Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, USA.
Herbert Wertheim School of Public Health and Human Longevity Science, University of California at San Diego, La Jolla, CA, USA.
Lancet Neurol. 2022 Sep;21(9):803-813. doi: 10.1016/S1474-4422(22)00256-3.
The prognostic value of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) as day-of-injury predictors of functional outcome after traumatic brain injury is not well understood. GFAP is a protein found in glial cells and UCH-L1 is found in neurons, and these biomarkers have been cleared to aid in decision making regarding whether brain CT should be performed after traumatic brain injury. We aimed to quantify their prognostic accuracy and investigate whether these biomarkers contribute novel prognostic information to existing clinical models.
We enrolled patients from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) observational cohort study. TRACK-TBI includes patients 17 years and older who are evaluated for TBI at 18 US level 1 trauma centres. All patients receive head CT at evaluation, have adequate visual acuity and hearing preinjury, and are fluent in either English or Spanish. In our analysis, we included participants aged 17-90 years who had day-of-injury plasma samples for measurement of GFAP and UCH-L1 and completed 6-month assessments for outcome due to traumatic brain injury with the Glasgow Outcome Scale-Extended (GOSE-TBI). Biomarkers were analysed as continuous variables and in quintiles. This study is registered with ClinicalTrials.gov, NCT02119182.
We enrolled 2552 patients from Feb 26, 2014, to Aug 8, 2018. Of the 1696 participants with brain injury and data available at baseline and at 6 months who were included in the analysis, 120 (7·1%) died (GOSE-TBI=1), 235 (13·9%) had an unfavourable outcome (ie, GOSE-TBI ≤4), 1135 (66·9%) had incomplete recovery (ie, GOSE-TBI <8), and 561 (33·1%) recovered fully (ie, GOSE-TBI=8). The area under the curve (AUC) of GFAP for predicting death at 6 months in all patients was 0·87 (95% CI 0·83-0·91), for unfavourable outcome was 0·86 (0·83-0·89), and for incomplete recovery was 0·62 (0·59-0·64). The corresponding AUCs for UCH-L1 were 0·89 (95% CI 0·86-0·92) for predicting death, 0·86 (0·84-0·89) for unfavourable outcome, and 0·61 (0·59-0·64) for incomplete recovery at 6 months. AUCs were higher for participants with traumatic brain injury and Glasgow Coma Scale (GCS) score of 3-12 than for those with GCS score of 13-15. Among participants with GCS score of 3-12 (n=353), adding GFAP and UCH-L1 (alone or combined) to each of the three International Mission for Prognosis and Analysis of Clinical Trials in traumatic brain injury models significantly increased their AUCs for predicting death (AUC range 0·90-0·94) and unfavourable outcome (AUC range 0·83-0·89). However, among participants with GCS score of 13-15 (n=1297), adding GFAP and UCH-L1 to the UPFRONT study model modestly increased the AUC for predicting incomplete recovery (AUC range 0·69-0·69, p=0·025).
In addition to their known diagnostic value, day-of-injury GFAP and UCH-L1 plasma concentrations have good to excellent prognostic value for predicting death and unfavourable outcome, but not for predicting incomplete recovery at 6 months. These biomarkers contribute the most prognostic information for participants presenting with a GCS score of 3-12.
US National Institutes of Health, National Institute of Neurologic Disorders and Stroke, US Department of Defense, One Mind, US Army Medical Research and Development Command.
胶质纤维酸性蛋白（GFAP）和泛素 C 端水解酶 L1（UCH-L1）作为伤后当天预测创伤性脑损伤后功能结局的预测因子的预后价值尚不清楚。GFAP 存在于神经胶质细胞中，UCH-L1 存在于神经元中，这些生物标志物已被批准用于辅助决策是否应在创伤性脑损伤后进行脑部 CT 检查。我们旨在量化它们的预后准确性，并研究这些生物标志物是否为现有临床模型提供新的预后信息。
我们从转化研究和临床知识在创伤性脑损伤（TRACK-TBI）观察性队列研究中招募了患者。TRACK-TBI 包括在 18 个美国 1 级创伤中心评估 TBI 的 17 岁及以上患者。所有患者在评估时均接受头部 CT 检查，受伤前有足够的视力和听力，并且能流利地使用英语或西班牙语。在我们的分析中，我们纳入了年龄在 17 至 90 岁之间、伤后当天有血浆样本用于测量 GFAP 和 UCH-L1 且因创伤性脑损伤完成了 6 个月格拉斯哥结局量表-扩展版（GOSE-TBI）评估的参与者。生物标志物以连续变量和五分位数进行分析。这项研究在 ClinicalTrials.gov 注册，NCT02119182。
我们于 2014 年 2 月 26 日至 2018 年 8 月 8 日招募了 2552 名患者。在纳入分析的 1696 名有脑损伤且基线和 6 个月时有数据的参与者中，120 名（7.1%）死亡（GOSE-TBI=1），235 名（13.9%）预后不良（即 GOSE-TBI≤4），1135 名（66.9%）不完全恢复（即 GOSE-TBI<8），561 名（33.1%）完全恢复（即 GOSE-TBI=8）。在所有患者中，GFAP 预测 6 个月死亡的曲线下面积（AUC）为 0.87（95%CI 0.83-0.91），预测预后不良的 AUC 为 0.86（0.83-0.89），预测不完全恢复的 AUC 为 0.62（0.59-0.64）。UCH-L1 的相应 AUC 为预测死亡的 0.89（95%CI 0.86-0.92）、预后不良的 0.86（0.84-0.89）和不完全恢复的 0.61（0.59-0.64）。与 GCS 评分为 13-15 的患者相比，GCS 评分为 3-12 的患者的 AUC 更高。在 GCS 评分为 3-12（n=353）的患者中，单独或联合添加 GFAP 和 UCH-L1 可显著提高其预测死亡（AUC 范围 0.90-0.94）和预后不良（AUC 范围 0.83-0.89）的 AUC。然而，在 GCS 评分为 13-15（n=1297）的患者中，将 GFAP 和 UCH-L1 添加到 UPFRONT 研究模型中仅适度提高了预测不完全恢复的 AUC（AUC 范围 0.69-0.69，p=0.025）。
除了已知的诊断价值外，伤后当天 GFAP 和 UCH-L1 血浆浓度对预测死亡和预后不良具有良好到极好的预后价值，但对预测 6 个月时的不完全恢复没有价值。这些生物标志物对 GCS 评分为 3-12 的患者提供了最多的预后信息。
美国国立卫生研究院、美国国立神经病学和中风研究所、美国国防部、One Mind、美国陆军医学研究与发展司令部。
