ArticlePediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies2019
A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure.
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, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 3 of them syntheses that pooled it.
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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
52 citing papers in PubMed, 3 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Surviving Sepsis Campaign International Guidelines for the Management of Sepsis and Septic Shock in Children 2026.Intensive care medicine · 2026Pooled it
- A Research Agenda for Precision Medicine in Sepsis and Acute Respiratory Distress Syndrome: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2021Guideline
- Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.Intensive care medicine · 2020Guideline
- Aptamer-based proteomics in pediatric patients with severe traumatic brain injury: a pilot study.Pediatric research · 2026Article
- Aberrant STAT signaling and T cell dysregulation define a targetable pediatric sepsis endotype.The Journal of clinical investigation · 2026Article
- Deleterious variants in LTBP4 are associated with severe pediatric sepsis.Pediatric research · 2026Article
- Plasma Linoleic Acid Is Associated With Pediatric Sepsis Phenotype and Acute Kidney Injury.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2026Article
- Pediatric Sepsis: Evolving Subphenotypes, Overlap Syndromes, and the Path to Precision Therapies.Clinics in chest medicine · 2026Review
- Microvascular phenotypes in pediatric sepsis identified by machine learning: prognostic implications for organ dysfunction and mortality.Critical care (London, England) · 2026Article
- Article
- The diagnostic and immunomodulatory role of IL-37 in pediatric sepsis.Frontiers in immunology · 2026Article
- Application of New Pediatric Sepsis Definition to a Multicenter Observational Cohort of Previously Enrolled Severe Sepsis Patients Defined by SIRS Plus Organ Dysfunction.Journal of intensive care medicine · 2025Observational
- Hyperferritinemia and Macrophage Activation Syndrome in Septic Shock: Recent Advances with a Pediatric Focus (2020-2025).Children (Basel, Switzerland) · 2025Review
- Epstein-Barr Virus Seropositivity, Immune Dysregulation, and Mortality in Pediatric Sepsis.JAMA network open · 2025Article
- Causal Discovery in Sepsis-A (Random) Walk in the Park?JAMA network open · 2025Article
- Metabolomic and cytokine profiles of high-risk sepsis phenotypes in children.Scientific reports · 2025Article
- Risk factors for prolonged infection and secondary infection in pediatric severe sepsis.Infection · 2025Article
- Thrombocytopenia in Critically Ill Children: A Review for Practicing Clinicians.Children (Basel, Switzerland) · 2025Review
- Age influences the circulating immune profile in pediatric sepsis.Frontiers in immunology · 2025Observational
- Digital solutions in paediatric sepsis: current state, challenges, and opportunities to improve care around the world.The Lancet. Digital health · 2024Review
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Authors and funding
20 authors at 8 institutions in 1 country.
Funding
Abstract
objectivesOngoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis.
designProspective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure.
settingNine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PATIENTS: Children with severe sepsis and indwelling arterial or central venous catheters.
interventionsClinical data collection and twice weekly blood sampling until PICU day 28 or discharge. MEASUREMENTS AND MAIN
resultsOf 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06-6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72-18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35-4.08).
conclusionsThese three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children.
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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.