Daily Sepsis Research Analysis
Three impactful studies advance sepsis care across prognosis, supportive therapy safety, and long-term outcomes. An immune-metabolic lactylation signature achieved strong early mortality prediction and prospective validation; a large cohort linked prophylactic PPI use to higher 90-day mortality; and a prospective ED cohort quantified 2-year mortality and key prognostic factors.
Summary
Three impactful studies advance sepsis care across prognosis, supportive therapy safety, and long-term outcomes. An immune-metabolic lactylation signature achieved strong early mortality prediction and prospective validation; a large cohort linked prophylactic PPI use to higher 90-day mortality; and a prospective ED cohort quantified 2-year mortality and key prognostic factors.
Research Themes
- Immune-metabolic biomarkers for sepsis prognosis
- Medication safety in supportive care (PPI use in sepsis)
- Long-term outcomes and risk stratification after sepsis
Selected Articles
1. A novel, rapid, and practical prognostic model for sepsis patients based on dysregulated immune cell lactylation.
Using bulk and single-cell transcriptomics, the authors built an eight-gene lactylation-associated signature that predicted early mortality in sepsis with strong performance (AUC up to 0.86) and prospectively validated it in 51 patients. Findings link dysregulated immune-cell lactylation to outcome and suggest actionable, metabolism-informed risk stratification.
Impact: Introduces a mechanistically grounded prognostic model with prospective validation, addressing a major gap in early risk stratification for sepsis.
Clinical Implications: The model could support early triage, monitoring intensity, and enrollment into targeted interventions; lactylation pathways (e.g., PPP1R15A) may represent therapeutic targets.
Key Findings
- An eight-gene lactylation-associated signature (CD160, HELB, ING4, PIP5K1C, SRPRA, CDCA7, FAM3A, PPP1R15A) was derived and externally validated.
- Predictive performance: AUC 0.78 (training), 0.73 (validation), and 0.82/0.80/0.86 for 7/14/28-day survival in a prospective cohort (N=51).
- THP-1 experiments with the PPP1R15A inhibitor (Sephin1) increased global lactylation, supporting a mechanistic link.
Methodological Strengths
- Integration of bulk and single-cell transcriptomics with machine learning and pseudotime analysis
- Prospective single-center clinical validation with time-resolved AUCs
Limitations
- Prospective validation cohort was single-center and relatively small (N=51)
- Lack of interventional testing; generalizability across care settings remains to be established
Future Directions: Multicenter prospective validation, integration into clinical workflows, and trials testing lactylation-modulating therapies or care pathways triggered by the signature.
2. Prophylactic proton pump inhibitor use and all-cause mortality in adult sepsis patients: a retrospective analysis based on the MIMIC-IV database.
In 18,198 ICU patients with sepsis from MIMIC-IV, prophylactic PPI use was associated with higher 90-day all-cause mortality and did not improve 28-day survival. Although ICU stay was reduced, total hospital stay was unchanged and clinically significant adverse events were more frequent.
Impact: Challenges routine prophylactic PPI use in sepsis by demonstrating potential harm at scale using contemporary real-world data.
Clinical Implications: Avoid routine prophylactic PPI in sepsis without a clear indication; reassess stress-ulcer prophylaxis policies and monitor for adverse events when PPIs are used.
Key Findings
- Prophylactic PPI use was associated with increased 90-day all-cause mortality after ICU admission.
- No improvement in 28-day survival; total hospital length of stay was not reduced despite shorter ICU stay.
- PPI administration was linked to clinically significant adverse reactions.
Methodological Strengths
- Very large sample size leveraging a well-curated critical care database (MIMIC-IV)
- Time-to-event analysis with multivariable Cox models and Kaplan–Meier estimates
Limitations
- Retrospective observational design with potential confounding by indication
- Medication exposure misclassification and unmeasured confounders cannot be excluded
Future Directions: Prospective, ideally randomized, studies to test risk-adjusted stress-ulcer prophylaxis strategies and head-to-head comparisons of PPI vs H2RA in sepsis.
3. Two-Year Mortality and Prognostic Factors in Sepsis: A Prospective Cohort Study of 714 Danish Emergency Department Patients.
In a prospective ED cohort of 714 adults with sepsis (SOFA ≥2), 2-year all-cause mortality was 49.6%. Independent predictors included older age, SOFA >4, malignancy, ischemic heart disease, dementia, prior sepsis, new-onset atrial fibrillation, and low hemoglobin; skin infection source was protective.
Impact: Provides robust long-term outcome data and pragmatic prognostic factors to inform post-discharge care and trial design in sepsis.
Clinical Implications: Supports risk-stratified follow-up after sepsis, with targeted surveillance for patients with high SOFA, malignancy, cardiovascular disease, dementia, anemia, and new-onset atrial fibrillation.
Key Findings
- Two-year all-cause mortality was 49.6% among 714 sepsis patients admitted via the ED.
- Independent risk factors: age 65–85 (aHR 1.89) and >85 (aHR 2.99), SOFA >4 (aHR 2.45), malignancy (aHR 1.91), ischemic heart disease (aHR 1.38), dementia (aHR 1.84), prior sepsis admission (aHR 1.45), new-onset atrial fibrillation (aHR 1.56), low hemoglobin (aHR up to 2.30).
- Skin infection source was associated with reduced mortality risk (aHR 0.50) compared with other sources.
Methodological Strengths
- Prospective design with standardized SOFA-based sepsis definition
- Time-to-event modeling with multivariable Cox adjustment
Limitations
- Single-center study in Denmark; generalizability may be limited
- Observational design cannot exclude residual confounding
Future Directions: Develop and test post-sepsis care pathways targeting identified high-risk groups, and validate these prognostic factors across diverse health systems.