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The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.

IMPORTANCE: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. OBJECTIVE: To identify pathological CT features associated with adverse outcomes after mTBI. DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale–Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. EXPOSURES: Acute nonpenetrating head trauma. MAIN OUTCOMES AND MEASURES: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. RESULTS: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. CONCLUSIONS AND RELEVANCE: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.

IMPORTANCE: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. OBJECTIVE: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. DESIGN, SETTING, AND PARTICIPANTS: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. EXPOSURES: Moderate or severe TBI. MAIN OUTCOMES AND MEASURES: The Glasgow Outcome Scale–Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. RESULTS: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. CONCLUSIONS AND RELEVANCE: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.

Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury.

IMPORTANCE: Most traumatic brain injuries (TBIs) are classified as mild (mTBI) based on admission Glasgow Coma Scale (GCS) scores of 13 to 15. The prevalence of persistent functional limitations for these patients is unclear. OBJECTIVES: To characterize the natural history of recovery of daily function following mTBI vs peripheral orthopedic traumatic injury in the first 12 months postinjury using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, and, using clinical computed tomographic (CT) scans, examine whether the presence (CT+) or absence (CT−) of acute intracranial findings in the mTBI group was associated with outcomes. DESIGN, SETTING, AND PARTICIPANTS: TRACK-TBI, a cohort study of patients with mTBI presenting to US level I trauma centers, enrolled patients from February 26, 2014, to August 8, 2018, and followed up for 12 months. A total of 1453 patients at 11 level I trauma center emergency departments or inpatient units met inclusion criteria (ie, mTBI [n = 1154] or peripheral orthopedic traumatic injury [n = 299]) and were enrolled within 24 hours of injury; mTBI participants had admission GCS scores of 13 to 15 and clinical head CT scans. Patients with peripheral orthopedic trauma injury served as the control (OTC) group. EXPOSURES: Participants with mTBI or OTC. MAIN OUTCOMES AND MEASURES: The Glasgow Outcome Scale Extended (GOSE) scale score, reflecting injury-related functional limitations across broad life domains at 2 weeks and 3, 6, and 12 months postinjury was the primary outcome. The possible score range of the GOSE score is 1 (dead) to 8 (upper good recovery), with a score less than 8 indicating some degree of functional impairment. RESULTS: Of the 1453 participants, 953 (65.6%) were men; mean (SD) age was 40.9 (17.1) years in the mTBI group and 40.9 (15.4) years in the OTC group. Most participants (mTBI, 87%; OTC, 93%) reported functional limitations (GOSE <8) at 2 weeks postinjury. At 12 months, the percentage of mTBI participants reporting functional limitations was 53% (95% CI, 49%-56%) vs 38% (95% CI, 30%-45%) for OTCs. A higher percentage of CT+ patients reported impairment (61%) compared with the mTBI CT− group (49%; relative risk [RR], 1.24; 95% CI, 1.08-1.43) and a higher percentage in the mTBI CT−group compared with the OTC group (RR, 1.28; 95% CI, 1.02-1.60). CONCLUSIONS AND RELEVANCE: Most patients with mTBI presenting to US level I trauma centers report persistent, injury-related life difficulties at 1 year postinjury, suggesting the need for more systematic follow-up of patients with mTBI to provide treatments and reduce the risk of chronic problems after mTBI.

IMPORTANCE: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. OBJECTIVE: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. DESIGN, SETTING, AND PARTICIPANTS: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. EXPOSURES: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. MAIN OUTCOMES AND MEASURES: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). RESULTS: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B?=?0.76; 5% false discovery rate–corrected P?=?.02) and somatic RPQ symptoms (B =?0.80; 5% false discovery rate–corrected P?=?.02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B =?1.65; P?=?.02) or older than 50 years (B =?1.66; P?=?.02). CONCLUSIONS AND RELEVANCE: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

IMPORTANCE: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. OBJECTIVE: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. EXPOSURES: TBI. MAIN OUTCOMES AND MEASURES: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale–Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). RESULTS: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase?=?0.09-0.19; SWLS R2 increase?=?0.12-0.22; QOLIBRI-OS R2 increase?=?0.14-0.32; RPQ R2?=?0.13-0.34). CONCLUSIONS AND RELEVANCE: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.