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.

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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DOI:
10.1001/jamanetworkopen.2020.37731
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发表时间:
2021-02-01
期刊:
影响因子:
13.8
通讯作者:
Svoboda S
Svoboda S
中科院分区:
医学1区
文献类型:
--
作者:
Giza CC;McCrea M;Huber D;Cameron KL;Houston MN;Jackson JC;McGinty G;Pasquina P;Broglio SP;Brooks A;DiFiori J;Duma S;Harezlak J;Goldman J;Guskiewicz K;McAllister TW;McArthur D;Meier TB;Mihalik JP;Nelson LD;Rowson S;Gill J;CARE Consortium Investigators;Foroud T;Katz B;Saykin A;Campbell DE;Svoboda S

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军事院校学员中,战斗训练中发生的脑震荡是否与创伤性脑损伤的蛋白质生物标志物的血液水平变化有关?在这项对美国103名军事服务学院学员的病例对照研究中,在战斗训练期间发生脑震荡的学员中,胶质细胞酸性蛋白和泛素C-末端水解酶-L1生物标志物的水平与基线值和参加相同战斗训练但未发生脑震荡的匹配学员中发现的值相比显着增加。神经丝轻链水平显着较高的学员与脑震荡相比,那些没有脑震荡,在受伤后不到6小时,恢复活动后7天。在这项研究中,血液生物标志物描绘了军事战斗训练期间发生的脑震荡后的生理变化,表明与运动相关脑震荡研究中报告的模式基本一致。验证蛋白质生物标志物用于军事战斗训练中的脑震荡诊断和管理非常重要,因为这些损伤发生在传统医疗保健环境之外,通常难以诊断。探讨军校学员在格斗训练相关脑震荡后的急性血蛋白水平。这项多中心前瞻性病例对照研究是由全国大学生体育协会和美国国防部脑震荡评估研究与教育(CARE)联盟于2015年2月20日至2018年5月31日进行的更大队列研究的一部分。这项研究是在来自两个CARE联盟高级研究核心地点的学员中进行的:美国军事学院西点和美国空军学院。将在格斗训练中发生脑震荡的学员(脑震荡组)与参加相同格斗训练但未发生脑震荡的学员(接触对照组)进行比较。在基线、急性损伤后时间点(<6小时)、损伤后24 - 48小时时间点、无症状损伤后时间点(定义为学员报告无症状并开始恢复活动方案的时间点)和恢复活动后7天进行临床测量和血样采集。对生物标志物水平和生物标志物水平的估计平均差异进行自然对数(ln)转换,以降低其分布的偏度。数据收集时间为2016年8月1日至2018年5月31日,分析时间为2019年3月1日至2020年1月14日。在格斗训练中造成的脑震荡。检查的蛋白质包括神经胶质细胞酸性蛋白、泛素C-末端水解酶-L1、神经丝轻链和tau蛋白。使用多重测定(Simoa; Quanterix Corp)进行定量。临床测量包括运动性脑震荡评估工具-第三版症状严重程度评估、脑震荡标准化评估、平衡误差评分系统和18项简明症状量表。在103名军校学员中,67名学员在战斗训练中发生脑震荡,36名参加相同训练演习的学员没有发生脑震荡。脑震荡组学员的平均(SD)年龄为18.6(1.3)岁,40名学员(59.7%)为男性。接触对照组中匹配学员的平均(SD)年龄为19.5(1.3)岁,25名学员(69.4%)为男性。与接触对照组相比,脑震荡组的胶质细胞酸性蛋白显著增加(ln值的平均差异,0.34; 95% CI,0.18 - 0.50; P <.001)和泛素C末端水解酶-L1(ln值的平均差异,0.97; 95%CI,0.44 - 1.50; P <0.001)。在伤后24 - 48小时,脑震荡组的胶质细胞酸性蛋白水平仍然高于接触对照组(ln值的平均差异,0.22; 95% CI,0.06 - 0.38; P = 0.007)和无症状损伤后点(ln值的平均差异,0.21; 95%CI,0.05 - 0.36; P = 0.01)。用于区分脑震荡组和接触对照组的所有生物标志物的曲线下面积在急性损伤后为0.80(95%CI,0.68 - 0.93; P <0.001)。这项研究的结果表明,血液生物标志物有可能用作研究工具,以更好地了解与脑震荡相关的病理生物学变化,并协助军事服务学院学员从战斗训练相关脑震荡中识别和恢复。这些结果扩展了先前对大学运动员运动相关脑震荡的研究结果。这项病例对照研究旨在探讨美国军事学院学员在战斗训练演习中发生脑震荡后,创伤性脑损伤的蛋白质生物标志物的血液水平是否发生变化。
Is concussion incurred during combative training associated with changes in blood levels of protein biomarkers for traumatic brain injury among military service academy cadets? In this case-control study of 103 military service academy cadets in the US, the levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 biomarkers among cadets who incurred concussions during combative training indicated significant increases compared with baseline values and values found in matched cadets who participated in the same combative training exercises but did not incur concussions. Neurofilament light chain levels were significantly higher among cadets with concussions compared with those without concussions at less than 6 hours after injury to 7 days after return to activity. In this study, blood biomarkers delineated physiological changes after concussions that were incurred during military combative training, indicating patterns that were largely consistent with those reported in studies of sport-associated concussions. 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. To investigate acute blood protein levels in military cadets after combative training–associated concussions. 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. Concussion incurred during combative training. 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. 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. 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. This case-control study examines whether blood levels of protein biomarkers for traumatic brain injury change after concussions incurred during combative training exercises among US military service academy cadets.
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