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This double-blind, placebo-controlled, randomized, parallel-group phase 2/3 study will study the utility of nebulized furosemide for pulmonary inflammation in Intubated, mechanically ventilated Patients with COVID-19. The primary objective of the study is to establish the efficacy and safety of nebulized furosemide for the treatment of respiratory failure secondary to COVID-19 infection requiring invasive mechanical ventilation. The secondary objective is to delineate the anti-inflammatory properties of furosemide in COVID- 19 patients using pharmacokinetic / pharmacodynamic analysis. The duration of the intervention will be up to 28 days of intervention and patients will be followed till 60 days post randomization. Participants will be randomized to either: Intervention Group: 40 mg furosemide per dose, given by nebulization (4 mL of 10 mg/mL furosemide in 0.9% saline solution) over 30 mins four times daily (Q6H) for up to 28 days OR Control Group: placebo, given by nebulization (4 mL of 0.9% saline solution) over 30 mins four times daily for up to 28 days. One hundred and forty-four (144) evaluable patients will be enrolled in the Phase 2 study. If evidence of efficacy is found in the Phase 2 portion, these patients will be enrolled in the Phase 3 study which aims to recruit 640 patients total (496 additional patients to the phase 2 patients).

This double-blind, placebo-controlled, randomized, parallel-group phase 2/3 study will study the utility of nebulized furosemide for pulmonary inflammation in Intubated, mechanically ventilated Patients with COVID-19.

Although non-infectious uveitis is rare in pediatric population, the irreversible visual impairment due to ocular complications, severe drug adverse effects are disturbing. There is a high rate of chronic disorder of ocular inflammation and unresponsiveness of therapy drugs in pediatric uveitis, which result in structure destruction and functional impairment including band keratopathy, posterior synechiae, cataract, and so on. The systemic and topical glucocorticoid are advocated to control inflammation but carry a high risk of lots of advert events.~Methotrexate is now highly recommended to control uveitis and most commonly prescribed in pediatric uveitis. it was benefit to prolong remission and reduce recurrence. However, despite early intervention 27-48% children do not achieve control of inflammation and 20% experience adverse events. Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, is effective in the treatment of many rheumatic diseases. ADA as the initial treatment in adult patients of uveitis lead to a more optimistic prognosis, a better visual acuity and a lower dose of dosage of daily glucocorticoid.~The investigators propose to test the efficacy and safety of ADA plus MTX for the treatment in non-infectious pediatric panuveitis who were followed up for 1 year.

The aim of this study is to determine the efficacy and safety of ADA plus MTX for the treatment in non-infectious pediatric panuveitis.

Purpose of the study: to develop a method of medical prevention of cardiovascular diseases caused by cardiotoxicity against the background of complex treatment of patients with primary resectable breast cancer to reduce the risk of cardiovascular complications

To develop a method of medical prevention of cardiovascular diseases caused by cardiotoxicity against the background of complex treatment of patients with primary resectable breast cancer to reduce the risk of cardiovascular complications

The purpose of this study is to determine the impact of a 6-week, virtually-delivered expressive writing intervention on resilience in a cohort of individuals currently navigating the COVID-19 pandemic during spring 2020.~Eligible subjects will be adults who are able to read and write in English and are cognitively able to provide informed consent. Potential subjects will be recruited through the Duke Health & Well-Being email lists. The entirely virtual 6-week expressive writing intervention will be delivered via Zoom, REDCap, and email, and subjects will complete measures at baseline, 6 weeks, and 10 weeks (1 month post-intervention). Each week of the intervention will invite participants to complete a series of expressive writing assignments designed to support emotional expression and cultivate resilience, and the assignments will take approximately 60-90 minutes each week to complete.~The primary outcome is the 25-item Connor-Davidson Resilience Scale (CD-RISC). Other measures will include a basic demographics survey, questions about COVID-19 impact, post-writing surveys collected after the writing assignments, the 10-item Perceived Stress Scale (PSS), the Center for Epidemiologic Studies Depression Scale-Revised, and the 21-item Post -Traumatic Growth Inventory (PTGI). Participants will also have the option to share the content of their writing assignments with the research team if they choose.~The risks of participation in this study are minimal and include the risk of mild sadness after the writing assignments and the risk of loss of confidentiality.

The purpose of this study is to determine the impact of a 6-week, virtually-delivered expressive writing intervention on resilience in a cohort of individuals currently navigating the COVID-19 pandemic during spring 2020.

Obesity is associated with increased mortality and morbidity and represents a worldwide epidemic that is increasing in prevalence and remains a significant problem in Canada and a burden on our healthcare system. Maintaining long-term weight loss is the Achilles' heel of obesity therapy. Since obesity is considered a chronic disease, we need better interventions than continued calorie restriction and increased physical activity.~Sustained weight loss during the first year is a predictive factor for successful weight loss after 4 years. Clinical trials employing an intensive lifestyle intervention demonstrate that a 5-10% weight loss translates into important reductions in metabolic and cardiovascular risk factors. This benefit however, is quite often mitigated by weight regain which could occur in approximately 50% of patients after 1 year. Further behaviour modification/lifestyle intervention and or pharmacotherapy are the main pillars for treating weight regain or achieving weight maintenance. This study will refine our knowledge and understanding about the most appropriate treatment for weight maintenance.~Contrave (naltrexone HCl and bupropion HCl) extended-release tablet is an approved drug and indicated to be used with a low calorie diet and increased physical activity for chronic weight management in obese adults (BMI 30 Kg/m2 or greater) or overweight adults (BMI 27 Kg/m2 or greater) with at least one weight related condition such as hypertension or diabetes. Presently we do not have any evidence for the use of Contrave for weight maintenance.~This is a 1 year, phase 4, prospective, pragmatic, randomized, double-blind, placebo controlled and crossover, observational study that will be conducted in two 6 month phases, across multiple Bariatric Centres of Excellence (BCoE) in Ontario. The first 6 months is the randomized, double blind, placebo controlled phase and participants will be randomly assigned to receive Contrave with usual care (dietary and behaviour counselling) or placebo with usual care. At 6 months and the end of the blinded phase, all participants will be administered Contrave for the remaining 6 month, open-label phase of the study. In other words, participants randomly allocated to receive Contrave will continue on Contrave for the final 6 months, and participants randomly assigned to placebo will crossover to treatment with Contrave for the final 6 months. All subjects will also continue to receive usual care.~The study includes several follow up visits to assess safety and treatment effects, some in person and others by telephone or video conferencing. Body weight, blood pressure, heart rate, waist circumference, lab tests, and subject completed questionnaires will be collected as part of usual care or for the study. Changes in medications and any possible side effects will also be monitored during the study.~To qualify, men and women must successfully complete the BCoE behaviour modification program and demonstrate ≥ 5% weight loss. All participants will be followed for 1 year with multiple visits to assess safety and treatment effects.~This study aims to demonstrate that in participants who have ≥ 5% weight loss following the completion of a behaviour modification program with meal replacements, Contrave combined with usual care will significantly improve maintenance of weight loss and promote further weight loss, compared to placebo with usual care.

Contrave (naltrexone HCl and bupropion HCl) extended-release tablet is an approved drug and indicated to be used with a low calorie diet and increased physical activity for chronic weight management in obese adults (BMI 30 Kg/m2 or greater) or overweight adults (BMI 27 Kg/m2 or greater) with at least one weight related condition such as hypertension or diabetes. Presently we do not have any evidence for the use of Contrave for weight maintenance.~The purpose of this study is to demonstrate that in participants who have ≥ 5% weight loss following the completion of a behaviour modification program with meal replacements, Contrave combined with usual care (dietary and behaviour counselling) will significantly improve maintenance of weight loss and promote further weight loss, compared to placebo with usual care.

The study is a randomized, double-blind, sham-controlled cross-over trial to assess the efficacy as well as safety and tolerability of auditory SWS enhancement on measured outcomes in PD patients with disturbed nighttime sleep. Patients will be randomized to 2 groups: Group 1 will first be treated with auditory stimulation for 3 nights and then - after a wash-out period of 4 nights - switched to 3 nights of sham stimulation. Group 2 will first receive sham-stimulation for 3 nights and then switch to 3 nights of auditory stimulation treatment. The wash-out period in between will be 4 nights. Patients and investigators assessing the outcomes will be blinded to the conditions. All interventions will take place at the patients' homes.~The pilot study is aimed at assessment of safety, tolerability, feasibility and efficacy of auditory SWS enhancement on measured outcomes in MCI and HD patients with disturbed nighttime sleep. Patients will be treated with verum or sham auditory stimulation for 2 consecutive nights. All interventions will take place at the patients' homes.

The study is a randomized, double-blind, sham-controlled cross-over trial to assess the efficacy as well as safety and tolerability of auditory SWS enhancement on measured outcomes in Parkinson disease (PD) patients with disturbed nighttime sleep.~Additionally, the investigators will assess the feasibility and efficacy of auditory slow-wave sleep (SWS) enhancement in Mild Cognitive Impairment (MCI) and Huntington Disease (HD) patients in a pilot study.

Schizophrenia (Sz) is associated with psychotic symptoms, such as hearing voices and paranoid beliefs that remain partially or fully refractory to standard antipsychotic medications for ~2/3 of patients. Alternative, glutamatergic approaches for treatment development have been proposed but have not yet led to FDA-approved medications. Moreover, several glutamate-targeted medications, such as pomaglumetad (POMA), have failed in pivotal clinical trials despite robust effectiveness in preclinical models. A major barrier to effective glutamatergic treatment development is the absence of validated measures for target engagement that can identify effective compounds and guide dose selection. Target refers to a factor that an intervention is intended to modify, leading to improvement in symptoms, and target engagement biomarkers are a measure of the ability of the intervention to engage the target.~As part of the recently completed NIMH multicenter FAST-PS initiative (IRB protocol 6925 and 7285), we evaluated ketamine-induced pharmacoBOLD (phBOLD) in healthy volunteers (HV) as a potential target engagement biomarker for development of metabotropic glutamate (mGluR2/3) agonists, as a prelude to planned studies in Sz. BOLD imaging indirectly measures brain energy, as a proxy for glutamate target engagement.~The present study will (1) build on these initial positive results to develop phBOLD for use in Sz, (2) optimize ketamine dosing to further increase sensitivity of the phBOLD approach, and (3) explore mechanisms of psychosis. The present study will enable a personalized medicine approach to target engagement and dose evaluation in Sz, while, in parallel, evaluating mechanisms in Sz.~The structure of this grant requires successful completion of Specific Aim (SA) 1 over the first 18 months prior to initiation of SA2 and SA3. We will amend the PSF and consent to include a full description of SA's 2 and 3 prior to its initiation.~In FAST-PS, we selected a high dose of ketamine (0.23 mg/kg) in order to produce robust pharmacological effects. Under SA1, we will titrate this dose downward in HV in order to identify doses that produce reduced psychotomimetic effects, but nevertheless sufficiently robust phBOLD effects.~50 HV will participate in 2 identical phBOLD sessions at least 7 days apart. In total, MRI scans will last approximately 45 minutes, including pre and post ketamine scan. The design is based on our published study(Javitt, Carter et al. 2018). On both days, clinical assessments will be performed following removal of the subject from the scanner.~HV will be discharged home after clearance by the study physician. Although we expect all HV to tolerate ketamine challenge, in the case that a subject does not tolerate it well, we have the capability of admitting a HV subject to an inpatient unit for monitoring and treatment if necessary.~SA1 will assign ketamine doses in successive 10 subject cohorts. The ketamine dose for the 1st cohort will start at 0.08 mg/kg. For subsequent cohorts, the bolus will be successively reduced or increased by 0.02 mg/kg (n=10/dose) to determine the lowest dose of ketamine that still produces a robust phBOLD response.~The study will be subject and rater blind, i.e. subjects and raters, will be blinded to the treatment (ketamine dose) group.~The study physician will be aware of the ketamine dose, and ketamine dose will be the same for both sessions.~Subjects will not be told what the exact ketamine dose they will receive, but it will be based on their weight and will be no higher than 0.08 mg/kg.

50 healthy volunteers (HV) will participate in 2 identical ketamine-induced pharmacoBOLD (phBOLD) sessions at least 7 days apart. On both days, clinical assessments will be performed following removal of the subject from the scanner.~HV will be discharged home after clearance by the study physician. This study will assign ketamine doses in successive 10 subject cohorts. The ketamine dose for the 1st cohort will start at 0.08 mg/kg. For subsequent cohorts, the bolus will be successively reduced or increased by 0.02 mg/kg (n=10/dose) to determine the lowest dose of ketamine that still produces a robust phBOLD response.~The study will be subject and rater blind, i.e. subjects and raters, will be blinded to the treatment (ketamine dose) group.~The study physician will be aware of the ketamine dose, and ketamine dose will be the same for both sessions.~Subjects will not be told what the exact ketamine dose they will receive, but it will be based on their weight and will be no higher than 0.08 mg/kg.

Patient-reported outcome measures (PROMs) is an umbrella term that refers to any report on a health status measure that is reported directly by the patient, without the influence of clinicians or anyone else. PROMs have been shown to more closely reflect a patient's daily health status when compared to physician-reported measures. However, research is needed to evaluate if patient symptom reporting during definitive-intent radiotherapy allows earlier and improved detection of treatment toxicity, and leads to individualized interventions which may improve the toxicity outcomes for patients with locally-advanced and oligometastatic cancer.~The investigators hypothesize that routine physician review of PROMs during on-treatment visits will (1) increase proportion of patients with an increased in their physician' s assessment of their overall toxicity burden during definitive radiotherapy, and (2) correspondingly increase the proportion of patients receiving physician-directed interventions for treatment-related symptoms.~The IMPROVE pilot study will describe the proportion of patients with cancer with changes in physician-perception of treatment-related toxicity that result from routine physician review of PROMs reported during definitive radiotherapy. The IMPROVE study will also describe (1) the proportion of patients with changes in the management of treatment-related symptoms and (2) the type of management changes that result from routine physician review of PROMs reported during definitive radiotherapy.

Patient-reported outcome measures (PROMs) is an umbrella term that refers to any report on a health status measure that is reported directly by the patient, without the influence of clinicians or anyone else. PROMs have been shown to more closely reflect a patient's daily health status when compared to physician-reported measures. However, research is needed to evaluate if patient symptom reporting during definitive-intent radiotherapy allows earlier and improved detection of treatment toxicity.~The IMPROVE pilot study will describe the proportion of patients with cancer with changes in physician-perception of treatment-related toxicity that result from routine physician review of PROMs reported during definitive radiotherapy.

A Phase 1, 3-part, randomized, double-blinded, placebo-controlled, first in human study.~Part A is a single ascending dose (SAD) study in up to 5 cohorts of 8 healthy subjects (6 active and 2 placebo).~Part B is a multiple ascending dose (MAD) study in up to 4 cohorts of 8 healthy subjects (6 active and 2 placebo).~Part C is a 28 day multiple-dose study in up to 2 cohorts of 12 IPF subjects (8 active and 4 placebo). The dose levels administered in Part C will not exceed those previously administered in Part B which were shown to be well tolerated.~Part D studies lung bioavailability and renal elimination in Healthy Subjects.

This is a Phase 1, 4-part, randomized, double-blinded, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-1058 inhaled solution. Part A is a SAD study in healthy subjects, Part B is a MAD study in healthy subjects, Part C is a multiple-dose study in subjects with IPF, and Part D studies lung bioavailability and renal elimination in Healthy Subjects.

This study is to systematically examine an existing candy, which is easily available and is intended to relieve or eliminate bad breath. The main aim of the study is to determine the effectiveness of the candies on the subjective perception of bad breath. The secondary outcome of the study is to investigate whether there is actually a decrease in volatile sulphur compounds (VSC) in the exhaled air and also a decrease in bad breath during organoleptic measurement.~The purpose of the study is to investigate whether the different candies can relieve or eliminate bad breath, both subjectively and objectively.

This study is to analyze whether the candies can relieve or eliminate bad breath, both subjectively and objectively.

This is a small-scale proof-of concept clinical trial of amobarbital as a treatment to prevent post-traumatic osteoarthritis in fractured ankle joints. The study is a double blind, prospective, randomized, placebo-controlled, stepwise trial. Amobarbital will be delivered to ankle joints in solution with hyaluronic acid (HA) as a vehicle. Amobarbital/HA injections (active dose) will be compared to HA alone (placebo dose). Our primary goal is to confirm safety, but we will also assess whether treatment improves chondrocyte viability and decreases synovial inflammation. The intervention that will be utilized has proven to be effective using vitro and in vivo models. The study team will assess safety and begin to evaluate efficacy of amobarbital/Gel-One in patients having sustained tibial pilon fractures. The study team will use advanced imaging-based methods we have developed to characterize how joints subjected to varying levels of fracture severity and residual elevated contact stress respond in treated and control groups.~Phase I:6 subjects will be treated with a single dose open label, and safety measures will be assessed.~Phase II: Once initial safety is confirmed, 20 amobarbital:10 control subjects will be treated with the single dose at the initial operation.~Assuming continued safety, an additional 20 amobarbital:10 control subjects will be treated with two doses and evaluated. The second dose of 2.5 mM amobarbital will be administered during the second operation.~Subjects will participate in the following procedures:~SOC surgical intervention Randomization to Amobarbital/Gel-One arm or control arm X-rays CT scans Blood and urine Questionnaires

This is a small-scale proof-of concept clinical trial of amobarbital as a treatment to prevent post-traumatic osteoarthritis in fractured ankle joints. The study is a double blind, prospective, randomized, placebo-controlled, stepwise trial. Amobarbital will be delivered to ankle joints in solution with hyaluronic acid (HA) as a vehicle. Amobarbital/HA injections (active dose) will be compared to HA alone (placebo dose). Our primary goal is to confirm safety, but we will also assess whether treatment improves chondrocyte viability and decreases synovial inflammation. The intervention that will be utilized has proven to be effective using vitro and in vivo models. The study team will assess safety and begin to evaluate efficacy of amobarbital/Gel-One in patients having sustained tibial pilon fractures. The study team will use advanced imaging-based methods we have developed to characterize how joints subjected to varying levels of fracture severity and residual elevated contact stress respond in treated and control groups.

This is an retrospective and prospective observational multinstitutional study to evaluate the impact on outcome of the combination of HMA plus venetoclax in patients with AML unfit for intensive chemotherapy in a real-life scenario. At least 104 AML adult patients ineligible for intensive chemotherapy treated with the combination HMA plus venetoclax under the Italian Law No.648/96 by December 2021 will be enrolled. No additional procedures or visits other than those required by normal clinical practice will be required. Patients will be observed for at least 24 months.

This is an retrospective and prospective observational multinstitutional study to evaluate the impact on outcome of the combination of HMA plus venetoclax in AML patients unfit for intensive chemotherapy in a real-life scenario. No additional procedures or visits other than those required by normal clinical practice will be required. Patients will be observed for at least 24 months.

At present, there are many clinical trials of chemotherapy drugs combined with anti-PD-1 antibody in the treatment of tumor, but the clinical study of CAV / IE chemotherapy combined with anti-PD-1 antibody in the treatment of advanced or non resectable bone and soft tissue sarcoma has not been started, and the related research is still in the blank state. In view of the above problems, to observe and evaluate the efficacy and safety of CAV / IE chemotherapy combined with toripalimab in the treatment of advanced or non resectable bone and soft tissue sarcoma patients, so as to provide more treatment options for patients with advanced or non resectable bone and soft tissue sarcoma.

The aim of this study was to investigate the efficacy and safety of CAV / IE chemotherapy combined with toripalimab in the treatment of patients with advanced or unresectable bone and soft tissue sarcomas who failed in standard treatment.

At present, there are a number of clinical trials of chemotherapy drugs combined with anti PD-1 antibody in the treatment of cancer, but the clinical research of chemotherapy containing adriamycin combined with anti-PD-1 antibody for advanced STS patients is almost blank. Regimen containing adriamycin is the standard chemotherapy regimen for advanced STS approved by international guidelines. As an innovative PD-1 monoclonal antibody, more phase II clinical studies are needed to evaluate the efficacy and safety of sintilimab in a variety of cancers. For patients who fail or cannot tolerate first-line treatment, treatment options are still limited. In view of the above problems, this study aims to observe and explore the efficacy and safety of chemotherapy including adriamycin combined with sintilimab in the second-line treatment of patients with advanced STS, so as to provide more and better treatment options for patients with advanced STS.

The aim of this study was to explore the efficacy and safety of adriamycin and ifosfamide combined with sintilimab in the treatment of advanced or unresectable soft tissue sarcoma.

The psychometric validation study will take place in the PICU of the Hospital of Padua. CAPD translation and cultural adaptation was developed within the Pediatric Cardiac Surgery Intensive Care Unit of the Federico II Polyclinic.~In this study we aim to perform the psychometric validation. 70 children (based on the inclusion and exclusion criteria described above) admitted in PICU will be daily assessed by two nurses (inter-evaluator agreement) using the Italian version of CAPD scale administered twice at a distance of 2 minutes (intra-evaluator agreement).~The score will be recorded in a data collection card, all the cards will be collected and then analyzed.

70 children (based on the inclusion and exclusion criteria described above) admitted in PICU will be daily assessed by two nurses (inter-evaluator agreement) using the Italian version of CAPD scale administered twice at a distance of 2 minutes (intra-evaluator agreement).

The intraoperative recognition of target structures, which need to be preserved or selectively removed, is of paramount importance during surgical procedures. This task relies mainly on the anatomical knowledge and experience of the operator. In the setting of minimally invasive surgery, there is a reduced tactile feedback and the surgeon's vision is the only clue to discriminate the tissues. Misperception of the anatomy, due to patient-specific pathologic conditions and/or to the surgeon's inexperience, can lead to an increased risk of iatrogenic injury of critical anatomical structures and can have devastating consequences. Hyperspectral imaging (HSI) represents a promising technology that combines a photo camera to a spectrometer and that is able to perform a real-time optical scanning over a large area, in a contrast-free manner, providing both spatial and spectral information, generated by the tissue/light interaction. The technology is based on the use of reflectance spectroscopic imaging measurements. The measurement consists in the irradiation of white light on the area (normal halogen lamps, in non-harmful intensity) and the recording of the remitted spectral intensities from the area in the form of remission spectra. The optical interaction (scattering, absorption) of the incident light with the various components (including the depth) of the target material (e.g. biological tissues) alters the spectral distribution of light so that the remitted light carries information about the current material or tissue composition and physiology (e.g. perfusion). HSI is an already established method of objectively classifying image information in a number of scientific fields (e.g. remote sensing), which was first applied in the area of human medicine about 15 years ago. Because of the intrinsic advantages of non-destructive sample collection, interfacing possibilities with common optical modalities (microscope, endoscope) and quantitative, examiner independent results, various approaches have been developed in the meantime to harness the potential of hyperspectral imaging in medicine.~Its usefulness in the biomedical field has been already extensively prove. It has been previously applied in digestive surgery to quantify intestinal oxygenated hemoglobin during several procedures, or in case of mesenteric ischemia. A number of previous works focused successfully on the ability of HSI to discriminate between normal and tumor tissue, in prostate cancer, colorectal cancer, gastric cancer, glioblastoma, head and neck cancers. In the oncological field, the advances in hyperspectral features classification have been remarkable and lead to the successful use of sophisticated deep learning algorithms. In surgery, the usefulness of HSI camera has been studied to visualize the operative field under difficult bleeding or to detect tumor presence within the resection margins after surgical excision.~A japanese group used an HSI system as additional visualization tool to detect intestinal ischemia and also to classify the intraabdominal anatomy. They identified a particular wavelength (756-830 nm) for the differentiation between healthy and less perfused bowel. They also demonstrated that the spleen, colon, small intestine, urinary bladder and peritoneum have different spectral features. This finding might enable in the future HSI-based navigation of the operation field. Our group recently employed HSI as intraoperative tool in the porcine model to quantify perfusion of the organs of the gastrointestinal tract against robust biological markers. Results showed that this technology is able to quantify bowel blood supply with a high degree of precision.~Other groups previously attempted to discriminate bile duct from the vessels, esophagus from tracheal tissue, thyroid from parathyroid gland, nerve and ureter from the surrounding tissue. However, those previous works directed on recognizing key anatomical structures were conducted using either simple feature discrimination algorithms or band selection methods. The amount of information obtained after each acquisition, varies according to the camera resolution, but is quite large, therefore machine and deep learning techniques for data classification and feature extraction are required. In a set of controlled experiments in the porcine model, hyperspectral signatures have been successfully used, coupled to machine learning algorithms, to discriminate fine anatomical structures such as nerves or ureters intraoperatively (unpublished data).~The i-EX-MACHYNA3 study aims at translating the HSI technology in combination with several deep learning algorithms to differentiate among different classes of human tissues (including key anatomical structures such as BD, nerves and ureters).

The intraoperative recognition of target structures, which need to be preserved or selectively removed, is of paramount importance during surgical procedures. This task relies mainly on the anatomical knowledge and experience of the operator. Misperception of the anatomy can have devastating consequences. Hyperspectral imaging (HSI) represents a promising technology that is able to perform a real-time optical scanning over a large area, providing both spatial and spectral information. HSI is an already established method of objectively classifying image information in a number of scientific fields (e.g. remote sensing).~Our group recently employed HSI as intraoperative tool in the porcine model to quantify perfusion of the organs of the gastrointestinal tract against robust biological markers. Results showed that this technology is able to quantify bowel blood supply with a high degree of precision. Hyperspectral signatures have been successfully used, coupled to machine learning algorithms, to discriminate fine anatomical structures such as nerves or ureters intraoperatively (unpublished data).~The i-EX-MACHYNA3 study aims at translating the HSI technology in combination with several deep learning algorithms to differentiate among different classes of human tissues (including key anatomical structures such as BD, nerves and ureters).

Study Rationale~COVID-19, the name given to the clinical syndrome associated with the newly recognized virus SARS-CoV-2, has become pandemic with a mortality estimated between 1-4% and complications among hospitalized patients leading to up to 15-25% of hospital admissions being admitted to the intensive care unit (ICU).~The term cytokine storm calls up vivid images of an immune system gone awry and an inflammatory response flaring out of control. The term has captured the attention of the public and the scientific community alike and is increasingly being used in both the popular media and the scientific literature. Indeed, a few publications have indicated an important part of the complications in COVID-19 are related to the cytokine storm (Huang et al. Lancet 2020, Mehta et al. Lancet 2020).~In a clinical study conducted in sepsis patients with Allocetra-OTS (ClinicalTrials.gov Identifier: NCT03925857) we observed that administration of Allocetra-OTS to patients with sepsis was safe and had a significant immuno-modulating effect, leading to resolution of the cytokine storm in these patients. There were indications that this treatment may also be efficacious, based on comparisons with mortality score prediction and historical matched-controls, and the resolution of organ dysfunction compared to matched historical controls.~A recent study published by Zou et al (Lancet 2020) showed increasing odds of in-hospital death in these COVID-19 patients associated with older age and higher Sequential Organ Failure Assessment (SOFA) score on admission.~Taken together, in patients with severe COVID-19, there may be a comparable underlying immunological mechanism of action as was recently demonstrated by us in sepsis; that is a hyper-inflammatory pathway associated with increased death. Therefore, a study of 5 patients was designed to determine the safety of this treatment in patients with severe COVID-19 and was approved by the Ministry of Health Ethical Committee. Based on the approved protocol, the intermediate clinical results of this trial show that the drug is safe and promising.~Study Design~This is a multi-center, open-label study evaluating the safety of Allocetra-OTS, in up to 24 adult patients with severe COVID-19 and respiratory dysfunction. Subjects, who will be identified as suffering from COVID-19, will be recruited.~After signing an informed consent by the patient and, within 24+6 hours following the time of eligibility (time 0), on Day 1, eligible recipient subjects will receive single intravenous (IV) administration of investigational product as described below:~● Allocetra-OTS treatment at 140 x 106 ±20% cells/kg body weight (screening body weight) in 375 mL of Ringer's lactate solution.~Subjects will be followed for efficacy and safety assessments over 28 days following investigational product administration.~Subjects will be hospitalized for COVID-19, and later as medically indicated. Following IP administration (Day 1), subjects will be followed for efficacy and safety assessments through 28 days. The number of visits for subjects participating in this study will be on days 3, 5, 7±1, 14±2, and 28±2. Visits on days 7 and 14 may be done via zoom or telephone.~Study Intervention, Route of Administration, and Dosage Form~Allocetra-OTS is a cell-based therapeutic composed of donor early apoptotic cells.~Patient Classification [National Institutes of Health (NIH)]- www.covid19treatmentguidelines.nih.gov/overview/management-of-covid-19/~In general, adults with COVID-19 can be grouped into the following severity of illness categories:~Asymptomatic or Pre-symptomatic Infection: Individuals who test positive for SARS-CoV-2 by virologic testing using a molecular diagnostic (e.g., polymerase chain reaction) or antigen test, but have no symptoms.~Mild Illness: Individuals who have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain) without shortness of breath, dyspnea, or abnormal chest imaging.~Moderate Illness: Individuals who have evidence of lower respiratory disease by clinical assessment or imaging and saturation of oxygen (SpO2) ≥94% on room air at sea level.~Severe Illness: Individuals who have respiratory frequency >30 breaths per minute, SpO2 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg, or lung infiltrates >50%~Critical Illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.~Standard of Care (SOC)~The SOC for COVID-19 will be according to institutional standards. Institutional SOC may include Clexane, anti-viral agents such as Remdesivir, corticosteroids, or other agents.~Concomitant Medications~Prohibited medications: Significant immune-suppressing agents before developing COVID-19, including chronic corticosteroids > 10 mg/day, Azathioprine, Cyclosporine, Cyclophosphamide, and any biological treatment.~The known SOC medications to treat COVID-19; Hydroxychloroquine, Chloroquine, and Azithromycin, are not known to have any possible interaction with Allocetra-OTS. Neither are anti-viral agents.~Concomitant Medical Conditions~Apart from patients with a tumor or end-stage organ condition, chronic diseases like cardiovascular or diabetes are allowed.

This is a multi-center, open-label study evaluating the safety of Allocetra-OTS, in up to 24 subjects with severe COVID-19 and respiratory dysfunction. Subjects, who will be identified as suffering from COVID-19, will be recruited.~After signing an informed consent by the patient and, within 24+6 hours following the time of eligibility (time 0), on Day 1, eligible recipient subjects will receive single intravenous (IV) administration of investigational product as described below.~Subjects will be hospitalized for COVID-19, and later as medically indicated. Following the investigational product (IP) administration (Day 1), subjects will be followed for efficacy and safety assessments through 28 days.

A recent study, where the authors studied the effectiveness of stenting of prolonged lesions (>200 mm) of the femoral-popliteal segment with nitinol stents (TASC II, D), showed unsatisfactory primary patency rates (45%) within 2 years follow up (Lin et al, 2015). One of the possible solutions to the problem of breakage of stents in the femoral-popliteal position is a modified method of their manufacture by braiding from nitinol wire. Another possible solution to the problem of stent breakage in the femoral-popliteal position is fasciotomy in Gunter's canal with dissection of the lamina vasto-adductoria. According to a pilot randomized study (Karpenko et al, 2019), the primary patency at 24 months was 60% in the stenting group supplemented with fasciotomy in Gunter's canal, and 28.5% in the stenting group without fasciotomy. These facts prove the need for a comparative study on a cohort of patients using a biomimetic interwoven nitinol stent. This is a pilot prospective, randomized, open-label study. The main objective of the study is to compare the clinical efficacy and safety of two methods of treating prolonged atherosclerotic lesions (TASC II, type D) of the arteries of the femoropopliteal segment above the knee.~Screening It is performed in patients with a verified diagnosed occlusive lesion of the femoropopliteal segment above the knee (type D by TASC II classification), with chronic limb ischemia (3-6 categories by Rutherford classification). Assessment of inclusion / exclusion criteria, assigning a patient number.~Study inclusion Collecting baseline information about the patient (anamnesis, including information about concomitant therapy, data from the initial physical examination, ultrasound data of the lower limb arteries, CT-angiography data, assessment of the quality of life using the SF-36 questionnaire). Randomization using the envelope method to one group or another.~Surgical intervention:~Group 1 (n=50): Recanalization of prolonged occlusion of the arteries of the femoral-popliteal segment above the knee with angioplasty and stenting with a biomimetic interwoven nitinol stent; Group 2 (n=50): Recanalization of prolonged occlusion of the arteries of the femoropopliteal segment above the knee with angioplasty and stenting with a biomimetic interwoven nitinol stent, supplemented by fasciotomy in Gunter's canal.~Follow up: 6, 12, 24 months.~Performed:~Triplex ultrasound of one lower limb (restenosis, thrombosis, stent breakage); Radiography of the operated limb in two projections, for patients in whom a stent breakage is suspected according to ultrasound; Consultation with a cardiovascular surgeon. For each patient participating in the study, a CRF is filled out in a form convenient for the Investigator. The creation of a folder Investigator's file is provided, which stores all the necessary documents provided for by the rules of Good Clinical Practice.

A recent study, where the authors studied the effectiveness of stenting of prolonged lesions (>200 mm) of the femoral-popliteal segment with nitinol stents (TASC II, D), showed unsatisfactory primary patency rates (45%) within 2 years follow up (Lin et al, 2015). One of the possible solutions to the problem of breakage of stents in the femoral-popliteal position is a modified method of their manufacture by braiding from nitinol wire. Another possible solution to the problem of stent breakage in the femoral-popliteal position is fasciotomy in Gunter's canal with dissection of the lamina vasto-adductoria. According to a pilot randomized study (Karpenko et al, 2019), the primary patency at 24 months was 60% in the stenting group supplemented with fasciotomy in Gunter's canal, and 28.5% in the stenting group without fasciotomy. These facts prove the need for a comparative study on a cohort of patients using a biomimetic interwoven nitinol stent. This is a pilot prospective, randomized, open-label study. The main objective of the study is to compare the clinical efficacy and safety of two methods of treating prolonged atherosclerotic lesions (TASC II, type D) of the arteries of the femoropopliteal segment above the knee.

This Phase 2b, open-label, single-arm, multi-center study will assess the efficacy and safety of adavosertib in eligible subjects with histologically confirmed recurrent or persistent USC, evidence of measurable disease as per Response Evaluation Criteria in Solid Tumors.(RECIST) v1.1, and who have received at least 1 prior platinum-based chemotherapy regimen for the management of USC. Subjects with carcinosarcomas are not eligible.

This Phase 2b study aims to evaluate the efficacy and safety of adavosertib, an inhibitor of the tyrosine kinase WEE1, in subjects with recurrent or persistent uterine serous carcinoma (USC) who have previously received at least 1 prior platinum-based chemotherapy regimen for the management of USC.

This Phase II randomized, double-blind, placebo-controlled, study will assess 2 different doses of GLS-1027 in the prevention of severe pneumonitis among those hospitalized with PCR confirmed SARS-CoV-2 infection. Subjects will be randomized at a 1:1:1 ratio to either Standard of Care (SOC) plus placebo, or SOC plus GLS-1027 at either 120 mg or 360 mg daily. Clinical status will be monitored through 56 days from the initiation of treatment.

This clinical trial will evaluate the safety, tolerability and efficacy of GLS-1027 in the prevention of severe pneumonitis caused by SARS-CoV-2 infection

According to the 2006 European guidelines, the target age for mammography screening is 50-69 years. For women aged 40-49, effectiveness is less and less certain. For those over 70, the most important concern is overdiagnosis. In Europe, so far, both age groups have been invited to screen only in a few countries and regional areas, including some Italian regions. Recently, new European guidelines have been published, developed in the framework of the European Commission Initiative on Breast Cancer. Although with caution, they recommend screening for both women aged 45-49 and those aged 70-74. The recommended interval is 2 or 3 years in the first case and 3 years in the second. The quality of the evidence on which these recommendations are based is defined as very low. Particularly for women aged 45-49, the new European guidelines indicate the need for a research effort, based on comparative studies, on the effectiveness of different screening intervals. This responsibility also falls on Italy, which is the only European country where women aged 45-49 are invited on an annual basis. Therefore, a research project is proposed which includes (1) a controlled, prospective randomized non-inferiority trial to determine the optimal screening interval for women aged 45-49, with and without high mammographic density, (2) a retrospective data collection, with the same purpose, on screening performed by women aged 70-74, and (3) a qualitative research to define the best communication strategy.~To define the best interval for screening women 45-49 years old a three-arm multicenter randomized non-inferiority trial will be conducted. Women signing the written informed consent will be randomized with a 1:1:1 ratio to:~Arm 1: 1-year screening interval; Arm 2: 2-year screening interval; Arm 3: tailored screening interval on the basis of breast density. Women with very dense breast (Breast Imaging-Reporting and Data System -BI-RADS- category D) will be referred to 1-year interval whereas women with less dense breast to 2-year interval (Breast Imaging-Reporting and Data System -BI-RADS- category A, B, C).~Enrollment will last 2.5 years and all women will be followed for 6 years. 60,000 women will be enrolled.~The primary objective is to compare the cumulative incidence of stage 2 or higher breast cancer between different screening intervals and this will be evaluated at the end of the 6-year follow-up period.~At the same time, data from all women registered in screening archives who have had a negative mammogram at the age of 69-71 years will be collected and analyzed. The data will be retrieved up to the age of 78 and will concern screening mammograms as well as other screening procedures (e.g. biopsies) and also mammograms performed outside the program. Data from screening and outpatient information systems as well as from cancer registries will be used.~To identify the best strategy to communicate changes in screening protocols, especially when the new protocol would be less intensive than the actual one, a qualitative research will be conducted. In particular the following steps will be considered:~Focus groups for discussing, with women from target population and health care professionals, key arguments identified in a preliminary research (i.e. scientific literature and case-studies research), with particular focus on how they should be translated into communication strategies.~Pre-test of the study's communication material through web-based semi-structured interviews to eligible women and key-informants.~Assessment of the effectiveness of the communication material through web-based semi-structured interviews to participants, that may bring insights on how planning communication strategies for the implementation of new screening protocols.

Italian, multicenter, study aimed at defining the best interval for screening women 45-49 and 70-74 years for Breast Cancer (BC). This research project includes (1) a controlled, prospective randomized non-inferiority trial to determine the optimal screening interval for women aged 45-49, with and without high mammographic density, (2) a retrospective data collection, with the same purpose, on screening performed by women aged 70-74, and (3) a qualitative research to define the best communication strategy.

This adaptive, randomized, placebo-controlled platform study is designed to rapidly assess multiple candidate agents as treatments for COVID-19 in hospitalized patients. Candidate agents will be evaluated frequently (through ongoing monitoring) for futility and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.~For inclusion, participants will need to be hospitalized with a clinical status of Grade 2 to Grade 5, as defined by the following Clinical Severity Status 8-Point Ordinal Scale:~Death~Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)~Hospitalized, on noninvasive ventilation or high-flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities~Participants will be randomized equally to either the candidate agent plus standard of care (SoC) or placebo plus SoC in a double-blind fashion. Participants who are randomized to placebo plus SoC will subsequently be randomized equally to a matching placebo corresponding to an available agent whose sub-protocol the patient qualified for (ie, a 2-stage randomization). Each participant in the placebo plus SoC group will only receive one type of placebo. Randomization will be stratified by baseline clinical severity of 2 on the 8-point ordinal scale (yes/no) and remdesivir use at baseline (yes/no).~The study will evaluate each candidate agent separately as an add-on to the SoC to assess safety and efficacy. The comparator group for a candidate agent will include participants randomized to the placebo arm of any sub-protocol according to the following conditions:~Apremilast sub-protocol: participants who were enrolled concurrently to apremilast and who would have been eligible for the apremilast sub-protocol.~Lanadelumab sub-protocol: at a site where at least one participant was randomized to either lanadelumab active or placebo arms.~Zilucoplan sub-protocol: at a site where at least one participant was randomized to either the zilucoplan active or placebo arms.

The primary objective of this study is to evaluate the time to confirmed clinical recovery in participants hospitalized with COVID-19. Candidate agents will be evaluated frequently for efficacy and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.

Preterm birth is not a single entity but rather multifactorial The mechanisms underlying preterm birth are multifactorial and include stretch, oxidative stress, inflammation, infection and thrombosis. 85% of women have no identifiable risk factors for preterm birth and there is a requirement to develop a biomarker which can be used early in pregnancy to identify such women at risk. Equally important is to have a detection tool which will allow us to offer an individualised approach to preterm birth prevention and the women to benefit personalised surveillance and timely preventative measures such as cervical cerclage or progesterone.~The aim of this study is to collect samples from pregnant women in order to identify biomarkers that relate to onset of spontaneous preterm labour. We will use maternal blood, urine and vaginal secretion to look for biomarkers in these samples which can be use in the clinical setting to determine which women will go on to give birth preterm. This will allow clinicians to correctly identify these women and initiate treatment in the right woman to prevent preterm labour and birth. Equally important it will reduce unnecessary intervention and admission in those women who are not at risk.

This study will collect samples from pregnant women in order to identify biomarkers that relate to onset of spontaneous preterm labour.

This is an open-label follow up study to evaluate the safety for the subjects with ALLO-ASC-DFU treatment in phase 3 clinical trial (ALLO-ASC-DFU-301) for 24 months. ALLO-ASC-DFU is a hydrogel sheet containing allogenic adipose-derived mesenchymal stem cells. Adipose-derived stem cells have anti-inflammatory effect and release growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), which can enhance wound healing and regeneration of new tissue, finally may provide a new option in treating a Diabetic Foot Ulcer.

This is a follow-up study to evaluate the safety for the subjects with ALLO-ASC-DFU treatment in phase 3 clinical trial (ALLO-ASC-DFU-301) for 24 months

Background- Adolescent idiopathic scoliosis is the most common indication for major surgery in adolescents (between 10 and 18 years of age). The current standard of care for adolescent idiopathic scoliosis (AIS) with a curve magnitude of over 40-50˚ in skeletally immature patients, is posterior spinal fusion with pedicle screws. The aim of spinal fusion is to prevent further curve progression but also to correct the spinal deformity and achieve a cosmetically pleasing result by reducing the rib hump and balancing the trunk and shoulders. While this procedure has been very successful, it has inherent downsides such as the decreased range of motion and loss of spinal mobility in addition to the inhibition of growth along the instrumentation. To prevent distal adding on (continued curve below instrumentation) due to continued anterior spinal growth, it is often necessary to fuse the spine into stable vertebra resulting into even longer spinal fusion levels in the lumbar spine (Sponseller et al. JPO 2016; Oksanen et al. SJS 2018). Spinal fusion increases loading of the remaining mobile segments (Parsch et al. JBJS Br 2001).~In a five-year follow-up study spinal fusion resulted into better health-related quality of life (HRQoL) as compared with untreated AIS (Helenius et al. JBJS 2019). However, the function domain of HRQoL was significantly less after spinal fusion as compared with healthy controls. In contrast, vertebral body tethering using screws connected by a tether in the anterior vertebral body, has the potential to initially correct the still flexible deformity, but most importantly modulate growth and ultimately result in scoliosis correction with a mobile spine.~There is currently a paucity of literature on the effectiveness of vertebral body tethering (VBT) with only retrospective case series published and reported in conference proceedings, and a comparative study is completely lacking. Initial complication rates with the implants for tethering have also sparked caution amongst surgeons and payers whether or not to adopt this technique despite its theoretical advantages. Thus, a high-quality comparative prospective study is missing to demonstrate the effectiveness and safety of vertebral body tethering compared to posterior spinal fusion. If this can be shown in a well-designed study, it is likely to result in a paradigm shift in the treatment of AIS similar to the impact earlier technical novelties and achievements had.~Randomised controlled trials are rare in paediatric orthopaedic research. It would be unprecedented that evidence from an RCT is driving a change in practice in scoliosis surgery.~Aims and hypothesis- To compare posterior fusion to VBT for the treatment of AIS. Aim is to demonstrate non-inferiority of VBT compared to posterior fusion in terms of main curve correction of AIS at the 2 year follow up, to demonstrate comparable outcomes for SRS-22/24 at the 2 year follow up. Aim is also to compare complication and revision rates and to compare spinal mobility including flexion and side bending between the study groups.~Inclusion criteria- The inclusion criteria would aim to restrict the study to paediatric patients with AIS and the following criteria: Lenke type I A,B or C, age 10-16 years, skeletally immature (Sanders classification between 2 and 5), Cobb angle 40-60˚, 50% flexibility on supine bending films, selective thoracic fusion feasible~Exclusion criteria- Any other than idiopathic scoliosis, less than 50% curve flexibility, skeletal maturity (Sanders >5), patients who have evidence of neurological disorders, patients who have undergone intrathoracic surgery Outcome parametres- Cobb angle correction of instrumented curve at 2 year follow up, total score of SRS questionnaire at 2 year follow up; secondary outcomes: Complication and revision rates, pulmonary function at 2-year follow-up, spinal mobility at 2-year follow-up~Interventions: AVBT from end to end vertebra. PSF levels using the Lenke criteria.~Ethical aspects- Each institution in each country is responsible for obtaining either institutional review board approval or approval from a national ethics committee as appropriate. An informed consent will be obtained from all children and their parents.~Time schedule and budget- The study will be started on beginning of 2021. Patient enrollment is expected to last to the end of 2023. There will be no extra costs as all information gathered will be part of normal surgical treatment of AIS. A part-time research nurse has been hired to take care of data collection into the database.~References:~Sponseller PD, Jain A, Newton PO et al. Posterior Spinal Fusion With Pedicle Screws in Patients With Idiopathic Scoliosis and Open Triradiate Cartilage: Does Deformity Progression Occur? J Pediatr Orthop 2016; 36:695-700.~Oksanen H, Lastikka M, Helenius L, et al. Posterior Spinal Fusion Extended to Stable Vertebra Provides Similar Outcome in Juvenile Idiopathic Scoliosis Patients Compared with Adolescents with Fusion to the Touched Vertebra. Scand J Surg 2019 Mar; 108(1):83-89.~Parsch et al. JBJS Br 2001~Helenius L, Diabakerli E, Grauers A, et al. Back Pain and Quality of Life after Surgical Treatment for Adolescent Idiopathic Scoliosis

Background- Adolescent idiopathic scoliosis is the most common indication for major surgery in adolescents. The current standard of care for adolescent idiopathic scoliosis (AIS) with a curve magnitude of over 40-50˚ in skeletally immature patients, is posterior spinal fusion with pedicle screws. Vertebral body tethering using screws connected by a tether in the anterior vertebral body, has the potential to initially correct the still flexible deformity, but most importantly modulate growth and ultimately result in scoliosis correction with a mobile spine. A high-quality comparative prospective study is missing to demonstrate the effectiveness and safety of vertebral body tethering compared to posterior spinal fusion.~Study Design- An international, randomized clinical trial on posterior spinal fusion with pedicle screws vs. Anterior vertebral body tethering in Adolescent Idiopathic Scoliosis (AIS)~Aims- To demonstrate non-inferiority of VBT compared to posterior fusion in terms of main curve correction of AIS at the 2 year follow up, to demonstrate comparable outcomes for SRS-22/24 at the 2 year follow up. Aim is also to compare complication and revision rates and to compare spinal mobility including flexion and side bending between the study groups.~Inclusion criteria- Lenke type I A,B or C, age 10-16 years, skeletally immature, Cobb angle 40-60˚, 50% flexibility on supine bending films, selective thoracic fusion feasible~Exclusion criteria- Any other than idiopathic scoliosis, less than 50% curve flexibility, skeletal maturity, patients who have evidence of neurological disorders, patients who have undergone intrathoracic surgery~Outcome parametres- Cobb angle correction of instrumented curve at 2 year follow up, total score of SRS questionnaire at 2 year follow up; secondary outcomes: Complication and revision rates, pulmonary function at 2-year follow-up, spinal mobility at 2-year follow-up~Ethical aspects- Each institution in each country is responsible for obtaining either institutional review board approval or approval from a national ethics committee as appropriate. An informed consent will be obtained from all children and their parents.

Background and Purposes: Constipation among children is a global health issue. It can distribute a significant impact on medical, social, and economic dimensions, and can delay children's growth. Without proper treatments on constipation, it would reduce the cure rate and increase recurrence rate. Early diagnosis can improve the prognosis of functional constipation. Only a few studies of children constipation are available in the literature, so it is critical to investigate the topic of constipation among children.~Methods: This is a quasi-experimental design study, which will enroll students in the 3rd to 6th grades of two primary schools and their parents in Yunlin. There will be 200 children in the experimental group and 200 in the control group; a total of 400 students and their parents. Parents in the experimental group will receive health educational leaflets every week and students will have to record the situation of defecation once a week. No intervention will be given to the control group. The 4-weeks intervention is scheduled to be from September to November 2020, with a total of 8 weeks. Both the experimental and control groups will be asked to fill up a questionnaire at the before and after the intervention. The questionnaire includes the defecation and constipation situation of children, physical activity, dietary behavior, life pressure, and parents' knowledge and attitude toward constipation. Both groups of children have to fill out the Stool diary record sheet, including the intervention period and the follow-up period for a total of 8 weeks Children with the first and second types of the Bristol Stool Scale will be defined as constipation.~Expected results: The study can provide the understanding of the current status of constipation in primary school children, parents' awareness and attitudes on constipation-related issues. Besides, through the study, a simple and feasible health educational program for parents of primary school children will be proposed, and the efficacy of the program will be evaluated.

The research adopts caregiver-mediated health educational intervention to Improve constipation status of primary school children. It is a quasi-experimental design study, which will enroll students in the 3rd to 6th grades of two primary schools and their parents in Yunlin County. There will be 200 children in the experimental group and 200 in the control group. Parents in the experimental group will receive health educational leaflets every week and no intervention will be given to the control group. Both the experimental and control groups students will be asked to fill up a questionnaire at the before and after the intervention with a total of 8 weeks. The study can provide the understanding of the current status of constipation in primary school children, parents' awareness and attitudes on constipation-related issues.

Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who had prior immune checkpoint inhibitor and platinum-based chemotherapy treatment will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab. Efficacy and safety assessments will be performed periodically from the time of enrollment and throughout the study. Patients in all arms will continue therapy until progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. All patients will be followed for survival after progression is confirmed.

This is a randomized, double-blind, multicenter, global Phase 3 study to assess the efficacy and safety of monalizumab and cetuximab, compared to placebo and cetuximab, in patients with recurrent or metastatic head and neck cancer.

Hip dysplasia is a common disease both worldwide and among the Danish population. The disease is characterized by a shallow and oblique acetabulum, resulting in insufficient coverage of the femoral head. The abnormalities of the dysplastic hip joint lead to altered biomechanical adaptations, highly affecting the physical capacity of patients. Studies have shown that patients with hip dysplasia experience reduced muscle strength and gait abnormalities, when compared to healthy controls.~Each year, approximately 200 Danes with hip dysplasia are treated with periacetabular osteotomy (PAO). As the preferable joint-preserving surgical treatment for younger patients with symptomatic hip dysplasia, the PAO reduces prevalence of muscle-tendon-related pain and improves hip and groin related patient-reported outcome measures (PROMs). By extension, studies report a hip survival rate of approximately 75% 12 years following PAO.~However, little is known about objective measures of physical capacity following PAO. Despite reducing muscle-tendon-related pain and improving PROMs, gait adaptations still remain and studies report no improvements in muscle strength, nor in the physical activity profile, 1 year following treatment with PAO. Thus, the field calls for research aiming to identify parameters of impaired physical capacity in patients treated with PAO. Thorough knowledge of physical capacity in these patients may contribute to the establishment of a science-based rehabilitation strategy, potentially improving physical activity, function, work capacity and quality of life.~The primary aim of this study is to analyse and identify parameters of impaired physical capacity in patients with hip dysplasia 1-5 years following treatment with PAO. Gait function, defined as peak hip extension angle and peak hip flexor moment, is chosen as the primary outcome, due to previously shown correlations between the extent of gait impairments and the Copenhagen Hip and Groin Outcome Score (HAGOS).~As recommended by the International Hip-related Pain Research Network (IHiPRN), measurements of physical capacity in patients with hip-related pain should include: clinical measures, laboratory-based measures, measures of physical activity and return to physical activity. Secondary outcomes of this study are: muscle activity during level walking and walking with inclination, endurance and pain during walking, range of motion (ROM), muscle strength, hip and muscle-tendon-related pain, radiographic measures and PROMs (present level of physical activity and sports & activity level prior to and after treatment with PAO).~We hypothesise that patients with the lowest scores of HAGOS subscales pain and sport/recreation will have the lowest physical capacity, measured as: gait impairments, reduced muscle strength and prevalence of muscle-tendon-related pain.~This is a cross-sectional study.~Thirty subjects from across the country, aged 18-40 years, who have undergone a PAO for hip dysplasia within the last 1-5 years, will be included in the study.~All testing will be performed at Copenhagen University Hospital, Hvidovre.

This cross-sectional study investigates the physical capacity of patients, who have undergone a periacetabular osteotomy for hip dysplasia within the last 1-5 years.

Inadequate bowel preparation is insufficient for identification of polyps greater than 5 mm. However, bowel preparation assessment involved subjectivity and uncertainty. We constructed a deep learning based system to calculate the proportion of Boston Bowel Prep Scale (BBPS) score of 0-1 during withdrawal phase and performed a prospective observational study to validate the threshold of the adequate proportion.The multi-center study is aimed to verify the extrapolation and robustness of the scoring threshold based on artificial intelligence intestinal cleanliness evaluation system explored in the early stage, and propose a more accurate and quantifiable threshold for evaluating the eligibility of intestinal preparation.

A deep learning based system to calculate the proportion of Boston Bowel Prep Scale (BBPS) score of 0-1 during withdrawal phase has been constructed previously. This multi-center study is going to perform a prospective observational study to validate the threshold of the adequate proportion.

Neurofeedback is a cognitive remediation technique that allows a subject to learn to regulate their cognitive and brain activity through information provided in real time about their brain activity, in particular electroencephalographic (EEG) brain activity. Neurofeedback has been used to regulate EEG amplitude in certain spectral bands, which correlate with the degree of neural synchronization. Neurofeedback makes it possible in particular to reduce the amplitude of the EEG theta spectral band (4-8 Hz) and to increase the EEG beta spectral band (> 12Hz).~This type of protocol has been used successfully to reduce the degree of neural synchronization and to stimulate arousal systems and sustained attention skills.~Studies on healthy subjects submitted to controlled sleep deprivation have shown that inducing a full night of sleep deprivation is a good model for studying the brain mechanisms of arousal and the links with cognitive functions, but also to assess the effectiveness of counter measures reducing the impact of sleep deprivation on cognitive performance. These experimental models provide a better understanding of the mechanisms and consequences of the complaint of excessive daytime sleepiness (EDS). EDS is indeed a frequent symptom affecting between 5% and 8% of the population. The consequence of EDS is a decrease in quality of life. In addition, the EDS entails a high medico-economic cost because of the accidental risk of the public and professional roads.~Neurofeedback could, through its impact on the degree of neuronal synchronization, help to reduce the impact of sleep deprivation on wakefulness and cognitive performance. Thus, it appears relevant to assess the effectiveness of neurofeedback, targeting activities in the theta / beta EEG spectral band, on wakefulness and cognitive performance in healthy subjects with EDS due to sleep deprivation. Targeting the degree of neuronal EEG synchronization would then be an innovative avenue for improving the physiological mobilization of arousal systems and wakefulness and cognitive performance in the event of EDS. This cognitive remediation technique could in particular be proposed as a complement to pharmacological treatment in treated patients suffering from hypersomnolence disorder presenting a residual EDS.~The main objective is to study the effect of a program of 8 sessions of neurofeedback targeting EEG theta / beta activities, to modify the degree of neuronal synchronization, on the ability to maintain objective wakefulness measured by a maintenance wakefulness test (MWT) in healthy subjects presenting objective excessive daytime sleepiness after a full night of sleep deprivation under controlled experimental conditions. The objective of this study will also provide a better understanding of the learning modulation mechanisms of arousal systems.~The secondary objectives are:~To study the effect of a program of 8 sessions of neurofeedback targeting theta / beta EEG activities, in healthy subjects after a full night of sleep deprivation presenting objective excessive daytime sleepiness, on the instantaneous subjective arousal level in a situation controlled (MWT and neurofeedback session) by the Karolinska sleepiness scale (KSS).~To study the effect of a program of 8 sessions of neurofeedback targeting theta / beta EEG activities, in healthy subjects after a full night of sleep deprivation presenting objective excessive daytime sleepiness, on the cognitive performance, before and after neurofeedback sessions, assessed by the Psychomotor Vigilance Task (PVT) and by the Test of Attentional Performance (TAP).~To study the functional reorganization of the EEG activities of the brain, in particular the degree of neuronal synchronization between the different regions of the scalp, in subjects presenting objective excessive daytime sleepiness after a full night of sleep deprivation and following a program of 8 neurofeedback sessions targeting EEG theta / beta activities.~To study a learning effect during the 8 neurofeedback sessions evaluated by measuring the evolution of the modulation of the spectral power in the theta / beta band during each neurofeedback session.~To study the prognostic learning factors during the 8 neurofeedback sessions.~To study the prognostic factors for clinical improvement of MWT, subjective EDS and cognitive performance.

Neurofeedback is a cognitive remediation technique that allows a subject to learn to regulate their cognitive and brain activity through information provided in real time about their brain activity, in particular electroencephalographic (EEG) brain activity. Neurofeedback could, through its impact on the degree of neuronal synchronization, help to reduce the impact of sleep deprivation on wakefulness and cognitive performance. The main objective is to study the effect of a program of 8 sessions of neurofeedback targeting EEG theta / beta activities, to modify the degree of neuronal synchronization, on the ability to maintain objective wakefulness measured by a maintenance wakefulness test (MWT) in healthy subjects presenting objective excessive daytime sleepiness after a full night of sleep deprivation under controlled experimental conditions. The objective of this study will also provide a better understanding of the learning modulation mechanisms of arousal systems.

This is an explorative phase 2 clinical trial which will be conducted in two phases. The aim of this study is to establish the safety and efficacy of treating patients with early colorectal cancer with intratumoral influenza vaccine as a down staging and immune response enhancing treatment prior to intended curative surgery.~The first part of the study will be conducted as a pilot study. Six patients with histologically verified or clinically suspicious sigmoid colon cancer who are planned to undergo curative surgery will be included. Patients will be recruited from the Department of Surgery, Zealand University Hospital after their case has been reviewed by the multidisciplinary team (MDT). Standard treatment involves intended curative surgery within two weeks after the diagnosis. The treatment will be performed within a few days and it will be ensured that the experimental treatment will not lead to a significant delay of intended curative surgery.~If the pilot study finishes without violating any stop rules and without any serious adverse events the second part of the study will be initiated. This will be conducted as a phase 2 study where 24 patients with histologically verified or clinically suspicious sigmoid colon cancer and rectal cancer will be included. Patients will be recruited from the Department of Surgery, Zealand University Hospital after their case has been reviewed by the multidisciplinary team (MDT). Standard treatment involves intended curative surgery within two weeks after the diagnosis. The treatment will be performed within a few days and it will be ensured that the experimental treatment will not lead to a significant delay of intended curative surgery.

The aim of this explorative phase II clinical trial is to establish the safety and efficacy of intratumoral influenza vaccine in patients with colorectal cancer, as an additive treatment prior to intended curative surgery.

Prospective, three-stage, single arm, multi-site, clinical investigation evaluating the safety and efficacy of the reSept ASD Occluder in treating clinically significant secundum ASD. Outcomes/endpoints of the clinical investigation will be compared with established performance goals for FDA approved transcatheter secundum ASD occluders.

Evaluation of the safety and efficacy of the reSept ASD Occluder to treat patients with clinically significant secundum atrial septal defect

This is an open label, balanced, randomised, four-treatment, four-period, four-sequence, single oral dose, crossover Pharmacokinetics study of WD-1603 carbidopa/levodopa extended-release tablets in normal, healthy, adult human subjects under fed conditions. A single oral dose of (either Treatment A or B or C or D) carbidopa/levodopa extended release tablets will be administered to each subject within 5 minutes after completion of standardized vegetarian breakfast under fed condition in each period as per randomization schedule.

An open label, balanced, randomised, four-treatment, four-period, four-sequence, single oral dose, crossover Pharmacokinetics study of WD-1603 carbidopa/levodopa extended-release tablets in normal, healthy, adult human subjects under fed conditions. A single oral dose of (either Treatment A or B or C or D) carbidopa/levodopa extended release tablets will be administered to each subject within 5 minutes after completion of standardized vegetarian breakfast under fed condition in each period as per randomization schedule.

Several publications document the occurrence of symptoms that persist or occur late, more than 3 weeks after the first clinical manifestations of an SARS-COV2 infection. These manifestations may be related to thromboembolic or inflammatory complications, superinfections, or other mechanisms not yet well understood, including potentially related to the persistence of SARS-COV2. The identification of the observed clinical manifestations and their clinical and paraclinical description are essential to better understand the natural evolution of COVID-19, to clarify the pathophysiological mechanism of these possible late manifestations, and to identify potential management options for patients.~Since this type of event is infrequent, a large-scale national multicenter cohort study focusing on symptomatic patients is needed. In parallel, the prevalence of the main symptoms observed more than 3 weeks after the onset of a COVID-19 will be estimated through partnerships with existing cohort studies in the general population or in the population followed for COVID-19, still symptomatic or not at 3 weeks of infection.~Longitudinal implementation of bio-libraries will allow this cohort to also constitute a bridge between clinicians and researchers.

Several publications document the occurrence of symptoms that persist or occur late.~The identification of the observed clinical manifestations and their clinical and paraclinical description are essential to better understand the natural evolution of COVID-19, to clarify the pathophysiological mechanism of these possible late manifestations, and to identify potential management options for patients.~Since this type of event is infrequent, a large-scale national multicenter cohort study focusing on symptomatic patients is needed.

Background: In many cases, the manometric examination is not feasible because of the pharyngeal sinusitis or pharyngeal torsion. In addition, although previous conventional manometry was used to estimate pharyngeal swallowing, the bolus flow transmission was still not evaluated, which still depended on the videofluoscopic swallowing studies. High resolution impedance manometry could help us to measure the bolus flow according to the impedance changes. However, the comparison between two approach methods of postoperative recovery of swallowing function is still inconclusive.~Objectives: The objective of the current study was to examine the correlation between high-resolution manometric and videofluoroscopic measurements of the swallowing function.~Patients and methods: Consecutive patients who will fulfill the criteria of postoperative cervical spine surgery patients aged >= 20 will be enrolled and the dysphagia questionnaire score (EAT-10) was higher than 3, including 3. After got the inform consent, these patients receive the swallowing function by videofluroscopy and HRIM.~Expected result: The investigator will evaluate the swallowing changes of these postoperative cervical spine patients with suspected dysphagia. The investigator expected that the highly correlation between the HRIM and VFSS.

In many cases, the manometric examination is not feasible because of the pharyngeal sinusitis or pharyngeal torsion. In addition, although previous conventional manometry was used to estimate pharyngeal swallowing, the bolus flow transmission was still not evaluated, which still depended on the videofluoscopic swallowing studies. High resolution impedance manometry could help us to measure the bolus flow according to the impedance changes. However, the comparison between two approach methods of postoperative recovery of swallowing function is still inconclusive. The investigator aimed to examine the correlation between high-resolution manometric and videofluoroscopic measurements of the swallowing function.

All hospitalised patients with COVID-19 who have positive RT-PCR for SARS-COV-2 will be included in the study.~The patients will be divided into two groups, as diabetics and non-diabetics. The diagnosis of diabetes mellitus will be extracted from the medical records and medical history of the patients hospitalised with COVID-19.~The COVID-19 patients medical records will be evaluated and compared in terms of the duration of hospitalization, the presence of lung involvement in Computerised Tomography, the need for intensive care unit and mortality rates in patients with and without diabetes.

All hospitalised patients with COVID-19 who have positive RT-PCR for SARS-COV-2 will be included in the study.~The patients will be divided into two groups, as diabetics and non-diabetics. The COVID-19 patients' medical records will be evaluated and compared in terms of the duration of hospitalization, the presence of lung involvement in Computerised Tomography, the need for intensive care unit and mortality rates in patients with and without diabetes.

Initially developed in Japan for the treatment of endemic superficial gastric cancers, endoscopic submucosal dissection (ESD) allows resection of pre-neoplastic and neoplastic lesions of the digestive tract into a single fragment. It allows a perfect pathological analysis, and decreases the rate of recurrence of the adenoma to less than 2%. However, this procedure, which is technically more challenging, is also more risky (perforation rate at 4% vs. 1% for WF-EMR) and longer. Submucosal dissection is also more expensive in terms of equipment, but this difference can be offset by the cost of the high number of iterative colonoscopies required in patients who have had endoscopic resection by WF-EMR.~Scientific debate is agitating the Western world1,2 and Japanese experts do not perform WF-EMR anymore, whereas no comparative prospective study has compared these two procedures.~A lot of centers in France performed colorectal ESD even for benign lesions and nationwide data about safety and efficiency is required to confirm the place of ESD for treatment of large superficial colorectal lesions.

Initially developed in Japan for the treatment of endemic superficial gastric cancers, endoscopic submucosal dissection (ESD) allows resection of pre-neoplastic and neoplastic lesions of the digestive tract into a single fragment. It allows a perfect pathological analysis, and decreases the rate of recurrence of the adenoma to less than 2%. However, this procedure, which is technically more challenging, is also more risky (perforation rate at 4% vs. 1% for WF-EMR) and longer. Submucosal dissection is also more expensive in terms of equipment, but this difference can be offset by the cost of the high number of iterative colonoscopies required in patients who have had endoscopic resection by WF-EMR.~Scientific debate is agitating the Western world1,2 and Japanese experts do not perform WF-EMR anymore, whereas no comparative prospective study has compared these two procedures.~A lot of centers in France performed colorectal ESD even for benign lesions and nationwide data about safety and efficiency is required to confirm the place of ESD for treatment of large superficial colorectal lesions.

This is a Phase Ib study to evaluate the safety and efficacy of TACE combined with sintilimab and bevacizumab in patients with unresectable intermediate or advanced HCC.~36-39 subjects with unresectable intermediate or advanced HCC will be enrolled in the study.~This study includes dose escalation and dose expansion stage. 6-9 subjects will be enrolled in dose escalation stage for the safety evaluation. Then, sintilimab 200mg/kg IV. every three weeks (q3w) + the select specific dose of bevacizumab 7.5mg/kg (group 1) or 15mg/kg (group2) IV q3w, expand to 36 patients (18 patients each group) for the further safety and efficacy study.~Sintilimab and bevacizumab will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated based on the evaluation of follow-up laboratory and imaging examination. And the study treatment of sintilimab and bevacizumab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first.

This study is to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with sintilimab and bevacizumab in patients with unresectable intermediate or advanced hepatocellular carcinoma (HCC).

In this time pediods, all patients with RT-PCR positive for SARS-COV-2 will be analysed for the presence of diabetes mellitus. Previous HbA1c levels will be obtained from hospital records. In these patients, previous A1c levels and A1c levels 3 months after the SARS-COV-2 infection will be compared.

The study aimed to evaluate the effect of SARS-COV-2 infection on metabolic status in patients with diabetes mellitus. Patients' HbA1c levels before and after SARS-COV-2 infection will be evaluated.

Retinal diseases seriously threaten vision and quality of life, but they often develop insidiously. To date, deep learning (DL) algorithms have shown high prospects in biomedical science, particularly in the diagnosis of ocular diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, glaucoma, and papilledema. However, there is still a lack of a single algorithm that can classify multi-diseases from fundus photography.~This cross-sectional study will establish a DL algorithm to automatically classify multi-diseases from fundus photography and differentiate major vision-threatening conditions and other retinal abnormalities. We will use the receiver operating characteristic (ROC) curve to examine the ability of recognition and classification of diseases. Taken the results of the expert panel as the gold standard, we will use the evaluation indexes, such as sensitivity, specificity, accuracy, positive predictive value, negative predictive value, etc, to compare the diagnostic capacity between the AI recognition system and human ophthalmologist.

The objective of this study is to establish deep learning (DL) algorithm to automatically classify multi-diseases from fundus photography and differentiate major vision-threatening conditions and other retinal abnormalities. The effectiveness and accuracy of the established algorithm will be evaluated in community derived dataset.

The overall goal of this five-year R01 study is to test the Coalition Check-Up (CCU) technical assistance (TA) system for supporting community coalitions' implementation of evidence-based drug prevention programs (EBPs). Over 5,000 community anti-drug coalitions operating in the U.S serve as a cornerstone of federal drug prevention. These coalitions, however, have only demonstrated efficacy in preventing substance use when they use TA and implement EBPs, a key research-to-practice gap. The CCU supports coalitions by identifying and addressing gaps in EBP implementation capacity. The proposed study advances implementation science by applying Wandersman's Interactive Systems Framework to test the effects of CCU on coalition EBP implementation capacity and youth outcomes. Despite the popularity of community anti-drug coalitions as a mechanism for EBP dissemination, scant research addresses how to support coalitions for optimal EBP implementation. Lacking adequate support, coalitions and EBPs often fail. Intensive TA provided in evidence-based coalition models is effective but often too expensive to scale in real-world settings. The CCU provides a lower-cost TA system that is broadly applicable across coalition models. The study's main objective is to test the overall effectiveness of the CCU, including how it contributes to EBP implementation and prevention of youth substance use. Building on the Interactive System Framework, the central hypothesis is that the CCU can enhance the prevention support system, thereby increasing coalition capacity for EBP implementation and the probability that EBPs will reduce youth substance use. The study will test this central hypothesis by pursuing three specific aims. The first aim is to estimate the impact of the CCU on coalition capacity, including team processes, network composition, and collaborative structure. Coalitions will be randomly assigned to the CCU or a 'TA as usual' condition. The second aim is to estimate the impact of the CCU on implementation of EBPs, including EBP reach, implementation quality, and sustainability. The third aim is to estimate the impact of the CCU on youth substance use, including alcohol, tobacco, marijuana, and opioids. The CCU is innovative in its emphasis on proactive monitoring and data-driven TA, its use of motivational interviewing to enhance coalition-driven action planning, and its examination of network structure to enhance coalition capacity. The proposed study's contribution is highly significant because the field currently lacks clear evidence of the effectiveness of a TA model applicable to the heterogeneous mix of drug prevention coalitions in operation. The research will enhance community coalition ability to bridge the research to practice gap in drug prevention programming. Results are expected to have a positive impact on the field by establishing the evidence-base for a low-cost, data-driven, manualized TA model that identifies how to intervene with community coalitions to support sustained implementation of evidence-based drug prevention programs and policies known to promote community health.

This project is designed to test the Coalition Check-Up (CCU)-a theory-based and data-driven technical assistance (TA) system that supports community coalitions' implementation of evidence-based programs (EBPs) for drug prevention. The primary aims of the project are to: 1) Estimate the impact of the CCU on coalition capacity. Coalitions will be randomly assigned to the CCU or a 'TA as usual' condition to evaluate whether the CCU improves coalition capacity as measured by coalition member reports of team processes, network composition, and collaborative structure. 2) Estimate the impact of the CCU on implementation of evidence-based programs. The study will test the hypothesis that coalitions receiving the CCU will implement EBPs with greater: a) quantity, b) quality, and c) sustainability. The study will also test coalition capacity as a mediator of CCU impact on EBP implementation. 3) Estimate the impact of the CCU on youth substance use. The study will test the hypothesis that communities receiving the CCU will reduce youth substance use relative to communities in the comparison condition. The study will also test EBP implementation as a mediator of CCU impact on youth substance use.

The primary endpoints is to evaluate whether a multimodal intervention supported by the POSITIVE technological ecosystem improves frailty in at least 1 point in Fried's Criteria and 5 points in FTS-5 during a 6-month follow-up period.~This objective will be investigated through a multi-centre, non-inferiority, randomized, simple blind and prospective pilot study with an intervention lasting for 6 months. The study will be carried out in Spain, Sweden and Poland. 150 participants (50 per site) will be randomized into two groups. The control group will receive usual medical care. The intervention group will receive, in addition, the POSITIVE frailty home monitoring and intervention system.~Both groups will be assessed with the same instruments. This assessment will be conducted at baseline (in the beginning of the trial period), at the middle (month 3) and at the end of the intervention (month 6).~A stratified randomization technique will be applied in each of the study groups based on: age group (70-85,> 85), history of cognitive impairment, history of stroke to guarantee the existence of comparable groups. These factors have been significantly associated with frailty and pre-frailty status (stroke OR =3.11 (1.05-9.18), age, per 1-year OR = 1.14 (1.08-1.21); cognitive impairment OR = 8.37 (4.43-15.83)).

The POSITIVE platform offers the possibility of unsupervised monitoring of pre-frailty and frailty status in a community setting, to detect the onset of frailty and to assess its evolution.~The primary objective of the study is to evaluate whether the POSITIVE system improves frailty in at least 1 point in the Fried's Criteria and 5 points in the FTS-5.~This is a multi-centre, non-inferiority, randomized, simple blind and prospective pilot study with a 12-month follow up duration. The study will be carried out in Spain, Sweden and Poland. 150 participants will be randomized into two groups. The control group will receive usual medical care. The intervention group will receive, in addition, the POSITIVE frailty home monitoring and intervention system.

This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial includes a screening period of up to 28 days, an 8-week treatment period (comprising a 2-week titration phase and a 6-week maintenance phase), and a 2-week follow-up period.~At screening (Visit 1), all participants will receive instructions on how to complete a writing exercise (Exposure Writing Exercise) related to their traumatic experience. Prior to the baseline visit (Visit 2), participants must complete an approximate 30-minute writing exercise outside of the trial site and should have re-read the write up at least once to be eligible for enrollment.~Throughout the screening and treatment periods, the dose of SSRI/SNRI used as background therapy, if any, should remain unchanged. On Day 1, eligible participants will be randomly assigned to either nabiximols or placebo in a 1:1 ratio.~Participants will be advised to titrate the investigational medicinal product (IMP), beginning with 1 spray/day, to an optimized dose that relieves their most bothersome symptom of PTSD or to a maximum of 12 sprays/day over the first 14 days of treatment. Participants should continue at the same dose level achieved at the end of the titration phase ±1 spray divided into a morning dose and an evening dose for the remainder of the treatment period.~Health-related quality of life, safety, and tolerability will be evaluated during the treatment period.~Participants who complete the trial will participate for a total of approximately 14 weeks (99 days), including the 28-day Screening period.

This study will be conducted to evaluate the efficacy of nabiximols for the treatment of symptoms of post-traumatic stress disorder (PTSD) in participants receiving selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) pharmacotherapy.

This is a Phase 2 study to compare efficacy, safety and PK of palonosetron, a long acting 5-HT3 receptor antagonist, by buccal film compared to iv injection for moderately emetogenic chemotherapy-induced nausea or vomiting (CINV) in cancer patients. Subjects are randomized into three treatment groups, two with the experimental study drug palonosetron in buccal film at one of two different doses or the control treatment using Palonosetron hydrochloride iv injection. Palonosetron PK will be assessed in a subgroup of each treatment group.

Phase 2 study to compare efficacy, safety and PK of palonosetron, a long acting 5-HT3 receptor antagonist, by buccal film delivery compared to iv injection for chemotherapy induced nausea or vomiting (CINV). Subjects receive a single dose of palonosetron prior to moderately emetogenic chemotherapy.

We will conduct a double arm, randomized, double-blinded placebo controlled trial of oxaloacetate for treatment of fatigue in women with a history of COVID-19 infection, resolution of the infection, and remaining fatigue that interfere with everyday activities, based on use of a standardized questionnaire to screen for impairment. Women will be recruited from a variety of settings including clinics affiliated with our existing doctor base, outreach through social media and notification of community organizations that serve this patient population. The study will take place at the residences of the participants, being performed virtually after receipt of informed consent paperwork, COVID-19 positive test data, and COVID -19 negative resolution data by us, and by receipt of the test product by the participant. Efforts will be made to conduct as much of this trial virtually as possible due to the Covid-19 pandemic. Women who could potentially be pregnant will undergo pregnancy testing and determination of menopausal status, if appropriate. Participants will complete baseline questionnaires that assess fatigue and depressive symptoms.~Subsequently, the participants will receive a 6-week supply of the active or placebo and will be asked to take one capsule twice a day with water and food. They will be contacted weekly for two weeks by the study coordinator to assess for any side effects or difficulty taking the medication. They will be asked to again to complete the standardized questionnaire to screen for impairment after 2 weeks, and again at the end of the study at 6 weeks. Finally, any adverse reactions and symptoms will be evaluated once again four weeks later to ensure that any symptoms that may have been present during treatment have resolved.

We will conduct a double arm, randomized, double-blinded placebo controlled trial of oxaloacetate for treatment of fatigue in women with a history of COVID-19 infection, resolution of the infection, and remaining fatigue that interfere with everyday activities, based on use of a standardized questionnaire to screen for impairment.~Participants will receive a 6-week supply of the active or placebo and will be asked to take one capsule twice a day with water and food. They will be contacted weekly for two weeks by the study coordinator to assess for any side effects or difficulty taking the medication. They will be asked to again to complete the standardized questionnaire to screen for impairment after 2 weeks, and again at the end of the study at 6 weeks. Finally, any adverse reactions and symptoms will be evaluated once again four weeks later to ensure that any symptoms that may have been present during treatment have resolved.

A large retrospective observational study, including 4-years of elective procedures with intravascular iodinated contrast administration in eGFR<30mL/min/1.73m2 patients at Maastricht UMC+, found that prophylactic intravenous hydration might confer some benefit for renal function. For patients who had received prophylactic hydration, adjusted odds ratios for risk of post-contrast acute kidney injury, and 1-month eGFR decline and dialysis were all lower than 1. These results were not significant, but suggest that hydration may be protective. On the other hand, adjusted odds ratios for all-cause mortality within 1-month post-contrast were higher than 1, with point estimates indicating a trend toward higher risk of short-term mortality after prophylaxis as compared to no prophylaxis. Confounding by indication may be responsible for the observed increased risk of short-term mortality, but complications of the prophylaxis did contribute towards the risk. Amongst the 281 eGFR<30mL/min/1.73m2 prophylaxis patients studied, 18 (6.4%) serious complications occurred: 3 arrhythmias, and 15 heart failures including 5 deaths. Of all 21 deaths recorded for the prophylaxis patients, 24% (5/21) were considered to be related to intravenous fluids. An exploration of differences in baseline characteristics between patients with and without serious complications suggested that these can be avoided if cardiac function parameters are given extra and individual attention before deciding whether to administer prophylaxis to high-risk patients with eGFR<30mL/min/1.73m2. At Maastricht UMC+ a specialised unit (called the CVP) was established where a dual screening process including both renal and cardiac parameters is used to minimize the risk of contrast-induced acute kidney injury as well as the risk of prophylactic hydration in eGFR<30mL/min/1.73m2 patients. In order to enable real function follow-up, the CVP registers data on all patients with eGFR <30 receiving intravascular iodinated contrast material, including acute patients who did not receive the dual screening process prior to prophylactic intravenous hydration. The current study aims to describe post-contrast outcomes of patients to whom the CVP screening method has been applied and to compare them to earlier outcomes of patients to whom the screening was not applied.

At Maastricht University Medical Centre (Maastricht UMC+) a specialised unit was established where a dual screening process including both renal and cardiac parameters is used to minimize the risk of contrast-induced acute kidney injury as well as the risk of prophylactic hydration in eGFR<30mL/min/1.73m2 patients. Very little data exists on patients with eGFR <30mL/min/1.73m2 in this context. The current study aims to describe post-contrast outcomes of patients to whom this screening method has been applied.

The very high power-short duration (vHPSD) catheter, is a novel CF catheter optimized for temperature-controlled ablation with microelectrodes and 6 thermocouples for real-time temperature monitoring during ablation. The associated vHPSD algorithm modulates power to maintain target temperature during these vHPSD lesions (90 W, 4 s). In preclinical models, vHPSD ablation with this novel catheter has improved atrial linear lesion contiguity, transmurality, and durability and has substantially reduced radiofrequency ablation times, but with a safety profile similar to those of standard irrigated radiofrequency ablation catheters.~The QDOT -FAST study demonstrated the clinical feasibility and safety of vHPSD ablation. Procedure and fluoroscopy times were substantially lower than historical standard ablation with point-by-point catheters.~The aim of the present study is to compare the safety and short-term performance between THERMOCOOL SMARTTOUCH SF-5D QDOT system used with fast ablation mode and the standard Thermocool Smartouch SF in treatment of patients with atrial fibrillation (AF).

The aim of the present study is to compare the safety and short-term performance between THERMOCOOL SMARTTOUCH SF-5D QDOT system used with fast ablation mode and the standard Thermocool Smartouch SF in treatment of patients with atrial fibrillation (AF).

This is a single-center, pilot study to assess the feasibility of a study show the effectiveness of the genicular artery embolization (GAE) in reducing arthritic pain and dysfunction associated with mild to moderate Bilateral or unilateral osteoarthritis of the knee. Patients with bilateral or unilateral Grade 1-3 Osteoarthritis as diagnosed on standing weight-bearing knee radiographs per the Kellen-Lawrence Grading scale, will be offered enrollment to the study. Following a screening questionnaire, these patients will then be enrolled in this study. Baseline MRI will be obtained prior to the GAE procedure. Follow up intervals will include 3, 6, 9, and 12 months with the primary objective measured by a clinician as the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score, Knee Injury and Osteoarthritis Outcome (KOOS) score, and Oswestry Disability Index at the 12-month follow up visit. Patients will also undergo 1 year follow up MRI to be interpreted by a diagnostic radiologist with subspecialty training in musculoskeletal radiology. This radiologist will compare the treated knee to the baseline screening according to the WORMS classification (Whole Organ Magnetic Resonance Scoring) to assess for radiologic changes of osteoarthritis and any adverse effects.

The goal of this study is to perform a feasibility study to show the effectiveness of the genicular artery embolization procedure in reducing bilateral or unilateral osteoarthritic knee pain at 12 months as measured by WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score, Knee Injury and Osteoarthritis Outcome (KOOS) score, and Oswestry Disability Index.

There are approximately 2.5 million hospital visits in the US each year for traumatic brain injury. Vestibular dysfunction is a common sequela of traumatic brain injury (TBI) affecting up to 50% of TBI patients at 5 years after injury. It is one of the most distressing problems for caregivers following TBI. Further complicating this issue is the fact that many individuals with TBI underestimate the severity of their balance deficits, which may further increase the risk of falls and subsequent injury. Sitting balance on admission to inpatient rehabilitation following TBI has been found to be one of the strongest predictors of functional status at discharge from inpatient rehabilitation. Due to the multifaceted presentation of vestibular dysfunction, evaluation is challenging, and there is currently no standardized approach to screening. While the incidence of vestibular dysfunction has been studied in mild TBI (mTBI) and sports related concussions, there is a gap in the literature regarding the incidence of vestibular dysfunction in moderate to severe TBI patients in acute inpatient rehabilitation.~The benefits of having an established vestibular dysfunction screening and rehabilitation program are multifold. Vestibular rehabilitation following TBI has demonstrated improvements in cognitive function, ability to return to activities of daily living, ability to return to work, and the need for assistance. While one prior single blind randomized controlled trial aimed to evaluate the effectiveness of a structured vestibular rehabilitation program in TBI individuals, there is a need for a large-scale study to evaluate the effectiveness of screening for vestibular dysfunction in order to create a systematic approach. Many TBI patients are not diagnosed with vestibular dysfunction until much later in their hospital course which impedes participation in therapy and likely has a detrimental effect on their rate of recovery. Identifying these patients earlier in their rehabilitation course will allow interventions that will improve and accelerate patient outcomes. An additional benefit of this study is to determine the incidence of vestibular dysfunction in moderate to severe TBI patients to outline the necessary resources to care for patients with this problem. Data collected will be utilized to validate the AVeST and the AVeST+. Additionally, this study will fill a gap in the literature in delineating the incidence of vestibular impairment in individuals with moderate to severe brain injury, a population heretofore not previously studied.

The purpose of this study is to determine the incidence of vestibular dysfunction in traumatic brain injury patients admitted to acute inpatient rehabilitation. This study also seeks to validate the AbilityLab Vestibular Screening Tool (AVeST) and the AVeST+, tools designed to quickly screen individuals for vestibular dysfunction following traumatic brain injury.

Calciphylaxis is a rare, devastating disorder causing excruciatingly painful ischemic skin lesions. Sepsis due to the infection of ulcerated wounds is a common cause of death. To date, practical therapies typically include wound care, pain management, anti-infection and aggressive treatment of predisposing conditions. Drugs such as sodium thiosulfate, bisphosphonate, and cinacalcet are also suggested. However, it's still a lethal disease with 1-year mortality up to 80% for dialysis patients. Here the investigators plan to treat uremic calciphylaxis patients with human amniotic mesenchymal stem cells (hAMSCs).

Treatment for Uremic Calciphylaxis Patients with Human Amniotic Mesenchymal Stem Cells

This is a phase 2 randomized, double blind, placebo controlled study evaluating the efficacy and safety of AL002 administered intravenously in participants with Early Alzheimer's Disease.

A phase 2 randomized, double blind, placebo controlled study evaluating the efficacy and safety of AL002 in participants with Early Alzheimer's Disease.

Aim of the Work~Compare the success rate of misoprostol with versus without letrozole as a pretreatment for medical termination of pregnancy during the first trimester.~Hypothesis:~Letrozole value as a pre-treatment medication for misoprostol in induction of abortion during the first trimester.~Research question:~Will letrozole- misoprostol protocol give better results than misoprostol- alone protocol in induction of abortion during the first trimester?~Primary outcome:~Complete abortion (complete expulsion of products of conception with no need for curettage) within one week from the first dose of misoprostol.~Secondary outcome:~• Curettage (surgical evacuation of the products of conception)~Incomplete abortion (retained products of conception).~Considerable bleeding that necessitates immediate evacuation.

Aim of study Compare the success rate of misoprostol with versus without letrozole as a pretreatment for medical termination of pregnancy during the first trimester.~Hypothesis:~Letrozole value as a pre-treatment medication for misoprostol in induction of abortion during the first trimester.~Research question:~Will letrozole- misoprostol protocol give better results than misoprostol- alone protocol in induction of abortion during the first trimester?

This study will investigate the effectiveness of a rehabilitation program in improving fatigue, negative emotions , sleep quality, circadian rhythms and quality of life in patients with gastric cancer undergoing gastrectomy in Taiwan.

This study will investigate the effectiveness of a rehabilitation program in improving fatigue, negative emotions , sleep quality, circadian rhythms and quality of life in patients with gastric cancer undergoing gastrectomy in Taiwan.~Hypothesis:~The fatigue in exercise group is significant improving than usual-care group at 1st, 2nd, 3rd, 6th, 12th, 24th and 36th month.~The negative emotions in exercise group is significant improving than usual-care group at 1st, 2nd, 3rd, 6th, 12th, 24th and 36th month.~The sleep quality in exercise group is significant improving than usual-care group at 1st, 2nd, 3rd, 6th, 12th, 24th and 36th month.~The quality of life in exercise group is significant improving than usual-care group at 1st, 2nd,3rd, 6th, 12th, 24th and 36th month.

Purpose and rationale: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock are major public health problems killing one in every three patients. Microcirculatory dysfunction is frequent in septic shock. The duration and severity of this dysfunction have a prognostic impact by being associated with organ failure and mortality. Our study purposes to demonstrate the feasibility of OCTA to improve assessment of microcirculatory dysfunction by showing that retinal and choroidal microcirculatory changes with prognostic impact are present during septic shock.~Primary objective (specific aim 1): To characterize the alterations of retinal and choroidal microcirculation in septic shock.~We will test the hypothesis that retinal and/or choroidal microcirculation shows dysfunctional changes (lower vascular density, lower percentage of perfused small vessel, lower blood flow index and higher vascular heterogeneity) in septic shock patients.~Secondary objective (specific aim 2): To test the prognostic value of retinal and choroidal microcirculatory dysfunction in septic shock.~We will test the hypothesis that higher magnitude and persistence of retinal and/or choroidal microcirculatory dysfunction beyond the successful macro-hemodynamic resuscitation are independent predictors of organ failure and mortality in septic shock patients.~Study type: Two sequential observational studies.~Study design: A cross-sectional case-control study followed by a prospective cohort study with a 90-days longitudinal follow-up period.~Study population: 165 septic shock patients and 30 healthy controls. Power and sample size calculations: Based on sublingual percentage of perfused small vessel (PPV) difference previously reported between septic shock patients and healthy controls (60% vs. 95%), we estimate that we will need to enrol 27 patients and 27 controls to demonstrate the same difference at the retina and choroid. To show a PPV difference between survivors and non-survivors (70% vs. 46%) in the septic shock group, also based on previous reports at the sublingual microcirculatory level, we estimate that we will need to enrol 150 septic shock patients. These calculations assumed an alpha level of 0.05 and a power of 80%. Our Department admits about 200 septic shock patients annually, so to account for drop-outs and limitations with enrolment (10-20% refusal to participate) we decided to increase our enrolment goal by 10% to 165 septic shock patients and 30 healthy controls.~Recruitment and inform consent: Recruitment will take place at the Intensive Care Medicine Department of Hospital da Luz Lisboa. Patients admitted to the Department with the diagnosis of septic shock will be screened for eligibility. If the patients are eligible to participate, they will be invited to enrol in the study by the principal investigator or other ICU medical team member. The study objectives and procedures will be explained to them. If the patient agrees to participate in the study, a written informed consent will be sign before enrolment. If the patient is unable to give informed consent to participate in the study, it will be asked to the reference next of kin using the same procedures as described before.~Study duration: 90 days from enrolment to final follow-up assessment. One to two years of enrolment.~Study procedures:~Baseline Assessment: After confirmation of eligibility and enrolment in the studies, demographic data (age, gender), type of admission (urgent/elective, medical/surgical/trauma), patient origin (emergency department, ward, operation room), source of infection (lung, urinary tract, intra-abdominal, skin and soft tissues, others), prognostic scores (APACHE II, SAPS II) and organic dysfunction scores (SOFA, quick SOFA) will be collected at baseline for septic shock patients.~Study Assessments:~OCTA: OCTA examination will be performed daily to septic shock patients from day 1 (less than 24 hours after diagnosis) until successful shock resolution (weaning from vasopressors) or until a maximum of 7 days. The healthy controls will be submitted to a single OCTA evaluation. We will use the Spectralis® OCTA system (Heidelberg, Germany) and the interpretation of OCTA images will be performed by two independent specialized ophthalmologists blinded to the clinical condition of patients. Images will be stored at the device working station.~Hemodynamic assessment: Every septic shock patient will have a central venous catheter and an arterial line in place according to the standard of care. Daily, during or within a maximum of 1 hour of OCTA examination, we will record the values of temperature, heart rate, mean arterial pressure, capillary refill time, central venous pressure, cardiac index, pH, PaCO2, PaO2, PvCO2, SaO2, SvO2, haemoglobin, serum lactate, fluid balance, oxygen delivery, oxygen consumption and oxygen extraction ratio.~Vasoactive and sedo-analgesic drugs: Daily we will record the vasoactive and sedo-analgesic drugs administered to septic shock patients and its total daily dose until complete weaning (defined as 24 hours free of vasopressors). Daily vasopressor score will also be calculated as suggested by Póvoa, P. et al.~Ventilatory and renal replacement therapy support: Daily we will record the type of ventilatory support (oxygen therapy, high flow oxygen therapy, non-invasive ventilation, invasive ventilation) and of renal replacement therapy (continuous, sustained low-efficiency, intermittent) used, if needed, until complete weaning.~Data analysis: In both studies, we will perform a descriptive statistical analysis of studied variables. Comparisons between healthy controls (single OCTA) and septic shock patients (first OCTA) to address endpoints related to specific aim 1 will be performed using t-Student test or Mann-Whitney test as appropriate. To address endpoints related to specific aim 2, we will compare survivors to non-survivors by doing a survival analysis using Kaplan-Meyer curves and Cox proportional hazards multivariable regression with microcirculatory measures as predictors. Additional comparisons will be performed using χ2 test, t-Student test, Mann-Whitney test and logistic regression as appropriate. We will assess confounding by adding significant variables in the regression models. We intend to perform a prespecified subgroup analysis of septic shock patients by serum lactate <4mmol/L vs. ≥4mmol/L and <2mmol/L vs. ≥2mmol/L. The correlation between retinal and choroidal microcirculation variables and macrohemodynamic variables will be assessed by the Spearman rank correlation coefficient. Area under Receiver Operating Characteristic curve of OCTA for prognostic outcomes will be calculated. A p-value < 0.05 will be considered statistically significant. Statistical analysis will be performed with STATA® 15 (StataCorp, Texas, USA).

Purpose and rationale: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock are major public health problems killing one in every three patients. Microcirculatory dysfunction is frequent in septic shock. The duration and severity of this dysfunction have a prognostic impact by being associated with organ failure and mortality. Our study purposes to demonstrate the feasibility of optical coherence tomography angiography (OCTA) to improve assessment of microcirculatory dysfunction by showing that retinal and choroidal microcirculatory changes with prognostic impact are present during septic shock.~Primary objective: To characterize the alterations of retinal and choroidal microcirculation in septic shock.~We will test the hypothesis that retinal and/or choroidal microcirculation shows dysfunctional changes (lower vascular density, lower percentage of perfused small vessel, lower blood flow index and higher vascular heterogeneity) in septic shock patients.~Secondary objective: To test the prognostic value of retinal and choroidal microcirculatory dysfunction in septic shock.~We will test the hypothesis that higher magnitude and persistence of retinal and/or choroidal microcirculatory dysfunction beyond the successful macro-hemodynamic resuscitation are independent predictors of organ failure and mortality in septic shock patients.~Study type: Two sequential observational studies.~Study design: A cross-sectional case-control study followed by a prospective cohort study with a 90-days longitudinal follow-up period.~Study population: 165 septic shock patients and 30 healthy controls.~Study duration: 90 days from enrolment to final follow-up assessment. One to two years of enrolment.

This is a tree-arm RCT focused on the safety and potential effectiveness of the multicomponent program VIRTUAL SFCAMINA as coadjuvant of treatmentas- usual (TAU) vs. TAU alone.~VIRTUAL SFCAMINA combines multicomponent approach based on Pain Neuroscience Education (PNE), therapeutic exercise, Cognitive Behavioural Therapy (CBT) and Mindfulness training.~The main hypothesis is that improvement on fatigue of patients with fibromyalgia can be achieved by the direct intervention on mechanisms such as kinesiophobia, fear avoidance and by individualized therapeutic exercise.

The main objective of this study is to analyse the effectiveness of the VIRTUAL SFCAMINA multicomponent treatment program as coadjuvant of treatmentas- usual (TAU) compared to TAU alone. In this Randomized Controlled Trial (RCT), in addition to evaluating the clinical effects of VIRTUAL SFCAMINA treatment in the short- and long term.

Stereotactic Body Radiotherapy (SBRT) represents the cutting edge within high conformal and modulated radiotherapy techniques; it can provide high local control (LC) for curative-intent of low burden metastatic, persistent and metastatic lesions in face of minimal acute and late toxicities. SBRT is amenable even in patients who had already been managed by radiotherapy. In addition, SBRT has been shown to be active in chemoresistant disease, and potentially able to mount immune response through the release of tumor neoantigens after cell killing, thus allowing to synergize with immunotherapeutic approaches. SBRT has been widely adopted in the clinical setting of oligometastatic/persistent/recurrent (MPR) disease (up to <5 lesions) in several malignancies including also ovarian cancer (OC); the recently published retrospective, multicenter Italian study (MITO-RT1) has confirmed the activity and safety of SBRT in MPR OC, thus providing a model able to predict the higher chance of complete response of tumor lesions to SBRT, and local control rate.~The MITO-RT3/RAD trial is a prospective, Italian multicenter Phase II study aimed at evaluating the activity and safety of SBRT in MPR-OC patients. Clinical and imaging data, as well as SBRT technical parameters, would be analyzed with the aim to identify potential predictors of response to treatment and clinical outcome: in this context, additional insights into the tissue features of tumor lesions would be of clinical interest in the context of the personalized treatment, as testified by studies demonstrating that image-based quantitative features from pre-treatment imaging could predict clinical outcomes in several malignancies.~Furthermore, given the crucial role played by the mutational status of BRCA 1/2 genes in this disease, the assessment of BRCA gene status was considered mandatory, thus representing inclusion criteria.~The study will include patients with oligo-metastatic/persistent/recurrent lesions (MPR) from OC patients for which salvage surgery or other local therapies resulted not feasible, as per relative contraindication to further systemic therapy because of serious comorbidities, as per previous severe toxicity, unavailability of potentially active chemotherapy, or patient refusal of systemic therapy

This is a prospective, multicenter, Phase II study aimed at defining the activity and safety of SBRT in MPR-OC. Clinical and imaging data as well as SBRT parameters would be analyzed with the aim to identify potential predictors of response to treatment and clinical outcome.

This is a single-center, open-label, single-arm phase II clinical study to exploratory observe and evaluate the efficacy and safety of anti-PD-1 antibody (Camrelizumab for Injection) in patients with malignant melanoma of the female genital tract.~The patients were divided into two cohorts according to their conditions: Cohort 1: patients with postoperative recurrence of malignant melanoma of the female genital tract requiring adjuvant therapy；Cohort 2: patients with metastatic or unresectable malignant melanoma of the female genital tract who were screened eligible and received study treatment after being fully informed and signing the informed consent form.~Camrelizumab will be administered at a fixed dose of 200 mg intravenously (iv) on D1 in a 14-day cycle. All subjects will be administered until they reach the end of treatment standard specified in the protocol.~Subjects were to have a safety visit 3 days prior to dosing in each treatment cycle after the study. Imaging was performed every 8 weeks to assess efficacy until radiographic progression, initiation of new antineoplastic therapy, withdrawal of consent, or subject lost to follow-up/death.~After the end of treatment, an end-of-treatment visit and a post-treatment safety visit will also be performed. Subjects who have concluded the study treatment for reasons other than disease progression will receive imaging assessment at the end of treatment (if imaging evaluation is not performed at 4 months) and imaging assessment every 3 months after the end of treatment to assess the time to disease progression. After the end of treatment, subjects will also be followed up for survival (every 3 months for years 1 to 2, every 4 months for years 3, every 6 months for years 4 to 5, and annually from year 6) to collect and record the survival status of subjects and subsequent anti-tumor treatment.~Tumor tissue samples, sections, paraffin blocks or biopsy blocks, and biomarkers, including but not limited to PD-L1 expression level and the proportion of positive cells, TMB level and MMR status, will be collected from subjects during the screening period after the most recent previous treatment.

This is a single-center, open-label, single-arm phase II clinical study to exploratory observe and evaluate the efficacy and safety of anti-PD-1 antibody (Camrelizumab for Injection) in patients with malignant melanoma of the female genital tract.~Subjects were to have a safety visit 3 days prior to dosing in each treatment cycle after the study. Imaging was performed every 8 weeks to assess efficacy until radiographic progression, initiation of new antineoplastic therapy, withdrawal of consent, or subject lost to follow-up/death.~After the end of treatment, an end-of-treatment visit and a post-treatment safety visit will also be performed. After the end of treatment, subjects will also be followed up for survival (every 3 months for years 1 to 2, every 4 months for years 3, every 6 months for years 4 to 5, and annually from year 6) to collect and record the survival status of subjects and subsequent anti-tumor treatment.

This is an open-label study in healthy volunteers to evaluate the safety, tolerability and pharmacokinetics of four formulations of LY03009 (F1, F2, F3, F4) after a single intramuscular injection.~Approximately 40 healthy subjects are planned to be enrolled in this study and assigned to four cohorts (F1, F2, F3, F4) sequentially, 10 subjects per group at a fixed dose of 112 mg for F1~F3 and 224 mg for F4. Each subject will receive only one dose in this study.

The purpose of this study is to Evaluate the Safety, Tolerability and Pharmacokinetics of Four Formulations of LY03009 in Healthy Volunteers.

Recent studies showed that vitamin D and A has an effect in improving sputum conversion in tuberculosis. This study aims to find out the effect of vitamin D 1000 IU and A 6000 IU supplementation on Tuberculosis patients with vitamin D receptor gene polymorphism, who live in North Sumatera, Indonesia. This study is a randomized control clinical trial, with 48 tuberculosis patients with vitamin D receptor gene polymorphism which are TaqI and FokI participating, divided into two groups, each with 24 participants, which are treatment group (I) which receives nutritional counseling, vitamin D 1000 IU, vitamin A 6000 IU, and control group (C) which only receives nutritional counseling for 28 days. Patients who participated was found to be heterozygous with TaqI (T>C) or FokI (C>T) genotype variants. The result of this study showed that at the start, serum 25(OH)D levels in group I were lower compared to group C (19.746.59 ng/mL vs 25.21±7.57 ng/mL). Group I showed significant correlation between vitamin D level categories with sputum conversion (mean: standard deviation= 2.25±0.68 weeks). Supplementation of vitamin D 1000 IU provides an accelerated sputum conversion in tuberculosis patients with vitamin D receptor gene polymorphism.

Recent studies showed that vitamin D and A has an effect in improving sputum conversion in tuberculosis. This study aims to find out the effect of vitamin D 1000 IU and A 6000 IU supplementation on Tuberculosis patients with vitamin D receptor gene polymorphism, who live in North Sumatera, Indonesia. This study is a randomized control clinical trial, with 48 tuberculosis patients with vitamin D receptor gene polymorphism which are TaqI and FokI participating, divided into two groups, each with 24 participants, which are treatment group (I) which receives nutritional counseling, vitamin D 1000 IU, vitamin A 6000 IU, and control group (C) which only receives nutritional counseling for 28 days. Patients who participated was found to be heterozygous with TaqI (T>C) or FokI (C>T) genotype variants.

Developing clinical and psychological markers which characterise the large subgroup of patients with major depression who do not benefit from serotonergic antidepressants offered as first line treatment is of utmost clinical importance but has so far not been achieved. Clinical and psychological indicators would be ideal in predicting non-response to antidepressant medications, given their wide availability. So far, however, these measures have failed to provide accurate predictions at the individual level. Novel predictors of prognosis and treatment response in major depressive disorder (MDD) can add value to the development of targeted treatments and stratified approaches to improve long-term outcomes of individuals with MDD.~The psychological underpinnings of patients' response to treatment have been an important direction of research. As proposed by the revised learned helplessness model, one central cognitive vulnerability to MDD is the tendency to excessively blame oneself for negative events occurring in one's life. Consistent with the theory, previous studies have demonstrated the importance of self-blaming bias both as a vulnerability factor and as a symptom of depression. For example, it has been shown that individuals with remitted MDD had increased self-contempt biases compared to healthy control participants in a recent study. As MDD is a life-long diagnosis, understanding the differences between remitted MDD and healthy controls could help to identify vulnerability traits associated with MDD. Thus, the finding of self-blaming biases in remitted MDD demonstrate the potential role of self-blame as a vulnerability trait and a novel cognitive marker for MDD that remain present during remission and possibly constitute vulnerability for recurrence. However, one limitation in previous studies is that people might have experienced difficulties distinguishing their moral emotions such as shame and guilt under certain circumstances. Previous measures assessing these emotions largely depended on participants' subjective rating and are thus problematic in terms of differentiating the moral emotions.~In addition, these measures fail to address the adaptive or maladaptive nature of moral emotions. As proposed by Tangney, moral emotions can be either adaptive and maladaptive, and this difference is possibly determined by an individual's different action tendencies associated with their moral emotions. Action tendencies describe an implicit cognitive and motivational state before an action is taken. It was suggested that adaptive action tendencies, such as feeling like apologizing, were associated with self-blaming emotions such as guilt, and maladaptive action tendencies such as feeling like hiding and creating a distance from oneself were associated with shame. However, an empirical investigation of the associations between action tendencies and self-blaming emotions is lacking. Further investigations of this topic are important for understanding the potential role of action tendencies as a novel measure of self-blame and its association to the vulnerability to MDD. It is important to develop measures of action tendencies with a high ecological validity. In previous studies, our research group has developed a computerised task that measures action tendencies and used it to predict prognosis in MDD. It was found that this task can predict recurrence risk in people with MDD, showing a large effect size (Cohen's d=.96). However, there were two major limitations. First, the task used in a verbal format and included abstract descriptions of scenarios (e.g. You act stingily towards your friend), which makes the task dependent on how well participants can imagine the scenarios. Second, the lack of immersiveness of the task made it difficult to engage, which may limit the task's ecological validity.~Virtual reality (VR)-based assessment is a new paradigm for cognitive evaluation compared to the traditional paper-and-pencil or computerized assessment. VR scenarios were suggested to be promising tools for cognitive assessments and have been demonstrated as safe for the assessment of anxiety disorders and depression. Importantly, the interactive and immersive nature of virtual reality makes it possible to develop a cognitive task that is engaging and has a higher ecologically validity, which would be ideal for identifying novel cognitive markers of MDD outcomes. Thus, this study will aim to employ a virtual reality task to measure blame-related action tendencies.~There are three major research questions of this study~Is MDD associated with a higher proneness towards maladaptive action tendencies, such as self-distancing and hiding, compared with a non-MDD control group?~Are maladaptive self-blame-related action tendencies associated with a poor prognosis for current major depressive disorder when treated as usual in primary care?~Can maladaptive self-blame-related action tendencies be used to predict prognosis in MDD at the individual level when combined with other predictors using a nested elastic-net regularised doubly-cross-validated regression model? (https://github.com/AndrewLawrence/dCVnet). This will use both primary and secondary predictors in the same model.~Our proposed primary predictors of prognosis for major depressive disorder are the following (these will be used in a non-regularised multiple regression model):~Percentage of trials during which hiding was chosen as measured by the VR-task~Percentage of trials during which self-distancing was chosen as measured by the VR-task~Autonomy total score as measured by the Personal Style Inventory~Sociotropy total score as measured by the Personal Style Inventory~Maudsley Staging Model total score~Compliance with treatment as measured on an ordinal scale (how regularly have you taken your antidepressants over the last month at the prescribed dose? 0=Never, 1=Some of the time, 2=More than half the time, 3=Most of the time, 4=Almost every day, 5=Every day)~Social support received as measured by the Social Support Scale~Baseline depression score as measured by the Self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) and the Maudsley-Modified Patient Health Questionnaire -9 (MM-PHQ-9, two separate models will be run for using either QIDS-SR-16 or the MM-PHQ-9 as the outcome variable).~Baseline anxiety symptoms as measured by the Generalised Anxiety Disorder assessment~Optimisation of antidepressant medication during the follow-up period on an ordinal scale (0=no new antidepressant/stopping current antidepressant or lowering its dose, 1=increase from effective dose to a higher dose, 2=increase from ineffective to effective dose /or change to another antidepressant at effective dose)~Other potential predictors in secondary analyses for a non-regularised regression model:~Coping mechanism as measured by the Brief COPE~Type of treatment obtained during the four months (e.g. SSRI or Non-SSRI)~Affective Lability~Early life trauma~Physical co-morbidity~Age~Gender~Education~Age of onset~Number of previous episodes

Predicting the prognosis and treatment responses in individuals with major depressive disorder (MDD) is currently based on trial and error, because some treatments work for some individuals, but not others. Novel predictors of prognosis and treatment response in MDD can add value to the development of targeted treatments and the stratified approaches to improve long-term outcomes of individuals with MDD. This study uses a novel virtual-reality-based measure of blame-related action tendencies and combines this with established predictors of treatment response and prognosis in individuals with MDD.

The EM-HEART study is a prospective, multi-centre stepped wedge cluster randomized trial to evaluate the effectiveness of a pragmatic EM program to improve patient-centred and clinical outcomes in older adults with acute CV disease. There will be 256 participants ≥60 years old with acute CV disease enrolled at 6 participating Canadian hospitals. The study will investigate whether EM improves functional status during admission, as compared to usual care, and whether this leads to improved health-related quality of life post-hospitalization. Functional status will be measured with the validated Level of Function Mobility Scale. The primary outcome will be the Short-Form SF-36 physical component scale score at 1-month post-hospitalization. Secondary outcomes include functional status and hospital readmission at 1-month post-hospitalization. Nested cohort studies will explore (1) the relationship between EM, sedentary time, and posthospitalization outcomes and (2) the impact of EM on muscle mass loss and inflammation in older adults with acute CV disease.

The EM-HEART study is a prospective, multi-centre stepped wedge cluster randomized trial to evaluate the effectiveness of a pragmatic early mobilization (EM) program to improve patient-centred and clinical outcomes in older adults with acute CV disease. There will be 256 participants ≥60 years old with acute CV disease enrolled at 6 participating Canadian hospitals. The study will investigate whether EM improves functional status during admission, as compared to usual care, and whether this leads to improved health-related quality of life post-hospitalization. Functional status will be measured with the validated Level of Function Mobility Scale. The primary outcome will be the Short-Form SF-36 physical component scale score at 1-month post-hospitalization. Secondary outcomes include functional status and hospital readmission at 1-month post-hospitalization.

Research purpose Patients with locally advanced gastric adenocarcinoma (CT2-4A N-/+ M0) were selected as study subjects to investigate the safety, efficacy, and feasibility of ICG near-infrared imaging tracing in guiding laparoscopic D2 lymph node dissection for gastric cancer by comparing injection ICG group and non-injection ICG group~Research design prospective, multicenter, randomized controlled, open-control, Parallel assignment, superiority test 2.1 multicenter This study came from Fujian Medical university union hospital, Beijing University Cancer Hospital, Zhongshan Hospital, Fudan University, The First Hospital of Pu Tian City, Zhangzhou Affiliated Hospital of Fujian Medical University, Affiliated Cancer Hospital of Harbin Medical University, The first affiliated Hospital of Ji Lin University ,Nan fang Hospital, Southern Medical University, The first affiliated Hospital of Nan Jing University, Affiliated Hospital of Qinghai University, Qi Lu Hospital of Shang Dong University, Ren ji Hospital, Shanghai Jiao Tong University School of Medicine, Air Force Medical University（Fourth Military Medical University）Tang du Hospital, The first affiliated Hospital of USTC AnHui Provincial Hospital, Cancer Hospital Chinese academy of Medical Science, Sun Yat-Sen University Cancer Center, which jointly attended by 16 centers.~2.2 Case group Group A (Study Group): Laparoscopic gastrectomy Group with the use of near-infrared imaging (ICG group) Group B (Control Group): Laparoscopic gastrectomy Group without the use of near-infrared imaging (Non-ICG group) 2.3 Estimate Sample Size 3 years disease-free survival (DFS) is the main effectiveness evaluation index in this study. The study is superiority test, assuming that the team's three years DFS is better than that of control group,23, according to previous research results of laparoscopic local advanced gastric cancer surgery ,three years DFS is 65.2%, the control group 3 years DFS is 65.2%, assuming that the experimental group 3 years DFS can be increased by 9%, that is 74.2%, inspection level 0.025 (unilateral), take 0.9 inspection efficiency, using PASS 11 Logrank tests (Lakatos)[Proportion surviving] Calculated: Sample size N=428, that is, each group needed 428 people to consider possible exclusion and loss of follow-up cases (20% drop rate). The final sample size for each group was 535 cases, and a total of 1070 cases were initially assigned to 66-67 cases in each center 2.4 randomization Stay into the group of cases after laparoscopic exploration, make sure comply with the standards, can be randomized groups in this study we adopt the central dynamic layered segment randomized method, considering the control factors are age, gender tumor site preoperative staging research center of the given seed number and segment length, application of SAS9.2 programming to produce serial number is 0001 ~ 1070 by corresponding treatment allocation, reserved in the data center and research center has the specialist is responsible for the cases of group information (age, gender tumor site preoperative staging research center) via email A telephone call or text message will be sent to the randomization implementation department of the data center, and the central randomization department will analyze the case information to determine the case enrollment and inform the research center where the case is located 2.5 Blinding Method: This research adopts an open design. 2.6 Research cycle: Estimated enrollment cycle: complete enrollment within 2 years. Follow-up period: the enrollment of the first case and the postoperative pathological report (generally 2 weeks after surgery) was the end point of follow-up for secondary study purposes other than 3-year overall survival rate and 3-year recurrence type Estimated time: 2020.10（to complete enrollment）-2022.09（to complete follow-up）~Study Objects All patients who meet the inclusion criteria and do not conform to the exclusion criteria are qualified for this study.

Patients with locally advanced gastric adenocarcinoma (CT2-4A N-/+ M0) were selected as study subjects to investigate the safety, efficacy, and feasibility of ICG near-infrared imaging tracing in guiding laparoscopic D2 lymph node dissection for gastric cancer by comparing injection ICG group and non-injection ICG group.

Prior to the commencement of the study, the Investigator/his authorized officer will contact the subject and/or guardian to enroll the candidate subjects and invite them to participate in the study.Subjects who are eligible for screening receive the drug number in the order they arrive at the random number allocation room.During the screening period, physical examination, vital signs, blood routine, urine routine, blood biochemistry, electrocardiogram, HIV antibody test and blood pregnancy test (only women of childbearing age).Inverstigator absorb and inject 0.1ml drug into the upper and middle 1/3 of the left forearm by Mondo's method. The reaction of the injection site was checked and photographed at 0min, 48h and 72h after the skin test. Meanwhile, the transverse and longitudinal diameers of skin induration and redness were measured at 48h and 72h after the skin test.Vital signs are checked at 30min after skin test.Vital signs examination, injection site photography and reaction measurement are performed 48h and 72h after skin test.Physical examination, vital signs, routine blood test, routine urine test, biochemical test, electrocardiogram and blood pregnancy test are performed again 7 days after skin test.All AE occurred within 7 days after skin test were recorded by a diary card. AE related to the test drug should be followed up to the end of the event.Skin test of subjects aged 18-45 years shall be conducted first. After safety assessment, skin test of subjects aged 46-65 years old, 6-17 years old and under 6 years old shall be conducted successively.

A total of 80 healthy people aged 65 years and below who are randomly assigned to the experimental group and the control group. The experimental group is injected with BCG-PPD test drug once, and the control group is injected with BCG-PPD control drug once.Subjects will undergo physical examination, vital signs, blood routine, urine routine, blood biochemistry, electrocardiogram, HIV antibody test and blood pregnancy test for women of childbearing age during the screening period.Vital signs were checked before skin test, the injection site was photographed at 0min after skin test, and vital signs were checked at 30min after skin test.Vital signs examination, injection site photography and injection site reaction measurement were performed 48h and 72h after skin test.Physical examination, vital signs, routine blood test, routine urine test, biochemical test, electrocardiogram and blood pregnancy test of women of childbearing age were performed again 7 days after skin test to evaluate the safety of BCG-PPD.

Orthopedic fractures are a common acute health issue, which often accompanied with life-long burden, accounts up to 34% total lifetime medical costs in the United States. It may also lead to significant long-term morbidity and, potentially, mortality if treated Improperly. Initial management is particularly crucial in helping the bone fracture healing process and reducing comorbidity. Apart from fracture fixation through nonoperative/conservative or operative methods in aim to restore anatomic alignment, oral analgesics are same important in Orthopedics patients in symptomatic control and for early mobilization. Non-opioid medication such as Acetaminophen or NSAIDs are routinely used for injury or postoperative pain management, despite that inevitable side effects including gastrointestinal bleeding and inconsistent show concerns of NSAIDs impairing bone healing in historical animal-based studies.~In which case, topical agents used in traditional chinese medicine(TCM) usually become a well-placed supplement to relieve inflammatory conditions. In spite of the lack of scientific evidence of efficacy, topical applications such as Ru- Yih-Jin-Huang-Saan (RYJHS) and Wan-Yin-Gao(WYG) have been used on musculoskeletal injuries in oriented countries for centuries, as their transcutaneous transport of the herbal chemicals to deeper tissues show biological activities of anti-inflammation, reducing swelling soft tissue, angiogenesis, fracture healing and cellular proliferation.~To date, there is no study evaluating the clinical effect of traditional chinese medicine in topical use on musculotendinous injury, nor is that investigating the effectiveness on bone fracture healing. We hypothesize that with aid of topical chinese herbal medicine in addition to oral analgesics can be more beneficial in treating post traumatic injury, launching early mobilization, and enhancing fracture healing process.

There is no study evaluating the clinical effect of traditional chinese medicine(TCM) in topical use on musculotendinous injury, nor is that investigating the effectiveness on bone fracture healing. We hypothesize that with aid of topical chinese herbal medicine in addition to oral analgesics can be more beneficial in treating post traumatic injury, launching early mobilization, and enhancing fracture healing process.

Chronic tic disorder (CTD) may have a huge impact on life quality. Habit Reversal Training (HRT) and Exposure Response Prevention (ERP) are known to be effective therapeutic modalities. Little is known about the effect of group therapy, the effect of combining HRT and ERP training, and of the long-term effect of treatment. This study therefore wanted to examine the effect of a combined treatment using both HRT and ERP in children and adolescents with CTD. The participants were randomized to treatment either in groups or in an individual setting. The parents were included in the training programme. The participants were asked to fulfill questionnaires concerning anxiety, mood, life quality, their thoughts about tics and the experienced premonitory urge. Furthermore, they were interviewed with the semistructured interview Yale Global Tic Severity Scale (YGTSS).~Data was obtained from patient files as to examine possible predictors of both acute and long-term treatment effects. The evaluators were a specialized psychologist and a child and adolescent psychiatrist with several years of experience in diagnosing, evaluating and treating tic disorders. A random sample of 10% were audiotaped and evaluated by another rater with extensive experience and expertise in the use of the YGTSS. The evaluator was not blinded to the treatment allocation, yet not involved in the treatment of the patient, and blinded to any previous evaluations

Chronic tic disorder (CTD) may have a huge impact on life quality. Habit Reversal Training (HRT) and Exposure Response Prevention (ERP) are effective therapeutic modalities. This study examined the effect of a combined treatment using both HRT and ERP in children and adolescents with CTD. The treatment outcome was examined as an individual treatment compared to a group setting. There was no control group. The study examined both acute outcome and outcome at one year of follow-up. Predictive factors for treatment outcome were evaluated.

Eligible pregnant women in the first or second trimester who carry a diagnosis of iron deficiency anemia as defined by the American College of Obstetrics and Gynecology will be approached, consented, and randomized to receive either daily oral ferrous sulfate (325mg) supplementation or every other day oral ferrous sulfate (650mg). Participants will undergo a phone survey 2-4 weeks after starting the study to assess for side effects. Participants will continue routine care and surveillance of iron deficiency in pregnancy until the end of pregnancy.

The target population for our study is pregnant women in the first or second trimester with a diagnosis of iron deficiency anemia. If a subject is eligible, written consent will be obtained by person to person contact. Eligible participants will be randomized to receive either daily oral iron supplementation or every other day oral iron supplementation.

SUMMARY Rationale If a stone obstructs the ureter and impairs urine-efflux from the kidney this may cause infection, pain resulting from a renal colic and/or renal impairment. Drainage of the kidney may be necessary and can be established by placement of either a percutaneous nephrostomy (PCN) or a retrograde double J catheter (JJ). Considering method of drainage, setting, room in which drainage procedures takes place and anesthesia method, there are in fact 16 different approaches for drainage available, each with its own consequences for the patient and on expenses. Although evidence is poor, both methods of drainage are to be considered as equal.[1] This is reflected by the differences in preference between different countries.[2] In 2016 the Dutch association for urology (Nederlandse Vereniging voor Urologie (NVU)) marked this subject as one of the primary knowledge gaps in urology in The Netherlands and gave it priority on the national knowledge agenda for urology.[3] From patients' as well as from societal perspective it is of importance that the decision for placement of either PCN or JJ will be made based on evidence based arguments and in a uniform way.~Hypothesis: Percutaneous nephrostomy is non inferior to retrograde double J catheter regarding time to clinical recovery. Secondly, patient reported outcome measures (PROMS) comparing treatment room and OR settings of drainage procedures will most likely not be significantly different.~Finally, because percutaneous nephrostomy catheters are more often placed in a (outpatient) urological or radiological treatment room, this is expected to be less expensive than placement of a double J catheter (more often placed in the OR). Objective: To investigate the effectiveness of percutaneous nephrostomy catheter placement versus retrograde double J catheter placement in patients with symptoms of obstructive kidney disease (with either infection and/or pain and/or kidney function deterioration) caused by urolithiasis.~Study design: Multicenter prospective randomized controlled non-inferiority trial.~Study population: Male and female adult patients with signs of obstructive kidney disease with kidney or ureteral lithiasis as an underlying cause and with an indication for drainage based on symptoms of or laboratory tests indicating infection and/or pain and/or kidney function.~Intervention: One group receives drainage by percutaneous nephrostomy catheter placement as opposed to the other group which will receive drainage by retrograde double J catheter placement.~Main study parameters/endpoints:~The primary objective is to assess whether a PCN is non-inferior to double J catheter regarding time to clinical recovery in patients with obstructive kidney disease resulting from urolithiasis.~The primary outcome parameter is time to clinical recovery. Clinical recovery is defined as reaching one or more of the following criteria. The mandatory amount of criteria to achieve clinical recovery is dependent on the indication for placement of a PCN or a JJ.~If indication for drainage is infection: improvement of infection, indicated by a decrease of WBC in two executive laboratory results and below 15.000 mm3 and a body temperature of 36-38.5 C. and/or~If indication for drainage is untreatable pain: Numeric rating score (NRS) considering pain resulting from a renal colic is improved and < 3 points and/or~If indication for drainage is deterioration of kidney function: improvement of creatinine/ Glomerular Filtration Rate (GFR) in two executive laboratory results It may occur that the indication for drainage is a combination of the above named indications. Clinical recovery will then be reached in case all parameters related to the different indications are within the set range. Secondary outcomes are further clinical data, PROMS (measured by the EQ-5D-5L, NRS, a satisfaction scale and a catheter questionnaire) and societal costs (measured by a diseasespecified iMCQ questionnaire).~Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The placement of either PCN or double J catheter is standard care. Currently the choice for PCN or a double J catheter is based on expert opinion and may be driven by arguments considering logistics or assumptions about the quality of life for a patient after placement.~Considering the difference in rate of placement of both PCN and double J catheter between various hospitals and different countries, it is believed experts have no uniform work method to handle the dilemma of choosing between these two techniques.[2] Furthermore the current EAU-guideline 2018 states that both methods of drainage are to be considered as equal.[1] Therefore there is no reason to believe, patients will be affected negatively by being placed randomly in either the double J group or the PCN group. Questionnaires will be filled in daily during hospitalization and twice or less afterwards. This is not considered to be a risk for the patient. The longest questionnaires (EQ-5D-5L and iMCQ) will take approximately 10-20 minutes to fill in, additional to the shorter scales (NRS, satisfaction scale) which will take approximately 1 minute to fill in. Generally It will take 90 minutes, spread over the course of three months, to fill in all questionnaires. For frequency and timing of the questionnaires. Finally, no additional visits to a hospital, withdrawal of blood samples or exposure to radiation is to be expected when taking part in this study.

To investigate the effectiveness of percutaneous nephrostomy catheter placement versus retrograde double J catheter placement in patients with symptoms of obstructive kidney disease (with either infection and/or pain and/or kidney function deterioration) caused by urolithiasis.

Pupillometric pain measurements helps clinicians determine and administer the optimized amount of opioids and so avoids opioid-induced side effects.The study will be designed to investigate the effect of pupillometry guided compared to non-PPI-guided postoperative pain therapy, conducted before extubation, on total postoperative opioid consumption during the first 2 postoperative hours after elective ENT surgery.~Background The evaluation of pain intensity during the immediate postoperative period in the operating room (OR) is a key factor for post interventional pain treatment. However, this evaluation may be difficult when patients are still intubated, restricted in consciousness or are showing verbal impairment due to ENT surgery. Verbally impaired patients are at increased risk of under treatment for pain.~With rising opioid consumption, the risk of postoperative side effects like nausea and vomiting, sedation with a longer recovery time or respiratory depression increases. Especially in the cohort of ENT surgery patients, where a difficult airway is regularly presented, such side effects should be avoided. A means of predicting immediate postoperative pain after surgery and the response to opiate analgesics would therefore be highly desirable.~The pupillary dilatation reflex (PDR), measured by pupillometry, has been successfully used to assess intraoperative analgesic component of anesthetic regimes and correlates with pain intensity measured on a numeric rating scale (NRS).~Aims~Primary aim of this study is to investigate if a pupillometry-guided opioid administration immediately postoperative in the OR leads to less opioid requirement during the first 2 postoperative hours compared to a non-pupillometry-guided treatment.~Secondary aim is to evaluate postoperative pain intensity during the first 2 postoperative hours in patients after pupillometry-guided versus non-pupillometry -guided opioid therapy in the OR.~Hypotheses~The investigators hypothesis that through a targeted pain therapy based on the measurement of immediate postoperative pupillometry scores, opioid consumption and pain intensity can be reduced during the first 2 postoperative hours.~Methods~The study will be done by observing postoperative pain intensity using pupillometry in patients scheduled for elective ENT surgery, carrying out pain intervention (opioid therapy) and re-observing to verify the effectiveness of the targeted postoperative opioid administration in the OR. Pain on an 11-point verbal Likert response score and total opioid consumption will be recorded by a blinded investigator at 30-minute intervals for the initial 2 postoperative hours.

The study will be designed to investigate the effect of pupillometry guided compared to non-PPI-guided postoperative pain therapy, conducted immediately at the end of surgery before extubation, on total postoperative opioid consumption during the first 2 postoperative hours after elective ear nose throat (ENT) surgery.

A multi-center prospective cohort study will be conducted to explore the change trend of eosinophil in peritoneal dialysis effluent during peritoneal dialysis-associated peritonitis, and to explore the relationship between eosinophil increase, peritonitis severity and antibiotic use. In this study, 100 patients with peritoneal dialysis-associated peritonitis who meet the inclusion criteria will be selected. Demographic data, laboratory variables, peritoneal fluid cytology and bacterial culture will be collected within 24 hours of peritonitis (day 1). Peritoneal fluid cytology includes leukocyte classification and eosinophilic leukocyte count will be examined at day 3, 5, 7, 10, 14, 21, 30, 60 and 90 after peritonitis. All patients will be followed up for 90 days, and their peritonitis outcome will be recorded. The primary endpoint is the prevalence of eosinophil increase in peritoneal effluent, which is defined as >100 eosinophils/mm^3, or >10% eosinophils of the total non-erythrocyte count. Secondary end points are peritonitis outcome at month 1 and 3 including transfer to hemodialysis , death.

A multi-center prospective cohort study will be conducted to explore the change trend of eosinophil in peritoneal dialysis effluent during peritoneal dialysis-associated peritonitis, and to explore the relationship between eosinophil increase, peritonitis severity and antibiotic use. This study will provide evidence for routine eosinophil testing

This study will evaluate clinical outcome on patients who undergo ceramic on ceramic (CoC) bearing total hip arthroplasty (THA) using Delta TT cup. Specifically the study intends to address the following research topics:~The incidence of squeaking after CoC THA using Delta TT cup.~The dislocation rate and survival rate of CoC THA using Delta TT cup.

This study will evaluate clinical outcome on patients who undergo ceramic on ceramic (CoC) bearing total hip arthroplasty (THA) using Delta TT cup.

Postoperative pulmonary hypertension (PHT) is the most challenging complication of valvular heart disease about 73% of the patients particularly in those posted for mitral valve replacement surgery Methods This prospective study was conducted in 120 patients aged from 54-65 years scheduled for elective valve replacement surgeries. Patients were randomly allocated to either nitro glycerine or PGI2 groups. Patients of nitro glycerine group received nebulized nitro glycerine (its starting concentration was 200 mcg/ml); nitro glycerine was delivered at a rate of 2.5-5 mcg/kg/min (5 mg, 1 mg/ml) over 10 minutes by ultrasonic nebuliser connected to the inspiratory limb of the breathing circuit. Patients of PGI2 group received nebulized PGI2 (epoprostenol), 20000 ng/ml (20000 ng/ml in 60 ml syringe was attached to an intravenous pump which delivers a titrating rate of 8 ml/h to the nebulizer compartment. The primary outcome was mean pulmonary artery pressure. The secondary outcomes included mean arterial blood pressure (MAP) (mmHg), PaO2/FiO2 ratio, cardiac index (CI) (l/min/m2) right ventricular ejection fraction (RVEF), central venous pressure(CVP) measured at the end of cardiopulmonary bypass then 30 minutes after start of treatment then 4 hours after start of treatment, 30-day mortality rate and the incidence of complications such as facial flushing, hypotension and re-exploration for bleeding.

This study was conducted in 120 patients aged from 54-65 years scheduled for elective valve replacement surgeries. Patients were randomly allocated to nitro glycerine or PGI2 groups. Patients of nitro glycerine group received nebulized nitro glycerine at a rate of 2.5-5 mcg/kg/min (5 mg, 1 mg/ml) over 10 minutes by ultrasonic nebuliser. Patients of PGI2 group received nebulized PGI2 (epoprostenol), 20000 ng/ml (20000 ng/ml in 60 ml syringe was attached to an intravenous pump which delivers a titrating rate of 8 ml/h . The primary outcome was mean pulmonary artery pressure. The secondary outcomes included mean arterial blood pressure (MAP) (mmHg), PaO2/FiO2 ratio, cardiac index (CI) (l/min/m2) right ventricular ejection fraction (RVEF), central venous pressure(CVP) , 30-day mortality rate and the incidence of complications such as facial flushing, hypotension and re-exploration for bleeding.

Patients aged ≥75 year scheduled for CRC surgery were studied (104 cases) and variables associated with major postoperative complications / mortality were evaluated. The MPI (multidimensional prognostic index)-score resulted strongly associated with major complications. also, it was a primary component of an individual prediction model (LASSO model).

Patients aged ≥75 year scheduled for CRC surgery were studied (104 cases) and variables associated with major postoperative complications / mortality were evaluated. The importance of this report is that MPI-score resulted strongly associated with major complications and it was a primary component of an individual prediction model.

Background: Atrial fibrillation (AF) is estimated to affect over 33 million people worldwide and is often associated with significant co-morbidities such as myocardial infarction, heart failure, dementia, and embolic stroke. Consequently, AF poses a significant burden to the healthcare system, in both direct and indirect costs of disease.~The management of AF in the acute setting is complex, especially for patients who suffer from persistent AF, defined as sustained AF for > 7 days. While one possible treatment strategy involves allowing AF to continue whilst controlling the ventricular rate (i.e. rate control), in certain cases, it is preferable to terminate the AF and restore normal sinus rhythm (i.e. rhythm control) for relief of intolerable symptoms associated with AF.~There are several methods currently in use for rhythm control, including observation without intervention, use of oral and/or intravenous anti-arrhythmic drugs for pharmacological cardioversion, and electrical cardioversion. However, each of these strategies come with significant limitations. Amiodarone was originally developed for treatment of angina, but is now widely recognized for its anti-arrhythmic properties. Current American College of Cardiology/American Heart Association/European Society of Cardiology guidelines recommend the use of amiodarone as a cardioversion agent in both intravenous and oral administration. Furthermore, the use of oral amiodarone is considered the standard of care for rhythm management in AF. Prior studies have demonstrated that the administration of a single, oral converting dose of amiodarone has similar rates of sinus rhythm conversion at 24 hours post-intervention compared to Vaughan-Williams Class 1C anti-arrhythmic medications. The use of amiodarone as a first-line therapy for AF is appealing when considering its safety profile.~Objectives: To determine the safety and efficacy of high-dose amiodarone, given as a single uniform oral dose, for the treatment of acute AF in a hospital inpatient setting and acute persistent AF in an outpatient ambulatory clinic.~Methods: This study will be a double-blind randomized controlled trial in patients with symptomatic AF. Amiodarone and placebo capsules will be prepared in single dose packs. A single dose pack will consist of either 2000 mg of amiodarone hydrochloride crushed and placed in 10 gel capsules of 200 mg each, or 10 gel capsules of crushed placebo. Individual dose packs will then be randomly assigned to participants with a unique research number.~Candidate inpatients will be identified through emergency room presentation, outpatient clinic admissions, or inpatient consultation. Once participants have been consented and allocated a study number, they will be randomly assigned a dose pack. Participants will be required to ingest the entire 10 capsule dose pack in one sitting with food witnessed by one of the study investigators or a designated study nurse. Following drug administration, participants will have cardiac monitoring and regular vital sign measurements for up to 48 hours. The investigators will provide the participants with a diary to record any potential adverse side effect symptoms, and the participant will be given the phone number of a study team member to contact if they are concerned about any adverse effects. After the 48 hour period, a study team member will contact the participant and ask specifically about potential adverse events.~Candidate outpatients will be identified through emergency room presentation or outpatient clinics not requiring hospital admission. Once participants have been consented and allocated a study number, they will be assigned a dose pack. Participants will be required to ingest the entire 10 capsule dose pack in one sitting with food. The time of capsule ingestion will be recorded. Following drug administration, participants will be provided with a portable cardiac monitor to wear for 48 hours. History taking of potential adverse side effect symptoms will be performed on a daily basis, or more frequently if required. After the 48 hour period, a 12-lead electrocardiogram with be performed to confirm of successful reversion to sinus rhythm, continuing AF, or other heart rhythm. The portable cardiac monitor will be retrieved and analyzed for evidence of time to successful reversion to sinus rhythm.~The investigators plan to enrol 42 AF patients, with 21 patients randomized to oral amiodarone and 21 patients randomized to placebo.

The investigators will seek to determine the safety and efficacy of high-dose amiodarone (2000mg), given as a single uniform oral dose, for the treatment of acute atrial fibrillation in both a hospital inpatient and ambulatory outpatient setting. The investigators will conduct a placebo-controlled randomized trial, with outcome ascertainment at 48h.

In current Dermatology practice, options for moderate acne vulgaris remain limited. Moderate acne is clinically defined as acne that has not responded to at least three months of topical therapy and is not severe enough for initial treatment with a conventional course of isotretinoin (formerly known as Accutane). The mainstay of treatment for moderate acne remains long courses of oral antibiotics, mainly tetracyclines (doxycycline, minocycline) and occasionally trimethoprim-sulfamethoxazole. Males with moderate acne, in particular, are especially limited in their treatment options as they are not eligible for hormonal management (spironolactone, oral contraceptive pills) like their female counterparts. Additionally, even for those regardless of gender who may eventually qualify for a traditional isotretinoin course, many insurance companies first require failure to respond to at least three months of oral antibiotics. Nagler et. al found that the average antibiotic use for moderate to severe acne prior to receiving isotretinoin was 331 days, with 15.3% of patients prescribed antibiotics for three months or less, 88% for six months or more, and 46% for at least one year.1 Despite the widespread use of oral antibiotics in acne, antibiotic resistance is considered a global threat per the CDC2, and there have been calls to limit their use in acne because of concerns of bacterial resistance3,4,5. Because of this, there is a significant need for more research on alternative treatment options for moderate acne.~Once weekly isotretinoin dosing has the potential to significantly improve moderate acne with good patient satisfaction and safety profile; however, no study findings on this treatment option have been published to date. The efficacy of isotretinoin, an oral vitamin A derivative, for treatment of acne has been well established. The traditional treatment course for severe acne consists of once to twice daily dosing (0.5-1 mg/kg/day) for 4-7 months (or 150mg/kg total cumulative dose). Though efficacious, there are numerous reported side-effects due to achieving the cumulative dose rapidly by once to twice daily dosing, such as severe dry skin, lips, and eyes, as well as liver enzyme and lipid abnormalities. Because of this, there have been studies exploring alternative isotretinoin dosing regimens including microdose, lower daily dose regimens (0.15-0.4 mg/kg/day6, 0.25-0.4 mg/kg/day7, 0.3-0.4 mg/kg/day8,9, in addition to 5 mg/day10 and 0.15-0.28 mg/kg/day with additional of local application of 1% clindamycin gel every other day11) and daily dosing for 7-10 consecutive days (0.5-0.7 mg/kg/day) out of each month only.7,12,13,14 All studies had favorable outcomes with alternative dosing, despite the lower total cumulative dose versus conventional dosing. Those who also analyzed adverse effect rates with alternative isotretinoin dosing found that these were either rarely observed or similar to conventional dosing.6,8,9,10,12,14 In contrast, the potential adverse effects of oral antibiotics used for acne include photosensitivity and nausea/vomiting (doxycycline), drug-induced pigment deposition and drug-induced systemic lupus erythematosus (minocycline), and angioedema and drug rashes including drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome (trimethoprim-sulfamethoxazole). Interestingly, rates of acne recurrence between alternative isotretinoin dosing and conventional dosing were similar at follow-up,6,7,9 despite a much older study from 1984 that found otherwise.15 Additionally, cost of alternative isotretinoin dosing was lower than with conventional dosing,8,9,13 and patient satisfaction was highest in the alternative dosing groups.7,10 For these reasons, this study aims to evaluate the efficacy of once weekly isotretinoin dosing (1-1.5 mg/kg/week) as a potential alternative to oral antibiotics for the treatment of patients with moderate acne. Secondary endpoints include patient satisfaction and adverse effects.

In current Dermatology practice, options for moderate acne vulgaris remain limited. The mainstay of treatment for moderate acne remains long courses of oral antibiotics despite emerging antibiotic resistance. The efficacy of daily to twice daily dosed isotretinoin, an oral vitamin A derivative, for treatment of severe acne has been well established. The purpose of this study is to determine if once weekly dosed isotretinoin is effective for the treatment of patients with moderate acne. Additionally, the study aims to evaluate patient satisfaction and identify any adverse effects on this alternative dosing regimen.

After the approval of the institutional review board and the Ethics Committee of Al Fayoum University number (D228) , and written informed consent from all patientṣ Pilot study will be done to confirm this sample size .The patients are classified in two groups group P for cervical epidural and group F for facet injection. Patients Inclusion criteria of chronic cervical pain syndromes will be made from their history, symptoms, and imaging diagnosis. Patients will be lying down on the prone position. In group( F) Under the C-arm fluoroscopic guidance targeted zygapophyseal joints will be identified. The mixture of 2 mL of 2% lidocaine with 2 ml of beta methasone (6 mg/ml) will be injected in the joints unilaterally or bilaterally according to complaints of patients. Another group ( P) patients will undergo translaminar or interspinous cervical epidural block (CEBs). The translaminar or interlaminar approach is considered the safest and most effective technique for cervical epidural placement.The patient will be in a prone position. This procedure will be performed with fluoroscopic guidance. The patient will be placed in an optimal flexed cervical spine posture stabilized with enough resistance to prevent movement of the head during the procedure. The skin will be prepared with an antiseptic solution. The midline of the selected interspace will be identified under fluroscopic guidance. LA, such as lidocaine, will be used, to mark the intended site of skin entry. As much as 1 mL of lidocaine will be used to infiltrate the skin and subcutaneous tissues. We will insert a 25-gauge, 2-inch needle exactly into the targeted midline. After the LA has been given time to anesthetize the area,we will hold the needle firmly at the hub with the left thumb and index finger. Then the palm of the left hand will be placed firmly against the patient's neck, so that the left hand acts as a unit to stabilize, protect, and control the needle's trajectory and its metered ingress from any unexpected patient activity. The needle will be then advanced with the left hand, which is braced against the neck with the needle hub held tightly between the left thumb and forefinger. We will use the right hand to monitor resistance through a syringe containing air. With constant pressure applied to the plunger of the syringe through light pressure applied by the right thumb, the needle and syringe will be advanced in a slow and deliberate manner. As the bevel passes through the ligament flavum and enters the epidural space, a sudden loss of resistance that we will appreciate also we can appreciate the entrence the epidural space under fluroscopic guidance in condition that not to cross J line (a line appear under flouroscopy imaging facet joint articulation if crossing this line we will puncture the dura).~Needle position within the epidural space will be checked by using fluoroscopic verification and by repeating the loss of resistance maneuver. The cervical epidural space should accept 0.5-1 mL of air or sterile preservative free saline without significant resistance. The force required to depress the plunger should not exceed that which is necessary to overcome the resistance of the needle. Any significant pain or sudden increase in resistance during the injection suggests incorrect needle placement, so the injection will be stopped and we will assess the position of the needle using fluoroscopy. If the needle remains satisfactorily placed and loss of resistance within the epidural space is confirmed without additional patient report of pain, gentle aspiration will be checked to assure that the needle is not positioned in the subarachnoid space or that it's not intravascular. If cerebrospinal fluid (CSF) is aspirated, we will repeat the block attempt at a different interspace. If aspiration of blood occurs, the needle will be tightly rotated and the aspiration test will be repeated. If the aspiration of blood continues, the procedure will be aborted due to the danger of developing an epidural hematoma and possibly neurological compromise. when the needle is correctly placed in the midline of the epidural space, then injection of the mixture of 2 mL of 2% lidocaine with 2 ml of beta methasone (6 mg/ml) will be done .

After approval of the institutional review board and the Ethics Committee of Al Fayoum University number (D228) , and written informed consent from all patientṣ Pilot study will be done to confirm this sample size .The patients are classified in two groups group P for cervical epidural and group F for facet injection To compare effectivness of cervical epidural versus cervical facet injection under fluroscopic guidance in patients sufferring from chronic neck pain.

Edoxaban was recently approved by The Turkish Medicines and Medical Devices Agency for the prevention of stroke and systemic embolism in adult patients with Nonvalvular Atrial Fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, diabetes mellitus, prior stroke or transient ischemic attack (TIA). Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of recurrent DVT and PE in adults.~The study will evaluate the safety of Edoxaban in patients diagnosed with AF who are currently on Edoxaban therapy for prevention of stroke in routine clinical practice in Turkey for stroke prevention up to 1 year following treatment by specialized as well as non-specialized physicians in hospital centers.

This is a national, multi-center, prospective study to evaluate the safety of Edoxaban in patients diagnosed with AF who are currently using Edoxaban for stroke prevention.~The primary objective:~To evaluate safety of Edoxaban treatment in patients with atrial fibrillation (AF) on Edoxaban therapy in routine clinical practice in Turkey.

The introduction of specific biliary lumen-apposing metal stents (LAMS) represented a great technical improvement in EUS-guided transmural Biliary drainage (BD) of distal malignant biliary obstruction Data is still limited, but recent studies and reviews have been reported with acceptable technical and clinical success. However, some concerns exist regarding its safety, as secondary adverse events~There are doubts concerning the possible benefits derived from the insertion of double-pigtail plastic stents (DPS) within the lumen-apposing metal stents (LAMS) in the EUS-guided choledochoduodenostomy (CDS). Our hypothesis is that adding a coaxial plastic stent may offer benefits in terms of safety in CDS.

The aim of the study is to evaluate technical, clinical and safety outcomes of lumen-apposing metal stent (LAMS) with and without a coaxial double-pigtail plastic stent (DPS) in EUS-guided choledochoduodenostomies (CDS) for the management of biliary obstruction.

This study is co-sponsored by University of Loyola, Seville, Spain and from University of Minho, Braga Portugal. Emma Motrico and Ana Mesquita as Principal Investigators of the study are the Responsible Parties.~Coronavirus disease 2019 (COVID-19) is a new pathology, declared a public health emergency by the World Health Organization that appeared more benign for pregnant women than for their newborns. COVID-19 pandemic is causing fear, anxiety and depression in the population. At the same time, pregnancy and postpartum is a period of increased risk for mental illness. It is estimated that 1 in 5 women will develop a mental illness in the perinatal period. Perinatal depression is the most common mental illness experienced during pregnancy and postpartum and has long-lasting adverse effects on women and their babies, bringing a strong burden to their families and society as a whole. The current COVID-19 pandemic is a unique stressor with potentially wide-ranging consequences in the perinatal period. Evidence coming from past epidemics, namely ZIKV infection (Zika virus) highlight the importance of examining mental health in light of stressful events experienced during pregnancy and the postpartum period and of long-term support for these mothers. There has been an increase in the prevalence of perinatal depression, anxiety and psychological distress after the announcement of the SARS-CoV-2 outbreak.~The project Research Innovation and Sustainable Pan-European Network in Peripartum Depression Disorder - Riseup-PPD (CA18138) is a Cost Action (European Cooperation in Science and Technology) funded by the Horizon 2020 Framework Programme of the European Union. The project aims to establish a European multidisciplinary network of experts dedicated to the understanding of Peripartum Depression (PPD), from its prevention and assessment to its treatment and evaluation of impact, considering the women, the newborns and the wider family and social systems. Researchers from different core expertise (clinical medicine, psychology, health sciences, mathematic, media and communications) from 23 European countries and six international countries participate in the COST Action Riseup-PPD. In order to promote best practices in perinatal mental health that may mitigate the impact of COVID-19 management in women's mental health, the COST Action Riseup- PPD has decided to create a new Task Force Perinatal Mental Health and COVID-19 pandemic. One of the main objectives of this crosscutting Task Force is to evaluate the impact of COVID-19 on perinatal mental health. Aims: Test the hypothesis that COVID-19 pandemic is associated with increased perinatal mental illness.~Methods Study design: Prospective observational study, with a baseline assessment and three follow-ups: one-month; three months; and six-months.~Setting: 11 European countries - Albania, Bulgaria, Cyprus, France, Greece, Israel, Malta, Portugal, Spain, Turkey, United Kingdom - Chile and Brazil. Participants: Pregnant women and new mothers with an infant under six months of age. Data from additional countries could also be include in the future to this study, if using the same instruments.~Study size: A representative sample was calculated according to number of newborns in the previous year in each country. The investigators estimate a minimum group size of 300 women per country. The estimation is based on an α-level of 0.05 and heterogeneity equal to 50%.~Variables and questionnaires Predictor variables/independent variables:~COVID-19 and Public health measures. Data on COVID-19 includes for each country (1) date of first confirmed case, (2) date of first death, and (3) at the date of questionnaire release: (3.1) number of confirmed cases, (3.2) number of recoveries (3.3) number of deaths. Data on public health measures adopted to contain the COVID-19 pandemic will include date and guidelines for (1) general restrictions (events, sports, religious ceremonies); (2) home confinement; (3) social distancing; (4) schools and services closing; and (5) restrictions to circulation within the country and between countries (including external border closure). Data on the deconfinement plan, including (1) general deconfinement (events, sports, religious ceremonies); (2) rules for circulating in public transport and services (including mandatory use of face masks); (3) schools reopening; and (4) services reopening.~Sociodemographic variables: date of birth, ethnicity, education, marital status, residence and questions about number of people living at home and numbers of weeks in confinement.~Coronavirus Perinatal Experiences Impact Survey (COPE-IS) - perinatal experiences; exposure and symptoms; financial impact; social support impact; social distancing and activity restriction; coping and adjustment; emotional impact; health background, mental health, and substance use.~In the follow-up assessments, experiences of new and expectant mothers will be measured with the Coronavirus Perinatal Experiences Scale-Impact Update (COPE-IU) and the Coronavirus Perinatal Experiences Scale - Care Follow Up (COPE-CF). The COPEIU evaluates exposure to COVID-19 and symptoms; impact on daily life, experiences, and feelings; the COPE-CF evaluates perceived support and care and the social and financial impact of the pandemic.~Perinatal experiences: Includes questions about if it is/was her first pregnancy, health problems during pregnancy, type of pregnancy, pre and postnatal care support, resources available from pre and postnatal care, changes experienced as a result of COVID-19 and question related to concerns about changes in family/friends support, medical care during the baby´s birth and child´s health as a result of the COVID-19 outbreak. Specifically, for women of a child younger than six months, this also includes other questions about city and place of birth, breastfeeding, changes experienced in birth plans and level of distress experienced related to changes in baby´s birth and postnatal experiences. Exposures and symptoms: Pregnant women/ new mothers and their family have been exposed to or are experiencing any symptoms like those seen in COVID-19. This includes questions about the diagnosis of COVID-19, symptoms compatible with coronavirus, contact with someone who has been diagnosed withCOVID-19, anyone close died due to COVID-19, and the degree of distress about COVID-19 related symptoms or potential illness. Financial impact: type of employment, impact of the pandemic on future employment and financial impact of the COVID-19 outbreak.~Social support impact: Support seeking, support provided, need for support, perceived support, and level of distress experienced with disruptions to social support due to the COVID-19 outbreak.~Coping and adjustment: Includes 23 coping strategies (problem-focused or emotion-focused) in response the stress related to the COVID-19 outbreak.~Emotional impact: Impact of COVID-19 on mental health - subjective impact of the COVID-19 outbreak on stress levels and mental health, sleep, and daily energy levels and the positive and negative impacts of the COVID-19 outbreak on daily life.~Health background, mental health, and substance use: Five mental health and substance use questions from the John's Hopkins COVID-19 Mental Health Measurement Working Group: 1) the woman's history of medical conditions; 2) household history of medical conditions; 3) current mental illness; 4) current substance use; and 5) treatment of medical conditions.~Psychological distress using the Brief Symptom Inventory-18 (BSI-18), omitting suicidality.~Dependent/outcome variables: Maternal and perinatal mental health outcomes will be evaluated - depression, anxiety and Posttraumatic Stress Disorder (PTSD), Measurements include the Edinburgh Postnatal Depression Scale (EPDS), the Generalized Anxiety Disorder Screener (GAD-7), a subset of 10 questions from the Posttraumatic Stress Disorder (PTSD) Checklist for DSM-5 related with COVID-19 included in COPE-IS and COPE-IU questionnaire [~(1) Feeling super alert or watchful or on guard; 2) Feeling jumpy or easily startled; 3) Having difficulty concentrating; 4) Trouble experiencing positive feelings; 5) Feeling guilty or blaming yourself; 6) Feeling irritable, angry or aggressive; 7) Repeated disturbing and unwanted thoughts about the COVID-19 outbreak; 8) Repeated disturbing dreams about the COVID-19 outbreak; 9) Trying to avoid information or reminders about the COVID-19 outbreak; and 10) Taking too many risks or doing things that could cause the participants harm]~Data collection: Participants will be recruited through social media (Twitter, WhatsApp, Facebook and Instagram, Reddit, Researchgate, Linkedin, Ya, etc.), networks of organizations (including universities, health centers, NGOs working on the field of perinatal mental health), policymakers, local organizations, and other stakeholders. Participants will also be recruited directly by message or email.~Participants are provided with a link to a digital survey that will direct them to an electronic consent form that provides an overview of what to expect and states that participation is voluntary, the purpose of research, possible risks, possible benefits, confidentiality protection, and appropriate alternatives. The baseline assessment is anticipated to be 20 minutes long. Eligible participants who complete the initial survey will be asked to participate in follow-up assessments.~Participation in the follow-ups will be optional and participants will have to provide their consent to be contacted by email or phone; attached to this request the investigators will provide a clear plan to protect confidentiality of information and contact information data protection plan (this will also be provided in the Informed Consent).~Ethical standards and safety monitoring: The study and handling of the data will follow all national required data protection standards. Each researcher (or team of researchers) involved will submit the project to local ethical committee before starting the project. Participants are provided with a link to an informed consent form before starting the study. If they agree to participate, only then will they proceed to the online survey. The consent form provides an overview of the aims of the study, what to expect and explains how confidentiality will be protected. Clarification of the voluntary nature of participation in the survey and of absence of compensation will be provided. Data should be collected anonymously, although email or/and phone number will be necessary for the follow-up assessments. Inclusion of vulnerable subjects is justified for this study because the purpose of the study is to examine pregnant or breastfeeding women. The research contains negligible risks as there is no more foreseeable risk of harm or discomfort other than potential inconvenience during participation. The study does not include deception, but some questions of the survey can elicit changes in the emotional state of participants. In order to address this issue, a debriefing procedure will be made available; at the end of the survey, information about resources in each country on mental health, perinatal care and COVID-19 as well as contacts of the research team will be given in case participants would like to have additional information. Information about the global results of the study will be provided upon request.

Introduction: Coronavirus disease 2019 (COVID-19) is a new pathology, declared a public health emergency by the World Health Organization, which can have negative consequences for pregnant women and their newborns. It is estimated that 1 in 5 women will develop a mental illness in the perinatal period. COVID-19 pandemic has been associated with anxiety and depression in the population. The current pandemic is a unique stressor with potentially wide-ranging consequences in the perinatal period, but little is known about the impact of COVID-19 on perinatal mental health. Thus, the objective of this study is to explore the experiences of pregnant and new mothers during the current pandemic, particularly its impact on perinatal mental health (including depression, anxiety, PTSD and psychological distress). Methods: The study design is a prospective observational study, with a baseline assessment and three follow-ups: one month; three months; and six months post baseline. This international study will be carried out in 11 European countries (Albania, Bulgaria, Cyprus, France, Greece, Israel, Malta, Portugal, Spain, Turkey, United Kingdom) Chile and Brazil. The study population will comprise pregnant women and new mothers with an infant under six months of age, covering a broad range of women across the perinatal period. Ethics and dissemination: The study and handling of the data will follow all national required data protection standards. Each researcher (or team of researchers) involved will submit the project to their local ethical committee before starting the project. Results from the project will be disseminated in peer reviewed journals and international conferences.

This study is an early, open, single-centered trial. The major aim of this study is to evaluate the safety and tolerance of GC019F CAR-T cell immunotherapy in relapsed or refractory B-ALL. The study will include 6-12 subjects to receive GC019F single infusion.

The study is an early, open, single-centered trial. The aim of this study is to evaluate the safety and tolerance of GC019F CAR-T cell immunotherapy in relapsed or refractory B-ALL. The study will include 6-12 subjects to receive GC019F therapy.

The study will examine the lymphatic functional and morphological status in patients with moderate tricuspid valve regurgitation compared to healthy age and gender-matched controls.~Subjects will be examined at one occasion using t2-weighted MRIs to evaluated lymphatic anatomy and Near-infrared fluorescence imaging for evaluation of superficial peripheral lymphatic function. Finally, the capillary filtration rate will be estimated using plethysmography.

The study will examine the lymphatic functional and morphological status in patients with moderate tricuspid valve regurgitation compared to healthy age and gender-matched controls.~The study will use t2 weighted MRI, Near-infrared fluorescence imaging, and plethysmography to examine the above-mentioned question.

Multi-resistant bacteria (MRB) are associated with high antibiotic consumption and designated by WHO as one of the major threats to the world. In Denmark, the incidence of MRB is generally increasing, and every 20th patient admitted to Danish Emergency Department (ED), is infected with resistant bacteria. Respiratory tract infection is a serious condition, with 3 million death worldwide every year, and about 20-40% of the patients with community-acquired pneumonia need hospitalization. Data from the ED at Hospital Sønderjylland shows that 6% of the patients are registered with a respiratory tract infection, including pneumonia. Treatment of pneumonia should be initiated within a few hours, therefore early and precise diagnostic is extremely important. An imprecise or delayed diagnostic will often result in overconsumption of broad-spectrum antibiotics, contributing to an increase in the development of MRB threatening future treatments possibilities. Currently, pneumonia diagnosis is based on clinical symptoms such as cough, expectoration, chest pain, fever or breathlessness, combined with an x-ray of the lungs, relevant blood tests and microbiological analyses of sputum samples. However, X-ray is an imprecise diagnostic tool, and sputum test responses are first available after 2 days. Thus, the diagnostic is challenged by unspecific symptoms, unsure diagnostic methods and prolonged waiting time for results of up to several days. Sputum can be cultivated to determine the bacterial agent. However, the sputum samples are often of poor quality and many patients cannot deliver a sample. A recently published Danish study shows, that only half of the patients at the ED have sputum samples collected for culturing and none of them had their antibiotic treatment adjusted based on the microbiological results of the sputum. Despite, the use of different microbiological analysis methods to detect bacteria or virus causative of pneumonia, common to the methods is that a representative specimen from the lower respiratory tract is crucial for optimal sensitivity and specificity. Despite technological advances in molecular diagnostics, identifying the etiology of pneumonia remains a challenge. Consequently, identification of optimal sputum collecting method and investigation of an alternative sputum analyses assessment is needed to improve specimens' suitability to identify the etiology of pneumonia.~Clinical experience indicates that an inhalation mask with saline solution can induce a successful sputum sampling. Tracheal suction is often used on intubated patients in the intensive care unit to collect sputum, and this method has become the standard procedure at several ED. A comparison of the two methods has not been investigated in an ED context nor has the quality of the collected sputum samples and relevance for clinical practice been explored.~Ensuring the optimal sputum collection is of particular relevance during the COVID-19 pandemic. An optimal sputum collection is important to be able to determine if the pneumonia is caused by SARS-CoV-2 or a bacterium - especially in situations where the swab from throat or pharynx presents a negative result, as the method is not sensitive enough to rule out COVID-19 in patients with pneumonia. Accordingly, the Health Board in Denmark recommends tracheal suction of patients admitted with suspected COVID-19 in case of symptoms of the lower respiratory tract, and only in cases the symptoms originates from the upper airways a swab can be performed~1.1 Hypothesis and purpose The hypotheses is that methods without suction (forced expiratory technique and induced sputum) are just as effective as tracheal suction for obtaining a representative specimen from the lower respiratory tract..~The purpose of this study is to determine the most optimal method for obtaining high-quality sputum samples.~Following research questions will be explored:~What is the difference between the conventional sampling by tracheal suction comparing to sampling using forced expiratory or induced sputum techniques in relation to the suitability of collected specimens from the lower respiratory tract~Identification of possible adverse events during sputum collection~How do patients experience the two sputum sample collecting procedures?~Collection of sputum and adverse events After consent, the patient will be randomized in two groups with 1:1 allocation using permuting blocks. The software tool 'Randomized' offered by Open Patient data Explorative Network (OPEN) will be used.~ORGANIZATION The project is anchored in the Research unit of Emergency Medicine, the ED of Hospital Sønderjylland and the Department of Regional Health Research, University of Southern Denmark. The project is a research collaboration between clinicians and researchers in the field of emergency medicine and microbiology at Hospital Sønderjylland (SHS) and Odense University Hospital (OUH).

Respiratory tract infection is a serious condition causing 3 million deaths worldwide every year. Approximately 20-40% of patients with community-acquired pneumonia are hospitalised. Treatment of pneumonia should be initiated as quickly as possible and therefore an early and precise diagnostic is extremely important. Imprecise or delayed diagnosis often results in overconsumption of broad-spectrum antibiotics that contribute to the development of antibiotic resistance. Unspecific symptoms, unsure diagnosis methods and a wait time of up to several days for results challenge a quick and effective diagnosis and treatment of pneumonia. Microbiological analysis of sputum samples is used to identify pathogens causative to pneumonia. However, obtaining specimens of good quality is challenging and affects the sensitivity and specificity of the results. Therefore, the identification of the optimal sputum collecting method is needed to ensure an improved identification process of the pathogen causing pneumonia.~The purpose of this study is to determine the most optimal method for obtaining good quality sputum samples when comparing tracheal suction to methods without suction. A more accurate diagnosis will lead to more appropriate antibiotic consumption and will reduce the general development of antibiotic resistance.

The early diagnosis of the periprocedural myocardial infarction (MI) due to the bypass graft occlusion is an important element, in order to introduce early therapeutic strategies. Invasive coronary angiography (CA) is the gold standard to evaluate the postoperative myocardial ischemia due to the graft occlusion. Since this procedure has several important risks, such as thromboembolic events, dissection, bleeding, and contrast dye-induced nephropathy, in daily clinical practice, only patients with strong clinical suspicion of early MI following coronary artery bypass grafting (CABG) undergo this invasive procedure. There is a clinical need for the development of safe and accurate non-invasive diagnostic approaches to assess the early coronary bypass graft occlusion and to predict the consequent MI. A new clinical approach for the identification of the early post-procedural graft occlusion in patients undergoing CABG surgery is the high-sensitivity cardiac troponin (hs-cTn) cut-off level. The peri-operative bypass occlusion will be assessed by a Coronary Computed Tomography (CCT) scan which is a widely available non-invasive approach that permits an accurate evaluation of coronary stenosis. This study is to evaluate the correlation between hs-cTn level as cardiac biomarker for ischemia and early graft occlusion as assessed by CCT in patients undergoing coronary bypass surgery.

This study is to evaluate the correlation between hs-cTn level as cardiac biomarker for ischemia and early graft occlusion as assessed by CCT in patients undergoing coronary bypass surgery.

This study is a phase IV study in subjects with acute drug-induced liver injury. As designed, the study will include a screening period of up to 1 week, 2 to 4 weeks of treatment, and 1 week of safety follow-up. The eligible subjects will randomly be assigned to polyene phosphatidylcholine group or magnesium isoglycyrrhizinate group to receive single-blind treatment with a ratio of 1:1.

The purpose of this study is to explore the efficacy and the safety of polyene phosphatidylcholine Injection in patients with acute drug-induced liver injury after 2-4 weeks of treatment.

This is a single site, single arm Phase II trial pilot study to explore if chemo-embolization increases progression free and/or overall survival in a subpopulation of cisplatin-ineligible head and neck cancer patients with an acceptable morbidity rate in the U.S. Chemo-embolization will serve as adjuvant therapy performed in addition to standard of care radiation and chemo- and/or immunotherapy. Within UAB, the Investigators plan to recruit 48 patients to implement the intervention, within a two-year period. Progression free survival will be assessed at 3, 6 and 24 months (if available) after intervention, which is determined based upon the results of follow-up Head and Neck imaging (CT or MRI) interpreted by a Radiologist not involved in the study, per standard of care. Overall survival will be reported by the patients' Oncology team on a monthly basis. The trial endpoints will form the basis of how PFS and OS compare to historical outcomes in a similar cohort of patients.

The study will evaluate whether adjuvant chemo-embolization increases progression free and/or overall survival relative to standard of care radiation and chemo- and/or immunotherapy in cisplatin-ineligible head and neck cancer patients with an acceptable morbidity rate.

Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine.~In the Phase I part safety and toxicity of the combination will be assessed using a 3+3 design. The recommended dose for the Phase II will be determined.~In the Phase II part there will be 4 different cohorts:~Cohort 1: Undifferentiated pleomorphic sarcoma (UPS) Cohort 2: Leiomyosarcoma (LMS) Cohort 3: Alveolar soft-part sarcoma (ASPS) Cohort 4: Osteosarcoma Patients will be randomized for phase II part only (except in cohort 3) in an open-label way to receive selinexor in combination with gemcitabine versus gemcitabine alone

Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine.

This 8-week study will investigate whether the application of blood flow restriction (BFR) therapy augments rotator cuff strength in untrained individuals. This is a RCT with subjects randomized to a BFR or a non-BFR group. Both groups will perform the same training program 2 times a week over 8 weeks with one group performing the lower extremity exercises under occlusion (i.e., BFR applied to the proximal thigh of the dominant leg).~Prior to starting the study the subjects will have their strength assessed by a blinded physical therapist using a hand held dynamometer. The muscles assessed will be the: quadriceps, the hamstrings, the supraspinatus, and the external rotators of the shoulder. Another blinded physical therapist will assess the cross-sectional area of the quadriceps and the supraspinatus tendon using ultrasonography. These tests will be repeated at the conclusion of the study.~Subjects' training weight will be 30% of their 1 repetition max (1RM). 1RM will be determined using hand held dumbbells for the shoulder exercises and machines (knee extension, knee curl machines) for the lower extremity exercises.~Subjects will be randomized to either the BFR or non-BFR group. Subjects in the BFR group will perform the lower extremity exercises under occlusion (i.e., BFR applied to the proximal thigh of the dominant lower extremity). Both groups will perform 4 sets of each lower extremity exercise for 30/15/15/15 reps. After completing the lower extremity exercises the subjects will perform the shoulder exercises (scaption, sidelying external rotation) for 3 sets of 15 repetitions each. The shoulder exercises will not be performed with BFR in either group.

This 8-week study will investigate whether the application of blood flow restriction (BFR) therapy augments rotator cuff strength in untrained individuals. This is a RCT with subjects randomized to a BFR or non-BFR group. Both groups will do the same training program: 1) first sitting unilateral knee extension and standing unilateral knee curls (w/ or w/o BFR; 4 sets, 30/15/15/15 reps) and 2) scaption and sidelying external rotation (no BFR for either group; 3 sets x 15 reps each).

Skin lesions, more or less deep, are areas of rupture and tissue loss with exposure of the underlying tissues.~The term external lesion or wound indicates the morphological and functional destruction of the continuity of the superficial skin layers and, in the most serious cases, of the deep subcutaneous layers.~The lesions are evaluated and cataloged on the basis of their width, depth and characteristics. Furthermore, the development, the causes (etiopathogenesis) and the pathophysiological context of the wound are considered.~Superficial, slight lesions affect only the epidermis, the dermis and at most part of the hypodermis; the deeper ones involve all the subcutaneous tissue (fat) up to the muscles, the periosteum, reaching the exposure of the bone or supporting structures (tendons and cartilages); the most severe (chronic) are characterized by loss of substance in the skin and a poor tendency to healing.~According to the timing of healing, the lesions are divided into acute and chronic.~Acute injuries heal through 3 different phases and reach tissue repair within 8/10 weeks. Beyond this time the lesion becomes chronic and, if not acted correctly, the wound becomes more complicated and degrades in increasingly serious stages / degrees.~The acute wounds that the healthcare professional must treat most frequently are surgical wounds. Depending on their extent, acute wounds can be distinguished into stab wounds, puncture wounds, lacerated wounds and lacerated-contused wounds.~This type of acute wounds can generally heal in a physiological way or be induced to healing through the use of dressings, which reduce healing times.~The main dressings used to treat these lesions are hyaluronic acid-based dressings containing antiseptics, such as silver sulphadiazine to prevent the risk of contamination and colonization by microorganisms. In these dressings, hyaluronic acid promotes the acceleration of the tissue repair process.~However, among the main products used by hospital and non-hospital surgeries there are also dressings based on Rigenase® (aqueous extract of triticum vulgare) and polyhexanide. Rigenase®, containing the aqueous extract of triticum vulgare, has pro-proliferative, anti-inflammatory and antioxidant activity. These activities are attested by recent literature which indicates that the aqueous extract of triticum vulgare has pro-proliferative activity on fibroblasts and keratinocytes, the main cells involved in proliferation during the lesion repair process; in addition, the aqueous extract of triticum vulgare also has a documented anti-inflammatory activity, mediated by the reduction of the main cytokines responsible for skin inflammation, and an anti-metalloprotease9 activity, the main actor of inflammation in skin lesions. The antioxidant activity of Rigenase®, verified on the hemolysis of erythrocytes, is comparable to that of ascorbic acid.~The activity of polyhexanide is also fundamental for the prevention of the risk of colonization and contamination by microorganisms in acute skin lesions. In fact, this latest generation antiseptic has a consolidated antiseptic activity on gram positive and gram negative bacteria, on fungi and on some viruses, without the development of resistance both in vitro and in vivo.~Based on the foregoing, this study aims to compare the efficacy and clinical tolerability of two medical devices in gauze and cream containing the aqueous extract of triticum vulgare and polyhexanide in comparison with two medical devices containing hyaluronic acid and silver sulfadiazine. in the treatment of acute skin lesions. The reason why the two types of devices are compared is because hyaluronic acid and silver sulfadiazine represent the gold standard for the treatment of acute skin lesions. Therefore, making a comparison between the activity of the aqueous extract of triticum vulgare and polyhexanide and this gold standard of control in the treatment of acute skin lesions, is useful to better define the efficacy and tolerability of both medical devices in order to to possibly expand the therapeutic armamentarium available for the treatment of acute skin lesions

This study aims to compare the efficacy and clinical tolerability of two medical devices in gauze and cream containing the aqueous extract of triticum vulgare and polyhexanide in comparison with two medical devices containing hyaluronic acid and silver sulfadiazine in the treatment of acute skin lesions . The reason why the two types of devices are compared is because hyaluronic acid and silver sulfadiazine represent the gold standard for the treatment of acute skin lesions. Therefore, making a comparison between the activity of the aqueous extract of triticum vulgare and polyhexanide and this gold standard of control in the treatment of acute skin lesions, is useful to better define the efficacy and tolerability of both medical devices in order to eventually expand the therapeutic armamentarium available for the treatment of acute skin lesions

This study will evaluate the clinical efficacy and safety of the BTL-899 device for changes in subcutaneous fat tissue and muscle tissue of inner thighs. The study is a prospective multi-center open-label single-arm study. The subjects will be enrolled and assigned into a single study group. Subjects will be required to complete four (4) treatment visits and two follow-up visits. All of the study subjects will receive the treatment with the subject device.~At the baseline visit, MRI imaging will be performed; the subject's weight and thigh circumference will be recorded. Photos of the treated area will be taken.~The treatment administration phase will consist of four (4) treatments, delivered 5-10 days apart. The applicator of BTL-899 will be applied over the treatment area. The device will induce visible muscle contractions along with heating of the subcutaneous fat. Each therapy session will last 30 minutes.~At the last therapy visit, the subject's weight and thigh circumference will be recorded, and photos of the treated area will be taken. In addition, subjects will receive a Subject Satisfaction Questionnaire to fill in.~Safety measures will include documentation of adverse events (AE), including the subject's experience of pain or discomfort after each procedure. Following each treatment administration and at all of the follow-up visits, subjects will be checked for immediate post-procedure adverse event assessment.~During the post-procedure visits (at 1-month and 3-month follow-up visits), the subjects will undergo a MRI imaging. Also, the subject's satisfaction will be noted, and weight with thigh circumference will be recorded. Photographs of the treated area will be taken. In addition, subjects will receive a Lifestyle Change Questionnaire to fill in.

This study will evaluate the clinical efficacy and safety of the BTL-899 device for changes in subcutaneous fat tissue and muscle tissue of inner thighs. The study is a prospective multi-center open-label single-arm study. The subjects will be enrolled and assigned into a single study group. Subjects will be required to complete four (4) treatment visits and two follow-up visits. All of the study subjects will receive the treatment with the subject device

This study will evaluate the clinical efficacy and safety of the BTL-899 device for changes in subcutaneous fat tissue and muscle tissue of arms. The study is a prospective multi-center open-label single-arm study. The subjects will be enrolled and assigned into a single study group. Subjects will be required to complete four (4) treatment visits and two follow-up visits. All of the study subjects will receive the treatment with the subject device.~At the baseline visit, MRI imaging will be performed; the subject's weight and arm circumference will be recorded. Photos of the treated area will be taken.~The treatment administration phase will consist of four (4) treatments, delivered 5-10 days apart. The applicator of BTL-899 will be applied over the treatment area. The device will induce visible muscle contractions along with heating of the subcutaneous fat. Each therapy session will last 30 minutes.~At the last therapy visit, the subject's weight and arm circumference will be recorded, and photos of the treated area will be taken. In addition, subjects will receive a Subject Satisfaction Questionnaire to fill in.~Safety measures will include documentation of adverse events (AE), including the subject's experience of pain or discomfort after each procedure. Following each treatment administration and at all of the follow-up visits, subjects will be checked for immediate post-procedure adverse event assessment.~During the post-procedure visits (at 1-month and 3-month follow-up visits), the subjects will undergo a MRI imaging. Also, the subject's satisfaction will be noted, and weight with arm circumference will be recorded. Photographs of the treated area will be taken. In addition, subjects will receive a Lifestyle Change Questionnaire to fill in.

This study will evaluate the clinical efficacy and safety of the BTL-899 device for changes in subcutaneous fat tissue and muscle tissue of arms. The study is a prospective multi-center open-label single-arm study. The subjects will be enrolled and assigned into a single study group. Subjects will be required to complete four (4) treatment visits and two follow-up visits. All of the study subjects will receive the treatment with the subject device.

This is one of two replicate randomized, double-blind, placebo-controlled, parallel arm trials to determine the safety and efficacy of two different dose levels of SEL-212 compared to placebo. 112 and 153 patients, stratified as to the presence or absence of tophi, were randomized in a 1:1:1 allocation ratio prior to Baseline to receive treatment with one of two dose levels of SEL-212 or placebo every 28 days for approximately 6 months in each trial respectively (SEL-212/301 and SEL-212/302). The SEL-212 doses differed as to the SEL-110.36 component. Participants received SEL-037 administered at a dose of 0.2 mg/kg via intravenous (IV) infusion immediately after receiving SEL-110.36 at a dose of either 0.1 mg/kg (SEL-212 low-dose) or 0.15 mg/kg (SEL-212 high-dose) via IV infusion. The placebo consisted of normal saline.~Placebo subjects who completed the study will be offered enrollment in an open-label extension study for treatment with SEL-212 (SEL-212/303).~Efficacy assessments were conducted at intervals that are appropriate to determine treatment effect with samples for the primary endpoint drawn during Treatment Period 6. Safety was monitored throughout the study with an independent data safety monitoring board (DSMB).

This is one of two replicate randomized, double-blind, placebo-controlled, parallel arm trials to determine the safety and efficacy of two different dose levels of SEL-212 compared to placebo. 112 and 153 patients, stratified as to the presence or absence of tophi, were randomized in a 1:1:1 allocation ratio prior to Baseline to receive treatment with one of two dose levels of SEL-212 or placebo every 28 days for approximately 6 months in each trial respectively (SEL-212/301 and SEL-212/302). Analysis of primary and key efficacy were performed at Day 28 of Treatment Period 6. Safety was monitored throughout the study.

Probiotics have been shown in previous pilot studies to be helpful in acne and this study aims to examine how the gut microbiome and skin biophysical properties are shifted in those with acne vulgaris. In particular, this study will assess the influence of oral spore based probiotics on the skin sebum production and will assess how probiotics influence the gut microbiome and the blood levels of short chain fatty acids.

The purpose of this study is to determine how probiotics affect sebum production and gut health in those with acne vulgaris.

Aim: Orthognathic surgeries are extensive surgeries including both soft and hard tissues of the facial region of the skull associated with blood loss, inflammatory reactions, massive swelling, postoperative nausea vomiting (PONV), and severe pain. Therefore; in most of the patients who are with dentofacial deformity and undergo orthognathic surgery, postoperative recovery generally requires a long troublesome period. The aim of this study is to improve postoperative outcome by the use of Enhanced Recovery After Surgery (ERAS) protocols.~Material methods: After Ethics Committee approval (2020/965), the data of 90 patients who underwent elective orthognathic surgery, were investigated. Following standard monitorization and general anesthesia; Group 1 patients were applied traditional approach and received intraoperative 10 mL/kg/h IV izolen infusion. Rescue analgesics and PONV prophylaxis were applied when required through the postoperative first 48 hours. Group 2 received ERAS approach. Patients in Group 2 did not preoperatively smoke for 48 hours, drank clear liquids until the last 2 hours, and received 6 mL/kg/h IV izolen infusion intraoperatively. In these; gastric aspiration was also applied before extubation, PONV prophylaxis was supported routinely, and patient controlled analgesia was added to the routine analgesia plan for the first postoperative 48 hours. The primary endpoint was length of hospital stay. The secondary endpoints were intraoperative follow-up data, numeric rating scale (NRS) pain scores, opioid consumption, PONV incidences, length of postanesthesia care unit (PACU) stay, satisfaction scores of two groups through the postoperative first 48 hours.

Aim: Orthognathic surgeries are generally associated with blood loss, swelling, postoperative nausea vomiting (PONV), and pain. The aim of this study is to improve postoperative outcome in patients undergoing orthognatic surgeries by the use of Enhanced Recovery After Surgery (ERAS) protocols.~Material methods: After Ethics Committee approval (2020/965), the data of 90 patients who underwent elective orthognathic surgery, were investigated. Following standard monitorization and general anesthesia; Group 1 patients were applied traditional approach and received intraoperative 10 mL/kg/h IV izolen infusion. Group 2 received ERAS approach. Patients in Group 2 did not preoperatively smoke for 48 hours, drank clear liquids until the last 2 hours, and received 6 mL/kg/h IV izolen intraoperatively. In these; gastric aspiration was also applied before extubation, PONV prophylaxis and patient controlled analgesia was added to the routine plans for the first postoperative 48 hours. The primary endpoint was length of hospital stay. The secondary endpoints were intraoperative follow-up data, length of postanesthesia care unit (PACU) stay, numeric rating scale (NRS) pain scores, opioid consumption and PONV incidences through the postoperative first 48 hours, and satisfaction scores.

Aim: The number of obese patients (body mass index (BMI)≥30) has increased dramatically worldwide, and we, as anesthesiologists, routinely come up against them in our daily clinical practice. Although the preference of various peripheral and neuroaxial regional anesthesia (RA) techniques seems to be advantageous in the anesthetic management of these patients, their performances can also be associated with technical difficulties and greater failure rates. The aim of this study is to compare the performance properties and analgesic efficacy of ultrasound (US)-guided thoracic paravertebral blocks (TPVBs) in obese and non-obese patients.~Material methods: After obtaining ethics committee approval; data of 82 patients, who underwent elective bilateral reduction mammaplasty under general anesthesia with adjunctive TPVB analgesia between December of 2016 and February of 2020, were reviewed. Patients were allocated into two groups with respect to their BMI scores (Group NO: BMI<30 and Group O: BMI≥30). Demographics, TPVB ideal US image visualization and performance times, needle tip visualisation and TPVB performance difficulties, number of needle maneuvers, surgical, anesthetic and analgesic follow-up parameters, incidence of postoperative nausea vomiting (PONV), sleep duration, length of postanesthesia care unit (PACU) and hospital stay, patient and surgeon satisfaction scores were all investigated and compared. Student's t, Mann-Whitney-U and Chi-square tests were used for statistical analysis.

Aim: Although regional anesthesia (RA) techniques are advantageous in the anesthetic management of obese patients (body mass index (BMI)≥30); their performances can still be associated with technical difficulties and greater failure rates. The aim of this study is to compare the performance properties and analgesic efficacy of ultrasound (US)-guided bilateral thoracic paravertebral blocks (TPVBs) in obese and non-obese patients.~Material methods: After obtaining ethics committee approval; data of 82 patients, who underwent elective bilateral reduction mammaplasty under general anesthesia with adjunctive TPVB analgesia between December of 2016 and February of 2020, were reviewed. Patients were allocated into two groups with respect to their BMI scores (Group NO: BMI<30 and Group O: BMI≥30). Demographics, TPVB ideal US image visualization and performance times, needle tip visualisation and TPVB performance difficulties, number of needle maneuvers, surgical, anesthetic and analgesic follow-up parameters, incidence of postoperative nausea vomiting (PONV), sleep duration, length of postanesthesia care unit (PACU) and hospital stay, patient and surgeon satisfaction scores were all investigated and compared.

Women with PCOS appear to exhibit impaired progesterone (P4) augmentation of gonadotropin release (positive feedback), and this is at least partly independent of BMI differences. To test more directly the role of hyperandrogenemia/hyperandrogenism (HA), we will assess if the androgen-receptor blocker flutamide enhances P4 augmentation of gonadotropin release in estradiol (E2)-treated women with PCOS. We will study 10 women with PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study, with subjects undergoing two assessments of P4 positive feedback - once after 4 weeks' pretreatment with flutamide and once after 4-weeks' pretreatment with placebo (in random order). We will assess P4 positive feedback via frequent sampling for 16 hours. Subjects will be pretreated for 3 days (prior to CRU admission) with transdermal E2 (0.2 mg/day), starting no earlier than cycle day 7. Subjects will be admitted to the CRU the evening of day 3 of E2 treatment. Starting at 0200 h, blood will be collected for 16 hours. After 6 h of sampling (0800 h), subjects will receive a single oral dose of P4. A second CRU admission - performed at least 2 months later to permit adequate washout of flutamide (as needed) - will be identical to the first except that placebo pretreatment will be exchanged for flutamide pretreatment or vice versa. We will assess the P4-mediated augmentation of FSH release, with secondary endpoints including the P4-mediated augmentation of LH release. We hypothesize that in E2-pretreated women with PCOS, acute P4 augmentation of FSH release (positive feedback) will be enhanced by androgen-receptor blockade (flutamide).

This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. The investigators hypothesize that in estradiol-pretreated women with PCOS, acute progesterone augmentation of FSH release (positive feedback) will be enhanced by flutamide.

Type II DM is a highly prevalent and heterogeneous condition. New treatment modalities to complement existing interventions are therefore of great interest, including dietary interventions for primary prevention or as a possible therapeutic option that may confer benefits beyond currently recommended conventional therapies. Hence, the present work aims to evaluate the efficacy of instant multigrain supplementation on the glycemic status, cardiometabolic implications, oxidative stress and nutritional status in Type II DM patients, as compare to standardized medication regimen.

The objective of this study is to evaluate the efficacy of instant multigrain supplementation on the glycemic status, cardiometabolic implications, oxidative stress and nutritional status in Type II DM patients.

This is a randomized, multicenter, clinical trial in which 598 patients with advanced gastric cancer at high risk of peritoneal metastases are randomly allocated to receive either preoperative hyperthermic intraperitoneal chemotherapy (HIPEC) plus gastrectomy (experimental group) or gastrectomy alone (control group). All patients, regardless of allocation, will additionally receive 4 cycles of FLOT chemotherapy (docetaxel 50 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 and 5-fluorouracil 2600 mg/m2) before surgery ± HIPEC and 4 cycles of FLOT chemotherapy after gastrectomy. The main outcome is frequency of peritoneal recurrence by 6-months post-operative. Patients will be followed for 5 years and undergo additional evaluations at 6 months, 1 year, 3 and 5 years.~The study will take place at 7 hospitals across Poland. All participating centers have the equipment and skills to perform all necessary procedures in this study. The below centers specialize in the treatment of stomach cancer with many documented years of experience. They are trained in the maintenance of a register, possess the skills to conduct appropriate research analyses and are equipped with a system for assessing the quality of both surgical and oncological treatment.

The study was designed to evaluate the efficacy of perioperative FLOT chemotherapy in combination with perioperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced gastric cancer at high risk of peritoneal metastases. The impact of treatment on peritoneal recurrence and survival over 6 months, 1, 3 and 5 years will be assessed.

ZAP-DENGUE is a pilot randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of five days of intravenous zanamivir treatment to treat vascular permeability syndrome which is the main cause of death in dengue fever. Our central hypothesis is that zanamivir treatment is safe in patients with dengue infection, will significantly decrease serum sialic acid levels, and will result in fewer patients with the development of moderate or severe clinical plasma leakage. 74 male and non-pregnant female volunteers age 7 years and older from Colombia with a diagnosis of dengue fever with warning signs or severe dengue as per the World Health Organization 2009 definition with the presence of fever and positive rapid test for the presence of dengue non-structural protein-1 (NS1) will be randomized to zanamivir versus placebo. In the treatment group, all participants weighing less than 50 kg will receive 12 mg/kg and all participants weighing 50 kg and above will receive 600 mg as the initial dose intravenously every twelve hours for 5 days adjusted for renal function. In the placebo group, participants will receive placebo normal saline solution intravenously every twelve hours for 5 days.~All patients will receive blood draws for assessment of hematocrit, renal function, and biologic efficacy endpoints and clinical evaluation of signs and symptoms of vascular permeability (which may include ultrasound and radiograph) and adverse events daily during the five days of medication administration and once at follow up at 14 days.

ZAP-DENGUE is a pilot randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of five days of intravenous zanamivir treatment to treat vascular permeability syndrome which is the main cause of death in dengue fever.

This phase II study is a randomized, double-blind study that seeks to evaluate the clinical effects and safety of fucoidan in the treatment of cancer patients with stage III/IV head and neck squamous cell carcinoma.~Patients will be centrally randomized in a 1:1 ratio to receive either Fucoidan or placebo (potato starch) Eligible subjects will receive fucoidan twice daily (BID) in combination with chemotherapy and radiation therapy over a 24-week treatment period.~Clinical effects and safety parameters for all subjects who complete the treatment period will be followed for an additional 72 weeks after the treatment period.~The total length of the study for each subject will be approximately 100 weeks, comprising the following time periods: screening period (28 days), treatment period (24 weeks), and follow-up period (72 weeks).

This phase II study is a randomized, double-blind study that seeks to evaluate the clinical effects and safety of fucoidan in the treatment of cancer patients with stage III/IV head and neck squamous cell carcinoma.~Patients will be centrally randomized in a 1:1 ratio to receive either Fucoidan or placebo (potato starch) Eligible subjects will receive fucoidan twice daily (BID) in combination with chemotherapy and radiation therapy over a 24-week treatment period.~Clinical effects and safety parameters for all subjects who complete the treatment period will be followed for an additional 72 weeks after the treatment period.

Breast enlargement reductions are frequent interventions. One of the main issue associated with this surgery remains the ransom scar, wide at the periareolar level, vertical at the subareolar level and in the submammary groove. In addition, this intervention remains subject to the vagaries of hypertrophic or even keloid scarring, especially in young women.~The current research project is based on the hypothesis that the same technique could be used in the context of a reduction of breast enlargement on a smaller surface allowing the determination of a perimammary halo of scar retraction. The project consists in removing a breast disc at the base, thus causing a sagging skin cut of 2 to 3 cm but this time, circular.~The expected result is to achieve a reduction in breast enlargement with no visible scar, using Da Vinci Xi robot.

Breast enlargement reductions are frequent interventions. One of the main issue associated with this surgery remains the ransom scar, wide at the periareolar level, vertical at the subareolar level and in the submammary groove.~The expected result is to achieve a reduction in breast enlargement with no visible scar using Da Da Vinci Xi robot.

This study is a 56-week, open-label, one-arm extension study in participants who have completed the CRTH258A2303 study (TALON). Participants who consent and meet all the inclusion and none of the exclusion criteria will be enrolled into this extension study and receive brolucizumab 6 mg in a TtC regimen, irrespective of the treatment received in the core study.~It is estimated that 622 participants from the core study will enter the extension study (10% dropout rate expected). The maximum study duration for one participant is 56 weeks, including post-treatment follow-up.~There will be two periods in this study:~Treat-to-Control treatment period: from Baseline (Day 1) to Week 52~Post-treatment follow-up period: from Week 52 to Week 56.~All participants will be treated with brolucizumab regardless of their treatment in the TALON study (brolucizumab or aflibercept).~Treatment intervals can then be extended by 4 weeks at a time based on the investigator's judgment of visual and/or anatomic outcomes. The treatment intervals should be by 4 weeks at a time if disease activity recurs.

The purpose of this extension study is to evaluate the efficacy and safety of brolucizumab used in a Treat-to-Control-regimen for treatment of patients with neovascular age-related macular degeneration who have completed the CRTH258A2303 (TALON) study. The main objective is to assess brolucizumab's potential for long durability up to 20 weeks.~All eligible participants will be treated with brolucizumab regardless of their treatment in the TALON study.~The study period is 56 weeks including post-treatment follow-up.