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Browsing by Author "Huber, Daniel L."

Now showing 1 - 4 of 4
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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.; McCrea, Michael A.; Huber, Daniel L.; Cameron, Kenneth L.; Houston, Megan N.; Jackson, Jonathan C.; McGinty, Gerald T.; Pasquina, Paul; Broglio, Steven P.; Brooks, M. Alison; DiFiori, John P.; Duma, Stefan M.; Harezlak, Jaroslaw; Goldman, Joshua T.; Guskiewicz, Kevin M.; McAllister, Thomas W.; McArthur, David; Meier, Timothy B.; Mihalik, Jason P.; Nelson, Lindsay D.; Rowson, Steven; Gill, Jessica M. (2021-02-22)
    Importance 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. Objective To investigate acute blood protein levels in military cadets after combative training-associated concussions. Design, Setting, and Participants This multicenter prospective case-control study was part of a larger cohort study conducted by the National Collegiate Athletic Association and the US Department of Defense Concussion Assessment Research and Education (CARE) Consortium from February 20, 2015, to May 31, 2018. The study was performed among cadets from 2 CARE Consortium Advanced Research Core sites: the US Military Academy at West Point and the US Air Force Academy. Cadets who incurred concussions during combative training (concussion group) were compared with cadets who participated in the same combative training exercises but did not incur concussions (contact-control group). Clinical measures and blood sample collection occurred at baseline, the acute postinjury point (<6 hours), the 24- to 48-hour postinjury point, the asymptomatic postinjury point (defined as the point at which the cadet reported being asymptomatic and began the return-to-activity protocol), and 7 days after return to activity. Biomarker levels and estimated mean differences in biomarker levels were natural log (ln) transformed to decrease the skewness of their distributions. Data were collected from August 1, 2016, to May 31, 2018, and analyses were conducted from March 1, 2019, to January 14, 2020. Exposure Concussion incurred during combative training. Main Outcomes and Measures Proteins examined included glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, neurofilament light chain, and tau. Quantification was conducted using a multiplex assay (Simoa; Quanterix Corp). Clinical measures included the Sport Concussion Assessment Tool-Third Edition symptom severity evaluation, the Standardized Assessment of Concussion, the Balance Error Scoring System, and the 18-item Brief Symptom Inventory. Results Among 103 military service academy cadets, 67 cadets incurred concussions during combative training, and 36 matched cadets who engaged in the same training exercises did not incur concussions. The mean (SD) age of cadets in the concussion group was 18.6 (1.3) years, and 40 cadets (59.7%) were male. The mean (SD) age of matched cadets in the contact-control group was 19.5 (1.3) years, and 25 cadets (69.4%) were male. Compared with cadets in the contact-control group, those in the concussion group had significant increases in glial fibrillary acidic protein (mean difference in ln values, 0.34; 95% CI, 0.18-0.50; P < .001) and ubiquitin C-terminal hydrolase-L1 (mean difference in ln values, 0.97; 95% CI, 0.44-1.50; P < .001) levels at the acute postinjury point. The glial fibrillary acidic protein level remained high in the concussion group compared with the contact-control group at the 24- to 48-hour postinjury point (mean difference in ln values, 0.22; 95% CI, 0.06-0.38; P = .007) and the asymptomatic postinjury point (mean difference in ln values, 0.21; 95% CI, 0.05-0.36; P = .01). The area under the curve for all biomarkers combined, which was used to differentiate cadets in the concussion and contact-control groups, was 0.80 (95% CI, 0.68-0.93; P < .001) at the acute postinjury point. Conclusions and Relevance This study's findings indicate that blood biomarkers have potential for use as research tools to better understand the pathobiological changes associated with concussion and to assist with injury identification and recovery from combative training-associated concussions among military service academy cadets. These results extend the previous findings of studies of collegiate athletes with sport-associated concussions.
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    Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium
    McCrea, Michael A.; Broglio, Steven P.; McAllister, Thomas W.; Gill, Jessica M.; Giza, Christopher C.; Huber, Daniel L.; Harezlak, Jaroslaw; Cameron, Kenneth L.; Houston, Megan N.; McGinty, Gerald T.; Jackson, Jonathan C.; Guskiewicz, Kevin M.; Mihalik, Jason P.; Brooks, M. Alison; Duma, Stefan M.; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; Meier, Timothy B.; Foroud, Tatiana; Katz, Barry P.; Saykin, Andrew J.; Campbell, Darren E.; Svoboda, Steven J.; Goldman, Joshua T.; DiFiori, John P. (2020-01-24)
    Question Is sport-related concussion associated with levels of traumatic brain injury biomarkers in collegiate athletes? Findings In this case-control study of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport athletes, the athletes with concussion had significant elevations in multiple traumatic brain injury biomarkers compared with preseason baseline and with 2 groups of control athletes without concussion during the acute postinjury period. Meaning These 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 sport-related concussion. This case-control study examines the association between sport-related concussion and levels of traumatic brain injury biomarkers in collegiate athletes. 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 x visit) was found for GFAP (F-7,F-1507.36 = 16.18, P < .001), UCH-L1 (F-7,F-1153.09 = 5.71, P < .001), and tau (F-7,F-1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F-7,F-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 (beta = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (beta = 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.
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    Cumulative Effects of Prior Concussion and Primary Sport Participation on Brain Morphometry in Collegiate Athletes: A Study From the NCAA-DoD CARE Consortium
    Brett, Benjamin L.; Bobholz, Samuel A.; Espana, Lezlie Y.; Huber, Daniel L.; Mayer, Andrew R.; Harezlak, Jaroslaw; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Meier, Timothy B.; DiFiori, John P.; Saykin, Andrew J.; Wu, Yu-Chien; Nencka, Andrew S.; Giza, Christopher C.; Goldman, Joshua T.; Mihalik, Jason P.; Brooks, M. Alison; Duma, Stefan M.; Rowson, Steven (2020-07-28)
    Prior studies have reported long-term differences in brain structure (brain morphometry) as being associated with cumulative concussion and contact sport participation. There is emerging evidence to suggest that similar effects of prior concussion and contact sport participation on brain morphometry may be present in younger cohorts of active athletes. We investigated the relationship between prior concussion and primary sport participation with subcortical and cortical structures in active collegiate contact sport and non-contact sport athletes. Contact sport athletes (CS;N= 190) and matched non-contact sport athletes (NCS;N= 95) completed baseline clinical testing and participated in up to four serial neuroimaging sessions across a 6-months period. Subcortical and cortical structural metrics were derived using FreeSurfer. Linear mixed-effects (LME) models examined the effects of years of primary sport participation and prior concussion (0, 1+) on brain structure and baseline clinical variables. Athletes with prior concussion across both groups reported significantly more baseline concussion and psychological symptoms (allps < 0.05). The relationship between years of primary sport participation and thalamic volume differed between CS and NCS (p= 0.015), driven by a significant inverse association between primary years of participation and thalamic volume in CS (p= 0.007). Additional analyses limited to CS alone showed that the relationship between years of primary sport participation and dorsal striatal volume was moderated by concussion history (p= 0.042). Finally, CS with prior concussion had larger hippocampal volumes than CS without prior concussion (p= 0.015). Years of contact sport exposure and prior concussion(s) are associated with differences in subcortical volumes in young-adult, active collegiate athletes, consistent with prior literature in retired, primarily symptomatic contact sport athletes. Longitudinal follow-up studies in these athletes are needed to determine clinical significance of current findings.
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    Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes-A Concussion Assessment, Research, and Education (CARE) Consortium Study
    Pattinson, Cassandra L.; Meier, Timothy B.; Guedes, Vivian A.; Lai, Chen; Devoto, Christina; Haight, Thaddeus; Broglio, Steven P.; McAllister, Thomas W.; Giza, Christopher C.; Huber, Daniel L.; Harezlak, Jaroslaw; Cameron, Kenneth L.; McGinty, Gerald T.; Jackson, Jonathan C.; Guskiewicz, Kevin M.; Mihalik, Jason P.; Brooks, M. Alison; Duma, Stefan M.; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; McCrea, Michael A.; Gill, Jessica M. (2020-08-27)
    Question Are plasma biomarkers associated with a return-to-sport period of less than 14 days vs 14 days or more in male and female collegiate athletes following a sport-related concussion? Findings This diagnostic study, which included 127 collegiate athletes who had sustained a sports-related concussion, found that higher total tau concentrations 24 to 48 hours after injury and at the time of symptom resolution as well as lower glial fibrillary acidic protein levels acutely postinjury were associated with return-to-sport decisions. Meaning In this study, total tau and glial fibrillary acidic protein levels were associated with return to sport in male and female collegiate athletes following a sports-related concussion. This diagnostic study examines whether plasma biomarkers can differentiate collegiate athletes who return to sport in less than 14 days vs 14 days or more following a sports-related concussion. Importance Identifying plasma biomarkers associated with the amount of time an athlete may need before they return to sport (RTS) following a sport-related concussion (SRC) is important because it may help to improve the health and safety of athletes. Objective To examine whether plasma biomarkers can differentiate collegiate athletes who RTS in less than 14 days or 14 days or more following SRC. Design, Setting, and Participants This multicenter prospective diagnostic study, conducted by the National Collegiate Athletics Association-Department of Defense Concussion Assessment, Research, and Education Consortium, included 127 male and female athletes who had sustained an SRC while enrolled at 6 Concussion Assessment, Research, and Education Consortium Advanced Research Core sites as well as 2 partial-Advanced Research Core military service academies. Data were collected between February 2015 and May 2018. Athletes with SRC completed clinical testing and blood collection at preseason (baseline), postinjury (0-21 hours), 24 to 48 hours postinjury, time of symptom resolution, and 7 days after unrestricted RTS. Main Outcomes and Measures A total of 3 plasma biomarkers (ie, total tau protein, glial fibrillary acidic protein [GFAP], and neurofilament light chain protein [Nf-L]) were measured using an ultrasensitive single molecule array technology and were included in the final analysis. RTS was examined between athletes who took less than 14 days vs those who took 14 days or more to RTS following SRC. Linear mixed models were used to identify significant interactions between period by RTS group. Area under the receiver operating characteristic curve analyses were conducted to examine whether these plasma biomarkers could discriminate between RTS groups. Results The 127 participants had a mean (SD) age of 18.9 (1.3) years, and 97 (76.4%) were men; 65 (51.2%) took less than 14 days to RTS, and 62 (48.8%) took 14 days or more to RTS. Linear mixed models identified significant associations for both mean (SE) plasma total tau (24-48 hours postinjury, <14 days RTS vs >= 14 days RTS: -0.65 [0.12] pg/mL vs -0.14 [0.14] pg/mL; P = .008) and GFAP (postinjury, 14 days RTS vs >= 14 days RTS: 4.72 [0.12] pg/mL vs 4.39 [0.11] pg/mL; P = .04). Total tau at the time of symptom resolution had acceptable discrimination power (area under the receiver operating characteristic curve, 0.75; 95% CI, 0.63-0.86; P < .001). We also examined a combined plasma biomarker panel that incorporated Nf-L, GFAP, and total tau at each period to discriminate RTS groups. Although the analyses did reach significance at each time period when combined, results indicated that they were poor at distinguishing the groups (area under the receiver operating characteristic curve, <0.7). Conclusions and Relevance The findings of this study suggest that measures of total tau and GFAP may identify athletes who will require more time to RTS. However, further research is needed to improve our ability to determine recovery following an SRC.