Daily Sepsis Research Analysis

BACKGROUND: Early enteral nutrition (EEN) has been proposed to improve clinical outcomes in critically ill patients with sepsis. However, the survival benefit of EEN remains uncertain. This meta-analysis aimed to evaluate the effect of EEN on all-cause mortality in adult patients with sepsis. METHODS: A systematic search of PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang was conducted up to May 25, 2025. Randomized controlled trials (RCTs) comparing EEN (initiated within 24-48 h of admission or sepsis diagnosis) vs. non-early enteral nutrition (delayed enteral nutrition or parenteral nutrition) in adult septic patients were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model by incorporating the influence of potential heterogeneity. RESULTS: Ten RCTs involving 582 patients (281 EEN, 301 controls) were included. Compared to controls, EEN significantly reduced all-cause mortality (OR: 0.59; 95% CI 0.37-0.94; p = 0.03), with no significant statistical heterogeneity (I CONCLUSIONS: EEN significantly reduces mortality in adult patients with sepsis. High-quality RCTs are warranted to determine the optimal regimen of EEN in this population.

Aging substantially increases susceptibility to sepsis, yet the underlying mechanisms of immune dysfunction in the elderly remain incompletely understood. Polymicrobial sepsis was induced in young and aged male mice via cecal ligation and puncture (CLP). Bone marrow from four groups (Y-Sham, n = 2; Y-CLP, n = 3; A-Sham, n = 2; A-CLP, n = 3) was analyzed by single-cell RNA sequencing and intercellular communication inferred via CellChat. Age-related immune changes were evaluated, and Transwell assays were used to assess myeloid cell migration. Aged septic mice showed worsened organ damage and systemic inflammation, with reduced adaptive (18.7% vs. 41.3%) and increased innate immunity (58.8% vs. 37.7%, A-CLP vs. Y-CLP). Neutrophil chemotaxis was impaired; monocytes and macrophages adopted a hyperinflammatory yet functionally exhausted phenotype; dendritic cells showed increased antigen presentation with diminished mobility; B cell maturation was disrupted with regression to earlier developmental stages; and T cells shifted toward stress-responsive and regulatory programs. We identified a cluster-specific expansion of HSCs in aged sepsis (39.8% vs. 31.2% in A-CLP vs. Y-CLP) with impaired Lgals9-Cd44-mediated intercellular communication. Myeloid cell migration was impaired in A-CLP but partially restored by Lgals9-Cd44 activation. This study presents a comprehensive single-cell map of bone marrow immune dysfunction in aged sepsis and identifies impaired HSC-myeloid communication as a critical mechanism driving immune failure. Therapeutically targeting the Lgals9-Cd44 axis may restore immune coordination in elderly sepsis, although its clinical feasibility and safety remain to be validated.

IMPORTANCE: Female sex has been identified as a risk factor for mortality in Staphylococcus aureus bloodstream infection (SA-BSI). It is unknown whether this association extends to bloodstream infections with other bacterial species. OBJECTIVE: To investigate whether female sex is associated with increased mortality risk among patients with gram-negative bloodstream infection (GN-BSI). DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception to January 8, 2025. STUDY SELECTION: Study inclusion criteria were randomized or observational studies assessing adults with GN-BSI that included at least 100 patients and reported mortality at or before 90 days following GN-BSI, with mortality stratified by sex and, when applicable, by gram-negative bacterial species. Studies with polymicrobial GN-BSI were excluded. For inclusion in the primary analysis, studies must have stratified or statistically adjusted for confounding variables between female and male patients with GN-BSI. A secondary analysis included studies that reported sex-stratified unadjusted mortality. DATA EXTRACTION AND SYNTHESIS: One reviewer conducted extraction and quality assessment, which was verified by a second reviewer. Risk of bias and quality were assessed with the Newcastle-Ottawa Quality Assessment Scale. Mortality data were combined as odds ratios (ORs). The study followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. MAIN OUTCOME AND MEASURES: Mortality at or before 90 days following GN-BSI, stratified by sex. RESULTS: From 9752 studies retrieved, 25 (16 350 patients; 4017 female [25%], 12 333 male [75%]) were included in the primary analysis. Female patients with GN-BSI did not have increased risk of mortality relative to male patients (pooled OR, 0.98 [95% CI, 0.81-1.17]). No publication bias was identified. Subset analyses based on medical comorbidities, timing of mortality end point, bacterial species group, antibiotic resistance phenotype, and publication date did not reveal a set of patients with differences in sex-stratified mortality. A total of 321 studies (147 810 patients) that reported unadjusted mortality were included in a secondary analysis. In this analysis, female sex was associated with decreased risk of mortality (pooled OR, 0.90 [95% CI, 0.86-0.94]). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, female patients with GN-BSI were not at higher risk than male patients of mortality after statistical adjustment. GN-BSI and SA-BSI thus differ in sex-specific mortality outcomes, highlighting the need for further research into the immunological, pathophysiological, and clinical management factors that may be associated with sex disparities in SA-BSI but not in GN-BSI.