Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injury.

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI:10.1016/j.ebiom.2024.105298

Lindsay Wilson, Virginia F J Newcombe, Daniel P Whitehouse, Stefania Mondello, Andrew I R Maas, David K Menon

{"title":"Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injury.","authors":"Lindsay Wilson, Virginia F J Newcombe, Daniel P Whitehouse, Stefania Mondello, Andrew I R Maas, David K Menon","doi":"10.1016/j.ebiom.2024.105298","DOIUrl":null,"url":null,"abstract":"Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury.Methods: Exposure-response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates.Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13-15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 and positive CT (1.21-2.81), GCS 9-12 (1.16-2.02), GCS 3-8 (1.09-1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) percentages of unfavourable outcome were 37-51% in the lowest quintiles of biomarker levels and reached 90-94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), the percentages were 2-4% and 19-28% in the lowest and highest biomarker quintiles, respectively.Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity.Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11400615/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EBioMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ebiom.2024.105298","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury.

Methods: Exposure-response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates.

Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13-15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 and positive CT (1.21-2.81), GCS 9-12 (1.16-2.02), GCS 3-8 (1.09-1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) percentages of unfavourable outcome were 37-51% in the lowest quintiles of biomarker levels and reached 90-94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), the percentages were 2-4% and 19-28% in the lowest and highest biomarker quintiles, respectively.

Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity.

Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

查看原文本刊更多论文

脑外伤传统严重程度类别中早期血液生物标志物与 6 个月功能结果的关联：捕捉连续的损伤谱。

背景：按照传统的格拉斯哥昏迷量表（GCS），创伤性脑损伤可分为轻度、中度和重度。最近开发的生物标志物可提供更客观、更细致的脑损伤程度测量方法：方法：对参加欧洲创伤性脑损伤神经创伤有效性合作研究（CENTER-TBI）前瞻性观察队列研究的 2479 名年龄≥16 岁的患者进行了暴露-反应关系调查。在最初 24 小时内采集的血清样本中检测了神经丝蛋白-光（NFL）、泛素羧基末端水解酶 L1（UCH-L1）和胶质纤维酸性蛋白（GFAP）的浓度；在 GCS 严重程度组内将浓度分为五等分。使用改良泊松回归（包括年龄、性别、主要颅外损伤、采样时间和生物标记物浓度对数作为协变量）检验了与格拉斯哥结果量表扩展版之间的关系：在对共变量进行调整后，严重程度组内的生物标志物与结果之间存在关联：GCS 13-15 和阴性 CT 成像（相对风险 [RRs] 从 1.28 到 3.72），GCS 13-15 和阳性 CT（1.21-2.81），GCS 9-12（1.16-2.02），GCS 3-8（1.09-1.94）。RRs与预后预期的临床重要差异有关。在 GCS 3（RRs 为 1.51-1.80）的患者中，生物标记物水平最低五分位数的不利预后百分比为 37-51%，最高五分位数的不利预后百分比达到 90-94%。同样，对于 GCS 15（RRs 1.83-3.79），生物标志物水平最低和最高五分位数的百分比分别为 2-4%和 19-28%：解读：传统的创伤性脑损伤严重程度分类是不够的，而且低估了脑损伤的异质性和相关结果。采用循环生物标志物可增加对损伤严重程度的临床评估：欧盟第七框架计划（EC grant 602150）、Hannelore Kohl Stiftung、One Mind、Integra LifeSciences、Neuro-Trauma Sciences、NIHR Rosetrees Trust。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.