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.

项目总结/摘要 每年，在美国诊断出24，000例胸腹主动脉瘤（TAAA）的新病例。 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较高， 导致主动脉瘤（AA）的发生率增加，这些主动脉瘤通过开放手术或外科手术修复， 胸部修复（OR）或胸主动脉腔内修复（TEVAR）。这两种修复都可能导致截瘫， 手术的可怕和毁灭性的并发症，这大大降低了生活质量和寿命， 1 -8手术后截瘫的发生率为9.2-20%，而TEVAR后截瘫的发生率为15- 17% 1，7 - 10，14 - 1 - 8。的 2018年主动脉瘤的全球市场规模为25亿美元，预计复合年增长率为 2019- 2026年的8.6%。19截瘫在患者的一生中可能花费超过230万美元。20因此，消除 两种AA修复方法后的截瘫代表了一种极端的紧迫性以及巨大的挑战。 自从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）组织的可用性和缺乏TEVAR的大型动物模型。因此，我们认为， 需要采取新的创新办法，以便在这一领域取得实质性进展。主动脉修复术后截瘫 是一种“人为”的病理学，发生在受控的医疗环境中，因此， 临床设置。由于AA患者在手术前一天入院，这是前所未有的 有机会收集他们的血液，尿液和脑脊液（CSF），以研究分子功能障碍 导致手术后截瘫目前的理解是，OR与TEVAR引起的SC损伤是 不同的，提高了需要具体的治疗干预，以防止截瘫。它是假设 OR与TEVAR后的SC损伤是两种不同的病理，需要具体、独立的考虑。 这次拟议的会议的第一个目标是讨论可以采取哪些行动的潜在机制， 解决AA修复手术后瘫痪的问题，建立协作团队， 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 行业来解决这个问题。在会议结束时，预计将有一个明确的路线图， 从临床和基础研究两个方面提出了解决问题的策略。讨论 将重点介绍AA手术修复的全球临床前景，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国家， 多中心生物银行，在全国各地的地点，将储存血液，脑脊液，和尿液的瘫痪， AA手术后的非瘫痪患者，这对于理解导致AA的分子机制至关重要。 手术或TEVAR后瘫痪。只有更好地理解分子故障， 我们将能够设计未来的治疗性预防和治疗。