Division of Psychology, University of Stirling, Stirling, United Kingdom.
Division of Anaesthesia and PACE, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
EBioMedicine. 2024 Sep;107:105298. doi: 10.1016/j.ebiom.2024.105298. Epub 2024 Aug 26.
Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury.
Exposure-response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates.
Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13-15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 and positive CT (1.21-2.81), GCS 9-12 (1.16-2.02), GCS 3-8 (1.09-1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) percentages of unfavourable outcome were 37-51% in the lowest quintiles of biomarker levels and reached 90-94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), the percentages were 2-4% and 19-28% in the lowest and highest biomarker quintiles, respectively.
Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity.
European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.
传统上，根据格拉斯哥昏迷量表（GCS）将创伤性脑损伤分为轻度、中度和重度。最近开发的生物标志物可以提供更客观和细致的脑损伤程度测量。
在协作性欧洲神经创伤有效性研究颅脑损伤（CENTER-TBI）前瞻性观察队列研究中，对 2479 名年龄≥16 岁的患者进行了暴露-反应关系研究。在第 1 天采集血清，检测神经丝轻链蛋白（NFL）、泛素羧基末端水解酶 L1（UCH-L1）和胶质纤维酸性蛋白（GFAP）；在 GCS 严重程度组内将浓度分为五分位数。使用改良泊松回归包括年龄、性别、主要颅外损伤、样本采集时间和生物标志物浓度对数作为协变量，研究与格拉斯哥结局量表扩展版的关系。
在调整协变量后，在严重程度组内，生物标志物与结局之间存在关联：GCS 13-15 且 CT 扫描阴性（相对风险 [RR] 为 1.28 至 3.72）、GCS 13-15 且 CT 扫描阳性（1.21-2.81）、GCS 9-12（1.16-2.02）、GCS 3-8（1.09-1.94）。RR 与预后的临床重要差异有关。在 GCS 3 的患者中（RR 1.51-1.80），在生物标志物水平最低五分位数的不良结局百分比为 37-51%，在最高五分位数的不良结局百分比达到 90-94%。同样，对于 GCS 15（RR 1.83-3.79），在最低和最高生物标志物五分位数中，不良结局的百分比分别为 2-4%和 19-28%。
传统的 TBI 严重程度分类是不充分的，低估了脑损伤的异质性和相关结局。循环生物标志物的采用可以补充对损伤严重程度的临床评估。
欧盟第七框架计划（欧盟赠款 602150）、Hannelore Kohl 基金会、One Mind、Integra LifeSciences、Neuro-Trauma Sciences、NIHR Rosetrees Trust。
