Wichmann Thea Overgaard, Babaee Ayad, Duch Kirsten, Rasmussen Mikkel Mylius, Lesbo Maj, Brink Ole, Borris Lars C, Hviid Claus V B
Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
Department of Surgery and Intensive Care, Viborg Regional Hospital, Viborg, Denmark.
Scand J Trauma Resusc Emerg Med. 2025 Mar 25;33(1):52. doi: 10.1186/s13049-025-01364-9.
Few countries recommend glial fibrillary protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a substitute for S100 astroglial calcium-binding protein B (S100B) in early detection of traumatic intracranial lesions in mild TBI (mTBI). This study aims to evaluate the classification agreement between S100B and GFAP/UCH-L1 in a Scandinavian trauma cohort, to evaluate the performance characteristics of S100B and GFAP/UCH-L1 for detection of traumatic intracranial lesions, and lastly to evaluate the laboratory performance of the GFAP/UCH-L1 assay.
Prospectively collected data from an unselected cohort of 379 adult trauma patients admitted to a level I trauma center at Aarhus University Hospital, Denmark, were retrospectively analyzed. Analyses were performed in the unselected cohort, in sub-cohort 1 (n = 218) i.e. patients with any evidence of TBI in their chart as well as in sub-cohort 2 (n = 105) i.e. patients with mTBI defined as Glasgow Coma Scale score ≥ 14, an injury severity score ≤ 15, and blood sampling within 6 h or 12 h after trauma. Plasma-samples were used for GFAP/UCH-L1 measurement and serum-samples were used for S100B measurement. Data analysis involved agreement analysis using Cohens kappa and sensitivity, specificity, positive predictive value and negative predictive value for each biomarker in each of the three cohorts. Lastly, levels of GFAP/UCH-L1 measured by the Alinity-I platform and the Simoa platform were compared.
Classification agreement between GFAP/UCH-L1 and S100B was high in all three cohorts, but Cohens kappa improved with increasing proximity to clinical biomarker use and reached an almost perfect identity in sub-cohort 2 (0.70, 95% CI 0.62-0.92). S100b had a sensitivity and negative predictive value of 100% in sub-cohort 2, while GFAP/UCH-L1 reached 100% across all three cohorts. The specificities for both S100B and GFAP/UCH-L1 were relatively low. Comparing GFAP/UCH-L1 levels between platforms revealed a low concordance with the Alinity-I platform measuring GFAP levels on average 65% lower and UCH-L1 levels 84% higher than the Simoa platform.
In this study, S100B and GFAP/UCH-L1 had an almost perfect agreement for classification of mTBI patients and comparable diagnostic performances for detecting traumatic intracranial lesions. Our results therefore support GFAP/UCH-L1 as a feasible alternative to S100B for detecting traumatic intracranial lesions in mTBI.
在轻度创伤性脑损伤（mTBI）的创伤性颅内病变早期检测中，很少有国家推荐使用胶质纤维酸性蛋白（GFAP）和泛素C末端水解酶-L1（UCH-L1）替代S100星形胶质细胞钙结合蛋白B（S100B）。本研究旨在评估斯堪的纳维亚创伤队列中S100B与GFAP/UCH-L1之间的分类一致性，评估S100B和GFAP/UCH-L1检测创伤性颅内病变的性能特征，最后评估GFAP/UCH-L1检测方法的实验室性能。
回顾性分析了从丹麦奥胡斯大学医院一级创伤中心前瞻性收集的379例成年创伤患者的未选择队列数据。分析在未选择队列、亚队列1（n = 218）即病历中有任何TBI证据的患者以及亚队列2（n = 105）即定义为格拉斯哥昏迷量表评分≥14、损伤严重程度评分≤15且在创伤后6小时或12小时内采血的mTBI患者中进行。血浆样本用于GFAP/UCH-L1测量，血清样本用于S100B测量。数据分析包括使用科恩kappa进行一致性分析以及对三个队列中每个生物标志物的敏感性、特异性、阳性预测值和阴性预测值进行分析。最后，比较了Alinity-I平台和Simoa平台测量的GFAP/UCH-L1水平。
在所有三个队列中，GFAP/UCH-L1与S100B之间的分类一致性都很高，但随着与临床生物标志物使用的接近程度增加，科恩kappa有所改善，在亚队列2中达到了几乎完美的一致性（0.70，95%CI 0.62 - 0.92）。在亚队列2中，S100b的敏感性和阴性预测值为100%，而GFAP/UCH-L1在所有三个队列中均达到100%。S100B和GFAP/UCH-L1的特异性都相对较低。比较不同平台之间的GFAP/UCH-L1水平发现一致性较低，Alinity-I平台测量的GFAP水平平均比Simoa平台低65%，UCH-L1水平高84%。
在本研究中，S100B和GFAP/UCH-L1在mTBI患者分类方面几乎完全一致，在检测创伤性颅内病变方面具有可比的诊断性能。因此，我们的结果支持GFAP/UCH-L1作为检测mTBI创伤性颅内病变的S100B的可行替代物。
