Department of Emergency Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Technical University of Munich, Klinikum rechts der Isar, Munich, Germany.
Lancet Neurol. 2018 Sep;17(9):782-789. doi: 10.1016/S1474-4422(18)30231-X. Epub 2018 Jul 24.
More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI.
This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT.
Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative.
These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted.
Banyan Biomarkers and US Army Medical Research and Materiel Command.
全球每年有超过 5000 万人遭受创伤性脑损伤（TBI）。颅内损伤的检测依赖于头部 CT，而头部 CT 过度使用且资源密集。基于血液的脑生物标志物有可能预测颅内损伤的缺失，从而减少不必要的头部 CT 扫描。我们试图验证一种测试，该测试将泛素 C 末端水解酶-L1（UCH-L1）和神经胶质纤维酸性蛋白（GFAP）结合起来，在 TBI 后急性头部 CT 扫描时使用预定的截断值预测创伤性颅内损伤。
这项前瞻性、多中心观察性试验纳入了年龄在 18 岁及以上的成年人，他们因疑似非穿透性 TBI 并伴有格拉斯哥昏迷量表（GCS）评分 9-15 分而就诊于参与的急诊部门。如果患者符合以下标准，他们将有资格入组：在标准急救护理中进行头部 CT 检查，且在损伤后 12 小时内进行血液采集。在血清中测量 UCH-L1 和 GFAP，并分别使用 327 pg/ml 和 22 pg/ml 的预设截断值进行分析。将 UCH-L1 和 GFAP 检测结果合并为单个测试结果，并与头部 CT 结果进行比较。主要研究结果是该测试结果对头部 CT 检测创伤性颅内损伤的敏感性和阴性预测值（NPV）。
2012 年 12 月 6 日至 2014 年 3 月 20 日期间，共招募了 1977 名患者，其中 1959 名患者有可分析的数据。125 名（6%）患者的头部 CT 检测到颅内损伤，8 名（<1%）患者有神经外科可管理的损伤。1288 名（66%）患者的 UCH-L1 和 GFAP 检测结果为阳性，671 名（34%）患者的检测结果为阴性。对于颅内损伤的检测，该测试的敏感性为 0.976（95%CI 0.931-0.995），NPV 为 0.996（0.987-0.999）。在 1959 名患者中，有 3 名（<1%）患者的 CT 扫描为阳性，而检测结果为阴性。
这些结果表明 UCH-L1 和 GFAP 测试的高敏感性和 NPV。这支持了它在急诊科因疑似 TBI 就诊的患者中对 CT 扫描的潜在临床作用，在这些患者中，头部 CT 被认为具有临床指征。未来的研究可以确定这种生物标志物测试对头部 CT 临床决策规则的附加值。
Banyan Biomarkers 和美国陆军军医研究与物资司令部。
