ArticleCritical care (London, England)2023
Hyperferritinemic sepsis, macrophage activation syndrome, and mortality in a pediatric research network: a causal inference analysis.
Article in Critical care (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 20 citations in OpenAlex.
- Evaluation of the effect of therapeutic plasma exchange on serum cytokine levels in pediatric intensive care unit.Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy · 2026Trial
- Diagnostic and Prognostic Value of Ferritin and Soluble Interleukin-2 Receptor α in Critically Ill Children with Hyperferritinemia.Diagnostics (Basel, Switzerland) · 2026Article
- Toward a Unified Neuroimmune Framework for Infection-Associated Psychiatric Disorders.Diseases (Basel, Switzerland) · 2026Review
- Loss of IL10 Signaling Promotes TLR9-Driven Liver Dysfunction by Allowing T Cell Receptor-Mediated T Cell Activation.Research square · 2026Article
- Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS.Critical care (London, England) · 2026Observational
- Soluble CD25 as a potential prognostic biomarker for pediatric septic shock and its comparison with hemophagocytic lymphohistiocytosis.BMC research notes · 2026Article
- A novel two-hit murine model of viral-primed sepsis-associated acute kidney injury.American journal of physiology. Renal physiology · 2026Article
- Diagnostic utility of serum ferritin in culture proven bacterial infection: an observational study.BMC infectious diseases · 2026Observational
- Normoferritinemic Versus Hyperferritinemic Inflammation in Patients Admitted to the Department of Internal Medicine.Journal of clinical medicine · 2026Article
- Pediatric Sepsis: Evolving Subphenotypes, Overlap Syndromes, and the Path to Precision Therapies.Clinics in chest medicine · 2026Review
- The "cytokine storm" in infection and sepsis: win the battle but lose the war.Military Medical Research · 2026Review
- The Interleukin Network in Sepsis: From Cytokine Storm to Clinical Applications.Diagnostics (Basel, Switzerland) · 2025Review
- Hyperferritinemia and Macrophage Activation Syndrome in Septic Shock: Recent Advances with a Pediatric Focus (2020-2025).Children (Basel, Switzerland) · 2025Review
- Targeting hemostatic enzymes: from mechanistic insights to therapeutic frontiers.Current opinion in hematology · 2025Review
- Causal Discovery in Sepsis-A (Random) Walk in the Park?JAMA network open · 2025Article
- Ferritin's role in infectious diseases: Exploring pathogenic mechanisms and clinical implications.New microbes and new infections · 2025Review
- Thrombocytopenia in Critically Ill Children: A Review for Practicing Clinicians.Children (Basel, Switzerland) · 2025Review
- Functional immune profiling of hyper- and hypo-inflammatory subphenotypes of critical illness: a secondary analysis.Frontiers in immunology · 2025Article
- Article
- Hyperferritinemia is Associated with Thrombocytopenia and Increased Mortality Risk in Adult Sepsis Patients: A Retrospective Study of Two Observational Cohorts.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisObservational
Corrections and comments
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Authors and funding
20 authors at 11 institutions in 1 country.
Funding
Abstract
backgroundOne of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network's objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis.
methodsWe assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis without hyperferritinemia. Causal inference analysis of these 41 variables, MAS, and mortality was performed.
resultsMortality was increased in children with hyperferritinemic sepsis (27/117, 23% vs 16/280, 5.7%; Odds Ratio = 4.85, 95% CI [2.55-9.60]; z = 4.728; P-value < 0.0001). Hyperferritinemic sepsis had higher C-reactive protein, sCD163, IL-22, IL-18, IL-18 binding protein, MIG/CXCL9, IL-1β, IL-6, IL-8, IL-10, IL-17a, IFN-γ, IP10/CXCL10, MCP-1/CCL2, MIP-1α, MIP-1β, TNF, MCP-3, IL-2RA (sCD25), IL-16, M-CSF, and SCF levels; lower ADAMTS13 activity, sFasL, whole blood ex vivo TNF response to endotoxin, and TRAIL levels; more Adenovirus, BK virus, and multiple virus DNAemias; and more MAS (P-value < 0.05). Among these variables, only MCP-1/CCL2 (the monocyte chemoattractant protein), MAS, and ferritin levels were directly causally associated with mortality. MCP-1/CCL2 and hyperferritinemia showed direct causal association with depressed ex vivo whole blood TNF response to endotoxin. MCP-1/CCL2 was a mediator of MAS. MCP-1/CCL2 and MAS were mediators of hyperferritinemia.
conclusionsThese findings establish hyperferritinemic sepsis as a high-risk condition characterized by increased cytokinemia, viral DNAemia, thrombotic microangiopathy, immune depression, macrophage activation syndrome, and death. The causal analysis provides rationale for designing anti-inflammatory trials that reduce macrophage activation to improve survival and enhance infection clearance in pediatric hyperferritinemic sepsis.
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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 Socratic graph.