ArticleScience translational medicine2019
Prospective clinical testing and experimental validation of the Pediatric Sepsis Biomarker Risk Model.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05311046 (Biomarker-enhanced Artificial Intelligence Based Pediatric Sepsis Screening Tool Towards Early Recognition and Personalized Therapeutics), which is not on this map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Biomarker-enhanced Artificial Intelligence Based Pediatric Sepsis Screening Tool Towards Early Recognition and Personalized Therapeutics
Who cites it
44 citing papers in PubMed, 99 citations in OpenAlex.
- Aberrant STAT signaling and T cell dysregulation define a targetable pediatric sepsis endotype.The Journal of clinical investigation · 2026Article
- External Validation, Molecular Signatures, and Therapeutic Relevance of Pediatric Sepsis-Associated Acute Kidney Injury Subphenotypes.Critical care medicine · 2026Observational
- PPARγ Variant rs10865710 and Mortality in Pediatric Septic Shock Stratified by Corticosteroid Exposure.Critical care explorations · 2026Observational
- Pediatric Sepsis: Evolving Subphenotypes, Overlap Syndromes, and the Path to Precision Therapies.Clinics in chest medicine · 2026Review
- Dynamic biomarker profiling and phenotyping in burn sepsis: a retrospective cohort study using growth mixture modeling.Frontiers in cellular and infection microbiology · 2026Article
- The Clinical View of Sepsis-Associated AKI: How Basic Science Can Help Solve This Problem.Seminars in nephrology · 2025Review
- Derivation and Validation of a Clinical and Endothelial Biomarker Risk Model to Predict Persistent Pediatric Sepsis-Associated Acute Respiratory Dysfunction.CHEST critical care · 2025Article
- Neutrophil dysregulation differentiates pediatric septic shock biomarker-based mortality-risk strata: insights from weighted gene co-expression network and transcriptomic analyses.Frontiers in immunology · 2025Article
- Molecular mechanisms and potential implications of ferroptosis, cuproptosis, and disulfidptosis in septic lung injury.Frontiers in medicine · 2025Review
- Functional immune profiling of hyper- and hypo-inflammatory subphenotypes of critical illness: a secondary analysis.Frontiers in immunology · 2025Article
- Identification and transcriptomic assessment of latent profile pediatric septic shock phenotypes.Critical care (London, England) · 2024Observational
- Biological basis of critical illness subclasses: from the bedside to the bench and back again.Critical care (London, England) · 2024Review
- The Translational Value of Rodent Models of Sepsis.American journal of respiratory and critical care medicine · 2024Article
- Revisiting Post-ICU Admission Fluid Balance Across Pediatric Sepsis Mortality Risk Strata: A Secondary Analysis of a Prospective Observational Cohort Study.Critical care explorations · 2024Article
- Derivation, validation, and transcriptomic assessment of pediatric septic shock phenotypes identified through latent profile analyses: Results from a prospective multi-center observational cohort.Research square · 2023Article
- External validation of the modified sepsis renal angina index for prediction of severe acute kidney injury in children with septic shock.Critical care (London, England) · 2023Observational
- Serum renin and prorenin concentrations predict severe persistent acute kidney injury and mortality in pediatric septic shock.Pediatric nephrology (Berlin, Germany) · 2023Observational
- External validation and biomarker assessment of a high-risk, data-driven pediatric sepsis phenotype characterized by persistent hypoxemia, encephalopathy, and shock.Research square · 2023Article
- Prognostic and predictive value of endothelial dysfunction biomarkers in sepsis-associated acute kidney injury: risk-stratified analysis from a prospective observational cohort of pediatric septic shock.Critical care (London, England) · 2023Observational
- Increasing angiotensin-converting enzyme concentrations and absent angiotensin-converting enzyme activity are associated with adverse kidney outcomes in pediatric septic shock.Critical care (London, England) · 2023Observational
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Authors and funding
17 authors at 15 institutions in 2 countries.
Funding
Abstract
Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rational development, testing, and targeting of new therapies. We previously developed the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate mortality risk and proposed its use as a prognostic enrichment tool in sepsis clinical trials; prognostic enrichment selects patients based on mortality risk independent of treatment. Here, we show that PERSEVERE has excellent performance in a diverse cohort of children with septic shock with potential for use as a predictive enrichment strategy; predictive enrichment selects patients based on likely response to treatment. We demonstrate that the PERSEVERE biomarkers are reliably associated with mortality in mice challenged with experimental sepsis, thus providing an opportunity to test precision medicine strategies in the preclinical setting. Using this model, we tested two clinically feasible therapeutic strategies, guided by the PERSEVERE-based enrichment, and found that mice identified as high risk for mortality had a greater bacterial burden and could be rescued by higher doses of antibiotics. The association between higher pathogen burden and higher mortality risk was corroborated among critically ill children with septic shock. This bedside to bench to bedside approach provides proof of principle for PERSEVERE-guided application of precision medicine in sepsis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.