Human serum metabolites associate with severity and patient outcomes in traumatic brain injury

Matej Oresic (Corresponding Author), 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 (Corresponding Author), Olli Tenovuo (Corresponding Author), Tuulia Hyötyläinen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

29 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)118-126
JournalEBioMedicine
Volume12
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

Fingerprint

Metabolites
Brain
Serum
Decanoic Acids
Hospitalization
Caprylates
Brain Concussion
Glasgow Coma Scale
Traumatic Brain Injury
Validation Studies
Blood-Brain Barrier
Craniocerebral Trauma
Area Under Curve
Orthopedics
Young Adult
Cause of Death
Fatty Acids
Metabolism
Sugars
Tomography

Keywords

  • biomarkers
  • mass spectrometry
  • metabolomics
  • traumatic brain injury

Cite this

Oresic, M., Posti, J. P., Kamstrup-Nielsen, M. H., Takala, R. S. K., Lingsma, H. F., Mattila, I., ... Hyötyläinen, T. (2016). Human serum metabolites associate with severity and patient outcomes in traumatic brain injury. EBioMedicine, 12, 118-126. https://doi.org/10.1016/j.ebiom.2016.07.015
Oresic, Matej ; Posti, Jussi P. ; Kamstrup-Nielsen, Maja H. ; Takala, Riikka S.K. ; Lingsma, Hester F. ; Mattila, Ismo ; Jäntti, Sirkku ; Katila, Ari J. ; Carpenter, Keri L.H. ; Ala-Seppälä, Henna ; Kyllönen, Anna ; Maanpää, Henna-Riikka ; Tallus, Jussi ; Coles, Jonathan P. ; Heino, Iiro ; Frantzén, Janek ; Hutchinson, Peter J. ; Menon, David K. ; Tenovuo, Olli ; Hyötyläinen, Tuulia. / Human serum metabolites associate with severity and patient outcomes in traumatic brain injury. In: EBioMedicine. 2016 ; Vol. 12. pp. 118-126.
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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.",
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Oresic, M, Posti, JP, Kamstrup-Nielsen, MH, Takala, RSK, Lingsma, HF, Mattila, I, Jäntti, S, Katila, AJ, Carpenter, KLH, Ala-Seppälä, H, Kyllönen, A, Maanpää, H-R, Tallus, J, Coles, JP, Heino, I, Frantzén, J, Hutchinson, PJ, Menon, DK, Tenovuo, O & Hyötyläinen, T 2016, 'Human serum metabolites associate with severity and patient outcomes in traumatic brain injury', EBioMedicine, vol. 12, pp. 118-126. https://doi.org/10.1016/j.ebiom.2016.07.015

Human serum metabolites associate with severity and patient outcomes in traumatic brain injury. / Oresic, Matej (Corresponding Author); Posti, Jussi P.; Kamstrup-Nielsen, Maja H.; Takala, Riikka S.K.; Lingsma, Hester F.; Mattila, Ismo; Jäntti, Sirkku; Katila, Ari J.; Carpenter, Keri L.H.; Ala-Seppälä, Henna; Kyllönen, Anna; Maanpää, Henna-Riikka; Tallus, Jussi; Coles, Jonathan P.; Heino, Iiro; Frantzén, Janek; Hutchinson, Peter J.; Menon, David K. (Corresponding Author); Tenovuo, Olli (Corresponding Author); Hyötyläinen, Tuulia (Corresponding Author).

In: EBioMedicine, Vol. 12, 2016, p. 118-126.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Human serum metabolites associate with severity and patient outcomes in traumatic brain injury

AU - Oresic, Matej

AU - Posti, Jussi P.

AU - Kamstrup-Nielsen, Maja H.

AU - Takala, Riikka S.K.

AU - Lingsma, Hester F.

AU - Mattila, Ismo

AU - Jäntti, Sirkku

AU - Katila, Ari J.

AU - Carpenter, Keri L.H.

AU - Ala-Seppälä, Henna

AU - Kyllönen, Anna

AU - Maanpää, Henna-Riikka

AU - Tallus, Jussi

AU - Coles, Jonathan P.

AU - Heino, Iiro

AU - Frantzén, Janek

AU - Hutchinson, Peter J.

AU - Menon, David K.

AU - Tenovuo, Olli

AU - Hyötyläinen, Tuulia

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - biomarkers

KW - mass spectrometry

KW - metabolomics

KW - traumatic brain injury

U2 - 10.1016/j.ebiom.2016.07.015

DO - 10.1016/j.ebiom.2016.07.015

M3 - Article

VL - 12

SP - 118

EP - 126

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -

Oresic M, Posti JP, Kamstrup-Nielsen MH, Takala RSK, Lingsma HF, Mattila I et al. Human serum metabolites associate with severity and patient outcomes in traumatic brain injury. EBioMedicine. 2016;12:118-126. https://doi.org/10.1016/j.ebiom.2016.07.015