Neurofilament light chain for prognostication after cardiac arrest-first steps towards validation

IF 9.3 1区医学 Q1 CRITICAL CARE MEDICINE

Critical Care Pub Date : 2025-08-06 DOI:10.1186/s13054-025-05579-1

Martin A. S. Meyer, Rasmus P. Beske, Simon Mølstrøm, Johannes Grand, Laust E. R. Obling, Sebastian Wiberg, Britt Borregaard, Simon Schneekloth, Sif Grau Kaad, Pernille M. Christensen, Christina Christoffersen, Ruth Frikke-Schmidt, Henrik Schmidt, Jacob E. Møller, Jesper Kjaergaard, Christian Hassager

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引用次数: 0

Abstract

After cardiac arrest, many patients remain comatose, and a substantial proportion do not survive. Neuroprognostication is essential for identifying patients with potential for recovery, and those with severe, irreversible hypoxic-ischemic brain injury. Neurofilament light chain (NfL) is a blood-based marker of neuronal injury that is under evaluation for neuroprognostication. NfL have potential advantages over the currently only guideline recommended blood biomarker for neuroprognostication, neuron-specific enolase, including earlier applicability. However, there is no consensus on optimal NfL cut-off levels. A previous large investigation in OHCA patients, identified NfL thresholds with high specificity for poor outcome, and the purpose of the present investigation is to validate these cutoffs. The Blood Pressure and Oxygenation Targets in Post Resuscitation Care (BOX) trial included OHCA patients who were comatose at admission. Patients with at least one plasma biobank sample available at 24–48 h were included in this investigation. NfL was quantified by ELISA. Cerebral performance category score was estimated at 1 year. Diagnostic precision of NfL for prediction of poor neurologic outcome (CPC > 2) was determined by area under the receiver operator curve (AUROC), and the performance of previously identified cut-offs for a specificity of 100% were investigated. A total of 638 patients had a NfL measurement at either 24 or 48 h. The AUROC for prediction of poor neurologic outcome was 0.95 and 0.95 at 24 and 48 h, respectively. At 24 h, a cut-off of 1232 pg/mL had a specificity of 98%, for prediction of poor neurologic outcome, and false-positive results for 7 patients (1.4%). At 48 h, a cut-off of 1539 pg/ml similarly had a specificity of 98%, and false-positive results for 7 patients (1.3%). The results of this investigation confirm the prognostic value of NfL for identification of risk of poor neurologic outcome after cardiac arrest. Previously identified cut-offs of 1232 pg/mL at 24 h, and 1539 pg/mL at 48 h, performed excellent with a very high specificity. This indicates that application of NfL will allow for reliable neuroprognostication as early as 24 h after cardiac arrest. ClinicalTrials.gov NCT03141099, registered April 30 2017

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神经丝轻链用于心脏骤停后的预测——迈向验证的第一步

在心脏骤停后，许多患者仍处于昏迷状态，相当一部分患者无法存活。神经预后对于识别有恢复潜力的患者以及那些严重的、不可逆的缺氧缺血性脑损伤患者至关重要。神经丝轻链（NfL）是一种基于血液的神经元损伤标志物，目前正在评估神经预后。与目前唯一的指南推荐的神经预后血液生物标志物、神经元特异性烯醇化酶相比，NfL具有潜在的优势，包括更早的适用性。然而，对于最佳的NfL临界值并没有达成共识。先前在OHCA患者中进行的一项大型调查发现，NfL阈值对不良结果具有高特异性，本研究的目的是验证这些截止值。复苏后护理中的血压和氧合指标（BOX）试验包括入院时处于昏迷状态的OHCA患者。在24-48小时内至少有一个血浆生物库样本的患者被纳入本研究。采用ELISA法定量测定NfL。脑功能分类评分在1年时进行评估。NfL预测神经系统预后不良（CPC bbbb2）的诊断精度由受试者操作曲线下面积（AUROC）确定，并研究了先前确定的特异性为100%的截断值的性能。共有638名患者在24或48小时进行了NfL测量。预测神经系统预后不良的AUROC在24和48小时分别为0.95和0.95。24小时时，1232 pg/mL的临界值特异性为98%，用于预测不良的神经预后，7例患者（1.4%）出现假阳性结果。48小时时，1539 pg/ml的临界值同样具有98%的特异性，7例患者（1.3%）出现假阳性结果。本研究的结果证实了NfL对心脏骤停后神经系统预后不良风险的预测价值。先前鉴定的24小时1232 pg/mL和48小时1539 pg/mL的切断值具有非常高的特异性，表现优异。这表明，应用NfL将允许在心脏骤停后24小时进行可靠的神经预后。ClinicalTrials.gov NCT03141099，注册于2017年4月30日

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来源期刊

Critical Care 医学-危重病医学

CiteScore

20.60

自引率

3.30%

发文量

348

审稿时长

1.5 months

期刊介绍： Critical Care is an esteemed international medical journal that undergoes a rigorous peer-review process to maintain its high quality standards. Its primary objective is to enhance the healthcare services offered to critically ill patients. To achieve this, the journal focuses on gathering, exchanging, disseminating, and endorsing evidence-based information that is highly relevant to intensivists. By doing so, Critical Care seeks to provide a thorough and inclusive examination of the intensive care field.