验证一种临床遗传学评分，以预测 rtPA 后出血性转化。
Validation of a clinical-genetics score to predict hemorrhagic transformations after rtPA.
机构信息
From the Neurovascular Research Laboratory (C.C., A.B.), Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona; Stroke Pharmacogenomics and Genetics (N.C., N.-T.A.) and Stroke Genomics and Genetics (E.M.), Fundació Docència i Recerca Mútua Terrassa; Department of Neuroscience (A.D.), Hospital Germans Trias i Pujol; Stroke Unit (E.L.-C.), Hospital Universitario Central de Asturias; Stroke Unit (M.R., C.A.M.), Hospital Universitari Vall d'Hebron; Stroke Unit, Hospital Universitari Vall d'Hebron; Department of Neurology (E.G.-S., C.S.-T., M.M.-C., J.J.-C., J.R.), Neurovascular Research Group, IMIM-Hospital del Mar; Neurobiology Laboratory (C.V.-B.), Institut d'Investigacio Sanitaria de Palma; Department of Neurology (R.D.N.), Hospital Universitari Son Espases; Department of Neurology (V.O.), Hospital Clínic i Provincial de Barcelona; Department of Neurology (J.F.A.), Hospital Clínico Universitario, University of Valladolid; Department of Neurology (T.S.) and Experimental Research Unit (G.S.-H.), Hospital Universitario de Albacete; Department of Neurology (J.M.-F.), Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau; Department of Neurology (M.F.), Hospital de Basurto; Department of Neurology (J.A.C.), Virgen del Rocío & Macarena Hospitals, IBIS, Spain; Department of Clinical Neuroscience/Neurology (T.T.), Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Sweden; Division of Emergency Medicine (L.H.), Department of Psychiatry (L.I., C.C.), and Department of Neurology (J.-M.L.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (D.S.), Helsinki University Hospital, Finland; Department of Neurology (J.M.), Virgen del Rocío & Macarena Hospitals, IBIS. Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona; and Stroke Pharmacogenomics and Genetics (I.F.-C.), Fundació Docència i Recerca Mútua Terrassa, Hospital Universitari Mútua de Terrassa, Stroke Pharmacogenomics and Genetics, IIB-Sant Pau, Spain.
出版信息
Neurology. 2019 Aug 27;93(9):e851-e863. doi: 10.1212/WNL.0000000000007997. Epub 2019 Jul 31.
OBJECTIVE
To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke.
METHODS
We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum.
RESULTS
Genot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score ( = 2.02 × 10, = 0.023, = 0.033); PH prediction was associated in cohorts A through C ( = 0.012, = 0.034, = 5.32 × 10). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%-15.7%, cohort B 1.5%-18.2%, cohort C 0%-100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46-18.08, = 0.009).
CONCLUSION
The Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients.
目的
验证 Genot-PA 评分，这是一种临床遗传学逻辑回归评分，可对溶栓治疗的安全性进行分层，在新的卒中患者队列中进行验证。
方法
我们纳入了 2003 年至 2016 年期间来自西班牙和芬兰的 1482 例接受重组组织型纤溶酶原激活物（rtPA）治疗的卒中患者。队列分析基于种族和治疗方法：西班牙患者在发病后 4.5 小时内接受 IV rtPA（队列 A 和 B）或在发病后 6 小时内接受 rtPA 联合机械血栓切除术（队列 C）治疗，芬兰患者在发病后 4.5 小时内接受 IV rtPA（队列 D）治疗。计算 Genot-PA 评分，并确定每个评分层的出血转化（HT）和实质血肿（PH）风险。
结果
在 1324 例（队列 A：n = 726；B：n = 334；C：n = 54；D：n = 210）具有足够信息完成评分的患者中，对 Genot-PA 评分进行了检验。其中，213 例（16.1%）患者发生 HT，85 例（6.4%）发生 PH。在队列 A、B 和 D 中，评分预测了 HT 的发生（ = 2.02×10 ， = 0.023， = 0.033）；在队列 A 至 C 中，PH 预测与评分相关（ = 0.012， = 0.034， = 5.32×10 ）。发现从最低风险组到最高风险组的 PH 事件发生频率增加（队列 A 4%-15.7%，队列 B 1.5%-18.2%，队列 C 0%-100%）。在最高风险组中，PH 预测的最佳比值比在队列 A 中获得（比值比 5.16，95%置信区间 1.46-18.08， = 0.009）。
结论
Genot-PA 评分可预测接受 IV rtPA 治疗的卒中患者的 HT。此外，在一项探索性研究中，该评分与机械血栓切除术治疗患者的 PH 风险相关。
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