ArticlePediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies2024
Biomarker Assessment of a High-Risk, Data-Driven Pediatric Sepsis Phenotype Characterized by Persistent Hypoxemia, Encephalopathy, and Shock.
Article in Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 10 citations in OpenAlex.
- Microvascular phenotypes in pediatric sepsis identified by machine learning: prognostic implications for organ dysfunction and mortality.Critical care (London, England) · 2026Article
- Metabolomic and cytokine profiles of high-risk sepsis phenotypes in children.Scientific reports · 2025Article
- Pediatric Sepsis Phenotype in a Single-Center Cohort Covering 2010-2020: Evolution in Day 1-Day 3 Trajectory and Potential Prognostic Value.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2025Article
- The Resuscitation, Equilibrium and De-escalation (RED) strategy: a phased, personalized hemodynamic support in children with sepsis.Frontiers in pediatrics · 2025Review
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16 authors at 7 institutions in 1 country.
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Abstract
objectivesIdentification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. We sought to the determine reproducibility of the data-driven "persistent hypoxemia, encephalopathy, and shock" (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk strata.
designWe retrained and validated a random forest classifier using organ dysfunction subscores in the 2012-2018 electronic health record (EHR) dataset used to derive the PHES phenotype. We used this classifier to assign phenotype membership in a test set consisting of prospectively (2003-2023) enrolled pediatric septic shock patients. We compared profiles of the PERSEVERE family of biomarkers among those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk strata.
settingTwenty-five PICUs across the United States. PATIENTS: EHR data from 15,246 critically ill patients with sepsis-associated MODS split into derivation and validation sets and 1,270 pediatric septic shock patients in the test set of whom 615 had complete biomarker data.
interventionsNone. MEASUREMENTS AND MAIN
resultsThe area under the receiver operator characteristic curve of the modified classifier to predict PHES phenotype membership was 0.91 (95% CI, 0.90-0.92) in the EHR validation set. In the test set, PHES phenotype membership was associated with both increased adjusted odds of complicated course (adjusted odds ratio [aOR] 4.1; 95% CI, 3.2-5.4) and 28-day mortality (aOR of 4.8; 95% CI, 3.11-7.25) after controlling for age, severity of illness, and immunocompromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and were more likely to be stratified as high risk based on PERSEVERE biomarkers predictive of death and persistent MODS.
conclusionsThe PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlapped with higher risk strata based on prospectively validated biomarker approaches.
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