Paolo Mastandrea, Silvia Mengozzi, Sergio Bernardini
{"title":"对评估神经胶质纤维酸性蛋白 (GFAP) 和泛素 C 端水解酶 L1 (UCHL1) 作为成年受试者轻度急性创伤性脑损伤 (mTBI) 或运动相关脑震荡 (SRC) 血液生物标记物的观察性研究进行系统回顾和荟萃分析。","authors":"Paolo Mastandrea, Silvia Mengozzi, Sergio Bernardini","doi":"10.1515/dx-2024-0078","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Neurotrauma is the leading cause of death in individuals <45 years old. Many of the published articles on UCHL1 and GFAP lack rigorous methods and reporting.</p><p><strong>Content: </strong>Due to the high heterogeneity between studies, we evaluated blood GFAP and UCHL1 levels in the same subjects. We determined the biomarker congruence among areas under the ROC curves (AUCs), sensitivities, specificities, and laboratory values in ng/L to avoid spurious results. The definitive meta-analysis included 1,880 subjects in eight studies. The items with the highest risk of bias were as follows: cut-off not prespecified and case-control design not avoided. The AUC of GFAP was greater than the AUC of UCHL1, with a lower prediction interval (PI) limit of 50.1 % for GFAP and 37.3 % for UCHL1, and a significantly greater percentage of GFAP Sp. The PI of laboratory results for GFAP and UCHL1 were 0.517-7,518 ng/L (diseased), 1.2-255 ng/L (nondiseased), and 3-4,180 vs. 3.2-1,297 ng/L, respectively.</p><p><strong>Summary: </strong>Only the GFAP positive cut-off (255 ng/L) appears to be reliable. The negative COs appear unreliable.</p><p><strong>Outlook: </strong>GFAP needs better standardization. However, the AUCs of the phospho-Tau and phospho-Tau/Tau proteins resulted not significantly lower than AUC of GFAP, but this result needs further verifications.</p>","PeriodicalId":11273,"journal":{"name":"Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Systematic review and meta-analysis of observational studies evaluating glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCHL1) as blood biomarkers of mild acute traumatic brain injury (mTBI) or sport-related concussion (SRC) in adult subjects.\",\"authors\":\"Paolo Mastandrea, Silvia Mengozzi, Sergio Bernardini\",\"doi\":\"10.1515/dx-2024-0078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Neurotrauma is the leading cause of death in individuals <45 years old. Many of the published articles on UCHL1 and GFAP lack rigorous methods and reporting.</p><p><strong>Content: </strong>Due to the high heterogeneity between studies, we evaluated blood GFAP and UCHL1 levels in the same subjects. We determined the biomarker congruence among areas under the ROC curves (AUCs), sensitivities, specificities, and laboratory values in ng/L to avoid spurious results. The definitive meta-analysis included 1,880 subjects in eight studies. The items with the highest risk of bias were as follows: cut-off not prespecified and case-control design not avoided. The AUC of GFAP was greater than the AUC of UCHL1, with a lower prediction interval (PI) limit of 50.1 % for GFAP and 37.3 % for UCHL1, and a significantly greater percentage of GFAP Sp. The PI of laboratory results for GFAP and UCHL1 were 0.517-7,518 ng/L (diseased), 1.2-255 ng/L (nondiseased), and 3-4,180 vs. 3.2-1,297 ng/L, respectively.</p><p><strong>Summary: </strong>Only the GFAP positive cut-off (255 ng/L) appears to be reliable. The negative COs appear unreliable.</p><p><strong>Outlook: </strong>GFAP needs better standardization. However, the AUCs of the phospho-Tau and phospho-Tau/Tau proteins resulted not significantly lower than AUC of GFAP, but this result needs further verifications.</p>\",\"PeriodicalId\":11273,\"journal\":{\"name\":\"Diagnosis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-08-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diagnosis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1515/dx-2024-0078\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diagnosis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/dx-2024-0078","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Systematic review and meta-analysis of observational studies evaluating glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCHL1) as blood biomarkers of mild acute traumatic brain injury (mTBI) or sport-related concussion (SRC) in adult subjects.
Introduction: Neurotrauma is the leading cause of death in individuals <45 years old. Many of the published articles on UCHL1 and GFAP lack rigorous methods and reporting.
Content: Due to the high heterogeneity between studies, we evaluated blood GFAP and UCHL1 levels in the same subjects. We determined the biomarker congruence among areas under the ROC curves (AUCs), sensitivities, specificities, and laboratory values in ng/L to avoid spurious results. The definitive meta-analysis included 1,880 subjects in eight studies. The items with the highest risk of bias were as follows: cut-off not prespecified and case-control design not avoided. The AUC of GFAP was greater than the AUC of UCHL1, with a lower prediction interval (PI) limit of 50.1 % for GFAP and 37.3 % for UCHL1, and a significantly greater percentage of GFAP Sp. The PI of laboratory results for GFAP and UCHL1 were 0.517-7,518 ng/L (diseased), 1.2-255 ng/L (nondiseased), and 3-4,180 vs. 3.2-1,297 ng/L, respectively.
Summary: Only the GFAP positive cut-off (255 ng/L) appears to be reliable. The negative COs appear unreliable.
Outlook: GFAP needs better standardization. However, the AUCs of the phospho-Tau and phospho-Tau/Tau proteins resulted not significantly lower than AUC of GFAP, but this result needs further verifications.
期刊介绍:
Diagnosis focuses on how diagnosis can be advanced, how it is taught, and how and why it can fail, leading to diagnostic errors. The journal welcomes both fundamental and applied works, improvement initiatives, opinions, and debates to encourage new thinking on improving this critical aspect of healthcare quality. Topics: -Factors that promote diagnostic quality and safety -Clinical reasoning -Diagnostic errors in medicine -The factors that contribute to diagnostic error: human factors, cognitive issues, and system-related breakdowns -Improving the value of diagnosis – eliminating waste and unnecessary testing -How culture and removing blame promote awareness of diagnostic errors -Training and education related to clinical reasoning and diagnostic skills -Advances in laboratory testing and imaging that improve diagnostic capability -Local, national and international initiatives to reduce diagnostic error