Using metabolomics to predict severe traumatic brain injury outcome (GOSE) at 3 and 12 months

Critical Care

Research

William Panenka¹  David S. Wishart²  Chel Hee Lee³  Mohammad M. Banoei³  Brent W. Winston⁴  James Hutchison⁵  Cheryl Wellington⁶ 

[1]BC Mental Health and Substance Use Research Institute and the Department of Psychiatry, Faculty of Medicine, University of British Colombia, British Colombia, Canada

[2]Department of Biological Sciences, Computing Sciences and Medicine and Dentistry, University of Alberta, Alberta, Canada

[3]Department of Critical Care Medicine, University of Calgary, Alberta, Canada

[4]Department of Critical Care Medicine, University of Calgary, Alberta, Canada

[5]Department of Critical Care Medicine, Medicine and Biochemistry and Molecular Biology, University of Calgary, Health Research Innovation Center (HRIC), Room 4C64, 3280 Hospital Drive N.W., T2N 4Z6, Calgary, AB, Canada

[6]Department of Pediatrics and Critical Care and Neuroscience and Mental Health Research Program, SickKids and Interdepartmental Division of Critical Care and Institute for Medical Science, The University of Toronto, Toronto, ON, Canada

[7]Djavad Mowafaghian Centre for Brain Health, University of British Columbia, British Colombia, Canada

关键词: Severe TBI;    Metabolomics;    Outcome prediction;    Prediction modelling;   

DOI  :  10.1186/s13054-023-04573-9

 received in 2023-02-21, accepted in 2023-07-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPrognostication is very important to clinicians and families during the early management of severe traumatic brain injury (sTBI), however, there are no gold standard biomarkers to determine prognosis in sTBI. As has been demonstrated in several diseases, early measurement of serum metabolomic profiles can be used as sensitive and specific biomarkers to predict outcomes.MethodsWe prospectively enrolled 59 adults with sTBI (Glasgow coma scale, GCS ≤ 8) in a multicenter Canadian TBI (CanTBI) study. Serum samples were drawn for metabolomic profiling on the 1st and 4th days following injury. The Glasgow outcome scale extended (GOSE) was collected at 3- and 12-months post-injury. Targeted direct infusion liquid chromatography-tandem mass spectrometry (DI/LC–MS/MS) and untargeted proton nuclear magnetic resonance spectroscopy (1H-NMR) were used to profile serum metabolites. Multivariate analysis was used to determine the association between serum metabolomics and GOSE, dichotomized into favorable (GOSE 5–8) and unfavorable (GOSE 1–4), outcomes.ResultsSerum metabolic profiles on days 1 and 4 post-injury were highly predictive (Q2 > 0.4–0.5) and highly accurate (AUC > 0.99) to predict GOSE outcome at 3- and 12-months post-injury and mortality at 3 months. The metabolic profiles on day 4 were more predictive (Q2 > 0.55) than those measured on day 1 post-injury. Unfavorable outcomes were associated with considerable metabolite changes from day 1 to day 4 compared to favorable outcomes. Increased lysophosphatidylcholines, acylcarnitines, energy-related metabolites (glucose, lactate), aromatic amino acids, and glutamate were associated with poor outcomes and mortality.DiscussionMetabolomic profiles were strongly associated with the prognosis of GOSE outcome at 3 and 12 months and mortality following sTBI in adults. The metabolic phenotypes on day 4 post-injury were more predictive and significant for predicting the sTBI outcome compared to the day 1 sample. This may reflect the larger contribution of secondary brain injury (day 4) to sTBI outcome. Patients with unfavorable outcomes demonstrated more metabolite changes from day 1 to day 4 post-injury. These findings highlighted increased concentration of neurobiomarkers such as N-acetylaspartate (NAA) and tyrosine, decreased concentrations of ketone bodies, and decreased urea cycle metabolites on day 4 presenting potential metabolites to predict the outcome. The current findings strongly support the use of serum metabolomics, that are shown to be better than clinical data, in determining prognosis in adults with sTBI in the early days post-injury. Our findings, however, require validation in a larger cohort of adults with sTBI to be used for clinical practice.

【 授权许可】

CC BY   
© The Author(s) 2023

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