Research
Aristidis Veves, MD, ScD
Rongxiang Xu, MD, Professor of Surgery, Harvard Medical School
Director, Rongxiang Xu, MD, Center for Regenerative Therapeutics at BIDMC
Research Group
- George Theocharidis, PhD
- Jie Dong, MD
- Lihong Chen, MD
- Ying Zhang, MD
- Ikram Mezghani, MS
- Navin Jayaswal, BA
Response to Covid-19 pandemic: Study about the Covid toe syndrome
Covid-19 main presenting symptoms are fever, dry cough, dyspnea, fatigue, anorexia, ageusia and anosmia. However, in a smaller portion of patients, skin symptoms in the form of erythematous lesions, dengue-like petechiae and urticaria and chickenpox-like vesicles have been described. In a recent study that included 277 patients, skin manifestations with skin manifestation, acral lesions were observed in more than half of the patients. More severe cases include the presence of toe cyanosis, bulla and dry gangrene. The frequency of this condition and its clinical characteristics are currently not well understood.
The pathophysiology of this condition is also not well understood and, given the lack of data, at this point only hypotheses can be made. The most fitting hypothesis is that it is related to the Covid-19 related endothelialitis. More specifically, recent reports from lung biopsies have indicated that patients who died from Covid-19–associated or influenza-associated respiratory failure had severe endothelial injury and intussusceptive angiogenesis. In addition, Covid-19 patients also present with high blood pressure, arterial and venous thromboembolism, while conditions that are known to be associated with endothelial dysfunction, such as hypertension, obesity and diabetes mellitus are risk factors.
Study Rationale
There is very little information regarding the frequency and severity of the Covid toe syndrome. Furthermore, it is not known whether condition that are known to cause lower extremity problems, such as diabetes mellitus or peripheral vascular disease are also risk factors in the development of this syndrome. As this condition is very close to the mission and interests of the Xu Center at BIDMC, a multicenter study will be conducted with the primary aim to collect data that can provide reliable information related to the above questions.
Study Objectives
The primary objective is to evaluate the frequency and clinical course of the COVID toe syndrome.
The secondary objective is to describe cases treated with various modalities and collect preliminary data that can lead to subsequent clinical trials. The collected date will include serum measurements of inflammatory cytokines and markers of endothelial function and histopathological analysis of available tissues.
Study Methodology
This is a study that will initially retrospectively try to identify cases of Covid toe in participating centers. At the same time, new patients will be prospectively followed up. The main aim will be to get a better estimation of the frequency of this condition, its clinical features and the natural course of the disease.
In addition, in selected centers, patients receiving care for Covid-related foot wounds will be followed for a maximum of 8 weeks or until complete healing occurs, whichever comes first. The main aim of this case series study is to collect preliminary data that will lead to further clinical trials.
Study Site(s)
Approximately 6-8 clinical sites in the U.S. U.S, China or other countries.
The leading center will be the Rongxiang Xu, MD, Center for Regenerative Therapeutics and the Joslin-Beth Israel Deaconess Foot Center, both located at Beth Israel Deaconess Medical Center.
The leading PI will be Dr. Aristidis Veves, MD, DSC, Rongxiang Xu, MD, Professor of Surgery, Harvard Medical School, Director, The Rongxiang Xu, MD, Center for Regenerative Therapeutics, Research Director, Joslin-Beth Israel Deaconess Foot Center.
The steering committee will include Dr. Aristidis Veves, MD, Dr. John Giurini, DPM, Chief of Podiatry at Beth Israel Deaconess Medical Center and Associate Professor of Surgery, Harvard Medical School, Dr. Ryan Cauley MD, MPH, Reconstructive Microsurgery, Plastic and Reconstructive Surgery, Instructor in Surgery, Beth Israel Deaconess Medical Center and Dr. Georgios Theocharidis, PhD, Instructor in Surgery.
The study is expected to activated soon and will be conducted in collaboration with the National Rongxiang Xu Foundation.
Research Focus
I am mainly involved in ‘bench to bedside’ research. My main research field is diabetes and its complications, with the main emphasis on wound healing and cardiovascular disease. Approximately 90 percent of my effort is dedicated to research, 5 percent for teaching and an additional 5 percent for administrative and other relevant professional activities.
Translational research is a major part of my research activities. My work mainly focuses on the interaction between neuropathy and microvascular disease in the development of diabetic foot ulceration and the subsequent impairment of wound healing. This work has been supported by the NIH and nonprofit organizations. I collaborate with investigators from various departments at BIDMC, and investigators from other institutions, such as Brigham and Women's Hospital, to conduct additional translational research.
I conduct investigator-initiated research studies that examine the effects of various FDA-approved medications on cardiovascular function. These studies, although funded by industry, have been conceived, designed, and executed by my unit and focus on possible new mechanisms through which these medications exert their beneficial effects. I have also served as the lead investigator and lead author in industry sponsored multicenter trials that investigated the efficacy of new therapeutic interventions for the management of diabetic foot ulceration.
I also run my own basic research laboratory that mainly explores the findings of this translational research and tries to identify mechanisms underlying the observed results. My laboratory works closely with other laboratories in BIDMC and is funded by NIH grants and a DARPA grant. I also collaborate with Dr. David Mooney’s laboratory at the Wyss Institute and Harvard Engineering School and Dr. Jonathan Garlick’s at Tufts Medical School. The main aim of our collaboration is the development of new wound-healing products. This collaboration has resulted in NIH funding of our grant applications.
The results of my research have been published in prestigious medical journals, including Lancet, Diabetes, and Circulation. My work, according to Google Scholar as of June 2020, has resulted in more than 21,200 citations an h-index of 27 and i10-index of 172.
I have also been the Director of the Rongxiang Xu, MD, Center for Regenerative Therapeutics since its establishment in December 2015. The center was established after a generous donation from the National Rongxiang Xu Foundation and its mission is to further advance the treatment of patients throughout the world with chronic wounds, burns, and other conditions resulting from a failure of tissue repair and regeneration. As part of its mission, the Center provides resources for the conduction of collaborative bench-to-bedside research with investigators worldwide, as well as the education of physicians and scientists internationally.
Teaching, Training, and Education
My teaching responsibilities include participation in the training of podiatry residents, supervision of the fellows and junior faculty in my laboratory, and participation in mentorship committees of junior faculty members from other units. I am also involved in educational activities of the Center for Education at BIDMC, which provides guidance to candidates for NIH K-series awards. Finally, I participated as series editor, book editor or co-editor and author in numerous textbooks. One of these textbooks (Diabetes and Cardiovascular Disease) has been already translated to the Italian language and another one (Diabetic Foot) to the Greek language while a translation to Chinese language is in progress.