table_1.DOCX

Objectives<p>Our objective was to compare the prevalence and outcomes of pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria and Berlin definitions.</p>Methods<p>We screened case records of all children aged 1 month to 17 years of age admitted to the Pediatric Intensive Care Unit (PICU) over a 3-year period (2015–2017) for presence of any respiratory difficulty at admission or during PICU stay. We applied both PALICC and Berlin criteria to these patients. Data collection included definition and outcome related variables. Data were compared between the “PALICC only group” and the “Berlin with or without PALICC” group using Stata 11.</p>Results<p>Of a total of 615 admissions, 246 were identified as having respiratory difficulty at admission or during PICU stay. A total of 61 children (prevalence 9.9%; 95% CI: 7.8–12.4) fulfilled the definition of acute respiratory distress syndrome (ARDS) with either of the two criteria. While 60 children (98%) fulfilled PALICC criteria, only 26 children (43%) fulfilled Berlin definition. There was moderate agreement between the two definitions (Kappa: 0.51; 95% CI: 0.40–0.62; observed agreement 85%). Greater proportion of patients had severe ARDS in the “Berlin with or without PALICC group” as compared to the “PALICC only” group (50 vs. 19%). There was no difference between the groups with regard to key clinical outcomes such as duration of ventilation (7 vs. 8 days) or mortality [51.4 vs. 57.7%: RR (95% CI): 0.99 (0.64–1.5)].</p>Conclusion<p>In comparison to Berlin definition, the PALICC criteria identified more number of patients with ARDS. Proportion with severe ARDS and complications was greater in the “Berlin with or without PALICC” group as compared to the “PALICC only” group. There were no differences in clinical outcomes between the groups.</p

Severe dengue disease occurs in both primary and secondary infections.

<p>(A) Patients with primary and secondary dengue infections (N = 97) were stratified based on severity at the time of admission. DI–Dengue infection, DW- Dengue with Warning signs and SD–Severe Dengue. Patients with primary and secondary dengue infections with day of fever < 3 (B), <4 (C) or <5 (D) were stratified based on severity at the time of admission (N = 36, 45 and 64 respectively).</p

Transient increase in intermediate monocytes at early time points in DENV infection and monocyte infection with DENV.

<p>(A) Representative plots showing analytical multicolor flow cytometry of classical, non-classical and intermediate monocytes based on CD14 and CD16 expression <i>ex vivo</i> from PBMCs isolated from DENV-infected patients at indicated days of fever. (B) Cumulative frequencies of CD14+CD16+ intermediate monocytes as shown in scatter plot above. Unpaired, two-tailed t test was used for statistical analysis and P values were interpreted as * P<0.01 and ** P<0.001. (C) Ex vivo intracellular DENV staining was performed on total PBMCs stained with surface receptor antibodies for CD3, CD19, CD14, CD16 along with fixable viable dye to exclude dead cells. Representative histograms show intensity of DENV staining within each of the gated populations described. (D) Cumulative mean fluorescent intensities of DENV staining in the indicated cell populations (N = 31) is shown. Error bars represent Mean wth SD.</p

Multivariate selection of features of dengue severity and recovery.

<p>(A) The boxplots represent the distribution of variable importances after adjusting for the interactions among the variables. The minimal set of selected features (green) are the ones whose medians lie above the maximal possible median importance in the shadow data (see text for description). Eight parameters out of all available clinical and biochemical parameters were selected as important for prediction of the severity classes (SD, DW and DI). (B) Identifying markers of recovery from SD using the Boruta algorithm. All parameters from SD patients whose disease status improved clinically from first to second bleed were considered for analysis. Three delta parameters out of all the delta (absolute and relative changes across the first and second bleed, see text) were significantly important for prediction of recovery from SD and were consistent with findings in the univariate analysis.</p

Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India—Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity

<div><p>Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14⁺CD16⁺ intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis.</p></div

Cytokine profile in dengue patients on indicated days of fever and disease severity.

<p>Plasma levels of cytokines/chemokines/inflammatory mediators in dengue patients were measured by multiplex magnetic bead assays. (A) IFN-α (B) IFN-γ (C) IL-6, (D) IL-7, (E) IL-8, (F) IL-10 (G) MCP-1 (H) sCD40L, (I) TNF-α and (J) VEGF. Data are segregated into days of fever and disease severities within each group. Median value of cytokines in dengue illness (DI), dengue with warning signs (DW) and severe dengue (SD) is indicated by the respective color-coded bar. Dotted line represents the limit of detection. Statistical significance was determined by Mann-Whitney test.</p

Clinical and laboratory data on the day of admission of patients with dengue illness.

<p>Clinical and laboratory data on the day of admission of patients with dengue illness.</p

Quantitation of inflammatory mediators in dengue patients with different disease severities.

<p>Quantitation of inflammatory mediators in dengue patients with different disease severities.</p

Disease severity of enrolled patients at the time of admission (bleed 1) and repeat bleeds at around 48 h post-admission (bleed 2) with primary and secondary dengue infections.

<p>Disease severity of enrolled patients at the time of admission (bleed 1) and repeat bleeds at around 48 h post-admission (bleed 2) with primary and secondary dengue infections.</p

Age distribution of chikungunya patients at hospitals in Karnataka and Rajasthan, June 2008 through May 2009.

<p>Age distribution of chikungunya patients at hospitals in Karnataka and Rajasthan, June 2008 through May 2009.</p