Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
J Neurotrauma. 2013 Sep 1;30(17):1490-7. doi: 10.1089/neu.2013.2883. Epub 2013 Aug 1.
Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. Participants were identified as part of the prospective Transforming Research And Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. Acute plasma samples (<24 h post-injury) were collected from patients presenting with brain injury who had CT imaging. The ability of GFAP-BDP level to discriminate patients with demonstrable traumatic lesions on CT, and with failure to return to pre-injury baseline at 6 months, was evaluated by the area under the receiver operating characteristic curve (AUC). Of the 215 patients included for analysis, 83% had mild, 4% had moderate, and 13% had severe TBI; 54% had acute traumatic lesions on CT. The ability of GFAP-BDP level to discriminate patients with traumatic lesions on CT as evaluated by AUC was 0.88 (95% confidence interval [CI], 0.84-0.93). The optimal cutoff of 0.68 ng/mL for plasma GFAP-BDP level was associated with a 21.61 odds ratio for traumatic findings on head CT. Discriminatory ability of unfavorable 6 month outcome was lower, AUC 0.65 (95% CI, 0.55-0.74), with a 2.07 odds ratio. GFAP-BDP levels reliably distinguish the presence and severity of CT scan findings in TBI patients. Although these findings confirm and extend prior studies, a larger prospective trial is still needed to validate the use of GFAP-BDP as a routine diagnostic biomarker for patient care and clinical research. The term "mild" continues to be a misnomer for this patient population, and underscores the need for evolving classification strategies for TBI targeted therapy. (ClinicalTrials.gov number NCT01565551; NIH Grant 1RC2 NS069409).
可靠的创伤性脑损伤 (TBI) 诊断是一项重大的公共卫生需求。胶质纤维酸性蛋白 (GFAP) 在中枢神经系统中表达，在实质脑损伤后释放其降解产物 (GFAP-BDP)。在这里，我们评估了血浆 GFAP-BDP 升高水平在 TBI 中的诊断准确性。参与者是前瞻性转化研究和临床知识在创伤性脑损伤 (TRACK-TBI) 研究的一部分。从有 CT 成像的脑损伤患者中采集发病后 24 小时内的急性血浆样本。通过接受者操作特征曲线 (AUC) 下的面积来评估 GFAP-BDP 水平区分 CT 上有明显创伤性病变的患者以及在 6 个月时未能恢复到损伤前基线的能力。在纳入分析的 215 名患者中，83%为轻度，4%为中度，13%为重度 TBI；54%的患者 CT 上有急性创伤性病变。GFAP-BDP 水平区分 CT 上有创伤性病变的患者的 AUC 为 0.88(95%置信区间[CI]，0.84-0.93)。血浆 GFAP-BDP 水平的最佳截断值为 0.68ng/ml，与头部 CT 上有创伤性发现的 21.61 比值比相关。6 个月不良结局的鉴别能力较低，AUC 为 0.65(95%CI，0.55-0.74)，比值比为 2.07。GFAP-BDP 水平可靠地区分 TBI 患者 CT 扫描结果的存在和严重程度。尽管这些发现证实并扩展了先前的研究，但仍需要更大规模的前瞻性试验来验证 GFAP-BDP 作为常规诊断生物标志物用于患者护理和临床研究的使用。“轻度”一词对该患者群体仍然是一个错误的称呼，并强调需要为 TBI 靶向治疗制定不断发展的分类策略。(临床试验.gov 编号 NCT01565551；NIH 拨款 1RC2 NS069409)。
