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，并将其定制为一个翻译的以患者为导向的成果倡议。该提案的重点是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和生物信息学的工作知识，并将其应用于人类疾病。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本课程，以及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，以在佛罗里达大学创建手部和上肢功能结局登记。我选择的导师是唯一有资格塑造一个年轻的学术外科医生的职业生涯，顾问小组由血液动力学生理学，血管生物学，生物信息学，外周神经功能/测试和临床试验设计的专家组成。教学大纲遵循该大学临床研究K30高级研究生课程的详细课程。它概述了高级神经生理学，统计学/生物信息学，流行病学，临床调查以及道德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对所得数据集的应用方面的实践培训将通过与我的导师/顾问的直接互动来进行。总之，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。 该翻译功能结局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-肌电图实验室;两者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具有公认的专业知识。使用这些资源，我将测试的假设，即预先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后动静脉瘘放置导致的频谱的手/上肢神经肌肉功能障碍常见于术后间隔。预期这种反应在所有患者中并不一致，而是受到某些术前遗传易感性或神经肌肉功能差异调节的调节，最终产生手/肢体残疾的临床表型。手谱 功能障碍可能发生在血液通路创建之后，并且通常对生活质量具有深远的负面影响。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学的新见解，并可能导致新的策略，以改善现有的方法，术前预测（与由此产生的患者咨询）和术后早期补救。此外，该计划将提供肢体功能障碍整体管理方面的新知识，这些知识可能更广泛地外推至其他疾病状态（肌营养不良、下肢外周动脉闭塞性疾病和术后创伤）。

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).