SCHOLARLY INTERESTS
Synthesis of scientific and clinical information in the areas of electrotherapy and electrophysiological evaluation. Clinical Electrophysiology: Electrotherapy and Electrophysiologic Testing. 3rd Edition, Robinson, AJ and Snyder-Mackler, L, Lippincott, Williams and Wilkins, Baltimore, MD, 2008.
Organized by therapeutic goals, the Third Edition of this comprehensive textbook on electrotherapies provides a fundamental understanding of contemporary, evidence-based intervention and assessment procedures. The text takes a problem-oriented approach and recommends interventions consistent with both theory and the clinical efficacy of the intervention for specific, clearly identified clinical disorders.
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Background: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking.
Conclusions: Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life.
In honor of National Heart Month, our February Faculty Spotlight is Dr. Melissa R. Robinson, clinical associate professor (Cardiology) and Director of the Complex Ablation Program and Electrophysiology (EP) Service. Robinson is an expert in complex arrhythmia management, including ablation, device and medical therapy.
She also enjoys engaging with the active conference and symposia community around electrophysiology, participating in education events for attendings, fellows and allied health professionals across the country.
Dr. Robinson's clinical practice is focused on the treatment of individuals with work-related injuries, vestibular dysfunction, and peripheral neuropathy. She has a special interest in performing arts medicine, treating individuals with injuries resulting from playing a string instrument.
I am a neurobiologist interested in the cognitive symptoms of neurofibromatosis type 1 (NF1) and other Rasopathies, which involve altered cell signaling by the Ras family of proteins. My lab investigates the structure and function of neural circuits involved in reward, motivation and attention in mouse models of NF1 using cutting-edge systems neuroscience technologies. These technologies include genetically encoded calcium and neurotransmitter sensors, optogenetics, patch clamp electrophysiology and viral vector-based circuit mapping techniques. Additionally, I am working to develop systemic adeno-associated virus (AAV) gene therapies to restore normal brain function in NF1 and other Rasopathies. These efforts and future research plans are shaped by my strong interest in improving children's lives through translational neuroscience.
Dr. Reddy is a Professor of Medicine at the University of Kansas Medical Center. He completed his residency and cardiovascular fellowships at Creighton University in Omaha Nebraska, Upon completion he did his fellowship in clinical cardiac electrophysiology at the University of Kansas Medical Center.
Dr. Reddy is the Chief of the Division of Cardiac Electrophysiology (Heart Rhythm Services) for the Department of Cardiovascular Medicine. He also the Program Director for the Clinical Cardiac Electrophysiology Fellowship and the Cardiac Arrhythmia programs.
In addition to being very busy clinically, Dr. Reddy is very passionate about teaching and clinical research. His research interests include left atrial appendage occlusion, artificial intelligence in medicine, complex arrhythmia management including ventricular tachycardia ablation and atrial fibrillation ablation.
He has had more than 100 articles published in peer reviewed medical journals to date and more than 250 abstracts presented at national and international meetings. He is invited as a faculty at multiple regional, national and international conferences.
The fellowship may consist of a single accredited clinical year, as outlined here, or structured as a two-year experience, with the first year dedicated to research and the second to the accredited clinical year. A variety of research opportunities exist, including in basic and clinical research.
Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in NaV1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to NaV1.5 upregulation after RT. Clinically, RT was associated with increased NaV1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients.
Cardiac RT is an emerging treatment option for patients with refractory VT. The objective of this study was to define the structural, functional, and molecular effects of focused, single-fraction RT in the adult mammalian heart. Our findings suggest that radiation may be used therapeutically to modulate cardiac electrophysiology for VT management.
Previous preclinical studies have reported increases in global levels and lateralization of Cx43 after carbon radiation to the heart42,43,44, and increased gap junction formation was reported after radiation to other tissue types45,46. In these studies, the mechanism of Cx43 upregulation and the functional consequences of lateralization remain unclear. In the current study using photon-based IR, we also observed IR-associated increases in Cx43 protein; however, we did not observe changes in Cx43 lateralization or conduction anisotropy. Future studies are warranted to determine whether there are differences in NaV1.5 and Cx43 responses, as well as dosing considerations, among different radiation modalities, including X-ray, carbon ion, and proton beam cardiac RT.
In patients, total sample size was powered to demonstrate acute safety and preliminary efficacy of noninvasive radiation therapy for treatment of refractory ventricular tachycardia under the ENCORE-VT (NCT02919618) clinical trial, a single-arm Phase I/II trial, in which 19 patients were enrolled and treated10. Patients with refractory VT (i.e., failed at least one CA or was contraindicated to CA and failed/became intolerant to at least one antiarrhythmic medication) and met all inclusion/exclusion criteria were enrolled into the study. Patient-level data were restricted to paired, binary intra-patient comparisons (non-targeted versus targeted and/or pretreatment versus posttreatment).
D.M.Z., U.G., J.K.S., and S.L.R. conceived the study, designed experiments, and participated in data interpretation. D.M.Z., R.N., T.Y., U.G., C.K., C.E.L., Y.Q., S.H., and G.L. performed experiments and analyzed experimental data. J.S. performed bioinformatic analyses and assisted in designing the experiments. A.L. collected and interpreted pathology. U.G. performed image-segmented pathology analysis. C.M., C.B., B.E.R., and J.K.S. developed treatment plans for animal experiments. K.M.S.M. coordinated the ENCORE-VT study and collected clinical data and specimens. R.N. and P.S.C. interpreted ECGs. C.G.R. and P.S.C. developed patient treatment plans, collected and analyzed patient data, and participated in data interpretation. C.B., C.G.R., P.S.C., and J.K.S. provided scientific feedback. D.M.Z. and S.L.R. drafted the manuscript. All authors read, contributed to editing, and approved the manuscript.
Robert Robinson, MD, FACS, is board-certified in general surgery and is a fellow of the American College of Surgeons. Dr. Robinson's clinical interests include surgical critical care, minimally invasive gastrointestinal (GI) and trauma surgery, as well as surgical oncology, including liver and pancreatic surgery. Dr. Robinson performs daVinci robotic-assisted surgery for hernia, gallbladder, hiatal hernia, liver, pancreas and colon.
How have you benefitted from the project?
I was beyond lucky to benefit from this experience in ways far greater than I expected going into the program. First and foremost, I have Dr. Robinson and Dr. Sorensen to thank. One, for choosing me through the recruiting process, but two, and more importantly for fostering the amazing summer that I was able to have. They were able to mentor me in ways that I have not had the privilege of in the past. I benefited from this experience with the relationships I was able to walk away with, the hours and hours of shadowing pediatric cardiology electrophysiology, the technical knowledge I obtained from operating REDCap, the clinical outreach experience, and then to finish off with a public speaking presentation grounding framework for my future. 2351a5e196
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