Baseline Characteristics of Patients With Cavernous Angiomas With Symptomatic Hemorrhage in Multisite Trial Readiness Project.
Baseline Characteristics of Patients With Cavernous Angiomas With Symptomatic Hemorrhage in Multisite Trial Readiness Project.
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DOI：
10.1161/strokeaha.120.033487
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发表时间：
2021-12
期刊：
影响因子：
8.3
通讯作者：
Awad I
中科院分区：
文献类型：
--
作者：
Kim H;Flemming KD;Nelson JA;Lui A;Majersik JJ;Cruz MD;Zabramski J;Trevizo O;Lanzino G;Zafar A;Torbey M;Mabray MC;Robinson M;Narvid J;Lupo J;Thompson RE;Hanley DF Jr;McBee N;Treine K;Ostapkovich N;Stadnik A;Piedad K;Hobson N;Carroll T;Shkoukani A;Carrión-Penagos J;Mendoza-Puccini C;Koenig JI;Awad I
脑海绵状血管瘤伴症状性出血（CASH）有很高的风险，神经功能障碍的复发性出血。需要对基线特征进行系统评估，并对新型MRI生物标志物进行多中心验证，以优化CASH中针对新型药物治疗的临床试验设计。这项前瞻性、多中心、观察性队列研究纳入了前一年内患有未切除、裁定的脑CASH的成人。从2018年8月开始，6家美国研究中心筛选并招募了患者。使用描述性统计量总结基线人口统计学、临床和影像学特征、功能状态（改良兰金量表，mRS和NIH卒中量表，NIHSS）和患者生活质量（QoL）结局（PROMIS-29和EuroQol EQ-5D）。PROMIS-29评分相对于参考人群标准化（平均值50，标准差10），并对每个领域进行单样本t检验。一个亚组接受了病灶铁含量与定量磁敏感性标测（QSM）和血管通透性与动态对比增强定量灌注（DCEQP）的协调MRI评估。截至2020年5月，849名患者接受了筛查，110例CASH病例入组（符合试验条件病例的患病率为13%）。知情同意时的平均年龄为46±16岁，53%为女性，41%为家族性，43%为脑干病变。入组时，≥90%的队列患者有独立的功能结局（mRS≤2和NIHSS<5）。然而，在>30%的患者中报告了影响QoL的自觉健康问题（EQ-5D）。与一般参考人群相比，患者的PROMIS-29焦虑评分显著更差（p=0.007），但抑郁评分（p=0.002）和社会满意度评分（p=0.012）更好。CASH病变的平均基线QSM和渗透性分别为0.45 ± 0.17 ppm和0.39 ± 0.31 mL/100 g/min，与历史CASH病例相似，并且在各研究中心之间一致。这些基线特征将有助于研究者对患者进行分层，并确定CASH中新兴药物治疗临床试验的最适当结局指标。
Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel MRI biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH. This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six U.S. sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale, mRS, and NIH Stroke Scale, NIHSS), and patient quality of life (QoL) outcomes (PROMIS-29 and EuroQol EQ-5D) were summarized using descriptive statistics. PROMIS-29 scores standardized against a reference population (mean 50, standard deviation 10) and one sample t-test was performed for each domain. A subgroup underwent harmonized MRI assessment of lesional iron content with quantitative susceptibility mapping (QSM) and vascular permeability with dynamic contrast enhanced quantitative perfusion (DCEQP). As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (mRS≤2 and NIHSS<5). However, perceived health problems affecting QoL were reported in >30% of patients (EQ-5D). Patients had significantly worse PROMIS-29 scores for anxiety (p=0.007), but better depression (p=0.002) and social satisfaction scores (p=0.012) compared to the general reference population. Mean baseline QSM and permeability of CASH lesion was 0.45 ± 0.17 ppm and 0.39 ± 0.31 mL/100g/min, respectively, which were similar to historical CASH cases and consistent across sites. These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.