Eliminating Ischemic Spinal Cord Injury and Paralysis after Aortic Aneurysm Surgery

消除主动脉瘤手术后的缺血性脊髓损伤和瘫痪

• 批准号: 10469194
• 负责人: Hamdy M. Elsayed-Awad
• 金额: $ 2万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469194
• 关键词: Abdominal Aortic Aneurysm; Academia; Address; Animal Model; Aortic Aneurysm; Area; Basic Science; Biological Markers; Blood; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cerebrospinal Fluid; Chest; Clinical; Clinical Research; Collaborations; Complication; Country; Development; Diagnosis; Diet Habits; Drainage procedure; Environment; European; Family; Fright; Functional disorder; Future; Goals; Growth; Hospitals; Incidence; Industry; Institution; Intervention; Lead; Life; Location; Longevity; Manufacturer Name; Maps; Medical; Methods; Molecular; Multiomic Data; Operative Surgical Procedures; Paralysed; Paraplegia; Pathology; Patients; Pattern; Perfusion; Perioperative; Persons; Pharmaceutical Preparations; Pharmacology; Physicians; Prevention; Prevention strategy; Problem Solving; Process; Publishing; Quality of life; RNA; Research; Research Personnel; Saliva; Science; Scientist; Side; Smoking; Societies; Spinal Cord; Spinal cord damage; Spinal cord injury; Stents; Strategic Planning; Surgeon; Surgical complication; Techniques; Therapeutic; Therapeutic Intervention; Tissues; United States; Urine; Work; aging population; base; biobank; clinical care; cost; data integration; design; experience; innovation; interdisciplinary approach; ischemic injury; man; meetings; multiple omics; natural hypothermia; pressure; prevent; prognostic indicator; protein metabolite; repaired; symposium; therapeutic target

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.

项目概要/摘要 美国每年诊断出 24,000 例新的胸腹主动脉瘤 (TAAA) 病例。 人口老龄化、不良饮食习惯、吸烟等导致心血管疾病发病率升高 导致主动脉瘤 (AA) 的发病率增加，这些瘤可通过开放手术修复 胸部修复术（OR）或胸主动脉腔内修复术（TEVAR）这两种修复术都可能导致截瘫。 令人恐惧的毁灭性手术并发症，显着恶化患者的生活质量和寿命 1-8 OR 术后截瘫发生率为 9.2-20%，而 TEVAR 术后截瘫发生率为 15-17%1,7-10,14-18。 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 2019-2026 年为 8.6%。19 截瘫在患者一生中可能花费超过 230 万美元。 20 因此，消除 两种 AA 修复方法后的截瘫既是一项极其紧迫的任务，也是一项巨大的挑战。 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 患者脊髓 (SC) 组织的可用性以及缺乏 TEVAR 大型动物模型。 需要新的创新方法才能在主动脉修复术后截瘫领域取得实质性进展。 是一种“人为”病理，发生在受控的医疗环境中，因此可以在 由于AA患者在手术前一天入院，这在临床上是史无前例的。 有机会收集他们的血液、尿液和脑脊液 (CSF) 以研究分子故障 导致术后截瘫目前的认识是OR vs TEVAR造成的SC损伤。 明显的，增加了对预防截瘫的特定治疗干预的需要。 OR 术后 SC 损伤与 TEVAR 是两种不同的病理，需要具体、独立的考虑。 这次拟议会议的首要目标是讨论可以采取哪些措施的潜在机制 解决AA修复手术后瘫痪的问题，建立协作团队，产生新的、创新的 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 会议结束时，将制定一个明确的路线图来解决这一问题。 从临床端和基础研究端来讨论解决问题的策略。 将重点关注AA手术修复的全球临床前景、预防AA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 会议的第二个目标是建立一个全国性的、消除截瘫的计划。 多中心生物库，其地点遍布全国，将储存瘫痪患者的血液、脑脊液和尿液 AA 手术后非瘫痪患者的研究对于理解 AA 手术后的分子机制至关重要 只有更好地了解导致 OR 或 TEVAR 后的瘫痪。 AA修复后的截瘫将使我们能够设计未来的治疗预防和治疗。