine passed freely; no abdominal tenderness; whole condition except suppression of lochia, apparently . Vaginal examination revealed nothing abnormal; parts were not heated nor dry; nor was there any indication of action. Lochia completely suppressed since third day, on which, I now learned, she had been up and about her room a good deal, having no one to attend her. Lacteal good and abundant. The patient was firmly persuaded that she was going to die. Her mental condition was much like that in hysteria, without the convulsive seizures; a state of perfect melancholia. She was convinced that her husband and his brother were determined to poison her, and 'would take nourishment nor medicine from them. The hygienic in her surroundings room, attendance, etc. were as bad as they could be. On the eighth day, at evening, she jumped from the bed, and seizing her brother-in-law, shook him violently; whether aggravated thereto, or simply from frenzy. I could not learn. This was the only approach to convulsion which she manifested. Saw her at midnight. Heart's action o was then quite irregular; frequent cessation of pulsation, etc., but no sign of organic disease. Excessive wakefulness had been a prominent symptom. Persuaded her to eat some beefsteak and bread, and drink some tea, after which she had a natural and refreshing sleep of two hours. She had for several days persistently refused all nourishment, except a few dry crackers, and had no sleep for two days and nights. She awoke in the same state of profound melancholia, and continued in much the same condition refusing, finally, to take anything at all, or medicine; sitting moody and silent, or muttering to herself until the twelth day, when she died. Although a firm persuasion of the certainty of death is, in any disease, almost enough to ensure its fatality, or, perhaps, existing as a consequence, shows that a fatal issue is to take place, yet, this conviction alone is not enough to cause death. There must, therefore, have been some pathological condition behind all this. I do not pretend to decide what it was, but have ventured to suppose that it might have been a latent metritis (what our German brethren would term dunkel ausgesprochen), consequent upon suppression of the lochia, and producing a toxsemic condition. A. post mortem might have this point, but could not be obtained. Cases of puerperal mania, resulting from the same cause, and manifesting similar to the above, have, doubtless, occurred to almost every one engaged in obstetric practice. Their true pathology seems to be not well understood. There is, probably, some depravation of the blood connected with it. ATRESIA VAGINAS. N. H., aged 3 months. The mother informed me that a few days after the birth of this infant she noticed a "string of blood" between its labia vulvse, and on looking more closely found no appearance of any vaginal orifice. I found, upon , the parts normal in every respect, except complete occlusion of the vagina; its site being covered by skin in no way different from ordinary integument, except that it was lighter, and marked perpendicularly by a faintly perceptible raphPS. The clotted blood spoken of by the mother, and the existence of the raphti, led me to conclude that this occlusion was traumatic, and not due to any erroi' of development; and, further, that the vagina probably existed normally behind this wall of integument. I accordingly divided it with a bistoury, and gently introducing a female catheter a short distance, found the canal pervious, as I had anticipated. A tent introduced to prevent reunion of the edges of the wound completed the curve. Had there been complete imperforation of the vagina in this case, I should, of course, have advised to defer any operation for reopening the canal, or forming an artificial vagina, until the occurrence of puberty should have demonstrated the of ovaries, and accumulation of menstrual fluid the of a uterus. It is difficult to assign any cause which could operate in utero to occasion traumatic closure of the vagina. The skin was, however, too perfect to have grown in the few days following the child's birth; and, on the other hand, the presence of the clotted blood is difficult to account for, if the deformity be to be congenital. Dr. A. W. Heise, of Joliet, has related to me, from memory, two cases of interest, of which the following are the leading features: ARORTION AT FOURTH MONTH, FOLLOWED BY PREMATURE OF SECOND FOETUS AT SEVENTH MONTH. Case I. Mrs. C., aged 32 years, German, mother of four children. Landed in the U. S. three months since. The of this woman called upon Dr. H., and requested him to prescribe for his wife who was flooding. On visiting the , found her apparently threatened with miscarriage; enlarged, as though pregnant. The patient, however, stoutly maintained that she was not, and could not be, ; stating that, three months previously, on the passage across the Atlantic, she had miscarried with a foetus of about four months, according to her own calculation of her pregnancy, and to the statement of the midwife who attended her upon shipboard; that she had herself seen the child after its birth, and there could be no mistake about it; that she had been , more or less, at intervals, ever since, and had had no intercourse since that time. The Doctor accordingly that this was a case of retention of some of the , or of polypus, or mole. The woman was having pains, and, upon vaginal examination, the Doctor a mass advancing, though he did not recognize the part presenting sufficiently to diagnose what it might be. The was soon delivered, however, of a foetus completely upon itself in emprosthotonos, the convexity of the spine presenting. The foetus was apparently of the sixth month, and partially decomposed. Granting the correctness of the woman's statement, in reference to the previous abortion, the present foetus must have lived twTo months after the birth of its twin. No examination was instituted as to the existence of a double uterus. TRAUMATIC ATRESIA AND IMPERFORATION OF VAGINA. Case II. Mrs. A., aged 20, primipara. Dr. Heise was asked to visit this case in consultation with Dr. Bacon, of . Patient had been 24 hours in strong labor, with no . Dr. B. stated that he had not been able to ascertain the presentation, as he could not introduce the finger into the vagina. Dr. II., attempting an examination, found the canal completely occluded by a tense, firm membrane, about one-third of an inch from its external orifice. There was a small , sufficient to admit a good-sized probe, at the upper or pubic part of this membrane, but no justifiable force could make way for the finger. Through this opening the waters had discharged some 10 or 12 hours previously, since which time the patient had been in strong labor, with constant expulsive pains. The husband being asked if he had ever had complete connection with his wife, replied that "he had," but on being questioned closer, stated that he "had some time ago, but not recently." On being pressed for his knowledge of any cause for her present condition, he acknowledged that he had been married only about two months, that he had had sexual intercourse with his wife some time previous to their marriage, that finding herself encinte, they had procured the services of an abortionist, who had operated upon her for 15 minutes with a wire, and the operation complete; that after this operation she was sick and confined to her bed for six weeks, purulent and bloody discharges taking place from the vagina. Inasmuch as the passage of a probe through the orifice in the membrane showed a cavity beyond it, Dr. II. hoped it might be the only obstruction. On dividing it, however, he found still others, in the form of fibrous bands, stretching obliquely across the vaginal canal, interlacing with each other, the whole length of the vagina, and very firm and strong. Carefully dividing these, the foetal head was plainly felt in the first position, and the patient was soon delivered of a healthy child. Severe of the vagina, womb, and peritoneum supervened, and she died on the ninth or tenth day thereafter.
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(ft fl 1tD r 1111 New Mercy Hospital. The corner stone of the new Mercy Hospital building was laid, with due ceremony, on the 25th of July. A very large number of citizens were present, and in the exercises. The public address, together with a description of the building, will be given in the September number of the Examiner. College Lecture Fees. We see it stated in some of the medical journals that the American Medical Association, at its recent annual meeting, adopted resolutions declaring the fee for a regular college lecture term should be $120, and that such colleges as refused to comply with that rate should be denied representation in said Association. The statement, however, is an error. The Association did adopt a simple declaration of opinion, that the minimum fee for a regular lecture term should be $120. It did not adopt any in relation to denying representation to such colleges as did not accept the standard proposed. And, so far as we have learned, the colleges generally are issuing their circulars with the same rate of fees for the coming session as had been during the past year. The action of the Association was in the form of a simple expression of opinion, and nothing more. Medical Controversies. Perhaps there is no one thing calculated to impair the honor and usefulness of the medical profession, than the bitter personal controversies, or, more speaking, quarrels, that every now and then spring up among its members, and find ventilation either through the medical or secular press. Some men appear to be so constituted that they cannot the errors, refute the arguments, or point out the of others, without directly attacking their personal characters. Such men are continually acting as though the most violent denunciation constituted the most conclusive , and the blackening of the character the most complete correction of all misrepresentations. They are practically of discussing any subject, either on the platform or through the press, without involving themselves in personalties altogether foreign to the subject itself. These thoughts have been suggested chiefly by an article in a recent number of the Nashville Medical and Surgical Journal, by T. S. Bell, M.D., of Louisville, concerning E. S. Gaillard, M.D., of the same city. From this article it would appear that Dr. Bell had at some previous time delivered and published a lecture on a subject relating to antiquarian researches. Dn Gaillard, in his capacity of editor of the Richmond and Medical Journal, reviews this lecture, pointing out what he supposed to be defects in its style and logic. Ostensibly for this Dr. Bell writes a dozen pages of the most violent personal abuse of Dr. Gaillard; and what is perhaps even less excusable, the editor of the Nashville Medical Journal permits the article to appear in his columns. We say less , because the editor, as a third party, is supposed to be free from the personal feeling that actuates the writer, and consequently capable of seeing the injurious bearing of such papers, both on the writer and on the profession at large. If he had returned the manuscript to Dr. Bell, with the friendly advice to burn it up, or reduce it to a simple dignified of whatever errors or misstatements he supposed to have been made in the Richmond and Louisville Journal, how much of censure and scandal would have been saved to all parties. Viewed in the light simply of a reply to the review of his lecture in the Richmond and Louisville Medical Journal, the article of Dr. Bell, in the Nashville Journal, is in the highest degree censurable. If the editor of a medical journal cannot exercise the right of noticing the publications of the day, and in such notices pointing out their defects or errors, or both, calling out in return such a torrent of personal detraction as we find in the article of Dr. Bell, then is the position of a medical editor a very undesirable one indeed. But the truth seems to be, that the review in the JfoeAfflonrf and Louisville Journal only served Dr. Bell for a pretext, the real cause of his article being a bitter feud which had existed many months between Drs. Bell, Gaillard, and others connected with the two medical colleges in Louisville; a feud which had found vent in the newspapers of that city, and which the profession generally will regard as * reflecting no credit upon any of the parties concerned. We can excuse men for getting into a passion when assailed unexpectedly in conversation, but to dip a pen into gall and sit deliberately down to expose the predominence of our passions over our judgment, is to show the weak side of poor human nature unnecessarily. "Sweet Quinine." The preparation largely advertised this name has been analyzed by the editor of the American Journal of Pharmacy, who states that it is not quinine at all, "but mainly the alkaloid cinchonia precipitated from the , dried and triturated with an impure glycyrrhizin prepared from liquorice root," in the proportion of about three parts of cinchonia to one of inpure glycyrrhizin. The Journal adds: "Cinchonia, however tasteless, is not quinine, nor does its value approach that of quinine so nearly as it is made to do in the garb of'sweet quinine.' When physicians want cinchonia they can get it by prescription, and it is not in with our ideas of fair dealing to serve it up as a new ." N. Y. Med. Gazette. Cholera and Yellow Fever in Cuba. Sickness is in the ranks of the Spanish and rebel forces, and the is frightful. It is estimated that the deaths amount to 15 per cent, monthly, of the men in the field on both sides. The troops are afflicted with vomito, while the insurgents suffer from cholera and diarrhoea, caused especially by want and . When the hot and rainy seasons are past the volunteers will go into active service in the field and reinforcements will arrive from Spain. Havana, July 17th. The Messrs. Johnson, of Philadelphia, announce an work on " The Jurisprudence of Medicine in its relations to the Law of Contracts, Torts, and Evidence," by Professor John Ordronaux. Such a work has long been needed, and the author's reputation gives assurance that the hiatus will be filled. N. Y. Med. Gazette. Impurity of Water. In every 100,000 tons of the water supplied to London, the solid impurity averages from to forty-two tons; in Edinburgh, from eleven to fourteen tons; Bristol, twenty-eight tons; Manchester, six tons; Dublin, six tons; and Glasgow, only three tons. Ibid. The Contagion of Consumption. M. Chauveau, Professor in the Lyons Veterinary School, continues perseveringly his researches on the contagiousness of Tuberculosis. He has of late selected the intestinal surface as the field for his , and through it by introducing tuberculous matter into the circulatory current he has produced at will general tubercle. The Union Medicale reports that he lately purchased four heifers, and he tuberculized three of them by causing them to swallow 30 grammes each of tuberculous matter taken from the body of an old phthisical cow. The rapidity of the result was extraordinary. At the end of twenty days the first heifer had lost flesh to a surprising extent, its pulse was quick and full, and coughed incessantly. At the end of fifty-two days it was killed, and it presented perfectly marked tuberculous lesions, situated especially about the mesentry and intestine. The mesenteric glands presented infiltrarion in so high a degree that many were of the size of the first. Their total mass 1650 grammes. All the ganglia of the bronchi and were enlarged, and the lung was full of crude tubercle. The other two heifers presented not less perfectly marked , while the fourth, to which none of the tuberculous matter had been administered, remained intact and increased in flesh. It is proved, therefore, that animals of the bovine species contract tuberculosis by digestive ingestion, just as they take carbuncle and cowpock, as sheep take the rot, as the horse takes glanders, and as man takes small-pox. The human digestive tube constitutes an easy channel for tuberculous contagion. If bovine phthisis be identical with tuberculosis in the human species, there is, in the use of the flesh of tuberculous animals, a danger to which the poor are more especially exposed. Med. Press and Circular. Mortality for the Month of June, 1869: CAUSES OF DEATH. Accidents, burned,___ 1 " drowned,____5 " concussion of brain, 1 11 in plaining " poisoned,___ 1 " injuries from knife,_____ 1 " railroad, 5 " swallowing foreign , ___ 1 " scalded,____ 1 Abscess-pelvic,_______ 1 Apoplexy,_____________ 7 Asphyxia,_____________ 2 Births, premature,___23 " still,___________40 Bowels, inflammation, 4 Brain, congestion of, _ 3 " disease of,____ 2 " inflammation,- 11 " & lungs, " 1 " softening of,__1 Bronchitis,___________ 3 " hepatitis & icterus, 1 " capillary, _ 1 Breast, cancer of, 2 Cerebntis,_____________ 1 Cholera infantum,_____14 Convulsions,__________33 Consumption,_________37 Croup,________________ 1 " membranous,______ 1 Cyanch, maligna,_____ 1 Debility, 2 " & convulsions, 1 Delirium tremens,____ 3 Diarrhoea,_____________ 7 " chronic,____ 4 Diphtheria,___________ 2 Dropsy,_______________ 6 " abdominal,_______ 1 Dysentery, 6 " & convulsions, 1 Embrolism of artery from , 1 Entero-colitis,______ 1 Enteritis, 1 Erysipelas, 1 " of face,_______ 1 Fever, congestive, 1 " puerperal, 5 " remittent,______ 1 " scarlet, 50 " " and , _ 1 " typhoid,________12 " typhus, 2 Gastritis, 4 " and bowels , _ 1 Haemoptysis, 1 Heart, disease of, 4 " valvular " 1 Hernia, incarcerated,- 1 Hydrothorax, 1 Hydrocephalus,_______ 9 " acute,. 2 Inanition,___________ 13 Intemperance,________ 2 Kidneys, Bright's of,______________ 1 " and cystitis, 1 Larynx, stricture of, 1 Laryngitis, 1 Liver, congestion and inflammation with uremia,_________ 1 " softening of,_____1 Lungs, congestion of,_ 2 " emphysema of, 1 Measles,_____________31 " and diarrhcea, 2 Meningitis, , _____________ 3 tubercular, 3 Nutrition, defective, _ 1 Old-age,_____________ 5 Paralysis,___________ 3 Putella, fracture of,_ 1 Peritonitis,___________ 1 " puerperal, _ 2 " traumatic,- 1 Pharynx, cancer of,__1 Pneumonia,____________22 " and measles, 1 " broncho, __ 3 " typhoid,___ 2 Rheumatism, , _____________ 1 Scrofula,______________ 1 Spine, fracture of, 1 Shock from injuries, _ 1 Suicide, 2 Small pox, 2 Tabes mesenterica, 8 Teething,_____________ 7 " and convulsions, 5 " and diarrhcea, 3 Tetanus, traumatic, 1 Tongue, cancer of, 1 Thrush,_______________ 1 Urine, suppression of, 1 Vitality, deficient,__ 1 Whooping-cough,______ 8 " and , 1 Unknown, 5 Total,__________434 COMPARISON. Deaths in June, 1869, 434 | Deaths in June, 1868, 305 | Increase,_129 Deaths in May, 1869,____________ 372 | Increase,____________________62 AGES. Under 1 122 1 to 3______________ 96 3 to 5______________ 36 5 to 10 35 10 to 20____________ 14 20 to 30________ 36 10 to 40____________ 31 10 to 50____________ 21 50 to 60 *_____________ 23 30 to 70____________ 10 70 to 80_____________ 8 80 to 90___________ 0 90 to 100__________ 1 Unknown____________ 1 Total,___________434 Males, 241 | Females, 193 | Total,__________434 Single,______________334 | Married 100 | Total,__________434 White,_______________429 I Colored, 5 I Total,__________434 NATIVITY. Bohemia,____________ 4 Canada, 6 Chicago, Native,___ 61 Chicago, Foreign,__132 U. S., other parts, 56 Denmark,____________ 3 England,____________ 7 Oermany, 56 Holland, 7 Ireland, 38 New Brunswick,_____ 1 Norway, 17 Poland, 1 Prince Edward Island 1 Scotland,____________ 3 Sweden,_____________ 37 Switzerland,_________ 1 Wales,_______________ 1 Unknown, 2 Total, 434 MORTALITY BY WARDS FOR THE MONTH. Wards. Mortality. Pop. in 1868. One death in 1 8 9,094 l,136f 2 18 13,074 726| 3 21 15,076 718 4 21 17,796 847| 5 29 16,033 552 5-6 6 18 13,083 726 5-6 7 40 25,492 637J 8___ 30 15,813 523$ 9 25 19,297 772 10___ 7 12,925 1,846| 11 18 14,340 796$ 12 36 17,485 485$ 13 11 11,164 1,015 14_______ 14 14,839 1,052$ 15 29 21,078 726 4-5 16 13 15,465 1,189$ Mortality. Unknown Ward,______________________ 1 Accidents,_________________________17 County Hospital,___________________10 Home for Friendless,_______________ 3 Immigrants,_______________________ 42 Mercy Hospital,____________________ 4 Protestant Orphan Asylum, 2 St. Luke's Hospital,_______________ 1 St. Joseph Orphan Asylum, __13 Suicide,___________________________ 2 Police Station,____________________ 1 Total,_______________________434
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THE CHICAGO MEDICAL EXAMINER. N. S. DAVIS, M.D., Editor. VOL. X. MARCH, 1869. NO. 3. d i' i n i ii it 1 0o n n* i n u 11 o n s ARTICLE XI. "IS THE PROTECTIVE POWER OF VACCINATION AFFECTED BY THE LAPSE OF TIME?" By F. K. BAILEY, M.D., Knoxville, Tennessee. The above question is made the subject of a clinical by Grraily Newell, M.D., at St. Mary's Hospital Medical School. My attention was directed to it in looking over the Examiner for November, 1863, where the lecture is copied from the Lancet of June 13th, 1863. This is a question which should deeply interest not only every medical man, but also all men and women who wish for themselves or their children to retain a face unspotted, or rather unpitted. I well remember, when a child, that a man in our village had small-pox. He had taken it the "natural way" and, as generally is the case, died. At dead of night he was buried, and his only attendants to the grave were some of his who had had small-pox. At that time I was vaccinated; and "it worked finely;" leaving a scar, which, in after-life, was considered an indication of immunity from the terrible malady. How much it proved a protection, the sequel of this will tell. Very singularly, I had lived to be nearly 40 years of age, without being near enough to a case of small-pox to be exposed. Meanwhile, I had at various times introduced virus to my own arm, while vaccinating others, but without effect, except the itching known to all. In December, 1862, while in charge of a division of the U. S. General Hospital at Quincy, Illinois, a private, to the 4th Minnesota Infantry, on duty as cook, contracted small-pox. As soon as it was known that we had this disease in our wards, every one in the hospital was vaccinated, myself among the rest. The patient died on the 16th, and about the same time I was taken suddenly, and severely, sick. There was headache, and pain in the lumbar region, with a most vomiting, which sedatives and correctives failed to allay. There was the horrible cold stage, followed with terrible heat of surface, and, in fine, all the commonly-described symptoms of variola. Still, it could not be small-pox, if vaccination, and revaccination, oft repeated, had been of any avail. But, after more than forty-eight hours of suffering more than I had ever before endured, a profuse sweating , accompanied by a very welcome relief from distress. On putting my hand to the edge of the hairs about the , and upon the face, there were to be felt minute points, like as if small shot were imbedded in the dermis. In fact, I had varioloid most firmly developed. Here was a case, the question now under consideration. Enough had been endured to render it personally interesting. Fortunately, no other cases of either variola or varioloid occurred at this time. There were some exposed at the time, who never had been vaccinated, as will be seen in the following. From notes now in my possession, there were then in the division seventy-one persons, who had been more or less exposed to the contagion. Of this number, ten gave no evidence of having been . There were no scars to be found upon their arms, nor could they remember that it had ever been attempted. Four had had small-pox. Forty-five had been vaccinated before puberty, and twelve subsequent to that period. The ten unprotected persons were vaccinated, as stated above, with results. Of the revaccinations, forty-eight were unsuccessful, and ten successful; one of which was upon a person who had had . By a successful revaccination is meant, a case where a scar could be found, but all the phenomena as seen in original vaccination, were noticed. It is noted, also, that among the whole seventy-one individuals, there were three who had had varioloid, but they stated that they were vaccinated in early life. During the winter of '62 and '63, no patients were sent to my division till February. The following is a copy of the made at the end of the month: Whole No. of patients, 106 Number who gave no evidence of having been vaccinated, 17 " " had been vaccinated before, 89 " " had had small-pox, 8 " of revaccinations successful, 25 " " vaccinations do., 8 " successfully revaccinated who had had small-pox, 3 Nine (9) of the seventeen reported as unprotected, in whom vaccination was not successful, were subsequently carefully , but of the result no record is at hand. A portion of them might have once been successfully vaccinated, and the evidence by scar might have been upon the lower limbs, as the arms only were examined. No cases occurred till the next December, although patients were constantly arriving. and revaccination were carefully attended to, and monthly reports of results made, but no copies were preserved, to which reference can now be made. On December 2d, about fifty patients were admitted, mostly from Nashville, Tennessee. Many of them had been vaccinated at different hospitals South; and some even had crusts upon the arms, not sufficiently mature to be removed. But the orders were, that the operation should be repeated in all cases of admission, without exception, and regardless of what had been done previously. In one case, there was a crust upon the arm, and the soldier very naturally objected to the annoyance, but yielded, because it was the " order." Virus was carefully inserted in the arm, near to the scab so nearly matured, and nothing more thought of the case, till in a few days he was taken with characteristic symptoms of variolous disease, followed, in <lue time, by a fine crop of eruption. lie was at once sent to small-pox hospital, and the case proved to be one of unmodified small-pox. The eruption became , and pits were left upon the face. In another case, a soldier belonging to the 125th Illinois, was admitted December 2d, and, with the others, was . Upon his arm was a large and distinctly-formed scar, and I inserted the virus upon each side of the original scar. The vaccination worked finely, and scabs formed at each point. After the crusts had begun to dry, and were nearly ready to separate, he was taken with small-pox in a very violent form, and died January 8th. During the month of December, there were a great many cases of varioloid, characterized by febrile symptoms, and a slight eruption, but of undoubted genuineness. Among those were many I had vaccinated and revaccinated at former periods, and it seemed evident that they were from the influence of contagion. The mild cases, that required no nursing from others, were merely transferred to the fourth-story ward of the building; and as many as twenty were in that room at one time. They were isolated merely long enough for the vesicles to dry, which seldom required more than a week or ten days. During the intense cold weather in January, 1864, the disease was very malignant, and seemed determined to general; and no one felt secure, because so many were affected who were supposed to be well protected. The young man who was detailed as prescription clerk in the dispensary had well-developed varioloid, although the virus had been in his arm at several different times. At this period, unmodified variola also prevailed in the four or five divisions of the General Hospital, as well as among the people in the city. I will mention another case, showing the potency of contagion under certain circumstances. A corporal belonging to Company "I," 72d Illinois, was a convalescent in hospital, and had been in the wards as nurse for some months. In the notes of vaccination, it is stated that he was vaccinated at the age of 15, and revaccinated twice before coming under my care. The operation was repeated by myself on his , with all the others, and was considered as exempt from contagion as he could well be. Among the patients was a young man who had lost an arm; and the corporal, having the care of dressing the stump, had formed a strong attachment to him. Some time in January the young man was taken with characteristic symptoms, which proved to be a severe case of modified small-pox. When he was sent to small-pox hospital, the corporal to accompany him as a special nurse. I objected to his going, for the reason that none were sent as nurses, except those who had had small-pox, or varioloid. But, as he had been so much exposed to severe cases that had occurred at different periods in the same ward, it was thought that he would be safe; and, as he assumed all the responsibility in case he should contract the disease, he was allowed to accompany his young comrade. The room to which they were assigned at the pest-house was one in which a man was recovering from the disease in a form, and the corporal staid with both of them, night and day. In twelve days the corporal was attacked, and had the symptoms in a severe form. The eruption came out very thickly, and the case was one of well-developed modified small-pox. This, we see, was an instance where the person had the contagion in a less degree of intensity for some time, but succumbed after remaining constantly in a room with the disease. The corporal soon recovered; and it would seem that he could, after such an experience, be considered exempt, if any one ever could. During this period, there were three or four cases of well-developed varioloid in persons whose faces were already pitted, and had, as well as all the rest, been under the general order. When a Teuton or a Celt, who, in the Old Country, had had. small-pox from inoculation, became subjects of varioloid, our faith in such a thing as was considerably shaken. Late reports from California state that serious doubts are entertained upon this subject in that region. One thing is very conclusively shown, which is, that epidemic influence will, in this disease now under , as well as some others, render all rules and laws liable to exceptions. It is very evident that people generally are becoming indifferent to vaccination in their families. We hear, when it is suggested to a mother that her should be vaccinated, the exclamation, "Why! is the small-pox about?" When informed that it is not, but liable to occur at any time, she will say, "Then I will wait, for I don't want the little thing to be sick." The late war found great numbers of men who stated that they were vaccinated in childhood, "but that it did not work," and the operation was never repeated. But very few had been revaccinated, and consequently, in cases where the original , although successful, had "run out," they were fit for variola, especially when prevailing as an epidemic. Had they remained at home in their rural neighborhoods, they might never have been exposed. One reason of the indifference of people upon the subject of being protected from variolous contagion is, that but few have ever seen a case of small-pox. One walk through the rooms of a "Pest-House" (which every one, of all things, will avoid) would suffice to cause alarm, and awake attention to . In conclusion, then, it may be remarked, that even if is not an absolute immunity from variola, still, the is so much modified, that fatal results seldom follow. The case mentioned above, of the soldier in the 125th Illinois, is the only exception, in some hundreds of individuals, during an observation extending over a period of nearly three years. As a result of these observations, it is clear, that if every could be vaccinated in infancy, revaccinated at the age of puberty, and at the age of twenty-one, there will be a degree of immunity as nearly absolute as can be conceived. But, while one can have varioloid without serious results to himself, still, the mildest form is capable of communicating to an unprotected person the disease in an unmodified and fatal type. The above observations are given, in the main, from facts only deduced from memory. If access could be had to official reports made from month to month, many more cases might be presented of a similar nature. Others may have observed the same facts; but, if so, they have not given publicity to the results of their observations.
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X' ru ns n i s>o r i e 1it s CHICAGO MEDICAL SOCIETY. Friday Evening, Jan. 15, 1869. The Society was called to order, President Marguerat in the chair. Secretary Macdonald then read the proceedings of the last meeting, which were duly approved, and ordered to be placed on file. The Society next proceeded to the discussion of "the action and value of mercury and its preparations." Dr. Loverin opened the discussion, by reading an interesting history of the mineral, where obtained; its different , and modes of preparing them. Entered into the uses of the most common preparations, including chloridum mite; hydrargyri bichloridum; hydrargyri ammoniatum; hydrargyri iodidum; hydrargyri biniodidum; unguentum hydrargyri nitrico-oxidi; together with the strong and mild preparations of unguentum hydrargyri. Dr. Loverin believes mencury very useful in aesthenic . Dr. Bevan says that for the past four or five years he has been in the habit of treating acne with an ointment containing of hydr. biniodidi g. iij. to vij. to SS>j. of lard. Says that 5 grs. to the ounce will sometimes produce vesication. In some cases, where treatment was continued from two to eight months, has seen chronic acne of two years' standing entirely cured. In addition, it is sometimes necessary to give cod-liver oil and tonics. Has seen cases recover under this treatment when there was no benefit derived from sulphur, camphor, and , as recommended by Wilson. Dr. Wanzer said he had treated a chronic ulcer of the leg by administering 1^. Hydr. bichlor, gr. |, Opii gr. f, three times a day, with perfect success, and that he is curing one at present. Says that he recommended the above treatment to the physician in charge of the Poor-House, who also treated several ulcers of similar character with success, and has never seen but one exception. Thinks the way calomel cures is by diminishing the plasticity of the blood. Dr. Quails asked Dr. Wanzer if he made any distinction the specific and non-specific form of ulcer in his ? Dr. W. replied that he did not. Dr. Weller was permitted to make some remarks. Stated that he had treated acne successfully with the bychloride ; also used it in diphtheritic ophthalmia and diphtheria of the throat. Has used it in the abortive treatment of felons, by preventing suppuration. Uses a solution consisting of . hydr. gr, j. to alcohol dilute Sj. Cited a case which had been progressing four days, in which, by the application of the solution on a piece of cloth, all swelling subsided in fourteen hours. Dr. Davis says it has generally been stated that mercury the plasticity of the blood. Thinks it true of some of its preparations. But much depends on the way it is used. Does not think its action always the same. Thinks the use of bichlor, hydrargyri beneficial in chronic albuminuria or Bright's disease of the kidneys, when the blood is spansemic. Speaks of its use by Dr. Johnson in the New York hospitals twenty years ago, in the latter-named disease; also of his own use, in combination with the tincture of cinchona, bichlor, hydr. gr. j. and tinct. cinchona SSij., of which a teaspoonful was given three times a day. After continuing several days, the tinct. of was increased to SSiij., the dose being the same, with an intermission of three or four days, to prevent salivation. After two months, there was but a scanty precipitate of albumen to be found in the urine. In one year the patient had gained very much, and was able to work two-thirds of a day in a, , although not entirely free from the disease. Has it in a number of cases since, and in most cases with some benefit. Speaks of its beneficial use in irritable corneitic inflammation, charaterized by the red zone around the cornea, with little ulcers upon its surface, and great sensitiveness to light. The class of children affected by this disease are of the scrofulous diathesis. For twenty years has hardly met with a case but what has yielded under the following : 1^. Tinct. Cinchona, SSij. Bichlor. Hydr., gr. j. M. Twenty drops of which may be given to a child five or six years old, three times a day. They do not generally begin to derive benefit from the medicine until it has been given four or five days. The photophobia and irritability being removed in three or four weeks. Sometimes it is necessary to use anodynes locally. For this he uses morphia, 4 grs. in water gj., dropped into the eye three times a day; also veratria, grs. iij. to SSiv. dilute alcohol, which may be applied as a wash over the eyebrows each night and morning. After the inflammatory symptoms have disappeared, he often substitutes syrup of iodide of iron or of lime for the bichloride and tincture of cinchona. After some brief remarks by Drs. Wanzer and Loverin, the discussion was closed, and the Society proceeded to Business. The President announced that at the last meeting there was an assessment of $1.00 made on each member of the Society. Drs. Davis, Paoli, and Holmes were appointed on the " of proper subjects for discussion by the Society." Dr. Davis wished to know if any members had information regarding the Bill now pending before the State Legislature to regulate medical practice. Dr. Seely remarked, he had read of such in the city, papers, and believed such a Bill should be passed. Upon his motion, Dr. Davis was appoidted a Committee to report on the subject at next meeting of the Society. Society adjourned. Friday Evening, Jan. 22, 1869. The Society was called to order, President Marguerat in the chair. Secretary Macdonald read the minutes of the last meeting of the Society, which were duly approved. Dr. Clarke called for the law governing the non-attendance of members, which was read by the Secretary, setting forth, "that if a member was absent three successive meetings notifying the Society of the necessity of his absence, he is liable to have his name stricken from the register as a member of the Society." Dr. Reid reported several cases of neuralgia, which he had found quite obstinate in treatment: Case I. A lady, who suffered great pain in her head morning, and truly paroxysmal in character. Gave quinine in large doses, and partially succeeded in allaying her sufferings. Then gave arsenious acid and Indian hemp, with marked improvement. She has been under treatment about three weeks, and is now in the use of iron, and nearly . Case II. Old gentleman. Pain along the sciatic nerve. Bowels constipated. Gave quinia, which diminished pain . Tried arsenious acid, without much benefit. Upon purging, there were hard, impacted faeces passed, and the was better afterwards. Tried the Voltaic battery, with some benefit. Pain left ankle, and went to hip. Blisters were applied, and patient seemed to improve for a few days, but is now nearly as bad as ever. Treated several cases successfully by the use of arsenic and quinine. Case III. Lady. Neuralgia of bladder every night. Gave purgative, when a great quantity of hardened faeces were . Gave quinia, with benefit. Gave Dr. Gross's colchicum and morphia treatment, which was followed by great of the bowels and severe purging. Patient improved . Thinks there is great benefit derived from purging. Dr. Paoli says that he has used in these obstinate cases of neuralgia the permanganate of potassa, in |-gr. doses, three times a day, with marked benefit; also using a strong solution externaly. Dr. Clarke says that he has had a number of cases of of late, also a case of sciatica, in which quinia and arsenic had been administered, without benefit. Most of the cases were very obstinate, but had very good results from of potassa. Dr. ITamill reported the case of a lady who had neuralgia of crural nerve, which wTas paroxysmal in character. An hour before the paroxysm was expected, he introduced, by injection, morphia, gr. |, into the inner part of the thigh. The paroxysm was arrested, but it left the pain diffused over a larger surface. Then gave 1^. Bromide Potassa, 5ss. ' Tinct. Gelseminum, gtt. v., every three hours, when the pain was overcome. Treated cases of sciatica by the use of tinct. guaiac and , equal parts; a teaspoonful of which may be given every four or six hours. Dr. Loverin said he had treated a case of sciatica successfully by the use of cathartics, anodynes, Fowler's solution, and . Says he has heard recommended large doses of the of iron, and also nydroganic acid. Dr. Davis made the following report regarding the Medical Bill now before the Legislature. Stated that he had written a letter to Springfield requesting a* copy of the bill, but he was unable to obtain it. He believed, from the knowledge he had received from his friend in Springfield, that the principal bill now before the Legislature is the one introduced by Dr. Edgar, the substance of which is: that it requires every man proposing to practice medicine in the State of Illinois to show that he lias received a medical education; and that such persons having no diploma are to be examined by a medical board, and, if found competent, will receive a license, on payment of $25; and those physicians having diplomas, and presenting the same, upon payment of $5, would be registered. He was of the opinion that the two bills in the respective houses were somewhat the same; the objoct being to restrict the practice of medicine to such persons who had actually received a competent medical education. By this means, the community would be, in a great measure, protected against imposition. He also considered that so far as protecting the medical faculty was concerned, it only imposed upon them an additional burden, in the interest of the public. He hoped that the Society would take action in favor of having the bill passed and made a law, as the at Jacksonville and Springfield are evidently laboring to secure its passage. Dr. Wickershain stated that he was opposed to the bill, and announced himself a radical on the question. lie had not given twenty years of his life for the privilege of associating himself with quackery. He said he was surprised, and regretted, to see Dr. Davis favor the bill. He believed if our Legislature would pass a law excluding from the papers and periodicals quack medical advertisements, it would confer a great favor upon the public; but was entirely opposed to the Societie's taking any action on this matter whatever; for he was firm in the belief that nearly all medical advertisers had diplomas from medical schools, and that this very bill would protect them in their , for they could easily obtain certificates from the State Board. Dr. Clarke expressed his views in favor of the bill, and we are in much need of such a law for protection of the people. Does not think more than one-tenth of the advertising quacks are graduates of our regular medical colleges. Dr. Reid hoped the Society would act only upon a more knowledge of the details of the bill. Dr. Davis remarked that he was not a strenuous advocate of legislation for the profession, and said that any fair rendering of the bill would cut of those who were not legitimate members of the profession. The bill simply refers to medical education and medical practice, without recognizing homeopathy, or any other ism. Dr. Ilamill did not favor the further action in the matter, until the Society knew more respecting it; and moved that the matter be laid on the table. Dr. Fitch hoped the Society would take immediate action, and adopt measures to secure the passage of the bill. Dr. Wicksrsham was in favor of the Societie's passing a resolution against the enactment of such a law as the one . He believed this was the age of medical, political, and religious quackery, and, as such, should be recognized and acted upon. Dr. Paoli believed the profession should be entirely of all isms. He hoped all future action of the Society would be based on a copy of the bill. Dr. Davis said he was confident that no legislature would pass a law creating a board of medical examiners, to examine those recommended by the medical profession. The motion of Dr. Hamill being called for, the whole matter was laid on the table. Society adjourned.
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"in-vitro" should be described in Italic font. Make sure all related points and revise them. "xx um (SD+-xx um)" should be simplified to "xx +- xx um". Materials and methods "a standard tessellation language" should be modified to "a stereolithography". A later standard tessellation language could be described as STL. ".,." is a typo. Some company names appeared many times after the first description. "stl" should be modified to "STL". "300.000" might be modified to "300,000". MAE might be used as a candidate evaluation criteria. Reviewer #3: This was an in vitro study to compare conventional and digital/printed models. Abstract: I find that there were too much abbreviations that it took me a long time to work out what the abstract was describing. I think the authors should limit the abbreviations and formulas to the content of the manuscript to enable readers to understand what the whole text would be about. Manuscript I think the author should consider the clinical importance of their study. Clinically acceptable threshold should be explained early in the text. The authors should consider if the study is really about the superiority of the printed models or clinically acceptability? What would be the added value for the more complex digital workflow which may be more costly than conventional, when the latter is already practical. Furthermore, if the machines are for industrial, how can the clinicians relate as what's accessible to them are commercial machines? Given that the study is only about DLP printer, it would benefit the reader that a general term use for [PRINT] be more specific to DLP. This is now relevant because other types of 3D printers are so easily accessible that readers would now want to focus which printer the study is about. for ease of readership, I would suggest for the authors to minimise using formulas in text and describe their work. The conclusion should reflect the outcome based on the aims of the study. Reviewer #4: Accuracy of conventional and printed casts for orthodontic purposes General * This is a well written report. * The study was thoroughly carried out. TITLE Adequate ABSTRACT Adequate INTRODUCTION Adequate MATERIALS AND METHODS Materials & Instruments: 1. Clarify if the reference cast was scanned and digitized 5 times (line no.89) or 10 times (line no.186). 2. Please describe further details of the standardization of application of artificial saliva (especially in relation to the amount) before taking alginate impression (line no. 104). 3. As described in Discussion (line no.) which states the moisture sensitive property of alginate, report on the time taken after impression until casting and whether moisture loss from alginate impression was minimized similar to normal clinical situation. RESULTS 4. Suggest reporting on precision analysis results of the high-resolution scans of the reference cast [REF] (line no.185). DISCUSSION 5. Discuss the widening of the arch in the molar area with intraoral scanning. LIMITATIONS 6. Limitations need to be addressed, comment on inherent weakness of in vitro studying, focusing on possible differences in clinical situation. For example, intraoral scanning of the reference cast for the digital workflow was done on dry cast which may not truly reflect oral condition, and the interdental undercuts of the reference cast was blocked out with wax before alginate impression and this may not be standard clinical practice. CONCLUSION Suggest using the term 'superior precision results' to be more specific to the study findings. ACKNOWLEDGEMENT Suggest indicating if Berfin Yatmaz is a person or a company ********** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose "no", your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No Reviewer #3: No Reviewer #4: Yes: MANG CHEK WEY ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at [email protected]. Please note that Supporting Information files do not need this step. Attachment Submitted filename: Plos One.docx Click here for additional data file. 10.1371/journal.pone.0282840.r002 Author response to Decision Letter 0 Submission Version1 27 Aug 2022 Dear reviewer Thank you very much for the revision of our manuscript entitled 'In-vitro accuracy of casts for orthodontic purposes obtained by a conventional and by a printer workflow - Accuracy of conventional and printed casts for orthodontic purposes'. Attached you will find the item-by-item response. Thank you very much for the over-all assessment. Attachment Submitted filename: 2022.08.20_Plos One.docx Click here for additional data file. 10.1371/journal.pone.0282840.r003 Decision Letter 1 Baig Mirza Rustum Academic Editor (c) 2023 Mirza Rustum Baig 2023 Mirza Rustum Baig This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version1 2 Oct 2022 PONE-D-22-10316R1In-vitro accuracy of casts for orthodontic purposes obtained by a conventional and by a printer workflowPLOS ONE Dear Dr. Berndt, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE's publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Kindly address the concerns raised by the reviewers. I look forward to receiving your revised version of the manuscript. Please submit your revised manuscript by Nov 16 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at [email protected]. When you're ready to submit your revision, log on to and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript:A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at We look forward to receiving your revised manuscript. Kind regards, Mirza Rustum Baig Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the "Comments to the Author" section, enter your conflict of interest statement in the "Confidential to Editor" section, and submit your "Accept" recommendation. Reviewer #1: (No Response) Reviewer #2: (No Response) ********** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ********** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data e.g. participant privacy or use of data from a third party those must be specified. Reviewer #1: Yes Reviewer #2: Yes ********** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Unfortunately, in their response to comments, the authors have decided to dodge some concerns or flat out double down on their shortcomings in the study. There seems to be some confusion in the their arguments against the "conventional workflow". Nowadays, even when physical impressions are made for the sake of aligner fabrication, gypsum casts are seldom used. Yes, in orthodontics we still typically use stone casts for diagnosis, retainer fabrication etc, but who produces a series of gypsum casts for aligner fabrication?? This is obviously the case because it would be pointless to digitally "move" the teeth and create stages then go back to gypsum casts. Once in the digital format, it is typically printed. Regardless, the study is slightly improved compared to last version. I still have some feedback and comments below. With minor tweaks, it will be more acceptable. 1)The IOS and alginate impressions were obtained under different circumstances. It would have been very easy for the authors to use artificial saliva and wax block-out for the IOS too. This should be highlighted in the limitations 2) The authors need to report the details of the type and properties of the "gypsum used" as different types of dental stones have different properties. 3) DLP printers differ significantly in print quality. The high-end printer and resin used might not be completely comparable to lower-end or more affordable options. This no way a criticism of the study, just a mere comment. 4) Was it not possible for the authors to directly compare DLP vs. Gypsum in table 1 5) In the discussion, line 285, it is not relevant to the study to mention brackets. As stated by the authors, the study is about aligners, which makes brackets irrelevant. 6)Tthe conclusions need some editing. Point 1 and 2 of the conclusions can be merged together. 7) Replace the term "conventional" with "alginate-based" OR "alginate/gypsum" in the conclusions. Reviewer #2: Dear Authors, The manuscript was mostly revised according to the reviewer's comments. However, all figures were still not visible from the embedded link. The link has been expired. Please put all figures in the main text. ********** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose "no", your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at [email protected]. Please note that Supporting Information files do not need this step. 10.1371/journal.pone.0282840.r004 Author response to Decision Letter 1 Submission Version2 17 Nov 2022 Dear reviewer Thank you very much for the revision of our manuscript entitled 'In-vitro accuracy of casts for orthodontic purposes obtained by a conventional and by a printer workflow - Accuracy of conventional and printed casts for orthodontic purposes'. Attached you will find the item-by-item response. Thank you very much for the over-all assessment. Attachment Submitted filename: 2022.11.04_Review2.docx Click here for additional data file. 10.1371/journal.pone.0282840.r005 Decision Letter 2 Bencharit Sompop Academic Editor (c) 2023 Sompop Bencharit 2023 Sompop Bencharit This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version2 24 Feb 2023 In-vitro accuracy of casts for orthodontic purposes obtained by a conventional and by a printer workflow PONE-D-22-10316R2 Dear Dr. Berndt, We're pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you'll receive an e-mail detailing the required amendments. When these have been addressed, you'll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at [email protected]. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact [email protected]. Kind regards, Sompop Bencharit, DDS, MS, PhD, FACP Academic Editor PLOS ONE Additional Editor Comments (optional): The reviewer and editor were pleased with the revised manuscript. We appreciate your time and contribution. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the "Comments to the Author" section, enter your conflict of interest statement in the "Confidential to Editor" section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed ********** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ********** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data e.g. participant privacy or use of data from a third party those must be specified. Reviewer #2: Yes ********** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: Dear Authors, The manuscript was appropriately revised according to the reviewer comment. Thanks for your effort. ********** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose "no", your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: No ********** 10.1371/journal.pone.0282840.r006 Acceptance letter Bencharit Sompop Academic Editor (c) 2023 Sompop Bencharit 2023 Sompop Bencharit This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 6 Mar 2023 PONE-D-22-10316R2 In-vitro accuracy of casts for orthodontic purposes obtained by a conventional and by a printer workflow Dear Dr. Berndt: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact [email protected]. If we can help with anything else, please email us at [email protected]. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Sompop Bencharit Academic Editor PLOS ONE
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ion of the text is well prepared. introduction is sufficiently. methods are unadequate . The difference in numbers between the groups is very large. It must be balanced. 5-The results are enough. discussion is very short.it should be confused. Its mechanisms should be discussed. Tables and the figures are sufficient. , -, Discussion must contain comparison of similar studies that found association between The Hemogram Parameters and other cardiovasculer diseases diseases (i.e. " Association of mean platelet volume and red blood cell distribution width with coronary collateral development in stable coronary artery disease.DOI: ) 9-Please format references according to the journal style. Major revision ********** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose "no", your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: Yes: no ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at [email protected]. Please note that Supporting Information files do not need this step. 10.1371/journal.pone.0283008.r002 Author response to Decision Letter 0 Submission Version1 26 Jan 2023 Dear Academic Editor Gulali Aktas, Please find enclosed a revised version of the manuscript PONE-D-22-29441 (PLOS ONE) with the title "Association of Lymphopenia and RDW Elevation with Risk of Mortality in Acute Aortic Dissection". We were pleased by the reviewers' comments and their constructive suggestions for the improvement of our manuscript. We included changes and new data based on the reviewers' comments within the revised version. We feel that the new data generated following the suggestions supports our conclusions and strengthen the manuscript. The changes addressing the points raised by the reviewers were shown as track changes in the marked-up copy. The manuscript were also revised to meet PLOS ONE's style requirements and the captions for supporting information files were listed at the end of our manuscript. This research was funded by grant CSCF2020B03 from the Chinese Society of Cardiology Foun-dation and the National Natural Science Foundation of China (8187021109, 8207021929, 82100510) and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Appended is our detailed point-by-point response to the reviewers' comments. We are looking forward to hearing from you. Sincerely, Hesong Zeng Reviewer 1 We thank the reviewer for her/his valuable and constructive suggestions and comments which we believe significantly improved the quality of the manuscript. We have addressed all the comments point by point as follows: Comment 1: Some of the references used in the article are more than 10 years old, and it would be good if possible to re-edit these references with current literature information. Answer 1: We thank the reviewer for pinpointing this issue and we apologize for the inadvertence. After carefully checked the references in our manuscript, 6 articles which were published over 10 years ago were re-edited with current literature information. The updated and the original references were listed below. Original citations: 8. Luo F, Zhou XL, Li JJ, Hui RT. Inflammatory response is associated with aortic dissection. Ageing Res Rev. 2009;8(1):31-5. PMID: 18789403 9. Dinarello CA. Anti-inflammatory Agents: Present and Future. Cell. 2010;140(6):935-50. PMID: 20303881 10. Quintans J. Immunity and inflammation: the cosmic view. Immunol Cell Biol. 1994;72(3):262-6. PMID: 8088865 22. Tonelli M, Sacks F, Arnold M, Moye L, Davis B, Pfeffer M, et al. Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People with Coronary Disease. Circulation. 2008;117(2):163-8. PMID: 18172029 27. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12(3):204-12. PMID: 21321594 37. Allen LA, Felker GM, Mehra MR, Chiong JR, Dunlap SH, Ghali JK, et al. Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure. J Card Fail. 2010;16(3):230-8. PMID: 20206898 Changed citations: 8. Shen YH, LeMaire SA, Webb NR, Cassis LA, Daugherty A, Lu HS. Aortic Aneurysms and Dissections Series. Arterioscler Thromb Vasc Biol. 2020;40(3):e37-e46. PMID: 32101472 9 Sun L, Wang X, Saredy J, Yuan Z, Yang X, Wang H. Innate-adaptive immunity interplay and redox regulation in immune response. Redox Biol. 2020;37:101759. PMID: 33086106 10. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9(6):7204-18. PMID: 29467962 22. Danese E, Lippi G, Montagnana M. Red blood cell distribution width and cardiovascular diseases. J Thorac Dis. 2015;7(10):E402-11. PMID: 26623117 27. Lawler PR, Bhatt DL, Godoy LC, Luscher TF, Bonow RO, Verma S, et al. Targeting cardiovascular inflammation: next steps in clinical translation. Eur Heart J. 2021;42(1):113-31. PMID: 32176778 40. Talarico M, Manicardi M, Vitolo M, Malavasi VL, Valenti AC, Sgreccia D, et al. Red Cell Distribution Width and Patient Outcome in Cardiovascular Disease: A ''Real-World'' Analysis. J Cardiovasc Dev Dis. 2021;8(10). PMID: 34677189 Comment 2: English is used at an intermediate level in the article. Answer 2: We thank the reviewer to bring this issue up and apologize for the insufficient English expression level in our manuscript. We have now worked on both language and readability and have also involved native English speakers for language corrections. We really hope that the flow and language level have been substantially improved. Reviewer 2 We thank all the comments that are valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. The following are the responses and revisions we have made in response to reviewer's questions and suggestions on an item-by-item basis. Comment 1: The topic of the article is interesting. Answer 1: We highly appreciate the positive evaluation. Comment 2: Abstraction of the text is well prepared. Answer 2: We thank the reviewer for her/his positive evaluation. Comment 3: The introduction is sufficiently. Answer 3: Thank you for the positive comments and evaluation of our study. Comment 4: The methods are unadequate. The difference in numbers between the groups is very large. It must be balanced. Answer 4: We thank the reviewer for the careful review of our manuscript and considerate comments. As mentioned by the reviewer that it is indeed there is some difference between the groups in table 1, while we only aimed to present the real baseline characteristics of enrolled patients. when we focused on exploring the association of lymphopenia and RDW elevation with risk of mortality in acute aortic dissection, stepwise multivariable Cox proportional hazard regression models were performed to investigate the association and all the models were successively adjusted for age (continuous), sex (female, male), smoking history (yes, no), hypertension history (yes, no), diabetes history (yes, no), aortic valve replacement history (yes, no), anatomical classification (DeBakey I, DeBakey II, DeBakey IIIa, DeBakey IIIb, or isolated abdominal AAD), etiology (genetic, traumatic, congenital disorder, vascular inflammation, infectious disease, or sporadic), aorta diameter (>= 5.5 cm, < 5.5 cm), onset time (< 24h, 1-7d, 8-14d), and hospital centers (Tongji Hospital, People's Hospital of Zhengzhou University, Central China Fuwai Hospital of Zhengzhou University, the Third Affiliated Hospital of Xinxiang Medical University, or the Second Affiliated Hospital of Chongqing Medical University). We even performed stratified analyses across ages, sexes, smoking history, hypertension history, diabetes history, aortic valve replacement history, anatomical classifications, etiologies, aorta diameter, onset time and hospital centers to calculate the p-value for interaction to examine the consistency of patterns in the main results. Of note, these associations remained robust after stepwise adjustment for confounders and stratified analyses. Additionally, we added analysis with the propensity score matching (PSM) method. PSM was performed to adjust for differences in baseline characteristics between in-hospital alive and in-hospital dead groups. Cox proportional hazard regression models were re-fitted in the matched population to test the stability and reliability of our results. Eventually, the association of lymphopenia and elevated RDW with the risk of in-hospital mortality in AAD was similar with the results in Table 2. Comment 5: The results are enough. Answer 5: We thank the reviewer for this positive evaluation. Comment 6: The discussion is very short. it should be confused. Its mechanisms should be discussed. Answer 6: We appreciate the thoughtful comment of the reviewer. we have revised the manuscript and added the description of mechanisms exploration in the second and third paragraphs of discussion section. Comment 7: The Tables and the figures are sufficient. Answer 7: We do thank the reviewer's positive evaluation. Comment 8: Also, discussion must contain comparison of similar studies that found association between the hemogram parameters and other cardiovascular diseases (i.e., " Association of mean platelet volume and red blood cell distribution width with coronary collateral development in stable coronary artery disease.DOI: ) Answer 8: We thank the reviewer for pointing out this critical point and giving us the constructive suggestion. We have added a paragraph in discussion to elaborate the association between the hemogram parameters and other cardiovascular diseases and citated 3 studies to support our viewpoint ("Sincer I, Gunes Y, Mansiroglu AK, Cosgun M, Aktas G. Association of mean platelet volume and red blood cell distribution width with coronary collateral development in stable coronary artery disease. Postepy Kardiol Interwencyjnej. 2018;14(3):263-9. PMID: 30302102", " Ornek E, Kurtul A. Relationship of mean platelet volume to lymphocyte ratio and coronary collateral circulation in patients with stable angina pectoris. Coron Artery Dis. 2017;28(6):492-7. PMID: 28678144", " Sincer I, Mansiroglu AK, Aktas G, Gunes Y, Kocak MZ. Association between Hemogram Parameters and Coronary Collateral Development in Subjects with Non-ST-Elevation Myocardial Infarction. Rev Assoc Med Bras (1992). 2020;66(2):160-5. PMID: 32428150"). We have tried our best to illustrate the extensively clinical value of hemogram parameters in assessing different cardiovascular diseases in our revised manuscript. Comment 9: Please format references according to the journal style. Answer 9: We thank this reviewer to bring this issue up. After careful inspection of the format of references in our manuscript, we revised all the citations to meet PLOS ONE's style requirements. Attachment Submitted filename: Response to Reviewers.docx Click here for additional data file. 10.1371/journal.pone.0283008.r003 Decision Letter 1 Aktas Gulali Academic Editor (c) 2023 Gulali Aktas 2023 Gulali Aktas This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version1 1 Mar 2023 Association of Lymphopenia and RDW Elevation with Risk of Mortality in Acute Aortic Dissection PONE-D-22-29441R1 Dear Dr. Zeng, We're pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you'll receive an e-mail detailing the required amendments. When these have been addressed, you'll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at [email protected]. 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Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ********** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ********** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data e.g. participant privacy or use of data from a third party those must be specified. Reviewer #1: Yes Reviewer #2: Yes ********** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The article is very well revised in accordance with the previous suggestions. I recommend publication. Reviewer #2: Dear Editor I carefully read the article titled "Association of Lymphopenia and RDW Elevation with Risk of Mortality in Acute Aortic Dissection ". The topic of the article is really interesting. Abstraction of the text is well prepared. The introduction is sufficiently a.The methods are adequate. Therefore, results of the study are enought .The discussion is satisfactory . For this reasons, I recommend publication of the article. ********** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. 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Reviewer #1: Yes: Tuba Taslamacioglu Duman Reviewer #2: No ********** Attachment Submitted filename: accept.docx Click here for additional data file. 10.1371/journal.pone.0283008.r004 Acceptance letter Aktas Gulali Academic Editor (c) 2023 Gulali Aktas 2023 Gulali Aktas This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 6 Mar 2023 PONE-D-22-29441R1 Association of Lymphopenia and RDW Elevation with Risk of Mortality in Acute Aortic Dissection Dear Dr. Zeng: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact [email protected]. If we can help with anything else, please email us at [email protected]. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Gulali Aktas Academic Editor PLOS ONE
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). REPLY - Agreed. This was deleted from the manuscript. COMMENT - I suggest to write the taxa (pg 2, Abstract). REPLY - Agreed. The five main taxa of both datasets have been added. COMMENT - Materials? Experiential benefits? Explain better (pg 3, pp 1, Introduction). REPLY - Agreed. Examples have been added to the sentence for a clearer explanation. COMMENT - I suggest to break the sentence into ".... STE program launched in 2007 (www.steproject.org)" (pg 4, pp 1, Introduction). REPLY - Agreed. The suggested modification of the sentence was added to the manuscript. COMMENT - I suggest to change in some sentences the term volunteers into recreational divers (pp 4, pp 1, Introduction). REPLY - Agreed. Some of the terms "volunteers" were changed to divers or participants. COMMENT - Delete "of their choosing" (pg 4, pp 1, Introduction). REPLY - Agreed. This phrase was deleted for a more concise sentence. COMMENT - What does no behavioral change of the divers mean? (pg 4, pp 1, Introduction). REPLY - Agreed. The following sentence was added to explain: This approach to citizen science allows participants to carry out their normal activities (volunteer behavior is unchanged throughout the survey), and the collection of casually observed data. COMMENT - What does it mean, please explain? Regarding "based on correlations to reference researchers" (pg 4, pp 1, Introduction). REPLY - Agreed. It has been explained that the validation trials were ran by comparing volunteer collected data to those of data collected by "control divers" (marine biologists). COMMENT - What is Consistency, please explain (pg 4, pp 1, Introduction). REPLY - Agreed. The extrapolation "Consistency, or the similarity of data collected by individual volunteers during the same dive" was added to the manuscript. COMMENT - What is Percent Identified, please explain (pg 4, pp 1, Introduction). REPLY - Agreed. The sentence "The percentage recorded of the total number of taxa present (acquired from control diver data), or the Percent Identified, was the highest-ranking parameter" was added to the manuscript. COMMENT - I suggest "however" instead of "overall" (pg 4, pp 1, Introduction). REPLY - Agreed. We have modified the text according to the suggestion. COMMENT - In this part, the wreck study should be supported by an introduction of the importance of wreck studies for communities and/or recovery species. I suggest the readings of paper Peirano (2013) and references therein (pg 4, pp 1, Introduction). REPLY - Agreed. The importance of wreck studies for communities was discussed within the Discussion of the manuscript and has now been moved to the Introduction where Peirano (2013) was also included as a source along with additional sources from that publication. COMMENT - Please rearrange the sentences describing the ship. What is important is the geographical position, the depth, the height, and the length (pg 4, pp 2, Introduction). REPLY - Agreed. The sentence was made shorter and more concise with the suggested dimensions added. COMMENT - The ship was heavily damaged also by plundering of souvenirs by recreational divers (pg 5, pp 1, Introduction). REPLY - Agreed. An additional sentence was added to the manuscript to describe the destruction of the SS Thistlegorm by looting. COMMENT - Far? How many miles far? Today you can visit the wreck with boats that can reach it within a few hours. (pg 5, pp 2, Introduction). REPLY - Agreed. The distance from the main resorts in the Sharm el Sheikh area has been added to the manuscript. COMMENT - I think that all the part evidenced in green should be used in the conclusion rather than the introduction (pg 5, pp 2, Introduction). REPLY - Agreed. This section has been moved to the discussion. COMMET - deletion of "one of the most top-ranking dive sites in the world (pg 6, pp 2, Introduction). REPLY - Agreed. This was removed from the manuscript. COMMENT - delete "data were collected within" and "whose efforts" (pg 6, pp 3, Materials and Methods - Data collection and isolation). REPLY - Agreed. These were deleted to form a more concise sentence. COMMENT - Please explain, regarding "the behavior of underwater tourists is unaltered" (pg 6, pp 3, Materials and Methods - data collection and isolation). REPLY - Agreed. Further details of this concept were added when it was introduced within the Introduction of the manuscript. COMMENT - Change "participant volunteers" to "recreational SCUBA divers" (pg 6, pp 3, Materials and Methods - data collection and isolation). REPLY - Agreed. We have modified the text according to the suggestion. COMMENT - Introduce here the codes used in the results (T, RTD, PY etc.) (pg 6, pp3, Materials and Methods - Data collection and Isolation). REPLY - Agreed. The codes were have been introduced within the materials and methods section. COMMENT - Sightings of what? Fishes, coral? Marked on tablets? Please give some explanations, this is the core of the methods. (pg 6, pp 3, Materials and Methods - Data collection and Isolation). REPLY - Agreed. The sentence "The 72 faunal taxa were chosen because they are representative of the main ecosystem trophic levels within the Red Sea, they are common/abundant, and they are easily identifiable by recreational divers" Was added to the manuscript. It was also explained that the sightings were recorded on the questionnaires immediately following the dive without the use of tablets or recording material during the dive. COMMENT - Deletion of "for detailed methods, see.." (pg 6, pp 3, Materials and Methods - Data collection and isolation). Reply - Agreed. This was deleted from the manuscript and the methods were explained in more detail within. COMMENT - I think that the shipwreck could be introduced at the start of the materials and methods section as Study Site. It should describe the wreck, its position on the bottom, type of bottom, presence of reefs in the surroundings, currents, type of construction (particularly that it is full of cars, motorbike, explosives etc that could be harmful to the marine environment. (pg 6, pp 3, Materials and Methods - data collection and isolation). REPLY - Agreed. A new subsection titled "The Study Site" under materials and methods was added to the manuscript and described the location, cargo, currents, type of construction, and substrate. COMMENT - Deletion of "were isolated from the entire STE data set". (pg 6, pp 3, Materials and Methods - data collection and isolation). REPLY - Agreed. This was deleted from the manuscript. COMMENT - This section along with Table 1, should be moved to the Results (pg 6, pp 3, Materials and Methods - data collection and isolation). REPLY - Agreed. The section regarding number of questionnaires used or removed from the study was moved to the Results section. COMMENT - It is strange this ratio (pg 7, pp 2, Materials and Methods - Preliminary analysis and treatment). REPLY - Agreed. The equation has now been inverted to its correct form in the manuscript. COMMENT - I do not understand how it is calculated the average sighting abundance (pg 7, pp 2, Materials and Methods - Preliminary treatment and analysis). REPLY - Agreed. The description "For each of the taxa sighted, the divers also recorded an estimated Sighting Abundance according to 3 classes: 1, 2, and 3 (rare, frequent, and very frequent respectively). The classes were weighted to each taxon's individual expected occurrence" was added to the Data collection and isolation section of the Materials and Methods. COMMENT - Deletion of BVSTEP (pg 7, pp 3, Materials and Methods - preliminary analysis and treatment). REPLY - Agreed. This was deleted from the citation. COMMENT - Deletion of Relate (pg 7, pp 4, Materials and Methods - preliminary analysis and treatment). REPLY - Agreed. This was deleted from the citation. COMMENT - Deletion of DistLM (pg 7, pp 5, Materials and Methods - preliminary analysis and treatment). REPLY - Agreed. This was deleted from the citation. COMMENT - This sentence should introduce (at the start) of the description of the analysis (pg 8, pp 3, Materials and Methods - preliminary analysis and treatment). REPLY - Agreed. The sentence was moved to the beginning of the section. COMMENT - This paragraph should be moved to the beginning of preliminary analysis and treatment (pg 8, pp 4, Materials and Methods - preliminary analysis and treatment) REPLY - Agreed. The paragraph was moved to the beginning of the preliminary analysis and treatment section of the manuscript. COMMENT - What does it mean (regarding "best subset of taxa") (pg 8, pp 5, Materials and Methods - temporal analysis). REPLY - Agreed. The sentence was modified to "...only the BVSTEP best subsets of taxa representing the community structure from any individual year were obtained...". COMMENT - Why "again"? (pg 8, pp 5, Materials and Methods - temporal analysis). REPLY - Agreed. The word was deleted from the manuscript. COMMENT - Deletion of "Bray-Curtis similarity" from citation (pg 8, pp 5, Materials and Methods - temporal analysis). REPLY - Agreed. This was deleted form the manuscript. COMMENT - Deletion of "CLUSTER" from citation (pg 8, pp 5, Materials and Methods - temporal analysis). REPLY - Agreed. This was deleted form the manuscript. COMMENT - Deletion of "BVSTEP" from citation (pg 8, pp 5, Materials and Methods - temporal analysis). REPLY - Agreed. This was deleted form the manuscript. COMMENT - Add significance level after "correlated" (pg 9, pp2, Results - preliminary analysis and treatment). REPLY - Agreed. Significance level was added just after "correlated" and deleted from the end of the sentence. COMMENT - Add significance level after "significantly related" (pg 9, pp2, Results - preliminary analysis and treatment). REPLY - Agreed. Significance level was added just after "significantly related" and deleted from the end of the sentence. COMMENT - Change p to P (pg 10, table 2 caption, Results - preliminary analysis and treatment). REPLY - Agreed. "p" was changed to "P" in the table caption. COMMENT - Of what? Regarding "abundance and presence/absence" data (pg 10, table 2 caption, Results - preliminary analysis and treatment). REPLY - Agreed. "Taxa" abundance and "taxa" presence/absence data were added to the Table 2 caption. COMMENT - Percentage of what? Previously PY was described as date (pg 10, Table 2 caption, Results - preliminary analysis and treatment). REPLY - Agreed. The sentence was changed to "... PY as date (expressed as the percentage of year) ...". COMMENT - Percentage of what? Previously FD was described as hour (pg 10, Table 2 caption, Results - preliminary analysis and treatment). REPLY - Agreed. The sentence was changed to "... FD as hour (expressed as the percentage of day) ...". COMMENT - Presence/absence? Regarding "p/a" (pg 10, pp 1, Results - Preliminary analysis and treatment). REPLY - Agreed. "p/a" was redefined in this section. COMMENT - Change "Relate" to "RELATE" (pg 10, pp1, Results - Preliminary analysis). REPLY - Agreed. The suggested modification was changed within the manuscript. COMMENT - You mean "in" 2007, not "from" 2007 (pg 10, pp 1, Results - preliminary analysis and treatment). REPLY - Agreed. "In" was changed to "from" in the manuscript. COMMENT - you present data on taxa abundance and community structure. however, as written in one note in the material and methods part, you did not write about what have you considered as targets ( fish ?, corals?) and what you means as community structure.For example a coral community is formed by benthic corals and fishes.Caranxes are pelagic fishes.You have done a great work, please spend some time to clear all these points.(pg 10, pp 4, Results - Temporal analysis). REPLY - Agreed. An explanation of how the target taxa were chosen has been added to the manuscript (i.e. The 72 faunal taxa were chosen because they are representative of the main ecosystem trophic levels within the Red Sea, they are common/abundant, and they are easily identifiable by recreational divers). COMMENT - One species? Regarding the BVSTEP best species of centroidal data (pg 11, pp 2, Results - temporal analysis). REPLY - Agreed. The scientific names of the species/genre/families were added to the manuscript. COMMENT - This part could be used in the Introduction (pg 12, pp 1, Discussion). REPLY - Agreed. This part, involving the discussion of the importance of wrecks to marine communities was moved to the Introduction upon earlier request. COMMENT - I do not know if in your data we can talk about diversity, if so, you can show this in the results (pg 13, pp 2, Discussion). REPLY - Agreed. Diversity is no longer discussed in reference to our data but only in reference to external sources. COMMENT - I think you should consider the different approach of your study with touristic divers and the species list proposed for the cited papers. I should be cautious in your species richness (we don't have the data in you MS) with cited data (pg 13, pp 2, Discussion). REPLY - Agreed. The methodology of the paper cited regarding this comment was described and added to the manuscript. COMMENT - Also in Mediterranean there are studies on this subject (pg 13, pp 2, Discussion) REPLY - Agreed. Additional sources have been added to describe studies that have taken place within the Mediterranean. COMMENT - Incorrect spelling of "correlated" (pg 14, pp 2, Discussion). REPLY - Agreed. The misspelling was corrected. COMMENT - All of the following parameters are interesting, however, to talk about them they should be proposed in results at least in figures/tables (I cannot see the appendix). I think you should propose figures showing the fluctuation of recorded parameters (pg 14, pp 3, Discussion). REPLY - Agreed. These tables are already included in the supporting Information file of the manuscript which was unavailable for you to download at the time. We hope that it is made available in the current version. COMMENT - I do not know the species you are talking about however I do not think that some shallow water species cannot be found at 30 m depth. Maybe the distance from the coast, the type of substratum, or currents may influence the colonization. But you agree with me in the following sentences? Or not? (pg 14, pp 3, Discussion). REPLY - Agreed. We believe the sentences following the statement agree with your supposition. If corals can occupy deeper in the water column, they usually have a greater depth range of colonization. The sentence was rearranged to "In fact, coral species that have narrower depth ranges tend occupy shallower waters..." to clarify the statement. COMMENT - I think that the following sentences evidenced in green should be moved to the results (pg 15-16, pp 2 and 3, pp 2, Discussion). REPLY - The suggested sections were moved to the results. Reviewer #2 COMMENT - Maybe add citizen science to the keywords (pg 1, Keywords). REPLY - Agreed. The term "citizen science" was added to Keywords. COMMENT - I think that it is more appropriate to use the term "resistance" because, as you said, there have been few bleaching events thus corals have resisted to temperature anomalies (pg 3, pp 2, Introduction). REPLY - Agree. The term "resilience" was replaced with "resistance". COMMENT - We do not "use" citizen science, we practice it. It is a way of doing citizen science and therefore cannot be considered as a tool (pg 3, pp 3, Introduction). REPLY - Agreed. The term "use" was changed to "practice" in the manuscript. COMMENT - The term stakeholder should be changed to the plural form (pg 4, pp 1, Introduction). REPLY - Agreed. The word was changed to plural. COMMENT - You are talking about people, not objects. Better to use a more appropriate synonym regarding the term "utilized" (pg 4, pp 1, Introduction). REPLY - Agreed. The term "utilized" was replaced with "involving". COMMENT - Add "." (pg 4, pp 2, Introduction). REPLY - Agreed. "." Was added to the manuscript. COMMENT - Add "." (pg 6, pp 1, Introduction). REPLY - Agreed. "." Was added to the manuscript. COMMENT - Please cite the reference number in square brackets (pg 14, pp 3, Discussion). REPLY - Agreed. The reference number in brackets was added to the manuscript. COMMENT - Please cite the reference number in square brackets (pg 14, pp 3, Discussion). REPLY - Agreed. the reference number in brackets was added to the manuscript. COMMENT - This section sounds like results and all those numbers make it hard to read. Please move them to the results and limit here the discussion of those results (pg 15, pp 2, Discussion) REPLY - Agreed. Most of the section selected was moved to the results section. COMMENT - Remove "best" (pg 16, pp 2, Discussion). REPLY - Agreed. The sentence was restructured to define the BVSTEP Best test. 10.1371/journal.pone.0282239.r003 Decision Letter 1 Bianchi Carlo Nike Academic Editor (c) 2023 Carlo Nike Bianchi 2023 Carlo Nike Bianchi This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version1 10 Feb 2023 Eight years of community structure monitoring through recreational citizen science at the "SS Thistlegorm" wreck (Red Sea) PONE-D-22-26446R1 Dear Dr. Caroselli, We're pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you'll receive an e-mail detailing the required amendments. When these have been addressed, you'll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at [email protected]. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact [email protected]. Kind regards, Carlo Nike Bianchi Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: 10.1371/journal.pone.0282239.r004 Acceptance letter Bianchi Carlo Nike Academic Editor (c) 2023 Carlo Nike Bianchi 2023 Carlo Nike Bianchi This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 17 Feb 2023 PONE-D-22-26446R1 Eight years of community structure monitoring through recreational citizen science at the "SS Thistlegorm" wreck (Red Sea) Dear Dr. Caroselli: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact [email protected]. If we can help with anything else, please email us at [email protected]. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Carlo Nike Bianchi Academic Editor PLOS ONE
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34904 Internal Medicine Rheumatology Sarcoid Here, Sarcoid There, Sarcoid Everywhere Muacevic Alexander Adler John R Iskander Peter A 1 Patel Preya 1 Patel Ronakkumar 1 Shafi Chilsia 1 Zheng Jiayi 1 Iskander Anthony 2 Miller Jacob 3 1 Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, USA 2 Internal Medicine, Xavier University School of Medicine, Oranjestad, ABW 3 Internal Medicine, Wilkes-Barre VA Medical Center, Scranton, USA Peter A. Iskander [email protected] 12 2 2023 2 2023 15 2 e3490412 2 2023 Copyright (c) 2023, Iskander et al. 2023 Iskander et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Although usually more associated with the lungs, sarcoidosis can have multiple extrapulmonary manifestations. We present a case of a patient with previous biopsy-proven sarcoidosis who was admitted to the hospital secondary to worsening shortness of breath. The patient was found to be positive for Respiratory Syncytial Virus (RSV) which was believed to have exacerbated his pulmonary symptoms. He was treated with IV steroids, nebulizers, and antibiotics which ultimately helped relieve his symptoms. In terms of his sarcoidosis, he was previously treated in the past with steroids in regards to this pathology (which is the mainstay of treatment); while on the regimen, the patient noted his breathing was improved. Of note, he did also have a history of renal cell carcinoma (RCC) status post nephrectomy which was initially evaluated for possible sarcoidosis involvement. This medical therapy could also have been the reason his sarcoidosis did not progress to involve other organs. hypocalcemia anemia renal cell carcinoma extrapulmonary manifestations sarcoidosis The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Although typically associated with respiratory complications, sarcoidosis can affect many other organs; symptoms can mimic each other and so can lead to deviations in diagnosis paths. With its characteristic noncaseating granulomas, it is more typically seen in African American females . In one US study from 2010-2013, it was noted that incidence and prevalence were significantly higher in African Americans when compared to the White, Hispanic, or Asian population . Knowledge of proper suspicious findings is important in patient workup to help differentiate sarcoidosis manifestations (whether it be pulmonary or extrapulmonary) with other pathologies as the treatment regimen path can vary vastly. Good history taking, physical findings, laboratory tests, and proper imaging are all crucial parts in helping lead to the most accurate diagnosis. Case presentation A 56-year-old male with a past medical history of renal carcinoma status post nephrectomy, hypertension, and IV drug use presented to the emergency room with complaints of progressively increasing shortness of breath over a period of four days. Symptoms were associated with acute onset of yellowish sputum production. The patient denied any fevers, weight loss, or chest pain. He was an active smoker with a 40-pack-year history. Lab work was remarkable for elevated troponins and positive Respiratory Syncytial Virus (RSV) testing; the remainder was within normal limits. CT chest noted multiple pulmonary nodules in the mediastinal, subcarinal and paratracheal lymph nodes, and a 4.5 cm upper pole right kidney density with increased area of calcification. He was admitted for an acute chronic obstructive pulmonary disease (COPD) exacerbation thought to be triggered by the RSV virus. He was initiated on IV methylprednisolone, Duonebs, and Doxycycline. Prior to this, in 2007 he had a granuloma on the left arm which was thought to be secondary to a foreign body as the pathology had talc and cotton, and he was an IV drug user. Of note, in 2008 he underwent Endobronchial Ultrasound (EBUS) with pathology-proven granulomatous disease; he was prescribed a short duration of prednisone in May of 2008 following which he had modest improvement in his Forced Expiratory Volume (FEV1) as well as his symptoms. Upon cessation of steroid therapy, however, he quickly returned to his diminished baseline respiratory function. Additionally, during his hospital stay, the patient had multiple episodes of symptomatic bradycardia for which Cardiology was consulted; Zio-patch was placed on discharge and he was recommended to undergo further screening for cardiac involvement of his sarcoidosis. Discussion Laboratory testing Sarcoidosis is a disease that can affect multiple organs and so various workup and diagnostic testing must be performed to help differentiate it from other similar presenting pathologies. Diagnosis can be narrowed down via imaging, symptoms, biopsy-proven noncaseating granulomas, as well as exclusion of other pathology/malignancy . Someone presenting with unexplained shortness of breath, constitutional symptoms and hilar lymphadenopathy, for example, should raise suspicion for sarcoid pathology and warrant further investigation . Figure 1 Image depicting a lymph node biopsy of a noncaseating granuloma Bronchoalveolar lavage (BAL) can be a useful tool in differentiating sarcoidosis from other lung pathologies. In one study that compared BAL fluid analysis of healthy lungs to those of symptomatic untreated sarcoidosis patients, it was noted that the lymphocyte count, CD4/CD8 ratio, as well as total cell count were all elevated . Angiotensin-converting enzyme (ACE) is also a marker of disease severity. Although also elevated in other granulomatous diseases, ACE levels in patients with sarcoidosis are correlated to the severity of whole-body granuloma presence . These levels can therefore be used to monitor for disease improvement vs progression during treatment. Imaging With regards to imaging, chest radiography is the most common modality utilized and can help with the initial staging (0-4) based off criteria such as bilateral hilar lymphadenopathy and the presence of fibrosis (Table 1) . Table 1 Table indicating progressive radiologic staging of sarcoidosis Stage Number Radiographic Findings 0 Normal Radiograph 1 Bilateral hilar lymphadenopathy 2 Bilateral hilar adenopathy with parenchymal infiltrates 3 Parenchymal infiltrates only 4 Pulmonary fibrosis CT and MR imaging can also be utilized to help further investigate the extent of disease, especially when evaluating for extrapulmonary spread; they are more sensitive in detecting parenchymal pathology and lymphadenopathy. CT in particular can be useful for guidance when trying to obtain biopsy specimens as well . Management At this time treatment of asymptomatic sarcoidosis is not currently indicated; those with pulmonary and extrapulmonary manifestations, however, do warrant further management. Although there is no official guideline regarding treatment, current therapy recommendations involve IV vs oral corticosteroids based on disease severity. They have been shown to be an effective management strategy, especially in patients with sarcoid-induced renal impairment . In a study by Naderi et al. patients diagnosed with sarcoid underwent kidney biopsy; all patients were noted to have kidney failure secondary to interstitial nephritis with and without granulomas. After a mean follow-up of 59 months, they noted that Prednisolone 0.5 mg/kg seemed to be a sufficient dose to achieve remission . In those whose disease is refractory to steroid treatment, various biologics can be utilized in conjunction. Subgroups Lofgren syndrome is one disease associated with sarcoidosis. Its pathology can be indicated by the acuteness of symptoms when compared to the more chronic ones seen in general sarcoidosis. Other manifestations can include Erythema Nodosum, arthritis, constitutional symptoms, as well as similar hilar lymphadenopathy. The overall prognosis is generally noted to be better in this subgroup . Heerfordt-Waldenstrom syndrome is another rare presentation. It can be characterized by its neurologic involvement. Patients with this subgroup can present with facial nerve palsy, parotid gland involvement, as well as uveitis . These manifestations are likely due to the granulomatous presence secondary to the underlying sarcoidosis. Granulomas within the neural fibers in the face can lead to inflammation and impingement causing weakness. Those that develop within the parotid glands can lead to nearby infections or even difficulty swallowing secondary to mass effect and local swelling/inflammation. Finally, with regards to the eyes, uveitis can develop causing pain, erythema, and blurriness of vision. Extrapulmonary manifestations With regards to renal manifestations, sarcoidosis can present in a number of different ways including electrolyte imbalances, masses, nodules, etc. These can therefore be confused with primary renal pathologies or malignancies, for which our patient did have history of . Due to the granuloma formation associated with the disease, there is an activation of enzymes; predominantly alpha-1-hydroxylase. The overall effect is the net conversion of inactive 25-hydroxyvitamin D to its active form of 1,25 Hydroxyvitamin D; this can lead to an increase in calcium absorption causing hypercalcemia and hypercalciuria . Elevated levels of calcium can lead to nephrolithiasis and nephrocalcinosis which can cause kidney damage . If remained untreated, this can progress to end-stage renal disease requiring hemodialysis . Rhythm issues in patients with known sarcoidosis can warrant evaluation for possible cardiac involvement. As with our patient, he did have multiple episodes of symptomatic bradycardia when hospitalized. Other known manifestations of cardiac sarcoidosis involve heart block, chest pain, arrhythmias, and shortness of breath; the latter of which the patient also endorsed and was hospitalized for . Further workup to include EKG, echocardiograms, and evaluation for ICD should be pursued. Anemia is also another manifestation that can be due to the formation of non-caseating granulomas produced in the bone marrow and kidneys. Renal cell carcinoma (RCC) can also present with similar findings. This can be due to the involved kidney damage from the RCC causing decrease in erythropoietin release . The incidence of RCC has steadily been increasing every year, roughly 2-4% per year, and has one of the highest mortality rates of genitourinary malignancies . Only roughly 10% present with the "classic triad" of hematuria, flank pain, and palpable mass . These manifestations can mimic those with sarcoidosis who have renal involvement. Sarcoid-like granulomatous reactions can also be seen in various malignancies and so careful workup needs to be completed to be able to differentiate the etiology of the granulomas . Conclusions Sarcoidosis can have vague presentations when affecting the renal or other system and so its involvement can potentially be overlooked. Similar manifestations (such as anemia, flank pain/mass, electrolyte imbalances) can mimic other pathologies. Granulomas, in particular, can be of concern as their etiology can be from the sarcoidosis or various other reasons. It is then crucial that proper workup be done to be able to differentiate it, as the management can be very different; possible nephrectomy in those with RCC, for example, as opposed to steroid management with sarcoid-induced kidney injury. Mortality from sarcoidosis has been slowly rising, but early interventions and younger diagnosis age can be good prognostic factors that can help significantly decrease the risk of death and long-term complications. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Renal manifestations of sarcoidosis: from accurate diagnosis to specific treatment Int Braz J Urol Correia FA Marchini GS Torricelli FC 15 25 46 2020 31851454 2 Sarcoidosis in America. Analysis based on health care use Ann Am Thorac Soc Baughman RP Field S Costabel U 1244 1252 13 2016 27509154 3 Diagnostic criteria for sarcoidosis Autoimmun Rev Heinle R Chang C 383 387 13 2014 24424172 4 Intramedullary spinal cord involvement: a rare presentation of sarcoidosis Int Med Case Rep J Padooru KR Sen M 199 203 12 2019 31308764 5 BAL fluid cells in newly diagnosed pulmonary sarcoidosis with different clinical activity Ups J Med Sci Danila E Jurgauskiene L Norkuniene J Malickaite R 26 31 114 2009 19242869 6 Serum ACE level in sarcoidosis patients with typical and atypical HRCT manifestation Pol J Radiol Kahkouee S Samadi K Alai A Abedini A Rezaiian L 458 461 81 2016 27733890 7 Extrapulmonary manifestations of sarcoidosis Rheum Dis Clin North Am Rao DA Dellaripa PF 277 297 39 2013 23597964 8 Sarcoidosis from head to toe: what the radiologist needs to know Radiographics Ganeshan D Menias CO Lubner MG Pickhardt PJ Sandrasegaran K Bhalla S 1180 1200 38 2018 29995619 9 Sarcoid tubulo-interstitial nephritis: long-term outcome and response to corticosteroid therapy Kidney Int Rajakariar R Sharples EJ Raftery MJ Sheaff M Yaqoob MM 165 169 70 2006 16688117 10 Renal involvement in sarcoidosis: histologic findings and clinical course Nephrology @ Point of Care Naderi S Amann K Janssen U 5 2019 11 Lofgren's syndrome: human leukocyte antigen strongly influences the disease course Am J Respir Crit Care Med Grunewald J Eklund A 307 312 179 2009 18996998 12 The Heerfordt-Waldenstrom syndrome as an initial presentation of sarcoidosis Proc (Bayl Univ Med Cent) Denny MC Fotino AD 390 392 26 2013 24082416 13 Renal manifestations of sarcoidosis Arch Intern Med Muther RS McCarron DA Bennett WM 643 645 141 1981 7224744 14 1alpha-Hydroxylase and the action of vitamin D J Mol Endocrinol Hewison M Zehnder D Bland R Stewart PM 141 148 25 2000 11013342 15 Sarcoidosis in native and transplanted kidneys: incidence, pathologic findings, and clinical course PLoS One Bagnasco SM Gottipati S Kraus E Alachkar N Montgomery RA Racusen LC Arend LJ 0 9 2014 16 Arrhythmias in cardiac sarcoidosis bench to bedside: a case-based review Circ Arrhythm Electrophysiol Rosenfeld LE Chung MK Harding CV 0 14 2021 17 The anemia of sarcoidosis Sarcoidosis Lower EE Smith JT Martelo OJ Baughman RP 51 55 5 1988 3381019 18 Renal cell carcinoma Cancer Biomark Cairns P 461 473 9 2010 22112490 19 Renal cell carcinoma a great mimicker Conn Med Mohammad A McClintock C 81 84 71 2007 17393899 20 Sarcoid-like granulomatous reaction in renal cell carcinoma: report of a case with review of the published reports Ann Saudi Med Burhan W Al Rowaie Z Rajih E Akhtar M 614 618 33 2013 24413868
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34917 Cardiac/Thoracic/Vascular Surgery General Surgery Trauma Abdominal Wall Evisceration Coupled With Iliac Vascular Injury After Blunt Trauma Muacevic Alexander Adler John R Novack Joseph C 1 Whitton Eric L 2 Smith Randi N 3 Sciarretta Jason D 3 Nguyen Jonathan 4 1 Department of Medicine, Emory University School of Medicine, Atlanta, USA 2 Department of Anesthesiology, Emory University School of Medicine, Atlanta, USA 3 Department of Surgery, Emory University School of Medicine, Atlanta, USA 4 Department of Surgery, Morehouse School of Medicine, Atlanta, USA Joseph C. Novack [email protected] 13 2 2023 2 2023 15 2 e3491713 2 2023 Copyright (c) 2023, Novack et al. 2023 Novack et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Abdominal evisceration after blunt trauma is uncommon and rarely survivable when coupled with a concomitant iliac vascular injury. Blunt abdominal injury is rarely a cause of abdominal evisceration but may, on occasion, present in patients affected by a unique or high-energy traumatic injury. In these instances, major vascular injury is exceedingly rare but is associated with a high mortality rate. Damage to important vessels that may present more subtly, such as iliac arterial injury, can still be lethal and are important to evaluate in the trauma workup for blunt evisceration. We report the case of a 20-year-old woman who survived an abdominal wall and vascular injury in a motor vehicle accident. Management of this unusual association is discussed. blunt abdominal trauma concomitant vascular injury major vascular injury abdominal evisceration blunt force trauma The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Traumatic injuries are the most common causes of mortality afflicting the young population, with blunt trauma from car accidents among the most common method of injury . Abdominal evisceration from blunt trauma is an exceedingly rare occurrence. Only a small percentage of patients affected by blunt trauma sustain injuries to their abdominal wall, and even fewer suffer the forces necessary to cause a total evisceration of the abdominal contents within . Surgeons evaluating a patient with blunt abdominal injury may not immediately consider major vascular injury as it is exceedingly rare. Among cases of blunt abdominal trauma, it has been shown to occur only 3% of the time with injury to the iliac arteries rarely if ever recorded . While prompt surgical intervention can save a patient with blunt abdominal evisceration, a missed concurrent major vascular injury can result in death. Iliac artery trauma specifically is associated with a mortality rate as high as 60%, and while shown to be exceedingly rare in the context of blunt trauma, it should be kept in mind during assessment . Although management and outcomes may vary greatly when abdominal evisceration and major vascular injury occur simultaneously in one patient, expeditious identification of such injuries is critical to patient care. We discuss the management of a patient with concomitant abdominal wall evisceration and major vascular injury. This paper was presented as a poster at the 86th Annual Meeting of the Southeastern Surgical Congress on February 12, 2018. Case presentation A 20-year-old woman was the restrained passenger in the front seat during a motor vehicle collision. Upon arrival, she was tachycardic with a heart rate of 130 beats per minute, her primary survey was intact, and her Glasgow Coma Scale (GCS) was 15. On further evaluation, her entire abdominal wall was disrupted transversely, violating the peritoneum and resulting in an evisceration of all her small bowels. Abrasions on the remaining skin appeared consistent with a seatbelt sign across the lower abdomen. The patient was taken emergently to the operating room. In addition to the eviscerated bowel, there was already a significant loss of domain in the anterior abdominal wall. A degloving injury similar to a Morel Lavallee lesion that extended laterally to the retroperitoneum near the iliac crests bilaterally was identified at the level of the lap belt rests. On further exploration, the patient had a partially avulsed appendix and a completely devascularized segment of the proximal ileum and sigmoid colon in a traditional bucket-handle fashion. An appendectomy, small bowel resection, and sigmoidectomy were performed. Although the operative site had significant devascularized bowel and necrotic fat, there were no signs of feculent peritonitis or purulence. A Hartmann's colostomy was matured superior to the transverse abdominal wall disruption. Two 19-French Blake drains were left in place, and the vertical midline fascia was reapproximated as best as possible to prevent further loss of domain. The skin was loosely reapproximated with staples. An immediate postoperative completion CT scan was performed to identify any additional injuries. It revealed complete occlusion of the right common iliac artery and no further significant injuries, as shown in Figure 1. The patient was subsequently taken back to the operating room for a right common iliac artery repair with an interposition polytetrafluoroethylene (PTFE) graft and complex abdominal wall reconstruction with biological mesh to reinforce the fascia. After the case, there were bounding peripheral pulses in the right lower extremity, and the compartments were soft. Figure 1 CT scan of the patient's postoperative abdomen depicting iliac artery injury (arrow), with circles highlighting the ostomy and a hernia left behind. CT, computed tomography In the intensive care unit, she was monitored for reperfusion injury and possible signs of compartment syndrome. Her only other complication was a persistent superficial wound infection, and the patient was subsequently discharged from the hospital to rehab at two weeks. At her three-month follow-up, her wounds had all healed and had no further untoward complications. Discussion Abdominal evisceration due to penetrating injury is fairly common, with one case study reporting 66 cases of evisceration due to abdominal stab wounds alone in three years . In cases of penetrating abdominal trauma, mortality is greatest in those who are affected by concomitant vascular injury . However, complete evisceration of the abdominal contents in the setting of blunt trauma is exceedingly rare. The grading system for these cases is ranked from I to VI, I being subcutaneous tissue contusion and VI being complete dissociation of the abdominal wall and herniation of the contents within . In recorded events with blunt trauma to the abdomen, less than 10% result in abdominal wall injury and less than 2% present with any amount of herniation. Fewer than 0.2% of patients sustain a grade VI injury with total evisceration . These injuries can often result from the impact of a motor vehicle collision, causing an acute increase in abdominal pressure that culminates in the tearing of fascia and expulsion of contents [7-9]. In most described case studies and retrospective evaluations, an immediate CT scan followed by emergent laparotomy is recommended . In a literature review of articles discussing abdominal evisceration due to blunt trauma, it is first apparent how unusual evisceration of the abdominal contents is due to a blunt impact. In one report of over 120,000 trauma cases in five years, only three cases of evisceration were found after blunt injury . Only nine previous case studies were noted featuring abdominal evisceration due to blunt trauma, and among these, not a single case of concomitant evisceration and major vascular injury was discussed as in our findings [7,8,11-13]. One study described a small injury to the jejunal arteries via a tear in the mesentery following perineal small bowel evisceration secondary to blunt abdominal trauma, but it was not classified as a major vascular injury . Similarly, aside from the injury to the aorta, blunt vascular injuries of the abdomen are exceedingly uncommon . In our situation, we elected to use PTFE to help avoid a size mismatch and narrowing of the reconstruction. Despite the contaminated nature of the wound, synthetic grafts have demonstrated similarly low complication rates when compared to vein grafts . We suspect that our patient's injury was caused by her lap belt restraint. On impact, the force of the collision was distributed across her body through the straps of the shoulder and lap seatbelt, resulting in abdominal rupture and bowel evisceration. Seatbelts in blunt trauma are known to cause pancreatic injuries, duodenal injuries, and thoracic spine injuries, and in this setting, they may have caused abdominal evisceration . In unusual cases with blunt abdominal evisceration, the major vascular injury should be excluded, and we suggest the following management. First, prompt operative management is required to ensure that there are no life-threatening injuries from hemorrhage and that any bowel spillage is contained. Second, an immediate CT scan should be conducted to identify and categorize all other injuries. Finally, the abdominal wall defect should be closed along with definitive management of all other injuries on time to prevent further retraction of the fascia. To preserve the abdominal wall and the patient's bowel function, rapid closure of the abdomen may be necessary, and the use of a biologic mesh was indicated in this case to relieve tension. Conclusions To our knowledge, there are no reported cases of patients who are affected by simultaneous abdominal wall evisceration and major vascular injury. Both abdominal evisceration and abdominal vascular injury are much more likely as a result of penetrating injury, but it is possible to encounter the two together due to blunt force injury. A very important factor in survival is surgical control of major hemorrhage, and due to the rare nature of arterial injury in blunt trauma, it is possible that a damaged artery could be initially overlooked in the operating room. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Traumatic injury in the United States: in-patient epidemiology 2000-2011 Injury DiMaggio C Ayoung-Chee P Shinseki M 1393 1403 47 2016 27157986 2 Abdominal wall disruption with evisceration after blunt trauma BMJ Case Rep Cawich S Islam S Harnarayan P Young-Pong C 2014 2014 3 Blunt abdominal trauma. A 5-year analysis of 870 patients requiring celiotomy Ann Surg Cox EF 467 474 199 1984 6712323 4 Damage control techniques for common and external iliac artery injuries: have temporary intravascular shunts replaced the need for ligation? J Vasc Surg Ball CG Feliciano DV 1112 1113 52 2010 5 Evisceration following abdominal stab wounds: analysis of 66 cases World J Surg da Silva M Navsaria PH Edu S Nicol AJ 215 219 33 2009 19023617 6 Abdominal vascular trauma Trauma Surg Acute Care Open Kobayashi LM Costantini TW Hamel MG Dierksheide JE Coimbra R 0 1 2016 7 Abdominal wall injuries occurring after blunt trauma: incidence and grading system Am J Surg Dennis RW Marshall A Deshmukh H Bender JS Kulvatunyou N Lees JS Albrecht RM 413 417 197 2009 19245925 8 Evisceration from blunt trauma in adults: an unusual injury pattern: 3 cases and a literature review Scand J Trauma Resusc Emerg Med Hardcastle T Coetzee G Wasserman L 234 235 13 2005 9 Traumatic lumbar hernia: report of cases and comprehensive review of the literature J Trauma Burt BM Afifi HY Wantz GE Barie PS 1361 1370 57 2004 15625480 10 Traumatic abdominal wall hernia (TAWH): a case study highlighting surgical management Yonsei Med J Choi HJ Park KJ Lee HY 549 553 48 2007 17594168 11 Blunt traumatic abdominal wall disruption with evisceration Int J Crit Illn Inj Sci McDaniel E Stawicki SP Bahner DP 164 166 1 2011 22229144 12 Evisceration of the intestine following blunt force impact: highlighting management J Health Spec Singal R Singal S Mittal A Gulati A Singh P 157 3 2015 13 A 6-year-old boy presenting with traumatic evisceration following a bicycle handle bar injury: a case report Cases J Nguyen MH Watson A Wong E 6315 2 2009 19829784 14 Perineal small bowel evisceration following blunt abdominal trauma ANZ J Surg Taylor AM Gundara JS Wines M Ruff S Samra JS 992 993 83 2013 24289053 15 Traumatic blunt injuries to the celiac artery: a 5-year review from a level I trauma center Am Surg Fitzgerald CA Tootla Y Morse BC Benarroch-Gampel J Ramos CR Nguyen J 1651 1655 86 2020 32683941 16 Common iliac artery dissection after blunt trauma: case report of endovascular repair and literature review J Trauma Lyden SP Srivastava SD Waldman DL Green RM 339 342 50 2001 11242303 17 In-hospital outcomes in autogenous vein versus synthetic graft interposition for traumatic arterial injury: a propensity-matched cohort from PROOVIT J Trauma Acute Care Surg Stonko DP Betzold RD Abdou H 407 412 92 2022 34789705 18 Delayed duodenal hematoma and pancreatitis from a seatbelt injury West J Emerg Med Deambrosis K Subramanya MS Memon B Memon MA 128 130 12 2011 21691489
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34909 Emergency Medicine Gastroenterology General Surgery Pneumatosis Intestinalis With Abdominal Wall Emphysema in Hypothermia Muacevic Alexander Adler John R Kuwahara Masaatsu 1 Otagaki Hiroko 1 Imanaka Hideaki 1 1 Department of Emergency Medicine, Takarazuka City Hospital, Takarazuka, JPN Masaatsu Kuwahara [email protected] 13 2 2023 2 2023 15 2 e3490913 2 2023 Copyright (c) 2023, Kuwahara et al. 2023 Kuwahara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from In this report, we present a case in which intestinal and abdominal wall emphysema was observed, but the patient was unconscious due to hypothermia, making it difficult to determine the indication for surgery. Pneumatosis intestinalis (PI) is a pathological condition characterized by the presence of gas within the walls of the small or large intestine and is considered a surgical emergency when accompanied by manifestations of peritonitis on abdominal examination, metabolic acidosis, and lactic acid levels above 2.0 mmol/L. In this specific case, the patient's blood draw results indicated the requirement for an emergency laparotomy; however, the patient's unconscious state became a challenge to make decision on informed consenting. The case illustrates the difficulties encountered in making treatment decisions in critically ill patients and the necessity for thorough assessments and close monitoring of vital signs in such patients. free air pneumatosis intestinalis laparotomy decision wall emphysema accidental hypothermia The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Pneumatosis intestinalis (PI) is a pathological condition characterized by the presence of gas within the walls of the small or large intestine. The signs of peritonitis on abdominal examination, metabolic acidosis (arterial pH of <7.3 and HCO3 of <20 mmol/L), lactic acid of >18 mg/dL, and portal vein gas are considered to necessitate an urgent exploratory laparotomy . We present a case in which the results of a blood draw indicated the need for an emergency exploratory laparotomy; however, the patient's inability to confirm the abdominal findings due to unconsciousness, resulting from accidental hypothermia, made it challenging to devise a treatment plan. Case presentation This case report presents the circumstances surrounding an 85-year-old female patient living alone who was taking sodium-glucose cotransporter-2 (SGLT2) inhibitors for preexisting heart failure. The patient's family alerted medical authorities after being unable to reach the patient by phone and subsequently finding her lying on the floor in her home, where the temperature was 3degC and the heating system was turned off. Upon arrival at the hospital, the patient exhibited moderate accidental hypothermia with a bladder temperature of 29.8degC, Glasgow Coma Scale score of 1-1-1, blood pressure of 105/89 mmHg, heart rate of 57 beats per minute, oxygen saturation of 96% on room air, and respiratory rate of 20 breaths per minute. Pupils were 2.5 mm in both right and left eyes, and the light reflex was dull. The abdomen was tender throughout, but the presence of tenderness or peritoneal irritation symptoms was unknown due to impaired consciousness. Therapeutic interventions were immediately initiated, including warming infusions and surface heating. A blood sample was taken, which revealed a low blood glucose level of 37 mg/dL (normal level: 73-109 mg/dL). Intravenous injection of 50% glucose was administered, resulting in an improvement in blood glucose to 160 mg/dL (normal level: 73-109 mg/dL) after 30 minutes. Despite this improvement, the patient's level of consciousness did not improve. Laboratory analysis revealed no other causes for the patient's impaired consciousness but did reveal high creatinine kinase (CK) levels of 1062 U/L (normal level: 59-248 U/L) and mild acidemia with a pH of 7.293 (normal level: 7.35-7.45), although bicarbonate levels had not decreased to 25.5 mmol/L (normal level: 21-28 mmol/L). Lactic acid levels were slightly elevated at 26 mg/dL (normal level: 4.5-14.4 mg/dL) (Table 1). Table 1 Blood data at admission T-bil, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; UN, urea nitrogen; CRE, creatinine; Na, sodium; K, potassium; CI, chloride ion; CK, creatine kinase; AMY, amylase; CRP, C-reactive protein; GLU, glucose; WBC, white blood cell; Hb, hemoglobin; PLT, platelet; PT, prothrombin time; APTT, activated partial thromboplastin time; Fib, fibrinogen; LAC, lactate Blood data Normal range Unit T-bil 1.3 0.4-1.5 mg/dL AST 58 13-30 U/L ALT 30 7-23 U/L UN 38.3 8-20 mg/dL CRE 0.87 0.46-0.79 mg/dL Na 138 138-145 mmol K 4 3.6-4.8 mmol CI 97 101-108 mmol CK 1062 41-153 U/L AMY 86 44-132 U/L CRP 0.66 <0.14 mg/dL GLU 36 73-109 mg/dL WBC 7340 3300-8600 /ml Hb 12.7 11.6-14.8 g/dL PLT 26.1x104 15.8-34.8x104 /ml PT 58 70-130 % APTT 38.3 <40 Fib 198 200-400 mg/dL D-dimer 5.5 <1.0 mg Lac 26 4.5-14.4 mg/dL In an effort to further investigate the cause of the patient's loss of consciousness, a CT scan of the head was performed, which revealed no apparent cause. Because the hypothermia could have been caused by an infection, we performed a thoracoabdominal CT. Additionally, thoracoabdominal CT scans showed PI in the small intestine of the left lower abdomen, as well as suspicious findings consistent with free air . Figure 1 Abdominal wall emphysema on admission In the left image, it is difficult to differentiate between abdominal wall emphysema and intra-abdominal free air. Changing the CT window width as shown in the image on the right reveals that it is abdominal wall emphysema Figure 2 PI on admission PI is seen in the left lower abdomen PI: pneumatosis intestinalis Surgical intervention was considered for possible intestinal perforation, but upon further examination, it was determined that the gas was not intra-abdominal gas but rather extra-abdominal gas, and the patient was diagnosed with abdominal wall emphysema. Given the patient's unconscious state and inability to accurately examine her abdominal findings, a conservative treatment approach was chosen, including fasting, intravenous infusions, and antimicrobial agents, with close monitoring of the patient's condition and abdominal findings. Fortunately, the patient's condition improved, with creatine kinase (CK) levels decreasing from 1062 U/L on admission to 793 U/L (normal level: 59-248 U/L) the following day, and no deterioration was noted. Additionally, blood culture results were negative for sepsis. Pneumatosis intestinalis had disappeared, and abdominal wall emphysema had decreased on follow-up CT scan. The patient subsequently began oral intake and was transferred to a rehabilitation facility without any worsening of her abdominal findings or general condition. Discussion Hypothermia is characterized by a profound decrease in the core body temperature to less than 35degC. The prevalent categorization of the stages of hypothermia in the literature includes mild hypothermia (core body temperature of 32degC-35degC), moderate hypothermia (28degC-32degC), and severe hypothermia (<28degC) . Moderate accidental hypothermia results in a decreased level of consciousness . The patient exhibited moderate hypothermia, the etiology of which was determined to be hypoglycemia caused by the administration of SGLT2 inhibitors for heart failure. We posit that the accidental hypothermia was exacerbated by the inability to activate heating despite a subsequent drop in temperature, further exacerbating the loss of consciousness. Although sepsis was considered as a differential diagnosis, blood culture results at the time of presentation were negative, and there were no other electrolyte abnormalities or abnormal findings on CT of the head. A CT scan of the abdomen upon the patient's arrival revealed PI and abdominal wall emphysema, which initially presented a challenge in distinguishing from free air. However, by altering the CT window value, differentiation between free air and PI, abdominal wall emphysema was possible. As reported by Hisanaga et al., this technique of altering the window value is effective in differentiating free air from PI, as was exemplified in the present case . PI is the presence of gas within the walls of the small or large intestine. It is either idiopathic (15%) or secondary (85%) in nature . The etiology of PI can be attributed to mechanical , bacterial , or biochemical causes, such as alpha-glucosidase internalization. In the present case, no bacteria were detected in the blood culture, and no alpha-glucosidase was taken internally. Ischemia of the intestine due to circulatory failure caused by hypothermia was also suspected, but trends in CK and lactate (LAC) were also negative for worsening intestinal ischemia. The management of PI includes emergency exploratory laparotomy in the presence of signs of peritonitis on abdominal examination, metabolic acidosis (arterial pH of <7.3 and HCO3 of <20 mmol/L), lactic acid of >18 mg/dL, portal vein gas, and the presence of PI on imaging . In the current case, the patient's arterial pH of 7.293 (normal level: 7.35-7.45) and lactic acid level of 26 mg/dL (normal level: 4.5-14.4 mg/dL) met the criteria for emergency exploratory laparotomy. Initially, the patient's disorientation caused by hypoglycemia and hypothermia precluded an accurate assessment of abdominal findings. After close monitoring of the patient's overall condition, including repeat blood gas tests, a conservative treatment approach was chosen. Once the patient's level of consciousness improved, abdominal findings were confirmed, and there was no indication of peritonitis. No portal vein gas was detected. The difficulty in obtaining abdominal findings in patients with impaired consciousness highlights the importance of obtaining such findings after improvement in consciousness, in order to reduce unnecessary patient invasiveness and to make an accurate determination of the indication for emergency exploratory laparotomy in cases of PI. Conclusions In conclusion, the determination of surgical indication in patients presenting with impaired consciousness can be a challenging task. However, if the disturbance in consciousness is reversible, it is crucial to closely monitor the patient and meticulously evaluate the abdominal findings once the patient regains consciousness to minimize unnecessary patient invasiveness and accurately determine the indication for surgery. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Pneumatosis intestinalis. Surgical management and clinical outcome Ann Surg Knechtle SJ Davidoff AM Rice RP 160 165 212 1990 2375647 2 Pneumatosis cystoides intestinalis: confirmation of diagnosis by endoscopic puncture a review of pathogenesis, associated disease and therapy and a new theory of cyst formation Endoscopy Hoer J Truong S Virnich N Fuzesi L Schumpelick V 793 799 30 1998 9932761 3 Cold stress, near drowning and accidental hypothermia: a review Aviat Space Environ Med Giesbrecht GG 733 752 71 2000 10902937 4 European Resuscitation Council guidelines 2021: cardiac arrest in special circumstances Resuscitation Lott C Truhlar A Alfonzo A 152 219 161 2021 33773826 5 Wilderness Medical Society clinical practice guidelines for the out-of-hospital evaluation and treatment of accidental hypothermia: 2019 update Wilderness Environ Med Dow J Giesbrecht GG Danzl DF 0 69 30 2019 6 Case of pneumatosis cystoides intestinalis with intra-abdominal free air developed during treatment with voglibose JGH Open Hisanaga E Sano T Kumakura Y Yokoyama Y Nakajima I Takagi H 643 646 6 2022 36091325 7 Pneumatosis intestinalis: a review Radiology Pear BL 13 19 207 1998 9530294 8 The bacterial etiology of pneumatosis cystoides intestinalis Arch Surg Yale CE Balish E Wu JP 89 94 109 1974 4365449 9 Pneumatosis cystoides intestinalis after alpha-glucosidase inhibitor treatment in a patient with interstitial pneumonitis Intern Med Hisamoto A Mizushima T Sato K Haruta Y Tanimoto Y Tanimoto M Matsuo K 73 76 45 2006 16484742
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34923 Cardiology Internal Medicine Acute-on-Chronic Pattern of Isolated Upper Back Pain in a Patient With Acute Coronary Syndrome Muacevic Alexander Adler John R Harada Yukinori 1 Masuyama Taiki 2 Yokose Masashi 1 Shimizu Taro 1 1 Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Mibu, JPN 2 Department of Cardiovascular Medicine, Dokkyo Medical University Hospital, Mibu, JPN Yukinori Harada [email protected] 13 2 2023 2 2023 15 2 e3492313 2 2023 Copyright (c) 2023, Harada et al. 2023 Harada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from The aim of this case report is to describe the diagnostic pitfalls of acute coronary syndrome in patients with relatively atypical presentation and how we can prevent diagnostic errors in such a patient, particularly focusing on occupational information. A 66-year-old male, a professional taxi driver, presented with severely deteriorated chronic upper back pain on the left side. Furthermore, the upper back pain was exacerbated by changes in position. An orthopedist examined the patient and arrived at a provisional diagnosis of musculoskeletal pain. However, as the patient was concerned about his cardiopulmonary diseases, he visited another physician. Although musculoskeletal pain was still considered as the most possible diagnosis, the physician advised him additional tests for cardiovascular diseases because he had some risk factors such as smoking, hypertension, and dyslipidemia, and the physician thought that "taxi driving" was a high-risk occupation for cardiovascular diseases. Finally, the patient was diagnosed with acute coronary syndrome, and the pain abated soon after percutaneous coronary intervention. Musculoskeletal pain is very common in professional drivers, and isolated upper back pain worsened by changes in position is a characteristic of musculoskeletal disease. However, since professional drivers also have a higher risk of cardiovascular diseases, physicians should consider the coexistence of two types of conditions. This case underscores that if physicians could utilize occupational information to assess patients' risks, diagnostic accuracy would improve, particularly in patients presenting with atypical symptoms and signs, which are at risk of diagnostic errors. acute coronary syndrome non-st elevation myocardial infarction atypical presentation professional driver upper back pain The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Generally, in daily clinical practice, the patient's occupational background does not seem to be regarded as helpful information other than when occupation-related diseases are thought of. However, some occupations such as professional driver can be significant risk factors for some diseases (e.g., cancer, cardiovascular, and pulmonary diseases) [1-3]. Therefore, if physicians could utilize occupational information to assess the patient's risks, diagnostic accuracy would improve, particularly in patients presenting with atypical symptoms and signs, which are at risk of diagnostic errors. The aim of this case report is to describe the diagnostic pitfalls of acute coronary syndrome in patients with relatively atypical presentation and how we can prevent diagnostic errors in such a patient, particularly focusing on occupational information. Case presentation A 66-year-old male presented at the outpatient department of orthopedics in our hospital with a complaint of upper back pain on the left side. Although the patient noticed the discomfort and back pain while driving a taxi for around a month, he did not visit a doctor because he did not want to take a day off from work. However, the pain suddenly became severe, and the patient developed cold sweat three days before presenting to our hospital. When the pain continued for the next two days, the patient decided to visit the hospital. Other than driving, the pain worsened by motion and while taking a deep inspiration, whereas it lessened by rest. The pain was dull, persistent, and non-radiating. The patient had no symptoms such as chest pain, dyspnea, fatigue, or palpitation. The patient reported that elevated blood pressure, dyslipidemia, and arrhythmia were pointed out on the latest annual health checkup but was not on any medication. His family history revealed that his father suffered from gastric cancer and his mother from colon cancer; there was no family history of cardiovascular diseases. The patient was a current smoker with a history of 48 pack-years and drank 350 mL of beer every day. The patient was initially examined by an orthopedist. The patient admitted that the intensity of pain decreased on the day of presentation. The pain was experienced in the upper back on the left side. There was no tenderness, knock pain, or rash on the back. The pain increased by lateral flexion of the trunk toward the left but not by any other motions. Plain films of the thoracic and lumbar vertebrae and the ribs were normal. The orthopedist thought that musculoskeletal causes could explain the pain; however, as the patient was also concerned about pulmonary or cardiac diseases, the patient was referred to the department of general medicine on the same day. On reassessment of the patient at the department, he appeared well. The height and weight were 162 cm and 63 kg, respectively; the body mass index was 24.0. On physical examination, the blood pressure was 136/88 mmHg measured on the right arm, without significant difference between the arms. The pulse rate was 71 beats per minute, respiratory rate was 16 breaths per minute, body temperature was 36.6degC, and oxygen saturation was 98% on ambient air. There were no abnormal lung sounds or murmurs. Since the patient had pain for approximately one month and had risk factors for lung cancer, such as smoking and taxi driving , the physician believed that pleural invasion of lung cancer was the most likely cause of the pain. However, considering that the patient also experienced sudden worsening of the pain and the associated cardiovascular risk factors such as smoking, elevated blood pressure, dyslipidemia, and taxi driving , acute coronary syndrome and aortic dissection were also of concern. An electrocardiogram showed premature ventricular contractions without ST segment abnormalities . Figure 1 Electrocardiogram on the day of presentation An electrocardiogram showing premature ventricular contractions without ST segment abnormalities Chest computed tomography (CT) without contrast showed no evidence of fracture, pleural effusion, pneumothorax, abnormal opacities, or aortic and pulmonary artery dilatation. The probability of being a musculoskeletal pain seemed to increase; however, the high-sensitivity troponin I level turned out to be 150.15 ng/L. Since the patient's aortic dissection detection risk score was 1 and D-dimer level was below 300 ng/mL, aortic dissection seemed unlikely . Other laboratory results included white blood cell count, 7,100/mL; hemoglobin, 15.3 g/dL; platelet count, 26.9/mL; lactate dehydrogenase, 193 U/L; creatine kinase, 79 U/L; total cholesterol, 303 mg/dL; triglyceride, 757 mg/dL; low-density lipoprotein cholesterol, 213 mg/dL; glucose, 102 mg/dL; and glycated hemoglobin, 5.5%. Acute myocardial injury due to coronary artery diseases, myocarditis, or Takotsubo cardiomyopathy were considered as differential diagnoses, and the patient was referred to the department of cardiology for further evaluation. The patient was evaluated by a cardiologist. Transthoracic echocardiography revealed mild hypokinesis in the anterior-anteroseptal and inferior-anteroseptal regions. Chest and abdominal contrast-enhanced CT ruled out the possibility of aortic dissection and pulmonary embolism, while coronary CT showed stenoses in the right coronary artery. Subsequently, coronary angiography was performed immediately, which showed multiple stenoses in the right coronary artery . Figure 2 Coronary angiogram Coronary angiogram showing multiple stenoses in the right coronary artery The patient was diagnosed with non-ST elevation myocardial infarction; thus, he underwent percutaneous coronary intervention with drug-eluting stent placement. After the procedure, the pain rapidly disappeared. Although the patient's condition was well, since the patient needed to complete an in-hospital cardiac rehabilitation program, the patient was hospitalized until day 10. Discussion This was a case successfully managed with a timely correct diagnosis of acute coronary syndrome in a patient with an atypical presentation and with an acute-on-chronic isolated upper back pain. It has been said that only the "typicality" of presentation may lead physicians to make incorrect decisions while discriminating acute coronary syndrome from other diseases . Indeed, only three of 13 common symptoms were reported to be predictive of a diagnosis of acute coronary syndrome versus non-acute coronary syndrome . Furthermore, the "typical" presentation of acute coronary syndrome varies with several factors such as age, sex, and comorbidity . Therefore, not only symptoms but also the risk factors of patients can impact the decision of correct diagnosis of acute coronary syndrome with an "atypical" presentation. Regarding the background of patients, occupational information can sometimes be a key factor in the assumption of the risk factors for specific diseases. In this case, the patient's occupation, "taxi driver," prompted the physician to consider cancer and cardiovascular diseases, which resulted in the correct diagnosis. Meanwhile, musculoskeletal upper back pain being common among professional drivers , the information "taxi driver" would have misled to an incorrect diagnosis if the orthopedist would have anchored the patient to musculoskeletal pain and did not refer him to another physician. This case illustrates the challenging situation of arriving at a correct diagnosis in patients who engage in a specific occupation that carries high risks for several diseases, such as a professional driver. Upper back pain is a common symptom among professional drivers, including taxi drivers. In a previous systematic review, approximately 25% (up to 60%) of professional drivers experienced musculoskeletal upper back pain . Based on the data, the information "taxi driver" seems to be a driving force for physicians to assume musculoskeletal pain as the most likely cause in patients with upper back pain. On the other hand, upper back pain is also a common type of pain in patients with acute coronary syndrome (around 20%) . Furthermore, taxi drivers have been known to be a high-risk population for cardiovascular diseases including ischemic heart disease . From this viewpoint, the information "taxi driver" seems to be a driving force for physicians to suspect cardiovascular diseases in patients with upper back pain. However, a recent study conducted in Japan suggested that the risk of acute myocardial infarction was not higher in taxi drivers compared to other occupations after adjusting several factors such as smoking history . Indeed, it is also reported that taxi drivers have multiple background risk factors for cardiovascular diseases such as hypertension, diabetes, dyslipidemia, drinking alcohol, smoking, and insufficient physical activity , as some of which were observed in this case. These results indicated that the information "taxi driver" itself may not be an independent risk for acute coronary syndrome but rather the trigger information for physicians to take a further history of risk factors for cardiovascular disease, which can result in the right direction for the correct diagnosis of the acute coronary syndrome. Hence, when a piece of clinical information carries multiple risks, it is inevitable for physicians to be aware of every single risk factor and to be careful not to anchor it to just one risk factor. Furthermore, precise, thorough assessment by depicting a whole picture of a patient can be a turning point for whether physicians can utilize occupational information as a driving force for the correct diagnosis of the cause of upper back pain in patients who are taxi drivers. In this case, the pain of the patient developed around one month prior, and the characteristics seemed to be consistent with musculoskeletal pain; however, the pain suddenly worsened and was accompanied by cold sweat, which indicated that a new additional event occurred in the patient with a chronic condition. Since the pain abated soon after percutaneous coronary intervention, the suddenly worsened upper back pain could have been mainly caused by acute myocardial infarction. On the other hand, since the exacerbation of pain with changes in position in this patient was atypical for acute coronary syndrome , the sudden worsening of the upper back pain in this patient was also thought to be partly derived from musculoskeletal causes. Therefore, the acute upper back pain in this patient may have been explained by the coexistence of acute myocardial infarction and musculoskeletal disease. Conclusions Acute coronary syndrome is a common and critical disease that physicians should not miss. However, it is well known that there are wide variations of clinical manifestations of acute coronary syndrome, which can easily lead physicians to misdiagnose. Increasing awareness of important information suggesting acute coronary syndrome, which can reduce the risk of cognitive biases such as anchoring and premature closure, is warranted to avoid diagnostic errors of acute coronary syndrome. In this case, all physicians engaged in the care of a patient could successfully use medical histories such as smoking, hypertension, dyslipidemia, and the "driver" information for a timely correct diagnosis of acute myocardial infarction. In summary, physicians should know that easily missed information, such as occupation, can sometimes drive the correct diagnosis of specific diseases. Such awareness may help physicians correctly diagnose patients with atypical presentations. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Cancer risk in road transportation workers: a national representative cohort study with 600,000 person-years of follow-up Sci Rep Lee W Kang MY Kim J Lim SS Yoon JH 11331 10 2020 32647239 2 Hospital admissions among male drivers in Denmark Occup Environ Med Hannerz H Tuchsen F 253 260 58 2001 11245742 3 10-year risk for cardiovascular disease among male workers in small-sized industries J Cardiovasc Nurs Park K Hwang SY 267 273 30 2015 24743651 4 Systematic review of aortic dissection detection risk score plus D-dimer for diagnostic rule-out of suspected acute aortic syndromes Acad Emerg Med Bima P Pivetta E Nazerian P 1013 1027 27 2020 32187432 5 Accuracy of aortic dissection detection risk score alone or with D-dimer: a systematic review and meta-analysis Eur Heart J Acute Cardiovasc Care Tsutsumi Y Tsujimoto Y Takahashi S Tsuchiya A Fukuma S Yamamoto Y Fukuhara S 0 9 9 2020 6 Typical and atypical symptoms of acute coronary syndrome: time to retire the terms? J Am Heart Assoc DeVon HA Mirzaei S Zegre-Hemsey J 0 9 2020 7 Utility of the history and physical examination in the detection of acute coronary syndromes in emergency department patients West J Emerg Med Dezman ZD Mattu A Body R 752 760 18 2017 28611898 8 Sensitivity, specificity, and sex differences in symptoms reported on the 13-item acute coronary syndrome checklist J Am Heart Assoc Devon HA Rosenfeld A Steffen AD Daya M 0 3 2014 9 Impact of comorbidities by age on symptom presentation for suspected acute coronary syndromes in the emergency department Eur J Cardiovasc Nurs Burke LA Rosenfeld AG Daya MR 511 521 16 2017 28198635 10 Prevalence of musculoskeletal pain among professional drivers: a systematic review J Occup Health Joseph L Standen M Paungmali A Kuisma R Sitilertpisan P Pirunsan U 0 62 2020 11 A case control study of occupation and cardiovascular disease risk in Japanese men and women Sci Rep Fukai K Furuya Y Nakazawa S Kojimahara N Hoshi K Toyota A Tatemichi M 23983 11 2021 34907236 12 Cardiovascular risk factors of taxi drivers J Urban Health Elshatarat RA Burgel BJ 589 606 93 2016 27151321 13 Value and limitations of chest pain history in the evaluation of patients with suspected acute coronary syndromes JAMA Swap CJ Nagurney JT 2623 2629 294 2005 16304077
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34941 Internal Medicine Infectious Disease Rheumatology A Case of Microscopic Polyangiitis Complicated by Mucormycosis: A Dangerous Balancing Act Muacevic Alexander Adler John R Valle Ana 1 Tagoe Clement 2 1 Division of Internal Medicine, Montefiore Medical Center, Bronx, USA 2 Division of Rheumatology, Montefiore Medical Center, Bronx, USA Ana Valle [email protected] 13 2 2023 2 2023 15 2 e3494112 2 2023 Copyright (c) 2023, Valle et al. 2023 Valle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Microscopic polyangiitis (MPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis marked by renal involvement, which often leads to rapidly progressive glomerulonephritis. Immunosuppressive treatment is necessary to prevent irreparable organ damage. On the other hand, mucormycosis is a rare and devastating opportunistic fungal infection with a high mortality rate in both immunosuppressed and immunocompetent individuals. It requires a high index of suspicion at the time of diagnosis since any delay in treatment may lead to severe morbidity or death. Here, we present the case of a diabetic patient diagnosed with MPA who received partial induction treatment, subsequently developed mucormycosis, survived, yet required continued immunosuppressive treatment for active MPA while imaging was concerning for a persistent mucormycosis infection. This case highlights the barriers to early mucormycosis detection specific to vasculitis patients, mucormycosis considerations unique to the rheumatologic population, and discusses how to balance immunosuppressive treatment in the setting of a deadly opportunistic infection. corticosteroids rhizopus mucormycosis microscopic polyangiitis anca-associated vasculitis The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases defined by small vessel vasculitis associated with the presence of ANCA . Signs and symptoms are variable, given they are manifestations secondary to the inflamed vascular bed and affect the organs reliant on that vessel. The rupture of vessels may cause purpura on the skin or alveolar hemorrhage within the lungs, while vessel occlusion may lead to organ ischemia or infarction. The upper and lower respiratory tracts and kidneys are the organs most commonly and severely affected. Patients usually present with asymmetrical peripheral motor neuropathy and constitutional symptoms, such as fatigue, fever, and arthralgias . Microscopic polyangiitis (MPA) is a type of AAV marked by renal involvement, which often leads to rapidly progressive glomerulonephritis and the presence of myeloperoxidase-ANCA (MPO-ANCA; although proteinase 3 (PR3)-ANCA has also been reported). It has an incidence of 1.5-16 per million person-years, and diagnosis is made with a renal biopsy. Rituximab coupled with systemic, high-dose glucocorticoids is the ideal treatment for active, severe MPA. Cyclophosphamide was previously considered first-line therapy as well, and it remains non-inferior to rituximab when combined with glucocorticoids; however, it is more toxic in comparison to rituximab. Thus, current recommendations only suggest cyclophosphamide as an alternative to rituximab for patients who did not clinically respond to rituximab or were unable to receive it for another reason . Mucormycosis is an opportunistic fungal infection most often described in patients who are immunocompromised due to diabetes mellitus, transplant, or malignancy . With one to two cases per one million people, it is considered a rare disease, although there is some evidence that its global incidence is increasing. Ubiquitous fungal species, such as Rhizopus and Mucor, are responsible for the infection . These fungi flourish in damp, acidic environments rich in free iron . In diabetes mellitus, other mechanisms in addition to free iron, such as the upregulation of fungal proteins and mammalian endothelial receptors, are thought to increase the susceptibility of tissue to fungal penetration . Mucormycosis can disseminate or localize to a specific organ system. Most commonly, it affects rhino-orbital-cerebral areas, leading to acute sinusitis associated with fever, nasal congestion, purulent nasal discharge, and sinus pain. Regardless of location, it causes local destruction, tissue infarction, and necrosis as the hyphae rapidly invade the area . Urgent surgical debridement and amphotericin B are first-line treatments, yet mortality remains high at 46% . Those who survive may be left with disfiguring cosmetic outcomes. Case presentation A 55-year-old female presented to an emergency department in the Bronx, New York, due to bilateral lower extremity edema. She was afebrile and hemodynamically stable. Her past medical conditions included hypertension, hyperlipidemia, and insulin-dependent type 2 diabetes mellitus (hemoglobin A1c (HA1c) 7.7 during this admission). Laboratory data revealed a new creatinine elevation of 1.7 mg/dL and proteinuria of >5 g per day as well as a positive myeloperoxidase antibody of 3 AI determined by enzyme-linked immunoassay. HIV, anti-glomerular basement membrane (GBM), PR3, double-stranded DNA, and Smith antibodies were negative, and complements were within normal limits. She had microscopic hematuria with 4-10 red blood cells/high power field (HPF), and no red blood cell casts were noted. Renal biopsy showed "diffuse crescentic glomerulonephritis, MPO-ANCA associated...no immune complexes seen on electron microscopy." The diagnosis of MPA was made based on these findings consistent with the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA . She received one dose of cyclophosphamide and began prednisone 60 mg daily before leaving against medical advice. She continued taking prednisone 60 mg daily at home and did not have any medical follow-up until she returned to the emergency department two months later due to one day of intermittent right facial paresthesia and numbness associated with unilateral blurry vision of the right eye. Stroke imaging was unremarkable, but her glucose level was noted to be elevated to 500 mg/dL. She was admitted for insulin regimen adjustments. Her facial neurological symptoms were attributed to hyperglycemia and AAV. The patient was discharged with a rheumatology appointment and a plan to pursue rituximab to decrease the risk of relapse in the outpatient setting. However, she returned to the emergency department five days later due to a recurrence of right facial numbness, which was now accompanied by left periorbital pain with photophobia, rhinorrhea, and purulent green nasal discharge. She had a temperature of 100.6degF but was hemodynamically stable. Neurological exam confirmed facial numbness in the left maxillary nerve distribution, including hard palate, and ophthalmologic exam was unremarkable. MRI of the brain and orbits revealed abnormal enhancement in the left masticator space, pterygoid muscles, temporalis muscle, nasal turbinates, and sinuses along with mild, asymmetric enhancement of the maxillary division of the left trigeminal nerve at the foramen rotundum and mandibular division near its exit through the foramen ovale concerning for an invasive fungal species . Direct nasopharyngoscopy evaluation revealed the inferior turbinate appeared dusky. The patient was taken for nasal cavity exploration and debridement the following day. Surgical cultures obtained grew Rhizopus and Serratia marcescens. Amphotericin B and ceftriaxone were initiated, and prednisone was reduced to 20 mg daily. MRI of the sinuses on postoperative day 2 revealed increased enhancement, so the patient returned to the operating room for further debridement of necrotic tissue. A repeat postoperative MRI on postoperative day 4 once again revealed continued abnormal enhancement that was worse in comparison with previous imaging, and the patient returned to the operating room for additional debridement. The patient completed a two-week course of amphotericin B followed by posaconazole for six months, atovaquone for Pneumocystis jirovecii pneumonia prophylaxis, and continued prednisone 20 mg daily Figure 1 Patient's first MRI which revealed a mild enlargement and asymmetric enhancement of the left trigeminal nerve maxillary division at the foramen rotundum and mandibular division near its exit through the foramen ovale (arrow). An MRI of the sinuses and orbits two months after debridement revealed decreased but persistent abnormal enhancement in the left retromaxillary fat and masticator space, left periorbital soft tissues and orbit, left pterygomaxillary fissure, left foramen rotundum, and in the dura along the left medial middle cranial fossa, left inferior anterior cranial fossa, and right inferior frontal lobe . Through shared decision-making, it was decided to proceed with decreasing her prednisone dose to 5 mg daily and closely monitor without further debridement. Figure 2 Patient's last MRI which revealed a persistent abnormal signal and enhancement in the left pterygomaxillary fissure and left foramen rotundum although mild dural enhancement along the left medial middle cranial fossa had decreased (arrow). Outcome and follow-up Since her debridement, the patient has had a persistent, unchanged loss of sensation in the distribution of the left maxillary nerve. Over the next year, she remained on prednisone 5 mg daily. Her kidney function continued to deteriorate, and 15 months after her initial presentation of MPA, she transitioned to end-stage renal disease and initiated hemodialysis. At the time of this paper, the patient has not had any recurrence of mucormycosis or MPA in other organ systems. Discussion This is the case of a diabetic patient who was diagnosed with MPA that required high-dose glucocorticoids and subsequently developed mucormycosis. The development of mucormycosis in a diabetic is well documented . However, one must also speculate whether her rheumatic condition or its treatment contributed to the development of mucormycosis. Furthermore, the non-fatal and relatively chronic disease course of this patient's mucormycosis requires examination and begs the question of how to balance a lethal opportunistic infection with AAV treatment to preserve organ function. The use of biologics has vastly improved AAV outcomes; greater than 90% of patients now achieve remission in what was once a deadly disease . However, this requires tolerance of immunosuppressive regimens, which almost always include high-dose corticosteroids, which may lead to infection and may be limited by renal impairment. In fact, infection is now the leading cause of death within the first year of AAV diagnosis rather than active disease . Our case is an example of how treatment can be repeatedly delayed due to active infection. After stabilization of the fungal disease, MRI was concerned for persistent infection in the cranium base, as seen in Figure 2. Rituximab, azathioprine, or another potent biologic could not be considered when the risk of mucormycosis reemergence was possible. Intravenous immune globulin (IVIG) had been discussed as an alternative to biologics, but our patient faced significant financial and social barriers obtaining this medication. One must also recall that its use in AAV is not discussed in the most recent treatment guidelines . At the time of this case, there were no alternatives available to steroids. However, avacopan, a steroid-sparing complement C5a receptor inhibitor, has recently received approval . Its performance in comparison with steroids was non-inferior, and it had a decreased risk of infection in comparison to glucocorticoids . Despite advancements in AAV treatment, mucormycosis remains a lethal infection, with the majority of cases diagnosed postmortem. A case described a diabetic AAV patient who expired shortly after presenting with a frontal headache, imaging consistent with sinusitis, and a cerebrovascular event attributed to an AAV flare. The diagnosis of mucormycosis was only established at autopsy . Our patient initially presented with right facial paresthesia and numbness associated with unilateral blurry vision of the right eye. Her symptoms were initially attributed to cranial nerve palsy secondary to severe hyperglycemia and an AAV flare. Only when she presented again with more classic mucormycosis symptoms, such as purulent green nasal discharge, did she receive an accurate diagnosis. This highlights the difficulty of distinguishing vasculitis from infections with similar presentations. One case of mucormycosis in a patient who presented with diabetic ketoacidosis after cyclophosphamide induction and three months of steroid treatment for idiopathic rapidly progressive glomerulonephritis has been described. However, this patient's renal disease was near remission, so prednisolone was discontinued soon after . In comparison, our patient still had active, rapidly progressive glomerulonephritis with worsening renal function. This is compounded by amphotericin B's nephrotoxicity, even when a lipid-based formulation is used. Studies have questioned whether there is a role for antifungal prophylaxis in immunocompromised patients, such as the case we have described here. However, there is little support for this due to increasing antifungal resistance and breakthrough mucormycosis infections . While our patient's diabetes may have potentiated the development of mucormycosis, the role of her autoimmune disease must be emphasized. It was due to MPA that she began chronic, high-dose corticosteroids, which is a risk factor for mucormycosis independent of diabetes . In a systemic review of mucormycosis in rheumatic diseases, Royer et al. found that the majority of patients (14/22) lacked a history of diabetes, yet all of them were exposed to corticosteroids . This hints that patients with rheumatic diseases or the treatment of these diseases may also modulate their risk of mucormycosis. In addition, one can speculate whether the local nasopharyngeal destruction caused by MPA may have created a nidus for the rhino-cerebral mucormycosis infection. Penetrating trauma has been known to predispose patients to mucormycosis. However, this is far more frequent in cutaneous forms of mucormycosis . Furthermore, due to our patient's MPA, there was a delay in the diagnosis, given the similarities in presentation between AAV and mucormycosis. This raises the concern that mucormycosis infections in AAV are underreported and likely undertreated, despite deadly outcomes. Another review of mucormycosis in patients with autoimmune conditions reported a higher mortality rate of 58% in this population, which may be due to delays in diagnosis and balancing immunosuppressive medications, both of which we described in our case . We recommend a high index of suspicion of mucormycosis in immunosuppressed patients. Additional reporting of these cases is necessary to develop alternative biologic and steroid-sparing, evidence-based treatment protocols that successfully achieve AAV remission without organ failure during an opportunistic infection. Conclusions Here, we presented the case of a patient with MPA who developed mucormycosis and survived despite delays in both the diagnosis of the deadly opportunistic infection and MPA treatment due to the active infection. Despite the patient's history of diabetes, this case highlights the barriers to early mucormycosis detection specific to vasculitis patients given the similar presentations between MPA and rhino-cerebral mucormycosis and reviews treatment alternatives, including avacopan and intravenous immune globulin therapy. It reinforces mucormycosis risk factors, such as steroid exposure, which are independent risk factors apart from diabetes, and highlights the need for more investigation regarding how destructive autoimmune processes themselves potentiate the risk of mucormycosis in addition to autoimmune disease treatments. As the global population of immunocompromised individuals increases, this case report is pertinent to increase discussions about balancing the diagnosis and treatment of autoimmune conditions with lethal opportunistic infections. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Microscopic polyangiitis Rheum Dis Clin North Am Chung SA Seo P 545 558 36 2010 20688249 2 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis Arthritis Rheumatol Chung SA Langford CA Maz M 1366 1383 73 2021 34235894 3 The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports Clin Microbiol Infect Jeong W Keighley C Wolfe R Lee WL Slavin MA Kong DCM Chen SC 26 34 25 2019 30036666 4 Global epidemiology of mucormycosis J Fungi (Basel) Prakash H Chakrabarti A 26 5 2019 30901907 5 Mucormycosis pathogenesis: beyond Rhizopus Virulence Spellberg B 1481 1482 17 2017 6 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis Ann Rheum Dis Suppiah R Robson JC Grayson PC 321 326 81 2022 35110332 7 Rhino-orbitocerebral mucormycosis in a patient with idiopathic crescentic glomerulonephritis Saudi J Kidney Dis Transpl Sanavi S Afshar R Afshin-Majd S 768 772 24 2013 23816728 8 Looks like a stroke, acts like a stroke, but it's more than a stroke: a case of cerebral mucormycosis J Stroke Cerebrovasc Dis Ermak D Kanekar S Specht CS Wojnar M Lowden M 0 4 23 2014 9 ANCA-associated vasculitis: an update J Clin Med Almaani S Fussner LA Brodsky S Meara AS Jayne D 1446 10 2021 33916214 10 Avacopan: first approval Drugs Lee A 79 85 82 2022 34826105 11 Avacopan for the treatment of ANCA-associated vasculitis N Engl J Med Jayne DR Merkel PA Schall TJ Bekker P 599 609 384 2021 33596356 12 Mucormycosis cerebral arteritis mimicking a flare in ANCA-associated vasculitis Lancet Infect Dis Royer M Cervera P Kahan A Menkes CJ Puechal X 182 110 13 2013 23347635 13 How I treat mucormycosis Blood Kontoyiannis DP Lewis RE 1216 1224 4 2011 14 Mucormycosis in systemic autoimmune diseases Joint Bone Spine Royer M Puechal X 303 307 81 2014 24603011 15 Epidemiology and outcome of zygomycosis: a review of 929 reported cases Clin Infect Dis Roden MM Zaoutis TE Buchanan WL 634 653 41 2005 16080086
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34910 Internal Medicine Allergy/Immunology Hematology Naproxen-Induced Evans Syndrome Muacevic Alexander Adler John R Ahoussougbemey Mele Ange 1 Chew Christopher 1 Ruiz Vega Ruben 1 Mahmood Riaz 1 AlRubaye Riyadh 1 1 Internal Medicine, Northeast Georgia Medical Center, Gainesville, USA Ange Ahoussougbemey Mele [email protected] 13 2 2023 2 2023 15 2 e3491013 2 2023 Copyright (c) 2023, Ahoussougbemey Mele et al. 2023 Ahoussougbemey Mele et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Evans syndrome is an autoimmune disorder characterized by the simultaneous occurrence of autoimmune hemolytic anemia and immune thrombocytopenic purpura. It can further be classified as primary Evans syndrome when it occurs by itself, or secondary Evans syndrome when it is associated with other autoimmune and lymphoproliferative disorders. Corticosteroids and immunoglobulins are the first-line treatments for primary Evans syndrome, and subsequent options include other immunosuppressive medications. Medical literature provides little information about the triggers of primary Evans syndrome. Knowing such information, however, is essential to recognize, treat and prevent the recurrence of the disease effectively. We report a 68-year-old female who presented with shortness of breath, cough, bruises, scleral icterus, and dark urine after several days of naproxen therapy for pain. Further workup noted direct antiglobulin test positive for IgG, anemia, and thrombocytopenia. Imaging studies showed deep venous thrombosis. She was diagnosed with Evans syndrome and improved following prompt treatment with corticosteroids, anticoagulants, blood transfusion therapies, and discontinuation of naproxen. The prognosis of Evans syndrome is poor, variable, and characterized by relapses. Early diagnosis and treatment are therefore associated with better prognosis. This case is critical because it shines a light on one of the major causes of Evans syndrome, reports a practical approach to treating the condition, and paves the way for future research on Evans syndrome. This case is also the first reported naproxen-induced Evans syndrome in the world's literature. hematology immune thrombocytopenic purpura autoimmune hemolytic anemia (aiha) naproxen evans' syndrome The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction A nationwide retrospective study performed in Denmark reporting 242 patients managed from 1977 to 2017 revealed the annual incidence of Evans syndrome was 1.8/million person-years, and the annual prevalence was 21.3/million persons . Evans et al. described Evans syndrome as a combination of autoimmune thrombocytopenia and AIHA in 1949 and 1951 . The widespread availability and use of non-steroidal anti-inflammatory drugs (NSAIDs) can contribute to the increased incidence of Evans syndrome. However, there needs to be more information regarding the precise mechanism of action of most nonsteroidal anti-inflammatory drugs. Naproxen is a cause of Evans syndrome that has remained unreported and warrants further research. Case presentation The patient is a 68-year-old female with a past medical history significant for chronic eosinophilia, chronic sinusitis, and environmental allergies who presented initially with shortness of breath and cough. She reported dark-colored urine after taking three doses of doxycycline prescribed for the treatment of sinusitis by her ENT physician. The patient moved to a new house within the last two weeks before arrival. Due to muscle pain, she had been using more cleaning detergents than usual and had taken increased amounts of naproxen over the past two weeks. The patient is also an active user of homeopathic medications but had not taken anything new over the last two years. The patient denied recent travels outside of the United States. A review of systems was positive for a bruise of the left lower extremity bilaterally, shortness of breath, cough, fatigue, and general weakness. Physical findings were notable for scleral icterus and jaundice. Upon arrival, the patient was in no acute distress and hemodynamically stable despite a hemoglobin of 6.1 g/dl. Other significant lab values included a platelet count of 62 K/uL, a white blood cell count of 18,000 K/uL, and a total bilirubin of 4.7 mg/dL, with the indirect bilirubin being 4.0 mg/dL. Further hemolytic anemia workup included a haptoglobin of less than one mg/dL, lactate dehydrogenase 1,555 U/L, a large amount of blood in the urine with negative red blood cells, 5.63% reticulocytes, and an immature reticulocyte fraction of 46.3%. Ferritin levels were 221.5 ng/ml, B12 923 pg /ml, folate 23.27 ng/ml, iron 279 ug/dl, and iron saturation of 92%. The direct antiglobulin test was positive for IgG and complement component 3 (C3). Also, the patient had a high eosinophilic percentage on the differential of 20%, and Pappenheimer bodies were present. Twelve hours after admission, the patient's hemoglobin was 5.4 g/dl, platelets of 34 k/ul with an immature platelet fracture of 14.1%, and a reticulocyte count of 26.73%. We started the patient on corticosteroids resulting in an up-trending hemoglobin and platelet count. A bone marrow biopsy demonstrated hypercellular bone marrow with erythroid hyperplasia, hypereosinophilia, and adequate non-erythroid iron stores . Figure 1 Core biopsy demonstrating hypereosinophilia, and hypercellularity with erythroid and megakaryocytic hyperplasia Figure 2 Core biopsy demonstrating hypereosinophilia, and hypercellularity with erythroid and megakaryocytic hyperplasia Peripheral smear was notable for severe anemia and thrombocytopenia with marked macrocytic anemia . Figure 3 Peripheral smear showing leukocytosis with hypereosinophilia and erythroblastosis, thrombocytopenia, and macrocytic anemia Figure 4 Peripheral smear showing leukocytosis with hypereosinophilia and erythroblastosis, thrombocytopenia, and macrocytic anemia Further workups while in the hospital for AIHA, which was negative, included lead screening, HIV, leukemia and lymphoma panel, hepatitis, fluorescence in situ hybridization (FISH) analysis, flow cytometry, antibodies to extract nuclear antigen, normal complement C3 and C4 levels, lupus anticoagulant, rheumatoid factor, antinuclear antibody (ANA), beta-2 glycoproteins, and Epstein-Barr virus. Positive tests included mycoplasma pneumonia IgG and parvovirus IgG. During her hospitalization, the computed tomography angiography (CTA) pulmonary was notable for minimal pulmonary thromboembolism findings with two small adherent filling defects representing thrombi in the right lower lobe pulmonary artery . The bilateral venous duplex was notable for deep venous thrombosis of the left peroneal vein. Figure 5 The CTA pulmonary was notable for minimal pulmonary thromboembolism findings with two small adherent filling defects representing thrombi in the right lower lobe pulmonary artery CTA: Computed tomography angiography The patient's blood counts remained stable, and she left the hospital on prednisone 60 milligrams daily for two weeks with a long taper to be managed by the hematology-oncology outpatient department for the diagnosis of Evan's syndrome, and apixaban 5 milligrams twice daily for three months for deep vein thrombosis and pulmonary embolisms. Discussion Evans syndrome is a rare autoimmune disorder characterized by autoimmune hemolytic anemia, immune thrombocytopenic purpura (ITP), and a positive direct antibody test for IgG. It can further be classified as a primary idiopathic disorder when it occurs by itself or as a secondary disorder in combination with other autoimmune or lymphoproliferative disorders. It is essential to distinguish between primary and secondary Evans syndrome as the treatment for both differs. As reported by Jaime-Perez et al., recent molecular theories explaining the pathophysiology of Evans syndrome include deficiencies in cytotoxic T-lymphocyte-associated antigen 4, lipopolysaccharide (LPS) response beige-like anchor protein, tripeptidyl peptidase two, and a decrease in the cluster of differentiation (CD)4/CD8 ratio . Moreover, while primary Evans syndrome is a diagnosis of exclusion, the diagnosis of secondary Evans syndrome requires the determination of the baseline disease. A Coomb's positive hemolytic anemia and positive antiplatelet antibodies are essential for Evans syndrome diagnosis. Clinicians rely on patient history, clinical evaluation, and laboratory exams to exclude other causes of AIHA and ITP. Our patient underwent extensive testing to rule out common conditions linked directly with AIHA and ITP. The precise cause of Evans syndrome in many patients is usually unknown. Thus, we must stress the importance of clinicians including Evans syndrome as a diagnosis in patients with AIHA and ITP when ruling out other etiologies. Keung et al. reported ace inhibitors as a cause of drug-induced Evans syndrome . Secondary Evans syndrome occurs with common variable immunodeficiency, systemic lupus erythematosus, an autoimmune lymphoproliferative syndrome in non-Hodgkin lymphoma, viral infections such as HIV and hepatitis C, Epstein-Barr virus infection, chronic lymphocytic leukemia and following allogeneic hematopoietic cell transplantation. As per Shaikh et al., the treatment options are different for both primary and secondary Evans syndrome, and pancytopenia is more severe in the setting of Evans syndrome than when presenting with AIHA and ITP alone . According to Sanford-Driscoll et al., a review of case reports, clinical studies, and in vitro research has shown that nonsteroidal anti-inflammatory drugs such as mefenamic acid, ibuprofen, sulindac, naproxen, tolmetin, feprazone, and aspirin are well-known culprits of cause autoimmune hemolytic anemia . Some of the most documented cases include mefenamic acid, which causes the condition by an autoimmune mechanism involving an anti-erythrocytic antibody of the IgG class , and aspirin which causes Evans syndrome by a complex immune mechanism. Our patient reported an increased naproxen intake in the days preceding her presentation. As such, naproxen is this patient's likely trigger of Evans syndrome. Per Barbaryan et al., drug-induced immune hemolytic anemia can be further classified depending on whether antibodies to the drug are present or absent . Drug-dependent antibodies are active only in the presence of the drug, whereas drug-independent antibodies are active in the absence of the drug. If the direct antiglobulin test is positive, an elution test to distinguish drug dependent from drug-independent antibodies is necessary. A negative elution test suggests drug-dependent antibodies since the drug is not present in vitro testing. In the case of drug-independent antibodies, both the direct antiglobulin test and the elution test will be positive. Drug-independent antibodies are almost identical to warm AIHA. The only way to distinguish both is to stop the causative agent and observe for the hematologic response. The treatment of drug-dependent antibodies is the discontinuation of the drug. In contrast, in the case of drug-independent antibodies, steroids should be added in addition to discontinuing the drug. Our patient's direct antiglobulin test was positive, and eluate evaluation was notable for pan agglutinin and warm autoantibodies. Her hematologic indices improved with the discontinuation of naproxen therapy and treatment with steroids. Naproxen causes Evans syndrome by a drug-independent antibody mechanism of action. According to Dhingra et al., bone marrow aspiration is necessary for the workup of Evans syndrome as it allows the clinician to rule out aplastic anemia or infiltrative disorders . The patient's bone marrow core biopsy was notable for hypercellularity with erythroid hyperplasia and mild megakaryocytic hyperplasia. It also demonstrates hypereosinophilia. Prussian blue stain showed adequate non-erythroid iron stores and was negative for increased ring sideroblasts. Furthermore, a peripheral blood smear was notable for leukocytosis with hypereosinophilia, erythroblastosis, thrombocytopenia, and macrocytic anemia. The patient's bone marrow and peripheral blood demonstrated reactive changes in response to AIHA, including erythroid hyperplasia, erythroblastosis, and polychromatophilia . A myeloid neoplasm was not seen based on the bone marrow's morphologic appearance, and flow cytometry showed no evidence of hematopoietic neoplasm. According to Norton et al., the first-line treatment for primary Evans syndrome involves corticosteroids, often administered with intravenous immunoglobulins . As per Godeau et al., steroids inhibit the ability of macrophages to clear platelets and erythrocytes, whereas immunoglobulins IgG blocks fragment crystallizable (Fc) gamma receptors on macrophages, thus hindering their effector functions such as phagocytosis . When there is no response to first-line therapies, the clinician can use second-line therapy. Rituximab is an anti-CD20 monoclonal antibody used in cases the disease process is refractory to corticosteroid therapy or relapses into Evans syndrome. Furthermore, other efficacious second-line interventions include mycophenolate mofetil which inhibits inosine monophosphate dehydrogenase, thus reducing lymphocyte proliferation. Howard et al. reported its efficacy in treating AIHA and ITP . Cyclosporine is an immunosuppressive medication that acts by inhibiting the activation of T-cells. As reported by Jaime-Perez et al., multiple studies have shown its efficacy in patients who have failed to respond to corticosteroids, intravenous immunoglobulins, and other immunosuppressants. Twenty-six out of the 28 patients treated with cyclosporine had achieved a good response to therapy . Finally, rituximab replaced splenectomy as a second-line treatment due to risks associated with surgery and the heterogeneous response noted in the treatment of Evans syndrome between 0% to 66% . Third-line agents include the alkylating agent cyclophosphamide, the anti-CD52 monoclonal antibody alemtuzumab, and thrombopoietin receptor agonists. As noted above, our patient responded well to first-line therapy with corticosteroids. When treating our thrombocytopenic patient, another important question asked was whether or not to use anticoagulants. As postulated by Balitsky et al., the two main premises are that a low platelet count does not protect from thrombosis, and in general, thrombotic complications are more dangerous than bleeding . Despite the available treatment options mentioned above, the prognosis of Evans syndrome is poor, variable, and characterized by relapses. A study by Michel et al. described the characteristics and outcomes of Evans syndrome in adults. Sixty-eight adults were selected, amongst which 34 patients had primary Evans syndrome and 34 had secondary Evans syndrome. All patients received corticosteroids, and 50 required a second-line treatment such as splenectomy and rituximab. After a mean follow-up of 4.8 years, 22 patients (32%) were in remission and off treatment. However, 16 patients (24%) died . A cohort study conducted in Denmark noted that the most common causes of death in Evans syndrome were bleeding, infections, and hematological cancer . It accentuates the importance of close follow-up of patients with Evans syndrome upon discharge from the hospital to ensure compliance with the care plan, monitor responses to therapy, and monitor comorbidities. Conclusions Drug-induced Evans syndrome is a potentially fatal complication of naproxen therapy. It is, therefore, essential to include Evans syndrome in the differential diagnosis of patients presenting with AIHA and ITP. Prompt discontinuation of NSAIDS and treatment with steroids can be lifesaving interventions. Our case reports naproxen as a novel culprit of drug-induced Evans syndrome and proposes an efficacious treatment approach. Human Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study References 1 Evans syndrome in adults - incidence, prevalence, and survival in a nationwide cohort Am J Hematol Hansen DL Moller S Andersen K Gaist D Frederiksen H 1081 1090 94 2019 31292991 2 Evans syndrome: clinical perspectives, biological insights and treatment modalities J Blood Med Jaime-Perez JC Aguilar-Calderon PE Salazar-Cavazos L Gomez-Almaguer D 171 184 9 2018 30349415 3 Drug-induced Evans syndrome Ann Intern Med Keung YK Mallarino MC Cobos E 327 128 1998 4 Evans Syndrome Shaikh H Mewawalla P Treasure Island, FL, USA StatPearls 2021 5 Induction of hemolytic anemia by nonsteroidal antiinflammatory drugs Drug Intell Clin Pharm Sanford-Driscoll M Knodel LC 925 934 20 1986 3545733 6 Autoimmune hemolytic anemia induced by mefenamic acid Schweiz Med Wochenschr Farquet JJ Dayer JM Miescher PA 1510 1512 108 1978 705303 7 Ibuprofen-induced hemolytic anemia Case Rep Hematol Barbaryan A Iyinagoro C Nwankwo N 142865 2013 2013 23710383 8 Evans syndrome: a study of six cases with review of literature Hematology Dhingra KK Jain D Mandal S Khurana N Singh T Gupta N 356 360 13 2008 19055865 9 Management of Evans syndrome Br J Haematol Norton A Roberts I 125 137 132 2006 16398647 10 Treatment of idiopathic thrombocytopenic purpura in adults Presse Med Godeau B Bierling P 1292 1298 37 2008 18644317 11 Mycophenolate mofetil for the treatment of refractory auto-immune haemolytic anaemia and auto-immune thrombocytopenia purpura Br J Haematol Howard J Hoffbrand AV Prentice HG Mehta A 712 715 117 2002 12028047 12 The use of anticoagulants in patients with thrombocytopenia Hematologist Balitsky A Arnold D 15 2018 13 The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases Blood Michel M Chanet V Dechartres A 3167 3172 114 2009 19638626
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Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34907 Endocrinology/Diabetes/Metabolism Internal Medicine Epidemiology/Public Health Prevalence of Overweight and Obesity in Jamaica From 2000 to 2016 Muacevic Alexander Adler John R Chambers Kevoyne H 1 Reid Rysheme M 2 Samuels Shania C 2 Cranston Sashana S 1 Barnes Orbin 3 Palmer Orlando D 4 1 Medicine, Jiangsu University, Zhenjiang, CHN 2 Medicine, Nanjing Medical University, Nanjing, CHN 3 Medicine, Jinzhou Medical University, Jinzhou, CHN 4 Hematology and Oncology, University Hospital of the West Indies, Kingston, JAM Kevoyne H. Chambers [email protected] 13 2 2023 2 2023 15 2 e3490712 2 2023 Copyright (c) 2023, Chambers et al. 2023 Chambers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from The prevalence of overweight and obesity in Jamaica has been steadily increasing over the past decade and is now a significant health issue. This paper focuses on the trends in the prevalence of overweight and obesity in Jamaica from 2000 to 2016. Overweight and obesity prevalence in adults increased from 43.8% in 2000 to 55.5% in 2016, from 34.2% in 2000 to 47.4% in 2016in adult males, and from 53.0% in 2000 to 63.6% in 2016 in adult females. In children/adolescents aged 10 to 19 years, the prevalence of obesity has doubled between 2000 and 2016. The data shows that the prevalence of overweight and obesity in children/adolescents increased from 5% in 2000 to 11.4% in 2016, from 4.4% in 2000 to 11.0% in 2016 in boys, and from 5.5% in 2000 to 11.9% in 2016 in girls. trends overweight obesity jamaica caribbean The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction The term overweight is defined as a body mass index (BMI) of over 25 kg/m2, while obesity is defined as a BMI of over 30 kg/m2 . Overweight and obesity have become significant global public health concerns with severe health, psychological, and economic burdens . The prevalence of overweight and obesity has been steadily increasing over the past four decades in both developed and developing countries . According to the World Health Organization (WHO), in 2016, more than 1.9 billion adults were overweight, and 650 million were obese. Being overweight and obese is associated with numerous health complications. The common ones are inflammation, diabetes mellitus, and cardiovascular disease. However, multiple studies have shown that there is an associated cancer burden in people with excess body weight; the ones with the most evidence are breast cancer, endometrial cancer, esophageal adenocarcinoma, and kidney cancers . There is also a link between asthma and obesity in childhood . Studies have also shown that severely obese people are at high risk for depression due to poor body image . Obesity can also have a severe financial burden on a country's economy . Based on a study conducted in 2015 the direct cost of diabetes mellitus in Jamaica was between US 567 million and US 765 million dollars . In 2017, Jamaica estimated that cardiovascular diseases and diabetes combined will cost US 77 billion dollars over the next 15 years, this involves treatment costs and the loss of productivity from persons who are affected within those two categories alone . These are all health complications that are associated with being overweight and obese. The prevalence of overweight and obesity has increased substantially and is now a significant health concern for Jamaica. In 2016 24.7%, approximately one in four adults in Jamaica were obese. That same year the country ranked 55 out of 191 countries worldwide based on the percentage of the adult population that was obese and ranked fourth among Caribbean Community and Common Market (CARICOM) member states . This report aims to describe the trends in the prevalence of overweight and obesity in Jamaica from 2000 to 2016. Data from the Pan American Health Organization (PAHO) shows a steady increase in the prevalence of overweight and obesity in Jamaica. Analyzing and highlighting the relevance of this data is vital to help reduce the prevalence of overweight and obesity throughout the next decade. Therefore, this may aid in establishing a solid foundation for better analysis of the root problem in the region so that prevention and treatment strategies may be better implemented. Materials and methods Study design This was a secondary analysis study of data obtained from the PAHO database . The data available for the prevalence of overweight and obesity from 2000 to 2016 among the Jamaican population was analyzed and summarized for both the adult and children/adolescent cohorts. Data collection The data used was collected from the PAHO core indicators database. The PAHO core indicators database provides the latest data on health indicators for 49 countries and territories in the Region of the Americas. The primary sources used to create these health indicators are demographic censuses, national health information systems, population surveys, and data from health facilities . Data analysis Values were expressed as a percentage of the population. The data obtained was organized and tabulated within Microsoft Excel (Microsoft Corp., Redmond, WA, USA). Further analysis to obtain the p-value and correlation of data was done using the SPSS (IBM Corp., Armonk, NY, USA) statistics tool. Results An overview of the data obtained from the PAHO on the prevalence of overweight and obesity from 2000 to 2016 in the Jamaican population is presented in Table 1. Figure 1 highlights the trend of overweight and obesity among adults, while Figure 2 highlights the trend of overweight and obesity among children/adolescents from 2000 to 2016. Table 1 Available data on overweight and obesity prevalence in Jamaica from 2000 to 2016 Source: Pan American Health Organization Indicator 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Prevalence of obesity in adults (%) 43.8 44.5 45.3 46.0 46.8 47.5 48.3 49.0 49.7 50.4 51.2 51.9 52.6 53.4 54.1 54.8 55.5 Prevalence of obesity in adults (%); male 34.2 35.0 35.8 36.6 37.4 38.2 39.0 39.8 40.7 41.5 42.3 43.1 44.0 44.8 45.7 46.5 47.4 Prevalence of obesity in adults (%); female 53.0 53.6 54.3 55.0 55.7 56.3 57.0 57.6 58.2 58.9 59.5 60.1 60.7 61.4 62.0 62.6 63.2 Prevalence of obesity in children/adolescents aged 10-19 years (%) 5.0 5.3 5.6 5.9 6.3 6.7 7.1 7.5 7.9 8.3 8.7 9.2 9.6 10.0 10.4 10.9 11.4 Prevalence of obesity in children/adolescents aged 10-19 years (%); male 4.4 4.7 5.0 5.4 5.7 6.1 6.5 6.9 7.3 7.8 8.2 8.6 9.0 9.4 9.9 10.4 11.0 Prevalence of obesity in children/adolescents aged 10-19 years (%); female 5.5 5.8 6.2 6.5 6.9 7.3 7.7 8.1 8.5 8.9 9.3 9.7 10.1 10.5 11.0 11.4 11.9 Figure 1 Prevalence of overweight and obesity trends in adults (%) in Jamaica from 2000 to 2016 Figure 2 Prevalence of overweight and obesity trends in children/adolescents aged 10 to 19 years (%) in Jamaica from 2000 to 2016 The data showed that the prevalence of overweight and obesity among the Jamaican population had been steadily increasing from 2000 to 2016, with the prevalence of overweight and obesity among the children/adolescents population doubling. From 2000 to 2016, there was a 13.2% and 10.2% increase in the prevalence of overweight and obesity in adult males and adult females, respectively. The average prevalence of overweight and obesity over the 16 years for adult males was 40.71% (standard deviation (SD)=4.16), while for adult females it was 49.69% (SD=3.70). In the children/adolescents population, there was a 6.6% increase in the male cohort and a 6.4% increase in the female cohort. The average prevalence of overweight and obesity over the 16 years for boys was 7.43% (SD=2.07), while for girls it was 8.45% (SD=2.02). Overall, the increase in the prevalence of overweight and obesity in the adult population was 10.2% with an average of 58.12% (SD=3.23) and 6.4% in the children/adolescents population with an average of 7.99% (SD=2.04). Discussion Being overweight and obese are serious and important issues for Jamaica. Obesity-related comorbidities such as diabetes mellitus and cardiovascular diseases have become one of the leading causes of death in the Jamaican population, with cardiovascular diseases alone accounting for 27% of deaths under 70 years . This indicates that appropriate prevention and treatment strategies are both crucial issues for the country. Adolescents/children with obesity are more likely to develop other serious health issues. Childhood obesity is associated with a higher chance of more aggressive asthma attacks, premature death, and disability in adulthood. Additionally, obese children may experience psychological issues such as depression . Given the long-term impact of obesity on children and the rapid rate of increase in its prevalence, acknowledging and tackling this issue is essential for the sustained health of Jamaican youth. In 2000, the prevalence of overweight and obesity was 34.2% in adult males, and 53.0% in adult females. In 2016 these percentages rose to 47.4% in adult males and 63.2% in adult females, which shows that the prevalence of overweight and obesity is much higher in adult females compared to adult males. Another crucial point to consider is that while the prevalence of obesity and overweight is higher in adult females, the absolute increase in adult males was 13.2% (p<0.01). In comparison, it was 10.2% in adult females (p<0.01), suggesting that the prevalence of overweight and obesity is increasing faster in adult males compared to adult females. In 2016, the prevalence for both genders was 55.5%, an 11.7% increase from the prevalence for both genders in 2000, which was 43.8%. For some context, the global prevalence of overweight and obesity in 2016 was 39.0%, which would put the prevalence of overweight and obesity among adults in Jamaica at 16.5% higher than the global average. In 2000, the prevalence of overweight and obesity in adolescents aged 10 to 19 years was 4.4% in males and 5.5% in females. These figures climbed to 11.0% and 11.9% in 2016. Females consistently maintained a higher prevalence of overweight and obesity throughout the 16 years. However, the absolute increase in the prevalence amongst males in this cohort is a significant observation to note as well. There was a 6.6% increase in males (p<0.01); in comparison, females had a lower absolute increase of 6.4% (p<0.01), indicating that even though the prevalence of obesity and overweight was higher in females, the rate of increase was slightly higher in males. In 2016 the prevalence for both genders was 11.4%, a 6.4% increase from the prevalence for both genders in 2000 which was 5.0%. The global prevalence of overweight and obesity among adolescents in 2016 was 18% . Jamaica's prevalence of overweight and obesity was only 6.6% lower than the global average. In 2011 the ministry of health, per the ministry of education in Jamaica, conducted a health-promoting school survey . The objective of this study was to gather data to aid in establishing policies and programs for school health. The study looked at various indicators that affect students' health in 60 schools across the 14 parishes of the country. This was an excellent initiative to promote proper health awareness among children/adolescents. However, this strategy should also be implemented in other sectors of the country. Health education should be provided to all people at all levels on the critical impacts of overweight and obesity on children and adults, thus increasing the public's awareness. This may be achieved through multilevel community and school-based interventions . Additionally, the prevalence of obesity may also be managed by implementing fitness programs in the curriculum of educational facilities and workplaces. A major limitation of this study is that the data analyzed and presented could only show the prevalence of overweight and obesity in the Jamaican population from a general perspective . The data available do not allow for analysis of the prevalence of overweight and obesity in various subgroups and geographical locations across the country. Conclusions The data reflects a significant increase in the prevalence of overweight and obesity in adults and children/adolescents in the Jamaican population between 2000 and 2016. For both age groups, females consistently had a higher prevalence than males. However, the data for males in both cohorts reflected a more significant rate of increase in the prevalence of overweight and obesity between 2000 and 2016. Orlando D. Palmer is the senior author of this paper. Human Ethics Animal Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. References 1 Obesity 1 2023 2023 2 Overweight and obesity: prevalence, consequences, and causes of a growing public health problem Curr Obes Rep 1 2023 Williams EP Mesidor M Winters K Dubbert PM Wyatt SB 363 370 4 2015 26627494 3 Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013 Lancet Ng M Fleming T Robinson M 766 781 384 2014 24880830 4 Global patterns in excess body weight and the associated cancer burden CA Cancer J Clin Sung H Siegel RL Torre LA 88 112 69 2019 30548482 5 The asthma-obesity link in childhood: open questions, complex evidence, a few answers only Clin Exp Allergy Matricardi PM Gruber C Wahn U Lau S 476 484 37 2007 17430342 6 Depression in association with severe obesity: changes with weight loss Arch Intern Med Dixon JB Dixon ME O'Brien PE 2058 2065 163 2003 14504119 7 Economic burden of obesity: a systematic literature review Int J Environ Res Public Health Tremmel M Gerdtham UG Nilsson PM Saha S 14 2017 8 The cost of diabetes in Latin America and the Caribbean in 2015: evidence for decision and policy makers J Glob Health Barcelo A Arredondo A Gordillo-Tobar A Segovia J Qiang A 20410 7 2017 9 Cardiovascular diseases and diabetes to cost $77 billion over next 15 years, Jamaica Information Service 2 2023 2017 10 Most obese countries in the world 2 2023 2022 11 Core indicators dashboard, PAHO/EIH Open Data 1 2023 2022 12 Health Indicators. Conceptual and operational considerations Health Indicators. Conceptual and operational considerations Pan American Health Organization Washington, D.C., USA PAHO 2018 13 Noncommunicable diseases data portal, Country profile 1 2023 14 Psychological aspects of obesity in children and adolescents Indian J Pediatr Sagar R Gupta T 554 559 85 2018 29150753 15 Health promoting school survey 2011 Chin D McFarlane N L Kingston, Jamaica Ministry of Health Jamaica 2013 16 Multilevel interventions to prevent and reduce obesity Curr Opin Endocr Metab Res Vo L Albrecht SS Kershaw KN 62 69 4 2019 31538131 17 Secondary analysis research J Adv Pract Oncol Wickham RJ 395 400 10 2019 33343987
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press 10.1136/postgradmedj-2020-137917 postgradmedj-2020-137917 Letter AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 COVID-19 and remote consulting strategies in managing trauma and orthopaedics Iyengar Karthikeyan Department of Orthopaedics, Southport and Ormskirk Hospital NHS Trust, Southport, UK Vaish Abhishek Department of Orthopaedics, Indraprastha Apollo Hospital, New Delhi, India Toh Eugene Department of Orthopaedics, Southport and Ormskirk Hospital NHS Trust, Southport, UK Vaishya Raju Department of Orthopaedics, Indraprastha Apollo Hospital, New Delhi, India Correspondence to Dr Karthikeyan Iyengar, Department of Orthopaedics, Southport and Ormskirk Hospital NHS Trust, Southport PR8 6PN, UK; [email protected] 7 2020 13 5 2020 13 5 2020 96 1137 438439 05 5 2020 (c) Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. 2020 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] telemedicine orthopaedic & trauma surgery adult orthopaedics trauma management diagnostic radiology pmcAs the COVID-19 pandemic took hold, the effect on healthcare systems, its resources and clinical services have been profound. With the novel coronavirus outbreak being highly contagious, there has been an ever urgent need to devise and identify new models of delivering care to avoid 'face-to-face' consultation between clinician and patient and thus reducing the risk of disease transmission. Managing acute trauma and orthopaedics had to be rationalised, reorganised and modified as new guidelines1 2 came into practice. In the UK, the National Health Service England Specialty Guides3 offers the primary guidance and forms the basis of all National Health Service (NHS) Trusts' responses to this pandemic. Current and evolving telecommunication technologies play a key role in exchange of valid information for diagnosis and management of diseases and injuries. The main modalities for remote consultations include telephone consultations, virtual fracture clinics (VFC) and video consultations (VCs). Remote telephone or VCs provide a vital strategy in the delivery of trauma and orthopaedic healthcare where prevention of disease transmission, for example, current COVID-19 outbreak is of paramount importance by avoiding face-to-face consultation. However, they are appropriate in settings where a clinical interaction can occur over telecommunication channels to provide a continuity of care. Telephone consultations form the primary and readily available modality of remote access alternative to face-to-face consultations to deliver patient care.4 It allows most of the suitable reasons when remote consultation would be appropriate with some limitations.5 It can provide a means of assessing clinical condition and discussing options for managing conditions remotely, for example, assessment of pain advice such as increasing or decreasing doses of medications or suggesting use of complimentary walking aid to improve mobility after recent surgery. It facilitates 'risk stratifying' a patient. For example, a patient who reports redness and pain around the postoperative wound site following recent hip surgery is at risk of surgical site infection and is actioned to be seen imminently for clinical examination. 'Safety advice' regarding weight-bearing status after limb surgery, for example, moving from two crutches to one following hip replacement surgery or advice regarding driving following an ankle injury can be given over telephone provided both the clinician and patient are fully aware of the boundaries of assessing patients this way. 'Safety netting' telephone consultations can be a means of assessing problems after interventions; for example, if a patient is being managed with a plaster of Paris cast for an ankle fracture or tendo-achilles injury, they can be risk assessed about symptoms of deep venous thrombosis (DVT), given appropriate advice regarding whom to contact according to local DVT management pathways or arrangements made for face-to-face evaluation. VFC is essentially an extended application from telephone consultation. It is a multidisciplinary set-up and decision-making involving the clinician, physiotherapist or advance nurse practitioner to provide therapy guidance and administrative support to type letters. In the field of trauma and orthopaedics, VFCs are an alternative to conventional face-to-face fracture clinics and are increasingly being used to manage certain musculoskeletal injuries.6 They allow initial assessment by a senior doctor from clinical history and imaging. Following this, a remote consultation is undertaken with the patient with advice and instructions for them to 'self-manage' their injury. A detailed letter is sent to the general practitioner (GP) with a copy to the patient with a clear diagnosis and treatment plan in terms that can be easily understood by a layperson. On the other hand, if the clinical situation necessitates a face-to-face consultation an appointment is made in the appropriate subspecialty fracture clinic. There is an option to arrange further imaging, for example, radiographs, MRI or CT scan prior to the face-to-face appointment. This service depends on an integrated 'electronic patient record' and 'picture archiving and communication imaging systems' that can be accessed remotely to review the case. The patient would also need to be able to be easily contactable for the VFC review. Many acute musculoskeletal injuries can be managed remotely for example, posting out patient information leaflets or signposting patients to web-based resources for managing common, stable soft issue or bony injuries such as ankle sprains or metatarsal fractures of the foot. This is particularly relevant in the current COVID-19 pandemic and supported by the British Orthopaedic Association emergency specialty guidelines.1 NHS England and NHS improvement7 have increased support to encourage secondary care providers to use VCs for managing patient care in appropriate situations. VC forms a part of wider strategy for remote management of trauma and orthopaedic conditions building on telephone and VFC consultations. Various documents including user guides to support providers with rolling out of VCs have been produced by NHS England and NHS Improvement7 as part of national digital strategy. Complementary articles on when VC are appropriate and processes in carrying out VCs have been recently published in literature.8 9 With advantages of high satisfaction among staff and patients and lower transaction costs compared with traditional clinic based care, VC may have found its opportunity in reaching the next step in the ladder of remote management of patients in current pandemic.8 Though VC is a highly promising technology which compliments telephone remote consultations, introducing VC can be a complex organisational change.8 Clinician and staff reservations about technical abilities required and operational issues can be barriers. However, the advantages of VC can be significant from general applications; for example, for patients' who do not need a physical examination and who can communicate via video to 'triage' and remote management of orthopaedic injuries. Furthermore, telecommunication, webinars and virtual learning can provide education and training to clinicians about managing patients in such circumstances.10 In a wider context, multidisciplinary team departmental trauma meetings, normally attended by orthopaedic team members, trauma coordinators, theatre staff and anaesthetists departments, could be undertaken by remote teleconference to formulate plan of management for patients, including the ability to view radiology images and surgical planning if necessary; for example, patients with complex fractures can have planned surgery to minimise length of stay or consider day-case treatment for periarticular fractures. This allows a coordinated team approach. Follow-up appointments can be delivered by telephone or video call in most instances especially with the current COVID-19 situation. A patient-initiated follow-up process can be organised and booked appointments should preferably be made only where it is unavoidable, for example, follow-up imaging required which may necessitate significant change in clinical management. In managing rehabilitation services, when face-to-face meetings are likely to be limited, for example, current coronavirus outbreak, musculoskeletal triage appointments can be undertaken by the physiotherapists and occupational therapists. Patients can be given appropriate tele-advice or 'signposted' to alternative resources such as written or web-based information to allow rehabilitation at home, for example, rehabilitation after hip surgery or therapy goals after recent joint replacement surgery. Medical telephone consultations have limitations; for example, inability to carry out a full clinical assessment and thereby may not be able to address a particular clinical problem or injury. Absence of visual clues and lack of physical examination are the key drawbacks. This can be overcome by enhanced documentation, shared decision-making and pragmatic management. Sending a copy of the letter to the patient and the GP, following the consultation will reinforce what was discussed in the consultation and minimise misunderstanding. Thus, though studies have reported that patients' are equally satisfied with both forms of consultation, that is, face-to-face and telephone, they do not necessarily reduce workload for clinicians.4 As strategies emerge and are emerging during the COVID-19, the way we deal with managing trauma and orthopaedics is likely to change in the future with increasing use of VFC in fracture care and tele-VCs in monitoring chronic orthopaedic conditions. Evolving mobile phone technologies will take these remote consultation strategies further. Footnotes Contributors: KPI provided the idea for the article and wrote the manuscript. ET and AV involved in researching relevant literature and references and edited the manuscript. RV involved in review of manuscript and approved the final draft. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; externally peer reviewed. References 1 British Orthopaedic Association . Speciality guidelines, 2020. Available: [Accessed 15 Apr 2020]. 2 NHS England and NHS Improvement Coronavirus . Specialty guides-Orthopaedic trauma, 2020. Available: content/uploads/sites/52/2020/03/C0070-specialty-guide-major-trauma-clinical-guide-14 .pdf 3 NHS England and NHS Improvement Coronavirus . Specialty guides for patient management secondary care, 2020. Available: [Accessed 15 Apr 2020]. 4 van Galen LS, Car J. Telephone consultations. BMJ 2018;360 :k1047.10.1136/bmj.k1047 29599197 5 Iyengar K, El-Nahas W. A brief guide to telephone medical consultation. British J Healthcare Manag 2020;26 :1-3.10.12968/bjhc.2020.0032 6 Logishetty K, Subramanyam S. Adopting and sustaining a Virtual Fracture Clinic model in the District Hospital setting - a quality improvement approach. BMJ Qual Improv Rep 2017;6 u220211.w7861.10.1136/bmjquality.u220211.w7861 7 Remote consultations . NHS England and NHS improvement coronavirus. specialty guides for patient management, 2020. Available: [Accessed 15 Apr 2020]. 8 Greenhalgh T, Wherton J, Shaw S, et al. Video consultations for covid-19. BMJ 2020;368 :m998.10.1136/bmj.m998 32165352 9 Greenhalgh T, Vijayaraghavan S, Wherton J, et al. Virtual online consultations: advantages and limitations (vocal) study. BMJ Open 2016;6 :e009388.10.1136/bmjopen-2015-009388 10 Lison T, et al. VISION2003: virtual learning units for medical training and education. Int J Med Inform 2004;73 :165-72.10.1016/j.ijmedinf.2003.11.025 15063376
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press 32404491 10.1136/postgradmedj-2020-138027 postgradmedj-2020-138027 Editorial AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 Clinical and health policy challenges in responding to the COVID-19 pandemic Singer Donald Fellowship of Postgraduate Medicine, London, UK Correspondence to Dr Donald Singer, Fellowship of Postgraduate Medicine, London W1G 9EB, UK; [email protected] 7 2020 13 5 2020 13 5 2020 96 1137 373374 28 4 2020 29 4 2020 (c) Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. 2020 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] health policy epidemiology infection control pmcSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease 2019 (COVID-19) pandemic, is the worst challenge for a century for international health and financial systems. It was declared a global pandemic on 11 March 2020, 6 weeks after it had first been reported from China as a new respiratory virus.1 By then, 118 000 cases had been reported from 114 countries and 4291 people reported to have lost their lives.1 Only 7 weeks later, as of 5 May, 3 544 222 cases of COVID-19, including 250 977 deaths, have been reported from 187 countries and regions, and maritime quarantine.2 While severity and mortality have been highest in people with underlying morbidities,3 no age group is immune from COVID-19 nor are the rich and famous. Reasons are unclear for more severe disease in males and, at least in the UK and USA, in ethnic minority groups. Members of many governments have been affected, including the British Prime Minister Boris Johnson, now discharged from hospital after a spell in intensive care. Reported mortality varies widely between countries with apparently similar economic development.4 Influences on reported case fatality ratios the number of deaths divided by the number of reported cases include the number tested, who is tested, test accuracy, demographics for age and comorbidity, and capacity and standards of healthcare staff and facilities. More reliable data, reported mortality, on 5 May ranged in the worst affected countries in Europe, for example, from 80 in Germany to 423 in the UK, 481 in Italy and 684 in Belgium per million in the general population2 and in North America 102 per million in Canada but 204 per million in the USA.2 These figures may reflect considerable underestimates of actual mortality, as deaths from COVID-19 among care home residents and deaths at home are typically not included. National and international responses to COVID-19 are proving exacting tests of how effectively science and politics can work together to protect the public health and wealth of nations. In our globally connected world, an obvious expectation is that citizens are protected from avoidable risk from communicable diseases. Humanitarian expectations extend to ensuring that less developed countries are also able to cope with epidemics. Public health approaches have included a portfolio of measures including border controls, restrictions on national and international travel, isolating the public at home, except for essential workers, quarantining contacts of affected patients, complimented by diagnostic testing, health screening, contact tracing and use of surveillance apps.5 There has also been dramatic scaling up of provision of intensive care facilities through, for example, use of conference centres as temporary hospitals in the UK, to new hospital building in China and field hospitals, for example, in Central Park in New York City. There has also been major recruitment internationally of medical students and retired health professionals to help contact, trace and manage patients with active COVID-19 infection. However, many diagnostic tests and digital health solutions are unreliable and are in use without proper evaluation.6 There are also concerns about surveillance apps about the trade-off between health versus privacy.6 There are serious gaps in response to the disease even in highly developed economies and healthcare systems. In the UK for example, it appeared to take modelling data from Ferguson's group7 to persuade the government and its advisors to move rapidly from a 'herd immunity' stance to a national lockdown strategy. The delay in China's reporting early cases did not help.8 Nor has the now revealed under-reporting to international public health authorities of mortality in China at least 50% higher than initially reported.9 'Fake news' has also complicated public responses to COVID-19 in many countries. This ranges from considering the virus the result of bioterrorism, to a disease caused by 5G wireless masts. Fake medicines are also a concern with (typically internet) vendors exploiting fears and concerns by falsely claiming that their products can treat or prevent COVID-19.10 To date, South Korea, which has a stringent detect, test, isolate, treat and contact trace policy, has reportedly had the greatest success in containing COVID-19. In the 14 days to 5 May, South Korea reported 2.4 new cases of COVID-19/million population and since the start of the pandemic 5.0 COVID-19 attributable deaths/million population, compared for example with the USA which, in the same two week period, reported 1203 new cases of COVID-19/million population and 204 COVID-19 attributable deaths/million population since the start of the pandemic.2 The European Union (EU) is showing its capacity to co-ordinate responses at several key levels. The EU's Centre for Disease Prevention and Control is an important resource for information about the virus.2 The EU is also co-ordinating member states in consortia aimed at commissioning essential medical supplies. The EU regulator, the European Medicines Agency, is working with other regulators, including the US Food and Drug Administration, to support research and development of new treatments, from vaccines for disease prevention to new or repurposed medicines for use during active SARS-COVID-19 disease. Among over 100 candidate treatments for COVID-19, the following currently authorised medicines are already undergoing clinical trials of their safety and effectiveness: the anti-HIV medicines lopinavir/ritonavir, chloroquine and hydroxychloroquine (authorised as anti-malarials and as anti-inflammatory treatments for autoimmune diseases, eg, rheumatoid arthritis), the investigational anti-viral agent remdesivir, and interferons and immune-modulating monoclonal antibodies.10 Several vaccines are already in phase I clinical trials in healthy volunteers.10 However, based on previous experience of vaccine development, even the new GSK-Sanofi vaccine partnership11 estimates that 12-18 months may be needed to provide adequate supplies of effective vaccines for the EU region alone. Personal protective equipment (PPE: masks, gowns, gloves and eye protection) for health professionals should be of high quality, be personalised for fit and be changed between patients. Among highly developed countries, the UK appears to be particularly unsuccessful in providing international standard PPE in sufficient quantities for acute healthcare staff and for the social care sector. Early approaches by UK manufacturers to provide supplies appear to have been largely ignored by the UK government in favour of international sources which, many weeks into the pandemic, have not as yet proved to be able to meet essential UK demand.12 The UK has also been very late in engaging with EU-led commissioning consortia to secure further PPE supplies and reportedly too late to join EU-led approaches to secure ventilators.12 There are continuing widespread reports in the UK of health professional staff not being provided with adequate PPE. If these reports are correct, the consequences are unacceptable avoidable deaths from COVID-19 in health professionals and their unaffected patients and social contacts. Use of face masks by the public is customary within East Asia. Concerns elsewhere about their use by the public include mask quality, over-confidence leading to less attention to social distancing, and with masks being in scarce supply, reduced availability for health professionals. Equipoise in other developed countries is however moving towards the precautionary principle.13 Face masks, for example, appear more likely to reduce risk of viral transmission, limiting particulate spread during speech, coughing and sneezing.13 The UK administration is not atypical in having prioritised economics over public health in rejecting recommendations of scientists within pandemic preparedness initiatives. In 2005, the then US President George W Bush launched an unsuccessful call at the US National Institutes of Health for a three-part approach, involving raising public awareness about epidemics and action needed, stockpiling PPE and other supplies, and acquiring rapid systems to develop treatments against major threats from communicable disease.14 An expected side effect of economic downturn because of COVID-19 has been a remarkable decrease in atmospheric pollution,15 a well-recognised contributor to severity of many clinical disorders, from heart and lung disease to cancers. Outcomes from COVID-19 appear worse in people historically exposed to atmospheric particulate pollutants and the inflammatory gas nitrogen dioxide.15 This should contribute to evidence to influence political support for continued reduction in harmful emissions into the atmosphere to reduce the severity of any future recurrent waves of COVID-19. International co-ordination is inconvenient for countries where business and other interests are pushing for early relaxation of public health controls. The USA is doing its best to undermine the WHO as a forum to plan for resolving the COVID-19 pandemic and for better preparedness for future pandemic infections.16 Tan and his colleagues from Toronto have put the case for a new dedicated international forum for pandemic preparedness.17 There are many questions to be answered by virologists, epidemiologists, geneticists, pharmacologists and other scientists. How did the virus become a human pathogen? The zoonotic transmission route for the virus is still unclear, let alone how to disrupt it. Identifying this is a priority, given the zoonotic origins of so many historical epidemics of communicable diseases. Scientific research is also needed into how the virus reproduces in the body, how it interacts with the immune system and risk factors that contribute to disease of severity. Experience of COVID-19 across the world indicates that pandemic preparedness in most countries appears at best to have been a paper exercise. Stockpiling essential medical supplies and having reserve health service capacity are undoubtedly costly. But so are the consequences for facing a pandemic unprepared. Developing vaccines and other treatments against an as yet unknown pathogen takes time. However, a much lower cost action could and should have been prepared in advance: achieving health literacy about pandemics in the population to support having the public 'on side' with necessary societal restrictions. Lack of this was reflected for example by Ferguson's group including a high public non-adherence factor in their models for the UK,7 and in the USA there have been armed demonstrators in the streets in Michigan protesting against restrictions on their activities. At this stage, it is too early to be clear about the longer-term severity and persistence of COVID-19 and therefore how long current public health controls should remain in place. However, early relaxation of social controls in some regions appears to be leading to a significant rise in incidence of the disease, for example, in Singapore and Japan, with reports also of significant COVID-19 resurgence in China.2 It remains to be seen how well the world's financial systems and businesses will survive the pandemic and how long it will take to emerge from the current major economic downturn. In prospect are sustained increases in remote ways of working, within business sectors generally, as well as within health services. This journal will continue to report on the implications of the COVID-19 pandemic and welcomes manuscripts on how best to be prepared for future epidemics and pandemics. Footnotes Twitter: Donald Singer @HealthMed Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: DS is the President of the Fellowship of Postgraduate Medicine, for which Health Policy and Technology is an official journal. During 2014, he was a physician and pharmacologist in Rwanda within the US AID and US CDC Human Resources for Health programme. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; internally peer reviewed. Author note: This editorial is to be published simultaneously with a similar editorial in Health Policy and Technology. References 1 WHO Director-General's opening remarks at the media briefing on COVID-19. Available: www.who.int 2 Website for the European Centre for Disease Prevention and Control. Available: www.ecdc.europa.eu 3 Guan W-J, Liang W-H, Zhao Y, et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: a nationwide analysis. Eur Respir J 2020:2000547.10.1183/13993003.00547-2020 4 Website for the Johns Hopkins University Coronavirus Center. Available: [Accessed 22 Apr 2020]. 5 Bedford J, Enria D, Giesecke J, et al. Strategic and technical advisory group for infectious hazards. COVID-19: towards controlling of a pandemic. Lancet 2020;395 :1015-8.32197103 6 Kyhlstedt M, Andersson SW. Diagnostic and digital solutions to address the COVID-19 pandemic: the need for international collaboration to close the gap. Health Policy Technol. In Press 2020. doi:10.1016/j.hlpt.2020.04.010. [Epub ahead of print: 25 Apr 2020]. 7 Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis 2020:S1473-3099(20)30243-7.10.1016/S1473-3099(20)30243-7 8 Horton R . Offline: 2019-nCoV outbreak-early lessons. Lancet 2020;395 :322.10.1016/S0140-6736(20)30212-9 32007152 9 Yan S . China adds nearly 1,300 coronavirus deaths to official Wuhan Toll, blaming reporting delays. The Daily Telegraph. Available: 10 Update to guidance on regulatory expectations in the context of COVID-19 pandemic. Available: www.ema.europa.eu 11 Abboud L, Neville S. GSK and Sanofi team up on Covid-19 vaccine. Financial Times. 12 Halliday J . Government misses out on 16m face masks for NHS in four weeks. The Guardian. Available: 13 Greenhalgh T, Schmid MB, Czypionka T, et al. Face masks for the public during the covid-19 crisis. BMJ 2020;369 :m1435.10.1136/bmj.m1435 32273267 14 Charatan F . Bush announces US plan for flu pandemic. BMJ 2005;331 :1103.3.10.1136/bmj.331.7525.1103-b 15 Dutheil F, Baker JS, Navel V. COVID-19 as a factor influencing air pollution? Environ Pollut 2020;263 :114466.10.1016/j.envpol.2020.114466 32283458 16 Mahase E . Covid-19: Trump threatens to stop funding WHO amid "China-centric" claims. BMJ 2020;369 :m1438.10.1136/bmj.m1438 32269034 17 Dey S, Cheng Q, Tan J. All for one and one for all: why a pandemic preparedness League of Nations? Health Policy Technol 2020.
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A novel coronavirus (severe acute respiratory syndrome-CoV-2) that initially originated from Wuhan, China, in December 2019 has already caused a pandemic. While this novel coronavirus disease (COVID-19) frequently induces mild diseases, it has also generated severe diseases among certain populations, including older-aged individuals with underlying diseases, such as cardiovascular disease and diabetes. As of 31 March 2020, a total of 9786 confirmed cases with COVID-19 have been reported in South Korea. South Korea has the highest diagnostic rate for COVID-19, which has been the major contributor in overcoming this outbreak. We are trying to reduce the reproduction number of COVID-19 to less than one and eventually succeed in controlling this outbreak using methods such as contact tracing, quarantine, testing, isolation, social distancing and school closure. This report aimed to describe the current situation of COVID-19 in South Korea and our response to this outbreak. infectious diseases the Ministry of Health & Welfare, Republic of Korea HI14C1324 the Korea Centers for Disease Control and Prevention 2019-ER5101-00 2019-ER5408-00 pmcIntroduction A novel coronavirus (severe acute respiratory syndrome (SARS)-CoV-2) that emerged from the city of Wuhan, China, in December 2019 has already caused a global pandemic and has been declared a public health emergency of international concern by the WHO.1 While this novel coronavirus disease (COVID-19) frequently induces mild symptoms, it has also generated severe illnesses among certain populations, including elderly individuals with underlying diseases such as cardiovascular disease and diabetes.2 As of 31 March 2020, a total of 9786 confirmed cases with COVID-19 have been reported in South Korea, including 162 deaths, 5408 recovered individuals released from isolation and 4216 patients staying in hospitals or non-hospital facility for isolation. In many countries such as the USA and European countries, the number of patients with COVID-19 is growing exponentially, and, at this point, South Korea is one of the few countries that have slowed the spread of COVID-19. This report aimed to describe the current situation of COVID-19 in South Korea and our response to this outbreak. Early stage of outbreak The first imported case of COVID-19 was confirmed in South Korea on 20 January 2020.3 A 35-year-old woman who lived in Wuhan, China, arrived at the Incheon Airport on 19 January 2020. During the quarantine inspection process at the airport, her body temperature was reported as 38.3degC on a thermal scanner. She was hospitalised at a designated isolation hospital. Pan coronavirus conventional PCR assay was positive for the throat swab sample, and sequencing of the PCR amplicon showed that the sequence was identical to that of the 2019-nCoV isolated from the Wuhan patient. Since the first case, cases imported from China and cases linked to the imported cases have been identified, and the sources of infection were traced by contact investigation until patient 29.4 Patient 29 was the first patient identified in Seoul who did not have an epidemiological link or travel history to China. From this patient, the possibility of community transmission was raised. As the number of confirmed cases was rapidly increasing, the Korean government raised the alert level from orange to red on 23 February 2020, resulting in the Ministry of Education ordering the closure of all schools and delaying the new school year opening by 1 week. Superspreading event and community transmission The epicentre of the COVID-19 outbreak in South Korea has been Daegu, a city of 2.5 million people, approximately 150 miles southeast of Seoul.5 The rapid spread of COVID-19 in South Korea is attributed to a superspreading event within a religious group called Shincheonji in the city of Daegu. This led to an explosive outbreak in the city of Daegu and Gyeongsangbuk-do. While the explosive outbreak has been controlled, sporadic spreading is still ongoing especially in mental health illness hospitals. The number of cases from Daegu and Gyeongsangbuk-do is attributed to 84% of all confirmed cases within South Korea as of 23 March 2020. Efforts in extensive testing, contact tracing, quarantine and isolation could effectively control the outbreak in these areas. However, a small number of outbreaks within some hospitals, including long-term care facilities, crowded facilities such as call centres, and household transmissions continues, and new cases imported from foreign countries such as European countries and the USA are emerging now. Figure 1 shows the daily trends of numbers of newly confirmed patients with COVID-19 and isolated patients with COVID-19 in South Korea. The number of newly confirmed cases was highest in 29 February 2020, and after that, the number gradually decreased until mid-March, but after 12 March, around 100 cases are steadily occurring every day. The number of patients in isolation was highest in 13 March 2020, but it has been decreasing ever since. This is because there are more patients who are cured and discharged than those who are newly isolated. Figure 1 Trends of daily number of newly confirmed cases and isolated cases. Epidemiological characteristics The Korea Centres for Disease Control and Prevention (KCDC) reported the basic epidemiological characteristics of 7755 patients with COVID-19 in South Korea as of 13 March 2020 using surveillance data retrieved from the KCDC-operated National Notifiable Disease Surveillance System.6 The female-to-male ratio was 62:38. The age group of 20-29 years accounted for 28.9% of all cases, followed by the age groups of 50-59 and 40-49 years. The case fatality proportion was 0.1% among the age groups of 30-39 and 40-49 years, then increased to 0.4% (50-59 years), 1.5% (60-69 years), 5.0% (70-79 years) and 8.5% (>=80 years). They described the characteristics of 66 fatal patients with COVID-19 as of 12 March 2020. The median age was 77 years (range 35-93 years), and the female-to-male ratio was 44:56. Of 63 cases, 96.8% were found to have coexisting conditions such as hypertension (47.6%), diabetes (36.5%), neurodegenerative disorders (16%) and pulmonary diseases (17.5%). The median interval between onset of symptom and death was 10 days (range 1-24 days), while the median interval between date of hospitalisation and the date of death was 5 days (range 0-16 days). Our responses South Korea had experienced the Middle East respiratory syndrome coronavirus infection outbreak in 2015. At that time, nosocomial spread and superspreading events within hospitals mainly contributed to the outbreak.7 Since 2015, KCDC and many hospitals of South Korea have been prepared for the next outbreak of infectious diseases. The preparations done were with respect to healthcare personnel, facilities and the system as a whole. However, many experts now think that the preparations were not enough. Infectious diseases-specialised hospitals were not built, and the KCDC is still not independent from the Ministry of Health and Welfare. Although the number of negative pressure rooms in hospitals has been increased, the healthcare system in South Korea is still vulnerable to the outbreak of respiratory infections. In the early stages of COVID-19 outbreak when imported cases from China and their linked cases were identified, KCDC actively performed contact tracing, quarantined the contacted persons, and diagnosed and isolated the COVID-19 cases as soon as possible. Some experts believe that entry from China should have been banned at an early stage of the outbreak, which the Korean government did not. After the SARS-CoV-2 emerged in China, KCDC rapidly developed tests according to the WHO guidelines and cooperated with diagnostic manufacturers to develop commercial test kits. The first test was approved on 7 February 2020, when the country had just a few cases, and it was then distributed to regional health centres. KCDC rapidly scaled up the diagnostic capacity within South Korea. Laboratory test for COVID-19 was initially performed at KCDC and then became available at 17 regional laboratories (Public Health and Environment Research Institute) throughout the nation, on 24 January 2020. Since 7 February 2020, the test facilities have been expanded to many laboratories, including tertiary hospitals, and more test centres were added later. Currently, 15 000-20 000 tests per day are being carried out by national central labs and 95 non-governmental clinical laboratories.8 These laboratories have been all certified by Korean Society for Laboratory Medicine and have also completed external quality assessments by the Korean Association of External Quality Assessment Service. When the explosive outbreak in the city of Daegu and Gyeongsangbuk-do occurred in February, mass screening efforts identified patients with mild or no symptoms, and it contributed in controlling the cluster. For safe and efficient screening for COVID-19, drive-through screening centres have been designed and implemented in South Korea.9 The steps of the drive-through screening centres include registration, examination, specimen collection and instructions. Increased testing capacity of over 100 tests per day and prevention of cross-infection among testees in the waiting space seem to be the major advantages. A modelling study showed that South Korea has the highest diagnostic rate for COVID-19, and the diagnostic capacity of South Korea has been the major contributor in overcoming this outbreak. However, we cannot exactly estimate how many hidden cases are spreading COVID-19 at present. The methods that can objectively verify the patient's route claims, such as medical facility records, global positioning system, card transactions and closed-circuit television, were used for COVID-19 contact investigations in South Korea.10 The methods could provide accurate information on the location and time of exposure and details of the situation, thus reducing omissions in a patient's route due to recall or confirmation bias that may have arisen from patient or proxy interviews. During the early stages of COVID-19, all confirmed cases could be hospitalised into the designated isolation hospitals. However, when an explosive outbreak at the epicentre occurred, the lack of medical resources had become a reality. Healthcare professionals from other regions of South Korea went to the epicentre area to help out, while many critically ill patients were transferred to tertiary hospitals in other areas. The Korean government has opened several non-hospital facilities for the isolation of asymptomatic patients or patients with mild symptoms. The basic reproduction number (R0) is an indicator for analysing and predicting the situation of an infectious disease, and the R0 of COVID-19 is around 2.5. This means that one patient spreads the disease to 2.5 during the period of transmission; if R0 is greater than 1, the infectious disease spreads gradually. We are trying to terminate the COVID-19 transmission chain and eventually succeed in controlling this outbreak with methods such as contact tracing, quarantine, testing, isolation, social distancing and school closure. A modelling analysis from the UK showed that these efforts for mitigation should last for months to control this outbreak temporarily; however, it remains to be seen whether these non-pharmaceutical interventions could be successful in controlling this outbreak in the long term.11 COVID-19 has unique characteristics. The R0 and mortality are higher than those of influenza, and the symptoms can be mild or absent even when the transmissibility is high. Many patients have developed pneumonia even though they have mild symptoms. These characteristics of the disease have shown us that it is a very difficult task to control this outbreak effectively. Maintaining the non-pharmaceutical interventions for a long time is a very challenging task for us. It is very important to minimise mortality from this disease while reducing the R0 to less than 1. Because the mortality rate of COVID-19 is higher in elderly people and those with underlying diseases, they should be protected from this disease. In order to lower the mortality rate, inpatients who are vulnerable to COVID-19 should be protected as much as possible. Many hospitals in South Korea have quickly implemented systems to protect patients and medical staff, including outdoor triage clinics for patients with fever or respiratory symptoms; pre-emptive isolation wards for patients with pneumonia; entrance surveillance using fever checks and questionnaires about respiratory symptoms and travel history; programmes for protecting high-risk units such as the intensive care unit (ICU), haemodialysis unit, and operation rooms; and surveillance for hospital employees. KCDC and other academic societies have issued a number of guidelines on diagnosis, treatment, infection control, quarantine and social distancing, and periodically update these guidelines. Korean scientists and medical doctors have been sharing their findings on COVID-19 globally through the latest and forthcoming publications. Currently, there is no established standard antiviral treatment for COVID-19 other than supportive treatment. Based on the limited data, many experts in South Korea are trying to administer several antiviral agents at the judgement of the attending physicians. Most patients with COVID-19 have mild diseases, and those patients can usually be recovered without any antiviral treatments. The antiviral agents are used for patients with moderate or severe diseases with pneumonia or respiratory distress. Table 1 shows the antiviral agents which are recommended for COVID-19 in South Korea and dosages of the antivirals for COVID-19.12 Lopinavir/ritonavir and hydroxychloroquine are the most commonly used antivirals for COVID-19 in South Korea. Remdesivir is available only for clinical trials. Table 1 Dosages of antiviral agents for COVID-19 Medication Normal renal function (CrCl >50 mL/min) Impaired renal function (CrCl 25-50 mL/min) Hemodialysis or CrCl <20 mL/min Lopinavir/ritonavir Lopinavir/ritonavir 400 mg/100 mg po every 12 hours Same dose Same dose Hydroxychloroquine Hydroxychloroquine 400 mg po 24 hours Data not available Data not available Interferon-b1b 0.25 mg/mL subcutaneous injection qEOD Data not available Data not available Remdesivir 200 mg loading dose on day 1 is given, followed by 100 mg intravenously once per day maintenance doses Same dose Same dose CrCl, creatinine clearance; po, by mouth. Conclusion KCDC; experts in infectious diseases, pulmonology, emergency medicine, laboratory medicine, infection control; healthcare providers; hospitals; and all Korean people are still trying hard to overcome the outbreak of COVID-19. The situation is changing rapidly as the outbreak evolves, so flexible evidence-based measures should be implemented for overcoming this outbreak. Although the rapid and sustained responses of South Korea to control the COVID-19 outbreak could slow the spread of the COVID-19 outbreak within this country, this outbreak could last for a long time, and at any time, unexpected surge may happen again. It is too early to say whether our response has been successful. Our actions should be evaluated after the outbreak ends. Main messages Various interventions such as contact-tracing, quarantine, testing, isolation, social distancing, and school closure are applied to control the COVID-19 outbreak in South Korea. South Korea has the highest diagnostic rate for COVID-19, which has been the major contributor in overcoming this outbreak. Although the rapid and sustained responses of South Korea to control the COVID-19 outbreak could slow the spread of the COVID-19 outbreak within this country, this outbreak could last for a long time, and at any time, unexpected surge may happen again. Current research questions What is the most effective antiviral agent for COVID-19? How can you develop the effective vaccine for COVID-19? What is the most suitable strategies to control COVID-19 outbreak? Key references Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020 (doi: 10.1056/NEJMoa2002032). Kim JY, Choe PG, Oh Y, et al. The first case of 2019 novel coronavirus pneumonia imported into Korea from Wuhan, China: implication for infection prevention and control measures. J Korean Med Sci 2020;35(5):e61. Korean Society of Infectious Diseases. Report on the epidemiological features of coronavirus disease 2019 (COVID-19) outbreak in the Republic of Korea from January 19 to March 2, 2020. J Korean Med Sci 2020;35(10):e112. Kim YJ, Sung H, Ki CS, et al. Covid-19 testing in South Korea: current status and the need for faster diagnostics. Ann Lab Med 2020;40:349-50 Kwon KT, Ko JH, Shin H, et al. Drive-through screening center for COVID-19: a safe and efficient screening system against massive community outbreak. J Korean Med Sci 2020;35(11):e123. Self-assessment questions While this novel coronavirus disease (COVID-19) frequently induces mild symptoms, it has also generated severe illnesses among certain populations including elderly individuals with underlying diseases such as cardiovascular disease and diabetes. South Korea has the highest diagnostic rate for COVID-19, which has been the major contributor in overcoming this outbreak. The basic reproduction number (R0) is an indicator for analysing and predicting the situation of an infectious disease, and the R0 of COVID-19 is around 2.5. Patients with COVID-19 with severe pneumonia have higher transmissibility than patients with mild diseases. Currently, there is no established standard antiviral treatment for COVID-19 other than supportive treatment. Answers True. True. True. False. True. Footnotes Contributors: JYC conceived and planned the idea and wrote the manuscript. Funding: This work was supported by the research programme funded by the Korea Centers for Disease Control and Prevention (2019-ER5408-00), research grants for deriving the major clinical and epidemiological indicators of people with HIV (Korea HIV/AIDS Cohort Study, 2019-ER5101-00) and a grant from the Ministry of Health & Welfare, Republic of Korea (grant number HI14C1324). Competing interests: None declared. Patient consent for publication: Not required. Ethics approval: This article does not contain any studies with human participants or animals performed by any of the authors. Provenance and peer review: Commissioned; externally peer reviewed.
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press postgradmedj-2020-138585 10.1136/postgradmedj-2020-138585 Letter AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 Chloroquine and hydroxychloroquine for COVID-19: time to close the chapter Gupta Anunay Cardiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India Malviya Amit Cardiology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, India Correspondence to Amit Malviya, Department of Cardiology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Mawdiangdiang, Shillong, Meghalaya, India; [email protected] 10 2021 11 8 2020 11 8 2020 97 1152 676677 30 6 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcCOVID-19 pandemic has brought about a surge in repurposing of drugs, either for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or for the pre-exposure and post-exposure prophylaxis. Many drugs are being tried, but 4-aminoquinolines (chloroquine and hydroxychloroquine) have attracted significant attraction and generated the maximum controversy. There is no domain left, be it political, social or scientific, where usage of 4-aminoquinolines for COVID-19 was undisputed. So far, the benevolent and propitious story of hydroxychloroquine is tainted by political controversies, death threats to researchers and scientific lapses.1-4 A significant part of this story appears to be fuelled with the fear generated by the current pandemic, lay media perusal, amplification by social media and political pressure rather than true scientific approach.4 5 At the ground level, self-medication and stockpiling are resulting in unavailability for those who really need it,6 7and millions of people are exposed to its rare but potentially serious adverse effects including cardiac arrhythmias. As healthcare providers and as a scientific community at large, our fundamentals first guide us to do no harm to the people whose healthcare is in our hands. The dire need to quickly develop, assess and adopt medications during a public heath crisis can go off-centre at times. There has been an enormous discussion over the appropriate usage of this medication and at present, the bone of contention, is whether physicians should prescribe them or not? There indeed, is an urgency of care in ongoing novel coronavirus pandemic and physicians need to decide about appropriateness of this therapy. But now the time has come to close the chapter of controversies, because enough scientific evidence has accumulated to answer three basic logical questions relating to usage of chloroquine and hydroxychloroquine for treatment and prophylaxis of COVID-19. First, what are the specific mechanisms (in vitro effects) of 4-aminoquinolines on SARS-CoV-2? Second, what does the data say about its efficacy in properly conducted randomised control trials? And finally, what is the safety profile of this drug in specific reference to COVID-19? 4-Aminoquinolines have inhibitory in vitro effects on the replication of SARS-CoV-2, but these mechanisms are a part of its broad antiviral and immunomodulatory properties, and no specific mechanisms are described.8 9 In this context, it essential to mention that complex pharmacokinetics of these drugs makes it difficult to extrapolate laboratory dosing and drug concentrations in human subjects.10 Moreover, for the patients, clinical outcomes are more important than viral clearance in the laboratories. Experience and evidence from the past indicate that in vitro efficacy of majority of the molecules does not replicate in biological systems. There are numerous studies including randomised trials on this subject, but they are marked either by poor study design, low sample size, unvalidated end points, substantial confounders or insufficient data11-14 and they cannot be relied upon to reach any meaningful conclusion. However, there are studies with proper methodology and reliable data. From these studies, it can be safely concluded that hydroxychloroquine is not effective as post-exposure prophylaxis, it does not lead to reduction in mortality or need of mechanical ventilation for sick patients and is associated with more adverse events.15-19 Recently, large international trials such as RECOVERY(Randomised Evaluation of Covid-19 Therapy ), SOLIDARITY(International trial by World Health Organisation) and DISCOVERY(Trial of Treatments for COVID-19 in Hospitalized Adults) have halted the hydroxychloroquine arm, citing internal and external data showing no benefits with such therapy.20-22 As far as safety is concerned, many are advocating this drug as very safe based on safety data from patients with rheumatic diseases, but application of such data for COVID-19 is biologically not plausible. The disease process and its metabolic consequences promote a proarrhythmic milieu, and added side effects of medication can be devastating.11 23 In patients with severe COVID-19 with hepatic and renal dysfunction who are administered other medications, the metabolism and clearance of hydroxychloroquine are altered and the safety of hydroxychloroquine is yet to be proven conclusively. The United States Food and Drug Administration (FDA) has revoked the emergency use authorisation of chloroquine and hydroxychloroquine to treat hospitalised patients with COVID-19. The FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19, and serious cardiac adverse events and other potentially serious side effects outweigh the known and potential benefits of chloroquine and hydroxychloroquine.24 It can be concluded now that 4-aminquinolines have some in vitro activity on SARS-CoV-2, but its efficacy on human disease is doubtful. It does not work for treatment of severe illness and does not prevent infection after high to moderate risk exposure. Its role in pre-exposure prophylaxis and treatment of mild-to-moderate disease remains to be investigated. As far as pre-exposure prophylaxis is concerned, other preventive methods exist which have proven efficacy,25 and exposing a large population to a potentially toxic drug when its benefits are not proven beyond doubts is not justified. The Indian Council of Medical Research recently published a case-control investigation asserting that four or more doses of hydroxychloroquine results in a significant decline in the odds of catching infection.26 Moreover, this study is severely limited by its design and case-control methodology. Recent practice guidelines by the American College of Physicians do not recommend chloroquine or hydroxychloroquine either for prophylaxis or treatment.27 Treatment of mild or moderate COVID-19 illness responds well to conservative therapy or approved antiviral agents, and the same logic as metioned earlier applies for not using hydroxychloroquine in this subset of patients as well. This becomes even more relevant because RECOVERY trial data have shown mortality benefit with dexamethasone, which is much cheaper, more easily available in and arrhythmic risk is least as compared to hydroxychloroquine. Finally, pursuing and investing in this direction does not appear to be prudent and it is time to close the chapter of 4-aminoquinolines for usage in COVID-19. Footnotes Contributors: Both authors contributed equally in conceptualisation, research and final drafting of the manuscript. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Provenance and peer review: Not commissioned; internally peer reviewed. References 1 Ektorp E . Death threats after a trial on chloroquine for COVID-19. Lancet Infect Dis 2020;20 :661.10.1016/s1473-3099(20)30383-2.32473139 2 Jaffe S , Regulators split on antimalarials for COVID-19. Lancet (London, England) 2020;395 :1179.10.1016/s0140-6736(20)30817-5.32278373 3 Mehra MR, Ruschitzka F, Patel AN. Retraction-hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet (London, England) 2020.10.1016/s0140-6736(20)31324-6. 4 Rome BN, Avorn J. Drug evaluation during the COVID-19 pandemic. N Engl J Med 2020;382 :2282-4.10.1056/nejmp2009457.32289216 5 Sayare S. He was a science star. Then he promoted a questionable cure for COVID-19. New York Times Magazine. Available (accessed May 12, 2020) (accessed May 12, 2020) 6 Rathi S, Ish P, Kalantri A, et al. Hydroxychloroquine prophylaxis for COVID-19 contacts in India. Lancet Infect Dis 2020.10.1016/s1473-3099(20)30313-3. 7 Kim AHJ, Sparks JA, Liew JW, et al. A rush to judgment? Rapid reporting and dissemination of results and its consequences regarding the use of hydroxychloroquine for COVID-19 [published correction appears in Ann Intern Med. 2020 Jun 16;172(12):844]. Ann Intern Med 2020;172 :819-21.10.7326/M20-1223 32227189 8 Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020;ciaa237.10.1093/cid/ciaa237.32150618 9 Savarino A, Boelaert JR, Cassone A, et al. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis 2003;3 :722-7.10.1016/s1473-3099(03)00806-5.14592603 10 Akpovwa H , Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity. Cell Biochem Funct 2016;34 :191-6. pmid:27001679.10.1002/cbf.3182.27001679 11 Ferner RE, Aronson JK, Chloroquine and hydroxychloroquine in COVID-19. BMJ (Clinical Research Ed ) 2020;369 :m1432.10.1136/bmj.m1432. 12 Rubin EJ, Harrington DP, Hogan JW, et al. The urgency of care during the COVID-19 pandemic - learning as we go. N Engl J Med 2020;382 :2461-2.10.1056/nejme2015903 32379956 13 Cohen MS . Hydroxychloroquine for the prevention of COVID-19 - searching for evidence. N Engl J Med 2020.10.1056/nejme2020388. 14 Alexander PE, Debono VB, Mammen MJ, et al. COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine. J Clin Epidemiol 2020;123 :120-6.10.1016/j.jclinepi.2020.04.016 32330521 15 Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19. Med 2020.10.1016/j.medj.2020.06.001. 16 Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with COVID-19 [published online ahead of print, 2020 May 7]. N Engl J Med 2020. NEJMoa2012410.10.1056/NEJMoa2012410. 17 Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19 [published online ahead of print, 2020 Jun 3]. N Engl J Med 2020.10.1056/NEJMoa2016638. 18 Shamshirian A, Hessami A, Heydari K, et al. Hydroxychloroquine versus COVID-19: a periodic systematic review and meta-analysis. medRxiv 2020. 04.14.20065276.10.1101/2020.04.14.20065276. 19 Taccone FS, Gorham J, Vincent JL. Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base. Lancet Respir Med 2020;8 :539-41.10.1016/S2213-2600(20)30172-7.32304640 20 No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19. Available (asscessed 18 Jun 2020) (asscessed 18 Jun 2020) 21 "Solidarity" clinical trial for COVID-19 treatments. Available (accessed 18 Jun 2020) (accessed 18 Jun 2020) 22 Trial of treatments for COVID-19 in hospitalized adults (DisCoVeRy). Available (accessed 18 Jun 2020) (accessed 18 Jun 2020) 23 Funck-Brentano C, Salem JE. Chloroquine or hydroxychloroquine for COVID-19: why might they be hazardous? Lancet (London, England) 2020.10.1016/s0140-6736(20)31174-0. 24 FDA news release . Coronavirus (COVID-19) update: FDA revokes emergency use authorization for chloroquine and hydroxychloroquine. 15 June 2020. Available (accessed 18 Jun 2020). (accessed 18 Jun 2020). 25 Kucharski AJ, Klepac P, Conlan AJK, et al. Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study. Lancet Infect Dis 2020.10.1016/S1473-3099(20)30457-6. 26 Chatterjee P, Anand T, Singh KJ, et al. Healthcare workers & SARS-CoV-2 infection in India: a case-control investigation in the time of COVID-19. Indian J Med Res Epub ahead of print.10.4103/ijmr.IJMR_2234_20. 27 Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al. Should clinicians use chloroquine or hydroxychloroquine alone or in combination with azithromycin for the prophylaxis or treatment of COVID-19? [published online ahead of print, 2020 May 13] [published correction appears in ann intern med 2020 may 26]. Ann Intern Med 2020;M20-1998.10.7326/M20-1998.
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press 32883766 postgradmedj-2020-138782 10.1136/postgradmedj-2020-138782 Quality Improvement Report AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 Junior doctors: when fresh blood fast-tracks the fight against COVID-19 Ashton Elisabeth Oncology Department, Assistance Publique des Hopitaux de Paris (APHP), Cochin Hospital, Paris, France Faculte de Medecine, Universite de Paris, Paris, France Skayem Charbel Faculte de Medecine, Universite de Paris, Paris, France Hopital Henri Mondor, Assistance Publique des Hopitaux de Paris, Creteil, France Ouazana-Vedrines Charles Faculte de Medecine, Universite de Paris, Paris, France Psychiatry Department, HEGP Hospital, AP-HP,Paris, France Hamann Pierre Dermatology Department, Institut Gustave-Roussy,Villejuif, France Faculte de Medecine du Kremlin Bicetre, Universite Paris-Saclay, Paris, France Correspondence to Pierre Hamann, Department of Dermatology, Institut Gustave Roussy, 114 Rue Edouard Vaillant, Villejuif 94800, France; [email protected] 3 2021 03 9 2020 03 9 2020 97 1145 185187 28 7 2020 06 8 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcINTRODUCTION On 11 March 2020, the WHO declared COVID-19 as a Public Health Emergency of International Concern. In Europe, particularly in France, hospitals were urged to take prompt measures: cancellation of non-emergent procedures, dedication of units and wards to patients with COVID, and reallocations of medical and non-medical staff.1 Paris and its surrounding region, Ile-de-France, were the most severely impacted regions in France. With a total population of 12 million inhabitants (19% of the French population), hospitals had to provide up to 2600 additional beds in intensive care units (ICUs) (100% more than available) to cope with the pandemic. Medical residents in France represent 32% of public hospital physicians. In the Parisian area, there are 5400 residents, all specialities included, distributed in 100 hospitals. Residents were, along with the other healthcare professionals, on the front line of the fight against COVID-19. Every year, up to 1000 residents are not assigned to any hospital unit, for personal reasons or scientific research projects. At the beginning of the outbreak in early March, identifying this unallocated manpower was essential to alleviate work pressure within hospitals, yet very challenging. Thus, dispatching non-assigned volunteers to departments in need was non-trivial. In France, this mission is usually managed by the Regional Health Agency (Agence Regionale de Sante (ARS)). In the context of the COVID-19 epidemic, ARS and Paris Public Hospitals (Assistance Publique Hopitaux de Paris) were overwhelmed by overall health management issues, including addition of hospital beds, supply of personal protective equipment and identification of available non-medical staff. On 16 March 2020, three residents who had never worked together one oncologist, one psychiatrist, one dermatologist formed a crisis management team (CMT). These three volunteers offered their support to the ARS, and they were delegated for this mission. Their main targets were to list voluntary available residents based on their skills, to identify hospitals requiring human support and to eventually allocate the appropriate human resources in the identified units. This new self-managed organisation was set up in record time using information communication technology (ICT) tools to dispatch non-assigned volunteers during this unprecedented COVID-19 crisis. Our objective is to highlight efficiency that millennials can bring in times of crisis, by presenting the initiative that these residents took in the most impacted region in France during the COVID-19 outbreak. PROCESS To properly set up the CMT, residents of the CMT needed available manpower for organisation. These volunteers had to be off duty (for pregnancy, medical issues, etc). A call for volunteers to join the CMT was made on social networks. In 24 hours, 31 residents were recruited to form the monitoring team (17 residents) and the matching team (14 residents). A total of 250 residents already working in the Parisian region hospitals were chosen as a local source to evaluate staff needs in each hospital. Then, the step was to identify available volunteers to be dispatched to different hospitals. Volunteers had to fill out an electronic form, published by the two Paris Residents Unions on their usual social networks and email list. Collected data were as follows: the resident's speciality, year of speciality, skills (especially in emergency and critical care), availability, location and contacts. All information was collated in a web app to sort, organise and display the data. This app was developed within 48 hours by a computer engineer, a close relative of one of the crisis team founders (figure 1). Figure 1 Management of volunteer residents by the crisis team during COVID-19 outbreak in Paris.The monitoring team with the assessment of needs in the hospitals by our local contacts are represented on the left side. The functioning of the matching team and the reassignment of residents in understaffed departments according to the warning signal are represented on the right side. ED, emergency department ICU, intensive care unit. Departments in need had to be identified. For this, one or two residents, as local contact, were assigned by the CMT in each ICU, emergency department and inpatient ward. Their role was to identify the local problems faced by the residents, especially short staffing. Daily updates were provided to the CMT by using social networks. Each situation was classified by the monitoring team using an alert level code ranging from 1 (suitable number of residents) to 5 (understaffing requiring immediate action). Levels 4 and 5 triggered the workforce search process. Daily updates were provided to the CMT. Consequently, volunteers were dispatched by the matching team to the understaffed departments, according to their location and skills. Matching also took into consideration general conditions like housing, transportation, insurance coverage and wages. Then, two weekly follow-ups of the newly assigned resident were made to. After reassignment of the residents, the monitoring team made sure to follow up on their mental well-being and integration in the new departments. Volunteering psychiatry residents provided urgent moral support for all residents in distress. From 16 March until 10 May, a total of 1902 residents responded, of which 1203 volunteers within the first 48 hours. A total of 578 volunteers were dispatched between 22 March and 10 May: 230 in ICUs, 93 in emergency departments and 255 in inpatient wards. Approximately 85% of the volunteers were dispatched before 10h April, the peak of the epidemic in Ile-de-France. After 2 weeks of matching, all the available volunteers with intensive care competencies were reallocated with 30 residents from other regions of the country. Deploying residents to a different department of their hospital or to a new hospital was not easy. Amending some regulations was indispensable. The CMT decided to bring up their suggestion to higher authorities in the Ministry of Health and the Ministry of Education, with the help of the two Paris Residents Unions, and they succeeded.2 BEHIND THE RESIDENTS' INITIATIVE While millennials have a bad reputation in the medical circles, the traits that sometimes chafe their older colleagues may make the profession healthier and more technologically savvy. This was clearly highlighted in the COVID-19 pandemic in France whereby the CMT was able to overcome a major obstacle in controlling the outbreak in the Parisian region and its surrounding, which were the most impacted by the pandemic. Being digital natives, they are used to having information at their fingertips and having constant connection with peers.3 Speed and acceleration were the main characteristics of the residents' approach. This was made possible because of the fast pace in problem solutions that technology adapted them to. Globalisation and rapid advancements in technology require different communication and professional engagement styles, attitudes toward diversity and idealism about the future, which were well projected by the CMT team.4 Their capacity in fast networking helped them achieve a mission they were not in charge of. On the other hand, physicians from older generations, who tend to be less experienced in social media and technology, were unable to initiate a step to overcome the human resource obstacle. This reflects that millennial residents are responsible adults, who are showing leadership. They have begun to enter the physician workforce, with a vision of building a promising future for the medical field.5 CONCLUSION The COVID-19 pandemic has revealed the virtues of devotion and commitment that drove medical residents throughout their long curriculum. The crisis team has reflected the potential of millennial junior doctors to take lead in times of crisis. This self-managed organisation provided a reliable and agile answer to the staffing problem within hospitals, thanks to their familiarity with social networks and ICT tools. While COVID-19 revealed the responsible identity of future doctors, it has also disclosed current fundamental flaws in the healthcare system. Will this pandemic be the trigger to finally reshape health and development institutions? Acknowledgements We would like to deeply thank all the French residents, especially in Paris and Ile-de-France, for their commitment and dedication, which helped overcome the pandemic. We also thank all members of the crisis management team for their time, and Dr Tu-Anh DUONG for her exceptional support. Footnotes Contributors: EA, PH and CO-V contributed substantially to the conception and design of the work. EA and PH wrote the manuscript. CS critically reviewed the contents of the manuscript. All authors have approved the final version of the manuscript. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; internally peer reviewed. REFERENCES 1 Charlotte H. French Pandemic Resistance. N Engl J Med. 2020 May 7;382 :e51.10.1056/NEJMc2010122 32320557 2 Ministere des Solidarites et de la Sante . Ministere de l'Enseignement superieur. INSTRUCTION relative aux amenagements des modalites de formation pour les etudiants en sante [Internet]. Available 3 Mercer C . How millennials are disrupting medicine. CMAJ 2018;190 :E696-7.10.1503/cmaj.109-5605 29866899 4 Maiers M . Our future in the hands of millennials. J Can Chiropr Assoc 2017;61 :212-7.29430050 5 Jung P, Smith C. Medical millennials: a mismatch between training preferences and employment opportunities. Lancet Global Health 2019;7 :S38.10.1016/S2214-109X(19)30123-8
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press 32404497 10.1136/postgradmedj-2020-137876 postgradmedj-2020-137876 Editorial AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 COVID-19 changes medical education in Italy: will other countries follow? Lapolla Pierfrancesco Department of Surgery P. Valdoni, Policlinico Umberto I, Sapienza University of Rome, Roma, Italy Mingoli Andrea Department of Surgery P. Valdoni, Policlinico Umberto I, Sapienza University of Rome, Roma, Italy Correspondence to Mr Pierfrancesco Lapolla, Department of Surgery P. Valdoni, Policlinico Umberto I, Sapienza University of Rome, Roma 00185, Italy; [email protected] 7 2020 13 5 2020 13 5 2020 96 1137 375376 11 4 2020 24 4 2020 25 4 2020 (c) Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. 2020 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is bringing the world to its knees with over one million cases by 8 April 2020.1 Several governments have responded by locking down entire countries with dramatic repercussions for all sectors of society. Since 21 February, the total number of cases in Italy has followed an exponential trend with 139 422 (including 13 522 healthcare workers) by April 8, which is four times higher than 3 weeks before (35 713 confirmed cases on March 18).1 Among the currently active cases (n=95 262), 28 485 (29.9 %) are hospitalised and 3693 (3.87 %) in intensive care units (ICUs).1 Italy has overtaken China with the most SARS-CoV-2 deaths, reporting 17 669 fatalities,1 a fatality rate of 12.6% (of confirmed cases, table 1). Table 1 Estimated increase in hospital doctor workforce in the COVID-19 outbreak in Italy shown per region Regions of italy Final year medical students (n=9640)1 Hospital medical doctors (n=92 950)5 Estimated increase % in medical doctor workforce (10.3%) COVID-19 current positive cases (n=95 262)1 Hospitalised patients (n=28 485)1 29.9% Patients admitted to intensive care unit (n=3693)1 3.87% Deaths (n=17 669)1 Case fatality rate (12.6%)* Lombardy 795 16 114 4.9 28 545 11 719 1257 9722 18.2 Emilia Romagna 636 6844 9.3 1311 3769 361 2234 12.3 Piedmont 537 7530 7.1 10 989 3493 423 1378 9.9 Veneto 427 7347 5.8 10 171 1554 285 736 59.3 Liguria 112 3172 3.5 3245 1109 153 654 13.3 Marche 96 2412 4.0 3562 974 133 652 13.4 Tuscany 533 6921 7.7 5557 1066 260 392 6.1 Trento 0 915 0.0 194 354 77 255 9.8 Lazio 1403 8337 16.8 3448 1241 196 244 5.7 Campania 1789 6390 28.0 2859 608 97 221 6.8 Apulia 510 6094 8.4 2238 639 90 219 8.3 Bolzano 0 945 0.0 1281 268 65 183 10.0 Abruzzo 518 2044 25.3 1534 331 62 179 9.6 Friuli V.G. 87 2077 4.2 1415 162 41 169 7.6 Sicily 987 6786 14.5 1893 563 65 133 6.2 Aosta Valley 0 288 0.0 606 120 20 102 12.0 Calabria 144 2446 5.9 755 170 15 60 7.0 Sardinia 359 3318 10.8 840 112 31 59 6.1 Umbria 633 1632 38.8 823 155 41 50 3.9 Basilicata 0 913 0.0 270 48 17 14 4.7 Molise 74 425 17.4 181 30 4 13 5.8 Data are from the Italian Ministry of Health, Italian Ministry of Education University and Research. *Based on the total count of 139 422 confirmed cases on 8 April 2020, 17h00 UTC+1. The immediate and urgent demand for more doctors has led the Italian government to take unprecedented measures. On 17 March 2020, the Council of Ministers passed the Cura Italia decree which changed the rules of Italian medical board examinations.2 As a result, almost 10 000 Italian medical students from all medical schools will be fast-tracked into the healthcare system after graduation, without sitting the postgraduate examination which concludes the practical training.3 This change is permanent. In the UK, the Medical Schools Council has suggested the possibility of releasing final-year medical students, even before the conclusion of their clinical examinations, to be provisionally registered by the General Medical Council in order to help the healthcare system to cope with the developing crisis. Before Cura Italia, the Italian medical licence required postgraduate training and an exam. The new decree permanently makes the medical degree fully qualifying. Licence training will now take place in the years before graduation. Therefore, it is estimated that 9640 newly graduated medical doctors will be qualified earlier to join the healthcare system.4 This could see a rapid 10.3% increase in hospital doctors, supporting departments and ICU dedicated to COVID-19 treatment in all regions. For instance, Lombardy, with 9722 deaths,1 a 18.2% case fatality rate of confirmed cases, might benefit from a 4.9% increase in doctor numbers; Emilia Romagna, the second most affected region, could have an increase of 9.3% (table 1).5 Also, these graduates might cover roles in less front-line areas from which medical personnel have transferred to acute care. Italy is, therefore, the first country to respond formally to the COVID-19 emergency by permanently changing the medical board examinations and altering the curriculum. On the one hand, the decree shortens the licensing process by about 9 months,3 a crucial time for the immediate movement of thousands of new doctors into the workforce for the COVID-19 emergency. On the other hand, a shift from medical school to clinical work without a transition period might put graduates at a greater risk of work-related stress. Furthermore, without a written examination, more emphasis would be on the assessment of the practical training during medical school. The provisions adopted by the Italian government regarding the permanent change of the rules for the medical board examination and the consequent fast-tracking of doctors will affect medical education for future students and augment the healthcare workforce to improve care during the current crisis. Consequently, the new Italian model might be considered by other countries. However, transparency and clear guidelines for newly qualified doctors and precise human resource planning of the new healthcare workforce are essential to safeguard patient safety in one of the gravest challenges of our time. Acknowledgements We thank Dr. Regent Lee (University of Oxford) for providing guidance in manuscript submission. Footnotes Contributors: PL for study design, literature search, data analysis and interpretation, writing and table preparation and responsibility for overall content. AM for manuscript revision. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; internally peer reviewed. References 1 Italian Ministry of Health . COVID-19 Situazione in Italia, 2020. Available: (In Italian) [Accessed 8 Apr 2020]. 2 Official Gazette of the Italian Republic . Decreto-Legge "Cura Italia" n. 18. Misure di potenziamento del Servizio sanitario nazionale e di sostegno economico per famiglie, lavoratori e imprese connesse all'emergenza epidemiologica da COVID-19, 2020. Available: (In Italian) [Accessed 8 Apr 2020]. 3 AGI - Italian Journalist Agency . I giovani dottori lavoreranno subito sul territorio, addio all'esame di Stato, 2020. Available: (In Italian) [Accessed 8 Apr 2020]. 4 Italian Ministry of Education, University and Research . National student registry, 2020. Available: [Accessed 8 Apr 2020]. 5 Italian Ministry of Health . Personale del ssn, 2019. Available: (In Italian) [Accessed 8 Apr 2020].
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press 33011681 postgradmedj-2020-138726 10.1136/postgradmedj-2020-138726 Original Research AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 Virtual postgraduate orthopaedic practical examination: a pilot model Iyengar Karthikeyan P Mr Department of Orthopaedics, Southport and Ormskirk NHS Trust, Southport, UK Jain Vijay Kumar Department of Orthopaedics, Atal Bihari Vajpaee Institute of Medical Sciences, New Delhi, India Vaishya Raju Professor Orthopaedics, Indraprastha Apollo Hospital, New Delhi, India Correspondence to Vijay Kumar Jain, Department of Orthopaedics, Atal Bihari Vajpayee Institute of Medical Sciences, Dr Ram Manohar Lohia Hospital, New Delhi 110001, India; [email protected] 10 2021 03 10 2020 03 10 2020 97 1152 650654 19 7 2020 31 7 2020 30 7 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] ABSTRACT COVID-19 pandemic has had a profound impact on the delivery of medical education, training and examination schedule across the world both at undergraduate and at postgraduate (PG) levels. The novel coronavirus SARS-CoV-2 outbreak has resulted in the cancellation of traditional in-person meetings and clinical examination assessments, learning and education activities because of concern of viral transmission. Various medical universities, Royal Medical and Surgical Colleges in the UK have suspended delivery of qualifying examinations until they can be resumed safely with updated social distancing guidelines. This article evaluates the role and the possibility of virtual PG practical examination template based on authors' own recent experience of conducting successful virtual practical PG orthopaedic qualifying examinations during the COVID-19 pandemic in New Delhi, India. Advances in telecommunication technology can enable academic institution and orthopaedic educators to develop such a model and act as a blueprint for the future. Medical education & training pmcIntroduction The highly contagious novel coronavirus SARS-CoV-2 outbreak has necessitated a reduction of 'face-to-face' interactions and various infection prevention strategies including lockdown, social distancing measures and appropriate use of personal protective equipment to prevent viral transmission.1 2 Healthcare systems across the world have adapted, reorganised and restructured the delivery of healthcare to patients during the COVID-19 pandemic.3 Routine elective orthopaedic services have been suspended with 'face-to-face' clinic appointments being replaced by telemedicine virtual consultations to support the public health crisis.4 Teaching hospitals and regional deaneries have rapidly moved towards remote learning using online platforms and webinars. These actions have been found to be at least as effective as other methods of training.5 Qualifying exit undergraduate (UG) and postgraduate (PG) examinations are necessary elements of a medical doctor's career progression. In the UK, COVID-19 has prevented the preparation and organisation of traditional 'face-to-face' practical clinical and viva voce examinations at both the UG and PG levels. Proposed examination scheduled to be held in the spring of 2020 has been suspended until the near future following guidelines issued by the different Royal Medical and Surgical institutions.6 The trainees have been regularly updated about developments, and plans are afoot to resume examination activity from September 2020.7 This resumption in the examination activity is being planned with the expectation that social distancing measures will remain in place and will allow the safety of candidates, examiners and staff members. Hence, there is uncertainty about how practical examinations are going to unfold in the near future. The use of Video-Projected Structured Clinical Examination instead of the traditional oral (viva voce) examination in the assessment of final year medical students has been found to be an effective replacement in the past.8 Advances in telecommunication technology and computer software programs can provide us with an opportunity to apply these to conduct a virtual practical clinical assessment model for the PG candidates appearing for subspeciality examinations during the current pandemic and social distancing restriction guidelines, which we are likely to continue in the future. We propose a virtual PG practical orthopaedic examination template as a tentative blueprint for such examinations in the UK building on the authors own experience, in India. We believe a validated model can then be applied to other subspecialities. Traditional Orthopaedic Postgraduate Frcs (TR and ORTH) Exam The PG qualifying examination for Trauma and Orthopaedics in the UK is the FRCS (Tr and Orth). It is overseen by the Joint Committee on Intercollegiate Examinations (JCIE). Criteria and guidance apply for the exam via the JCIE website (www.jcie.org.uk). The FRCS (Tr and Orth) examination has a set format. It consists of two parts: Part 1 is the written section, delivered through computer-based testing system on an electronic format and consists of extended matching item questions and single best answers questions. The candidate qualifies for the second part following a successful result in Part 1. Part 2 is divided into two sections: (i) clinical examination and (ii) oral table viva voce section. This section requires 'face-to-face' interaction between the candidate, patient or simulated patients, and the examiner during the clinical examination section. The clinical examination section is broadly divided into (i) intermediate clinical examination of two cases: 15 min each, one on upper limb and one on lower limb pathologies. Candidates are expected to present a concise clinical history of the examined case, perform an observed clinical examination, provide a discussion on the approach and management of that particular patient; (ii) six short clinical cases usually divided with three upper limbs and three lower limb pathologies being analysed in 5 min each with focused clinical assessment. The oral table viva voce section has four examination stations on (i) trauma x 30 min, (ii) adult and pathology x 30 min, (iii) paediatric and hands x 30 min and (iv) basic science x 30 min. Current Challenges COVID-19 has created a situation in which conducting a traditional 'face-to-face' part 2 FRCS (Tr and Orth) examination is challenging, impractical and potentially unsafe with the need for infection control and social distancing guidelines. The safety of all those involved in the exam including the candidates, examiners, staff and the patients or examination volunteers acting as patients is of paramount importance. Hence, organisation of examination centres in a socially distanced context to prevent vector transmission is a prerequisite before 'face-to-face' evaluation can resume. A 'zero-patient contact virtual practical exit examination' for orthopaedic trainees can be explored with the assistance of Information and Communications Technology applications and computer-based platforms based on previous such endeavours.8 9 Strategies and Considerations for the Proposed Pathway Prevention of COVID-19 infection: The first and foremost objective is to prevent COVID-19 infection to the examiners, trainees, staff, patients and people involved with examinations. Maintenance of social distancing guidelines including using appropriate personal protective gears (eg, face mask, disposable gloves, etc) will be mandatory. Collection of clinical images: One of the drawbacks of virtual examination is the lack of multidimensional assessment of the patient. To replicate a real-life clinical patient scenario, the stations will have to be replaced with representative clinical images in a multidimensional and preferably a digital format (eg, in a virtual hip case examination scenario, pictures from the anterior, lateral and posterior aspects, in sitting and lying down position of the patient, can provide a complete inspection finding).10 However, it is essential that the patient images are taken, after an informed consent with an explicit explanation given to the patient as to the purpose it will be used for. The undertaking of clinical patient photographs and video recordings must follow the respective National Health Service (NHS) Trust and General Medical Council guidelines to protect patient confidentiality and privacy.11 Information governance and data protection: While making a digital pool of orthopaedic examination cases, data must be made, stored, transferred, protected or disposed as per data protection laws and NHS digital information governance guidelines to avoid any potential breaches. Collection of videos demonstrating patient's gait, clinical sign: Collection of videos demonstrating abnormal gait pattern should be part of clinical assessment in the practical section of the examination. A wide range of clinical knowledge can be assessed by showing such videos to the candidates.12 Preparation of a representative clinical case scenario: A concise clinical history with relevant questions can be put together to make a representative clinical case scenario of disease in such a way that can give clues to reach the proper diagnosis in an examination setting. One example of such a case scenario could be as follows: Tuberculosis of the hip joint in a 12-year-old man, of poor socioeconomic status with a history of low birth weight, presenting with a painful limp with right knee pain on and off for the last 5 months. There could be constitutional symptoms such as weight loss and poor appetite. Examination would reveal wasting of the thigh, limb length discrepancy with decreased abduction, and internal rotation at the hip. The viva can be further built up by asking questions about additional history and examination findings. Use of interactive screen: Use of interactive computer touch screen during the virtual examination can help the examiner to ask the students to draw clinically relevant anatomical angles or to demonstrate pertinent clinical findings (eg, surface making for the site of tenderness in the shoulder and hip pathologies, three-point bony landmarks in the elbow, an illustration of Bryant's triangle for supra-trochanteric shortening of the femur, demonstration of anterior superior iliac spine and measurement of limb lengthening and wasting, etc). The biomechanical axis of the lower limb can easily be drawn on a computer screen for viva purposes. Copyright requirements: If images being used in the virtual practical examinations are transferred from the internet or websites, the appropriate copyright and the licence agreement will have to be confirmed with the original author. Look, feel and move parts of clinical examination: These three steps form a key element of any clinical examination. Look (inspection) can be easily inferred from clinical photographs and video recordings. However, evaluation of palpation (feel), and range of movement (move) sections of the traditional examination is more difficult to replicate in a virtual practical orthopaedic examination but can be highlighted by innovative, interactive case videos and imaging technology. The anxiety of candidates will be expected as it is a new kind of experience to them. Prior information, orientation and demonstrating representative case scenarios on the examination website portal may help candidates and the examiners to acclimatise to the new concept and formally prepare for the virtual practical examination. The examiners should be reasonably considerate with the examinees in such a virtual exam, being a newer method of assessment. Training: Training and learning of skills in acclimatisation with this new concept of a virtual practical examination will be required. Familiarity with audiovisual technology will allow a smooth experience of the examination process which in itself can be an emotive experience. Supervision with regular review of practice will enhance understanding of the virtual clinical examination model, improve both candidate and examiner satisfaction with the process, and can be expanded to other subspeciality examinations. Figure 1 Considerations for setting up a virtual practical postgraduate orthopaedic examination. Figure 2 Flow chart showing organisation for virtual postgraduate orthopaedic clinical examination cases based on current FRCS (Tr and Orth) intercollegiate board, UK examination format. Figure 3 Alphabetical sub-cohorts of Clinical cases. Setting up the Virtual Practical Examination and Organisation A virtual digital library of orthopaedic cases with clinical details of patients including a detailed history, examination findings, multidimensional clinical photographs and/or videos with radiology workup is created. Infrastructure virtual examination cubicles/rooms set up with smart TV and computer and peripherals for digital access. Examiner briefing session. Candidates briefing session including instructions about housekeeping and social distancing guidelines. Intermediate case scenarios. Candidates are provided with information sheets containing brief clinical history and examination findings. Cross-examination of relevant questions to be asked during history undertaken. Pertinent clinical findings leading to diagnosis evaluated. Radiology and role of complementary imaging in arriving at a definitive diagnosis discussed. Short case the clinical picture of the patient with distinct findings can be provided and candidates asked to make a diagnosis and discuss management. Supplementary resources radiology imaging (such as X-rays, CT scan, MRI), orthosis prosthesis, instruments, pathological specimens, surgical approaches and osteology can be collected, and presentations can be made on Microsoft PowerPoint. These power points can be distributed to examiners. Organisation on The Day Digital pool of clinical cases divided into intermediate and short cases cohorts. Alphabetical subcohorts (eg, A to T) each with 2 intermediate and 6 x short cases. These subcohorts can be distributed to candidates with a token selection system in the morning and afternoon sessions depending on the number of examiners available, number of candidates who are appearing and maintenance of social distancing principles. The candidates can be assessed virtually on the digital collection of clinical cases. From a recent experience of conducting a virtual orthopaedic PG exam from the premier apex institution of All India Institute of Medical Sciences, New Delhi, India, there was an excellent overall satisfaction rate among the examinees (4.1 out of 5.0) and the examiners (4.5 out of 5.0). Furthermore, the higher scores were reported for questions related to safety of the exam, relevance and quality of the virtual cases, and so on. Hence, it was concluded that the orthopaedic PG exams can be successfully conducted during the COVID pandemic, by virtual means.13 Limitations of Virtual Practical Postgraduate Orthopaedic Examination There will be a need to ensure quality assurance and improvement of this model. It may be considered an interim solution. Regular audits will need to be undertaken to ensure quality assurance and monitor continual improvement. Serial reviews of practice and 'surveys' of experience of the virtual examination model from both the candidates and the examiners will give an insight into the shortcomings and how the virtual exam technique can be improved. Paucity of three dimensional (3D) evaluation may be another limitation that can be encountered with the virtual concept. However, with the availability of 3D monitors, multidimension imaging and even experience from various 'gaming' consoles can be explored to develop interactive virtual reality models to replicate 'real-life' patient experience. Doctor-patient relationship is an important part of any exam observed by the examiner and this cannot be assessed on virtual practical exams. Lack of overall assessment (general examination, built, mental status, etc) of a patient is not feasible in a virtual examination setting. However, virtual practical examination model is a novel concept put forward by the authors. The model will surely be developed further to become fair, consistent form of assessment as the process is refined. Conclusion It is acknowledged that the SARS-CoV-2 outbreak had a profound effect on the UG and PG training and education across the world. As COVID-19 pandemic currently restricts the possibility of traditional 'face-to-face' practical examination schedules due to social distancing guidelines, innovative models using information and communications technology applications and computer-based programmes as illustrated in this article can be a blueprint for virtual practical examination techniques in the future. It may not replace the traditional 'face-to-face' practical examination assessment, but as confidence in the virtual examination model improves, it can be a useful adjunct to the former. Main messages Social distancing and infection prevention guidelines due to COVID-19 have necessitated the need to discover alternatives to conventional 'face-to-face' practical postgraduate orthopaedic examination techniques. Virtual practical postgraduate orthopaedic examination model can be investigated to facilitate candidate evaluation. Advances in telecommunication technology including 3D monitors, multidimension imaging can be explored to develop interactive virtual reality models to replicate 'real-life' patient experience during the virtual practical examination model. Comparative studies between traditional and virtual modes of conducting practical postgraduate examination models will have to be undertaken to ensure an even platform of assessment. Current research questions How to develop validated tools to assess such a virtual practical examination model? How do we develop a standardisation and consistent evaluation system for the assessment of candidates? How to assess impact of reduced face-to-face and hands-on practical examinations? Footnotes Contributors: ZL conceptualised the study. ZL and SL analysed and interpreted the data, and drafted the manuscript. HF, YL and YZ collected the data. CL and LR contributed to the critical revision of the manuscript. All authors read and approved the final manuscript. Funding: This work was supported by the Science and Technology Research and Development Fund of Shenzhen (no. KJYY20180703165202011), Shenzhen Science and Technology Plan Project (no. JCYJ2017081 81 63505 850). Competing interests: None declared. Ethics approval: In accordance with the Declaration of Helsinki guidelines, the current study was performed and approved by the institutional medical ethical committee of the Shenzhen Second People's Hospital, Shenzhen, China. Provenance and peer review: Not commissioned; externally peer reviewed. Data availability statement: Data are available upon reasonable request. References 1 Centers for Disease Control and Prevention . 2020. Available (accessed 16 Jul 2020) 2 Public Health England . COVID-19: epidemiology, virology, and clinical features. 2020. Available (accessed 16 Jul 2020) 3 Haleem A, Mohd J, Raju V, et al. Effects of COVID-19 pandemic in the field of orthopaedics. J Clin Orthop Trauma 2020;11 :498-9.32405218 4 British Orthopaedic Association . Management of patients with urgent orthopaedic conditions and trauma during the coronavirus pandemic. 2020. Available (accessed 16 Jul 2020) 5 Maertens H, Madani A, Landry T, et al. Systematic review of e-learning for surgical training. Br J Surg 2016;103 :1428-37.27537708 6 Royal College of Surgeons of England . COVID-19 and exams. Available (accessed 16 Jul 2020) 7 Health Education England . Coronavirus (COVID-19) information for trainees. Available (accessed 16 Jul 2020) 8 El Shallaly G, Ali E. Use of Video-Projected Structured Clinical Examination (ViPSCE) instead of the traditional oral (Viva) examination in the assessment of final year medical students. Educ Health (Abingdon) 2004;17 :17-26.15203470 9 Vivekananda-Schmidt P, Lewis M, Coady D, et al. Exploring the use of videotaped objective structured clinical examination in the assessment of joint examination skills of medical students. Arthritis Rheum 2007;57 :869-76.17530689 10 Mutalik S . Digital clinical photography: practical tips. J Cutan Aesthet Surg 2010;3 :48-51.20606997 11 General Medical Council (GMC) . Guidance for doctors. Available (accessed 9 May 2020). 12 Jang HW, Kim KJ. Use of online clinical videos for clinical skills training for medical students: benefits and challenges. BMC Med Educ 2014;14 :56.24650290 13 Malhotra R, Deepak Gautam D, George J, et al. Conducting orthopaedic practical examination during the COVID-19 pandemic. J Clin Orthop Trauma 2020.
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press 32943473 postgradmedj-2020-138747 10.1136/postgradmedj-2020-138747 Editorial AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 'Sono-cardiopulmonary resuscitation' in COVID-19: a proposed algorithm RL Brunda Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India Keri Vishakh C Infectious Diseases (Medicine and Microbiology), All India Institute of Medical Sciences, New Delhi, India Sinha Tej Prakash Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India Bhoi Sanjeev Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India Mishra Prakash Ranjan Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India Correspondence to Tej Prakash Sinha, Emergency Medicine, New Delhi 110049, India; [email protected] 1 2021 17 9 2020 17 9 2020 97 1143 34 22 7 2020 09 8 2020 15 8 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcINTRODUCTION As cardiac arrest occurs in around 20% of the patients with severe COVID-19, a large number of them will require immediate resuscitative efforts.1 Cardiopulmonary resuscitation (CPR) in COVID-19 pandemic has become a source of speculation and debate worldwide. Healthcare professionals (HCPs) resuscitating this subset of patients are subject to fears and enormous mental stress pertaining to risk of transmission, breach in personal protective equipment (PPE), unsure effectiveness of PPE and nevertheless bleak positive outcomes in patients despite best resuscitative measures.2 CPR, which is conventionally deemed to be life-saving for patients, appears as an aerosol-generating procedure risking lives of HCPs caring for patients with COVID-19. Protected code blue algorithm has been formulated to address both performer and patient safety.3 POCUS-INTEGRATED CPR: WHY THE NEED IN COVID-19? Danilo Buonsenso and colleagues have described COVID-19 era as demanding less stethoscope and more ultrasound usage in clinical practice.4 PPE is now an essential measure for HCP protection, and goggles used as a part of PPE are associated with fogging and poor visibility. This coupled with the inability to confirm endotracheal tube position with stethoscope due to poor accessibility in PPE, increases the risk of oesophageal intubation, re-intubation attempts, aerosol generation and thus HCP exposure. Bedside ultrasound could act as visual stethoscope in the described scenario. Sono-CPR in COVID-19 can help intervene quickly in treatable cases and reduce the time spent by HCP in futile resuscitative efforts. Reduced time spent equates to reduced duration of aerosol exposure and thus reduced risk of transmission. Various algorithms are described for sono-cardiopulmonary resuscitation (sono-CPR) during cardiac arrest, but none are discussed to address patients with COVID-19.5 It would hence be wise to integrate bedside point-of-care ultrasound (POCUS) in the code blue algorithm. HOW THE BEDSIDE TOOL HELPS? Hypoxemia and respiratory failure attribute over 80% aetiology of cardiac arrest in patients with COVID-19.1 Prioritising oxygenation and ventilation using definitive airway and use of high-efficiency particulate air filters reduces airborne transmission, thereby making early intubation the dictum of resuscitation.3 Considering poor visualisation due to fogging with the goggles and face shield, inability to use stethoscope and lack of availability of end-tidal CO2 (EtCO2) in resource constraint settings, ultrasound-guided real-time intubation by trained HCP or endotracheal tube (ETT) placement confirmation post intubation could prove beneficial. Confirming ETT placement and direct visualisation of oesophagal lumen can be done using a linear ultrasound probe.6 In cases of oesophageal intubation, tissue-air hyperechoic lines are visualised in both trachea and oesophagus, referred to as 'double-track sign'. State of hypercoagulability and myocardial dysfunction exist in patients with COVID-19, hence increasing the likelihood of myocardial infarction or pulmonary thromboembolism as aetiologies of cardiac arrest.7 Regional wall motion abnormality, dilated right atrium or right ventricle, plethoric inferior vena cava are easily identified by goal-directed echocardiography. Pneumothorax has been reported in patients with COVID-19, and ultrasound can identify absence of lung sliding, helping in quick needle thoracocentesis in arrest and peri-arrest cases. Few cases of cardiac tamponade owing to myopericarditis have also been reported and bedside ultrasound can help diagnose and perform pericardiocentesis in such patients. Literature suggests that the chances of Return Of Spontaneous Circulation (ROSC) and survival to hospital admission at 24 hours is better in patients with baseline cardiac activity rather than no baseline cardiac activity. In patients with no baseline cardiac activity on arrival, one can withhold CPR, thereby protecting the HCP in this resource-intensive, aerosol-generating futile resuscitative effort.8 Asystole could be the disguised entity of fine ventricular fibrillation, which can be confirmed by fibrillatory cardiac activity on transthoracic echocardiography and can be defibrillated, thereby increasing the chances of earlier ROSC.9 POCUS-INTEGRATED CPR: THE PROPOSED ALGORITHM CPR is a chaotic scenario, and to prevent added chaos, there is a need for a well-trained ultrasound performer placed in an appropriate area (figure 1). Intubating room needs to consist of minimal necessary number of HCPs, and all of them should be equipped with full PPE. Ultrasound device could be a potential fomite facilitating cross-transmission and requires adequate protection of machine and its components with a transparent cover, sheet or bag. When unavailable, low-level disinfectant solution should be used between each patient. Figure 1 Proposed algorithm for integration of POCUS during CPR in patients with COVID-19 with team dynamics. The illustration is original work of the authors Dr Brunda RL and colleagues. CPR, cardiopulmonary resuscitation; HCP, healthcare professional; POCUS, point-of-care ultrasound; PPE, personal protective equipment; RA, right atrium; RV, right ventricle; VF, ventricular fibrillation; USG, ultrasonography. When a patient experiences cardiac arrest, there is a need for HCPs with full PPE to check pulse and begin CPR as per standard guidelines. After 2 min of CPR, if there is no ROSC, during the 10 second pause for rhythm assessment, a trained HCP can perform POCUS in a stepwise manner. Each step needs to be performed individually during 10 second pause without prolonging delay between chest compressions and compromising the quality of CPR. Any treatable aetiology identified during the algorithm requires immediate intervention. Step 1: Assess cardiac activity Sub-xiphoid view can be procured and cardiac activity assessed. If absent, consider termination of efforts, and if present, resuscitative efforts can be continued. After repeating 2 min cycle of CPR, if there has been no ROSC, consider hypoxic aetiology as the cause of arrest in patients with COVID-19 and intubate without delay. Withholding chest compressions during intubation is recommended.3 Step 2: Assess ETT placement At the level of thyroid gland, above the suprasternal notch, place ultrasound probe transversely and visualise the oesophagus.10 If the posterior wall of oesophagus is obscured by a dark acoustic shadow or if there is 'double-track' sign, consider failed endotracheal intubation and perform immediate re-intubation. Step 3: Assess lung for pneumothorax Assess lung sliding, and if absent look for 'stratosphere sign' in M-mode of ultrasound.10 If detected, perform immediate needle thoracocentesis. Step 4: Assess for Cardiac etiology of arrest Obtain sub-xiphoid window preferably, and look for the presence of cardiac tamponade, chamber dilatation or collapse, regional wall motion abnormality and cardiac contractility. Availability of trained personnel and smaller portable ultrasound devices makes its use during cardiac arrest plausible. CPR with the help of POCUS could thus prove to improve chances of ROSC and also reduced infection transmission to HCP by early identification, treatment of reversible causes and avoidance of prolonged efforts. Sono-CPR appears to be more HCP-friendly than prolonged blind CPR and necessitates its utility in the era of COVID-19 addressing performer safety as well as patient safety. Footnotes Contributors: BRL contributed to conceptualisation and initial manuscript writing. VCK contributed to conceptualisation, writing, drafting and initial editing of the manuscript. TPS contributed to manuscript editing and drafting. SB contributed to critical revision of the manuscript for important intellectual content. PRM contributed to editing and approval of final version of the manuscript submitted. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; externally peer reviewed. REFERENCES 1 Shao F, Xu S, Ma X, et al. In-hospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China. Resuscitation 2020;151 :18-23.10.1016/j.resuscitation.2020.04.005 32283117 2 Kramer DB, Lo B, Dickert NW. CPR in the COVID-19 era: an ethical framework. N Engl J Med 2020;383 :e6.10.1056/NEJMp2010758 32374958 3 Chan Paul S, Berg Robert A, Nadkarni Vinay M. Code blue during the COVID-19 pandemic. Circ Cardiovasc Qual Outcomes.10.1161/CIRCOUTCOMES.120.006779 4 Buonsenso D, Pata D, Chiaretti A. COVID-19 outbreak: less stethoscope, more ultrasound. Lancet Respir Med 2020.10.1016/S2213-2600(20)30120-X 5 Blanco P, Martinez Buendia C. Point-of-care ultrasound in cardiopulmonary resuscitation: a concise review. J Ultrasound 2017;20 :193-8.10.1007/s40477-017-0256-3 28900519 6 Link Mark S, Berkow Lauren C, Kudenchuk Peter J, et al. Part 7: adult advanced cardiovascular life support. Circulation 2015;132 :S444-S464.10.1161/CIR.0000000000000261 26472995 7 Clerkin Kevin J, Fried Justin A, Jayant R, et al. Coronavirus disease 2019 (COVID-19) and cardiovascular disease. Circulation.10.1161/CIRCULATIONAHA.120.046941 8 Kedan I, Ciozda W, Palatinus JA, et al. Prognostic value of point-of-care ultrasound during cardiac arrest: a systematic review. Cardiovasc Ultrasound 2020;18 :1.10.1186/s12947-020-0185-8 31931808 9 Amaya SC, Langsam A. Ultrasound detection of ventricular fibrillation disguised as asystole. Ann Emerg Med 1999;33 :344-6.10.1016/S0196-0644(99)70372-0 10036350 10 Mishra PR, Bhoi S, Sinha TP. Integration of point-of-care ultrasound during rapid sequence intubation in trauma resuscitation Mishra Prakash Ranjan, Bhoi Sanjeev, Sinha Tej Prakash. J Emerg Trauma Shock 2018;11 :92-7.10.4103/JETS.JETS_56_17 29937637
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press 33040026 postgradmedj-2020-138344 10.1136/postgradmedj-2020-138344 Ethics and Law AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 COVID-19 and medical professionalism in a pandemic Harkin Denis Regional Vascular Surgery Unit, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, Northern Ireland BT12 6BA, UK Correspondence to Denis Harkin, Regional Vascular Surgery Unit, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast BT12 6BA, UK; [email protected] 1 2021 10 10 2020 10 10 2020 97 1143 5354 28 5 2020 29 6 2020 25 6 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcEDITORIAL The global pandemic caused by transmission of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resultantCOVID-191 has created a crisis worldwide for health, healthcare and society. Doctors and healthcare workers will confront fears, and endure risks, making many difficult life-or-death decisions to treat patients and support colleagues as we confront this pandemic. United, in common purpose, we shall prevail against this generational challenge reliant upon our medical professionalism. On 31 December 2019, the WHO China country office was notified of a severe contagious novel pneumonia outbreak in Wuhan, China, and concerned by the severity of illness and rapidity of spread, it was declared a Public Health Emergency of International Concern on 31 December 2019.1 The infection due to SARS-CoV-2 and the resultant coronavirus sisease first identified in 2019 was named COVID-19 by the WHO and declared a global pandemic on 11 March 2020.1 2 COVID-19 is asymptomatic or causes mild illness in most, but in a significant minority causes severe interstitial pneumonia and type-1 respiratory failure with florid systemic inflammatory response leading to multisystem organ failure and death. Worldwide, millions of people have been infected and hundreds of thousands have died, and among them are many front-line healthcare workers and surgeons.1-4 Epicentres have been overwhelmed by the demand for critical care support even in countries with well-resourced healthcare networks and have had to divert any available resource to cope with the pandemic surge.1 2 5 6 Our doctors will be asked to make many challenging decisions as this global pandemic now rages across Europe, the UK and Ireland. Doctors will face unique challenges while managing the pandemic, including the personal risks of infection and the professional challenges of healthcare rationing, clinical priorities and working within a severely restricted health service.7 Doctors are also aware that significant collateral damage will arise from delays to diagnosis and treatment of other acute and chronic conditions. In practice, medical professionalism will involve the interaction between doctors and patients, and this should be a partnership based on respect, integrity and accountability.8 Prerequisite to a healthy patient-doctor relationship is trust; the patient must be able to place trust in their doctor to act in their best interests. Physicians in ancient times pledged upon the Oath of Hippocrates3 to act: 'for the benefit of my patients, and abstain from whatever is deleterious or mischievous'. More recently, the American Board of Internal Medicine Foundation defined three fundamental principles of professionalism: the primacy of patient welfare, patient autonomy and social justice.4 In the UK, the Royal Society of Physicians defined medical professionalism as 'a set of values, behaviours and relationships that underpins the trust the public has in doctors'.9 Upon these professional foundations are built the professional codes of both the UK's General Medical Council8 and Irish Medical Council.9 Here we discuss how the key principles of medical professionalism, as set out by the American Board of Internal Medicine Foundation,47-9 may guide us as we strive to act in patients' best interests and for the greater good of society during this greatest public health emergency for many generations. THE PRIMACY OF PATIENT WELFARE Doctors have a primary responsibility to act in the best interests of their patients, without being influenced by any personal consideration.7 8 10 We provide care with compassion to vulnerable patients in extraordinary moments of fear, anxiety and doubt. Patients with COVID-19 can progress rapidly to severe type-1 respiratory failure, necessitating intubation, ventilation and critical care management.1 2 5 6 In the earliest epicentre of the outbreak in Wuhan, China, the death rate was as high as 5.25%.2 5 Worldwide deaths have mostly occurred in elderly patients and those with co-morbid disease. Epicentres, overwhelmed by demand, have had insufficient ventilators for all in clinical need and have directed finite and scarce resources to those who are most likely to survive. Altruism is defined as the selfless concern for the well-being of others.8 COVID-19 has been transmitted within the hospital setting to infect healthcare workers, inpatients and visitors.6 Indeed, during the global pandemic, thousands of healthcare workers have died with COVID-19 succumbed to the disease. Our doctors, nurses and healthcare professionals, despite those risks, have continued to selflessly place themselves at risk to help patients and support each other. However, to sustainably care for others we must care for ourselves, and that demands we don effective personal protective equipment (PPE) and adhere to infection-control protocols even if that delays or reduces patient contact in an emergency. In a pandemic, some individual patients' best interests may come secondary to the primacy of societies greater good.8 PATIENT AUTONOMY In law, autonomy is often considered a negative right, rather a right to refuse treatment, sometimes termed non-interference.8 In contrast, to interpret autonomy positively would arguably entitle everyone to any requested treatment, regardless of medical advisability or competing claims for finite resources.8 11 12 However, to interpret autonomy in that positive respect would be considered incompatible with other ethical principles of non-maleficence (first do no harm), social justice (fair distribution of finite or scarce resources) and indeed with the practical reality of the provision of healthcare provision in a pandemic.12 In partnership with patients, the doctor has a duty to be honest, and educate and empower patients so they may make the appropriate informed choices about their medical care. During this pandemic, elderly patients and those with co-morbid disease may be considered most vulnerable, and yet are also the least likely to survive. We as doctors are not obligated to offer treatments that are considered to be futile. However, to withhold or withdraw precious life support from one individual considered less worthy for use in another more worthy patient creates a real dilemma for the doctor as patient advocate and public servant.8 The practice of medicine can be distinguished by the need for good judgement in the face of uncertainty. We must rely on our professionalism to do the right thing and be open and honest in communication with patients and families. If we are to maintain the public trust, we must also be candid when treatment choices are restricted by the availability of resources rather than the clinical needs. In a pandemic, when finite resources become scarce, some patient's choices will be restricted and in some situations withheld. SOCIAL JUSTICE The principle of social justice in healthcare obliges us to take into consideration the needs of all patients and availability of resources as we appraise our individual patients' needs.4 We have seen that in pandemic epicentres, highest death rates have coincided with a breakdown of overburdened local healthcare systems. The critical care demand has overwhelmed even well-resourced healthcare systems such that subjective evaluations of the benefits and burdens of life support have had to direct finite resources to those patients most likely to survive.5 6 12 Grave decisions such as these should not be taken alone but by working in partnership with patients, colleagues and teams. Barriers to multidisciplinary team (MDT) decision-making created by the pandemic can be ameliorated by senior front-line clinical leadership, the use of 'hot' (bedside) and 'virtual' (videoconferencing) MDTs, and by deferring those most difficult decisions on prioritisation and healthcare rationing to ethical review panels composed of both medical and lay experts. Social justice also dictates we must consider the indirect harm that will occur from delays to diagnosis, treatment, procedures and surgeries. As the pandemic surge dampens, we must advocate for the safe reintroduction of urgent and then routine care to minimise that collateral damage. To combat this pandemic, we need best guidance on the therapeutic strategies for COVID-19 and how best to protect ourselves and our patients.6 Reassuringly, collaborative efforts of academics and professional associations have rapidly and effectively disseminated best evidence and expert consensus to guide clinicians. Our employers also have a legal and ethical responsibility to protect staff and they must ensure they have sufficient PPE and training to minimise the risks of in-hospital transmission.6 Doctors will have to balance many competing interests, such as personal risk, best interests, society's interests, clinical priorities, ceilings-of-care, withholding and withdrawing care.12 They will also need to adapt to modified service delivery, intense work-patterns, moratoriums on annual and study leave, and altered career-pathways. In exceptional circumstance, staff and students will be asked to act outside of their normal role but should strive to work within their competence with rapid retraining, upskilling and supervision. Justice dictates that as doctors will endure these changes, society (including employers and our professional bodies) should ensure staff are appropriately supported through and beyond the pandemic in respect to health, well-being, career, indemnity, licencing and revalidation. CONCLUSIONS Doctors have a duty and responsibility to act according to the best values of medical professionalism, and society has a corresponding duty to ensure the infrastructure and support available allow doctors to deliver those responsibilities as safely as possible. Our professionalism will help guide doctors to do the right thing and strive to get the best available outcomes for their patients during this COVID-19 pandemic. There will of course be pain, but we shall persevere and together hope to build a better future to honour those who are lost along the way. Acknowledgements The responsibility for the content lies with the author and the views stated herein should not be taken to represent those of any organisations or groups with and for which he works. Footnotes Twitter: denisharkin. Contributors: DWH conceived, researched and wrote this article. Funding: The author has not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: The author has read and understood the policy on declaration of interests and has no relevant interests to declare. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; externally peer reviewed. REFERENCES 1 WHO director-general's opening remarks at the media briefing on COVID-19. Available (accessed 11 Mar 2020) 2 Guan WJ, Ni ZY, Hu Y, et al. China medical treatment expert group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382 :1708-20.10.1056/NEJMoa2002032.32109013 3 The Oath of Hippocrates . From the genuine works of hippocrates translated from the greek by Francis Adams, surgeon, volume 2. London, 1849. 4 American Board of Internal Medicine Foundation . American college of physicians: American society of internal medicine foundation. European Federation of Internal Medicine Medical professionalism in the new millennium: a physician charter. Ann Intern Med 2002;136 :243-6.10.7326/0003-4819-136-3-200202050-00012.11827500 5 Yang S, Cao P, Du P, et al. , Early estimation of the case fatality rate of COVID-19 in mainland China: a data-driven analysis. Ann Transl Med 2020;8 :128.10.21037/atm.2020.02.66.32175421 6 Gan N, Thomas N, CNN CD. Over 1,700 frontline medics infected with coronavirus in China, presenting new crisis for the government. 2020. Available (accessed 2 Mar 2020) 7 Harkin DW . Covid-19: balancing personal risk and professional duty. BMJ 2020;369 :m1606.10.1136/bmj.m1606.32350003 8 Harkin DW . Ethics for surgeons during the COVID-19 pandemic, review article. Ann Med Surg (Lond) 2020;55 :316-9.10.1016/j.amsu.2020.06.003.32537140 9 Working Party of the Royal College of Physicians . Doctors in society: medical professionalism in a changing world. Clin Med (Lond) 2005;5 :S5-40.16408403 10 General Medical Council . Good medical practice. 2013. Available (accessed 11 Mar 2020) 11 Guide to professional conduct and ethics for registered medical practitioners (amended) 8th edition. Available 12 Gedge E, Giacomini M, Cook D. Withholding and withdrawing life support in critical care settings: ethical issues concerning consent. J Med Ethics 2007;33 :215-8.10.1136/jme.2006.017038.17400619
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press postgradmedj-2020-138056 10.1136/postgradmedj-2020-138056 Letter AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 Risk-benefit analysis on the clinical significance of convalescent plasma therapy in the management of COVID-19 Dhanasekaran Sivaraman Department of Pharmacology and Toxicology, Centre for Laboratory Animal Technology and Research, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India School of Pharmacy, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India Vajravelu Leela Kagithakara Department of Microbiology, SRM Medical College Hospital and Research Centre, Kancheepuram, Tamil Nadu, India Venkatesalu Venugopal Department of Internal Medicine, Sundaram Health Centre, Sholinghur, Tamil Nadu, India Correspondence to Sivaraman Dhanasekaran, Department of Pharmacology and Toxicology, Centre for Laboratory Animal Technology and Research, Sathyabama Institute of Science and Technology, Jeppiaar Nagar, Rajiv Gandhi Road, Chennai, Tamil Nadu 600119, India; [email protected];[email protected] 7 2021 17 8 2020 17 8 2020 97 1149 467468 29 6 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcThe pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already on the list of the greatest threat that human beings have ever encountered in modern history. In the present scenario, SARS-CoV-2 has become a major burden on public health and economic stability of societies around the globe. Currently, there is no known cure attained for treating COVID-19. Epidemic forecast expecting higher incidence of mortality in severely affected zones. Despite global effort in finding suitable vaccine candidates for the pandemic SARS-CoV-2, re-emerging convalescent plasma (CP) therapy is an ideal strategy, which gains paramount importance.1 However, this strategy requires some crucial validation with respect to ethical consideration, criteria for donor selection, titer quantification, dose optimisation, limitation factors, chances of occurrence of transfusion events, etc.2 CP therapy benefits the society since several years. It has a long history of serving as a viable clinical remedy for treating a range of viral infections such as Spanish influenza, influenza A (H1N1pdm09),3 Middle East respiratory syndrome,4 Ebola,5 SARS6 and now for SARS-CoV-2.7 Documentary reports suggested that first-ever transfusion of CP attempted during the pandemic spread of Spanish influenza (1918-1920).8 In general, CP therapy drives through humoral immunity (antibody-oriented therapy) specific to immunogenic viral antigen. Immunologically individuals with SARS-CoV-2 infection adopt a unique mechanistic pathway in processing antigenic proteins.9 Adaptive immune mechanisms substantiate the initial phase of antigen processing, and this often fails in the majority of cases with COVID-19. Clinical outcomes clarify that failure of adaptive immunity in the SARS-CoV-2 infection will call for cytokine storms and thus leads to severe organ dysfunction.10 Hence, transfusion of CP in the early possible stage of infection will surely halt the viral replication, thereby flattening the viral load (viremia), and effectively counteracts inflammation-mediated tissue damage. Efficacy of CP therapy measured in the scale of emerging neutralising antibody titer (NAT) level in the recipient circulation. This implicates the tendency of the NAT to neutralise the viral antigen and lower the viral bioburden.11 Results of earlier studies demonstrated that the highest range of seroconversion in SARS-CoV-2 was observed between 8 and 21 days of onset of disease symptoms. Conceptually neutralising antibodies emerge into circulation within 14-21 days of infection. Other findings suggested that higher antibody titer documented in 14 days of mean time point of disease recovery. In this context as per regulatory procedure, the primary level of confirmation on antibody titer will be quantified prior to plasma collection. Outcome of recent clinical investigation on five critically ill cases with COVID-19 reveals that treatment with CP advocates considerable clinical improvement, ensures significant declination in viral load, improves retrieval from ventilation support and demonstrates high level of stability. Further, patients tested negative for viral RNA within 12 days of CP transfusion.12 Knowledge gaining part of this study is that quantification index on plasma collection specific for binding titer optimised as 1:1000 IgG and for neutralisation titer >40 dilution offers measurable recovery in treated cases. Another pilot study conducted in 10 cases with COVID-19 subjected to CP therapy reciprocates 100% clinical improvement with titer value >1:640, and 7 of 10 cases turn negative to viral RNA within 7 days of CP (200 mL) transfusion in addition to improved serological and radiology profile.13 Recently, the U.S. Food and Dug Administration (USFDA) issued guidelines favouring investigational protocol involving CP therapy for treating patients with COVID-19.14 It was observed as a conditional regulation for tier I (clinical trial under Investigational New Drug (IND)), tier II (expanded access for non-trial participants) and tier III (IND emergency therapy); further to it, FDA has not been approved CP regimen for prophylaxis. Informed consent from both donor and recipients has to be obtained prior to the start of the procedure. In case of critically ill recipients, consent may be advocated through attorney or by legally authorised healthcare proxy on their behalf in accordance with healthcare surrogate act. Two studies currently initiated with a base population of 10-20 patients with COVID-19 for investigating the transfusion benefits of CP as an empirical therapy are in early phase I.15 16 Clinical guideline intensifies the following inclusion criteria for donors,: (1) complete resolution of symptoms for at least 14 days prior to donation, (2) completed 28 days of post-recovery period, (3) reveals positive for SARS-CoV-2 antibodies in serology screening, (4) satisfies minimum two negative tests for viral RNA within 48 hours of repetition, (5) possess minimum antibody titer limit (1:160) and (6) donor should be free from other sorts of infections (hepatitis, HIV, syphilis, etc). In some special circumstances, donors are expected to satisfy human leukocyte antigen matching requirements before the start of plasma retrieval. Similarly, recipients should comply with the following inclusion criteria: (1) patients with laboratory-confirmed COVID-19 infection, (2) patients reported as critically ill (severe respiratory failure, septic shock, organ failure) and (3) preferably less than 21 days of report of illness.17 Transfusion will be initiated when both donors and recipients satisfy the regulatory needs. Clinical assessment of CP therapy was ascertained based on duration of hospital stay, clinical signs of recovery, change in serology/radiology findings, devoid of ventilation support and mortality index. In spite of proven clinical efficacy, CP therapy is subjected to certain limitations. The primary limiting factor on availing CP therapy relies on possible transmission of infection from donors, which includes hepatitis B/C, syphilis and HIV.18 Hence, adequate measures on screening pre-existing infections and other qualities of donors become highly mandatory. Another potential risk factor in CP therapy is chances of occurrence of life-threatening transfusion events such as anaphylactic shock, circulatory over stack, intensified lung injury, hemolytic reactions.19 Potentiation of antibody-dependent enhancement (ADE) is another considerable risk involved in CP transfusion.20 ADE occurs due to hyperactive antibodies that emerged in response to earlier viral infection. In cases with COVID-19, these antibodies upon exposure to antigen of different genomic origins further worsen the infection. In conclusion, globally, there are limited data available on the safety and efficacy of CP in treating patients with COVID-19. Outcome of preliminary studies shows promising therapeutic response; however, large-scale multicentric trials will be needed to ensure the effectiveness of the therapy across the globe. Acknowledgements The authors thank the financial contribution by the Indian Council of Medical Research (ICMR), New Delhi, India (Ref 35/2/2019-Nano/BMS). Footnotes Contributors: SD: study design, literature review, data collection, framework and drafting of the letter. LKV: data validation and critical revision of the letter. VV: framework and technical editing of the letter. All authors have read and approved the final version of the letter. Funding: This work was financially supported by the Indian Council of Medical Research (ICMR), New Delhi, India. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; externally peer reviewed. REFERENCES 1 Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: the reality and challenges. J Microbiol Immunol 2020.10.1016/j.jmii.2020.03.034. 2 Bloch EM, Shoham S, Casadevall A, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest 2020;130 :2757-65.10.1172/JCI138745. 32254064 3 Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis 2011;52 :447-56.10.1093/cid/ciq106 21248066 4 Ko JH, Seok H, Cho SY, et al. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir Ther 2018;23 :617-22.10.3851/IMP3243. 29923831 5 Sahr F, Ansumana R, Massaquoi TA, et al. Evaluation of convalescent whole blood for treating Ebola virus disease in Freetown, Sierra Leone. J Infect 2017;74 :302-9.10.1016/j.jinf.2016.11.009. 27867062 6 Zhang JS, Chen JT, Liu YX, et al. A serological survey on neutralizing antibody titer of SARS convalescent sera. J Med Virol 2005; 77 : 147-50. Available 16121363 7 Chen L, Xiong J, Bao L, et al. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020;20 :398-400.10.1016/S1473-3099(20)30141-9 32113510 8 Lesne E, Brodin P, Saint GF. Plasma therapy in influenza. Presse Med 1919;27 :181-2. 9 Kong WP, Xu L, Stadler K, et al. Modulation of the immune response to the severe acute respiratory syndrome spike glycoprotein by gene-based and inactivated virus immunization. J Virol 2005;79 :13915-23.10.1128/JVI.79.22.13915-13923.2005 16254327 10 Shi Y, Wang Y, Shao C, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ 2020;27 :1451-4.10.1038/s41418-020-0530-3 32205856 11 Marano G, Vaglio S, Pupella S, et al. Convalescent plasma: New evidence for an old therapeutic tool? Blood Transfus 2016;14 :152-7.10.2450/2015.0131-15 26674811 12 Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020;323 :1582.10.1001/jama.2020.4783 32219428 13 Duan K, Liu B, Li C, et al. The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study. medRxiv 2020;10.1101/2020.03.16.20036145 14 CBER . Investigational COVID-19 convalescent plasma - emergency INDs. Available (accessed 30 Apr 2020). (accessed 30 Apr 2020). 15 Pilot study for use of convalescent plasma collected from patients recovered from COVID-19 disease for transfusion as an empiric treatment during the 2020 pandemic at the University of Chicago Medical Center. ClinicalTrials.gov Identifier: NCT04340050. Available (accessed 30 Apr 2020). (accessed 30 Apr 2020). 16 Anti COVID-19 Convalescent Plasma Therapy . ClinicalTrials.gov Identifier: NCT04345679. Available (accessed 30 April, 2020). (accessed 30 April, 2020). 17 Recommendations for investigational COVID-19 convalescent plasma. Available (accessed 10 May 2020). (accessed 10 May 2020). 18 Fleming AB, Raabe V. Current studies of convalescent plasma therapy for COVID-19 may underestimate risk of antibody-dependent enhancement. J Clin Virol 2020;127 :104388.10.1016/j.jcv.2020.104388.32361326 19 Zhao Q, He Y. Challenges of convalescent plasma therapy on COVID-19. J Clin Virol 2020;127 :104358.10.1016/j.jcv.2020.104358.32305026 20 Katzelnick LC, Gresh L, Halloran ME, et al. Antibody-dependent enhancement of severe dengue disease in humans. Science 2017;358 :929-32.10.1126/science.aan6836. 29097492
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press postgradmedj-2020-137853 10.1136/postgradmedj-2020-137853 Letter AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 Point-of-care ultrasound in COVID-19 pandemic Bhoi Sanjeev Emergency Medicine, All India Institute of Medical Sciences, New Delhi, Delhi, India Sahu Ankit Kumar Emergency Medicine, All India Institute of Medical Sciences, New Delhi, Delhi, India Mathew Roshan Emergency Medicine, All India Institute of Medical Sciences, New Delhi, Delhi, India Sinha Tej Prakash Emergency Medicine, All India Institute of Medical Sciences, New Delhi, Delhi, India Correspondence to Dr Ankit Kumar Sahu, Emergency Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, India; [email protected] 1 2021 13 5 2020 13 5 2020 97 1143 6263 05 5 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcA multifold increase in patient volume presenting to emergency departments (EDs) during a pandemic demands escalation of surge capacity, including radiological services. In previous pandemics such as severe acute respiratory syndrome and Middle East respiratory syndrome, increased requirement for chest imaging had led to significant overloading of patients in the ED.1 2 As point-of-care ultrasound (POCUS) has been demonstrated to identify, in real time, various pathologies of the lung, integration of it was done during patient care in these pandemics and was found to be a great adjunct to clinical decisions.1 2 Very few case reports and case series have been published regarding the use of POCUS in the recent pandemic of COVID-19. In a case series of 20 patients with confirmed COVID-19 by Peng et al, lung sonographic findings were pleural line irregularity and thickening, focal B-lines, bilateral diffuse B-profile with spared areas, subpleural consolidation and, rarely, pleural effusion, which were consistent with CT findings.3 Similar findings were reported by Huang et al 4 in 20 patients, by Poggiali et al 5 in 12 patients and by Buonsenso et al 6 in a single patient. Additionally, a Doppler study showed poor blood flow in the COVID-19 consolidation, in contrast to abundant blood flow signal in inflammatory bacterial pneumonia.4 In this paper, we suggest a protocol of integration of POCUS in the holistic management of patients with COVID-19 (figure 1), from triage to ED to intensive care unit (ICU). Figure 1 Integration of POCUS in COVID-19 patient management. *Suspected or confirmed COVID-19 case on the basis of recent WHO case definitions. $Severity of cases: mild disease: no pneumonia or pneumonia; severe disease: dyspnoea or tachypnoea (respiratory rate>30 breaths/min); or critical disease: respiratory failure, septic shock or multiorgan dysfunction. **Differentiation of ARDS from CPE on the basis of presence of bilateral pleural line abnormality (thickening>2 mm, coarse pleural line), small subpleural consolidations, 'spared areas' in between B-lines, 'lung pulse' and reduced or absent lung sliding. ARDS, acute respiratory distress syndrome; CPE, cardiogenic pulmonary oedema; ED, emergency department; IVC, inferior vena cava; POCUS, point-of-care ultrasonography. All suspected or confirmed cases of COVID-19 as per WHO guidelines should be triaged on the basis of clinical stability7 and institutional triage protocol. Severe (dyspnoea, tachypnoea and hypoxia) or critically ill patients (respiratory failure, septic shock and multiorgan dysfunction) should be sent to ED without POCUS in the triage area. Patients with mild clinical features should undergo POCUS in the triage area for identifying lung pathologies like pleural line abnormalities, presence of B-lines, consolidation and pleural effusion.6 If any of the aforementioned is present, the patient should be shifted to ER for further diagnostic evaluation or otherwise can be sent for home isolation safely. In the ED, POCUS can be integrated in a fashion similar to that of primary survey. During 'airway' management, it can be used as an adjunct for endotracheal tube position confirmation. For 'breathing' assessment, detailed lung pathologies like pleural line irregularity or thickening, presence of B-lines, consolidations with or without air bronchograms, blood flow in consolidation, pleural effusion and pneumothorax can be assessed.3 4 Even complications like acute respiratory distress syndrome (ARDS) can be diagnosed by lung sonography and differentiated from cardiogenic pulmonary oedema on the basis of presence of bilateral pleural line abnormality (thickening>=2 mm, coarse pleural line), small subpleural consolidations, 'spared areas' in between B-lines, 'lung pulse', and reduced or absent lung sliding.8 It can also be used to assess cardiac contractility and fluid status by inferior vena cava diameter as a part of 'circulation' management. Once patients are admitted in the ICU, apart from using the same POCUS algorithm of ED, it can be used to monitor the course of disease like quantifying B-lines in different sonographic lung regions, size of consolidation or pleural effusion, and development or resolution of any other lung abnormalities. Further, lung recruitment manoeuvres for mechanical ventilation of patients with ARDS can be monitored. Even fluid therapy can be tailored on the basis of POCUS findings.3 Recognised limitations of lung ultrasonography (USG) are that findings in COVID-19 are non-specific and it cannot detect lesions that are deep within the lung; that is, the abnormality must extend to the pleural surface to be visible with on USG examination. Although sonographic findings of COVID-19 were predominant in posterior and inferior lung fields, it is feasible to use POCUS in patients with ARDS undergoing prone ventilation. Another limitation of lung USG is that is it an operator-dependent technique and needs close contact with the patient, which may contribute to the COVID transmission to the sonographer. A separate ultrasound machine and probe should be used for COVID-19 patient imaging to prevent cross infection. In the triage area and ED (during low-risk aerosol generating procedures), it is recommended that probe covers (if available) be used and that the surface of the USG machine that come into contact with either the patient or the clinician be disinfected with low-level disinfectants (LLDs; ethyl or isopropyl alcohol, 70%-90%). During high-risk aerosol-generating procedures like endotracheal intubation in the ED and ICU, the machine and its components should be protected with probe covers and draping material such as translucent bags. These covers should be discarded prior to exiting the patient's room, taking care to avoid cross contamination. LLDs should be used above the probe covers. Portable handheld USG devices are much easier to decontaminate and should be used if available.9 POCUS will help in initial screening and segregation of non-severe patients from severe ones.6 The utility of POCUS is more marked in temporary healthcare facilities like isolation wards, where availability of a routine X-ray and CT machines is not possible. The evaluating clinician in the ED or ICU can do lung sonography at bedside for evaluation and monitoring, rather than sending the patient to the X-ray or CT room or using a portable X-ray machine, which needs additional manpower. This will limit the potential exposure to other healthcare workers (HCWs) and people during in-hospital transfer. As recommended by the American College of Radiology, the imaging suite should be environmentally cleaned and decontaminated after every contact with suspected patients, which is obviously more tedious than cleaning a portable ultrasound machine.10 We therefore suggest that POCUS be used in COVID-19 patient management, starting from the triage area to ICU care. This will address the safe discharge of patients for home isolation, radiological surge capacity and frequent bedside monitoring, and will limit the biological and radiation exposures to HCWs. Footnotes Contributors: All authors contributed significantly to the paper and take full responsibility for its content. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; externally peer reviewed. References 1 Ho SSY, Chan PL, Wong PK, et al . Eye of the storm: the roles of a radiology department in the outbreak of severe acute respiratory syndrome. AJR Am J Roentgenol 2003;181 :19-24.10.2214/ajr.181.1.1810019 12818823 2 Das KM, Lee EY, Langer RD, et al . Middle East respiratory syndrome coronavirus: what does a radiologist need to know? AJR Am J Roentgenol 2016;206 :1193-201.10.2214/AJR.15.15363 26998804 3 Peng Q-Y, Wang X-T, Zhang L-N. Findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic. Intensive Care Med 2020;45 . 4 Huang Y, Wang S, Liu Y, et al . A preliminary study on the ultrasonic manifestations of Peripulmonary lesions of Non-Critical novel coronavirus pneumonia (COVID-19). SSRN Electronic Journal 2020. 5 Poggiali E, Dacrema A, Bastoni D, et al . Can lung us help critical care clinicians in the early diagnosis of novel coronavirus (COVID-19) pneumonia? Radiology 2020;200847 :200847. 10.1148/radiol.2020200847 6 Buonsenso D, Piano A, Raffaelli F, et al . Point-Of-Care lung ultrasound findings in novel coronavirus disease-19 pnemoniae: a case report and potential applications during COVID-19 outbreak n.d. 7 Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA 2020. 8 Copetti R, Soldati G, Copetti P. Chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome. Cardiovasc Ultrasound 2008;6 :16. 10.1186/1476-7120-6-16 18442425 9 American Institute of Ultrasound in Medicine (AIUM) . Quick guide on COVID-19 protections ultrasound transducers, equipment, and gel 2020. 10 Hosseiny M, Kooraki S, Gholamrezanezhad A, et al . Radiology perspective of coronavirus disease 2019 (COVID-19): lessons from severe acute respiratory syndrome and middle East respiratory syndrome. AJR Am J Roentgenol 2020;214 :1078-82.10.2214/AJR.20.22969 32108495
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Coronavirus has emerged as a global health threat due to its accelerated geographic spread over the last two decades. This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Historically, it has caused two pandemics: severe acute respiratory syndrome and Middle East respiratory syndrome followed by the present COVID-19 that emerged from China. The virus is believed to be acquired from zoonotic source and spreads through direct and contact transmission. The symptomatic phase manifests with fever, cough and myalgia to severe respiratory failure. The diagnosis is confirmed using reverse transcriptase PCR. Management of COVID-19 is mainly by supportive therapy along with mechanical ventilation in severe cases. Preventive strategies form the major role in reducing the public spread of virus along with successful disease isolation and community containment. Development of a vaccine to eliminate the virus from the host still remains an ongoing challenge. Pathology Histopathology Education and training (see medical education & training) Medical education and training Surgery Transplant surgery Hepatobiliary surgery Basic sciences Pathology pmcIntroduction Coronavirus (CoV) is derived from the word 'corona' meaning 'crown' in Latin.1 It causes a range of human respiratory tract infections varying from mild cold to severe respiratory distress syndrome.2 The present novel CoV disease also called as severe acute respiratory syndrome (SARS)-CoV-2 and coronavirus disease 2019 (COVID-19) is an emerging global health threat.3 The COVID-19 epidemic started from Wuhan city of China towards the end of December 2019 and since then spread rapidly to Thailand, Japan, South Korea, Singapore and Iran in the initial months.4-6 This was followed by wide viral dissemination around the world including Spain, Italy, USA, UAE and the UK.7 The WHO declared the COVID-19 outbreak as a pandemic.8 As of 6 May 2020, outbreaks and sporadic human infections have resulted in 3 732 046 confirmed cases and 261 517 deaths.7 The CoV has posed frequent challenges during its course ranging from virus isolation, detection, prevention to vaccine development.9 CoV belongs to the order Nidovirales and has the largest RNA genome.10 It is known to be acquired from a zoonotic source and typically spreads through contact and droplet transmission. The infected person presents with non-specific clinical features requiring virological detection and confirmation by molecular techniques.11-13 This article aims to give a detailed insight into the evolution, transmission and diagnosis of COVID-19. We further discuss the challenges encountered in the management of patients with COVID-19 and the current limitations in the investigational vaccine. Due to the rapidly evolving nature of COVID-19, the readers are requested to update themselves with the nature of change with this particular type of CoV. ORIGIN Historic perspective CoV was discovered during the 1960s. The Coronavirus Study Group under the International Committee on Taxonomy of Viruses used the principle of comparative genomics to further assess and partition the replicative proteins in open reading frames to identify the factors that differentiate CoV at different cluster ranks.14 15 CoV is associated with illness of varied intensity. The most severe type resulting in large-scale pandemics in the past are the SARS (in 2002-2003) and Middle East respiratory syndrome (MERS) (in 2012).16 17 Aetiology CoV are RNA viruses of the subfamily Coronavirinae. They belong to the family Coronaviridae and the order Nidovirales (nido Latin for 'nest'). The order Nidovirales is composed of Coronaviridae, Arteriviridae, Mesovirididae and Roniviridae families.10 18 The characteristic features of Nidovirales are as follows: they (1) contain very large genomes for RNA viruses, (2) are highly replicative due to conserved genomic organisation, (3) exhibit several unique enzymatic activities and (4) have extensive ribosomal frameshifting due to the expression of numerous non-structural genes. The Coronaviridae family have two subfamilies: Coronavirinae and Torovirinae. The subfamily Coronavirinae consist of alpha CoV, beta CoV, gamma CoV and delta CoV based on genomic structure.19 Viral structure The CoV are enveloped positive single-stranded RNA viruses having the largest known viral RNA genomes of 8.4-12 kDa in size.20 The viral genomes are made up of 5' and 3' terminal. The 5' terminal constitutes a major part of the genome and contains open reading frames, which encodes proteins responsible for viral replication. The 3' terminal contains the five structural proteins, namely the spike protein (S), membrane protein (M), nucleocapsid protein (N), envelope protein (E) and the haemagglutinin-esterase (HE) protein.21 22 The S protein mediates an attachment and fusion between the virus and host cell membrane and also between the infected and adjacent uninfected cells. They are the major inducers for neutralising antibodies in a vaccine. The N protein forms RNA complexes that aid in virus transcription and assembly. The M protein is the most abundant structural protein and also defines the viral envelope shape. The E protein is the most enigmatic and the smallest of the major structural protein, which is highly expressed within the infected cell during viral replication cycle. The HE protein is responsible for receptor binding and host specificity.20 23 SARS and MERS SARS was first recognised in Guangdong province, China, in November 2002. It advanced among 30 countries, infecting 79 000 people by 2003 with a fatality of 9.5%. SARS-CoV was traced and isolated from Himalayan palm civets found in a livestock market in Guangdong, China.16 24 The zoonotic origin of SARS was also discovered in racoon dogs, ferret badgers and in humans working at the same market. These market animals were therefore intermediate hosts that increased the transmission of virus to humans.15 24 Thereon, in 2012, Jeddah, Saudi Arabia, a patient presented with respiratory illness consistent with pneumonia along with features of renal failure.25 The patient's sputum analysis was done by reverse transciptase (RT-PCR) using pan-CoV primers revealing the viral RNA to be MERS-CoV.26 As of July 2013, 91 patients were infected with MERS-CoV and had a high fatality rate of 34%. Bats and Arabian dromedary camels were identified as potential hosts for MERS-CoV. Intermediate host reservoir species were also seen in goats, sheep and cows.27 28 Novel CoV In view of taxonomical classification, SARS-CoV-2 (COVID-19) is one among many other viruses in the species, SARS-related CoV. However, SARS-CoV and SARS-CoV-2 vary in terms of disease spectrum, modes of transmission and also diagnostic methods.9 28 The recent report on a cluster cases having respiratory illness in Wuhan, Central China, was followed by a global spread of the disease in a very short duration of time. The samples (oral and anal swabs, blood and broncho-alveolar fluid lavage) from patients admitted to the intensive care unit of Wuhan Jinyintan Hospital were sent to Wuhan Institute of Virology. Pan-CoV PCR primers were used and these samples were positive for CoV.1-3 29 This was followed by metagenomics analysis and genomic sequencing study. The results revealed that this virus was identical (79.6%) to the genetic sequence of SARS-CoVBJ01 leading the WHO to call it novel CoV-2019 (2019-nCoV).30 31 Transmission and Pathogenesis Zoonosis CoVs are widespread among birds and mammals with cements bats forming the major evolutionary reservoir and ecological drivers of CoV diversity.32 CoV causes a large variety of diseases in pigs, cows, chicken, dogs and cats. The major diseases caused by CoVs in animals are transmissible gastroenteritis virus, porcine epidemic diarrhoea virus, porcine hemagglutinating encephalomyelitis virus and murine hepatitis virus. In humans, alpha and beta CoV have caused a variety of illness ranging from mild-self-limiting respiratory infections (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) to severe acute respiratory distress syndrome (ARDS).16 33-35 Initial cases reported in Wuhan, China, are considered to be an acquired infection from a zoonotic source from Huanan wholesale seafood market which sold poultry, snake, bats and other farm animals.36 37 To isolate the possible virus reservoir, a comprehensive genetic sequence analysis was undertaken among different animal species.9 15 The results suggested that 2019-nCov is a recombinant virus between the bat CoV and an unknown origin CoV. A study revealed, based on relative synonymous codon usage (RSCU) on variety of animal species showed that bats are the most probable wildlife reservoir of 2019-nCov.10 This homologous recombination has proved previously in classical swine fever virus, hepatitis B virus, hepatitis C virus, HIV and dengue virus.38 Modes of spread Human-to-human transmission occurs through common routes such as direct transmission, contact transmission and airborne transmissions through aerosols and during medical procedures (figure 1). Cough, sneeze, droplet inhalation, contact with oral, nasal and eye mucous membranes are the common modes of spread. Viral shedding occurs from respiratory tract, saliva, faeces and urine resulting in other sources of virus spread.37 39 40 The viral load is higher and of longer duration in patients with severe COVID-19.41 Spread of COVID-19 from patients to health workers and flight attenders who were in close contact with the infected patients are also reported.42 Figure 1 Modes of transmission. Virus-host interaction Extensive structural analyses revealed atomic-level interactions between the CoV and the host. Cross-species and human-to-human transmission of COVID-19 is mainly dependent on spike protein receptor-binding domain and its host receptor ACE2.23 43 High expression of ACE2 was identified in lung (type II alveolar cells), oesophagus, ileum, colon, kidney (proximal convoluted tubules), myocardium, bladder (urothelial cells) and also recently the oral mucosa. ACE2 receptors provide entry of the virus into the host cells and also subsequent viral replication. The main factors involved in viral pathogenesis of 2019-nCov are spike 1 subunit protein, priming by transmembrane protease serine-2 (essential for entry and viral replication), ACE2 receptor-2019-nCov interaction and downregulation of ACE2 protein. These factors contribute to atrophy, fibrosis, inflammation and vasoconstriction resulting in host tissue injury.43-45 Clinical Presentation and Diagnosis Demographics Based on numerous studies published, the median age was 56 years (range 55-65 years) and males were predominately affected due to high ACE2 concentrations in them. The median onset of illness was 8 days (range 5-13 days).46 47 Due to limited comorbid data availability, it is important to correlate with previously proven susceptible factors to SARS and MERS-CoV infection, which includes smoking, hypertension, diabetes, cardiovascular disease and/or chronic illness.16 24 25 Based on the National Health Institute analysis in Italy, the average mortality age for patients suffering from COVID-19 was 81 years.48 In China, the case fatality rate (CFR) increased with age and showed CFR of 18% for patients above 80 years.49 This striking target to the elderly population is attributed to underlying chronic disorders and declined immune function. Declined immune function has been linked to cytokine storm syndrome (elevated circulating inflammatory cytokines) and hyper-inflammation syndrome. These syndromes are triggered by viral infections and are also predictors of fatality in patients with COVID-19.50 51 Children are less affected due to higher antibodies, lower prior exposure to the virus and relatively low levels of inflammatory cytokines in their systems. Signs and symptoms Clinical features varied from mild illness to severe or fatal illness. The most common symptoms of COVID-19 were non-specific and mainly included fever, cough and myalgia. Other minor symptoms were sore throat, headache, chills, nausea or vomiting, diarrhoea, ageusia and conjunctival congestion. The COVID-19 was clinically classified into mild to moderate disease (non-pneumonia and pneumonia), severe disease (dyspnoea, respiratory frequency over 30/min, oxygen saturation less than 93%, PaO2/FiO2 ratio less than 300 and/or lung infiltrates more than 50% of the lung field within 24-48 hours) and critical (respiratory failure, septic shock and/or multi-organ dysfunction/failure).12 52 Many of the elderly patients who had severe illness had evidence of chronic underlying illness such as cardiovascular disease, lung disease, kidney disease or malignant tumours.53 Laboratory evaluation and confirmation Laboratory findings most consistent with COVID-19 were lymphocytopenia, elevated C reactive protein and elevated erythrocyte sedimentation rate. Lymphocytopenia is due to necrosis or apoptosis of lymphocytes. The severity of lymphocytopenia reflects the severity of COVID-19.54-56 Procalcitonin was commonly elevated and was associated with coinfection in majority of reported paediatric cases.57 58 Detection of COVID-19 is based on virological detection by RT-PCR using swabs (nasopharynx, oropharynx), sputum and faeces, chest radiograph and dynamic monitoring of inflammatory mediators (eg, cytokines).59-61 Faecal specimens detected for COVID-19 nucleic acid was equally accurate as of pharyngeal swab specimens.60 Patients with COVID-19 showed high blood levels of cytokines and chemokines such as interleukin (IL)-7, IL-8, IL-9, IL-10, granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor ,tumour necrosis factor alpha and VEGFA.50 62 63 Radiological findings Most standard patterns observed on chest CT were ground-glass opacity, ill-defined margins, smooth or irregular interlobular septal thickening, air bronchogram, crazy-paving pattern and thickening of the adjacent pleura. Chest CT is considered to be a sensitive routine imaging tool for COVID-19.64-66 Management At the initial presentation of cluster infection, many cases were treated with antiviral therapy, antibacterial therapy and glucocorticoids. Observation forms the mainstay for those who have mild illness. Moderately ill patients with underlying chronic illness, immunocompromised conditions and pregnancy require hospitalisation.67 68 The anti-malarial drugs, hydroxychloroquine and chloroquine, showed promising results in early in vitro study.69 However, the most robust and recent study in patients with COVID-19 have not shown unequivocal evidence of benefits for the treatment with hydroxychloroquine or chloroquine.70-72 In fact, the largest analysis to date of the risks and benefits of treating COVID-19 patients with these anti-malarial drugs was unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19.70 Besides, this study of 96 000 hospitalised patients on six continents found that those who received the drugs had a significantly higher risk of death and an increased frequency of ventricular arrhythmias compared with those who did not use it.70 Treatment of systemic complications in COVID-19 Extracorporeal membrane oxygenation is an excellent choice for patients with ARDS progressing to respiratory failure. Other modes of treatment include high-flow nasal oxygen and endotracheal intubation. Patients experiencing persistent refractory hypoxemia need prone positioning followed by neuromuscular blockade, inhaled nitric oxide (at 5-20ppm) and also provide optimal end-expiratory pressure by inserting oesophagal balloon.73 74 In the presence of shock with acute renal failure, negative fluid balance needs to be achieved by dialysis. Antimicrobials are used for pre-exposure and post-exposure prophylaxis. This prevents illness from SARS-CoV-2 and also reduces the risk of acquiring secondary infection. Fluid management is important to reduce pulmonary oedema.67 68 75 Glucocorticoids are best avoided due to its harmful effects in viral pneumonia and ARDS.76 Rescue therapy by administration of intravenous infusion of vitamin C has been suggested to attenuate vascular injury and systemic inflammation in sepsis and ARDS.77 Role of vaccines Vaccine development is underway for COVID-19, but there are various limitations. This includes (1) the place for phase 3 vaccine trials are to be conducted in the locality of the ongoing transmission of disease, (2) vaccine manufactures need to work closely with biotechnology companies to develop effective vaccines which probably takes a minimum of 12-18 months and (3) regulators should evaluate safety with a range of virus strains in more than one animal model.78-80 The investigational vaccine has been currently developed using mRNA as its genetic platform using prior studies related to SARS and MERS.16 24 The basis of effective vaccine is immune targeted and involves identifying of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins among 120 available SARS-CoV-2 genetic sequences.24 Effective vaccination would play a vital role in reducing the viral spread and eliminate the virus from the host.81 Conclusion COVID-19 has presented itself as a global pandemic in a short time period resulting in rapid curve shift of infected patients, increasing death rates, huge global economic burden and widespread mobilisation of medical resource across the globe. Being a novel disease, COVID-19 has presented itself as a mystery infection to the medical field, also requiring tremendous research and insights about the nature of the virus, and posing frequent challenges for a successful vaccine outcome. The approach to this disease requires active loco-regional to international collaboration with regards to disease containment, preventive strategies and treatment approach. Main messages This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). It traces the origin of coronavirus as it emerged and differentiates the COVID-19 with specific features from SARS and MERS. We give a detailed insight into the modes of transmission, clinical manifestations, diagnosis and management. Also, it highlights the recent trends on vaccine development. Key references Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579:265-9. Raoult D, Zumla A, Locatelli F, et al. Coronavirus infections: epidemiological, clinical and immunological features and hypotheses. Cell Stress 2020. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13. Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics 2020; e20200702. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019;17:181-92. Self-assessment questions Dromedary camel was involved in zoonotic transmission in MERS form of CoV? Based on COVID-19 genomic structure, the protein that mediates an attachment and fusion between the virus and the host cell membrane is membrane (M) protein. Cross-species and human-to-human transmission of COVID-19 is mainly dependent on the host receptor ACE2 protein. Most consistent laboratory finding in COVID-19 patient is lymphopenia COVID-19 is confirmed by RT-PCR. Current research questions How does COVID-19 differ from SARS and MERS? Mention the factors responsible for virus-host interaction. List the specific laboratory findings in suspected cases of COVID-19. Elaborate the scheme of management in COVID-19. Self-assessment answers True False True True True Supplementary Material postgradmedj-96-753-DC1-inline-supplementary-material-1 Click here for additional data file. postgradmedj-96-753-DC2-inline-supplementary-material-2 Click here for additional data file. Footnotes Correction notice: This article has been corrected since it appeared Online First. Minor typographical errors have been corrected. Contributors: SU contributed to the conception and design of the work, data collection, drafting, revision and final version. PS contributed to the data analysis, interpretation, drafting the article and critical revision. AVR contributed to the data collection, analysis, revision and image concept. MMB contributed to the data collection and drafting. JSR contributed to the data analysis and interpretation. LFA-M, SD and HK contributed to the data collection and analysis DKV contributed to the data collection. All the contributors were involved in revising the final version and granting final approval for the article to be submitted for publication. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; internally peer reviewed.
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press postgradmedj-2020-138079 10.1136/postgradmedj-2020-138079 Letter AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 COVID-19 pandemic: stringent measures of Malaysia and implications for other countries Umair Sonia School of Business and Economics, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Waqas Umair School of Business and Economics, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Faheem Muhammad School of Business and Economics, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Correspondence to Dr Umair Waqas, School of business and economics, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; [email protected] 2 2021 19 6 2020 19 6 2020 97 1144 130132 20 5 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcIn December 2019, pneumonia of unknown cause jolted Wuhan city of Hubei province in China, spread across Asia and the world like wildfire, and, by the end of January 2020, was declared as a public health emergency of international concern by the WHO.1 New coronavirus (severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2) was identified as the cause of this disease and was named COVID-19 by the WHO.1 The symptoms of COVID-19 include fever, cough and breathing difficulties and can lead to death. These symptoms appear similar to common influenza, but the spread is way far speedier. Despite its low fatality as compared with severe acute respiratory syndrome, its high infection nature has led to a contagion of fear worldwide. Originated in China, the COVID-19 has now been spread across many other countries and has escalated as a global pandemic.2 As of 9 April 2020, the COVID-19 outbreaks reached 203 countries, affecting 1 476 819 persons, with 87 816 deaths (84 477 of which are outside China). In December 2019, pneumonia of unknown cause jolted Wuhan city of Hubei province in China, spread across Asia and the world like wildfire, and, by the end of January 2020, was declared as a public health emergency of international concern by the WHO.1 New coronavirus (severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2) was identified as the cause of this disease and was named COVID-19 by the WHO.1 The symptoms of COVID-19 include fever, cough and breathing difficulties and can lead to death. These symptoms appear similar to common influenza, but the spread is way far speedier. Despite its low fatality as compared with severe acute respiratory syndrome, its high infection nature has led to a contagion of fear worldwide. Originated in China, the COVID-19 has now been spread across many other countries and has escalated as a global pandemic.2 As of 9 April 2020, the COVID-19 outbreaks reached 203 countries, affecting 1 476 819 persons, with 87 816 deaths (84 477 of which are outside China). China has been the largest trading partner of Malaysia for the last 10 years. In Malaysia, the first COVID-19 case was detected on 25 January in travellers from China arriving via Singapore.3 The reported cases in Malaysia remained relatively low until the first wave of cases in late February. After the religious gathering held in Kuala Lumpur in late February and early March, localised clusters began to emerge in Malaysia, and within weeks, Malaysia recorded the largest cumulative number of confirmed COVID-19 cases in Southeast Asia, and by 13 April 2020, the total number of confirmed infections in the country raised to 4817 with a death toll of 77 cases.4 Importantly, since the emergence of COVID-19, the Malaysian government has taken serious comprehensive and nationwide measures set by the WHO. Experts across the country are dealing to prevent the spread of the virus widely. For this reason, the Malaysian government has achieved positive results. Here are some major steps, taken by the Malaysian government in response to the COVID-19 epidemic. The most immediate and direct effect of COVID-19 is on health and healthcare, and it is bound to have outsized economic ramifications. Malaysia started its plan to get prepared for the pandemic well ahead of time. Before the first case, on 20 January 2020, the Health Minister of Malaysia announced that the ministry was now in the process of collecting data on previously 'non-notifiable' influenza cases following the emergence of the Wuhan virus.5 Initially, the health ministry adopted public health measures of containment. The hospitals were identified to handle the patients, a rapid reverse transcriptase-PCR test on patients and contacts was developed, used and distributed to several government hospitals and medical laboratories, and management protocols were developed.6 The second wave of COVID-19 cases spiked on 27 February 2020, and later in mid-March 2020, after an increase in the confirmed cases, the government had to enforce mitigation measures. Initially, the government imposed a 2-week movement control order (MCO) starting from 18 to 31 March, which was extended to 14 April and then to 28 April. The main purpose of this MCO was to flatten the curve of new cases. The prohibition of movement and mass assembly included religious, business, education, sports, culture and social activities except for supermarkets, public markets, grocery stores and stores selling basic necessities.7 For community-based control measure, outdoor restriction measures were also enforced, whereby only one resident from a family was allowed to go out at one time and within 10 km of the residence. Checkpoints were set up to check the temperatures at the entry point of residences, supermarkets and food stores. For better prevention, citizens of Malaysia had been prohibited from leaving the country, and foreigners were also not allowed to enter the country. Due to the slowed-down business activities, the interrupted supply chain of enterprises and personnel quarantine, the outbreak of COVID-19 not only caused health concerns but also had severe impact on the Malaysian economy. Thus, to stable the economic growth, to promote investments and to encourage businesses, the Malaysian government announced an emergency stimulus package, which is among the largest in the world.8 When compared with the nation's gross domestic product, it is about 17%, more than the UK's 16% and the USA's 11%. The public, from entrepreneurs to farmers, from fishermen to those paid daily wages, are concerned about their finances. Thus, the government allocated a special package of RM 10 billion for small and medium-sized enterprises to ease the burden of small and medium enterprises.9 The main purpose of this package was to guarantee two-third of the country's workforce remains employed. The package could give benefits to about 4.8 million workers by giving them a subsidy of Rm 600-Rm 1200. A 6-month reprieve would be given to individuals and small and medium enterprises, on the repayment of their existing loans. Credit cardholders can choose to convert outstanding balances into term-loans. The corporate sector can restructure their bank loans. This will help to facilitate companies to retain the employment and carry out business activities soonest. Around the globe, this pandemic caused severe impacts on the education systems. To reduce the delays in education progress, the educational institutes were encouraged to start home-based learning using online classes and other innovative teaching practices. In the future, this can help to develop online educational platforms.2 Many universities also showed significant initiatives in taking on social responsibilities by providing food and other necessities to local and international students. International schools issued a subsidised fee for the new term. According to the early stage of the epidemic, the outbreak started in China and gradually increased its web and captured more than 150 countries by March 2020.2 Initially, many of the countries did not take serious actions to control the outbreak in their own countries by thinking it a 'Chinese virus'. Now governments and organisations are scrambling to manage the disaster caused by COVID-19. Europe and America are paying a high price for their initial ignorance, where America is facing the worst ever medical disaster in their history.10 The war against COVID-19 is far from over; however, since the first case, the Malaysian government's response to the outbreak was epic. On one side, the effective emergency plan launched by the government after just 500 cases across the country has helped to show a significant decline in new cases and a high ratio of recoveries. On the other side, Malaysians, regardless of race, religion and ideology, are trying to help the government and the country is going forward. For this reason, on the 34th day of the MCO, on 20 April 2020, the country reported no COVID-19 deaths, the first time in the month, and the country reported the lowest daily increase of the new cases.11 Malaysia's rapid response to this world pandemic also sets an example for countries that have insecure borders, significant mobile and vulnerable populations, and larger households in denser living conditions. In a study done by a Singapore research agency, Malaysia is ranked fourth in the world out of 105 countries in terms of people's satisfaction with the government's efforts in dealing with the COVID-19 outbreak.12 By 10 May 2020, from 1178 zones around the country, only 0.34% are in red zones, which is a signal of Malaysian victory against COVID-19. Other countries might need a timely emergency plan to be launched like Malaysia. They can focus on timely lockdown, high level of testing during the lockdown, and try to find clusters among confirmed cases and suspected areas, and cases should be monitored strictly. The government should timely educate the people about the importance of lockdown and the measures needed to be done during this time.2 For less infected countries, temperature checking and symptoms among people need to be monitored closely and regularly. Everyone needs to comply with the guidelines, including social distancing and avoiding public gatherings. 'Resolve, resilience, restart, recovery, revitalise and reform' is the new normal for the Malaysian people.13 It is a six-step plan by the Malaysian government to address the impact of COVID-19 and to make sure that the country emerges stronger despite this virus. Using this six-step plan, Malaysians try to adhere to new standards of operating procedures (SOPs) to prevent another wave of infections in the country and to revive the economy in stages. Despite the loss of millions of dollars, they still have imposed conditional MCO, whereby economic sectors have been allowed to open with enforced guidelines; however, interstate travels are still banned. Red zone areas are strictly being monitored. The education sector has already been shifted to home-based learning in the country. Cinemas, sports competitions, leisure clubs, weddings, social events and theme parks will remain closed. There are special SOPs for houses of all worship faiths. Any changes to the SOPs would be announced from time to time by the government. In spite of this world pandemic, its approach to international engagement also remains exemplary. To sustain its economy, Malaysia is working closely with China, South Korea, the United Arab Emirates and its ASEAN neighbours to maintain the supply of essential goods and services. Due to fragile borders, collaboration with ASEAN neighbours is vital to sustain virus suppression,14 and in a 'Special ASEAN Summit on COVID-19', Malaysia proposed a post-COVID-19 economic recovery plan to focus not only on the financial aspects but also on social safety nets, food security and education for the region's 600 million people. Like every other country tackling the crisis, Malaysia has been fighting hard to survive this pandemic and to rebuild the nation's economy. Nevertheless, Malaysia's health response deserves credit for limiting the spread of the virus and minimising avoidable deaths. Footnotes Contributors: MF planned the study. Initial research was performed by UW. The first draft of the study was written by SU. All authors read and approved the final draft of the study. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; internally peer reviewed. References 1 WHO . Coronavirus disease 2019 (COVID-19). Available: [Accessed 22 Mar 2020]. 2 Liu W, Yue X-G, Tchounwou PB. Response to the COVID-19 epidemic: the Chinese experience and implications for other countries. Int J Environ Res Public Health 2020;17 :2304.10.3390/ijerph17072304 32235413 3 Pfordten D, Ahmad R. Covid-19: current situation in Malaysia. Available: [Accessed 14 Apr 2020]. 4 Kaos J . Covid-19: 134 new cases, death toll now at 77. Available: [Accessed 14 Apr 2020]. 5 Habibu S . Wuhan outbreak: Malaysian health authorities on high alert. Available: [Accessed 20 Jan 2020]. 6 Kit PD . Covid-19: Malaysia's pandemic action plan activated for the coronavirus. Available: [Accessed 16 Mar 2020]. 7 Tang A . Malaysia announces movement control order after spike in Covid-19 cases (updated). Available: [Accessed 16 Mar 2020]. 8 Medina AF . Malaysia issues stimulus package to combat COVID-19 impact. Available: [Accessed 19 Mar 2020]. 9 Bernama, Prime Minister's Office of Malaysia. Additional RM10 billion economic package for SMEs - PM. Available: [Accessed 6 Apr 2020]. 10 Sivanandam H . Western countries suffering due to lack of 'discipline' in Covid-19 battle, says Dr M. Available: [Accessed 17 Apr 2020]. 11 Kaos J . Covid-19: 36 new cases, no deaths for first time in a month. Available: [Accessed 20 Apr 2020]. 12 Tang A . Muhyiddin: Most of the country are green zones, but Covid-19 remains the 'silent enemy'. Available: [Accessed 10 May 2020]. 13 The Straits Times . PM Muhyiddin shares Malaysia's six-pronged strategy in Covid-19 fight. Available: [Accessed 5 May 2020]. 14 Nixon S . Commentary: Malaysia is beating all these brutal COVID-19 expectations. CNA. Available: [Accessed 4 May 2020].
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press postgradmedj-2020-137988 10.1136/postgradmedj-2020-137988 Letter AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 Impact of coronavirus disease 2019 on healthcare workers: beyond the risk of exposure Giannis Dimitrios Institute of Health Innovations and Outcomes Research, Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, USA Geropoulos Georgios Thoracic Surgery Department, University College London Hospitals NHS Foundation Trust, London, UK Matenoglou Evangelia Medical School, Aristotle University of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece Moris Demetrios Duke Surgery, Duke University Medical Center, Durham, North Carolina, USA Correspondence to Dimitrios Giannis, Institute of Health Innovations and Outcomes Research, Feinstein Institute for Medical Research, 600 Community Drive - 4th Floor, Manhasset, NY, 11030, USA; [email protected]; [email protected] 5 2021 19 6 2020 19 6 2020 97 1147 326328 01 6 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcIn December 2019, a previously unknown coronavirus strain disease, the coronavirus disease 2019 (COVID-2019) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, and has rapidly spread worldwide.1 2 As of 5 April 2020, more than 1 000 000 people have been officially diagnosed and over 60 000 patients have died, while the pandemic is still spreading.3 Clinical manifestations range from asymptomatic or very mild to severe illness, sepsis and death. While information so far suggests that most COVID-19 illness is mild, severe illness occurs in up to 16% of cases.4 5 The clinical presentation is occasionally atypical, but patients usually present with fever (>80%), cough (>60%) and myalgia or fatigue (>40%).1 4 COVID-19 has been associated with high risk of acute respiratory distress syndrome and intensive care unit (ICU) admission.1 2 6 Currently, it is hard to predict the long-term impact of the pandemic on healthcare facilities and personnel. Healthcare workers, being in the frontline of an ongoing war against the pandemic, should be perceived as a discrete population in terms of both physical and mental health impact. During a crisis, similar to the COVID-19 pandemic, shortages of drug and life-saving equipment may occur.7 8 COVID-19 has overwhelmed the capacity of healthcare resources and has significantly changed the workplace rules of healthcare workers.9 10 It has been recognised that healthcare workers should take appropriate precautions to avoid contracting the disease and prevent spread within the hospital. However, during the early stages of the pandemic, the lack of knowledge resulted in high rates of transmission of COVID-19 to healthcare workers, due to inadequate protection.11 12 Currently, the unprecedented overwhelming demand of protective equipment, which includes masks, medical gowns, gloves and eye-face protective devices, poses a significant health risk. Contracting the infection results in missing workdays, due to placement on quarantine, and increases the risk of disease transmission to family members. If the healthcare worker becomes severely affected, the need for hospitalisation and/or ICU admission emerges. The combination of increased workload, personnel shortage, risk of transmission and lack of resources severely affects the physical and mental health of healthcare workers and places healthcare systems under extreme burden. This stressful situation and accumulated fatigue severely affect many aspects of work and personal life. Higher workload results in limited time for self-care, relaxation and even fulfilment of basic needs, including nutrition and self-hygiene.13 Social interaction is limited, while the application of social distancing in the healthcare workers' population is difficult. Clinic rounds, interactive cases' discussion, work-breaks for lunch occur within closed spaces and distancing is not always feasible.10 Isolation and self-neglect may eventually result in anger, irritability and mood instability. Further, the daily contact with patients and the scarcity of resources are factors that contribute to the overall stress that healthcare workers undergo during this time. One of the most important issues is that healthcare practitioners may occasionally be confronted with ethical dilemmas of prioritising patients, based on risk factors, disease severity and resources availability. Ethical dilemmas and constant exposure may result in detrimental effects, both long-term, in the mental health and well-being of this population. Kang and colleagues estimated the impact of the COVID-19 pandemic in the mental health of physicians and nurses in Wuhan, soon after the onset of the pandemic. Interestingly, half of the healthcare population had received psychological support through materials available online or provided by media, one out of three had obtained paper-based psychological counselling (brochures, leaflets or books), while approximately one out of five had received individual or group psychotherapy. Further, higher levels of healthcare workers' distress were associated with the degree of exposure to infected patients.14 Previously, during the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) 2003 outbreak, Wu et al reported a 10% frequency of post-traumatic stress (PTS) in hospital employees. Those who had been placed in quarantine, worked in high-risk facilities or had close contacts (friends or family members) affected by SARS-CoV-1 were at up to threefold higher risk of having severe PTS symptoms.15 Similarly, Chong and colleagues reported a 75.3% overall prevalence of psychiatric manifestations (anxiety, depression, sleep disturbances) in a population of healthcare workers employed in a tertiary hospital during the SARS-CoV-1 outbreak. The frequency was even higher during the subsiding/control phase (80.6%) compared with the early phase (71.3%) of the epidemic.16 The psychological stress imposed on healthcare practitioners varies and depends on physician expertise and practice site. As the pandemic continues to rapidly spread throughout the USA, one of the most severely affected physician groups are primary care doctors. Significant changes have occurred over a short period. Lack of official guidance and absence of a unified healthcare system that currently consists of small private practices and parts of community, university, federal or private hospital systems significantly hinder the rapid and effective application of proposed changes and regulations.17 Constantly changing recommendations on testing and patients' triage mostly affect small private practices, that suffer from lack of protective resources and are financially dependent on patients' visits, without any guarantee of reimbursement for telemedicine appointments.17 Recently, Greenhalgh and colleagues published a comprehensive guide about remote assessments in primary care to help primary care physicians to deal with video-based conversations with patients.18 The effective management of emerging issues depends on the successful collaboration between interested parts. Hospital committees, stakeholders and federal agencies should make sure that adequate protective devices and tools become available as soon as possible to healthcare workers. In China, a monitoring system of exposed healthcare personnel has been used to facilitate early detection, appropriate triage and prompt isolation of healthcare personnel.19 This approach should be taken cautiously, and issues regarding privacy and breach of confidentiality should be resolved prior to widespread implementation. In the USA, volunteer programmes have been established and are expected to significantly contribute to the relief of overwhelmed hospitals.20 21 In the presence of volunteers, physicians may need to slightly deviate from the established guidelines and many of them will need time to appropriately practice beyond their expertise areas. Notably, retired healthcare workers and recent graduates will need extensive training to practise medicine safely. Proposed measures to counteract the effect of COVID-19 pandemic on the mental health of healthcare workers include multidisciplinary psychiatric support teams, up-to-date information dissemination to relieve anxiety and uncertainty, psychological support through electronic devices (mobile phones), mental health screening and early, appropriate treatment in those affected by severe psychiatric symptoms.22 In addition, proper clinical recommendations for the management of patients treated for other diseases are of great importance, because healthcare workers are stressed by the possibility of disease transmission that may occur during rounds and between wards. Anelli and colleagues proposed that rapid tests, which provide results within 15-45 min, should be given to healthcare workers suspected of having COVID-19, even if they are experiencing only mild symptoms.23 To our perspective, this approach could significantly decrease the stress and doubts of healthcare workers that derive from the risk of potential transmission to close contacts and patients. Institutional agencies and supervisors should be able to recognise the detrimental effects of the pandemic on healthcare workers and should be willing to decrease working hours, apply flexible schedules and clearly assign roles and responsibilities to equally distribute the workload.13 24 Extended work shifts can potentially affect the overall health and predispose to higher risk of acquiring respiratory infections.25 26 Recent reports raised awareness about skin disease, including abrasions and ulcerations, on the hands and face of healthcare workers due to the prolonged or repeated use of gloves/antiseptics or facial goggles/N95 mask, respectively.27 Therefore, staff should be given the opportunity to discuss decisions regarding their tasks and the equipment they use, and should regularly be evaluated on their well-being. Healthcare managers should promote adequate sleep, hygiene and take initiatives to supply healthcare workers with water, food and short break intervals.28 In addition, authorities, legislators and government agencies should show support and empathy in the event of adverse outcomes.29 Once the pandemic is over, affected and/or involved healthcare workers must be followed-up, supported, and long-term consequences should be appropriately treated.30 Academic societies and scientific associations have published guidelines to deal with the emerging issues in populations hospitalised for other diseases.11 31-33 Guidelines, during this unprecedented event can significantly decrease the stress of dilemmas regarding the management of the elective, acutely ill and terminally-ill hospitalised population. Lastly, as a society, we owe a clear and honest 'Thank you for taking care of people' to the healthcare workers' population. As Bergman and colleagues state, what we need is physical distancing with social connectedness. This pandemic seems as a chance to reconsider and reinvest in relationships.34 No formalities, no excuses, no well-spoken politics. All they need is a 'thank you', from the bottom of our hearts, every time they sacrifice themselves to save people. Our people. Footnotes Contributors: DG and EM contributed to the concept, drafting the manuscript, analysis/interpretation of data, critical writing/editing and revising intellectual content. DG is the guarantor for the analysis and interpretation accuracy and is responsible for the overall content. GG and DM contributed to the concept, analysis/interpretation of data, critical writing/editing and revising intellectual content. All authors approved the final manuscript. Funding: No funding was received for the present work. Competing interests: All authors have read and understood PMJ policy on declaration of interests and declare that they have no competing interests. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; internally peer reviewed. REFERENCES 1 Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395 :497-506.10.1016/S0140-6736(20)30183-5 31986264 2 Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382 :727-33.10.1056/NEJMoa2001017 31978945 3 Novel coronavirus (2019-nCoV) situation reports. Available (accessed 5 Apr 2020). 4 Guan W-J, Ni Z-Y, Hu Y, et al. clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020.10.1056/NEJMoa2002032 5 CDC . Coronavirus disease 2019 (COVID-19) situation summary. Centers for Disease Control and Prevention. Available Published March 15, (accessed 5 Apr 2020). 6 Du Y, Tu L, Zhu P, et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan: a retrospective observational study. Am J Respir Crit Care Med 2020;10.1164/rccm.202003-0543OC 7 Cadogan CA, Hughes CM. On the frontline against COVID-19: community pharmacists' contribution during a public health crisis. Res Social Adm Pharm 2020.10.1016/j.sapharm.2020.03.015 8 Fox ER, Sweet BV, Jensen V. Drug shortages: a complex health care crisis. Mayo Clinic Proc 2014;89 :361-73.10.1016/j.mayocp.2013.11.014 9 Ji Y, Ma Z, Peppelenbosch MP, et al. Potential association between COVID-19 mortality and health-care resource availability. Lancet Global Health 2020;8 :e480.10.1016/S2214-109X(20)30068-1 32109372 10 Belingheri M, Paladino ME, Riva MA. Beyond the assistance: additional exposure situations to COVID-19 for healthcare workers. J Hosp Infect 2020.10.1016/j.jhin.2020.03.033 11 Chen W, Huang Y. To protect healthcare workers better, to save more lives. Anesth Analg 2020.10.1213/ANE.0000000000004834 12 Xiang Y-T, Jin Y, Wang Y, et al. Tribute to health workers in China: group of respectable population during the outbreak of the COVID-19. Int J Biol Sci 2020;16 :1739-40.10.7150/ijbs.45135 32226292 13 Petzold MB, Plag J, Strohle A. Umgang mit psychischer Belastung bei Gesundheitsfachkraften im Rahmen der COVID-19-Pandemie. Nervenarzt 2020.10.1007/s00115-020-00905-0 14 Kang L, Ma S, Chen M, et al. Impact on mental health and perceptions of psychological care among medical and nursing staff in Wuhan during the 2019 novel coronavirus disease outbreak: a cross-sectional study. Brain Behav Immun 2020.10.1016/j.bbi.2020.03.028 15 Wu P, Fang Y, Guan Z, et al. The psychological impact of the SARS epidemic on hospital employees in China: exposure, risk perception, and altruistic acceptance of risk. Can J Psychiatry 2009;54 :302-11.10.1177/070674370905400504 19497162 16 Chong M-Y, Wang W-C, Hsieh W-C, et al. Psychological impact of severe acute respiratory syndrome on health workers in a tertiary hospital. Br J Psychiatry 2004;185 :127-33.10.1192/bjp.185.2.127 15286063 17 Kamerow D . COVID-19: don't forget the impact on US family physicians. BMJ 2020;368 :m1260.10.1136/bmj.m1260 32217547 18 Greenhalgh T, Koh GCH, Car J. COVID-19: a remote assessment in primary care. BMJ 2020;368 .10.1136/bmj.m1182 19 Zhang Z, Liu S, Xiang M, et al. Protecting healthcare personnel from 2019-nCoV infection risks: lessons and suggestions. Front Med 2020;10.1007/s11684-020-0765-x 20 COVID-19: emergency health care response volunteer requests by state. American Association of Nurse Practitioners. Available (accessed 6 Apr 2020) 21 Help Now NYC . Available (accessed 6 Apr 2020) 22 Xiang Y-T, Yang Y, Li W, et al. Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed. Lancet Psychiatry 2020;7 :228-9.10.1016/S2215-0366(20)30046-8 32032543 23 Anelli F, Leoni G, Monaco R, et al. Italian doctors call for protecting healthcare workers and boosting community surveillance during COVID-19 outbreak. BMJ 2020;368 .10.1136/bmj.m1254 24 Interim briefing note addressing mental health and psychosocial aspects of COVID-19 outbreak (developed by the IASC's reference group on mental health and psychosocial support) | IASC. Available (accessed 6 Apr 2020) 25 Ran L, Chen X, Wang Y, et al. Risk factors of healthcare workers with corona virus disease 2019: a retrospective cohort study in a designated hospital of Wuhan in China. Clin Infect Dis 2020.10.1093/cid/ciaa287 26 Weaver MD, Landrigan CP, Sullivan JP, et al. The association between resident physician work hour regulations and physician safety and health. Am J Med 2020.10.1016/j.amjmed.2019.12.053 27 Lan J, Song Z, Miao X, et al. Skin damage among healthcare workers managing coronavirus disease-2019. J Am Acad Dermatol 2020.10.1016/j.jaad.2020.03.014 28 Dewey C, Hingle S, Goelz E, et al. Supporting clinicians during the COVID-19 pandemic. Ann Intern Med 2020.10.7326/M20-1033 29 Willan J, King AJ, Jeffery K, et al. Challenges for NHS hospitals during COVID-19 epidemic. BMJ 2020;368 .10.1136/bmj.m1117 30 Greenberg N, Docherty M, Gnanapragasam S, et al. Managing mental health challenges faced by healthcare workers during COVID-19 pandemic. BMJ 2020;368 .10.1136/bmj.m1211 31 Ngoi N, Lim J, Ow S, et al. A segregated-team model to maintain cancer care during the COVID-19 outbreak at an academic center in Singapore. Ann Oncol 2020.10.1016/j.annonc.2020.03.306 32 Akladios C, Azais H, Ballester M, et al. Recommendations for the surgical management of gynecological cancers during the COVID-19 pandemic - FRANCOGYN group for the CNGOF. J Gynecol Obstet Hum Reprod 2020;101729.10.1016/j.jogoh.2020.101729 32247066 33 Ahn C, Amer H, Anglicheau D, et al. Global transplantation COVID report march 2020. Transplantation 2020;10.1097/TP.0000000000003258 34 Bergman D, Bethell C, Gombojav N, et al. Physical distancing with social connectedness. Ann Fam Med 2020.10.1370/afm.2538
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Postgrad Med J Postgrad Med J pmj Postgraduate Medical Journal 0032-5473 1469-0756 Oxford University Press 32788316 postgradmedj-2020-138559 10.1136/postgradmedj-2020-138559 Education and Learning AcademicSubjects/MED00160 AcademicSubjects/MED00790 AcademicSubjects/MED00530 Medical students and COVID-19: lessons learnt from the 2020 pandemic de Andres Crespo Marta Medical Sciences Division, Oxford University, Oxford, UK Claireaux Henry University of Oxford Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, Oxford, UK Handa Ashok Inderraj Nuffield Department of Surgery, Oxford, UK Correspondence to Marta de Andres Crespo, Oxford University Medical School Division, Headley Way, Oxford OX3 9DU, UK; [email protected] 4 2021 11 8 2020 11 8 2020 97 1146 209210 26 6 2020 30 6 2020 (c) Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] pmcAt the start of 2020, a medical student's largest problem was passing their next exam at medical school. To doctors, these students were people who needed to be taught but were of minimal help in the hospital. The COVID-19 pandemic changed this for both parties. There are some crucial lessons to be learned. As COVID-19 started to overwhelm the National Health Service (NHS), final-year medical students saw exams cancelled, graduations accelerated and their career start date fast-forwarded. With this came student anxieties regarding their preparedness for the job and their fear of being ill-equipped. Starting as a doctor is a difficult transition under normal circumstances, but it is even tougher in a global pandemic. As these anxieties grew, some students wrote letters to publicise their concerns. One such letter was written relatively early on and published in the Lancet.1 It asked for greater guidance and transparency regarding indemnity, contracts, expected roles and responsibilities of students. As a result of this, a survey was conducted with Oxford University medical students to give students a voice and understand their involvement in the current pandemic. Many people experienced a significant degree of anxiety during the past 3 months and medical students are no exception. There are some key lessons to learn from the results of this survey to better equip this subset of the population in future, either for a second wave of COVID-19 or a different infectious pandemic altogether. It is inevitable that another pandemic will occur. The only questions are when, and if we will be better prepared for it next time. LESSON 1: MEDICAL STUDENTS PLAYED CRUCIAL ROLES IN HOSPITALS, PRIMARY CARE AND IN COMMUNITIES The vast majority (80%) of medical student respondents were working across NHS Trust hospitals, in primary care and in the community, with a further 11% still waiting to be tasked. In hospitals, students were placed in Accident and Emergency, triaging patients into either COVID-19-infected or non-infected groups. In the intensive care unit, they played key liaison roles with families who were not able to visit their loved ones. They also worked in hospitals in roles similar to foundation year doctors, taking bloods and placing cannulas. Others worked in hospital pharmacies delivering medications to the wards or in PCR labs carrying out testing of COVID-19. In primary care, students routinely telephoned elderly people to check on their welfare. They discussed important issues, including end-of-life considerations with patients. A daily teleconference with a doctor was used to discuss cases, carry out teaching on communication skills, develop primary care research skills and manage the students' own mental well-being. Lastly, in communities, students helped deliver groceries to those who had to isolate through various organisations. They also had managerial roles to organise community efforts and maximise efficiency. Several students remarked on the differences in volunteering effort between Oxford and more rural areas where their friends and families lived, giving examples of grandparents struggling to cope with less community support schemes in operation. From this, we are able to see that medical students played a vital role in the pandemic effort. They occupy a unique position in our society in that they are not laypeople but neither are they doctors so they are able to bridge the gap between the two. They are an extra pair of hands that can improve the efficiency of hospitals and free up more senior doctors for the management of complex cases. LESSON 2: CONTINUING MEDICAL EDUCATION ONLINE One of the most significant impacts of COVID-19 on medical students was that the medical school closed on March 13, 2020 and, along with it, the teaching it provided. Despite this, 71% of students were working on matters related to their degree, many of which were doing so alongside volunteering roles. Preclinical students had exams to revise for but clinical years had little guidance of what was expected. They turned to self-directed learning using textbooks and online resources. Oxford medical school has had to update its online resources extensively as all lectures for current 5th-year undergraduates have been cancelled and moved wholly online, with specific online modules to cover each topic. Medicine is one of the few degrees for which it is impossible to teach without any in-person contact. The vast majority of learning in clinical years depends on clinical placements and interactions with doctors and patients alike. However, it still involves building a mental model and pattern recognition, both of which can be learnt from the comfort of your own home. In an age where computers and technology are becoming increasingly prevalent in our lives, investing in online platforms and developing resources to teach the degree virtually, guarantees a continuation of teaching, even during a pandemic. LESSON 3: THE IMPACT OF COVID-19 ON MEDICAL STUDENT WELL-BEING AND HOW TO MANAGE THIS In our survey, 65% of respondents reported that COVID-19 had negatively impacted their mental well-being. Their concerns surrounded three key areas, the most significant of which was the risk of infection to others. Within Oxford, there was a heavy emphasis on following personal protective equipment (PPE) guidance and social distancing and yet students still felt unprepared. On a larger scale, from the news-reported nationwide PPE shortages, one can assume that not all medical schools and their students were as fortunate as those participating in this survey. The second main concern surrounded the impact of the pandemic on their education and ability to progress to the next year. This has already been addressed in Lesson 2. Finally, students, much like the general public, were particularly anxious about the uncertainty regarding the duration of social distancing measures and general isolation policy. Students too had lost loved ones in the pandemic and were unable to visit them. Despite the increased anxiety and poor mental health levels, social isolation measures meant that there was a reduction in access to help, with many students having to cope on their own. General coping strategies involved exercise (92%), keeping in touch with family and friends (92%) and music (67%), be it playing an instrument or simply listening to it. There were specific suggestions for medical school support, some of which have since been implemented by the Oxford medical school. First, 40% of students asked for more regular updates from the medical school, with three students suggesting a weekly newsletter. At the start of the pandemic, the medical school only updated its students when there was news to tell. In this survey, it was clear that students preferred being kept informed on a regular basis, even if little had changed. Since this survey was completed, Oxford medical school has indeed sent weekly emails on Friday afternoons to its students, explaining the next steps they are conducting in starting clinical placements and new online resources they have created. The survey respondents also suggested releasing a survey to students regarding their well-being and take a proactive approach to the problem. Though this was not done, the Oxford medical school created online 'drop-in' sessions that students could book if they felt they needed further support with their mental health. Conclusion A recent systematic review conducted by Ashcroft et al investigated the value of implementing a disaster training programme for medical students.2 They found that these improved preparedness, knowledge and skills that could be of use to medical students if another pandemic occurs and they are recruited to assist. This pandemic training programme could target some of the key lessons learnt from this survey. First, it could train medical students on managing emergency situations and conducting tasks in the hospital, primary care or in communities while minimising the risk of infection to themselves. Second, it could teach them to recognise burnout or anxiety as a result of a highly strenuous medical situation such as a pandemic and give them the tools to manage this when normal mental health resources are not open. Last, it would give students a platform to voice their concerns and have them addressed. Thankfully, the rates of COVID-19 infection are now on the decline and it appears the first wave of this pandemic is coming to an end. However, the threat of a potential second wave still exists and so it is of the utmost importance that we learn from the past few months. Medical student assistance has occurred across the country and it is highly plausible that more medical students will be needed in a future pandemic. Therefore, we should take the time we have now to re-assess and take note of the lessons learnt from the past 3 months. Main messages Medical students have played a variety of roles in the COVID-19 pandemic, working amongst healthcare professionals in hospitals, primary care and in communities. A significant proportion of students were still awaiting jobs when completing this survey. Thus, there is a lot of potential for the further use of medical students in future pandemics, if they are properly trained and incorporated into healthcare teams. Medical student learning should be adapted to include more online modules so that in future, if medical schools close, medical education does not need to come to a halt. Mental wellbeing is an important aspect of medical student health that should be investigated and addressed as the majority of students have found their mental health to be negatively impacted by the pandemic. Support measures should be put in place to help students with both the fears of the pandemic itself and the measures taken to combat it. Further investigation into this subset of the population is needed. Acknowledgements Dr E Ladds at Eynsham Medical Group Practices for information regarding student involvement in their GP practice. Footnotes Contributors: MdAC and HC contributed to idea conception, produced and revised the manuscript. AIH assisted with interpretation of findings and revision of the manuscript. The Oxford Medical Student Survey respondents assisted with designing the survey, detailed answers to the survey, revising the manuscript and approving it for publication and agreed to be equally accountable for this publication. The corresponding author attests that all listed authors meet authorship criteria and no others meeting the criteria have been omitted. Funding: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Not required. Provenance and peer review: Not commissioned; internally peer reviewed. REFERENCES 1 Baker DM, Bhatia S, Brown S, et al. Medical student involvement in the COVID-19 response. Lancet 2020;395 :1254.10.1016/S0140-6736(20)30795-9.32247322 2 Ashcroft J, Byrne MHV, Brennan PA, et al. Preparing medical students for a pandemic: a systematic review of student disaster training programmes. Postgrad Med J 2020;postgradmedj-2020-137906.10.1136/postgradmedj-2020-137906.
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