Department of Neurology, Emory University School of Medicine and Grady Hospital, Atlanta, Georgia.
Novartis Institutes of Biomedical Research, Cambridge, Massachusetts.
J Neurotrauma. 2019 Oct 15;36(20):2863-2871. doi: 10.1089/neu.2018.5809. Epub 2019 Jul 9.
Rapid risk-stratification of patients with acute traumatic brain injury (TBI) would inform management decisions and prognostication. The objective of this serum biomarker study (Biomarkers of Injury and Outcome [BIO]-Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment [ProTECT]) was to test the hypothesis that serum biomarkers of structural brain injury, measured at a single, very early time-point, add value beyond relevant clinical covariates when predicting unfavorable outcome 6 months after moderate-to-severe acute TBI. BIO-ProTECT utilized prospectively collected samples obtained from subjects with moderate-to-severe TBI enrolled in the ProTECT III clinical trial of progesterone. Serum samples were obtained within 4 h after injury. Glial fibrillary acidic protein (GFAP), S100B, αII-spectrin breakdown product of molecular weight 150 (SBDP150), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) were measured. The association between log-transformed biomarker levels and poor outcome, defined by a Glasgow Outcome Scale-Extended (GOS-E) score of 1-4 at 6 months post-injury, were estimated via logistic regression. Prognostic models and a biomarker risk score were developed using bootstrapping techniques. Of 882 ProTECT III subjects, samples were available for 566. Each biomarker was associated with 6-month GOS-E ( < 0.001). Compared with a model containing baseline patient variables/characteristics, inclusion of S100B and GFAP significantly improved prognostic capacity ( ≤ 0.05 both comparisons); conversely, UCH-L1 and SBDP did not. A final predictive model incorporating baseline patient variables/characteristics and biomarker data (S100B and GFAP) had the best prognostic capability (area under the curve [AUC] = 0.85, 95% confidence interval [CI]: CI 0.81-0.89). Very early measurements of brain-specific biomarkers are independently associated with 6-month outcome after moderate-to-severe TBI and enhance outcome prediction.
急性创伤性脑损伤（TBI）患者的快速风险分层将为管理决策和预后提供信息。本血清生物标志物研究（损伤和预后的生物标志物[BIO]-用于创伤性脑损伤的孕激素，实验性临床治疗[ProTECT]）的目的是检验以下假设，即在预测中至重度急性 TBI 后 6 个月的不良结局时，在单个非常早期时间点测量的结构性脑损伤血清生物标志物除了相关的临床协变量外，还有价值。BIO-ProTECT 使用了从 ProTECT III 临床试验中纳入的中重度 TBI 受试者前瞻性收集的样本。损伤后 4 小时内采集血清样本。测量了神经胶质纤维酸性蛋白（GFAP）、S100B、αII- spectrin 分子量 150 片段（SBDP150）和泛素 C 端水解酶-L1（UCH-L1）。通过逻辑回归估计了生物标志物水平与不良结局之间的关联，不良结局由损伤后 6 个月时的格拉斯哥结局量表扩展（GOS-E）评分 1-4 定义。使用 bootstrap 技术开发了预后模型和生物标志物风险评分。在 882 名 ProTECT III 受试者中，有 566 名受试者的样本可用。每个生物标志物都与 6 个月 GOS-E 相关（ < 0.001）。与包含基线患者变量/特征的模型相比，包含 S100B 和 GFAP 的模型显著改善了预后能力（两者比较 ≤ 0.05）；相反，UCH-L1 和 SBDP 则没有。最终的预测模型包含基线患者变量/特征和生物标志物数据（S100B 和 GFAP），具有最佳的预后能力（曲线下面积[AUC] = 0.85，95%置信区间[CI]：CI 0.81-0.89）。中重度 TBI 后 6 个月的预后与脑特异性生物标志物的早期测量结果独立相关，并增强了预后预测。
