***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective To evaluate the role of genetic polymorphisms of the bactericidal permeability increasing protein ( BPI ) in pediatric patients with sepsis . Design Prospect i ve , single-center , case-control study at the pediatric intensive care unit ( PICU ) of a university hospital . Patients 345 consecutive pediatric patients admitted to the PICU with fever , systemic inflammatory response syndrome ( SIRS ) , sepsis , severe sepsis , septic shock , or multiple organ distress syndrome ( MODS ) . Interventions DNA was isolated and two BPI gene polymorphisms BPI ( G545 > C ) Taq and BPI ( A645 > G ) 216 were studied in patients and compared with healthy controls . Measurements and results Genetic analysis of the BPI Taq gene revealed significant differences between healthy controls and the subgroup of febrile patients ( p = 0.0243 ) , the subgroup of SIRS and sepsis ( p = 0.0101 ) , and the subgroup of severe sepsis , septic shock , and MODS ( p = 0.0027 ) , respectively . No statistically significant differences for the BPI 216 gene polymorphism were found between patient and healthy control groups . A statistically significant predisposition to Gram-negative sepsis in patients carrying the BPI Taq GG variant together with the BPI 216 AG or GG variant was revealed ( p = 0.0081 ) , and these haplotypes were also associated with death due to sepsis-related complications . Conclusion BPI Taq gene polymorphism is the accurate predictor of the severity of sepsis in children admitted to the PICU Objective : We compared efficacy of dopamine and epinephrine as first-line vasoactive therapy in achieving resolution of shock in fluid-refractory hypotensive cold septic shock . Design : Double-blind , pilot , r and omized controlled study . Setting : Pediatric emergency and ICU of a tertiary care teaching hospital . Patients : Consecutive children 3 months to 12 years old , with fluid-refractory hypotensive septic shock , were enrolled between July 2013 and December 2014 . Intervention : Enrolled children were r and omized to receive either dopamine ( in incremental doses , 10 to 15 to 20 & mgr;g/kg/min ) or epinephrine ( 0.1 to 0.2 to 0.3 & mgr;g/kg/min ) till end points of resolution of shock were achieved . After reaching maximum doses of test drugs , open-label vasoactive was started as per discretion of treating team . Primary outcome was resolution of shock within first hour of resuscitation . The study was registered ( CTRI/2014/02/004393 ) and was approved by institute ethics committee . Measurements and Main Results : We enrolled 29 children in epinephrine group and 31 in dopamine group .  Resolution of shock within first hour was achieved in greater proportion of children receiving epinephrine ( n = 12 ; 41 % ) than dopamine ( n = 4 ; 13 % ) ( odds ratio , 4.8 ; 95 % CI , 1.3–17.2 ; p = 0.019 ) ; the trend persisted even at 6 hours ( 48.3 % vs 29 % ; p = 0.184 ) . Children in epinephrine group had lower Sequential Organ Function Assessment score on day 3 ( 8 vs 12 ; p = 0.05 ) and more organ failure – free days ( 24 vs 20 d ; p = 0.022 ) . No significant difference in adverse events ( 16.1 % vs 13.8 % ; p = 0.80 ) and mortality ( 58.1 % vs 48.3 % ; p = 0.605 ) was observed between the two groups . Conclusion : Epinephrine is more effective than dopamine in achieving resolution of fluid-refractory hypotensive cold shock within the first hour of resuscitation and improving organ functions We aim ed to investigate whether nuclear factor kappa-B activation , as evaluated by gene expression of its inhibitor ( I-κBα ) and cytokine serum levels , was associated with myocardial dysfunction and mortality in children with septic shock . Twenty children with septic shock were prospect ively enrolled and grouped according to ejection fraction ( EF ) < 45 % ( group 1 ) or EF ≥45 % ( group 2 ) on the first day after admission to the pediatric intensive care unit . No interventions were made . In the first day , patients from group 1 ( n = 6 ) exhibited significantly greater tumor necrosis factor-alpha ( TNF-α ) and interleukin (IL)-10 plasma levels . However , I-κBα gene expression was not different in both groups . Mortality and number of complications were significantly greater in group 1 . Patients who died had greater plasma concentrations of TNF-α . In conclusion , TNF-α and IL-10 are involved in myocardial dysfunction accompanying septic shock in children , and TNF-α is associated with mortality This prospect i ve study was conducted to determine the frequency , etiology , type and outcome of shock  in hospitalized children in the age group of 1 month to 15 years . There were 98 cases of shock , constituting 4.3 % out of total admissions . Mean age was 2.8 + /-3.4 years . Maximum number of patients ( 39 ) was seen in infancy . Hypovolemic shock due to acute diarrheal disease was the commonest type ( 45.9 % ) followed by septic , cardiogenic and distributive shock . Compensated stage was common in hypovolemic shock ( 88.9 % ) whereas majority of patients with septic shock ( 73.5 % ) presented in decompensated stage . Overall survival was 73.6 % . The survival rate was best in hypovolemic shock ( 97.7 % ; ) followed by septic(53.3 % ) and cardiogenic shock(43.7 % ) . Inotropes and ventilatory support were required in 46 % and 23 % patients , respectively . Diagnosis and management of shock in compensated stage carried better prognosis than in uncompensated shock irrespective of the age of the patient OBJECTIVE To determine whether plasma filtration improves 28-day survival in infants and children with severe sepsis . DESIGN A multicentre r and omised controlled trial . SETTING Paediatric intensive care units in teaching hospitals . PATIENTS Forty-eight infants and children with severe sepsis . INTERVENTIONS Patients were r and omly assigned to receive plasma filtration ( n = 25 ) or st and ard therapy ( n = 23 ) for the treatment of septic shock . The primary outcome measure was 28-day survival . Secondary outcome measures included the number of failed organ systems on Day 7 , a requirement for extracorporeal membrane oxygenation ( ECMO ) , and the modified Glasgow outcome score ( MGOS ) at 6 months ( where 1 is normal and 6 is dead ) . RESULTS The trial was stopped early due to poor recruitment . Patients in the plasma filtration group had higher initial disease severity as measured by serum lactate level , inotrope score and MGOS . Ten ( 40 % ) children died in the plasma filtration group and 4 ( 17 % ) died in the control group . With intention-to-treat analysis and adjustment for lactate level , ventilation index , inotrope score and MGOS at admission using logistic regression , the odds ratio for death with plasma filtration was 1.20 ( 95 % CI , 0.23 - 6.20 ; P = 0.82 ) . The median number of failing organ systems at 7 days was 2 ( interquartile range [ IQR ] , 1 - 4 ) in the plasma filtration group versus 2 ( IQR , 1 - 3 ) in the control group . Two children in the plasma filtration group required ECMO for 2.5 and 123 hours , and one child in the control group required ECMO for 45 hours . The median MGOS at 6 months was 4 ( IQR , 2 - 6 ) in the plasma filtration group and 2 ( IQR , 1 - 4 ) in the control group . CONCLUSIONS Our study did not recruit enough patients to test the hypothesis that addition of plasma filtration to our st and ard care protocol reduces 28-day mortality in children with severe sepsis . However , mortality in the treatment and control groups was not significantly different after adjustment for severity of illness at the time of r and omisation Objectives : There is paucity of data on the magnitude of absolute or relative adrenal insufficiency in septic shock , especially in children . We conducted a prospect i ve study to determine the prevalence of adrenal insufficiency in children with septic shock using a low-dose Synacthen ( 1 & mgr;g ) stimulation test . Design : Cross-sectional study . Setting : Pediatric intensive care unit in a tertiary care hospital in northern India . Patients : Children with septic shock . Interventions : None . Measurements and Main Results : We performed cortisol estimation at baseline and after low-dose Synacthen ( 1 & mgr;g ) stimulation at 30 and 60 mins in children with fluid refractory septic shock admitted to our pediatric intensive care unit .  Basal cortisol levels < 7 & mgr;g/dL and peak cortisol level < 18 & mgr;g/dL were used to define adrenal insufficiency . An increment of < 9 & mgr;g/dL after stimulation was used to diagnose relative adrenal insufficiency . As there is lack of consensus on the cutoffs for defining relative adrenal insufficiency using the low-dose adrenocorticotropic hormone test , we evaluated different cutoff values ( increment at 30 mins , increment at 60 mins , greater of the two increments ) and evaluated their association with the incidence of catecholamine refractory shock and outcomes . Children with sepsis but without septic shock were sample d for baseline cortisol levels as a comparison . Thirty children ( 15 girls ) with septic shock were included ; median age ( 95 % confidence interval ) was 36.5 ( 9.39– 58.45 ) months . Median Pediatric Risk of Mortality score was 22.5 ( 14.13–24.87 ) . Fifteen ( 50 % ) children survived . The median ( 95 % confidence interval ) cortisol values at baseline and 30 mins and 60 mins after stimulation were 71 ( 48.74–120.23 ) & mgr;g/dL , 78.1 ( 56.9–138.15 ) & mgr;g/dL , and 91 ( 56.17–166.44 ) & mgr;g/dL , respectively . The median baseline cortisol value in age- and gender-matched children with sepsis was 11.5 & mgr;g/dL. None of the children with septic shock fulfilled the criteria for absolute adrenal insufficiency . However , nine ( 30 % ) patients had relative adrenal insufficiency ( increment in cortisol < 9 & mgr;g/dL ) . Of these nine patients , five ( 56 % ) died ; of the 21 patients with a greater increment in cortisol after stimulation , ten died ( p = .69 ) . Compared with patients in septic shock with normal adrenal reserve , those with relative adrenal insufficiency had a higher incidence of catecholamine refractory shock ( p = .019 ) but no difference in mortality rate ( p = .69 ) . On the sensitivity and specificity analysis using various cutoffs of increment , the best discrimination for catecholamine refractory shock was obtained with a peak increment < 6 & mgr;g/dL. Conclusions : Relative adrenal insufficiency is common in children with septic shock and is associated with catecholamine refractory shock Objective : Stratification with an effective outcome biomarker could improve the design of interventional trials in pediatric septic shock . The objective of this study was to test the usefulness of chemokine ( C-C motif ) lig and 4 as an outcome biomarker for mortality in pediatric septic shock . Design : A cross-sectional , observational study . Setting : Eighteen pediatric intensive care units in the United States . Patients : One hundred fifty-six pediatric patients with septic shock . Interventions : Serum sample s were obtained within 24 hrs of admission to the pediatric intensive care unit . Serum levels of chemokine ( C-C motif ) lig and 4  were measured by enzyme-linked immunosorbent assay and compared with mortality in a training set of 34 patients . These data were used to generate a cutoff value whose usefulness was evaluated through prospect i ve application — without post hoc modification — to a larger validation set of 122 patients . Measurements and Main Results : On inspection of the training set data , a cutoff value of 140 pg/mL was chosen . When applied to the validation set , serum chemokine ( C-C motif ) lig and 4 levels > 140 pg/mL yielded a sensitivity of 92 % and a specificity of 40 % for mortality . A serum level of ≤140 pg/mL had a negative predictive value for mortality of 98 % . Conclusions : A serum level of chemokine ( C-C motif ) lig and 4 of ≤140 pg/mL , when obtained within 24 hrs of admission , predicts a very high likelihood of survival in pediatric septic shock . Exclusion of patients with a chemokine ( C-C motif ) lig and 4 level of ≤ 
    Output:
    
Time-trend analysis showed higher CFRs over time in developing countries than developed countries .
Conclusions and Relevance Despite the declining trend of pediatric severe sepsis and septic shock CFRs , the disparity between developing and developed countries persists .