Daily Sepsis Research Analysis
Across three high-impact studies, early enteral nutrition reduced mortality in adult sepsis, a single-cell atlas revealed aging-related bone marrow immune dysfunction with a targetable Lgals9–Cd44 axis, and a large meta-analysis showed no excess female mortality in gram-negative bacteremia after adjustment. Together, these findings inform supportive care, mechanistic targets in elderly sepsis, and sex-aware epidemiology.
Summary
Across three high-impact studies, early enteral nutrition reduced mortality in adult sepsis, a single-cell atlas revealed aging-related bone marrow immune dysfunction with a targetable Lgals9–Cd44 axis, and a large meta-analysis showed no excess female mortality in gram-negative bacteremia after adjustment. Together, these findings inform supportive care, mechanistic targets in elderly sepsis, and sex-aware epidemiology.
Research Themes
- Nutrition and supportive care in sepsis
- Aging-associated immune remodeling and targets
- Sex differences and epidemiology in bloodstream infections
Selected Articles
1. Influence of early enteral nutrition on mortality of adult patients with sepsis: a meta-analysis of randomized controlled trials.
Pooling 10 RCTs (n=582), early enteral nutrition within 24–48 hours reduced all-cause mortality (OR 0.59) without significant heterogeneity. Findings support incorporating EEN into sepsis care while calling for trials to optimize timing, dose, and protocols.
Impact: This is an RCT-only meta-analysis demonstrating a mortality benefit of a widely available supportive intervention in sepsis.
Clinical Implications: Adopt early enteral feeding (within 24–48 hours of diagnosis/admission) when feasible, integrate into sepsis bundles, and monitor tolerance. Tailor strategies to GI function and hemodynamic stability.
Key Findings
- Included 10 randomized controlled trials with 582 adult sepsis patients.
- Early enteral nutrition reduced all-cause mortality (OR 0.59; 95% CI 0.37–0.94; p=0.03).
- No significant statistical heterogeneity was detected across trials.
- Interventions contrasted early enteral nutrition vs delayed enteral or parenteral nutrition.
Methodological Strengths
- Meta-analysis restricted to randomized controlled trials with comprehensive multi-database search.
- Random-effects modeling with heterogeneity assessment and predefined early feeding window.
Limitations
- Aggregate sample size remains modest and feeding protocols varied across trials.
- Heterogeneity metrics and risk-of-bias details are limited in the abstract; subgroup effects remain uncertain.
Future Directions: Large, high-quality RCTs to define optimal timing, caloric/protein targets, and patient selection, including hemodynamic thresholds and GI intolerance management.
2. Single-cell transcriptomic analysis reveals immune remodeling in bone marrow during aged sepsis.
Single-cell RNA-seq of bone marrow in aged vs. young septic mice showed reduced adaptive and increased innate compartments in aged sepsis, with impaired neutrophil chemotaxis and exhausted myeloid programs. Aged sepsis featured HSC expansion with disrupted Lgals9–Cd44 communication; activating this axis partially restored myeloid migration.
Impact: Provides a mechanistic atlas of aged sepsis hematopoiesis and identifies a tractable communication pathway (Lgals9–Cd44) linking HSCs and myeloid dysfunction.
Clinical Implications: While preclinical, the Lgals9–Cd44 axis could inform immunorestorative strategies for elderly sepsis. The cellular map highlights candidate cell states for biomarker development and precision immunomodulation.
Key Findings
- Aged septic mice had decreased adaptive (18.7%) and increased innate immunity (58.8%) vs young (41.3% and 37.7%).
- Impaired neutrophil chemotaxis; hyperinflammatory yet exhausted monocyte/macrophage programs; disrupted B cell maturation; T cell stress/regulatory shifts.
- HSCs expanded (39.8% vs 31.2%) with impaired Lgals9–Cd44-mediated communication.
- Activating Lgals9–Cd44 partially restored myeloid cell migration in aged sepsis.
Methodological Strengths
- Single-cell RNA sequencing with intercellular communication inference (CellChat) across young and aged CLP models.
- Functional validation of migration defects and partial rescue via Lgals9–Cd44 activation (Transwell assays).
Limitations
- Small sample size and male-only murine models limit generalizability.
- Preclinical nature; safety and efficacy of targeting Lgals9–Cd44 in humans remain unknown.
Future Directions: Validate Lgals9–Cd44 targeting in diverse preclinical models (sex, comorbidities) and develop translational biomarkers of the identified cell states in elderly sepsis.
3. Female Sex and Mortality in Patients With Gram-Negative Bacteremia: A Systematic Review and Meta-Analysis.
Across 25 adjusted studies (n=16,350), female sex was not associated with higher mortality in gram-negative BSI (pooled OR 0.98), with consistent findings across subgroups and no publication bias. In 321 unadjusted studies, females had lower mortality (OR 0.90), underscoring confounding effects.
Impact: Clarifies that sex-specific mortality disparity seen in SA-BSI does not extend to gram-negative BSI after adjustment, refining risk stratification and research priorities.
Clinical Implications: Sex should not drive differential mortality risk assumptions or management in GN-BSI; focus should be on pathogen/resistance, source control, and comorbidity. Mechanistic work is needed to explain divergence from SA-BSI.
Key Findings
- Primary adjusted meta-analysis (25 studies; 16,350 patients) showed no higher female mortality (pooled OR 0.98; 95% CI 0.81–1.17).
- Secondary unadjusted analysis (321 studies; 147,810 patients) suggested lower female mortality (OR 0.90; 95% CI 0.86–0.94), indicating confounding.
- Subgroup analyses across comorbidities, endpoints, species groups, resistance, and publication dates found no sex-based differences.
Methodological Strengths
- Comprehensive multi-database search with adherence to MOOSE and risk-of-bias assessment (Newcastle-Ottawa Scale).
- Primary analysis restricted to studies with sex-stratified adjustment for confounders.
Limitations
- Observational nature of included studies leaves residual confounding possible.
- Heterogeneity in adjustment sets and mortality endpoints across studies.
Future Directions: Mechanistic and clinical studies to delineate why SA-BSI exhibits sex disparities while GN-BSI does not, including hormonal, immunologic, and care pathway factors.