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• W4385483407 abstract "Abstract Objective Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. Data-driven phenotyping approaches that leverage electronic health record (EHR) data hold promise given the widespread availability of EHRs. We sought to externally validate 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. Design: We trained and validated a random forest classifier using organ dysfunction subscores in the EHR dataset used to derive the PHES phenotype. We used the classifier to assign phenotype membership in a test set consisting of prospectively enrolled pediatric septic shock patients. We compared biomarker profiles of those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk-strata. Setting: 25 pediatric intensive care units (PICU) across the U.S. Patients: EHR data from 15,246 critically ill patients sepsis-associated MODS and 1,270 pediatric septic shock patients in the test cohort of whom 615 had biomarker data. Interventions: None Measurements and Main Results: The area under the receiver operator characteristic curve (AUROC) of the new classifier to predict PHES phenotype membership was 0.91(95%CI, 0.90–0.92) in the EHR validation set. In the test set, patients with the PHES phenotype were independently associated with both increased odds of complicated course (adjusted odds ratio [aOR] of 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 immuno-compromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and overlapped with high risk-strata based on PERSEVERE biomarkers predictive of death and persistent MODS. Conclusions The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlap with higher risk-strata based on validated biomarker approaches." @default.
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• W4385483407 date "2023-08-02" @default.
• W4385483407 modified "2023-10-16" @default.
• W4385483407 title "External validation and biomarker assessment of a high-risk, data-driven pediatric sepsis phenotype characterized by persistent hypoxemia, encephalopathy, and shock." @default.
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• W4385483407 doi "https://doi.org/10.21203/rs.3.rs-3216613/v1" @default.
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