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

Author

Orešič, 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, and Hyötyläinen, Tuulia

Published
2016
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5. Linoleic acid in adipose tissue and the risk of myocardial infarction:a case-cohort study

Author

Nielsen, Maja H., Frydenberg, Morten, Bork, Christian Sorensen, Veno, Stine Krogh, Tjonneland, Anne, Schmidt, Erik Berg, Overvad, Kim, Jakobsen, Marianne Uhre, Nielsen, Maja H., Frydenberg, Morten, Bork, Christian Sorensen, Veno, Stine Krogh, Tjonneland, Anne, Schmidt, Erik Berg, Overvad, Kim, and Jakobsen, Marianne Uhre

Abstract

Purpose We investigated risk of myocardial infarction (MI) associated with the content of linoleic acid (LA) in adipose tissue, a biomarker of long-term dietary intake of LA and a marker of endogenous LA exposure. Methods Between 1993 and 1997, 57,053 middle-aged subjects were included in the Danish Diet, Cancer and Health cohort. We performed a case-cohort study that included a random sample of the full cohort (n = 3167) and all incident MI cases appearing during 16 years of follow-up (n = 2819). Information on incident MI cases was obtained by linkage with Danish nationwide registries. Adipose tissue biopsies were taken from the buttocks of the participants, and their fatty acid composition was determined using gas chromatography. HRs (hazard ratios) with 95% confidence intervals (CIs) were used to describe the associations between content of LA in adipose tissue and the risk of MI. HRs were calculated using weighted Cox proportional hazards regression with robust variance. Results After adjustment for established risk factors of MI, adipose tissue content of LA was not associated with the risk of MI in men and women combined (quintiles 5 versus 1, HR, 1.03 (95% CI, 0.85-1.25), P-trend = 0.970) or in men and women separately (quintiles 5 versus 1, HR, 1.05 (95% CI, 0.83-1.33), P-trend = 0.871 and quintiles 5 versus 1, HR, 0.99 (95% CI 0.72-1.37), P-trend = 0.928, respectively). Investigating the association between LA and MI with a shorter, 5- or 10-year duration of follow-up provided similar results. Conclusion Content of LA in adipose tissue was not associated with the risk of MI.

Published
2021

8. Development and rheological profiling of biosimilar mucus

Author

Bøgh, Marie, Baldursdottir, Stefania G., Nielsen, Maja H., Müllertz, Anette, Nielsen, Hanne Mørck, Bøgh, Marie, Baldursdottir, Stefania G., Nielsen, Maja H., Müllertz, Anette, and Nielsen, Hanne Mørck

Published
2013

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

Author

Orešič, Matej, Posti, Jussi P, Kamstrup-Nielsen, Maja H, Takala, Riikka SK, Lingsma, Hester F, Mattila, Ismo, Jäntti, Sirkku, Katila, Ari J, Carpenter, Keri LH, 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, and Hyötyläinen, Tuulia

Subjects
Adult, Aged, 80 and over, Male, Mass spectrometry, Adolescent, Reproducibility of Results, Middle Aged, Prognosis, Severity of Illness Index, 3. Good health, Workflow, Patient Outcome Assessment, Young Adult, Traumatic brain injury, ROC Curve, Brain Injuries, Traumatic, Metabolome, Metabolomics, Humans, Female, Glasgow Coma Scale, Prospective Studies, Tomography, X-Ray Computed, Biomarkers, Aged
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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