Observational studyAmerican journal of respiratory and critical care medicine2017
Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP.
Observational study in American journal of respiratory and critical care medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immune System Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.Pediatrics · 2022Pooled it
- Trial
- Proteomic profiling and pathway analyses reveal molecular signatures and immune networks in pediatric sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Multi-omic and computational approaches for biomarker discovery and clinical translation in pediatric sepsis.Frontiers in pharmacology · 2026Review
- Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.Pediatric research · 2025Review
- Transcriptomic Biomarkers Associated With Microbiological Etiology and Disease Severity in Childhood Pneumonia.The Journal of infectious diseases · 2025Article
- Functional immune profiling of hyper- and hypo-inflammatory subphenotypes of critical illness: a secondary analysis.Frontiers in immunology · 2025Article
- Predictive gene expression signature diagnoses neonatal sepsis before clinical presentation.EBioMedicine · 2024Article
- Pediatric Sepsis Diagnosis, Management, and Sub-phenotypes.Pediatrics · 2024Article
- Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.Burns & trauma · 2024Review
- Article
- Drp1/p53 interaction mediates p53 mitochondrial localization and dysfunction in septic cardiomyopathy.Journal of molecular and cellular cardiology · 2023Article
- The Role of Transcriptomics in Redefining Critical Illness.Critical care (London, England) · 2023Review
- Precision diagnostics in children.Cambridge prisms. Precision medicine · 2023Review
- Refining empiric subgroups of pediatric sepsis using machine-learning techniques on observational data.Frontiers in pediatrics · 2023Review
- Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.Frontiers in immunology · 2023Article
- Pediatric sepsis biomarkers for prognostic and predictive enrichment.Pediatric research · 2022Review
- Pediatric Sepsis Research: Where Are We and Where Are We Going?Frontiers in pediatrics · 2022Review
- Endothelial Damage in Sepsis: The Importance of Systems Biology.Frontiers in pediatrics · 2022Review
- Comparison of Rapid Cytokine Immunoassays for Functional Immune Phenotyping.Frontiers in immunology · 2022Observational
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Authors and funding
19 authors.
Funding
Abstract
rationaleWe previously derived and validated the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate baseline mortality risk in children with septic shock. The PERSEVERE biomarkers are serum proteins selected from among the proteins directly related to 80 mortality risk assessment genes. The initial approach to selecting the PERSEVERE biomarkers left 68 genes unconsidered.
objectivesTo determine if the 68 previously unconsidered genes can improve upon the performance of PERSEVERE and to provide biological information regarding the pathophysiology of septic shock.
methodsWe reduced the number of variables by determining the biological linkage of the 68 previously unconsidered genes. The genes identified through variable reduction were combined with the PERSEVERE-based mortality probability to derive a risk stratification model for 28-day mortality using classification and regression tree methodology (n = 307). The derived tree, PERSEVERE-XP, was then tested in a separate cohort (n = 77). MEASUREMENTS AND MAIN
resultsVariable reduction revealed a network consisting of 18 mortality risk assessment genes related to tumor protein 53 (TP53). In the derivation cohort, PERSEVERE-XP had an area under the receiver operating characteristic curve (AUC) of 0.90 (95% confidence interval, 0.85-0.95) for differentiating between survivors and nonsurvivors. In the test cohort, the AUC was 0.96 (95% confidence interval, 0.91-1.0). The AUC of PERSEVERE-XP was superior to that of PERSEVERE.
conclusionsPERSEVERE-XP combines protein and mRNA biomarkers to provide mortality risk stratification with possible clinical utility. PERSEVERE-XP significantly improves on PERSEVERE and suggests a role for TP53-related cellular division, repair, and metabolism in the pathophysiology of septic shock.
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Registered trials
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