Marfan Syndrome

WEDNESDAY, Aug. 21, 2024 -- Artificial intelligence (AI) is able to distinguish Marfan from non-Marfan facial images using ordinary online photographs with an extremely high degree of accuracy, according to a study published in the July 15 issue of Heliyon . Danny Saksenberg, from the Yale University School of Medicine in New Haven, Connecticut, and colleagues explored the potential of AI in diagnosing Marfan syndrome from ordinary online facial images. The model was trained on 80 percent of 672 facial images (182 Marfan and 490 control), while the other 20 percent of images were used as the test set. The researchers found that overall accuracy was 98.5 percent (0 percent false positive; 2 percent false negative). For Marfan faces, the F1 score was 97 percent and the F1 score was 99 percent for non-Marfan faces. The area under the receiver operating curve was 100 percent. "Clinical usefulness of this program is anticipated. However, due to the limited and preliminary nature of this work, this should be viewed as only a pilot study," the authors write. "As AI continues to revolutionize health care, integrating such AI-based models into the diagnostic workflow could substantially enhance early detection and management of conditions like Marfan syndrome. It may be possible to deploy such models to allow for screening in nonspecialist settings, such as with general practitioners, nurses, schools and workplaces." Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Study led by experts at Cincinnati Children's sheds light at the cellular level on how heart valve tissues form. Findings eventually may improve survival odds for newborns with heart valve defects. CINCINNATI, July 30, 2024 /PRNewswire/ -- Imagine a future where doctors could detect and treat potentially fatal heart valve defects months before a baby is born. While this future is still a few years away, scientists have made significant progress by creating a detailed map of how human heart valves form. This new map, published July 24, 2024, in Nature Cardiovascular Research, will help guide future heart research. Continue Reading Healthy vs. defective heart valve formation: On the left side, representing healthy valve development, unidirectional blood flow induces Jag1 production in valve endothelial cells (VECs), which activates NOTCH2-mediated Notch signaling when these cells contact Elastin-expressing valve interstitial cells (VICs). This process promotes downstream elastogenesis-related gene expressions. On the right side, representing defective development, a lack of APOE in pulmonary stenosis patients suppresses Notch signaling, leading to elastogenesis defects. Emerging blueprint for replacement valves that can grow Heart valves might be small, but they're incredibly important. Doctors have been replacing damaged heart valves in adults for many years, and sometimes they can save newborns with artificial valve transplants. But these artificial valves aren't perfect. They don't have living cells, so they can't form a completely normal valve. They also don't grow with the child, which means the child might need several risky surgeries as they get older. "Engineered human heart valves with the appropriate cell types for transplantation would avoid repeated surgeries in babies and address the donor valve shortage," says corresponding author Mingxia Gu, MD, PhD, an expert in molecular and cardiovascular biology at Cincinnati Children's. "Now, we've achieved an unprecedented understanding of the cellular composition of human heart valves and how fetal heart valve tissue changes over time. This is a crucial first step for future human valve engineering." How do heart valve leaflets form? The human heart has four valves that control the flow of blood through the heart's chambers. Each valve has two or three thin and fragile-seeming leaflets that open and close more than 2.5 billion times across a lifetime. When a baby is growing in the womb, the cells that make up these leaflets change completely. At 14 weeks, the leaflets are mostly made of complex sugars. By 36 weeks, they turn into three-layered tissues with a mix of flexible and stiff fibers. If these leaflets don't form correctly, it can cause serious heart problems. Heart valve birth defects are rare. The most common type, called bicuspid aortic valve, occurs among an estimated 0.5% to 2% of people. This condition occurs when two of the normal three leaflets of the aortic valve stick together. Those affected need life-long monitoring may require valve replacement surgery at some point. Other conditions that can involve defective heart valves include valve prolapse in Marfan syndrome, a narrow pulmonary valve in tetralogy of Fallot, and a missing aortic valve in hypoplastic left heart syndrome. Unexpected role played by the gene APOE The Cincinnati Children's research team studied healthy and faulty heart valves all the way down to the single-cell level. They documented in unprecedented detail how various cell types signal each other to form valve tissues. In a key finding, the team discovered a cell type that expresses high levels of the gene APOE. This gene needs to work in concert with another gene called NOTCH2 to make the elastin fibers essential for heart valve function. The involvement of APOE was surprising because previously the gene had been known only for its role in atherosclerosis and Alzheimer's disease. The paper further describes signaling "crosstalk" among key genes as they instruct developing cells to form the heart valve tissues. This process continues as the fetus grows and continues after birth until the heart reaches its full adult size. "The finding of APOE as the top regulator in modulating elastin formation during early valve formation could yield a new angle for clinicians to understand heart valve underdevelopment," says co-corresponding author Yifei Miao, MBBS, PhD. How can these findings help people with heart valve defects? Researchers will need several more years to figure out how to use these new discoveries to help people. Knowing which genes are key for making the various parts of heart valves—and which ones function incorrectly in babies with heart valve defects—will provide vital clues for creating future gene or cell therapies. One exciting idea is to use the new atlas to engineer a "human valve" for valve replacement therapy. Currently, replacement valves include mechanical devices, biological ones made from cow or pig tissue, and some human valves obtained from donated organs. The new atlas may help scientists build or "grow" human-tissue valves in the lab. "This atlas provides insights into the similarities and differences among the four human valves, enabling more precise valve engineering and deep understanding of the valve-specific phenotypes in patients," Gu says. "The newly discovered APOE+ valve cell type could be crucial for seeding onto an engineered valve scaffold to mediate elastin fiber formation, which is essential for valve remodeling and function." About the study Cincinnati Children's co-authors also included Ziyi Liu, MD, Yu Liu, PhD, Zhiyun Yu, PhD, Cheng Tan, MD, Nicole Pek, BSc, Anna O'Donnell, BS, MBA, Minzhe Guo, PhD, Katherine Yutzey, PhD, and David Winlaw, MBBS, MD, (now at Lurie Children's Hospital). Co-authors also included experts with the Stanford School of Medicine, the University of Michigan, the University of Washington, and the Icahn School of Medicine at Mount Sinai, New York. Funding sources for this study include support from Additional Ventures (1019125), an Endowed Scholar Award from Cincinnati Children's, two grants from the Chan Zuckerberg Initiative (CZF2019-002440 and CZF2021-237566), and two American Heart Association Predoctoral Fellowship grants (1013861 and 906513). This research was further supported by the Cincinnati Children's Heart Institute Biorepository, the Discover Together Biobank, the Division of Pulmonary Biology, and core research facilities in Pathology and Confocal Imaging. SOURCE Cincinnati Children's Hospital Medical Center

2024 Harrington Prize for Innovation in Medicine Recognizes Pioneering Work in Immunology CLEVELAND, March 19, 2024 /PRNewswire/ -- The eleventh annual Harrington Prize for Innovation in Medicine has been awarded to Arlene H. Sharpe, MD, PhD, Kolokotrones University Professor and Chair of the Department of Immunology at Harvard Medical School. The award recognizes her breakthrough discoveries in immune regulation, which have established foundational principles in immunology and led to new cancer therapies that act by boosting the immune response to cancer. The Harrington Prize for Innovation in Medicine, established in 2014 by the Harrington Discovery Institute at University Hospitals and the American Society for Clinical Investigation (ASCI), honors physician-scientists who have moved science forward with achievements notable for innovation, creativity and potential for clinical application. Dr. Sharpe's research in immunology has led to significant advances in medical treatments. Her work helped identify key pathways that restrain the activity of T lymphocytes (immune cells) to fight cancer. Her work defined the PD-1 pathway and its immunoinhibitory functions as well as the inhibitory functions of CTLA-4 to restrain the activity of the immune system. Dr. Sharpe's research thus laid the foundation for the development of 'immune checkpoint inhibitors', drugs that target PD-1 and related pathways. These therapies, including pembrolizumab and nivolumab, have been approved by the FDA for treating numerous types of cancer. They work by preventing inhibition of T cell function, thereby unleashing the body's immune system to fight cancer cells more effectively. This approach has become a cornerstone in cancer treatment strategies. "Dr. Sharpe's body of work has shaped our understanding of the role of the T cell in regulating the immune response. Her innovative scientific discoveries are among the best examples of bench-to-bedside work in the past three decades," said Benjamin D. Humphreys, MD, PhD, Joseph Friedman Professor of Renal Diseases in Medicine and Chief, Division of Nephrology, Washington University in St. Louis and 2023-2024 President of the ASCI. "Immune checkpoint inhibitors are drugs that allow for dramatic remission, and even cures, of cancers that had previously been considered untreatable. Dr. Sharpe's foundational insights have thus been harnessed to transform cancer therapy. Her work provides a beautiful example of physician impact through creative science," said Jonathan S. Stamler, MD, President, Harrington Discovery Institute, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation and Professor of Medicine and of Biochemistry at University Hospitals and Case Western Reserve University. A committee composed of members of the ASCI Council and the Harrington Discovery Institute Scientific Advisory Board reviewed nominations from leading academic medical centers globally before selecting the 2024 Harrington Prize recipient. In addition to sharing the Prize's $20,000 honorarium, Dr. Sharpe will deliver the Harrington Prize Lecture at the 2024 AAP/ASCI/APSA Joint Meeting on April 5, will be a featured speaker at the 2024 Harrington Scientific Symposium May 22-23, and will publish an essay in the Journal of Clinical Investigation. The Harrington Prize has recognized outstanding and diverse innovations in medicine: 2014: Harry Dietz, MD, Johns Hopkins University, for his contributions to the understanding of the biology and treatment of Marfan syndrome, a disorder leading to deadly aneurysms in children and adults. 2015: Douglas R. Lowy, MD, The National Cancer Institute, in recognition of his discoveries that led to the development of the Human Papillomavirus vaccine to prevent cervical cancer. 2016: Jeffrey M. Friedman, MD, PhD, The Rockefeller University, for his discovery of leptin, which controls feeding behavior and is used to treat related clinical disorders. 2017: Jointly awarded to Daniel J. Drucker, MD, Mount Sinai Hospital, Canada, Joel F. Habener, MD, Massachusetts General Hospital, and Jens J. Holst, MD, DMSc, University of Copenhagen, Denmark, for their discovery of incretin hormones and for the translation of these findings into transformative therapies for major metabolic diseases such as diabetes. 2018: Helen H. Hobbs, MD, UT Southwestern Medical Center, for the discovery of the link between a gene mutation (PCSK9) and lower levels of LDL, which has improved the treatment of high cholesterol. 2019: Carl H. June, MD, University of Pennsylvania, for advancing the clinical application of CAR T therapy for cancer treatment, and for his sustained contributions to the field of cellular immunology. 2020: Stuart H. Orkin, MD, Harvard University, for breakthrough discoveries on red blood cells that offer new treatments for patients with sickle cell disease and beta-thalassemia, which are among the most common genetic disorders. 2021: Warren J. Leonard, MD, and John J. O'Shea, MD, NIH, for their respective contributions to the field of immunology, from fundamental discovery to therapeutic impact. 2022: James E. Crowe Jr., MD, and Michel C. Nussenzweig, MD, PhD, for their groundbreaking work, which has elucidated fundamental principles of the human immune response and enabled the use of human antibodies to treat COVID-19. 2023: Jean Bennett, MD, PhD, and Albert M. Maguire, MD, for their groundbreaking translational research to restore sight in inherited genetic diseases. SOURCE Harrington Discovery Institute