Daily Sepsis Research Analysis
Mechanistic and clinical sepsis research converged on three fronts: a multi-omics/mechanistic study uncovered a PIK3C3–MAPK14 axis linking impaired autophagy to M1 macrophage polarization in sepsis-induced acute lung injury; an ICU cohort showed hyperdynamic left ventricular ejection fraction (EF ≥70%) strongly predicts 28-day mortality in septic shock; and a proteomics analysis proposed a compact two-protein panel (ANXA6 + FIBG) to predict sepsis among trauma-induced SIRS. Together, these studi
Summary
Mechanistic and clinical sepsis research converged on three fronts: a multi-omics/mechanistic study uncovered a PIK3C3–MAPK14 axis linking impaired autophagy to M1 macrophage polarization in sepsis-induced acute lung injury; an ICU cohort showed hyperdynamic left ventricular ejection fraction (EF ≥70%) strongly predicts 28-day mortality in septic shock; and a proteomics analysis proposed a compact two-protein panel (ANXA6 + FIBG) to predict sepsis among trauma-induced SIRS. Together, these studies advance pathophysiology, risk stratification, and early diagnosis.
Research Themes
- Macrophage autophagy and polarization in sepsis-induced lung injury
- Cardiac echocardiographic risk markers in septic shock
- Proteomics-based early sepsis prediction in trauma-induced SIRS
Selected Articles
1. The PIK3C3/MAPK14 axis drives M1 polarization via autophagy Inhibition to exacerbate Sepsis-Induced acute lung injury.
Integrating transcriptomics, single-cell data, molecular docking, and wet-lab validation, the study identifies a PIK3C3–MAPK14 signaling axis that impairs autophagy and drives M1 macrophage polarization in sepsis-induced ALI. PIK3C3 downregulation upregulates MAPK14, reduces autophagic flux, and promotes pro-inflammatory phenotypes, positioning this axis as a druggable target.
Impact: This work offers a coherent mechanistic pathway connecting autophagy disruption to macrophage-driven lung injury in sepsis, advancing targetable biology beyond descriptive associations.
Clinical Implications: Although preclinical, modulating the PIK3C3–MAPK14 axis could underpin therapies aiming to restore autophagy and rebalance macrophage polarization in sepsis-induced lung injury.
Key Findings
- MAPK14 was identified as a core ALI gene with increased expression localized to pro-inflammatory macrophages by single-cell analysis.
- PIK3C3 downregulation increased MAPK14, impaired autophagic flux (LC3-II/I↓, TOM20↑, P62↑, HSP60↑), and promoted M1 polarization after LPS stimulation.
- RNA pull-down captured a PIK3C3–MAPK14 complex; molecular docking showed high-affinity interaction (ΔG-bind ≈ −128 kJ/mol), suggesting a functional axis.
Methodological Strengths
- Multi-omics integration with single-cell localization and machine-learning-guided gene prioritization
- Orthogonal wet-lab validations (WB, qRT-PCR, flow cytometry, ELISA, RNA pull-down) supporting a mechanistic axis
Limitations
- Predominantly in vitro without in vivo sepsis/ALI validation
- Reliance on molecular docking and correlation analyses may not fully capture causal dynamics in complex in vivo contexts
Future Directions: Validate the axis in animal models of sepsis-induced lung injury and test pharmacologic modulators of MAPK14 or PIK3C3 to assess therapeutic efficacy and safety.
2. Hyperdynamic left ventricular ejection fraction as a predictor of mortality in intensive care unit patients with septic shock.
In a 235-patient ICU cohort with septic shock, hyperdynamic EF (≥70%) was significantly associated with 28-day mortality (OR 4.822). Age, lower mean arterial pressure, higher SOFA scores, and elevated lactate independently predicted death; male sex had higher mortality. The study was preregistered and used standardized echocardiography.
Impact: Identifies a pragmatic echocardiographic metric (hyperdynamic EF) for early risk stratification in septic shock, linking cardiac function phenotype to mortality.
Clinical Implications: Incorporating EF ≥70% as a high-risk flag could prompt closer hemodynamic monitoring, refined fluid/vasopressor strategies, and earlier consultation for cardiovascular dysfunction in sepsis.
Key Findings
- Hyperdynamic EF was more prevalent in non-survivors, strongly associated with 28-day mortality (OR 4.822, 95% CI 1.467–8.852).
- Independent mortality predictors included older age, lower mean arterial pressure, higher SOFA scores, and elevated serum lactate.
- Male patients exhibited significantly higher mortality; echocardiography was performed by accredited operators within a preregistered protocol (NCT06993948).
Methodological Strengths
- Prospective daily SOFA assessment with standardized echocardiography by accredited clinicians
- Multivariable modeling identifying independent predictors; preregistration at ClinicalTrials.gov
Limitations
- Single-center observational design limits causal inference and generalizability
- EF measurements in the context of vasopressors and dynamic preload may confound interpretation; diastolic metrics were not detailed
Future Directions: Multicenter validation and incorporation of comprehensive diastolic and deformation indices to evaluate whether hyperdynamic EF-guided management improves outcomes.
3. Identifying Predictive Biomarkers for Sepsis in Trauma-Induced Systemic Inflammatory Response Syndrome Using Proteomics Data.
Retrospective analysis of plasma proteomics from 62 severe trauma patients identified 15 proteins distinguishing SIRS patients who developed sepsis versus those who did not. A minimal two-protein panel (ANXA6 + FIBG) achieved high predictive performance (AUC 0.9652), suggesting a feasible early risk stratification tool.
Impact: Proposes a compact biomarker panel with excellent discrimination to flag high-risk trauma patients before overt sepsis, potentially enabling earlier prevention and intervention.
Clinical Implications: If validated prospectively, an ANXA6+FIBG assay could guide targeted monitoring, antibiotic stewardship, and preemptive supportive care in trauma-induced SIRS.
Key Findings
- Identified 15 differentially expressed proteins between SIRS patients who developed sepsis (n=15) and those who did not (n=23).
- Top single markers showed strong discrimination: ANXA6 (AUC 0.881), FA12 (0.873), TRY2 (0.868), FIBG (0.759), DOPD (0.745).
- A two-protein panel (ANXA6 + FIBG) balanced parsimony and performance with AUC 0.9652; a five-marker combination reached AUC 0.9913.
Methodological Strengths
- Unbiased proteomics with ROC/AUC-based evaluation and model parsimony optimization
- Clear case definition within trauma-induced SIRS enabling clinically relevant comparison
Limitations
- Small, retrospective single-cohort analysis without external validation increases overfitting risk
- Timing of sampling and calibration/clinical utility metrics (e.g., decision-curve analysis) not reported
Future Directions: Prospective multicenter validation, assay development with clinical lab platforms, and assessment of clinical impact via decision-curve and implementation studies.