Evidence map›Paper›PMID 40459371›Full record

ArticleCritical care medicine2025

Plasma Soluble Intercellular Adhesion Molecule-1 Has a Central Role in Biomarker Network Analysis and Is Associated With Poor Outcomes in Two Distinct Pediatric Cohorts of Acute Respiratory Distress Syndrome and Acute Respiratory Failure.

Michelle J Lim, Jane E Whitney, Colin J Sallee, Daniela Markovic, Arunima Bera, Pratik Sinha, Angela Zeigler, Lucia Chen, Matt S Zinter, Arham Ali and 5 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Critical care medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

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. Observational
  2. Article
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

15 authors.

Michelle J LimDepartment of Pediatrics, Division of Critical Care, UC Davis Children's Hospital, UC Davis School of Medicine, Sacramento, CA.ORCID 0000-0003-0311-8832
Jane E WhitneyDivision of Medical Critical Care, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Colin J SalleeDepartment of Pediatrics, Division of Pediatric Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.
Daniela MarkovicDepartment of Pediatrics, Division of Pediatric Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.
Arunima BeraDepartment of Pediatrics, Division of Pediatric Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.
Pratik SinhaDivision of Clinical and Translational Research, Washington University School of Medicine, Saint Louis, MO.
Angela ZeiglerDepartment of Pediatrics, Division of Pediatric Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.
Lucia ChenDepartment of Pediatrics, Division of Pediatric Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.
Matt S ZinterDepartment of Pediatrics, Division of Critical Care, UCSF School of Medicine, Benioff Children's Hospital, San Francisco, CA.
Arham AliDepartment of Pediatrics, Division of Critical Care, Loma Linda University School of Medicine, Loma Linda University Children's Hospital, Loma Linda, CA.
Michael A MatthayDepartments of Medicine and Anesthesia, Cardiovascular Research Institute, UCSF, San Francisco, CA.
Andreas SchwingshacklDepartment of Pediatrics, Division of Pediatric Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.
Michael S D AgusDivision of Medical Critical Care, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Anil SapruDepartment of Pediatrics, Division of Pediatric Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0003-1528-8249
Pediatric Acute Lung Injury (PALI) and Coagulation and Fibrinolysis in Pediatric Insulin Titration Trial (CAF-PINT) Study Investigators

Funding

UC Davis Clinical and Translational Science CenterUL1TR001860 · NCATS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KENYON, NICHOLAS J., LYLES, COURTNEY REES · 2016 to 2025
$47.3M
Institutional Career Development Core (KL2)KL2TR001859 · NCATS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HOLMES, JAMES F. · 2016 to 2025
$10.1M
HALF-PINT: Heart and Lung Failure - Pediatric INsulin Titration trial - CCCU01HL107681 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI AGUS, MICHAEL SD, NADKARNI, VINAY M · 2011 to 2016
$9.6M
Precision Medicine in Sepsis with Critical IllnessR35GM142992 · NIGMS · WASHINGTON UNIVERSITY · PI Pratik Sinha · 2021 to 2026
$2.4M
Coagulation and Fibrinolysis in Pediatric Insulin Titration TrialR01HL114484 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAPRU, ANIL · 2012 to 2015
$1.6M
Targeted Genomic Analysis of Coagulation Pathways in Acute Lung InjuryK23HL085526 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAPRU, ANIL · 2007 to 2011
$756k
NCATS NIH HHS KL2 TR001859NCATS NIH HHS UL1 TR001860NHLBI NIH HHS K23 HL085526NHLBI NIH HHS R01 HL114484NHLBI NIH HHS U01 HL107681NIGMS NIH HHS R35 GM142992
6 · The paper itself

Abstract

objectivesIntercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on immune, endothelial, and epithelial cells. In the setting of inflammation, it becomes upregulated and spliced into a soluble form (soluble ICAM-1 [sICAM-1]). This study examined the association of sICAM-1 with clinical outcomes in two large pediatric cohorts with acute respiratory distress syndrome (ARDS) and acute respiratory failure (ARF) and examined the relationships between sICAM-1 and other protein biomarkers utilizing network analysis to contextualize its role in ARDS pathophysiology.

designSecondary analysis of prospective cohort studies.

settingMulticenter PICUs. PATIENTS OR SUBJECTS: Critically ill children with ARDS (Pediatric Acute Lung Injury [PALI], 2008-2014) and ARF (Coagulation and Fibrinolysis in Pediatric Insulin Titration Trial [CAF-PINT], 2012-2016).

interventionsNone. MEASUREMENTS AND MAIN

resultssICAM-1 levels were measured from plasma collected within 72 hours of diagnosis. The primary outcome was in-hospital mortality, and secondary outcomes included multiple organ dysfunction and ventilator-free days. We constructed a biomarker correlation-based network that included sICAM-1 and 32 plasma biomarkers reflective of inflammation, endothelial and epithelial injury, and extracellular matrix degradation. Key biomarkers with centrality metrics in the top 10% (≥ 90th percentile) were defined as critical hubs within the network. The study included 214 children from PALI and 251 from CAF-PINT. In-hospital mortality was 18% and 14%, respectively. Baseline median oxygenation index ratios were 10 (interquartile range [IQR], 5.6-19.7) and 8.5 (IQR, 3.5-17.7). Higher plasma sICAM-1 was associated with in-hospital mortality, multiple organ dysfunction, and fewer ventilator-free days in each of the two cohorts (all p < 0.05). Tissue inhibitor of metalloproteinase-1 (composite centrality, 0.99), tumor necrosis factor receptor-1 (0.83), sICAM-1 (0.74), and interleukin-8 (0.74) were identified as network hubs.

conclusionsElevated sICAM-1 levels were associated with poor outcomes in two separate cohorts of ARDS and ARF patients. Network analysis revealed sICAM-1 as a central hub, characterized by high centrality metrics. These findings underscore the multifaceted role of sICAM-1 in leukocyte transmigration, inflammation, and endothelial dysfunction and highlight its critical role in ARDS pathophysiology.

Indexed as

Intercellular Adhesion Molecule-1Respiratory Distress SyndromeRespiratory InsufficiencyAdolescentBiomarkersChildChild, PreschoolFemaleHumansInfantIntensive Care Units, PediatricMaleProspective StudiesBiomarkersICAM1 protein, humanIntercellular Adhesion Molecule-1acute respiratory distress syndromeacute respiratory failureinflammationnetwork analysispediatric acute respiratory distress syndromesoluble intercellular adhesion molecule

Identifiers

PMID40459371
PMCPMC12323721

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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 OpenQuestion graph.