Evidence map›Paper›PMID 41065504›Full record

Observational studyCritical care explorations2025

Biomarkers of Microcirculatory Dysfunction in Sepsis: A Pilot Prospective Observational Study.

August Longino, Katharine Martin, Stephen Bourland, Whitney Phinney, Timothy Wood, Eli Camargo, Ana Garcia, Judith Oakes, Terra Hiller, Ryan Weiss and 3 more

Abstract readObservational Study
In one paragraph

Observational study in Critical care explorations, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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.

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

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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

13 authors.

August LonginoDepartment of Hospital Medicine, Denver Health Medical Center, Denver, CO.ORCID 0000-0001-9963-5425
Katharine MartinDepartment of Internal Medicine, New York University Medical Center, New York City, NY.
Stephen BourlandDepartment of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO.
Whitney PhinneyBiochemical Genetics Laboratory, Children's Hospital of Colorado, Aurora, CO.
Timothy WoodBiochemical Genetics Laboratory, Children's Hospital of Colorado, Aurora, CO.
Eli CamargoDepartment of Pulmonary Critical Care, Denver Health Medical Center, Denver, CO.
Ana GarciaDepartment of Pulmonary Critical Care, Denver Health Medical Center, Denver, CO.
Judith OakesDepartment of Pulmonary Critical Care, Denver Health Medical Center, Denver, CO.
Terra HillerDepartment of Pulmonary Critical Care, Denver Health Medical Center, Denver, CO.
Ryan WeissComplex Carbohydrate Research Center, University of Georgia, Athens, GA.
Amrita BasuComplex Carbohydrate Research Center, University of Georgia, Athens, GA.
Ivor DouglasDepartment of Pulmonary Critical Care, Denver Health Medical Center, Denver, CO.
Jospeh HippensteelDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.

Funding

Lung-Brain Axis as a Mediator of DeliriumK08HL159353 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI HIPPENSTEEL, JOSEPH ALAN · 2021 to 2025
$809k
Endothelial Glycocalyx Degradation during Sepsis in AgingR03AG074056 · NIA · UNIVERSITY OF COLORADO DENVER · PI HIPPENSTEEL, JOSEPH ALAN · 2021 to 2022
$311k
NHLBI NIH HHS K08 HL159353NIA NIH HHS R03 AG074056
6 · The paper itself

Abstract

contextTo evaluate and compare sublingual microscopy (SLM) to urinary glycosaminoglycan (GAG) assays, dimethylmethylene blue (DMMB) assay, and liquid chromatography tandem mass spectrometry (LC-MS/MS) quantification of GAGs as biomarkers of microvascular dysfunction in patients with sepsis and septic shock. HYPOTHESIS: Indicators of microvascular dysfunction and markers of endothelial glycocalyx (eGC) degradation would be associated with sepsis. METHODS AND MODELS: Prospective, observational case-control study.

settingDenver Health Medical Center, a safety-net hospital in Denver, CO. SUBJECTS: Forty-four adult patients with sepsis or septic shock and 24 healthy control patients undergoing elective orthopedic procedures. Exclusion criteria included pregnancy and incarceration.

resultsSublingual microvascular parameters (De Backer Density, proportion of perfused vessels) were measured using darkfield sidestream microscopy, and urinary GAGs were measured via DMMB colorimetric assay and LC-MS/MS targeting heparan sulfate (HS), dermatan sulfate, and keratan sulfate. Validation of HS quantification was performed on a subset using hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS). LC-MS/MS HS was significantly higher in sepsis vs. controls (Area under the curve 0.85; 95% CI, 0.76-0.95), demonstrating higher diagnostic performance than SLM (De Backer Density AUC 0.71) and DMMB GAGs (AUC 0.62). LC-MS/MS and HILIC-MS HS levels were strongly correlated (R² = 0.97, p < 0.001). DMMB GAGs were associated with HS subtypes (p = 0.05) and SLM density (p = 0.03). No significant associations with in-hospital mortality or acute kidney injury were observed. INTERPRETATION AND

conclusionsAmong the evaluated modalities, LC-MS/MS quantification of HS showed the greatest discriminative ability for identifying sepsis and correlated strongly with established mass spectrometric methods. SLM exhibited moderate diagnostic utility and significant associations with GAG levels, reinforcing its biologic relevance. However, its bedside application may be limited by challenges in image acquisition and analysis. The concordance across SLM, DMMB, and LC-MS/MS supports eGC degradation as a key feature of sepsis pathophysiology. These findings highlight the promise of LC-MS/MS as a scalable, rapid, and mechanistically informed platform for biomarker-driven enrichment in future sepsis trials and clinical care.

Indexed as

MicrocirculationSepsisAdultAgedBiomarkersCase-Control StudiesChromatography, LiquidFemaleHeparan SulfateHumansKeratan SulfateMaleMicroscopyMiddle AgedPilot ProjectsProspective StudiesBiomarkersHeparan SulfateKeratan SulfatebiomarkersglycosaminoglycansmicrovasculatureSepsissublingual microscopy

Identifiers

PMID41065504
PMCPMC12513444

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.