MedicalResearch.com Interview with:
Yaa-Hui Dong PhD
Faculty of Pharmacy
National Yang-Ming University
MedicalResearch.com: What is the background for this study? Response: Previous observational studies found that fluoroquinolones may be associated with more than 2-fold increased risk of aortic aneurysm or aortic dissection (AA/AD). However, these studies might not well address the influence of concurrent infection, which is also a suggested risk factor for AA. Moreover, most of these studies compared fluoroquinolone use versus no fluoroquinolone use, which might overestimate the risk with fluoroquinolones as patients on fluoroquinolones may have more severe infection versus those not on fluoroquinolones.
MedicalResearch.com Interview with:
Scott A. LeMaire, MD
Jimmy and Roberta Howell Professor of Cardiovascular Surgery
Vice Chair for Research, Michael E. DeBakey Department of Surgery
Professor of Molecular Physiology and Biophysics
Director of Research, Division of Cardiothoracic Surgery
Baylor College of Medicine
Department of Cardiovascular Surgery
Texas Heart Institute
Baylor St. Luke’s Medical Center
CHI St. Luke’s Health
Editor-in-Chief, Journal of Surgical ResearchMedicalResearch.com: What is the background for this study? What are the main findings?Response: We performed this study because of concerns about the potential association between fluoroquinolones and aortic aneurysms and dissection raised in two large clinical studies. This concern was noted by the US Food and Drug Administration in May 2016, but the evidence was not deemed sufficient to warrant a warning. Hence, there was a clear need for additional studies to evaluate the problem. Our study was designed to determine whether there is biological evidence that ciprofloxacin—the most commonly prescribed fluoroquinolone—exacerbates aortic disease in a well-established mouse model. The model uses high-fat diet and angiotensin II infusion to stress the aorta and cause aneurysm and dissection. Using this model, we compared mice that received ciprofloxacin to control mice that received only vehicle, and we found that mice that received ciprofloxacin had significant increases in the incidence of aortic dilatation, severe aortic aneurysm and dissection, and aortic rupture and premature death. Importantly, these findings were consistent in male and female mice. Further, we investigated the potential underlying mechanisms and found that the aortas from mice that received ciprofloxacin had decreased levels of lysyl oxidase, increased levels of matrix metalloproteinases, and increased levels of apoptosis and necroptosis. (more…)
MedicalResearch.com Interview with: John A. Elefteriades, MD
William W.L. Glenn Professor of Surgery
Chief of Cardiothoracic Surgery
Director, Aortic Institute at Yale-New Haven
Yale University School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Elefteriades: The race to map the human genome was declared completed in 2003, at a cost of 3 billion dollars for the international collaborative university group and 300 million dollars for Craig Venter at Celera. Whole exome sequencing can now be performed at a cost of only several thousand dollars per individual. So, whole exome sequencing (also called Next Generation Sequencing) can now be applied to understand and treat diseases of many organ systems.
In this study, we applied whole exome sequencing to study over 100 patients with thoracic aneurysm.
In the late 1990s, both Dr. Diana Milewicz in Texas and our group at Yale had determined that many thoracic aortic aneurysms were genetically transmitted. Dr. Milewicz went on to identify many of the causative mutations. In this study, we were able to look, by whole exome sequencing performed on saliva, for all 21 mutations known to cause thoracic aortic aneurysm--all at one time in one comprehensive genetic test. We were able to protect patients with the most serious discovered mutations by early surgery, the need for which could not otherwise have been apparent. (more…)
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