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Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury

Authors :
Matej Orešič
Jussi P. Posti
Maja H. Kamstrup-Nielsen
Riikka S.K. Takala
Hester F. Lingsma
Ismo Mattila
Sirkku Jäntti
Ari J. Katila
Keri L.H. Carpenter
Henna Ala-Seppälä
Anna Kyllönen
Henna-Riikka Maanpää
Jussi Tallus
Jonathan P. Coles
Iiro Heino
Janek Frantzén
Peter J. Hutchinson
David K. Menon
Olli Tenovuo
Tuulia Hyötyläinen
Source :
EBioMedicine, Vol 12, Iss C, Pp 118-126 (2016)
Publication Year :
2016
Publisher :
Elsevier, 2016.

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n = 22), moderate (moTBI; n = 14) or mild TBI (mTBI; n = 108) according to Glasgow Coma Scale. The control group (n = 28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n = 23), moTBI (n = 7), mTBI (n = 37) patients and controls (n = 27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC = 0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified ‘TBI metabotype’ in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs.

Details

Language :
English
ISSN :
23523964
Volume :
12
Issue :
C
Database :
Directory of Open Access Journals
Journal :
EBioMedicine
Publication Type :
Academic Journal
Accession number :
edsdoj.7110dce9a4024de8863cdac90fb01489
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ebiom.2016.07.015