An early-stage clinical trial has found that, compared to a placebo, a novel medication significantly reduces potentially life-threatening episodes of swelling of the airway as well as the hands, feet, and abdomen of patients affected by a rare genetic disorder. The findings were published in the New England Journal of Medicine.
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After giving birth to her first child, Melinda Constantine was diagnosed with a rare type of heart failure that can happen during pregnancy or right after delivery. Under the care of Anelechi Anyanwu, MD, Surgical Director of the Mechanical Circulatory Support and Heart Transplant Program, and Sean P. Pinney, MD, Director of Heart Failure and Transplantation at Mount Sinai Heart, Melinda now has a mechanical pump and has been able to return to normal life.
Ram Roth, MD, a board certified anesthesiologist at Mount Sinai Queens, generally posts about anesthesiology, anesthesiologists’ advice to patients, and the surgical services offered at Mount Sinai Queens. This time, Dr. Roth is reporting from Liberia, the West African nation where a group from Mount Sinai recently provided much-needed medical care, surgical care, and education.
I’m sitting in the dark with two surgeons, a medical student, the director of events, and another anesthesiologist from within the Mount Sinai Health System. The lights in the compound just went out. We have no idea when they will come back on. Where are we and why are we sitting in the dark? Liberia. The country of about 4.3 million people was heavily hit by the 2014-2015 Ebola outbreak. (more…)
In a Q&A with Cardiovascular Business, Donna Mendes, MD, a vascular surgeon at Mount Sinai St. Luke’s and Mount Sinai West, talks about diversity at Mount Sinai, how the industry has become more diverse over the years, and why all providers should make it a priority.
From left: Martin John Walsh, PhD; and Stuart Sealfon, MD
Empirical evidence shows that exercise improves and prevents a large number of diseases, but the scientific basis and molecular mechanisms responsible for these beneficial effects are largely unknown. Two researchers at the Icahn School of Medicine at Mount Sinai have been awarded $15.5 million by the National Institutes of Health (NIH) Common Fund—designated as the Physical Activity Genomics, Epigenomics/transcriptomics Site (PAGES)—to advance this knowledge by mapping the molecular signals between different parts of the body during physical activity.
Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology, Director of the Center for Advanced Research on Diagnostic Assays, and Chairman Emeritus of the Department of Neurology; and Martin John Walsh, PhD, Director for the Center of RNA Biology and Medicine, and a Professor of Pharmacological Sciences, Genetics and Genomic Sciences, and Pediatrics, will employ the latest genomic technologies in their investigation. They are part of a $170 million NIH program called the Molecular Transducers of Physical Activity Consortium (MoTrPAC), which involves more than two dozen academic research institutions around the country.
Using various genomic, epigenomic, transcriptomic, proteomic, and metabolomic technologies, Drs. Sealfon and Walsh, together with MoTrPAC, will analyze tissue and blood from 3,000 individuals in diverse racial, ethnic, gender, and age groups, and fitness levels. The samples will identify exercise-related chemical messengers and molecular responses that can provide the scientific basis for developing more effective individualized prescriptions of exercise, as well as the development of new drug therapies.
Where exercise has been studied, the benefits are measured in results such as less body fat, and lower cholesterol, sugar levels, and blood pressure. At molecular dimensions, the links between exercise and health remain mysterious.
“How is physical activity preventing or improving various cancers?” Dr. Sealfon asks. “We really don’t know the mechanisms.” The same holds true for Parkinson’s and Alzheimer’s diseases, depression, and other illnesses that have been shown in clinical studies to respond to exercise.
Based on their future findings, Drs. Sealfon and Walsh can foresee the creation of medications that mimic the signals released by exercising—so-called exercise mimetics—that would be particularly beneficial for patients with disorders that prevent or restrain their movement. According to NIH Director Francis S. Collins, MD, PhD, the current availability of advanced technology has made it possible to launch this bold new study. “This is the right time to take that technology forward,” he said. “We can now contemplate doing something that even a year ago would have been pretty hard to imagine.”
Physicians nowadays prescribe exercise routinely with particular attention to heart disease, weight control, and stress-related ailments. But, ultimately, the goal is to help them prescribe exercise on an individual basis. Such specificity would be based upon a clear understanding of the physical activity needed to assist each patient, rather than a one-size-fits-all approach.
The information gathered by all of the research sites involved in the consortium will be stored in a publicly accessible database that scientists can use to study almost every organ and tissue in the body.
Says Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System: “To fully understand and subsequently transform clinical medicine’s use of physical activity for health management, a large-scale effort like this is imperative. Receiving this award is a testament to our outstanding faculty and our investment in genomics and systems biology research, which have positioned us to be able to contribute to this groundbreaking translational endeavor.”
Patients with more activity (the purple area throughout the image at right) in the brain’s center for stress and fear were more likely to have a heart attack or stroke, compared to patients with less activity (at left).
A Mount Sinai researcher has played a key role in tracing—for the first time—the mechanisms that link stress to cardiovascular events, like heart attack or stroke. Zahi A. Fayad, PhD, Director of the Translational and Molecular Imaging Institute at the Icahn School of Medicine at Mount Sinai, was co-senior author of a paper on the research, which was published January 12, 2017, in The Lancet. The work will be expanded in a five-year project, funded by a new $7 million grant from the National Institutes of Health (NIH).
The research found that people who had more activity in an area of the brain that regulates the body’s response to stress and fear, called the amygdala, were more likely to have a heart attack or stroke than those with less activity. The findings “provide more evidence of a heart-brain connection,” Dr. Fayad says. “It may seem obvious, but until now the evidence had not been shown. We had not seen the mechanistic link.”
The Lancet paper was based on two complementary studies. One study was led by the first author of the paper, Ahmed A. Tawakol, MD, Co-Director of the Cardiac MR PET CT Program at Massachusetts General Hospital in Boston. The study analyzed data from 293 people who from 2005 to 2008 underwent positron emission tomography–computed tomography (PET/CT) brain imaging, primarily for cancer screening, using a radiopharmaceutical called FDG that measures activity in the brain, vascular system, and bone marrow. Researchers found that over the next four years, 22 of the patients had cardiovascular events. In that group, many patients had initially shown a high level of activity in the amygdala and a greater amount of inflammation in the aorta, and in the bone marrow, where new blood cells are made. The latter two factors can contribute to atherosclerosis, the hardening and narrowing of the arteries, which increases the risk for heart disease. This pathway—from emotional stress to increased white blood cells to inflammation to atherosclerosis—has been identified in animals, but until now, not in humans.
Zahi A. Fayad, PhD
The second study, conducted by Dr. Fayad’s team at the Translational and Molecular Imaging Institute, examined 13 people who were being treated for post-traumatic stress disorder at Mount Sinai’s Mood and Anxiety Disorders Program. These patients completed a questionnaire about their perceived stress levels and underwent FDG-PET/MR scans. The team found that the patients’ stress levels were linked to increased activity in the amygdala, as well as increased inflammation in the blood vessels.
In the new project, Dr. Fayad—as overall principal investigator—will work with Dr. Tawakol; the leaders of the Mood and Anxiety Disorders Program, Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System; and Program Director James Murrough, MD, Assistant Professor of Psychiatry, and Neuroscience; and others at Mount Sinai.
The project is seeking to study three groups of patients: 80 who are being treated for PTSD; 80 who are “resilient,” with past exposure to trauma but a low perceived level of stress; and 80 who have not been exposed to trauma. It will explore the possibility that alleviating stress could not just improve patients’ psychological sense of well-being, but also improve their physical atherosclerotic health. “In the future, chronic stress can be treated as a risk factor for cardiovascular disease,” Dr. Fayad says, “so we can screen for it and manage it like other risk factors.”
A patient with high activity in the amygdala also showed inflammation in the aorta (top right) and bone marrow in the spinal column (bottom right). Another patient with low activity in the amygdala showed little or no inflammation in the aorta (top left) and bone marrow (bottom left).