Trial reportThe Journal of clinical investigation2026
Longitudinal multiomic signatures of ARDS and sepsis inflammatory phenotypes identify pathways associated with mortality.
Trial report in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed.
- Review
- Mesenchymal Stromal Cell-Based Therapies in Sepsis-Induced Acute Lung and Kidney Injury: Current Advances and Perspectives.International journal of molecular sciences · 2026Review
- Beyond Berlin: The multidimensional evolution of ARDS in the era of precision critical care.Journal of intensive medicine · 2026Article
- Acute hypoxemic respiratory failure: from static severity to trajectory-based phenotyping.Intensive care medicine · 2026Article
- The molecular ICU: a primer on omics, informatics and the future of precision critical care.Critical care (London, England) · 2026Review
- Admission Cytokine Profiling for ICU Mortality Prediction in Heterogeneous Acute Respiratory Failure: An Exploratory Cytokine Profiling Study.Diagnostics (Basel, Switzerland) · 2026Article
- The Tip of the Iceberg: Pathway Biology Must Anchor the Next Generation of Critical Care Trials.Critical care explorations · 2026Article
Corrections and comments
- Update of
Authors and funding
28 authors.
Funding
Abstract
BACKGROUNDCritically ill patients with acute respiratory distress syndrome (ARDS) and sepsis exhibit distinct inflammatory phenotypes with divergent clinical outcomes, but the underlying molecular mechanisms remain poorly understood. These phenotypes, derived from clinical data and protein biomarkers, were associated with metabolic differences in a pilot study.METHODSWe performed integrative multiomics analysis of blood samples from 160 patients with ARDS in the ROSE trial, randomly selecting 80 patients from each latent class analysis-defined inflammatory phenotype (hyperinflammatory and hypoinflammatory) with phenotype probability greater than 0.9. Untargeted plasma metabolomics and whole-blood transcriptomics at day 0 and day 2 were analyzed using multimodal factor analysis (MEFISTO). The primary outcome was 90-day mortality, with validation in an independent critically ill sepsis cohort (EARLI).RESULTSMultiomics integration revealed 4 molecular signatures associated with mortality: (a) enhanced innate immune activation coupled with increased glycolysis (associated with hyperinflammatory phenotype), (b) hepatic dysfunction and immune dysfunction paired with impaired fatty acid β-oxidation (associated with hyperinflammatory phenotype), (c) interferon program suppression coupled with altered mitochondrial respiration (associated with hyperinflammatory phenotype), and (d) redox impairment and cell proliferation pathways (not associated with inflammatory phenotype). These signatures persisted through day 2 of trial enrollment. Within-phenotype analysis revealed distinct mortality-associated pathways in each group. All molecular signatures were validated in the independent EARLI cohort.CONCLUSIONInflammatory phenotypes of ARDS reflect distinct underlying biological processes with both phenotype-specific and phenotype-independent pathways influencing patient outcomes, all characterized by mitochondrial dysfunction. These findings suggest potential therapeutic targets for precise treatment strategies in critical illness.FUNDINGNIH National Heart, Lung, and Blood Institute and National Institute of General Medical Sciences.
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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.