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心脏骤停时的血清tau蛋白与神经学转归

Serum tau and neurological outcome in cardiac arrest.

作者信息

Mattsson Niklas, Zetterberg Henrik, Nielsen Niklas, Blennow Kaj, Dankiewicz Josef, Friberg Hans, Lilja Gisela, Insel Philip S, Rylander Christian, Stammet Pascal, Aneman Anders, Hassager Christian, Kjaergaard Jesper, Kuiper Michael, Pellis Tommaso, Wetterslev Jørn, Wise Matthew, Cronberg Tobias

机构信息

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.

Department of Clinical Sciences, Neurology, Lund University, Skåne University Hospital, Lund, Sweden.

出版信息

Ann Neurol. 2017 Nov;82(5):665-675. doi: 10.1002/ana.25067. Epub 2017 Nov 2.

Abstract

OBJECTIVE

To test serum tau as a predictor of neurological outcome after cardiac arrest.

METHODS

We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3-5 at 6 months.

RESULTS

Increased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7-245ng/l in poor vs median = 1.5, IQR = 0.7-2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1-4%) with sensitivity = 66% (95% CI = 61-70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest.

INTERPRETATION

Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665-675.

摘要

目的

检测血清tau蛋白作为心脏骤停后神经功能转归预测指标的价值。

方法

在前瞻性国际目标体温管理试验中,我们对689例患者心脏骤停后24、48和72小时的血清神经元蛋白tau进行了检测。主要转归为神经功能转归不良,定义为6个月时脑功能分类为3 - 5级。

结果

tau蛋白升高与心脏骤停后6个月时的不良转归相关(72小时时,转归不良者tau蛋白中位数 = 38.5,四分位数间距[IQR] = 5.7 - 245 ng/L;转归良好者tau蛋白中位数 = 1.5,IQR = 0.7 - 2.4 ng/L,p < 0.0001)。与使用临床信息相比,tau蛋白改善了对不良转归的预测(p < 0.0001)。tau蛋白临界值对转归良好者的假阳性率(FPR)较低,同时对转归不良者保持高敏感性。例如,72小时时tau蛋白的FPR = 2%(95%可信区间[CI] = 1 - 4%),敏感性 = 66%(95% CI = 61 - 70%)。tau蛋白的准确性高于血清神经元特异性烯醇化酶(NSE);72小时时,tau蛋白的受试者工作特征曲线下面积为0.91,而NSE为0.86,p = 0.00024。在随访期间(长达956天),tau蛋白与总体生存率显著相关。对于心脏骤停后随机接受33℃和36℃目标体温的患者,血清tau蛋白预测转归的准确性同样很高。

解读

血清tau蛋白是预测心脏骤停患者神经功能转归的一种很有前景的新型生物标志物。它可能明显优于血清NSE,血清NSE在指南中有推荐,目前在一些国家的临床实践中用于预测心脏骤停后的转归。《神经病学纪事》2017年;82:665 - 675。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c15/5725735/11ec83aa1aa5/ANA-82-665-g001.jpg

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