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荧光分子过氧化物产物:溶栓后早期神经功能恶化的预后生物标志物。

Fluorescent molecular peroxidation products: a prognostic biomarker of early neurologic deterioration after thrombolysis.

机构信息

From Neurovascular Research Laboratory, Institut de Recerca Vall d'Hebron, Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Barcelona, Spain (V.L., A.B., T.G.-B., A.P., M.H.-G., D.G., A.R., J.M.); Biochemistry and Molecular Biology Research Centre for Nanomedicine, Hospital Universitari Vall d'Hebron, Instituto de Salud Carlos III, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain (C.D., V.R.-S., P.M.-G., A.V.); Neurovascular Unit, Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Spain (M. Rubiera, M. Ribó, C.A.M., J.A.-S.); Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany (C.E.); and Department of Neurology, University Hospital of Schleswig-Holstein, Kiel, Germany (C.E.).

出版信息

Stroke. 2014 Feb;45(2):432-7. doi: 10.1161/STROKEAHA.113.003431. Epub 2013 Dec 12.

Abstract

BACKGROUND AND PURPOSE

Fluorescent molecular peroxidation products (FMPPs) are considered potential markers of molecular oxidative damage and may provoke increased permeability and disruption of the blood-brain barrier. This study aimed to determine the value of FMPPs as a biomarker to predict neurological worsening related to early hemorrhagic transformation.

METHODS

Baseline FMPP levels were measured in 186 consecutive acute ischemic stroke patients before tissue plasminogen activator treatment was administered. A serial FMPP profile (baseline before tissue plasminogen activator treatment, and 1, 2, 12, and 24 hours from treatment) was determined in a subset of 100 patients. Computed tomographic scans were performed at admission and repeated at 24 to 48 hours or after neurological worsening occurred. Symptomatic intracranial hemorrhage was defined as blood at any site in the brain associated with neurological deterioration.

RESULTS

Patients who worsened had higher median FMPP levels compared with those who did not (59.68 [48.63-85.73] versus 44.87 [36.37-58.90] Uf/mL; P=0.035) at baseline. After logistic regression multivariate analysis, FMPP >48.2 Uf/mL together with age, hypertension, and systolic blood pressure remained baseline predictors of worsening at 48 hours. Moreover, baseline FMPP determination helped to distinguish between patients who worsened and those who did not (Integrated Discrimination Improvement index, 5.7%; P=0.0004). Finally, within patients who had worsened at 48 hours, those with symptomatic intracranial hemorrhage had higher FMPP levels (P=0.038).

CONCLUSIONS

FMPPs might be a valuable biomarker of poor early neurological outcome and be related to the appearance of symptomatic intracranial hemorrhage in tissue plasminogen activator-treated patients, one of the most feared neurological complications after thrombolytic treatment of acute ischemic stroke.

摘要

背景与目的

荧光分子过氧化物产物(FMPP)被认为是分子氧化损伤的潜在标志物,可能导致血脑屏障通透性增加和破裂。本研究旨在确定 FMPP 是否可作为预测与早期出血性转化相关的神经恶化的生物标志物。

方法

在组织型纤溶酶原激活物治疗前,对 186 例连续急性缺血性脑卒中患者进行基线 FMPP 水平测量。在 100 例患者的亚组中,确定了一系列 FMPP 谱(治疗前的基线,治疗后 1、2、12 和 24 小时)。入院时进行计算机断层扫描,在 24 至 48 小时或发生神经恶化后重复进行。症状性颅内出血定义为任何部位的脑内出血与神经功能恶化相关。

结果

与未恶化的患者相比,恶化的患者基线时 FMPP 水平更高(中位数 59.68 [48.63-85.73]与 44.87 [36.37-58.90] Uf/mL;P=0.035)。经过逻辑回归多变量分析,FMPP >48.2 Uf/mL 以及年龄、高血压和收缩压仍然是 48 小时时恶化的基线预测因素。此外,基线 FMPP 测定有助于区分恶化和未恶化的患者(综合判别改善指数,5.7%;P=0.0004)。最后,在 48 小时时恶化的患者中,有症状性颅内出血的患者 FMPP 水平更高(P=0.038)。

结论

FMPP 可能是早期神经预后不良的有价值的生物标志物,与组织型纤溶酶原激活物治疗的患者中出现症状性颅内出血有关,这是急性缺血性脑卒中溶栓治疗后最可怕的神经并发症之一。

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