Assessment of Blood Biomarker Profile After Acute Concussion During Combative Training Among US Military Cadets: A Prospective Study From the NCAA and US Department of Defense CARE Consortium.
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ABSTRACT:
SUBMITTER: Giza CC
PROVIDER: S-EPMC7900866 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
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Assessment of Blood Biomarker Profile After Acute Concussion During Combative Training Among US Military Cadets: A Prospective Study From the NCAA and US Department of Defense CARE Consortium.
Giza Christopher C CC McCrea Michael M Huber Daniel D Cameron Kenneth L KL Houston Megan N MN Jackson Jonathan C JC McGinty Gerald G Pasquina Paul P Broglio Steven P SP Brooks Alison A DiFiori John J Duma Stefan S Harezlak Jaroslaw J Goldman Joshua J Guskiewicz Kevin K McAllister Thomas W TW McArthur David D Meier Timothy B TB Mihalik Jason P JP Nelson Lindsay D LD Rowson Steven S Gill Jessica J Foroud Tatiana T Katz Barry B Saykin Andrew A Campbell Darren E DE Svoboda Steven S
JAMA network open 20210201 2
<h4>Importance</h4>Validation of protein biomarkers for concussion diagnosis and management in military combative training is important, as these injuries occur outside of traditional health care settings and are generally difficult to diagnose.<h4>Objective</h4>To investigate acute blood protein levels in military cadets after combative training-associated concussions.<h4>Design, setting, and participants</h4>This multicenter prospective case-control study was part of a larger cohort study cond ...[more]
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Project description:BackgroundCurrent protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion. Therefore, more accurate diagnostic markers are needed for sport-related concussion.MethodsThis was a multicenter, prospective, case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education Consortium conducted between 2015 and 2019. The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints. Athletes with concussion were divided into 6 h post-injury (0-6 h post-injury) and after 6 h post-injury (7-48 h post-injury) groups. We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305 proteins in plasma samples from athletes with and without sport-related concussion.ResultsA total of 140 athletes with concussion (79.3% males; aged 18.71 ± 1.10 years, mean ± SD) and 21 non-concussed athletes (76.2% males; 19.14 ± 1.10 years) were included in this study. We identified 338 plasma proteins that significantly differed in abundance (319 upregulated and 19 downregulated) in concussed athletes compared to non-concussed athletes. The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve (AUC) of 0.954 (95% confidence interval: 0.922‒0.986). Specifically, after 6 h of injury, the individual AUC of plasma erythrocyte membrane protein band 4.1 (EPB41) and alpha-synuclein (SNCA) were 0.956 and 0.875, respectively. The combination of EPB41 and SNCA provided the best AUC (1.000), which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury.ConclusionOur data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.
| S-EPMC10199139 | biostudies-literature
Project description:Importance:There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective:To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants:This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures:Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results:A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance:The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.
| S-EPMC6991302 | biostudies-literature
Project description:Objective To investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC). Methods This multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery <14-days (n = 99) and (2) recovery ≥14-days (n = 41). We applied a highly multiplexed proteomic technique that uses DNA aptamers assay to target 1,305 proteins in plasma samples from concussed athletes with <14-days and ≥14-days. Results We identified 87 plasma proteins significantly dysregulated (32 upregulated and 55 downregulated) in concussed athletes with recovery ≥14-days relative to recovery <14-days groups. The significantly dysregulated proteins were uploaded to Ingenuity Pathway Analysis (IPA) software for analysis. Pathway analysis showed that significantly dysregulated proteins were associated with STAT3 pathway, regulation of the epithelial mesenchymal transition by growth factors pathway, and acute phase response signaling. Conclusion Our data showed the feasibility of large-scale plasma proteomic profiling in concussed athletes with a <14-days and ≥ 14-days recovery. These findings provide a possible understanding of the pathophysiological mechanism in neurobiological recovery. Further study is required to determine whether these proteins can aid clinicians in RTS decisions.
| S-EPMC9343581 | biostudies-literature
Project description:ImportanceConcussions are a common occurrence in young athletes. Hypobaric hypoxemia, such as that experienced during airplane travel, can potentially cause alterations to cerebral blood flow and increased neuroinflammatory response. It remains unknown whether flying early after a concussion may influence the clinical course of injury.ObjectiveTo determine whether there is an association between concussion recovery and airplane travel in collegiate athletes and military cadets.Design, setting, and participantsThis cohort study was conducted by the National Collegiate Athletic Association and US Department of Defense Concussion Assessment, Research, and Education Consortium from August 3, 2014, to September 13, 2018. Participant groups were categorized by those who flew within 72 hours of injury and those who did not fly. All participants included in the final analyses had complete data of interest and only 1 injury during the study. Data analysis was performed from September 2018 to March 2020.Main outcomes and measuresRecovery outcome measures were defined as time (in days) from injury to return to activity, school, and baseline symptoms. Symptom and headache severity scores were derived from the Sports Concussion Assessment Tool-Third Edition. Scores for both groups were taken at baseline and a median of 2 days after injury.ResultsA total of 92 participants who flew (mean [SD] age, 19.1 [1.2] years; 55 male [59.8%]) and 1383 participants who did not fly (mean [SD] age, 18.9 [1.3] years; 809 male [58.5%]) were included in the analysis of symptom recovery outcomes (analysis 1). Similarly, 100 participants who flew (mean [SD] age, 19.2 [1.2] years; 63 male [63.0%]) and 1577 participants who did not fly (mean [SD] age, 18.9 [1.3] years; 916 male [58.1%]) were included in the analysis of symptom severity outcomes (analysis 2). No significant group differences were found regarding recovery outcome measures. Likewise, there were no group differences in symptom (estimated mean difference, 0.029; 95% CI, -0.083 to 0.144; P = .67) or headache (estimated mean difference, -0.007; 95% CI, -0.094 to 0.081; P = .91) severity scores.Conclusions and relevanceAirplane travel early after concussion was not associated with recovery or severity of concussion symptoms. These findings may help guide future recommendations on flight travel after concussion in athletes.
| S-EPMC7658735 | biostudies-literature
Project description:ObjectiveSince concussion is the most common injury in ice hockey, the objective of the current study was to elucidate risk factors, specific mechanisms, and clinical presentations of concussion in men's and women's ice hockey.MethodsIce hockey players from 5 institutions participating in the Concussion Assessment, Research, and Education Consortium were eligible for the current study. Participants who sustained a concussion outside of this sport were excluded. There were 332 (250 males, 82 females) athletes who participated in ice hockey, and 47 (36 males, 11 females) who sustained a concussion.ResultsPrevious concussion (odds ratio (OR) = 2.00; 95% confidence interval (95% CI): 1.02‒3.91) was associated with increased incident concussion odds, while wearing a mouthguard was protective against incident concussion (OR = 0.43; 95%CI: 0.22‒0.85). Overall, concussion mechanisms did not significantly differ between sexes. There were specific differences in how concussions presented clinically across male and female ice hockey players, however. Females (9.09%) were less likely than males (41.67%) to have a delayed symptom onset (p = 0.045). Additionally, females took significantly longer to reach asymptomatic (p = 0.015) and return-to-play clearance (p = 0.005). Within the first 2 weeks post-concussion, 86.11% of males reached asymptomatic, while only 45.50% of females reached the same phase of recovery. Most males (91.67%) were cleared for return to play within 3 weeks of their concussion, compared to less than half (45.50%) of females.ConclusionThe current study proposes possible risk factors, mechanisms, and clinical profiles to be validated in future concussions studies with larger female sample sizes. Understanding specific risk factors, concussion mechanisms, and clinical profiles of concussion in collegiate ice hockey may generate ideas for future concussion prevention or intervention studies.
| S-EPMC7987562 | biostudies-literature
Project description:ObjectiveTo describe sex differences in concussion characteristics in US Service Academy cadets.DesignDescriptive epidemiology study.SettingFour US service academies.Participants2209 cadets (n = 867 females, n = 1342 males).Independent variableSex.Outcome measuresInjury proportion ratios (IPR) compared the proportion of injuries by sex (females referent) for injury situation, certainty of diagnosis, prolonged recovery, recurrent injuries, mental status alterations, loss of consciousness (LOC), posttraumatic amnesia (PTA), retrograde amnesia (RGA), motor impairments, delayed symptom presentation, and immediate reporting.Main resultsConcussions from varsity/intercollegiate sports [IPR of 1.73, 95% confidence interval (CI) 1.43-2.10] and intramurals (IPR of 1.53, 95% CI 1.02-2.32) accounted for a larger proportion in males, whereas concussions outside of sport and military activities accounted for a smaller proportion among males (IPR of 0.70, 95% CI 0.58-0.85). The proportion of concussions with prolonged recovery was lower among males (IPR of 0.69, 95% CI 0.60-0.78), while concussions with altered mental status (IPR of 1.23, 95% CI 1.09-1.38), LOC (IPR of 1.67, 95% CI 1.17-2.37), PTA (IPR of 1.94, 95% CI 1.43-2.62), and RGA (IPR of 2.14, 95% CI 1.38-3.31) accounted for a larger proportion among males. A larger proportion of concussions that were immediately reported was observed in males (IPR of 1.15, 95% CI 1.00-2.31). Proportions of other characteristics (e.g., recurrent injuries) were not different between sexes.ConclusionsA higher proportion of concussions occurred outside of sport and military training for female cadets, who also displayed proportionally longer recovery times than males, despite males demonstrating a higher proportion of LOC, PTA, and RGA. Possible factors may include different mechanisms of injury outside of sport and military training, different biopsychosocial states associated with sex or injury context, and delayed injury reporting when outside of an observed environment, possibly secondary to perceived stigma about reporting injuries.
| S-EPMC11561049 | biostudies-literature
Project description:BackgroundConcussion diagnosis is typically made through clinical examination and supported by performance on clinical assessment tools. Performance on commonly implemented and emerging assessment tools is known to vary between administrations, in the absence of concussion.ObjectiveTo evaluate the test-retest reliability of commonly implemented and emerging concussion assessment tools across a large nationally representative sample of student-athletes.MethodsParticipants (n = 4874) from the Concussion Assessment, Research, and Education Consortium completed annual baseline assessments on two or three occasions. Each assessment included measures of self-reported concussion symptoms, motor control, brief and extended neurocognitive function, reaction time, oculomotor/oculovestibular function, and quality of life. Consistency between years 1 and 2 and 1 and 3 were estimated using intraclass correlation coefficients or Kappa and effect sizes (Cohen's d). Clinical interpretation guidelines were also generated using confidence intervals to account for non-normally distributed data.ResultsReliability for the self-reported concussion symptoms, motor control, and brief and extended neurocognitive assessments from year 1 to 2 ranged from 0.30 to 0.72 while effect sizes ranged from 0.01 to 0.28 (i.e., small). The reliability for these same measures ranged from 0.34 to 0.66 for the year 1-3 interval with effect sizes ranging from 0.05 to 0.42 (i.e., small to less than medium). The year 1-2 reliability for the reaction time, oculomotor/oculovestibular function, and quality-of-life measures ranged from 0.28 to 0.74 with effect sizes from 0.01 to 0.38 (i.e., small to less than medium effects).ConclusionsThis investigation noted less than optimal reliability for most common and emerging concussion assessment tools. Despite this finding, their use is still necessitated by the absence of a gold standard diagnostic measure, with the ultimate goal of developing more refined and sound tools for clinical use. Clinical interpretation guidelines are provided for the clinician to apply with a degree of certainty in application.
| S-EPMC5889766 | biostudies-literature
Project description:The NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium
| PRJNA671471 | ENA
Project description:The NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium
| PRJNA671472 | ENA
Project description:Sports-related concussion (SRC) is an important public health issue. Although standardized assessment tools are useful in the clinical management of acute concussion, the underlying pathophysiology of SRC and the time course of physiological recovery after injury remain unclear. In this study, we used diffusion tensor imaging (DTI) to detect white matter alterations in football players within 48 h after SRC. As part of the NCAA-DoD CARE Consortium study of SRC, 30 American football players diagnosed with acute concussion and 28 matched controls received clinical assessments and underwent advanced magnetic resonance imaging scans. To avoid selection bias and partial volume effects, whole-brain skeletonized white matter was examined by tract-based spatial statistics to investigate between-group differences in DTI metrics and their associations with clinical outcome measures. Mean diffusivity was significantly higher in brain white matter of concussed athletes, particularly in frontal and subfrontal long white matter tracts. In the concussed group, axial diffusivity was significantly correlated with the Brief Symptom Inventory and there was a similar trend with the symptom severity score of the Sport Concussion Assessment Tool. In addition, concussed athletes with higher fractional anisotropy performed better on the cognitive component of the Standardized Assessment of Concussion. Overall, the results of this study are consistent with the hypothesis that SRC is associated with changes in white matter tracts shortly after injury, and these differences are correlated clinically with acute symptoms and functional impairments.
| S-EPMC6238613 | biostudies-literature