AbstractElevated levels of CNS-derived serum proteins are associated with poor outcome in traumatic brain injury (TBI), but the value of adding acute serum biomarker levels to common clinical outcome predictors lacks evaluation. We analyzed admission serum samples for Total-Tau (T-Tau), Neurofilament light chain (Nfl), Glial fibrillary acidic protein (GFAP), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in a cohort of 396 trauma patients including 240 patients with TBI.

摘要中枢神经系统衍生的血清蛋白水平升高与创伤性脑损伤（TBI）预后不良有关，但将急性血清生物标志物水平添加到常见临床结果预测因子中的价值缺乏评估。。

We assessed the independent association of biomarkers with 1-year mortality and 6–12 months Glasgow Outcome Scale Extended (GOSE) score, as well as the additive and cumulative value of biomarkers on Glasgow Coma Scale (GCS) and Marshall Score for outcome prediction. Nfl and T-Tau levels were independently associated with outcome (OR: Nfl = 1.65, p = 0.01; T-Tau = 1.99, p < 0.01).

我们评估了生物标志物与1年死亡率和6-12个月格拉斯哥预后量表扩展（GOSE）评分的独立关联，以及生物标志物对格拉斯哥昏迷量表（GCS）和马歇尔评分的累加和累积值，以进行结果预测。Nfl和T-Tau水平与预后独立相关（OR:Nfl=1.65，p=0.01；T-Tau=1.99，p<0.01）。

Nfl or T-Tau improved outcome prediction by GCS (Wald Chi, Nfl = 6.8–8.8, p < 0.01; T-Tau 7.2–11.3, p < 0.01) and the Marshall score (Wald Chi, Nfl = 16.2–17.5, p < 0.01; T-Tau 8.7–12.4, p < 0.01). Adding T-Tau atop Nfl further improved outcome prediction in majority of tested models (Wald Chi range 3.8–9.4, p ≤ 0.05).

Nfl或T-Tau改善了GCS的预后预测（Wald Chi，Nfl=6.8-8.8，p＜0.01；；T-Tau 8.7-12.4，p<0.01）。在大多数测试模型中，在Nfl顶部添加T-Tau进一步改善了结果预测（Wald Chi范围3.8-9.4，p≤0.05）。

Our data suggest that acute levels of serum biomarkers are independently associated with outcome after TBI and add outcome predictive value to commonly used clinical scores..

我们的数据表明，血清生物标志物的急性水平与TBI后的结果独立相关，并为常用的临床评分增加了结果预测价值。。

IntroductionTraumatic brain injury (TBI) is a leading cause of mortality and disability among adults and is estimated to strike 69 million globally each year1,2. It is a highly heterogenous disease and prognostication of outcome can be challenging. Prediction of outcome is based on clinical assessment, clinical scores, and neuroradiology3.

引言创伤性脑损伤（TBI）是成年人死亡和残疾的主要原因，估计每年全球将达到6900万人1,2。这是一种高度异质性的疾病，预后可能具有挑战性。结果的预测基于临床评估，临床评分和神经放射学3。

In effort to improve outcome prediction, more complex statistical models including the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model have been developed4. However, such models are not routinely adapted to clinical use maybe because they are too complex to integrate into clinical workflow.

为了改进结果预测，已经开发了更复杂的统计模型，包括TBI（IMPACT）模型中临床试验的国际预后和分析任务4。然而，这些模型并没有常规地适应临床使用，可能是因为它们太复杂而无法集成到临床工作流程中。

This leaves tremendous potential for improvement of outcome prediction if more applicable paraclinical measures are developed.Along this line, an immense research effort has been put into development of serum biomarkers for TBI as easily accessible and objective tools for assessment of prognosis5,6,7,8.

如果开发出更适用的临床旁措施，这将为改善结果预测留下巨大潜力。沿着这条线，已经投入了巨大的研究工作来开发TBI的血清生物标志物，作为评估预后的容易获得和客观的工具5,6,7,8。

Central nervous system (CNS)-derived proteins are studied as candidate biomarkers as they are released into the peripheral blood upon damage to neuronal tissue9. With recent technical advances, these proteins are now detectable in serum, making them accessible with a simple blood test10,11.Total-Tau (T-Tau), Neurofilament light chain (Nfl), Glial fibrillary acidic protein (GFAP), and Ubiquitin C-terminal hydrolase L1 (UCHL1) are candidate biomarkers of TBI that have been intensively investigated.

中枢神经系统（CNS）衍生的蛋白质被研究为候选生物标志物，因为它们在神经元组织受损时被释放到外周血中9。。

T-Tau is a microtubule regulatory protein primarily found in cortical unmyelinated axons, Nfl is a cytoskeletal protein abundantly expressed in myelinated axons, GFAP is an astrocyte-specific cytoskeletal protein, and UHCL1 is a neuron-specific enzyme involved in the production of ubiquitin12,13,14,15.

T-Tau是一种主要存在于皮质无髓鞘轴突中的微管调节蛋白，Nfl是一种在有髓鞘轴突中大量表达的细胞骨架蛋白，GFAP是一种星形胶质细胞特异性细胞骨架蛋白，UHCL1是一种参与泛素产生的神经元特异性酶12,13,14,15。

As such, each.

因此，每个。

Data availability

数据可用性

The data that support the findings of this study can be made available from the corresponding author, Claus V. B. Hviid, upon reasonable request.

根据合理的要求，可以从通讯作者Claus V.B.Hviid处获得支持本研究结果的数据。

AbbreviationsAIS:

缩写AIS：

Abbreviated injury severity score

简化伤害严重程度评分

ATLS:

ATLS：

Advanced trauma life support

高级创伤生命支持

CNS:

中枢神经系统：

Central nervous system

中枢神经系统

CT:

CT：

Computed tomography

计算机断层扫描

CV:

简历：

Coefficient of variation

变异系数

IMPACT:

影响：

International mission for prognosis and analysis of clinical trials in TBI

国际创伤性脑损伤临床试验预后和分析任务

LLOD:

方式：

Lower limit of detection

检测下限

LLOQ:

LOQ：

Lower limit of quantification

定量下限

GCS:

地面军事系统：

Glasgow coma scale

格拉斯哥昏迷量表

GOSE:

GOSE：

Glasgow outcome score extended

格拉斯哥结局评分延长

GFAP:

GFAP公司：

Glial fibrillary acidic protein

胶质纤维酸性蛋白

Nfl:

Nfl：

Neurofilament light chain

神经丝轻链

NISS:

NISS：

New injury severity score

新伤害严重程度评分

PRS:

PRS：

Pupil reflex score

瞳孔反射评分

T-Tau:

T-Tau：

Total-Tau

总Tau

TBI:

待定：

Traumatic brain injury

创伤性脑损伤

TSCI:

TSCI：

Traumatic spinal cord injury

创伤性脊髓损伤

UCHL1:

公鸡1：

Ubiquitin C-terminal hydrolase L1

泛素C末端水解酶L1

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Download referencesAcknowledgementsThe authors thank laboratory technician Katrine Bremer for her skilled assistance in the biochemical analysis.FundingThis work was supported by the Danish Victims Foundation. The funders had no role in the study design, collection, analysis, and interpretation of data, nor in the writing of the manuscript and the decision to submit the article for publication.Author informationAuthors and AffiliationsDepartment of Clinical Biochemistry, Aarhus University Hospital, 8200, Aarhus, DenmarkIda A.

下载参考文献致谢作者感谢实验室技术人员Katrine Bremer在生化分析方面的熟练帮助。资助这项工作得到了丹麦受害者基金会的支持。资助者在研究设计，收集，分析和解释数据，撰写稿件和决定提交文章发表方面没有任何作用。作者信息作者和附属机构奥胡斯大学医院临床生物化学系，8200，奥胡斯，登马基达A。

Kaaber & Claus V. B. HviidDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkIda A. Kaaber, Mikkel M. Rasmussen & Claus V. B. HviidDepartment of Ortopedic Surgery, Viborg Regional Hospital, Viborg, DenmarkMaj LesboDepartment of Neurosurgery, Aarhus University Hospital, Aarhus, DenmarkThea O.

Kaaber＆Claus V.B.HviidDepartment of Clinical Medicine，奥胡斯大学，奥胡斯，登马基达A.Kaaber，Mikkel M.Rasmussen＆Claus V.B.HviidDepartment of Ortopedic Surgery，Viborg Regional Hospital，Viborg，DenmarkMaj Lesboddepartment of Neurosurograry，奥胡斯大学医院，奥胡斯，登马基达O。

Wichmann & Mikkel M. RasmussenDepartment of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, DenmarkDorte Aa. OlsenDepartment of Ortopedic Surgery, Aarhus University Hospital, Aarhus, DenmarkOle Brink & Lars C. BorrisDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkClaus V.

Wichmann＆Mikkel M.RasmussenDepartment of Biochemistry and Immunology，Lillebaelt Hospital，University Hospital of Southern DenmarkDorte，Vejle，DenmarkDorte Aa。OlsenDepartment of Ortopedic Surgery，Aarhus，DenmarkOle Brink＆Lars C.BorrisDepartment of Clinical Medicine，Aalborg University，Aalborg，Denmarklaus V。

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PubMed Google ScholarContributionsCVBH and IAK conceived and designed the study, IAK and ML acquired the data, and IAK, CVBH, TOW, and MMR analyzed and interpreted the data. IAK drafted the paper while CVBH revised it critically. The present manuscript has been read and approved in its present form by all authors who agree to be accountable for all aspects of the published work.Corresponding authorCorrespondence to.

PubMed Google ScholarContributionsCVBH和IAK构思并设计了这项研究，IAK和ML获得了数据，IAK，CVBH，TOW和MMR分析并解释了数据。IAK起草了这篇论文，而CVBH对其进行了严格的修订。所有同意对已发表作品的各个方面负责的作者均已阅读并批准了本手稿的当前形式。通讯作者回复。

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Reprints and permissionsAbout this articleCite this articleKaaber, I.A., Lesbo, M., Wichmann, T.O. et al. Admission levels of serum biomarkers have additive and cumulative prognostic value in traumatic brain injury.

转载和许可本文引用本文Kaaber，I.A.，Lesbo，M.，Wichmann，T.O.等人。血清生物标志物的入院水平在创伤性脑损伤中具有累加和累积的预后价值。

Sci Rep 14, 14139 (2024). https://doi.org/10.1038/s41598-024-64125-1Download citationReceived: 21 December 2023Accepted: 05 June 2024Published: 19 June 2024DOI: https://doi.org/10.1038/s41598-024-64125-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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