Objectives: Sepsis-3 consensus suggests “the need to develop similar updated definitions for pediatric populations.” Sequential organ failure assessment (SOFA) and systemic inflammatory response syndrome (SIRS) criteria are two systems widely used to define the status of infection. However, it is still unclear whether SOFA is more accurate than SIRS in predicting children mortality in low- and middle-income countries. Thus, we validated the accuracy of age-adapted SOFA and SIRS in predicating the poor prognosis of infected children in China's pediatric intensive care unit (PICU). Methods: We performed a retrospective and observational cohort study of children admitted for infection to PICU in the hospital between January 1, 2009 and December 31, 2017. The indexes within 24 h after intensive care unit (ICU) admission were analyzed according to age-adapted SOFA and SIRS, and all data were sourced from the hospital's electronic health record database. The prognosis was illustrated with primary outcome and secondary outcome. Primary outcome referred to in-hospital mortality, and secondary outcome to in-hospital mortality or ICU length of stay ≥ 7 days. The predictive power of age-adapted SOFA and SIRS was compared using crude and adjusted area under the receiver operating characteristic curve (AUROC). Results: Of 1,831 PICU-admitted children due to infection, 164 (9.0%) experienced primary outcome, and 948 (51.8%) secondary outcome. Of 164 deaths, 65.9% were males (median age of 7.53 months, range of 2.67–41.00 months). Children who scored ≥ 2 in age-adapted SOFA or met two SIRS criteria accounted for 92.5% and 73.3%, respectively. In addition, age-adapted SOFA score of ≥2 predicted adverse outcome more accurately than pediatric SIRS (adjusted AUROC, 0.753; 0.713–0.796 vs. 0.674; 0.631–0.702; P < 0.001). Conclusion: Compared with SIRS criteria, age-adapted SOFA score of ≥ 2 enjoys a more accuracy in predicting in-hospital mortality of PICU-admitted children, and a higher sensitivity in identifying children with severe infection.

BackgroundRecent studies have proved that autophagy dysfunction in proinflammatory cells is involved in tissue damage and an excessive inflammatory response in sepsis. In the present study, we identified that the human antimicrobial peptide LL-37 facilitates resistance to DNase II-induced mitochondrial DNA (mtDNA) degradation and subsequent autophagy.Material/MethodsWe found higher serum levels of LL-37 in patients with severe sepsis compared to that in patients with mild sepsis. Neutrophils isolated from mice with sepsis after treatment with Cramp-mtDNA produced an excess of proinflammatory cytokines, including IL-1β, IL-6, IL-8, MMP-8, and TNF-α. Cramp-mtDNA in the lung samples from model animals with sepsis was detected by immunohistochemical staining.ResultsExogenous delivery of Cramp-mtDNA complex significantly exacerbated lung inflammation but the antibody against Cramp-mtDNA attenuated the excessive inflammatory response in LPS-induced acute lung injury. The expression of proinflammatory cytokines in lungs was upregulated and downregulated after treatment with the complex and antibody, respectively. LC-3 expression in 16HBE cells increased after LPS induction, irrespective of stimulation with LL-37.ConclusionsThese data show that LL-37 treatment worsens local inflammation in sepsis-induced acute lung injury by preventing mtDNA degradation-induced autophagy.

Purpose Accumulating evidence demonstrates that genetic susceptibility genes can be used as biomarkers to assess sepsis susceptibility, and genetic variation is associated with susceptibility and clinical outcomes in patients with sepsis and inflammatory disease. Although studies have shown that the lncRNA CCAT2 is involved in inflammatory diseases, it remains unclear whether CCAT2 gene polymorphisms are associated with susceptibility to inflammatory diseases, such as sepsis, in children. Methods We genotyped the rs6983267 CCAT2 polymorphism in 474 cases (pediatric sepsis) and 678 controls using TaqMan methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of associations. Results Our results indicate that the rs6983267 T > G polymorphism is significantly associated with an increased risk of sepsis in children (TG and TT: adjusted OR = 1.311, 95% CI = 1.016–1.743, GG and TT: adjusted OR = 1.444, 95% CI = 1.025–2.034 dominant model: GG/TG vs TT adjusted OR = 1.362, 95% CI = 1.055–1.756). Furthermore, the risk effect was more pronounced in children younger than 60 months who were male and who had sepsis. Conclusion We found that the CCAT2 gene polymorphism rs6983267 T > G may be associated with an increased risk of pediatric sepsis in southern China. A larger multicenter study should be performed to confirm these results.

Background Severe fatal human adenoviral (HAdV) pneumonia is associated with significant mortality and no effective drug is available for clinical therapy. We evaluated the association and safety of high titer neutralizing antibodies (NAbs) plasma in pediatric patients with severe fatal HAdV pneumonia. Methods A retrospective cohort study was performed between January 2016 to June 2021 in pediatric intensive care unit. Pediatric patients with severe fatal HAdV pneumonia were included and divided into plasma group (conventional treatment plus high titer NAbs plasma treatment) and control group (conventional treatment alone). The primary outcome was mortality in hospital. Secondary outcomes were the duration of fever after adenovirus genotype determined, duration of invasive mechanical ventilation, length of hospital stay. T-test, Mann-Whitney U-test, chi-square test, univariable and multivariable logistic regression analysis, Kaplan-Meier method and log-rank test were adopted to compare differences between two groups. Results A total of 59 pediatric patients with severe fatal HAdV pneumonia were enrolled. They were divided into plasma group (n = 33) and control group (n = 26). The mortality in hospital was 28.8% (17/ 59). Significantly fewer patients progressed to death in plasma group than control group (18.2% vs 42.3%, p = 0.042). Sequential organ failure assessment (SOFA) score, oxygen index (OI) and high titer NAbs plasma treatment were included in multivariable logistic regression analysis for mortality risk factors. Consequentially, SOFA score (Hazard Ratio [HR] 7.686, 95% Confidence Interval [CI] 1.735–34.054, p = 0.007) and without high titer NAbs plasma treatment (HR 4.298, 95%CI 1.030–17.934, p = 0.045) were significantly associated with mortality. In addition, high titer NAbs plasma treatment were associated with faster temperature recovering in survivors (p = 0.031). No serious adverse effects occurred. Conclusions Administration of high titer NAbs plasma were associated with a lower hazard for mortality in pediatric patients with severe fatal HAdV pneumonia. For survivors, high titer NAbs plasma treatment shorten the duration of fever.