Measurement of the Glial Fibrillary Acidic Protein and Its Breakdown Products GFAP-BDP Biomarker for the Detection of Traumatic Brain Injury Compared to Computed Tomography and Magnetic Resonance Imaging

Measurement of the Glial Fibrillary Acidic Protein and Its Breakdown Products GFAP-BDP Biomarker for the Detection of Traumatic Brain Injury Compared to Computed Tomography and Magnetic Resonance Imaging
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DOI:
10.1089/neu.2014.3635
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发表时间:
2015-04-15
影响因子:
4.2
通讯作者:
Vassar, Mary J.
Vassar, Mary J.
中科院分区:
医学2区
文献类型:
--
作者:
McMahon, Paul J.;Panczykowski, David M.;Vassar, Mary J.

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胶质细胞酸性蛋白及其降解产物(GFAP-BDP)是脑创伤后释放到血清中的脑特异性蛋白质,是创伤性脑损伤(TBI)后病理生理反应的一部分。我们进行了一项多中心试验,以验证和表征GFAP-BDP水平在诊断颅内损伤中的应用,这些患者具有头部损伤的阳性临床筛查。这项多中心、前瞻性、队列研究纳入了因疑似TBI(意识丧失、创伤后遗忘症等)就诊于3家1级创伤中心的16-93岁患者。在24小时内抽取血清GFAP-BDP水平,并使用夹心酶联免疫吸附试验以盲法进行分析。通过多元回归分析GFAP-BDP预测入院时计算机断层扫描(CT)和延迟磁共振成像颅内损伤的能力,并通过受试者工作特征曲线下面积(AUC)进行评估。利用决策曲线分析评估GFAP-BDP预测损伤和减少不必要的CT扫描的效用。共纳入215例患者,其中83%患有轻度TBI,4%中度,12%重度;平均年龄为42.1 ± 18岁。51%的样本存在颅内损伤的证据(中位鹿特丹评分,2;四分位距,2)。GFAP-BDP表现出非常好的预测能力(AUC=0.87),并表现出损伤严重程度的显著区分(比值比,1.45; 95%置信区间,1.29-1.64)。使用GFAP-BDP产生的净效益高于单独的临床筛查,并将不必要的扫描净减少12- 30%。结合其他临床信息,GFAP-BDP的快速测量可用于确定或排除整个TBI范围内影像学明显颅内损伤的诊断。作为当前筛查实践的辅助手段,GFAP-BDP可能有助于避免不必要的CT扫描,而不会牺牲灵敏度(注册表:ClinicalTrials.gov标识符:NCT 01565551)。
Glial fibrillary acidic protein and its breakdown products (GFAP-BDP) are brain-specific proteins released into serum as part of the pathophysiological response after traumatic brain injury (TBI). We performed a multi-center trial to validate and characterize the use of GFAP-BDP levels in the diagnosis of intracranial injury in a broad population of patients with a positive clinical screen for head injury. This multi-center, prospective, cohort study included patients 16-93 years of age presenting to three level 1 trauma centers with suspected TBI (loss of consciousness, post-trauma amnesia, and so on). Serum GFAP-BDP levels were drawn within 24 h and analyzed, in a blinded fashion, using sandwich enzyme-linked immunosorbent assay. The ability of GFAP-BDP to predict intracranial injury on admission computed tomography (CT) as well as delayed magnetic resonance imaging was analyzed by multiple regression and assessed by the area under the receiver operating characteristic curve (AUC). Utility of GFAP-BDP to predict injury and reduce unnecessary CT scans was assessed utilizing decision curve analysis. A total of 215 patients were included, of which 83% suffered mild TBI, 4% moderate, and 12% severe; mean age was 42.1 +/- 18 years. Evidence of intracranial injury was present in 51% of the sample (median Rotterdam Score, 2; interquartile range, 2). GFAP-BDP demonstrated very good predictive ability (AUC=0.87) and demonstrated significant discrimination of injury severity (odds ratio, 1.45; 95% confidence interval, 1.29-1.64). Use of GFAP-BDP yielded a net benefit above clinical screening alone and a net reduction in unnecessary scans by 12-30%. Used in conjunction with other clinical information, rapid measurement of GFAP-BDP is useful in establishing or excluding the diagnosis of radiographically apparent intracranial injury throughout the spectrum of TBI. As an adjunct to current screening practices, GFAP-BDP may help avoid unnecessary CT scans without sacrificing sensitivity (Registry: ClinicalTrials.gov Identifier: NCT01565551).