Daily Sepsis Research Analysis
Analyzed 50 papers and selected 3 impactful papers.
Summary
Analyzed 50 papers and selected 3 impactful articles.
Selected Articles
1. Monotherapy or combinations? Intravenous vitamin C in sepsis and septic shock: An umbrella review of 31 systematic reviews.
Across 31 reviews, combination regimens of IV vitamin C (HAT or vitamin C+thiamine) do not reduce mortality; minor hemodynamic gains likely reflect corticosteroid effects. A narrow signal for benefit with vitamin C monotherapy exists when started within 24 hours at intermediate doses for 3–4 days, but certainty is low-to-moderate due to heterogeneity and bias. Routine use is not supported; tightly designed multicenter trials in defined scenarios are warranted.
Impact: Provides a high-level synthesis that de-implements ineffective combination regimens and narrows the plausible window for vitamin C monotherapy, directly informing practice and future RCT design.
Clinical Implications: Do not use IV vitamin C routinely for sepsis/septic shock. If considered, restrict to clinical trials focused on very-early monotherapy at intermediate dosing and short duration.
Key Findings
- HAT and vitamin C+thiamine combinations did not reduce 28–30-day mortality.
- Hemodynamic improvements (ΔSOFA, vasopressor hours) were modest and attributable mainly to corticosteroids.
- Vitamin C monotherapy showed a possible mortality benefit only when initiated ≤24 h at 25–100 mg/kg/day for 3–4 days, with low-to-moderate certainty.
Methodological Strengths
- Umbrella review integrating 31 reviews with AMSTAR 2 quality appraisal, CCA overlap assessment, and GRADE certainty ratings.
- Inclusion of component/network MA (CINeMA) and TSA where available; comprehensive multi-database search without language restriction.
Limitations
- Very high overlap among included reviews and substantial heterogeneity and imprecision.
- Potential publication bias and limited high-quality RCT evidence for the specific early monotherapy regimen.
Future Directions: Conduct pragmatic, multicenter RCTs testing early vitamin C monotherapy (≤24 h, intermediate dosing, 3–4 days) with rigorous allocation concealment, adherence monitoring, and patient-level phenotyping.
Intravenous (IV) vitamin C has been proposed as an adjuvant therapy in sepsis/septic shock due to its biological plausibility and safety profile, but the proliferation of reviews has not resolved its clinical utility. To synthesize the evidence on IV vitamin C (monotherapy, HAT-hydrocortisone+vitamin C+thiamine-and vitamin C+thiamine) in adults with sepsis/septic shock, prioritizing 28-30-day mortality. Umbrella review of systematic reviews and meta-analyses (MEDLINE/PubMed, Embase, Scopus, and Web of Science, without language restriction). Quality was assessed with AMSTAR 2, overlap with CCA, and when available, TSA and component/network meta-analysis (CINeMA). Certainty of evidence was graded using GRADE with an anchor estimator per outcome and regimen. Thirty-one reviews were included (30 quantitative: 28 SR/MA and 2 component/network MA; 1 qualitative). Combinations (HAT and vitamin C+thiamine) did not reduce mortality; hemodynamic improvements (small decreases in ΔSOFA and vasopressor hours) were modest, did not translate into survival benefits, and were primarily attributable to the corticosteroid. Monotherapy showed a possible mortality benefit signal under specific conditions (initiation ≤24 h, intermediate dose 25-100 mg/kg/day, 3-4-day courses; more pronounced in sepsis than shock), but with low-to-moderate certainty due to heterogeneity, imprecision, publication bias, and very high overlap among reviews. Combination regimens (HAT and vitamin C plus thiamine) did not reduce mortality; hemodynamic improvements were modest, did not translate into survival benefits, and were primarily attributable to the corticosteroid component. For monotherapy, a possible mortality benefit signal was identified under specific conditions (initiation within 24 h, intermediate dose 25-100 mg/kg/day, 3-4-day courses, more pronounced in sepsis than shock), but overall certainty remains low-to-moderate due to heterogeneity, imprecision, publication bias, and very high overlap among reviews. These findings do not support routine use of IV vitamin C in any regimen; for monotherapy, the identified signal warrants rigorous multicenter trials in well-defined clinical scenarios before any recommendation can be made.
2. Risk prediction of sepsis-associated acute kidney injury: development, validation of a machine learning model with multicenter data.
Using three multicenter ICU datasets, an XGBoost model based on 10 variables predicted SA-AKI with internal AUC 0.72 and external AUCs 0.82–0.84. SHAP showed PTT, creatinine, 24-hour urine output, and SAPS II as top contributors. A web-based calculator enables bedside risk stratification within 24 hours of ICU admission.
Impact: Delivers an externally validated, interpretable, and deployable prediction tool for SA-AKI, addressing a major gap in early detection and enabling targeted nephroprotective strategies.
Clinical Implications: Supports early identification of patients at high risk for SA-AKI to guide surveillance, fluid/vasopressor management, avoidance of nephrotoxins, and timely nephrology consultation.
Key Findings
- XGBoost achieved internal AUC 0.72 and external AUCs 0.82 (eICU-CRD) and 0.84 (BB-ICU) for SA-AKI prediction.
- Top SHAP features were PTT, creatinine, 24-hour urine output, and SAPS II.
- A web-based calculator (Shiny) operationalizes the model for bedside use within 24 hours of ICU admission.
Methodological Strengths
- External validation across two independent cohorts and an additional hospital dataset with decision curve analysis.
- Model interpretability via SHAP and parsimonious 10-variable feature set measured within 24 hours.
Limitations
- Retrospective design and moderate internal discrimination; prospective impact analyses are lacking.
- Potential dataset-specific biases; clinical integration pathways and thresholds require prospective refinement.
Future Directions: Prospective, multicenter implementation trials to evaluate clinical impact on SA-AKI incidence, RRT use, and outcomes; EHR integration with alert thresholds and clinician-in-the-loop workflows.
BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in intensive care unit (ICU) patients, with high incidence and mortality. Conventional diagnostic indicators, such as serum creatinine and urine output, have limitations in early identification. Existing machine learning (ML)-based prediction models are mostly single-center and lack interpretability, highlighting the clinical need for reliable and applicable early prediction tools. METHODS: Data were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV), eICU Collaborative Research Database (eICU-CRD), and Bobai County People's Hospital ICU (BB-ICU). Eligible patients were those meeting the Sepsis-3.0 criteria, with SA-AKI as the primary outcome. Ten core variables were selected from 83 indicators measured within 24 h of ICU admission through a four-step screening process. Six ML algorithms were optimized using grid search and five-fold cross-validation. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The optimal model was interpreted via SHAP, externally validated, and translated into a web-based calculator using the Shiny framework. RESULTS: The incidence of SA-AKI was 45.1% in MIMIC-IV, 28.1% in eICU-CRD, and 34.1% in BB-ICU. The XGBoost model performed best, with an internal area under the curve (AUC) of 0.72 and external validation AUCs of 0.82 (eICU-CRD) and 0.84 (BB-ICU). The XGBoost model also showed balanced classification metrics (sensitivity 0.73, specificity 0.60), a calibration curve close to the diagonal, and the highest net benefit in DCA. SHAP analysis identified partial thromboplastin time (PTT), creatinine, 24-hour urine output, and SAPSII as the key predictive factors. CONCLUSIONS: The ML model developed in this study demonstrates good discriminative ability, calibration, and clinical applicability. SHAP improves the model's interpretability, and the web-based tool supports early SA-AKI risk stratification. This study provides a technical basis for addressing the clinical challenge of early SA-AKI prediction.
3. Effect of Acetylsalicylic Acid on Mortality in Sepsis: A Systematic Review and Meta-Analysis.
Across five studies (n=25,138), aspirin use in adults with sepsis was associated with lower mortality (RR 0.77, 95% CI 0.66–0.89). The body of evidence includes one RCT and four nonrandomized studies with risk-of-bias assessments, indicating potential benefit but the need for definitive trials and careful safety evaluation.
Impact: Suggests a plausible mortality benefit signal for a widely available, low-cost drug in sepsis, potentially informing continuation strategies and prioritizing RCTs.
Clinical Implications: Routine initiation solely for sepsis cannot be recommended based on current evidence; however, continuation of pre-existing aspirin may be reasonable when bleeding risk is acceptable. High-quality RCTs are needed to clarify benefit-risk.
Key Findings
- Meta-analysis of five studies (n=25,138) showed lower mortality with aspirin (RR 0.77, 95% CI 0.66–0.89).
- Evidence base comprised one RCT and four nonrandomized studies with risk-of-bias assessments (RoB 2, ROBINS-I).
- Safety (major bleeding) was evaluated but requires further clarification in adequately powered trials.
Methodological Strengths
- Prospective registration (OSF) and comprehensive multi-database search strategy.
- Formal risk-of-bias assessments for both randomized and nonrandomized studies; random-effects meta-analysis.
Limitations
- Only one RCT; majority of evidence from observational studies susceptible to confounding.
- Incomplete reporting on bleeding outcomes across studies; heterogeneity not fully characterized in the abstract.
Future Directions: Design multicenter, placebo-controlled RCTs to test aspirin initiation/continuation strategies in sepsis with standardized bleeding surveillance and patient phenotyping.
BackgroundThe association between aspirin and mortality in patients with sepsis remains unclear. This study aimed to systematically evaluate the effects of aspirin on mortality and major bleeding in adults with sepsis.MethodsThis review was registered in Open Science Framework (DOI: 10.17605/OSF.IO/E5K87). We searched MEDLINE, Embase, CENTRAL, ICTRP, and ClinicalTrials.gov through May 9, 2025. We included one randomized controlled trial (RCT) and four non-randomized studies of interventions (NRSIs). Risk of bias was assessed using RoB 2 for RCTs and ROBINS-I for NRSIs. Random-effects meta-analysis was performed.ResultsFive studies involving 25 138 patients were included. Aspirin showed a possible reduction in mortality (RR 0.77, 95% CI 0.66-0.89; I