Analysis of the Plasma Metabolome after Trauma, Novel Circulating Sphingolipid Signatures, and In-Hospital Outcomes.
Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers
/ blood
Critical Care
/ methods
Critical Illness
Female
Humans
Injury Severity Score
Length of Stay
/ statistics & numerical data
Longitudinal Studies
Male
Metabolome
Metabolomics
Middle Aged
Organ Dysfunction Scores
Prognosis
Prospective Studies
Sphingolipids
/ blood
Wounds, Nonpenetrating
/ blood
Young Adult
Journal
Journal of the American College of Surgeons
ISSN: 1879-1190
Titre abrégé: J Am Coll Surg
Pays: United States
ID NLM: 9431305
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
28
09
2020
revised:
15
12
2020
accepted:
16
12
2020
pubmed:
17
1
2021
medline:
16
9
2021
entrez:
16
1
2021
Statut:
ppublish
Résumé
Trauma is the leading cause of death and disability for individuals under age 55. Many severely injured trauma patients experience complicated clinical courses despite appropriate initial therapy. We sought to identify novel circulating metabolomic signatures associated with clinical outcomes following trauma. Untargeted metabolomics and circulating plasma immune mediator analysis was performed on plasma collected during 3 post-injury time periods (<6 hours [h], 6 h-24h, day 2-day 5) in critically ill trauma patients enrolled between April 2004 and May 2013 at UPMC Presbyterian Hospital in Pittsburgh, PA. Inclusion criteria were age ≥ 18 years, blunt mechanism, ICU admission, and expected survival ≥ 24 h. Exclusion criteria were isolated head injury, spinal cord injury, and pregnancy. Exploratory endpoints included length of stay (overall and ICU), ventilator requirements, nosocomial infection, and Marshall organ dysfunction (MOD) score. The top 50 metabolites were isolated using repeated measures ANOVA and multivariate empirical Bayesian analysis for further study. Eighty-six patients were included for analysis. Sphingolipids were enriched significantly (chi-square, p < 10 Metabolomic analysis identified broad alterations in circulating plasma sphingolipids after blunt trauma. Circulating sphingolipid signatures and their association with both clinical outcomes and circulating inflammatory mediators suggest a possible link between sphingolipid metabolism and the immune response to trauma.
Sections du résumé
BACKGROUND
Trauma is the leading cause of death and disability for individuals under age 55. Many severely injured trauma patients experience complicated clinical courses despite appropriate initial therapy. We sought to identify novel circulating metabolomic signatures associated with clinical outcomes following trauma.
STUDY DESIGN
Untargeted metabolomics and circulating plasma immune mediator analysis was performed on plasma collected during 3 post-injury time periods (<6 hours [h], 6 h-24h, day 2-day 5) in critically ill trauma patients enrolled between April 2004 and May 2013 at UPMC Presbyterian Hospital in Pittsburgh, PA. Inclusion criteria were age ≥ 18 years, blunt mechanism, ICU admission, and expected survival ≥ 24 h. Exclusion criteria were isolated head injury, spinal cord injury, and pregnancy. Exploratory endpoints included length of stay (overall and ICU), ventilator requirements, nosocomial infection, and Marshall organ dysfunction (MOD) score. The top 50 metabolites were isolated using repeated measures ANOVA and multivariate empirical Bayesian analysis for further study.
RESULTS
Eighty-six patients were included for analysis. Sphingolipids were enriched significantly (chi-square, p < 10
CONCLUSIONS
Metabolomic analysis identified broad alterations in circulating plasma sphingolipids after blunt trauma. Circulating sphingolipid signatures and their association with both clinical outcomes and circulating inflammatory mediators suggest a possible link between sphingolipid metabolism and the immune response to trauma.
Identifiants
pubmed: 33453380
pii: S1072-7515(21)00007-7
doi: 10.1016/j.jamcollsurg.2020.12.022
pii:
doi:
Substances chimiques
Biomarkers
0
Sphingolipids
0
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
276-287.e1Subventions
Organisme : NIGMS NIH HHS
ID : P50 GM053789
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008516
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.