Daily Sepsis Research Analysis
A prospective triage screening tool in a Latin American pediatric ED showed high specificity and strong negative predictive value for early sepsis detection. Systems-level analyses identified CHIT1 as a neutrophil-centric biomarker with potential causal links to sepsis mortality, while preclinical work revealed ERRα as a regulator of microglial polarization and ferroptosis in sepsis-associated brain dysfunction.
Summary
A prospective triage screening tool in a Latin American pediatric ED showed high specificity and strong negative predictive value for early sepsis detection. Systems-level analyses identified CHIT1 as a neutrophil-centric biomarker with potential causal links to sepsis mortality, while preclinical work revealed ERRα as a regulator of microglial polarization and ferroptosis in sepsis-associated brain dysfunction.
Research Themes
- Early pediatric sepsis detection and triage
- Biomarker discovery and systems immunology in sepsis
- Neuroinflammation and organ dysfunction mechanisms in sepsis
Selected Articles
1. Development, Implementation, and Evaluation of an Early Sepsis Screening Tool at Triage in a Pediatric Emergency Department in Latin America.
A triage sepsis screening tool in a pediatric ED demonstrated high specificity (0.99) and good sensitivity (0.80), flagging a small subset (1.4%) with markedly higher acuity, hospitalization, PICU admission, and mortality. Key predictors included circulatory alteration in the Pediatric Assessment Triangle, abnormal capillary refill, and critical risk factors.
Impact: This pragmatic, prospective diagnostic evaluation provides actionable criteria for early pediatric sepsis recognition at triage with excellent rule-out performance. It is directly implementable and identifies high-risk children early.
Clinical Implications: Incorporating this tool at triage can streamline early antibiotic decisions, escalation of monitoring, and PICU triage. Emphasis on circulatory appearance and capillary refill may improve sensitivity without sacrificing specificity.
Key Findings
- Among 16,771 febrile/hypothermic pediatric ED patients, 1.4% (240/16,672) screened positive and had much higher acuity (triage level I–II 99.6% vs 4.8%), hospitalization (66% vs 5%), PICU admission (11% vs 0.03%), and mortality (3.8% vs 0.01%).
- For sepsis at case closure, the tool achieved sensitivity 0.80, specificity 0.99, PPV 0.33, NPV 1.00, PLR 84, and NLR 0.20.
- Independent predictors of sepsis included circulatory alteration in the PAT (OR 2.8), abnormal capillary refill (OR 1.9), and critical risk factors (OR 2.1).
Methodological Strengths
- Prospective diagnostic accuracy design with three reference standards
- Large real-world cohort and implementation at triage
Limitations
- Single health system in Latin America may limit generalizability
- Positive predictive value was modest (0.33), reflecting low prevalence
Future Directions: Multicenter external validation, integration with EHR decision support, and impact studies on time-to-antibiotics and mortality.
2. ERRα Knockout Promotes M2 Microglial Polarization and Inhibits Ferroptosis in Sepsis-Associated Brain Dysfunction.
ERRα deletion protected mice from sepsis-associated brain dysfunction by dampening NF-κB–mediated inflammation, promoting M2 microglial polarization, and suppressing ferroptosis. Findings were consistent across in vivo CLP models and LPS-stimulated BV2 microglia.
Impact: This work uncovers ERRα as a node linking neuroinflammation, microglial polarization, and ferroptosis in SABD, pointing to a tractable therapeutic target.
Clinical Implications: While preclinical, ERRα modulation could be explored to prevent or mitigate sepsis-associated encephalopathy. Biomarker studies in patients may identify those likely to benefit.
Key Findings
- ERRα knockout improved survival and neurological outcomes after CLP-induced sepsis, lowering TNF-α and IL-1β while increasing IL-10.
- ERRα deficiency promoted M2 microglial polarization and attenuated ferroptosis (reduced iron accumulation and lipid peroxidation; normalized mitochondrial morphology).
- Protective effects were mediated via NF-κB pathway inhibition and confirmed in LPS-stimulated BV2 microglia with ERRα knockdown.
Methodological Strengths
- Genetic knockout in an in vivo CLP model with multimodal readouts (cytokines, ferroptosis, ultrastructure)
- In vitro replication in BV2 microglia strengthens mechanistic inference
Limitations
- Preclinical mouse and cell models; no human validation
- No pharmacologic targeting of ERRα to assess translational feasibility
Future Directions: Test pharmacologic ERRα modulators in SABD models and validate pathway activation and biomarkers in clinical sepsis cohorts.
3. Integrated multiomics and Mendelian randomization identify CHIT1 as a novel sepsis biomarker and therapeutic target.
Across multiple transcriptomic datasets with MR support, CHIT1 emerged as a neutrophil-enriched biomarker associated with 28-day sepsis mortality. CHIT1+ neutrophils displayed heightened inflammatory signatures and reduced antigen-presentation genes, suggesting a role in concurrent hyperinflammation and immunosuppression.
Impact: This integrative analysis provides convergent genetic, transcriptomic, and single-cell evidence for CHIT1 as a prognostic biomarker and potential target, advancing neutrophil-focused sepsis immunobiology.
Clinical Implications: If prospectively validated, CHIT1 could support early risk stratification and guide development of CHIT1-targeted immunotherapies in sepsis.
Key Findings
- CHIT1 expression was higher in sepsis non-survivors and associated with 28-day mortality across public cohorts.
- scRNA-seq localized CHIT1 primarily to neutrophils, which showed increased S100A8/A9/A11/A12, IL1R2, IFNGR2, TLR2, CXCL8 and reduced HLA-DM/DP/DR genes in non-survivors.
- Cell–cell communication analysis suggested CHIT1+ neutrophils interact with NK cells, erythroid cells, monocytes/macrophages, and DC via ICAM1–(ITGAM+ITGB2).
Methodological Strengths
- Integration of bulk transcriptomics, single-cell RNA-seq, and Mendelian randomization
- Consistent findings across multiple independent datasets
Limitations
- Retrospective use of public datasets; lack of prospective clinical validation
- No interventional or functional blockade studies of CHIT1 in patients
Future Directions: Prospective validation with standardized CHIT1 assays, mechanistic studies of CHIT1 blockade, and evaluation of additive value over existing risk scores.