Daily Sepsis Research Analysis
Three studies advance sepsis science across diagnostics and prognosis. A bioinformatics and machine-learning analysis identifies S100A12 as a pyroptosis-linked diagnostic biomarker candidate; a 4-ICU cohort shows calprotectin underperforms CRP for sepsis diagnosis; and a prospective cohort finds noninvasive central blood pressure and augmentation index associate with mortality in shock.
Summary
Three studies advance sepsis science across diagnostics and prognosis. A bioinformatics and machine-learning analysis identifies S100A12 as a pyroptosis-linked diagnostic biomarker candidate; a 4-ICU cohort shows calprotectin underperforms CRP for sepsis diagnosis; and a prospective cohort finds noninvasive central blood pressure and augmentation index associate with mortality in shock.
Research Themes
- Sepsis biomarkers and diagnostic validity
- Noninvasive hemodynamic risk stratification in shock
- Data-driven discovery and translational bioinformatics
Selected Articles
1. Identification of pyroptosis-related gene S100A12 as a potential diagnostic biomarker for sepsis through bioinformatics analysis and machine learning.
Integrative transcriptomic analyses and machine learning identified S100A12 as a pyroptosis-linked hub gene with strong diagnostic performance across integrated and external datasets. Immune infiltration and single-cell analyses localized S100A12 expression to neutrophils and monocytes and showed positive correlations with their abundance.
Impact: This work uncovers a pyroptosis-related biomarker candidate (S100A12) for sepsis and triangulates evidence across bulk and single-cell datasets, advancing mechanistic and diagnostic understanding.
Clinical Implications: S100A12 could inform future diagnostic assays for sepsis, but prospective clinical validation (protein-level assays, predefined thresholds, and comparison with CRP/PCT) is required before clinical adoption.
Key Findings
- S100A12 was identified via differential expression, WGCNA, Friends' analysis, and machine learning as a central sepsis-related gene.
- S100A12 showed strong diagnostic capability in integrated and external validation datasets.
- Immune infiltration analysis showed increased monocytes, eosinophils, and neutrophils in sepsis, positively correlated with S100A12 expression.
- Single-cell analysis localized high S100A12 expression to neutrophils and monocytes.
Methodological Strengths
- Multi-method integration (WGCNA, machine learning) with external validation
- Concordant evidence from bulk transcriptomics, immune infiltration, and single-cell data
Limitations
- Bioinformatics-only; lacks prospective clinical and protein-level validation
- Sample sizes and cohorts are not detailed in the abstract; potential dataset heterogeneity
Future Directions: Prospective, pre-registered diagnostic studies measuring S100A12 protein, kinetics, and thresholds; mechanistic experiments linking pyroptosis pathways to S100A12 modulation.
2. Calprotectin as a sepsis diagnostic marker in critical care: a retrospective observational study.
Among 4,732 ICU admissions, calprotectin was higher in sepsis but showed inferior diagnostic accuracy to CRP (AUROC 0.61 vs 0.72). Fungal sepsis had the highest calprotectin levels, highlighting organism-specific biology but limited standalone diagnostic utility at admission.
Impact: Provides large-scale, comparative evidence that calprotectin underperforms CRP for sepsis diagnosis at ICU admission, a practice-relevant negative finding.
Clinical Implications: CRP should remain a primary inflammatory marker for sepsis triage at ICU admission; calprotectin should not replace CRP and may have niche value (e.g., fungal sepsis) pending further validation.
Key Findings
- Retrospective analysis of 4,732 ICU admissions across four ICUs (2015–2018).
- Calprotectin levels were higher in sepsis than non-sepsis (p < 0.001).
- Diagnostic AUROC: calprotectin 0.61 vs CRP 0.72 (p < 0.001), indicating inferior performance of calprotectin.
- Fungal sepsis subgroup had the highest calprotectin levels.
Methodological Strengths
- Large sample size with multi-ICU inclusion and biobanked specimens
- Direct marker-to-marker comparison using ROC analysis under Sepsis-3 criteria
Limitations
- Retrospective design with single time-point measurement at admission
- Potential misclassification and unmeasured confounding; lack of prospective validation or kinetic analyses
Future Directions: Prospective, pre-registered diagnostic studies evaluating calprotectin kinetics, integration into multimarker panels, and organism-specific performance (e.g., fungal sepsis).
3. Prognostic Value of Noninvasive Central Blood Pressure and Arterial Stiffness in Hemodynamic Shock.
In a prospective cohort of 57 ICU patients with septic or cardiogenic shock, low central systolic BP within 24 hours predicted 6-month mortality, and higher augmentation index predicted 14-day mortality; pulse wave velocity showed no prognostic value.
Impact: Highlights practical, noninvasive hemodynamic metrics with prognostic signal in shock, potentially informing early risk stratification and monitoring strategies.
Clinical Implications: Early noninvasive central BP and augmentation index measurements may support risk stratification in septic and cardiogenic shock, but require validation and should complement, not replace, standard invasive monitoring.
Key Findings
- Prospective monocenter cohort of 57 ICU patients with septic or cardiogenic shock.
- Central systolic BP in the first 24 hours predicted 6-month mortality (OR 0.9; p < 0.05) after adjustment.
- Augmentation index (Aix) was associated with 14-day mortality (OR 1.11; p = 0.03).
- Pulse wave velocity (PWV) was not associated with adverse outcomes.
Methodological Strengths
- Prospective design with predefined confounder adjustment
- Use of two validated noninvasive devices capturing central BP and stiffness indices
Limitations
- Single-center, small sample size limits generalizability
- Mixed shock etiologies (septic and cardiogenic) and device differences may introduce heterogeneity
Future Directions: Larger, multicenter cohorts to validate thresholds, assess dynamic changes, and test integration of central BP/Aix into sepsis shock management pathways.