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循环二肽基肽酶3(cDPP3)是动脉瘤性蛛网膜下腔出血后早期检测继发性脑损伤的潜在生物标志物。

Circulatory dipeptidyl peptidase 3 (cDPP3) is a potential biomarker for early detection of secondary brain injury after aneurysmal subarachnoid hemorrhage.

作者信息

Neumaier Felix, Stoppe Christian, Veldeman Michael, Weiss Miriam, Simon Tim, Hoellig Anke, Marx Gernot, Clusmann Hans, Albanna Walid

机构信息

Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Germany.

Department of Intensive Care and Intermediate Care, RWTH Aachen University, Aachen, Germany.

出版信息

J Neurol Sci. 2021 Mar 15;422:117333. doi: 10.1016/j.jns.2021.117333. Epub 2021 Jan 30.

Abstract

INTRODUCTION

Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) that can culminate in secondary brain damage. Although it remains one of the main preventable causes of aSAH-related morbidity, there is still a lack of prognostic criteria for identification of patients at risk of developing DCI. Because elevated circulatory levels of the enzyme dipeptidyl peptidase 3 (cDPP3) were recently identified as a potential biomarker for outcome prediction in critically ill patients, we evaluated the time-course of changes in cDPP3 levels after aSAH.

MATERIALS AND METHODS

cDPP3 levels were quantified in serum obtained from 96 confirmed aSAH patients during the early (EP: d), critical (CP: d, d, d) and late (LP: d) phase after aSAH onset. Associations between cDPP3 levels and demographic or clinical parameters were evaluated. The relations between cDPP3 levels and DCI, DCI-related infarctions and long-term clinical outcomes were examined by receiver operating characteristics (ROC) curve analysis and multivariate logistic regression.

RESULTS

Significantly higher cDPP3 levels during CP (d, d, d) were observed in patients with poor clinical (p < 0.001 to p = 0.033) or radiological (p = 0.012 to p = 0.039) status on admission, DCI (p < 0.001 to p = 0.001), DCI-related infarctions (p = 0.002 to p = 0.007), and poorer long-term outcome (p = 0.007 to p = 0.019). ROC curve analysis indicated that higher cDPP3 levels on d are predictive for a poor clinical outcome (area under the curve = 0.677, p = 0.007). In multivariate analysis, there was an independent association between cDPP3 levels on d and development of DCI-related infarctions (p = 0.038).

CONCLUSION

Our results provide first evidence that cDPP3 could serve as a promising biomarker for early diagnosis of DCI-related infarctions in poor grade aSAH patients.

摘要

引言

迟发性脑缺血(DCI)是动脉瘤性蛛网膜下腔出血(aSAH)后的常见并发症,可导致继发性脑损伤。尽管它仍然是aSAH相关发病的主要可预防原因之一,但仍缺乏用于识别有发生DCI风险患者的预后标准。由于最近发现循环中双肽基肽酶3(cDPP3)水平升高是危重症患者预后预测的潜在生物标志物,我们评估了aSAH后cDPP3水平变化的时间进程。

材料与方法

对96例确诊的aSAH患者在aSAH发作后的早期(EP:第1天)、关键期(CP:第3、7、14天)和晚期(LP:第28天)获得的血清中的cDPP3水平进行定量。评估cDPP3水平与人口统计学或临床参数之间的关联。通过受试者工作特征(ROC)曲线分析和多因素逻辑回归研究cDPP3水平与DCI、DCI相关梗死和长期临床结局之间的关系。

结果

入院时临床(p<0.001至p = 0.033)或影像学(p = 0.012至p = 0.039)状态较差、发生DCI(p<0.001至p = 0.001)、DCI相关梗死(p = 0.002至p = 0.007)以及长期预后较差(p = 0.007至p = 0.019)的患者在CP期(第3、7、14天)的cDPP3水平显著更高。ROC曲线分析表明,第1天较高的cDPP3水平可预测不良临床结局(曲线下面积=0.677,p = 0.007)。在多因素分析中,第1天的cDPP3水平与DCI相关梗死的发生之间存在独立关联(p = 0.038)。

结论

我们的结果首次证明cDPP3可作为低级别aSAH患者DCI相关梗死早期诊断的有前景的生物标志物。

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