Evidence map›Paper›PMID 41632536›Full record

Trial reportThe Journal of clinical investigation2026

Plasma chondroitin sulfate predicts the effectiveness of fluid resuscitation strategies in patients with sepsis.

Kaori Oshima, Bailu Yan, Ran Tao, Gustavo Amorim, Chiara Di Gravio, Sarah A McMurtry, Ryan C Burke, Yunbi Nam, Ina Nikolli, Max S Kravitz and 13 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

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. It is linked to trial NCT03434028 (Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

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.

NCT03434028 phase3completednot on this map

Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis

TypeinterventionalSponsorMassachusetts General HospitalRan2018 to 2022Enrolled1,563ConditionsSeptic ShockArmsEarly Vasopressors, Early Fluids
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Kaori OshimaDepartment of Medicine, Mass General Brigham, Boston, Massachusetts, USA.
Bailu YanDepartment of Biostatistics and.
Ran TaoDepartment of Biostatistics and.
Gustavo AmorimDepartment of Biostatistics and.
Chiara Di GravioDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
Sarah A McMurtryDepartment of Medicine, University of Colorado, Aurora, Colorado, USA.
Ryan C BurkeDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Yunbi NamDepartment of Biostatistics and.
Ina NikolliDepartment of Medicine, Mass General Brigham, Boston, Massachusetts, USA.
Max S KravitzDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Daniel StephensonDepartment of Biochemistry and Molecular Genetics, University of Colorado, Aurora, Colorado, USA.
Aaron IssaianDepartment of Biochemistry and Molecular Genetics, University of Colorado, Aurora, Colorado, USA.
Kirk C HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado, Aurora, Colorado, USA.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado, Aurora, Colorado, USA.
Ivor S DouglasDepartment of Medicine, University of Colorado, Aurora, Colorado, USA.
Wesley H SelfVanderbilt Institute for Clinical and Translational Research and Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Christopher J LindsellDepartment of Biostatistics and Bioinformatics and Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
Carolyn LerouxDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.
Angelika RingorDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.
Michael A MatthayDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.
Jonathan S SchildcroutDepartment of Biostatistics and.
Nathan I ShapiroDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Eric P SchmidtDepartment of Medicine, Mass General Brigham, Boston, Massachusetts, USA.

Funding

Outcome Dependent Sampling Studies of Longitudinal Data: Design and AnalysisR01HL094786 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jonathan Scott Schildcrout · 2009 to 2026
$6.1M
The Impact of Fluid Resuscitation on Glycocalyx Degradation in Septic ShockR01HL149422 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SCHMIDT, ERIC PETER, SHAPIRO, NATHAN I · 2019 to 2022
$1.7M
NHLBI NIH HHS R01 HL094786NHLBI NIH HHS R01 HL149422
6 · The paper itself

Abstract

BACKGROUNDPlasma heparan sulfate, a glycosaminoglycan released during endothelial glycocalyx degradation, predicts sepsis mortality. Chondroitin sulfate is a circulating glycosaminoglycan not specific to glycocalyx degradation; its relevance to sepsis is unknown.METHODSWe studied the associations of plasma chondroitin sulfate with (a) mortality in patients with sepsis-associated hypotension and (b) the relative effectiveness of a randomly assigned liberal versus restrictive intravenous fluid resuscitation strategy. We selected 574 patients enrolled in the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis trial using an outcome-enriched sampling strategy. We used liquid chromatography-mass spectrometry to quantify plasma chondroitin sulfate. In comparison, we measured hyaluronic acid as a glycocalyx degradation marker and IL-6 as an inflammatory biomarker. We conducted Cox proportional hazards regression analyses to examine associations of baseline biomarker concentrations with mortality and resuscitation strategy effectiveness. We used inverse probability of selection weights and generalized raking to account for the nonrepresentative sampling design.RESULTSPlasma chondroitin sulfate, hyaluronic acid, and IL-6 were associated with mortality within 90 days. As baseline chondroitin sulfate increased, subsequent randomization to a restrictive strategy was increasingly beneficial (P = 0.022): treatment effect hazard ratio (restrictive versus liberal) for mortality was estimated as 1.49 (95% CI, 0.98-2.27), 1.30 (95% CI, 1.00-1.69), 1.09 (95% CI, 0.82-1.44), 0.88 (95% CI, 0.66-1.16), and 0.71 (95% CI, 0.52-0.97) for 10th, 25th, 50th, 75th, and 90th percentiles of baseline chondroitin sulfate.CONCLUSIONPlasma chondroitin sulfate predicts sepsis mortality and may modify the response to a subsequent liberal versus restrictive intravenous fluid resuscitation strategy.TRIAL REGISTRATIONClinicalTrials.gov NCT03434028.FUNDINGNIH grants R01HL149422 and R01HL094786.

Indexed as

Chondroitin SulfatesFluid TherapyResuscitationSepsisAgedBiomarkersFemaleHumansHyaluronic AcidInterleukin-6MaleMiddle AgedBiomarkersChondroitin SulfatesHyaluronic AcidIL6 protein, humanInterleukin-6BiomarkersClinical ResearchGlycobiologyInfectious diseaseInflammation

Identifiers

PMID41632536
PMCPMC13038195

What OpenQuestion holds

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LicenceCC BY
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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.