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Metabolomic derangements are associated with mortality in critically ill adult patients.

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Date
2014
Authors
Rogers, Angela J
McGeachie, Michael
Baron, Rebecca M
Gazourian, Lee
Haspel, Jeffrey A
Nakahira, Kiichi
Fredenburgh, Laura E
Hunninghake, Gary M
Raby, Benjamin A
Matthay, Michael A
Otero, Ronny M
Fowler, Vance G
Rivers, Emanuel P
Woods, Christopher W
Kingsmore, Stephen
Kingsmore, Stephen
Langley, Ray J
Choi, Augustine MK
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(18 total)
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Abstract
OBJECTIVE: To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults. RATIONALE: Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible. METHODS: We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD) study. RESULTS: We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating metabolites included lipids (N = 14), amino acids or amino acid breakdown products (N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations). CONCLUSION: Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill patients.
Type
Journal article
Subject
Aged
Bayes Theorem
Biomarkers
Community-Acquired Infections
Critical Illness
Female
Hospital Mortality
Humans
Intensive Care Units
Male
Metabolomics
Middle Aged
Prognosis
Sepsis
Permalink
https://hdl.handle.net/10161/13313
Published Version (Please cite this version)
10.1371/journal.pone.0087538
Publication Info
Rogers, Angela J; McGeachie, Michael; Baron, Rebecca M; Gazourian, Lee; Haspel, Jeffrey A; Nakahira, Kiichi; ... Choi, Augustine MK (2014). Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS One, 9(1). pp. e87538. 10.1371/journal.pone.0087538. Retrieved from https://hdl.handle.net/10161/13313.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Fowler

Vance Garrison Fowler Jr.

Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
Woods

Christopher Wildrick Woods

Professor of Medicine
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases 4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance for communicable diseases 7. Antimicrobial resistance
Alphabetical list of authors with Scholars@Duke profiles.
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