Evidence mapPaperPMID 40794402Full record

ArticleCritical care explorations2025

Soluble Fms-Like Tyrosine Kinase-1 Associates With Risk of Acute Respiratory Distress Syndrome and Mortality in Sepsis.

Tiffanie K Jones, John P Reilly, Brian J Anderson, Todd A Miano, Brijesh Karanam, Caroline A G Ittner, Michael G S Shashaty, Rui Feng, Nuala J Meyer

Abstract read
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Article in Critical care explorations, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Tiffanie K JonesPulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
John P ReillyPulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Brian J AndersonPulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Todd A MianoDivision of Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Brijesh KaranamPulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Caroline A G IttnerPulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Michael G S ShashatyPulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Rui FengDivision of Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Nuala J MeyerPulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Funding

Investigating Individual Susceptibility and Host Response in Acute Respiratory Distress SyndromeR35HL161196 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$975k
An ABO Blood Type Defined ARDS Endotype in SepsisR01HL155159 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$506k
Operationalizing the RAGE Axis in Acute Respiratory Distress SyndromeK01HL149851 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Tiffanie Kae Jones · 2023 to 2023
$162k
NHLBI NIH HHS K01 HL149851NHLBI NIH HHS R01 HL155159NHLBI NIH HHS R35 HL161196NIH HHS S10 OD025172
6 · The paper itself

Abstract

importanceThe vascular endothelial growth factor (VEGF) signaling pathway is important in the pathogenesis of acute respiratory distress syndrome (ARDS) with supportive genetic and proteomic evidence. Genetic polymorphisms within FLT1, which encodes VEGF receptor 1, associate with risk of ARDS in sepsis. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is a secreted splice variant of FLT1 that acts as a potent antagonist to circulating VEGF.

objectivesTo assess the association between early plasma concentrations of sFlt-1 and risk of ARDS and to determine if ARDS mediates the relationship between sFlt-1 and mortality during sepsis. DESIGN, SETTING, AND

participantsIn a prospective cohort study, we enrolled 198 critically ill patients with sepsis per Sepsis-2 criteria. ARDS was defined per Berlin criteria. MAIN OUTCOMES AND MEASURES: Levels of sFlt-1 were quantified using electrochemiluminescence on plasma collected in the emergency department upon admission. We tested the association between plasma levels of sFlt-1 with ARDS and mortality using logistic regression adjusting for age, sex, and pulmonary versus nonpulmonary source of sepsis. We applied causal mediation analysis to determine the percentage of the total effect of sFlt-1 on mortality that was mediated by ARDS.

resultsWe enrolled 198 patients; ARDS developed within 6 days in 29%. Plasma levels of sFlt-1 were significantly associated with risk of ARDS in sepsis (odds ratio [OR], 1.91 per log increase; 95% CI, 1.31-2.76 per log increase; p < 0.01). Plasma sFlt-1 levels were also associated with mortality (OR, 2.19 per log increase; 95% CI, 1.57-3.08 per log increase; p < 0.01). ARDS mediated 20.3% (95% CI, 6.9-98.1%) of the total effect of sFlt-1 on mortality (p < 0.01). CONCLUSIONS AND RELEVANCE: Higher plasma levels of sFlt-1 were associated with an increased risk of ARDS and ARDS mediated a significant proportion of the sFlt-1-associated mortality observed during sepsis. Our findings further implicate dysregulated VEGF signaling in ARDS and suggest that plasma sFlt-1 merits further investigation as an early endothelial therapeutic target for sepsis-associated ARDS and mortality.

Indexed as

Respiratory Distress SyndromeSepsisVascular Endothelial Growth Factor Receptor-1AgedBiomarkersFemaleHumansMaleMiddle AgedProspective StudiesRisk FactorsBiomarkersFLT1 protein, humanVascular Endothelial Growth Factor Receptor-1acute respiratory distress syndromemortalitysepsis

Identifiers

PMID40794402
PMCPMC13157332

What Socratic holds

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Registered trials

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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.