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MedicalResearch.com Interview with: Dr. Cortes Canteli Marta Cortes Canteli, PhD Miguel Servet Research Fellow Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) Madrid, Spain MedicalResearch.com: What is the background for this study? Response: Alzheimer´s disease is the most common form of dementia affecting more than 30 million people worldwide. Research in recent years has linked the disease to a reduction in the cerebral circulation; this results in an insufficient supply of nutrients and oxygen to brain cells, leading to their death. Alzheimer disease is also known to be linked to an underlying chronic prothrombotic state. The present study combined physiological and molecular analyses to demonstrate that long-term anticoagulation effectively slows disease progression in a transgenic mouse model of Alzheimer disease. MedicalResearch.com: What are the main findings? Response: The main findings are that long-term anticoagulation with dabigatran, an already approved direct oral anticoagulant, inhibits the abnormal formation of fibrin clots in the Alzheimer´s disease brain, hence preserving blood flow and facilitating oxygen and nutrient delivery to the brain. This drug, in turn, also has a beneficial effect on controlling neuroinflammation, maintaining the integrity and functionality of the blood brain barrier and reducing amyloid, the main pathological hallmark of Alzheimer´s disease. MedicalResearch.com: What should readers take away from your report? Response: Long-term treatment with an oral direct anticoagulant ameliorates Alzheimer´s disease pathogenesis in a mouse model of the disease. A pro-thrombotic state is among the mechanisms contributing to Alzheimer´s disease pathogenesis and should be taken into account during diagnosis and treatment. MedicalResearch.com: What recommendations do you have for future research as a result of this work?  Response: Alzheimer´s disease is a multifactorial disorder. If we want to win the battle against it, efforts should be focused toward the development of multidrug individualized therapies targeting the various processes contributing to an individual’s pathology instead of the “1 target, 1 treatment” approach that has not been successful thus far. Our studies indicate that one of the pathological mechanism worth targeting in Alzheimer´s disease is the pro-coagulant state that, in combination with other disease-modifying compounds, might be instrumental in improving Alzheimer´s disease pathogenesis. MedicalResearch.com: Is there anything else you would like to add? Response: Our findings need to be replicated in other animal models, especially in large animals, to ensure robustness and support clinical trials of antithrombotic therapy for prevention or amelioration of Alzheimer´s disease. It is also important to mention that the use of anticoagulants has the important limitation of the increased incidence of bleeding associated with its use. This is especially critical in the frail and elderly Alzheimer´s disease patients who are prone to develop intracerebral hemorrhages. Dabigatran is one of the oral direct anticoagulants that presents a low risk of intracranial bleeding, but the risk is still present and dosing will need to be carefully evaluated by a heart–brain team of experts to ensure its use outweighs any bleeding risk. No disclosures.   Citation: Long-Term Dabigatran Treatment Delays Alzheimer's Disease Pathogenesis in the TgCRND8 Mouse Model Marta Cortes-Canteli, Anna Kruyer, Irene Fernandez-Nueda, Ana Marcos-Diaz, Carlos Ceron, Allison T. Richards, Odella C. Jno-Charles, Ignacio Rodriguez, Sergio Callejas, Erin H. Norris, Javier Sanchez-Gonzalez, Jesus Ruiz-Cabello, Borja Ibanez, Sidney Strickland and Valentin Fuster Journal of the American College of Cardiology Volume 74, Issue 15, October 2019DOI: 10.1016/j.jacc.2019.07.081             The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article

Dr. Atkins   Katelyn M. Atkins MD PhD Harvard Radiation Oncology Program Dana-Farber Cancer Institute Brigham and Women’s Hospital Boston, Massachusetts     MedicalResearch.com: What is the background for this study? What are the main findings?  Lung cancer remains the leading cause of cancer-related death worldwide and nearly half of patients will require radiation therapy as part of their care. Cardiac toxicity following radiotherapy has been well-studied in breast cancer and lymphomas, however the impact of cardiac toxicity following lung cancer radiotherapy has historically been under-appreciated due to the high risk of lung cancer death. Recent studies highlighting cardiac toxicity following lung cancer radiotherapy have been limited by small numbers of patients and, to our best knowledge, have not included validated cardiac event endpoints defined by the American Heart Association (AHA)/American College of Cardiology (ACC). MedicalResearch.com: What did you do to solve this problem in oncology?  We aimed to determine whether cardiac radiation dose exposure was associated with an increased risk of Major Adverse Cardiac Events (MACE), as defined by the AHA/ACC, and mortality. We performed this comprehensive analysis using one of the largest cohorts of locally-advanced lung cancer patients.  MedicalResearch.com: What are the main findings?  We found that despite a high competing risk of death from lung cancer, cardiac radiation dose exposure is a modifiable cardiac risk factor for Major Adverse Cardiac Events and mortality. In particular, patients without pre-existing heart disease had a significantly higher risk of Major Adverse Cardiac Events and mortality when they received higher cardiac radiation doses (≥10 Gy) versus lower cardiac radiation doses ( Read the full article

Dr. Solomon Scott David Solomon, MD Director, Noninvasive Cardiology Professor, Harvard Medical School Brigham and Women's Hospital  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The sodium glucose transport proteins are known to be important in regulating uptake of glucose. SGLT-1 is predominantly located in the gut and is responsible for uptake of glucose and galactose in the small intestine. Individuals born with severe mutations of this gene have severe malabsorption syndrome. We looked at genetic variants that lead to reduced function of the protein, but not complete loss of function, in a large cohort of individuals in the NIH funded Atherosclerosis Risk in Communities Study. We found that those with mutations in the gene had reduced glucose uptake, as measured by an oral glucose tolerance test, as well as less obesity, diabetes, heart failure and death. MedicalResearch.com: What should readers take away from your report? Response: These findings suggest that genetic variation can play a role in our propensity to absorb glucose in the gut and individuals with particular mutations might have a lower risk of cardio metabolic disease. These findings suggest that inhibiting the SGLT-1 receptor might be a useful therapeutic approach. MedicalResearch.com: What recommendations do you have for future research as a result of this work?  Response: It will be important to look at effects of mutations in SLGT-1 in other populations, and to determine if SLGT-1 inhibitors might provide similar benefits. Disclosure: ARIC was funded by the NHLBI. I have received  received research grants to my institution from Alnylam, Amgen, AstraZeneca, Bellerophon, BMS, Celladon, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur, Theracos,  and have consulted for Akros, Alnylam, Amgen, AstraZeneca, Bayer, BMS, Corvia, Gilead, GSK, Ironwood, Merck, Novartis, Pfizer, Roche, Takeda, Theracos, Quantum Genetics,  Cardurion, AoBiome, Janssen, Cardiac Dimensions. None of these grants or relationships funded or played a role in these analyses.  Citation: Genetic Variants in SGLT1, Glucose Tolerance, and Cardiometabolic Risk  Sara B. Seidelmann, Elena Feofanova, Bing Yu, Nora Franceschini, Brian Claggett, Mikko Kuokkanen, Hannu Puolijoki, Tapani Ebeling, Markus Perola, Veikko Salomaa, Amil Shah, Josef Coresh, Elizabeth Selvin, Calum A. MacRae, Susan Cheng, Eric Boerwinkle and Scott D. Solomon Journal of the American College of Cardiology Volume 72, Issue 15, October 2018 DOI: 10.1016/j.jacc.2018.07.061         The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article