Eliminating Ischemic Spinal Cord Injury and Paralysis after Aortic Aneurysm Surgery

项目摘要/摘要 在美国，每年新诊断的胸腹主动脉瘤(TAAA)病例有2.4万例。 人口老龄化、不良饮食习惯和吸烟导致心血管疾病的发病率更高， 会增加主动脉瘤(AA)的发病率，这些主动脉瘤是通过开放手术修复的 胸部修补术(OR)或胸主动脉腔内修补术(TEVAR)。这两种修复方法都会导致截瘫，最严重的 手术令人恐惧和毁灭性的并发症，这显著恶化了患者的生活质量和寿命 患者1~8术后截瘫发生率9.2~20%，TEVAR术后截瘫发生率15~17%，7~10，14~18岁。这个 2018年全球主动脉瘤市场规模为25亿美元，预计复合年增长率 2019年-2026.19截瘫8.6%的损失可能会在患者一生中造成230多万美元的损失。 两种AA修复方法后的截瘫既是一种极端的紧迫性，也是一种巨大的挑战。 自第一次主动脉修复手术导致瘫痪以来，进展甚微，这可能反映了缺乏 患者的脊髓(SC)组织可获得性以及缺乏TEVAR的大型动物模型。因此， 要在这一领域取得实质性进展，就需要采取新的创新办法。主动脉修复术后截瘫 是一种“人为”的病理，发生在受控的医疗环境中，因此在 临床环境。因为AA患者在手术前一天入院，这是史无前例的 有机会收集他们的血液、尿液和脑脊液(CSF)来研究分子故障 导致手术后截瘫。目前的理解是，OR和TEVAR造成的SC损伤是 截然不同的是，加强了对预防截瘫的具体治疗干预的需要。据推测， OR和TEVAR后SC损伤是两种不同的病理，需要具体的、独立的考虑。 这次拟议的会议的第一个目标是讨论可以做些什么的潜在机制 解决AA修复手术后瘫痪的问题，建立协作团队，产生新的创新 旨在预防SC损伤的特定研究领域的想法，并将医生、学术界和 行业来解决这一问题。在会议结束时，预计会有一份明确的路线图。 将从临床和基础研究两方面采取的策略来解决这个问题。讨论 将重点介绍世界范围内再障手术修复的临床前景、预防的最新进展。 截瘫，以及未来制定更有效的临床和研究战略计划，以确定目标和 该计划需要消除截瘫。会议的第二个目标是建立一个全国性的， 多中心生物库，在全国各地储存瘫痪和 AA手术后的非瘫痪患者将是理解导致 或或TEVAR后瘫痪。只有在更好地了解导致 AA修复后的截瘫，我们将能够设计未来的治疗性预防和治疗。

Project Summary/Abstract Each year, 24,000 new cases of thoracoabdominal aortic aneurysms (TAAA) are diagnosed in the United States. The aging population, poor dietary habits, and smoking lead to a higher incidence of cardiovascular disease that contributes to an increasing incidence of aortic aneurysms (AA) that are repaired surgically either through open chest repair (OR) or thoracic endovascular aortic repair (TEVAR). Both repairs can lead to paraplegia, the most feared and devastating complication of the surgery, which significantly worsens the quality of life and lifespan of the patient.1-8 The rate of paraplegia after OR is 9.2-20% while the rate after TEVAR is 15-17%1,7-10,14-18. The global market size for aortic aneurysms in 2018 was $2.5 billion with an expected compound annual growth rate of 8.6% for 2019-2026.19 Paraplegia can cost over $2.3 million over the patient’s lifetime.20 Therefore, eliminating paraplegia after both methods of AA repair represents an extreme urgency as well as an enormous challenge. Little progress has been made since the first aortic repair surgery resulting in paralysis, likely reflecting the lack of spinal cord (SC) tissue availability from patients and the lack of large animal models of TEVAR. Therefore, new, innovative approaches are needed to make substantial progress in the field. Paraplegia after aortic repair is a “man-made” pathology and occurs in a controlled medical environment, thus prevention is feasible in a clinical setting. Because AA patients are admitted to the hospital one day before surgery, an unprecedented opportunity exists to collect their blood, urine, and cerebrospinal fluid (CSF) to study the molecular malfunction leading to paraplegia after surgery. The current understanding is that the SC injury caused by OR vs TEVAR are distinct, heightening the need for specific therapeutic interventions to prevent paraplegia. It is hypothesized that SC injury after OR vs TEVAR are two different pathologies that will require specific, independent considerations. The first objective of this proposed conference is to discuss potential mechanisms on what can be done to address the problem of paralysis after AA repair surgery, build up collaboration teams, generate new, innovative ideas in specific areas of research aimed at preventing SC injury, and bring together physicians, academia, and industry to solve this problem. At the end of the conference, a clear road map will be anticipated of the potential strategies that will be taken from the clinical side and the basic research side to solve the problem. Discussions will focus on the worldwide clinical perspective of AA surgical repair, recent progress in the prevention of paraplegia, and future development of more effective clinical and research strategic plans to define the goal and the plan needed to eliminate paraplegia. The second objective of the conference is to establish a national, multicenter biobank with locations throughout the country that will store blood, CSF, and urine of paralyzed and non-paralyzed patients after AA surgery that will be critical for understanding the molecular mechanisms causing paralysis after either OR or TEVAR. Only with a better understanding of the molecular malfunctions leading to paraplegia after AA repair will we be able to design future therapeutic prevention and treatment.