Mechanisms of Hand Dysfunction following Hemodialysis Fistula Creation

描述(由申请者提供)：这个为期五年的培训计划旨在利用我的基本研究背景，并根据患者导向的成果倡议进行翻译。这项建议侧重于发展血液动力学生理学、神经传导研究、以患者为中心的结果以及具有功能性应用于人类疾病的生物信息学的实用知识。它概述了两个可实现的目标：1)获得临床转化科学证书所必需的基本课程，2)建立一个由临床医生、科学家和统计学家组成的多学科协作小组，以在佛罗里达大学创建手和上肢功能结果登记处。我选择的导师是唯一有资格塑造一名年轻学术外科医生职业生涯的人，顾问小组由血液动力学生理学、血管生物学、生物信息学、周围神经功能/测试和临床试验设计方面的专家组成。教学指导遵循的详细课程的高级研究生计划在临床调查K30计划在大学。它概述了高级神经生理学、统计学/生物信息学、流行病学、临床调查以及伦理和负责任的人类主题研究的课程。神经生理学测试、研究设计以及生物信息学工具在结果数据集上的应用方面的实践培训将通过与我的导师/顾问的直接互动进行。总而言之，这些要素将为我的职业生涯奠定基础，并最终成为一名独立的临床科学家。这一转换功能结果提案利用了佛罗里达大学的几项固有资产，其中最重要的是血管生物学实验室和临床神经生理学-肌电实验室；这两个实验室都在血流动力学扰动和神经肌肉测试应用于人类疾病方面拥有公认的专业知识。利用这些资源，我将检验这样一种假设，即动静脉瘘放置后，先前存在的具有异常适应反应的神经肌肉功能障碍和局部组织缺血导致了手术后经常出现的手/上肢神经肌肉功能障碍。人们的预期是，这种反应在所有患者中并不是一致的，而是受到某些术前遗传倾向或神经肌肉功能差异调节的调节，最终导致手/肢体残疾的临床表型。手部的光谱 功能障碍可能发生在创建HemoAccess之后，并经常对生活质量产生深远的负面影响。终末期肾病是一个重要的国家卫生保健问题，通过这项工作获得的信息将导致对这种上肢残疾的病因的新见解，并可能导致新的战略，以改进现有的术前预测(以及由此产生的患者咨询)和术后早期补救的方法。此外，这一倡议将在肢体功能障碍的整体管理方面提供新的知识，这些知识可能更广泛地推断到替代疾病状态(肌肉营养不良、下肢外周动脉闭塞疾病和手术后创伤)。

DESCRIPTION (provided by applicant): This five-year training program is designed to take advantage of my basic research background and tailor it to a translational patient-oriented outcomes initiative. This proposal focuses on the development of a working knowledge in hemodynamic physiology, nerve conduction studies, patient-centered outcomes, and bioinformatics with functional application to human disease. It outlines two achievable goals: 1) the basic coursework necessary to satisfy a Certificate in Clinical Translational Science, and 2) establishment of a multidisciplinary collaborative group of clinicians, scientists, and statisticias to create a hand and upper extremity functional outcomes registry at the University of Florida. My chosen mentor is uniquely qualified to mold the career of a young academic surgeon, and the advisory panel is comprised of experts in hemodynamic physiology, vascular biology, bioinformatics, peripheral nerve function/testing, and clinical trial design. The didactic instructon follows the detailed curriculum of the Advanced Postgraduate Program in Clinical Investigation K30 program at the University. It outlines coursework in advanced neurophysiology, statistics/bioinformatics, epidemiology, clinical investigation, and ethical and responsible human subject research. Practical training in neurophysiologic testing, study design, as well as, the application of bioinformatics tools to the resultant dataset will come through direct interaction with my mentor/advisors. In total, these elements will create the foundation on which I will build my career and ultimately become an independent clinical scientist. This translational functional outcomes proposal takes advantage of several intrinsic assets at the University of Florida, the most important of which is the Vascular Biology Laboratory and Clinical Neurophysiology- Electromyography Lab; both with recognized expertise in the application of hemodynamic perturbations and neuromuscular testing to human disease. Using these resources, I will test the hypothesis that pre-existing neuromuscular dysfunction with an aberrant adaptive response and local tissue ischemia following arteriovenous fistula placement causes the spectrum of hand/upper extremity neuromuscular disability seen frequently in the post-operative interval. The expectation is that this response is not uniform in all patients, but rather, is modulated by either some preoperative genetic predisposition or differential regulation of nerve-muscle function that ultimately creates the clinical phenotype of hand/limb disability. A spectrum of hand dysfunction may occur after hemoaccess creation and often has a profound negative impact on quality of life. End-stage renal disease is a significant national health care concern and the information gained through this work will lead to new insights about the etiology of this upper extremity disability and potentially lead to new strategies to improve existing approaches to pre-operative prediction (with resultant patient counseling) and early post-operative remediation. Additionally, this initiative will provide new knowledge in the overall management of limb dysfunction that can potentially be extrapolated more broadly to alternative disease states (muscular dystrophy, lower extremity peripheral arterial occlusive disease, and post- surgical trauma).