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创伤性脑损伤后与计算机断层扫描结果相关的血清代谢物。

Serum Metabolites Associated with Computed Tomography Findings after Traumatic Brain Injury.

机构信息

1 Turku Centre for Biotechnology, University of Turku , Turku, Finland .

2 Turku Brain Injury Centre, Turku University Hospital , Turku, Finland .

出版信息

J Neurotrauma. 2018 Nov 15;35(22):2673-2683. doi: 10.1089/neu.2017.5272. Epub 2018 Aug 21.

Abstract

There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of biomarkers to determine the need for CT and to distinguish among different types of injuries observed. Logistical regression models using metabolite data from the discovery cohort (n = 144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and those with negative findings on head CT. The resultant models were then tested in the validation cohort (n = 66, Cambridge, United Kingdom). The levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein biomarkers in patients with TBI, the model that determined the need for a CT scan validated poorly (area under the curve [AUC] = 0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, three sugar derivatives, and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC = 0.77 in Turku patients and AUC = 0.73 in Cambridge patients). Further, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC = 0.87 in Turku patients and AUC = 0.68 in Cambridge patients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.

摘要

需要快速检测出需要进行头部计算机断层扫描(CT)的创伤性脑损伤(TBI)患者。鉴于 TBI 后大脑的能量危机,我们假设血清代谢组学将是开发一组生物标志物以确定是否需要 CT 并区分观察到的不同类型损伤的有用工具。使用发现队列(n = 144,芬兰图尔库)中的代谢物数据的逻辑回归模型用于区分创伤性颅内发现的患者和头部 CT 检查结果为阴性的患者。然后在验证队列(n = 66,英国剑桥)中测试得出的模型。还定量分析了来自同一患者的血清中的神经胶质纤维酸性蛋白和泛素 C 端水解酶-L1 的水平。尽管 TBI 患者的蛋白质生物标志物存在显着差异,但确定 CT 扫描需求的模型验证效果不佳(曲线下面积 [AUC] = 0.64:剑桥患者)。然而,使用六种代谢物(两种氨基酸,三种糖衍生物和一种酮酸)的组合可以区分 CT 上有颅内异常的患者和 CT 正常的患者(图尔库患者的 AUC = 0.77,剑桥患者的 AUC = 0.73)。此外,三种代谢物的组合可以区分弥漫性脑损伤和肿块病变(图尔库患者的 AUC = 0.87,剑桥患者的 AUC = 0.68)。这项研究确定了一组经过验证的血清极性代谢物,这些代谢物与进行 CT 扫描的需求相关。此外,血清代谢物还可以预测脑损伤的性质。这些代谢物标志物可能可以防止不必要的 CT 扫描,从而降低诊断成本和辐射负荷。

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