Serum Metabolites Associated with Computed Tomography Findings after Traumatic Brain Injury.
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Authors
Dickens, Alex M
Posti, Jussi P
Takala, Riikka SK
Ala-Seppälä, Henna
Mattila, Ismo
Frantzén, Janek
Katila, Ari J
Kyllönen, Anna
Maanpää, Henna-Riikka
Tallus, Jussi
Hyötyläinen, Tuulia
Tenovuo, Olli
Orešic, Matej
Publication Date
2018-11-15Journal Title
J Neurotrauma
ISSN
0897-7151
Publisher
Mary Ann Liebert Inc
Volume
35
Issue
22
Pages
2673-2683
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Dickens, A. M., Posti, J. P., Takala, R. S., Ala-Seppälä, H., Mattila, I., Coles, J., Frantzén, J., et al. (2018). Serum Metabolites Associated with Computed Tomography Findings after Traumatic Brain Injury.. J Neurotrauma, 35 (22), 2673-2683. https://doi.org/10.1089/neu.2017.5272
Abstract
There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of biomarkers to determine the need for CT and to distinguish among different types of injuries observed. Logistical regression models using metabolite data from the discovery cohort (n = 144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and those with negative findings on head CT. The resultant models were then tested in the validation cohort (n = 66, Cambridge, United Kingdom). The levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein biomarkers in patients with TBI, the model that determined the need for a CT scan validated poorly (area under the curve [AUC] = 0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, three sugar derivatives, and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC = 0.77 in Turku patients and AUC = 0.73 in Cambridge patients). Further, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC = 0.87 in Turku patients and AUC = 0.68 in Cambridge patients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.
Keywords
Humans, Tomography, X-Ray Computed, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Biomarkers, Brain Injuries, Traumatic
Sponsorship
EU FP7 project TBIcare - Project ref. 270259
NIHR Cambridge Biomedical Research Centre
Funder references
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Academy of Medical Sciences (unknown)
Medical Research Council (G1002277)
Medical Research Council (G0601025)
Medical Research Council (G0600986)
Medical Research Council (G9439390)
NETSCC (None)
NETSCC (None)
TCC (None)
Identifiers
External DOI: https://doi.org/10.1089/neu.2017.5272
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282788
Rights
Licence:
http://www.rioxx.net/licenses/all-rights-reserved
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