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

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.

SUBMITTER: Oresic M

PROVIDER: S-EPMC5078571 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Orešič Matej M Posti Jussi P JP Kamstrup-Nielsen Maja H MH Takala Riikka S K RSK Lingsma Hester F HF Mattila Ismo I Jäntti Sirkku S Katila Ari J AJ Carpenter Keri L H KLH Ala-Seppälä Henna H Kyllönen Anna A Maanpää Henna-Riikka HR Tallus Jussi J Coles Jonathan P JP Heino Iiro I Frantzén Janek J Hutchinson Peter J PJ Menon David K DK Tenovuo Olli O Hyötyläinen Tuulia T

EBioMedicine 20160715

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 ...[more]

PMID: 27665050

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Project description:ObjectiveSpine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).MethodsData from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7-8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.ResultsA total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37-66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.ConclusionRates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.

Project description:ImportanceTraumatic brain injury (TBI) affects millions of people in the US each year. Most patients with TBI seen in emergency departments (EDs) have a Glasgow Coma Scale (GCS) score of 15 and a head computed tomography (CT) scan showing no acute intracranial traumatic injury (negative head CT scan), yet the short-term and long-term functional outcomes of this subset of patients remain unclear.ObjectiveTo describe the 2-week and 6-month recovery outcomes in a cohort of patients with mild TBI with a GCS score of 15 and a negative head CT scan.Design, setting, and participantsThis cohort study analyzed participants who were enrolled from January 1, 2014, to December 31, 2018, in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective, observational cohort study of patients with TBI that was conducted in EDs of 18 level I trauma centers in urban areas. Of the total 2697 participants in the TRACK-TBI study, 991 had a GCS score of 15 and negative head CT scan and were eligible for inclusion in this analysis. Data were analyzed from September 1, 2021, to May 30, 2022.Main outcomes and measuresThe primary outcome was the Glasgow Outcome Scale-Extended (GOS-E) score, which was stratified according to functional recovery (GOS-E score, 8) vs incomplete recovery (GOS-E score, <8), at 2 weeks and 6 months after the injury. The secondary outcome was severity of mild TBI-related symptoms assessed by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score.ResultsA total of 991 participants (mean [SD] age, 38.5 [15.8] years; 631 male individuals [64%]) were included. Of these participants, 751 (76%) were followed up at 2 weeks after the injury: 204 (27%) had a GOS-E score of 8 (functional recovery), and 547 (73%) had a GOS-E scores less than 8 (incomplete recovery). Of 659 participants (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery. Most participants with incomplete recovery reported that they had not returned to baseline or preinjury life (88% [479 of 546]; 95% CI, 85%-90%). Mean RPQ score was 16 (95% CI, 14-18; P < .001) points lower at 2 weeks (7 vs 23) and 18 (95% CI, 16-20; P < .001) points lower at 6 months (4 vs 22) in participants with a GOS-E score of 8 compared with those with a GOS-E score less than 8.Conclusions and relevanceThis study found that most participants with a GCS score of 15 and negative head CT scan reported incomplete recovery at 2 weeks and 6 months after their injury. The findings suggest that emergency department clinicians should recommend 2-week follow-up visits for these patients to identify those with incomplete recovery and to facilitate their rehabilitation.

Project description:Heterogeneity of injury severity among children with traumatic brain injury (TBI) classified by the Glasgow Coma Scale (GCS) makes comparisons across research cohorts, enrollment in clinical trials, and clinical predictions of outcomes difficult. The present study uses latent class analysis (LCA) to distinguish severity subgroups from a prospective cohort of 433 children 2.5-15 years of age with TBI who were recruited from two level 1 pediatric trauma centers. Indicator variables available within 48 h post-injury including emergency department (ED) GCS, hospital motor GCS, Abbreviated Injury Score (AIS), Rotterdam Score, hypotension in the ED, and pre-hospital loss of consciousness, intubation, seizures, and sedation were evaluated to define subgroups. To understand whether latent class subgroups were predictive of clinically meaningful outcomes, the Pediatric Injury Functional Outcome Scale (PIFOS) at 6 and 12 months, and the Behavior Rating Inventory of Executive Function at 12 months, were compared across subgroups. Then, outcomes were examined by GCS (primary) and AIS (secondary) classification alone to assess whether LCA provided improved outcome prediction. LCA identified four distinct increasing severity subgroups (1-4). Unlike GCS classification, mean outcome differences on PIFOS at 6 months showed decreasing function across classes. PIFOS differences relative to the lowest latent class (LC1) were: LC2 2.27 (0.83, 3.72), LC3 3.99 (1.88, 6.10), and LC4 11.2 (7.04, 15.4). Differences in 12 month outcomes were seen between the most and least severely injured groups. Differences in outcomes in relation to AIS were restricted to the most and less severely injured at both time points. This study distinguished four latent classes that are clinically meaningful, distinguished a more homogenous severe injury group, and separated children by 6-month functional outcomes better than GCS alone. Systematic reporting of these variables would allow comparisons across research cohorts, potentially improve clinical predictions, and increase sensitivity to treatment effects in clinical trials.

Project description:BackgroundTraumatic brain injury (TBI) is one of the leading causes of neurological disability. In this retrospective study, serum total cholinesterase (ChE) activities were analyzed in 188 patients for diagnostic as well as predictive values for mortality.Methods and findingsWithin 72 hours after injury, serum ChE activities including both acetylcholinesterase and butyrylcholinesterase were measured. Disease severity was evaluated with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow Coma Score, length of coma, post-traumatic amnesia and injury feature. Neurocognitive and functional scores were assessed using clinical records. Of 188 patients, 146 (77.7%) survived and 42 (22.3%) died within 90 days. Lower ChE activities were noted in the non-survivors vs. survivors (5.94±2.19 vs. 7.04±2.16 kU/L, p=0.023), in septic vs. non-infected patients (5.93±1.89 vs. 7.31±2.45 kU/L, p=0.0005) and in patients with extremely severe injury vs. mild injury (6.3±1.98 vs. 7.57±2.48 kU/L, p=0.049). The trajectories of serum ChE levels were also different between non-survivors and survivors, septic and non-infected patients, mild and severely injured patients, respectively. Admission ChE activities were closely correlated with blood cell counts, neurocognitive and functional scores both on admission and at discharge. Receiver operating characteristic analysis showed that the area under the curve for ChE was inferior to that for either APACHE II or white blood cell (WBC) count. However, at the optimal cutoff value of 5 kU/L, the sensitivity of ChE for correct prediction of 90-day mortality was 65.5% and the specificity was 86.4%. Kaplan-Meier analysis showed that lower ChE activity (<5 kU/L) was more closely correlated with poor survival than higher ChE activity (>5 kU/L) (p=0.04). After adjusting for other variables, ChE was identified as a borderline independent predictor for mortality as analyzed by Binary logistic regression (P=0.078).ConclusionsLowered ChE activity measured on admission appears to be associated with disease severity and outcome for TBI patients.

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

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

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