The efficacy and therapeutic mechanisms of continuous renal replacement therapy (CRRT) for improvement of oxygenation in acute respiratory distress syndrome (ARDS) remain controversial. These questions were addressed by retrospective analysis of severe ARDS patients admitted to the pediatric intensive care unit of our hospital from 2009 to 2015 who received high-volume continuous veno-venous hemofiltration during mechanical ventilation. There was a significant improvement in partial oxygen pressure/fraction of inspired oxygen (PaO2/FiO2) 24 hours after CRRT onset compared with baseline (median change = 51.5; range = −19 to 450.5; P < .001) as well as decreases in FiO2, peak inspiratory pressure, positive end-expiratory pressure, and mean airway pressure (P < .05). The majority of patients had a negative fluid balance after 24 hours of CRRT. White blood cell (WBC) count decreased in the subgroup with high baseline WBC count (P < .05). PaO2/FiO2 was higher in ARDS patients with extrapulmonary etiology than in those with pulmonary etiology (P < .05). Improvement in oxygenation is likely related to both restoration of fluid balance and clearance of inflammatory mediators.

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.

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Background Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China. Methods We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children’s Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis. Results Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community. Conclusion Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

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.

Human adenovirus (HAdV) is one of the most common respiratory pathogens affecting children. HAdV infection has high morbidity and mortality, and it may lead to severe complications and long-term pulmonary sequelae. However, the pathogenesis of pediatric HAdV-7-induced sepsis remains unclear. The analysis of DNA methylation profiles in peripheral blood is attracting increasing attention as an effective method for investigating the pathogenesis of various diseases and identifying biomarkers of disease progression. Here, we performed reduced representation bisulfite sequencing to analyze DNA methylation in peripheral blood samples collected from 11 children with HAdV-7-induced sepsis and 5 healthy children. The Metilene software was used to analyze differential methylation in the two groups. We also performed functional enrichment analysis of the genes with differentially methylated regions (DMRs). We detected 1,138 DMRs between the two groups. Additionally, 122 DMRs were detected between the HAdV-7-induced sepsis survivor and non-survivor groups. After screening based on biological and clinical significance, we found that a group of genes (KCNQ1OT1, KPNB1, GRB10, HOXA5, HOXA4, and BCL9L) with differential methylation played an essential role in Wnt signaling. Additionally, genes related to the Wnt/β-catenin signaling pathway, such as MEG3, GNAS-AS1, and GNAS, exhibited differential methylation in the survivor and non-survivor groups. Our data suggest that specific patterns of DNA methylation are associated with the occurrence and progression of HAdV-7-induced sepsis. Wnt signaling was also affected by the changes in methylation. Thus, we identified potential biomarkers and therapeutic targets for pediatric HAdV-7-induced sepsis.