Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury.
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.
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Steno Diabetes Center A/S, DK-2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, FI-02044, VTT, Espoo, Finland. Electronic address: matej.oresic@utu.fi.
Matej
M
Orešič
Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, FI-20521 Turku, Finland; Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, FI-20521 Turku, Finland; Department of Neurology, University of Turku, FI-20014 Turku, Finland.
Jussi P
JP
Posti
Steno Diabetes Center A/S, DK-2820 Gentofte, Denmark.
Maja H
MH
Kamstrup-Nielsen
Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, FI-20521 Turku, Finland.
Riikka S K
RSK
Takala
Department of Public Health, Erasmus MC-University Medical Center Rotterdam, The Netherlands.
Hester F
HF
Lingsma
Steno Diabetes Center A/S, DK-2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, FI-02044, VTT, Espoo, Finland.
Ismo
I
Mattila
VTT Technical Research Centre of Finland, FI-02044, VTT, Espoo, Finland.
Sirkku
S
Jäntti
Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, FI-20521 Turku, Finland.
Ari J
AJ
Katila
Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Box 167, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Keri L H
KLH
Carpenter
Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, FI-20521 Turku, Finland; Department of Neurology, University of Turku, FI-20014 Turku, Finland.
Henna
H
Ala-Seppälä
Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, FI-20521 Turku, Finland; Department of Neurology, University of Turku, FI-20014 Turku, Finland.
Anna
A
Kyllönen
Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, FI-20521 Turku, Finland; Department of Neurology, University of Turku, FI-20014 Turku, Finland.
Henna-Riikka
HR
Maanpää
Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, FI-20521 Turku, Finland; Department of Neurology, University of Turku, FI-20014 Turku, Finland.
Jussi
J
Tallus
Division of Anaesthesia, Department of Medicine, University of Cambridge, Box 93, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Jonathan P
JP
Coles
Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, FI-20521 Turku, Finland; Department of Neurology, University of Turku, FI-20014 Turku, Finland.
Iiro
I
Heino
Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, FI-20521 Turku, Finland; Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, FI-20521 Turku, Finland; Department of Neurology, University of Turku, FI-20014 Turku, Finland.
Janek
J
Frantzén
Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Box 167, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Peter J
PJ
Hutchinson
Division of Anaesthesia, Department of Medicine, University of Cambridge, Box 93, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. Electronic address: dkm13@wbic.cam.ac.uk.
David K
DK
Menon
Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, FI-20521 Turku, Finland; Department of Neurology, University of Turku, FI-20014 Turku, Finland. Electronic address: olli.tenovuo@tyks.fi.
Olli
O
Tenovuo
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Steno Diabetes Center A/S, DK-2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, FI-02044, VTT, Espoo, Finland; Clinical Research Institute, Helsinki University Central Hospital, FI-00290 Helsinki, Finland; Department of Chemistry, Örebro University, 702 81 Örebro, Sweden. Electronic address: tuulia.hyotylainen@oru.se.
Tuulia
T
Hyötyläinen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D057188:Workflow; D055815:Young Adult
D015415:Biomarkers
Biomarkers; Mass spectrometry; Metabolomics; Traumatic brain injury
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