Department of Specialities of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
NeuroCritical Care Unit, Virgen del Rocío University Hospital, Seville, Spain.
PLoS One. 2018 Jul 9;13(7):e0200394. doi: 10.1371/journal.pone.0200394. eCollection 2018.
Mild traumatic brain injury (mTBI) patients may have trauma-induced brain lesions detectable using CT scans. However, most patients will be CT-negative. There is thus a need for an additional tool to detect patients at risk. Single blood biomarkers, such as S100B and GFAP, have been widely studied in mTBI patients, but to date, none seems to perform well enough. In many different diseases, combining several biomarkers into panels has become increasingly interesting for diagnoses and to enhance classification performance. The present study evaluated 13 proteins individually-H-FABP, MMP-1, MMP-3, MMP-9, VCAM, ICAM, SAA, CRP, GSTP, NKDA, PRDX1, DJ-1 and IL-10-for their capacity to differentiate between patients with and without a brain lesion according to CT results. The best performing proteins were then compared and combined with the S100B and GFAP proteins into a CT-scan triage panel. Patients diagnosed with mTBI, with a Glasgow Coma Scale score of 15 and one additional clinical symptom were enrolled at three different European sites. A blood sample was collected at hospital admission, and a CT scan was performed. Patients were divided into two two-centre cohorts and further dichotomised into CT-positive and CT-negative groups for statistical analysis. Single markers and panels were evaluated using Cohort 1. Four proteins-H-FABP, IL-10, S100B and GFAP-showed significantly higher levels in CT-positive patients. The best-performing biomarker was H-FABP, with a specificity of 32% (95% CI 23-40) and sensitivity reaching 100%. The best-performing two-marker panel for Cohort 1, subsequently validated in Cohort 2, was a combination of H-FABP and GFAP, enhancing specificity to 46% (95% CI 36-55). When adding IL-10 to this panel, specificity reached 52% (95% CI 43-61) with 100% sensitivity. These results showed that proteins combined into panels could be used to efficiently classify CT-positive and CT-negative mTBI patients.
轻度创伤性脑损伤（mTBI）患者可能存在可通过 CT 扫描检测到的创伤性脑损伤。然而，大多数患者的 CT 扫描结果为阴性。因此，需要一种额外的工具来检测有风险的患者。S100B 和 GFAP 等单一血液生物标志物已在 mTBI 患者中得到广泛研究，但迄今为止，似乎没有一种生物标志物的性能足够好。在许多不同的疾病中，将几种生物标志物组合成面板对于诊断和提高分类性能变得越来越有趣。本研究评估了 13 种蛋白质（H-FABP、MMP-1、MMP-3、MMP-9、VCAM、ICAM、SAA、CRP、GSTP、NKDA、PRDX1、DJ-1 和 IL-10）的个体能力，根据 CT 结果将患者分为有脑损伤和无脑损伤。然后比较表现最佳的蛋白质，并将其与 S100B 和 GFAP 蛋白组合成 CT 扫描分诊面板。在三个不同的欧洲地点，根据格拉斯哥昏迷量表评分 15 分和另外一个临床症状，将诊断为 mTBI 的患者纳入研究。在入院时采集血样，并进行 CT 扫描。患者被分为两个双中心队列，并进一步分为 CT 阳性和 CT 阴性组进行统计分析。使用队列 1 评估单个标志物和面板。四种蛋白质（H-FABP、IL-10、S100B 和 GFAP）在 CT 阳性患者中的水平显著升高。表现最佳的生物标志物是 H-FABP，特异性为 32%（95%CI 23-40），敏感性达到 100%。在队列 1 中表现最佳的两个标志物组合，随后在队列 2 中得到验证，是 H-FABP 和 GFAP 的组合，特异性提高到 46%（95%CI 36-55）。当将 IL-10 添加到此面板时，特异性达到 52%（95%CI 43-61），敏感性为 100%。这些结果表明，组合成面板的蛋白质可用于有效分类 CT 阳性和 CT 阴性 mTBI 患者。
