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.
Sepsis is a non-discriminatory inflammatory reaction that can result in a diverse array of organ dysfunctions, which can be fatal. Pyroptosis is a programmed mechanism of cell death that is distinguishable from apoptosis and other forms of cellular demise. However, the role of pyroptosis in sepsis remains to be further explored. In this study, by employing a combination of the difference analysis, WGCNA, Friends' analysis, and machine learning, the central gene S100A12 was successfully identified. S100A12 demonstrated superb diagnostic capabilities in both the integrated and external validation datasets. Furthermore, significant disparities were observed in the levels of monocytes, eosinophils, and neutrophils between sepsis patients and the control group, as per the findings of immune infiltration analysis. The aforementioned immune infiltrating cells exhibited an increase in expression levels among patients diagnosed with sepsis and were found to be significantly and positively associated with S100A12 expression. The results of the single-cell analysis indicated a significant expression of S100A12 in both neutrophils and monocytes, which was in complete alignment with the outcomes of immune infiltration. In summary, the pyroptosis-related gene S100A12 represents a potential biomarker for the diagnosis and treatment of sepsis.
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).
Diagnosing sepsis in critical care remains a challenge due to the lack of gold-standard diagnostics. Calprotectin (S100A8/A9) has been proposed as a diagnostic marker to identify sepsis in critically ill patients. This study evaluated the diagnostic performance of calprotectin and C-reactive protein (CRP) to distinguish between sepsis and non-sepsis on intensive care unit (ICU) admission. Admission biobank blood samples from adult patients admitted to four ICUs (2015-2018) were used to analyse calprotectin and CRP. All adult patients were screened retrospectively for the sepsis-3 criteria at ICU admission. The diagnostic performance of calprotectin and CRP was evaluated using receiver operating characteristic (ROC) curves. We included 4732 patients, of whom 44% had sepsis. Calprotectin levels were higher in sepsis (p < 0.001). The area under the receiver operating curve (AUROC) to diagnose sepsis was 0.61 for calprotectin compared to 0.72 for CRP (p < 0.001). Among microbiological subgroups of sepsis patients, fungal sepsis had the highest level of calprotectin. We conclude that the diagnostic performance of calprotectin in identifying sepsis patients at ICU admission was inferior to that of CRP.
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.
OBJECTIVES: Elevated central blood pressure (BP) and arterial stiffness are risk factors for cardiovascular mortality. However, their prognostic value in patients with hemodynamic shock has not been studied broadly. Evolved BP monitoring devices enable the noninvasive assessment of central BP and arterial stiffness. The objective of this study was to evaluate the prognostic value of central BP and arterial stiffness measurements, delivered by 2 noninvasive devices, in patients with septic or cardiogenic shock admitted to the intensive care unit. DESIGN: This is a monocenter, prospective, cohort study. SETTING: This study was conducted in a tertiary university hospital. PARTICIPANTS: We enrolled 57 patients who were admitted to the intensive care unit with septic or cardiogenic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Central BP and arterial stiffness indices like pulse wave velocity (PWV) and Aix were recorded with a Mobil-o-Graph 24h PWA and SphygmoCor XCEL. Age, catecholamine dosage, resuscitation incidence before inclusion, C-reactive protein, leukocytes, and creatinine were recorded as possible confounders. With regard to the confounders, central systolic BP measured in the first 24 hours, was predictive of 6-month mortality (odds ratio, 0.9; p < 0.05). Aix, recorded by Mobil-o-Graph 24h PWA, was associated with death in the first 14 days (odds ratio, 1.11; p = 0.03). An increased PWV was not associated with adverse outcomes. CONCLUSIONS: Low central BP and increased Aix were linked to a higher mortality in shock patients. PWV had no prognostic value.