Updated on Jun 30, 2022 | Featured, Research
Icahn School of Medicine at Mount Sinai authors of the study included, from left: Ron Do, PhD, Assistant Professor, Genetics and Genomic Sciences; Girish Nadkarni, MD, Assistant Professor of Medicine (Nephrology); and Kumardeep Chaudhary, PhD, Senior Postdoctoral Fellow, Genetics and Genomic Sciences. Dr. Nadkarni and Dr. Do are Co-Directors of the BioMe Phenomics Center.
A genetic variation that is prevalent in people of African or Hispanic/Latino ancestry was significantly associated with heart failure in a study by researchers at the Icahn School of Medicine at Mount Sinai and the Perelman School of Medicine at the University of Pennsylvania. The study, published in December 2019 in JAMA: The Journal of the American Medical Association, found underdiagnosis of affected patients and made a strong argument for wider genetic screening of the potentially deadly mutation, researchers say.
The team reported a significant association between the variation, TTR V142I, and a serious heart disorder, hereditary transthyretin amyloid cardiomyopathy (hATTR-CM). The TTR V142I gene variant, previously known as TTR V122I, causes the liver to produce misformed molecules of the transthyretin protein. The protein forms clusters, called amyloids, that can deposit in tissues throughout the body, including the nerves, kidneys, and joints. When amyloids lodge in the heart, they cause hATTR-CM, in which the walls of the heart become thicker and stiffer—in the worst case leading to heart failure.
“Using clinical data linked to the genetic data at the BioMe™ Biobank of Mount Sinai, we found that up to 4 percent of African-Americans and 1 percent of Hispanic/Latino Americans carried this mutation,” says a corresponding author of the study, Girish Nadkarni, MD, Assistant Professor of Medicine (Nephrology), and Co-Director of the BioMe Phenomics Center in The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine. “They had a higher risk of heart failure compared to people who didn’t have this mutation, but strikingly, very few of them had been appropriately diagnosed.”
Patient Wilbert Gibson with Sumeet S. Mitter, MD, left, and Donna M. Mancini, MD, Professor of Medicine (Cardiology), and Population Health Science and Policy.
The association of the TTR V142I variant with the clinical diagnosis of heart failure was evaluated in 9,694 individuals of African and Hispanic/Latino ancestry, using health records linked to genetic data from the BioMe Biobank and the Penn Medicine Biobank. Among carriers of the TTR V142I variant, the rate of diagnosis with hATTR-CM was assessed. The findings indicated both high rates of underdiagnosis and prolonged time to the appropriate diagnosis, says senior author Ron Do, PhD, Assistant Professor of Genetics and Genomic Sciences, and Co-Director of the BioMe Phenomics Center. Only 11 percent of individuals with the genetic variant and heart failure had been diagnosed with hATTR-CM, with an average time to appropriate diagnosis of three years.
“Our hope is if we can find individuals with amyloid cardiomyopathy early through genetic screening, we can start them on therapy before a heart transplant becomes the only clinical solution,” says Sumeet S. Mitter, MD, Assistant Professor of Medicine (Cardiology), and a leader of the multidisciplinary Clinical Amyloid Program at the Icahn School of Medicine. “Early diagnosis is even more important, given recent advances in treatment for hATTR-CM.” Treatment was limited to supportive care until May 2019, when the U.S. Food and Drug Administration approved the breakthrough drug tafamidis, made by Pfizer. However, timely diagnosis is critical, since the therapy stops amyloids from depositing in tissues, but does not reverse the course of the disorder.
The experience of a Mount Sinai patient, Wilbert Gibson, is emblematic. Mr. Gibson, 63, began having worrisome symptoms in early 2019. “My weight shot up from about 170 to nearly 200 pounds.” he says. “My legs were swelling; I was having shortness of breath.” Mr. Gibson was diagnosed with cardiac amyloidosis and found to have the TTR V142I mutation. His heart failure was so advanced that he required a transplant. He received a new heart in June 2019 and says he feels restored and grateful. However, he echoes clinicians and researchers in calling for more awareness of the gene variant, its prevalence in some populations, and its association with heart failure. “People should know about this,” Mr. Gibson says.
Updated on Jun 30, 2022 | Featured, Research
Catherine Sinclair, MD, performed radiofrequency ablation at Mount Sinai West.
Mount Sinai has become one of the few health systems in the nation to offer a new minimally invasive procedure to treat noncancerous thyroid nodules. The procedure, called radiofrequency ablation (RFA), offers eligible patients a quicker recovery and minimal scarring, with preservation of surrounding healthy thyroid tissue.
Catherine Sinclair, MD, Associate Professor of Otolaryngology, Icahn School of Medicine at Mount Sinai, and Director of Head and Neck Surgery at Mount Sinai West, performed Mount Sinai’s first RFA procedures in August 2019. “I truly believe this procedure will change management and improve outcomes for a subset of patients with symptomatic, noncancerous thyroid nodules,” says Dr. Sinclair. Mount Sinai is also a leader in offering ethanol ablation, a similarly noninvasive procedure.
Thyroid nodules are masses composed of tissue or fluid, or both, that form in the thyroid, a butterfly-shaped gland near the front of the lower neck. Nodules are very common, estimated to be present in 50 percent of those aged 50 and older. More than 95 percent are noncancerous, and most require no intervention. “For noncancerous thyroid nodules, we intervene surgically or with RFA only if the nodules are very large or symptomatic,” Dr. Sinclair explains. “Symptoms may include neck discomfort, neck swelling, difficulty swallowing or breathing, or changes in the voice from pressure on the nerve to the larynx.”
Although invasive surgery is the most common management option, RFA is an important consideration for patients with noncancerous nodules, Dr. Sinclair says. With RFA, surgeons use guided ultrasound to deliver radiofrequency current to heat the thyroid nodule, which shrinks significantly over the next several months. Patients who undergo RFA can return to normal activity the next day and exercise normally within several days, compared with several weeks for patients who undergo standard thyroid surgery. In addition, RFA targets only the nodule, compared with traditional surgery, which usually removes one side of the thyroid and makes lifelong hormone supplements necessary for 20 to 30 percent of patients.
Catherine Sinclair, MD, left, and Maria Brito, MD.
“Radiofrequency ablation for thyroid nodules has been performed in Korea for over a decade and throughout Europe, and their outcomes are excellent. The published data show nodule shrinkage rates of more than 80 percent with RFA that is maintained over years of follow-up,” says Dr. Sinclair, who learned RFA from a pioneer in the field, Jung Hwan Baek, MD, PhD, at the Asan Medical Center in Seoul, South Korea.
Dr. Sinclair also has developed a continuous laryngeal reflex monitoring system that is used during RFA to prevent vocal cord damage and hoarseness, which are potential risks during both RFA and standard surgery. In the system, nerve fibers within the neck are continuously stimulated to check their function, allowing surgeons to quickly take preventive measures against injury. This innovative method does not require a neck incision and is the only monitoring technique available for noninvasive procedures such as RFA.
Mount Sinai is one of the few health systems in the region to offer ethanol ablation. In that procedure, an alcohol solution is injected into thyroid nodules, killing cells and causing the masses to slowly shrink. The procedure leaves only a small scar and is performed in the office with local anesthesia. Dr. Sinclair says ethanol ablation may be more effective than RFA for fluid-filled thyroid cysts, and RFA is a better noninvasive choice for large, solid nodules. A combination of both procedures can be used for cystic/solid lesions. Ethanol ablation is performed at the Mount Sinai Thyroid Center at Union Square by its Director, Maria Brito, MD, Assistant Professor of Medicine (Endocrinology, Diabetes and Bone Disease), Icahn School of Medicine; and Michael Via, MD, Associate Professor of Medicine (Endocrinology, Diabetes and Bone Disease), Icahn School of Medicine; and by Dr. Sinclair at Mount Sinai West.
“The procedures will not necessarily eliminate the nodule completely, and patients will still need to have ultrasound follow-ups to monitor the nodule,” Dr. Brito says. “But in appropriate cases, they are a terrific option. They make it very easy for
the patient.”
Updated on Jun 30, 2022 | Featured, Infectious Diseases, Research
Mount Sinai scientists, from left, Peter Palese, PhD; Florian Krammer, PhD, with a 3D model of the influenza virus hemagglutinin; and Adolfo García-Sastre, PhD.
The quest to develop a universal influenza vaccine that would be administered only once or twice in an individual’s lifetime and cover every strain of the virus moved closer to becoming a reality in October, when researchers at the Icahn School of Medicine at Mount Sinai showed that a novel method of protection against the influenza virus was safe and induced strong immune responses in humans.
The interim results of this phase 1 clinical trial—led by Mount Sinai scientists Florian Krammer, PhD; Peter Palese, PhD; and Adolfo García-Sastre, PhD—were published online in the October 17, 2019, issue of The Lancet Infectious Diseases.
Two types of proteins, hemagglutinin and neuraminidase, cover the surface of the influenza virus. Current influenza vaccines target the head of the hemagglutinin—a structure that changes often. Mount Sinai’s strategy, known as chimeric hemagglutinin (cHA), targets the stalk of the hemagglutinin, which is less variable.
In the Lancet Infectious Diseases study, the research team tested several cHA vaccine regimens in combination with an adjuvant, an ingredient that boosts the immune response to vaccines. All of the regimens induced antibody responses. But, “one vaccine regimen induced a broad antibody response after the first dose, and this response was not only cross-reactive for the currently circulating influenza virus but also to avian (bird) and bat influenza subtypes,” according to Dr. Krammer, Mount Sinai Professor of Vaccinology and Professor of Microbiology at the Icahn School of Medicine at Mount Sinai.
This, he says, showed that one vaccination might be enough to induce protection against changing seasonal influenza viruses and pandemic influenza viruses yet to arise. “The results indicate that we are moving toward a universal influenza vaccine, but these are still interim results.”
Dr. Palese, Horace W. Goldsmith Professor of Medicine, and Professor and Chair of the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, says the “ideal vaccine, given only once in a lifetime and protective against all influenza virus strains,” would go a long way in improving the health of millions of people in the United States and around the world.
A universal vaccine would overcome “antigenic drift,” the small changes in the genes of influenza viruses that render viruses different from one another and allow them to escape human immunity. This is the primary reason why influenza vaccines vary in effectiveness from one season to another and must be updated every year.
Still, influenza vaccines do offer protection from severe disease and physicians strongly recommend that patients get them annually. Despite their widespread availability, however, more than half of Americans were unvaccinated as of the beginning of December 2019, according to NORC at the University of Chicago, which conducts the National Immunization Survey for the U.S. Centers for Disease Control and Prevention (CDC).
Influenza remains deadly for some. The World Health Organization estimates that influenza-related respiratory illnesses account for between 290,000 and 650,000 deaths per year. Dr. Krammer says, “Developing new vaccines takes a lot of time and it’s hard to estimate how long it will take, but I firmly believe we will have a universal flu vaccine in our lifetime and probably sooner.”
In addition to Dr. García-Sastre, a co-senior researcher on the Lancet Infectious Diseases study, and the Irene and Dr. Arthur M. Fishberg Professor of Medicine, and Director of the Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, contributors included Cincinnati Children’s Hospital Medical Center; Duke University School of Medicine; the University of Chicago; and the nonprofit international health organization PATH. Funding was provided by a grant from the Bill & Melinda Gates Foundation.
Nov 25, 2019 | Artificial Intelligence, Featured, Research
Keynote speaker Michael Snyder, PhD
What is the role of artificial intelligence (AI) in medicine, and how is it changing the practice of health care as we know it? That was the subject of the eighth annual SinaInnovations Conference, held Tuesday, October 15, and Wednesday, October 16, in Stern Auditorium. The event featured leading physicians and scientists from academia and industry who spoke about their work in deploying AI—the most powerful technology under development—to augment discovery and clinical use.
Experts shared their experiences in using AI in a variety of ways, from medical imaging, to predicting disease, to keeping people healthy, and highlighted the massive transformation taking place in health care and medicine, where software is driving innovation.
Michael Snyder, PhD, Chair of the Department of Genetics, and Director of the Center for Genomics and Personalized Medicine at Stanford University, a keynote speaker, discussed the role of AI in advancing personalized medicine. “I see a world where, with genome sequencing and continuous monitoring using wearable devices, we can better manage people’s health and hopefully do this at an individual level, and have personal machine-learning algorithms that follow people and their health state,” Dr. Snyder said. “We’re very capable of measuring more things, and here’s an area where AI can make a big impact.”
Melissa A. Haendel, PhD, Director of Translational Data Science at Oregon State University, spoke about her work in leading the federally funded Monarch Initiative, which is building sophisticated algorithms that integrate a multitude of data about rare diseases in order to improve research and clinical care. “No one group is actually annotating a disease model that has all the same attributes,” Dr. Haendel said. “We can’t even count the number of rare diseases.” Her team’s goal, she said, is to pull all of the data together and use it to build models that help physicians make earlier diagnoses, identify biomarkers of disease, and find better treatments.
Conference participants Heather J. Lynch, PhD, Associate Professor of Ecology and Evolution, Stony Brook University, left, and Georgia D. Tourassi, PhD, Director, Health Data Sciences Institute, Oak Ridge National Laboratory.
David Sontag, PhD, Associate Professor of Electrical Engineering and Computer Science at Massachusetts Institute of Technology, discussed how AI can be used to redesign electronic medical records so they can yield more reliable information on the patient’s risk for various diseases. In one case, he said, his team developed a machine-learning algorithm to help an infectious disease clinician at Massachusetts General Hospital and Brigham and Women’s Hospital reduce the number of unnecessary prescriptions for antibiotics.
AI is already playing a role in augmenting radiology. Keith J. Dreyer, DO, PhD, Vice Chairman, Radiology, at Massachusetts General Hospital and Chief Science Officer of the American College of Radiology, told the audience that “AI has huge value” and will be increasingly useful over time as the field matures.
In his keynote address, Pieter Abbeel, PhD, an entrepreneur and Professor of Electrical Engineering and Computer Science at the University of California, Berkeley, showed how deep machine learning takes place through constant repetition. In one example, he illustrated how a robot learns to run. After 2,000 iterations, it will become proficient. By comparison, a healthy human child would learn to run proficiently after roughly two weeks of practice. In many cases, he said, machines have achieved human-level error rates.
Among the many algorithms Stanford University is working on is one that recognizes the photo of a radiological image taken with a mobile phone, according to Curtis Langlotz, MD, PhD, Director of Stanford’s Center for Artificial Intelligence in Medicine and Imaging. This technology would allow general practitioners and other health care professionals in remote areas to use their mobile phones to access an algorithm that would assist them in making medical decisions when a radiologist is not available. For example, they would be able to determine whether a patient with, say, tuberculosis, should be discharged from the hospital.
Speakers and attendees at the conference agreed that AI is both promising and challenging. Suresh Venkatasubramanian, PhD, Professor of Computing at the University of Utah, cautioned that inherent bias in the data will create bias in the algorithms. “Models are fragile,” he said. “The Achilles heel is that the more sophisticated a system gets, especially with deep learning, the more sensitive it gets to small perturbations, and this could wreak havoc on the system.”
Greg Zaharchuk, MD, PhD, Professor of Radiology (Neuroimaging and Neurointervention) at Stanford University, concluded his talk with a nod to the future. “I think we’re only scratching the surface. This is a moment of extreme creativity, and it’s a very exciting time to be in the field.” Rather than replacing radiologists and other medical specialists, he added, AI “is really going to extend our abilities as physicians.”
New Gift Supports Young Entrepreneurs at Mount Sinai
This year, for the first time, a nonprofit biotech accelerator company founded by five former postdocs at the Icahn School of Medicine at Mount Sinai presented the school with a five-year, $50,000 gift to support young entrepreneurs in the New York City area whose science is being used to create therapies, devices, and diagnostics that support human health. The gift from The Keystone for Incubating Innovation in Life Sciences (KiiLN) went to Raymond A. Alvarez, PhD, Assistant Professor of Medicine (Infectious Diseases) at the Icahn School of Medicine at Mount Sinai, who is working on a platform that identifies and studies the antibodies of individuals who are immune to hantaviruses, which are spread by rodents and have a 38 percent mortality rate. Currently, there are no vaccines or treatments for hantaviruses.
Nov 25, 2019 | Featured, Research
Rachel Yehuda, PhD
Rachel Yehuda, PhD, a world-renowned researcher whose pioneering discoveries have revolutionized the study and treatment of post-traumatic stress disorder (PTSD), has been elected to the National Academy of Medicine. Dr. Yehuda is Professor and Vice Chair for Veterans Affairs for the Department of Psychiatry, Professor of Neuroscience, and Director of the Traumatic Stress Studies Division at the Icahn School of Medicine at Mount Sinai. This Division also includes the PTSD Clinical Research Program and the Neurochemistry, Neuroendocrinology, and Molecular Biology Lab at the James J. Peters Veterans Affairs Medical Center in the Bronx.
The National Academy of Medicine is a nonprofit, nongovernmental organization that provides independent, objective analysis and advice on health issues. Its members are elected through a selective process, and election is considered one of the highest honors in health and medicine. With this election, Mount Sinai has 23 faculty members in the Academy.
Traumatic stress first interested Dr. Yehuda when she was a postdoctoral fellow in biological psychology at Yale Medical School in 1987. She and colleagues observed that Vietnam War combat veterans with PTSD had significantly lower levels of cortisol, a steroid hormone that helps regulate physiological responses to stress, compared to those without PTSD. It was a provocative discovery because elevated cortisol levels are typically associated with stress. The work led to a new understanding: In response to acute stress, ample cortisol levels are critical to mobilizing—and then containing—numerous stress-related mediators, such that those who have lower cortisol levels at the time of trauma exposure are at elevated risk for PTSD.
As Dr. Yehuda was concluding her fellowship and about to join the Icahn School of Medicine at Mount Sinai in 1991, she wondered if lower cortisol levels would also be present in other groups of trauma survivors, and initiated biological studies in Holocaust survivors. A pilot study of 100 survivors revealed that half had PTSD, and that they, too, had lower cortisol levels. To continue her work, she established a specialized treatment program for Holocaust survivors and their families at The Mount Sinai Hospital.
After years of study, Dr. Yehuda and her team of researchers had new revelations: that many Holocaust survivors and their adult offspring had epigenetic changes on the same region of a gene known as FKBP5 that is related to stress, demonstrating—for the first time in people—an epigenetic link between parental trauma and offspring effects.
Her current research interests include studying PTSD biomarkers, and other innovative PTSD prevention strategies and treatment, including the use of psychedelic medications. Today, the Icahn School of Medicine at Mount Sinai has one of the largest programs in the nation for the study of PTSD biomarkers.
In April, Dr. Yehuda was named principal investigator of a nearly $6 million grant from the United States Department of Defense through its U.S. Army Medical Research program to test whether a onetime dose of a drug—oral hydrocortisone—can prevent PTSD and related mental health disturbances in both civilians and military personnel.
Oral hydrocortisone is a synthetic glucocorticoid similar to the body’s own cortisol. The double-blind, randomized, placebo-controlled trial will be conducted on 220 recently traumatized patients presenting to the Emergency Department of The Mount Sinai Hospital and Chaim Sheba Medical Center in Israel, an academic research center.
“It has been a privilege to learn from trauma survivors and lead a first-rate research team that is devoted to developing strategies for treating PTSD,” says Dr. Yehuda. “The Icahn School of Medicine has provided the very best possible environment for fostering innovation in psychiatry research.”
Nov 25, 2019 | Artificial Intelligence, Featured, Research
The three team finalists were: George: Katie Depue, David Koellhofer, and Brendan Reilly. Deliberate: Marc Aafjes, Michael Balangue, Do Hyung Kwon, Hansaim Lim, and Paulo Serodio. Deep Brain Precision: John Di Capua, Taylor Miller, Ashley So, and Danielle Soldin.
One hundred eighty medical and graduate students, and others, formed 19 teams to participate in the fourth annual Mount Sinai Health Hackathon in October. The 48-hour competition, held over the weekend leading up to the SinaInnovations Conference, challenged the participants to create novel health care solutions that would expand the limits of human performance.
Three teams each received checks totaling $2,500 and will have the opportunity to pitch their ideas again in 2020 at Mount Sinai’s Innovation Showcase before a group of entrepreneurs and venture capitalists. They will be joined by a fourth wild-card team chosen from the non-finalists.
Scott L. Friedman, MD, Dean for Therapeutic Discovery, and Chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, told the participants, “We started this event four years ago as part of a larger effort to spur innovation. This is really the embodiment of our values about teamwork and doing great things.”
The three team finalists were:
Deliberate: Improving the quality of care in psychotherapy through confidential recording and analysis. Team members: Marc Aafjes, Michael Balangue, Do Hyung Kwon, Hansaim Lim, and Paulo Serodio.
George: An artificial intelligence application that allows dialysis providers to optimize scheduling and improve a clinic’s efficiency. Team members: Katie Depue, David Koellhofer, and Brendan Reilly.
Deep Brain Precision: An app that would allow physicians to monitor a patient’s progress after receiving deep brain stimulation for Parkinson’s disease and other motor disorders. Team members: John Di Capua, Taylor Miller, Ashley So, and Danielle Soldin.
Sponsors and partners: Accenture; Altice Business; Cisco; Farmer’s Fridge; Kitware; PepsiCo; Persistent Systems; the National Center for Advancing Translational Sciences, National Institutes of Health; and the Christopher & Dana Reeve Foundation.
