Daily Sepsis Research Analysis
Analyzed 11 papers and selected 3 impactful papers.
Summary
Three studies advance sepsis research across diagnosis and prognosis. A Sepsis-3–only meta-analysis shows presepsin has good diagnostic accuracy and rule-out value; a pediatric PICU study finds Phoenix Sepsis Criteria outperform SIRS for mortality prediction; and a multicenter prospective cohort shows low admission 25(OH)D independently predicts worse outcomes in older sepsis patients.
Research Themes
- Biomarker-based diagnosis in sepsis
- Sepsis case definition and risk stratification in pediatrics
- Prognostic biomarkers in older adults with sepsis
Selected Articles
1. Diagnostic accuracy of presepsin for sepsis in adult patients according to the criteria of sepsis-3: systematic review and meta-analysis.
Across 11 Sepsis-3–only studies (n=2248), presepsin showed good diagnostic accuracy (AUC 0.85), with pooled sensitivity 0.782 and specificity 0.739 at presentation; the negative likelihood ratio of 0.297 supports rule-out utility. Substantial heterogeneity and wide cut-off variation highlight the need for standardization before broad clinical adoption.
Impact: This is the first meta-analysis restricted to Sepsis-3, resolving case-mix bias from mixed-criteria syntheses and clarifying presepsin’s real-world performance.
Clinical Implications: Presepsin can support early diagnostic triage when sepsis is suspected, particularly as a rule-out adjunct alongside clinical assessment. Institutions should validate and standardize cut-offs in their populations before integration into sepsis pathways.
Key Findings
- Pooled sensitivity 0.782 (95% CI 0.755–0.807) and specificity 0.739 (95% CI 0.714–0.763) for sepsis diagnosis under Sepsis-3.
- Area under the SROC curve was 0.85, indicating good diagnostic accuracy.
- Negative likelihood ratio 0.297 supports rule-out utility at presentation.
- Substantial heterogeneity (I² > 75% for sensitivity and specificity).
- No Spearman-based threshold effect (p=0.326), but Moses’ model suggested a mild threshold effect (p=0.018).
- Meta-regression found cut-off value did not significantly influence diagnostic accuracy (p=0.878).
Methodological Strengths
- Restricted inclusion to Sepsis-3–defined studies to reduce case-mix bias.
- Used bivariate random-effects modeling with SROC and meta-regression to explore heterogeneity and threshold effects.
Limitations
- Substantial between-study heterogeneity limits generalizability.
- Wide variation in assay cut-offs; potential publication bias not fully addressed.
Future Directions: Prospective, standardized diagnostic accuracy studies with harmonized assays and predefined cut-offs are needed, along with impact analyses within sepsis care pathways.
BACKGROUND: Time-sensitive identification of sepsis plays an essential role in minimizing sepsis-related death. One of the latest and important markers recognized is presepsin, also known as sCD14-ST. After the publication of the Sepsis-3 criteria in 2016, there have been discrepancies found among meta-analyses using both old and new criteria combined. The purpose of this current analysis is to evaluate the performance of presepsin at presentation, using a scientific approach and only considering studies conducted using Sepsis-3 c
2. A comparison of pediatric sepsis definitions based on systemic inflammatory response syndrome and Phoenix criteria: a single-center PICU retrospective study.
In 1,034 PICU admissions with suspected/confirmed infection, agreement between SIRS and Phoenix Sepsis Criteria was poor (kappa 0.202). After adjustment, PSC independently predicted 28-day mortality (aOR 5.123), with superior discrimination over SIRS (C-statistic 0.809 vs 0.589); SIRS-positive/PSC-negative children had very low mortality (1.6%), suggesting higher specificity of PSC.
Impact: Validates the new Phoenix Criteria as prognostically superior to SIRS in a real-world PICU cohort, informing adoption and interpretation of legacy SIRS-based data.
Clinical Implications: PICUs should consider PSC for risk stratification and outcome prediction, while exercising caution when extrapolating results from SIRS-based cohorts to PSC-defined populations.
Key Findings
- Diagnostic agreement between SIRS and PSC was poor (kappa=0.202, 95% CI 0.143–0.261).
- PSC independently predicted 28-day mortality (adjusted OR 5.123, 95% CI 2.128–12.333; p<0.001), whereas SIRS did not (adjusted OR 0.937; p=0.827).
- Discrimination for mortality was superior with PSC vs SIRS (C-statistic 0.809 vs 0.589; p<0.001).
- 20.2% of SIRS-positive patients were PSC-negative and had very low mortality (1.6%), indicating higher specificity with PSC.
- Of 1,034 patients, 59.3% met SIRS sepsis (mortality 15.2%), 72.0% met PSC sepsis (mortality 16.3%), and 47.3% met both (mortality 18.6%).
Methodological Strengths
- Head-to-head application of both criteria with independent evaluation and adjusted logistic regression.
- Robust discrimination metrics (C-statistics) and agreement analysis (kappa) in a sizable PICU cohort.
Limitations
- Single-center retrospective design limits generalizability and introduces potential misclassification bias.
- Lack of external validation and prospective adjudication of organ dysfunction.
Future Directions: Prospective, multicenter validation of PSC thresholds and integration into sepsis pathways, with impact assessments on triage and outcomes.
BACKGROUND: The 2024 international pediatric sepsis consensus definition has undergone a paradigm shift from a systemic inflammatory response syndrome (SIRS)-based framework to the organ dysfunction-centered Phoenix Sepsis Criteria (PSC). We aimed to evaluate the diagnostic concordance, predictive performance for 28-day pediatric intensive care unit (PICU) mortality, and phenotypic overlap between these two pediatric sepsis definitions. METHODS: This single-center retrospective cohort study included 1034 children aged > 1 m
3. Vitamin D at hospital admission as an independent predictor of outcome of sepsis patients: Results of a secondary analysis from a "Need-Speed" trial prospective cohort.
In 829 confirmed sepsis patients (median age 81), admission 25(OH)D levels were markedly low (median 11.2 ng/mL) and independently associated with 90-day mortality and 15-day discharge. A threshold of 12 ng/mL predicted lower 90-day survival (OR 0.596) and reduced likelihood of early discharge (OR 1.606 inverse association), supporting 25(OH)D as a pragmatic prognostic marker.
Impact: Identifies a readily measurable admission biomarker with independent prognostic value in a multicenter prospective cohort of older sepsis patients.
Clinical Implications: Measuring 25(OH)D at admission may enhance early risk stratification in older sepsis patients and inform supportive care planning; interventional implications require randomized trials.
Key Findings
- Among 829 sepsis patients, median 25(OH)D was 11.2 ng/mL (IQR 8.0–19.4), indicating severe deficiency.
- Lower baseline 25(OH)D was associated with higher 30- and 90-day mortality and with lower probability of discharge alive by day 15 (p<0.05).
- Multivariate models confirmed 25(OH)D as an independent predictor of 90-day mortality and 15-day discharge.
- A threshold of 12 ng/mL independently predicted 90-day survival (OR 0.5961 [0.4068–0.8735]) and discharge alive by day 15 (OR 1.6055 [1.1738–2.1960]).
- Cohort was elderly (median age 81 years), underscoring geriatric relevance.
Methodological Strengths
- Multicenter prospective cohort with standardized chemiluminescence assay for 25(OH)D.
- Adjusted multivariable analyses and prespecified threshold exploration (12 ng/mL).
Limitations
- Secondary analysis of observational data limits causal inference.
- Elderly-skewed cohort may limit generalizability; residual confounding possible.
Future Directions: External validation in broader age ranges and randomized trials testing vitamin D repletion strategies in deficient septic patients.
BACKGROUND: Early prognostic stratification of septic patients at hospital admission is challenging, especially in the elderly. Considering the well-known immunomodulatory effects of vitamin D and its common deficiency among elderly, we aimed to evaluate if vitamin D plasma levels (25(OH)D) at hospital admission could be a prognostic biomarker in septic patients. METHODS: Secondary analysis of data and samples from the multicenter Need-Speed trial, a multicenter study involving the emergency and internal medicine wards of five