用于预测中重度创伤性脑损伤患者颅内出血和结局的基于血液的生物标志物。
Blood-based biomarkers for prediction of intracranial hemorrhage and outcome in patients with moderate or severe traumatic brain injury.
机构信息
From the School of Medicine (T.N.A.), Department of Neurology (H.E.H.), Department of Surgery (S.E.R.), Oregon Health and Science University, Portland, Oregon; Department of Biostatistics (J.H.), University of Washington, Seattle, Washington; College of Pharmacy (M.M.), Oregon State University, Corvallis, Oregon; Department of Emergency Medicine (L.P.), Orlando Regional Medical Center, Orlando, Florida; Department of Surgery (A.V.), Mercer University School of Medicine, Macon, Georgia; and Department of Surgery (S.E.R.), Duke University Medical Center, Durham, North Carolina.
出版信息
J Trauma Acute Care Surg. 2020 Jul;89(1):80-86. doi: 10.1097/TA.0000000000002706.
BACKGROUND
Early identification of traumatic intracranial hemorrhage (ICH) has implications for triage and intervention. Blood-based biomarkers were recently approved by the Food and Drug Administration (FDA) for prediction of ICH in patients with mild traumatic brain injury (TBI). We sought to determine if biomarkers measured early after injury improve prediction of mortality and clinical/radiologic outcomes compared with Glasgow Coma Scale (GCS) alone in patients with moderate or severe TBI (MS-TBI).
METHODS
We measured glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein-2 (MAP-2) on arrival to the emergency department (ED) in patients with blunt TBI enrolled in the placebo arm of the Prehospital TXA for TBI Trial (prehospital GCS score, 3-12; SPB, > 90). Biomarkers were modeled individually and together with prehospital predictor variables [PH] (GCS score, age, sex). Data were divided into a training data set and test data set for model derivation and evaluation. Models were evaluated for prediction of ICH, mass lesion, 48-hour and 28-day mortality, and 6-month Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). Area under the curve (AUC) was evaluated in test data for PH alone, PH + individual biomarkers, and PH + three biomarkers.
RESULTS
Of 243 patients with baseline samples (obtained a median of 84 minutes after injury), prehospital GCS score was 8 (interquartile range, 5-10), 55% had ICH, and 48-hour and 28-day mortality were 7% and 13%, respectively. Poor neurologic outcome at 6 months was observed in 34% based on GOS-E of 4 or less, and 24% based on DRS greater than or equal to7. Addition of each biomarker to PH improved AUC in the majority of predictive models. GFAP+PH compared with PH alone significantly improved AUC in all models (ICH, 0.82 vs. 0.64; 48-hour mortality, 0.84 vs. 0.71; 28-day mortality, 0.84 vs. 0.66; GOS-E, 0.78 vs. 0.69; DRS, 0.84 vs. 0.81, all p < 0.001).
CONCLUSION
Circulating blood-based biomarkers may improve prediction of neurological outcomes and mortality in patients with MS-TBI over prehospital characteristics alone. Glial fibrillary acidic protein appears to be the most promising. Future evaluation in the prehospital setting is warranted.
LEVEL OF EVIDENCE
Prospective, Prognostic and Epidemiological, level II.
背景
早期识别创伤性颅内出血（ICH）对分诊和干预具有重要意义。血液生物标志物最近已被美国食品和药物管理局（FDA）批准用于预测轻度创伤性脑损伤（TBI）患者的 ICH。我们旨在确定与格拉斯哥昏迷量表（GCS）单独评估相比，在中度或重度 TBI（MS-TBI）患者中，受伤后早期测量的生物标志物是否可以改善死亡率和临床/放射学结局的预测。
方法
我们在参加创伤前 TXA 治疗 TBI 试验（院前 GCS 评分为 3-12；SPB>90）的钝性 TBI 患者到达急诊室（ED）时测量了神经胶质纤维酸性蛋白（GFAP）、泛素 C 端水解酶 L1（UCH-L1）和微管相关蛋白-2（MAP-2）。分别对生物标志物和院前预测变量[PH]（GCS 评分、年龄、性别）进行建模。将数据分为训练数据集和测试数据集，用于模型推导和评估。使用测试数据评估模型对 ICH、肿块病变、48 小时和 28 天死亡率以及 6 个月格拉斯哥结局量表-扩展（GOS-E）和残疾评定量表（DRS）的预测。在测试数据中评估 PH 单独、PH+单个生物标志物和 PH+三个生物标志物的曲线下面积（AUC）。
结果
在 243 名基线样本患者中（受伤后中位数为 84 分钟采集），院前 GCS 评分为 8（四分位间距，5-10），55%有 ICH，48 小时和 28 天死亡率分别为 7%和 13%。根据 GOS-E 评分<4 或 DRS>7，6 个月时神经功能预后不良的比例分别为 34%和 24%。在大多数预测模型中，将每个生物标志物添加到 PH 都会提高 AUC。与 PH 单独比较，GFAP+PH 显著提高了所有模型的 AUC（ICH，0.82 与 0.64；48 小时死亡率，0.84 与 0.71；28 天死亡率，0.84 与 0.66；GOS-E，0.78 与 0.69；DRS，0.84 与 0.81，均 p<0.001）。
结论
循环血液生物标志物可能会提高对 MS-TBI 患者神经结局和死亡率的预测，优于院前特征。神经胶质纤维酸性蛋白似乎最有前途。未来有必要在院前环境中进行评估。
证据水平
前瞻性、预后和流行病学，II 级。
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