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).
Approximately half of all patients who receive an arteriovenous fistula will development some element of hand dysfunction. This training award seeks to understand the relative contribution of hemodynamic perturbations on muscle and nerve dysfunction that occur after fistula placement. Moreover, the patients underlying clinical and physiologic state in the context of local hand ischemia will be further studied and integrated with the measured neuromuscular dysfunction to develop predictive models of outcome.
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