Np Boeddha

Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units : A prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS)

BackgroundSepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability.MethodsData were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis.ResultsPatients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P < 0.01) and illness severity as measured by Pediatric Index of Mortality (PIM2) score (mortality OR 2.8, 95% CI 1.3–6.1, P < 0.01; disability OR 3.4, 95% CI 1.8–6.4, P < 0.001).ConclusionsDespite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.

Differences in IgG Fc glycosylation are associated with outcome of pediatric meningococcal sepsis

ABSTRACT Pediatric meningococcal sepsis often results in morbidity and/or death, especially in young children. Our understanding of the reasons why young children are more susceptible to both the meningococcal infection itself and a more fulminant course of the disease is limited. Immunoglobulin G (IgG) is involved in the adaptive immune response against meningococcal infections, and its effector functions are highly influenced by the glycan structure attached to the fragment crystallizable (Fc) region. It was hypothesized that IgG Fc glycosylation might be related to the susceptibility and severity of meningococcal sepsis. Because of this, the differences in IgG Fc glycosylation between 60 pediatric meningococcal sepsis patients admitted to the pediatric intensive care unit and 46 age-matched healthy controls were investigated, employing liquid chromatography with mass spectrometric detection of tryptic IgG glycopeptides. In addition, Fc glycosylation profiles were compared between patients with a severe outcome (death or the need for amputation) and a nonsevere outcome. Meningococcal sepsis patients under the age of 4 years showed lower IgG1 fucosylation and higher IgG1 bisection than age-matched healthy controls. This might be a direct effect of the disease; however, it can also be a reflection of previous immunologic challenges and/or a higher susceptibility of these children to develop meningococcal sepsis. Within the young patient group, levels of IgG1 hybrid-type glycans and IgG2/3 sialylation per galactose were associated with illness severity and severe outcome. Future studies in larger groups should explore whether IgG Fc glycosylation could be a reliable predictor for meningococcal sepsis outcome. IMPORTANCE Meningococcal sepsis causes significant mortality and morbidity worldwide, especially in young children. Identification of risk factors for a more fulminant infection would help to decide on appropriate treatment strategies for the individual patients. Immunoglobulin G (IgG) plays an essential role in humoral immune responses and is involved in the adaptive immune response against meningococcal infections. Of great influence on the receptor affinity of IgG is the N-glycan on its fragment crystallizable (Fc) portion. In the present study, we analyzed IgG glycosylation during the fast development of meningococcal sepsis in children, and we were able to identify glycosylation features that are different between meningococcal sepsis patients and healthy controls. These features might be indicative of a higher susceptibility to meningococcal sepsis. In addition, we found glycosylation features in the patients that were associated with illness severity and severe disease outcome, having the potential to serve as a disease outcome predictor. IMPORTANCE Meningococcal sepsis causes significant mortality and morbidity worldwide, especially in young children. Identification of risk factors for a more fulminant infection would help to decide on appropriate treatment strategies for the individual patients. Immunoglobulin G (IgG) plays an essential role in humoral immune responses and is involved in the adaptive immune response against meningococcal infections. Of great influence on the receptor affinity of IgG is the N-glycan on its fragment crystallizable (Fc) portion. In the present study, we analyzed IgG glycosylation during the fast development of meningococcal sepsis in children, and we were able to identify glycosylation features that are different between meningococcal sepsis patients and healthy controls. These features might be indicative of a higher susceptibility to meningococcal sepsis. In addition, we found glycosylation features in the patients that were associated with illness severity and severe disease outcome, having the potential to serve as a disease outcome predictor.

Translating Sepsis-3 Criteria in Children: Prognostic Accuracy of Age-Adjusted Quick SOFA Score in Children Visiting the Emergency Department With Suspected Bacterial Infection

Background: Recent attempts to translate Sepsis-3 criteria to children have been restricted to PICU patients and did not target children in emergency departments (ED). We assessed the prognostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) and compared the performance to SIRS and the quick Pediatric Logistic Organ Dysfunction-2 score (qPELOD-2). We studied whether the addition of lactate (qSOFA-L) would increase prognostic accuracy. Methods: Non-academic, single-center, retrospective study in children visiting the ED and admitted with suspected bacterial infection between March 2013 and January 2018. We defined suspected bacterial infection as initiation of antibiotic therapy within 24 h after ED entry. Age-adjusted qSOFA, SIRS, qPELOD-2, and qSOFA-L scores were compared by area under the receiver operating characteristics curve (AUROC) analysis. Primary outcome measure was PICU transfer and/or mortality and secondary outcome was prolonged hospital length of stay. Results: We included 864 ED visits [474 (55%) male; median age 2.5 years; IQR 9 months-6 years], of which 18 were transferred to a PICU and 6 ended in death [composite outcome PICU transfer and/or mortality; 23 admissions (2.7%)]. 179 (22.2%) admissions resulted in prolonged hospital length of stay. PICU transfer and/or death was present in 22.5% of visits with qSOFA≥2 (n = 40) compared to 2.0% of visits with qSOFA<2 (n = 444) (p < 0.01). qSOFA tends to be the best predictor of PICU transfer and/or mortality (AUROC 0.72 (95% CI, 0.57–0.86) compared to SIRS [0.64 (95% CI, 0.53–0.74), p = 0.23] and qPELOD-2 [0.60 (95% CI, 0.45–0.76), p = 0.03)]. Prolonged hospital length of stay was poorly predicted by qSOFA (AUROC 0.53, 95% CI 0.46–0.59), SIRS (0.49, 95% CI 0.44–0.54), and qPELOD-2 (0.51, 95%CI 0.45–0.57). qSOFA-L resulted in an AUROC of 0.67 (95% CI, 0.50–0.84) for PICU transfer and/or mortality and an AUROC of 0.56 (95% CI, 0.46–0.67) for prolonged hospital length of stay. Conclusion: The currently proposed bedside risk-stratification tool of Sepsis-3 criteria, qSOFA, shows moderate prognostic accuracy for PICU transfer and/or mortality in children visiting the ED with suspected bacterial infection. The addition of lactate did not improve prognostic accuracy. Future prospective studies in larger ED populations are needed to further determine the utility of the qSOFA score.

Gene Variations in the Protein C and Fibrinolytic Pathway: Relevance for Severity and Outcome in Pediatric Sepsis

&NA; The host response to infection involves complex interplays between inflammation, coagulation, and fibrinolysis. Deregulation of hemostasis and fibrinolysis are major causes of critical illness and important determinants of outcome in severe sepsis. The hemostatic responses to infection vary widely between individuals, and are in part explained by polymorphisms in genes responsible for the protein C and fibrinolytic pathway. This review gives an overview of genetic polymorphisms in the protein C and fibrinolytic pathway associated with susceptibility and severity of pediatric sepsis. In addition, genetic polymorphisms associated with adult sepsis and other pediatric thromboembolic disorders are discussed, as these polymorphisms might be candidates for future molecular genetic research in pediatric sepsis.

Circadian variation of plasminogen-activator-inhibitor-1 levels in children with meningococcal sepsis

Objective To study whether the circadian variation of plasminogen-activator-inhibitor-1 (PAI-1) levels, with high morning levels, is associated with poor outcome of children with meningococcal sepsis presenting in the morning hours. Design Retrospective analysis of prospectively collected clinical and laboratory data. Setting Single center study at Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands. Subjects 184 patients aged 3 weeks to 18 years with meningococcal sepsis. In 36 of these children, PAI-1 levels at admission to the PICU were measured in plasma by ELISA. Interventions None. Measurements and main results Circadian variation was studied by dividing one day in blocks of 6 hours. Patients admitted between 6:00 am and 12:00 am had increased illness severity scores and higher PAI-1 levels (n = 9, median 6912 ng/mL, IQR 5808–15600) compared to patients admitted at night (P = 0.019, n = 9, median 3546 ng/mL, IQR 1668–6118) or in the afternoon (P = 0.007, n = 7, median 4224 ng/mL, IQR 1804–5790). In 184 patients, analysis of circadian variation in relation to outcome showed more deaths, amputations and need for skin grafts in patients admitted to the PICU between 6:00 am and 12:00 am than patients admitted during the rest of the day (P = 0.009). Conclusions Circadian variation of PAI-1 levels is present in children with meningococcal sepsis and is associated with illness severity, with a peak level in the morning. Whether circadian variation is an independent risk factor for morbidity and mortality in meningococcal sepsis needs to be explored in future studies.