Bustamante Alejandro, López-Cancio Elena, Pich Sara, Penalba Anna, Giralt Dolors, García-Berrocoso Teresa, Ferrer-Costa Carles, Gasull Teresa, Hernández-Pérez María, Millan Mónica, Rubiera Marta, Cardona Pedro, Cano Luis, Quesada Helena, Terceño Mikel, Silva Yolanda, Castellanos Mar, Garces Moisés, Reverté Silvia, Ustrell Xavier, Marés Rafael, Baiges Joan Josep, Serena Joaquín, Rubio Francisco, Salas Eduardo, Dávalos Antoni, Montaner Joan
From the Neurovascular Research Laboratory, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain (A.B., A.P., D.G., T.G.-B., J.M.); Stroke Unit, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain (E.L.-C., M.H.-P., M.M., A.D.); Gendiag.exe, S.L., Barcelona, Spain (S.P., C.F.-C., E.S.); Cellular and Molecular Neurobiology Research Group, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain (T.G.); Stroke Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain (M.R., J.M.); Stroke Unit, Hospital Universitari de Bellvitge, Barcelona, Spain (P.C., L.C., H.Q., F.R.); Stroke Unit, Hospital Universitari Josep Trueta, Girona, Spain (M.T., Y.S., J.S.); Complejo Hospitalario Universitario A Coruña, Spain (M.C.); Stroke Unit, Hospital Universitari Verge de la Cinta de Tortosa, Spain (M.G., S.R., J.J.B.); and Stroke Unit, Hospital Universitari Joan XXIII, Tarragona, Spain (X.U., R.M.).
Stroke. 2017 Sep;48(9):2419-2425. doi: 10.1161/STROKEAHA.117.017076. Epub 2017 Jul 17.
Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase.
The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves.
From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55-3.71; <0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19-3.45; =0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%.
The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke.
在急性期，中风诊断可能具有挑战性。我们旨在开发一种基于血液的诊断工具，以区分真正的中风与中风模拟疾病，以及区分超急性期的缺血性中风和出血性中风。
中风芯片研究是一项前瞻性、观察性、多中心研究，在加泰罗尼亚的6个中风中心进行。症状发作后的前6小时内，连续纳入疑似中风患者，入院后立即采集血样。通过免疫测定法检测从先前结果和文献中选出的一个包含21种生物标志物的组合。结果指标为区分真正的中风与中风模拟疾病，以及区分缺血性中风和出血性中风。通过在逻辑回归模型中结合生物标志物和临床变量来开发预测模型。使用受试者工作特征曲线评估准确性。
2012年8月至2013年12月，共纳入1308例患者（71.9%为缺血性中风，14.8%为中风模拟疾病，13.3%为出血性中风）。对于中风与中风模拟疾病的比较，逻辑回归模型中未纳入任何生物标志物，仅纳入了临床变量，预测准确性为80.8%。对于缺血性中风与出血性中风的比较，N端前脑钠肽（NT-proBNP）>4.9（比值比，2.40；95%置信区间，1.55 - 3.71；P<0.0001）和内皮抑素>4.7（比值比，2.02；95%置信区间，1.19 - 3.45；P = 0.010），连同年龄、性别、血压、中风严重程度、心房颤动和高血压一起纳入模型。预测准确性为80.6%。
在超急性期，所研究的生物标志物不足以对中风进行准确的鉴别诊断。为实现中风的分子诊断，似乎有必要进一步发现新的生物标志物并改进实验室技术。
