Mechanisms of Hand Dysfunction following Hemodialysis Fistula Creation

描述（由申请人提供）：这个为期五年的培训计划旨在利用我的基础研究背景，并将其调整为以患者为导向的转化结果倡议。本建议侧重于血流动力学生理学、神经传导研究、以患者为中心的结果和生物信息学在人类疾病中的功能应用方面的工作知识的发展。它概述了两个可实现的目标：1)满足临床转化科学证书所需的基础课程；2)建立一个由临床医生、科学家和统计学家组成的多学科合作小组，在佛罗里达大学建立一个手部和上肢功能结果登记处。我选择的导师是唯一有资格塑造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。教学指导遵循大学临床研究高级研究生课程K30课程的详细课程。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。在神经生理学测试、研究设计以及将生物信息学工具应用于结果数据集方面的实践培训将通过与我的导师/顾问的直接互动进行。总的来说，这些因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。这项转化功能结果提案利用了佛罗里达大学的几个固有资产，其中最重要的是血管生物学实验室和临床神经生理学-肌电图实验室；在血液动力学摄动和神经肌肉测试对人类疾病的应用方面都有公认的专业知识。利用这些资源，我将验证先前存在的神经肌肉功能障碍与异常的适应性反应和局部组织缺血在动静脉瘘置入后导致了手/上肢神经肌肉功能障碍的假设。期望这种反应在所有患者中不是统一的，而是由一些术前遗传易感性或神经肌肉功能的差异调节，最终产生手/肢体残疾的临床表型。手的谱

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).