Author Interviews, Heart Disease, Nature, Stanford / 30.06.2016

MedicalResearch.com Interview with: Mark Mercola, Ph.D. Professor, Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute La Jolla, California 92037 Professor, Stanford Cardiovascular Institute and Stanford University School of Medicine Stanford, CA, 94305, MedicalResearch.com: What is the background for this study? What are the main findings? Response: Heart disease, especially after heart attack (myocardial infarction) is a major cause of death worldwide, accounting for over 13% of all human mortality. There is a major search for ways to treat the immediate cause or lessen the effect of a heart attack. One way researchers have considered is to boost the blood vessels that nourish the heart muscle. The heart muscle is nourished by many small blood vessels. We found a normal protein that acts as a high level regulator of blood vessel formation in the heart. This protein, known as RBPJ, suppresses the factors that make vessels grow. Therefore, we found that inhibiting this protein made more vessels, and consequently protected the hearts from the damage of a heart attack. (more…)
Author Interviews, Emergency Care, Neurological Disorders, NYU, Pain Research / 30.06.2016

MedicalResearch.com Interview with: Mia Minen, MD, MPH Assistant Professor of Neurology NYU Langone Medical Center MedicalResearch.com Editor’s note: The American Headache Society has issued new guidelines on “The Management of Adults With Acute Migraine in the Emergency Department” (1,2) Dr. Minen, Director of Headache Services at NYU Langone Medical Center, discusses these new guidelines below. MedicalResearch.com: What is the background for these new guidelines? How common/severe is the issue of migraine or headache presentation to the ER? Dr. Minen: These guidelines were needed because previous research shows that there are about 1.2. million visits to the emergency department (ED) each year for migraine, and over 25 different medications are sometimes used for treatment. Many of these medications don’t have evidence-based data to back their usage, and opioids are especially likely to be prescribed in between 60 and 70 percent of these cases, despite their lack of efficacy and risks. The American Headache Society convened an expert panel to review the existing evidence on all the medications used to treat migraines in the ED, and we developed these new treatment guidelines. (more…)
Author Interviews, Cancer Research, Leukemia, NEJM, Stanford / 29.06.2016

MedicalResearch.com Interview with: Jason R. Gotlib, MD The Clinical Investigator Pathway Hematology Division Stanford University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background is that advanced forms of systemic mastocytosis, which are blood cancers characterized by accumulation of abnormal mast cells in the bone marrow and additional organs, represent a group of orphan diseases with a large unmet need. Approximately 90% of patients harbor the acquired KIT D816V mutation, a mutated receptor tyrosine kinase on the surface of mast cells which a primary driver of disease pathogenesis. Only 1 drug is approved for patients with one form of advanced systemic mastocytosis, termed ‘aggressive systemic mastocytosis, or ‘ASM’. This therapy is imatinib (Gleevec), but it is only approved for patients without the KIT D816V mutation, or with KIT mutation status unknown because the KIT D816V mutation is resistant to imatinib. Therefore, this drug may only be useful for approximately 10% of patients. Other drugs that have been used off-label for systemic mastocytosis (but are not approved for this indication) include interferon-alpha or cladribine, which show some activity, but their evaluation to date has been primarily limited to small case series which are usually retrospective in nature, and include mixed populations of systemic mastocytosis patients who have both early stage disease without organ damage (e.g. indolent systemic mastocytosis) and and advanced stage patients, as included in this trial, who have one or more findings of organ damage. Also, those trials employed differing response criteria and no central adjudication of eligibility and response assessments was undertaken. Midostaurin is a multikinase inhibitor with activity against both wild-type KIT, but most importantly, KIT D816V (in contrast to imatinib). Prior work demonstrated that cell lines transformed with the KIT D816V mutation can be inhibited at relatively low concentrations of midostaurin. These concentrations could also be achieved in vivo (e.g. at concentrations achievable in the blood of patients). Cell lines transformed by KIT D816V could not be inhibited by imatinib. (more…)
Author Interviews, Dermatology, JAMA, OBGYNE, Sexual Health, Social Issues, UCSF / 29.06.2016

MedicalResearch.com Interview with: Tami Rowen MD MS Obstetrics, Gynecology and Reproductive Sciences UCSF MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study sought to answer the question of which women are engaging in genital grooming and understand their motivations. Prior studies have been limited by geography and age thus our goal was to provide a nationally representative sample of women. (more…)
Author Interviews, CHEST, Critical Care - Intensive Care - ICUs, Heart Disease, University of Michigan / 29.06.2016

MedicalResearch.com Interview with: Thomas Valley, MD, MSc Fellow, Pulmonary and Critical Care University of Michigan Ann Arbor, MI 48109-2800 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hospitalizations for cardiovascular condition such as acute myocardial infarction (AMI) and heart failure (HF) are incredibly common and costly. Yet, about 20% of hospitalized patients with these conditions receive substandard care. We assessed whether there was an association between the quality of care a hospital provided for AMI or heart failure and how frequently a hospital used the ICU. We found that hospitals with the highest rates of ICU use for AMI or HF delivered worse quality of care and had higher 30-day mortality for these conditions. (more…)
Author Interviews, Heart Disease, PNAS, UT Southwestern / 28.06.2016

MedicalResearch.com Interview with: Dr. Audrey Chang, PhD Kamm-Stull Lab UT Southwestern Medical Center [email protected] MedicalResearch.com: What is the background for this study? What are the main findings? Response: The heart is a singular kind of muscle that contracts and relaxes continuously over a lifetime to pump blood to the body’s organs. Contractions depend on a motor protein myosin pulling on actin filaments in specialized structures. Heart contraction is improved when myosin has a phosphate molecule attached to it (phosphorylation), and a constant amount of phosphorylation is essential for normal heart function. The amount of phosphorylation necessary for optimal cardiac performance is maintained by a balance in the activities of myosin kinase enzymes that add the phosphate and an opposing phosphatase enzyme that removes the phosphate. If the amount of phosphorylation is too low, heart failure results. Animal models with increased myosin phosphorylation have enhanced cardiac performance that resist stresses that cause heart failure. In this recent study reported in PNAS, a new kinase that phosphorylates myosin in heart muscle, MLCK4, was discovered and its crystal structure reported, a first for any myosin kinase family member. Compared to distinct myosin kinases in other kinds of muscles (skeletal and smooth), this cardiac-specific kinase lacks a conserved regulatory segment that inhibits kinase activity consistent with biochemical studies that it is always turned on. Additionally, another related myosin kinase found only in heart muscle (MLCK3) contains a modified regulatory segment, allowing partial activity enhanced by the calcium modulator protein, calmodulin. Thus, both myosin kinases unique to cardiac muscle provide phosphate to myosin in normal beating hearts to optimize performance and prevent heart failure induced by stresses. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Memory, University Texas / 28.06.2016

MedicalResearch.com Interview with: Timothy Q. Duong, Ph.D Stanley I. Glickman MD Professor of Ophthalmology, Radiology, and Physiology South Texas Veterans Health Care System, VA Southwest National Primate Research Center University of Texas Health Science Center San Antonio, Texas MedicalResearch.com: What is the background for this study? What are the main findings? Response: A single oral dose of methylene blue increased fMRI response in the bilateral insular cortex during a task that measured reaction time to a visual stimulus. The fMRI results also showed an increased response during short-term memory tasks involving the brain’s prefrontal cortex, which controls processing of memories. Methylene blue was also associated with a 7 percent increase in correct responses during memory retrieval. The findings suggest that methylene blue can regulate certain brain networks related to sustained attention and short-term memory after a single oral low dose. (more…)
Author Interviews, Beth Israel Deaconess, Nature, Vaccine Studies, Zika / 28.06.2016

MedicalResearch.com Interview with: Dan Barouch, M.D., Ph.D. Professor of Medicine Harvard Medical School Ragon Institute of MGH, MIT, and Harvard Director, Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: We showed that two vaccines, a DNA vaccine and a purified inactivated virus vaccine, both provided complete protection against Zika virus challenge in mice. To the best of our knowledge, this is the first demonstration of Zika vaccine protection in any animal model. (more…)
Addiction, Annals Internal Medicine, Author Interviews, Opiods, UCSF / 28.06.2016

MedicalResearch.com Interview with: Phillip O. Coffin, MD, MIA Director of Substance Use Research San Francisco Department of Public Health Assistant Professor, Division of HIV, ID & Global Health University of California, San Francisco MedicalResearch.com: What is the background for this study? What are the main findings? Response: San Francisco has a longstanding naloxone distribution program that primarily works out of syringe exchange programs and is temporally associated with a substantial decline in opioid overdose death due to heroin or involving injection drug use. Over 90% of opioid overdose deaths from 2010-2012 were due to prescription opioids in the absence of heroin, and most of those decedents were prescribed opioids in primary care settings. Based on these data, as well as anecdotal reports from sites such as U.S. Army Fort Bragg in North Carolina - where providing naloxone to pain patients appeared to be associated with a radical decline in opioid overdose admissions to the emergency department - we implemented a naloxone prescribing program in the safety net primary care clinics. We recommended that providers offer naloxone to all patients who used opioids on a regular basis, or were otherwise at risk for experiencing or witnessing an opioid overdose, although we only measured outcomes related to patients who were prescribed opioids for chronic pain. We also recommended that providers avoid the term "overdose" as that term does not properly reflect the epidemiology of opioid poisoning and is interpreted by many to mean intentionally consuming a large amount of opioids; instead we recommended saying things like: "Opioids can cause bad reactions where you stop breathing or can't be woken up." Providers prescribed mostly the jerry-rigged nasal device, with the atomizer and a brochure dispensed at clinic and the naloxone picked up at the patients' usual pharmacies, to approximate real-world medical practice. (more…)
Author Interviews, NYU, Sleep Disorders / 27.06.2016

MedicalResearch.com Interview with: Valerie Newsome, PhD, Postdoctoral fellow Department of Population Health, Division of Health and Behavior NYU Langone Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although sleep duration has been related to a number of negative health outcomes, few studies have examined the relationship between place of birth and sleep duration. We examined data for 416,152 adult participants living in the United States between 2000-2013 who responded to the National Health Interview Survey (NHIS); associations were explored between healthy sleep duration (7-8hrs.), references to unhealthy sleep duration (8 hrs.) and place of birth. After adjusting for socio-demographic factors, health risks, and physician-diagnosed medical conditions, multivariate logistic regression revealed that respondents born in the Indian subcontinent were more likely to report healthy sleep duration, compared with US-born respondents (OR=1.86, 95% CI: 1.57-2.20, p < 0.001), while individuals born on the continent of Africa were least likely to report healthy sleep duration (OR= 0. 86, 95% CI: 0.73-1.02, p< 0.001). We also noted a trend suggesting that the longer immigrants reside in the U.S., the greater their likelihood to experience unhealthy sleep. (more…)
Author Interviews, BMJ, Immunotherapy, Johns Hopkins, Rheumatology / 27.06.2016

MedicalResearch.com Interview with: Laura C. Cappelli, M.D Johns Hopkins University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: We had been referred several patients with inflammatory arthritis or dry mouth and dry eyes after being treated with immune checkpoint inhibitors. When searching the literature for information on how to evaluate and treat these patients, we realized that there was minimal information available. We wanted to describe our experience and inform the medical community about these events so that recognition could increase. (more…)
Author Interviews, Heart Disease, JAMA, Pharmacology, UCSF / 27.06.2016

MedicalResearch.com Interview with: Dr. Gregory M. Marcus MD Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS Director of Clinical Research Division of Cardiology Endowed Professor of Atrial Fibrillation Research  University of California, San Francisco MedicalResearch.com: What is the background for this study? What are the main findings? Response: Conduction system disease, or blockages in the electrically system (as opposed to blockages in the blood vessels, of which most are well-aware), is a common condition responsible for both heart failure in many patients as well as the need for pacemaker implantation. Although treatments for the disease are available, there are no known means to prevent it. This is important as the primary treatment, a pacemaker, can itself cause problems (including procedural complications, a long-term risk of infection with repeated battery changes, and even a greater risk of heart failure). In addition, predictors of what types of individuals are at risk for developing conduction disease has largely remained unknown. Based on the fact that the majority of conduction disease is due to fibrosis, or scarring, of the conduction system, we sought to test the hypothesis that a common drug for high blood pressure with anti-fibrotic properties, Lisinopril, might reduce the risk of new conduction system disease. We took advantage of the fact that more than 20,000 patients with hypertension were randomized to three common high blood pressure drugs that work via different mechanisms in the ALLHAT trial: Lisinopril, amlodipine, and chlorthalidone. We found that participants randomly assigned to Lisinopril were statistically significantly less likely to develop conduction disease. In addition, our analyses revealed several risk factors for the development of conduction disease: older age, male sex, diabetes, smoking, a thicker heart, and white race (compared to black race). (more…)
Author Interviews, Colon Cancer, Geriatrics, Kaiser Permanente, NIH / 27.06.2016

MedicalResearch.com Interview with: Carrie N. Klabunde, PhD Office of Disease Prevention Office of the Director NIH Rockville MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many studies of colorectal cancer screening focus on adults 50-75 years of age; few specifically look at screening in the elderly. We wanted to examine colorectal cancer screening use, including follow-up diagnostic testing for those with abnormal fecal blood screening tests, in adults 65 years of age and older. We also wanted to assess whether screening use in this population is influenced more by elderly individual’s chronological age, or their health status (called comorbidity in our study). The study was conducted in three large, integrated healthcare systems: Kaiser Permanente in Northern California and Southern California, and Group Health in Washington state and Idaho. We examined data on nearly 850,000 patients aged 65-89. (more…)
Author Interviews, NEJM, OBGYNE, University Texas, Zika / 26.06.2016

MedicalResearch.com Interview with: Abigail R.A. Aiken, MD, MPH, PhD Assistant Professor LBJ School of Public Affairs University of Texas at Austin Austin, TX, 78713 MedicalResearch.com: What is the background for this study? Response: As Zika began to emerge as an epidemic in Latin America and its links with microcephaly began to be realized, we were aware that women in the region who were already pregnant or who would become pregnant would have a very limited set of reproductive options. Research and media attention about the possible biological effects of Zika in pregnancy began to appear rapidly. But much less attention was been paid to the impacts of Zika on women. We followed the responses of governments and health organizations and when they began to issue advisories warning women to avoid pregnancy, we knew it would be important to investigate the impacts of those advisories. A country-wide policy that is impossible to follow if you are pregnant or cannot avoid pregnancy is an unusual and important public issue. Accurate data on abortion are very difficult to obtain in Latin America because in most countries, abortion is highly restricted. We wanted to provide a window on the issue of how women were responding to the risks of Zika and its associated advisories, so we worked with Women on Web (WoW), an online non-profit telemedicine initiative that provides safe medical abortion to women in countries where safe, legal abortion is not universally available. (more…)
Author Interviews, Bone Density, Endocrinology, Menopause, Mineral Metabolism, UCLA / 25.06.2016

MedicalResearch.com Interview with: Albert Shieh, MD Division of Endocrinology, Diabetes and Hypertension David Geffen School of Medicine University of California, Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Response: Whether an individual loses or gains bone mass is dependent on how much bone is being broken down (by osteoclasts) and being formed (by osteoblasts). Both processes occur simultaneously in the human body. At present, we can measure markers of bone breakdown (resorption) and formation. However, we hypothesized that to better predict the amount of bone mass that will be lost in the future, these markers should be combined in an "index" to reflect both processes, rather than being interpreted in isolation. Indeed, we found that the ability of our new bone balance index predicted future bone loss across the menopause transition better than the bone resorption marker alone. (more…)
Author Interviews, Genetic Research, Science, University Texas / 25.06.2016

MedicalResearch.com Interview with: Jared Ellefson, PhD Postdoctoral fellow University of Texas Austin's Center for Systems and Synthetic Biology MedicalResearch.com: What is the background for this study? What are the main findings? Response: Reverse transcriptases (RT) have revolutionized the field of biology - enabling the conversion of RNA into DNA. This initially allowed the cloning of mature messenger RNA into cDNA libraries (e.g. cloning human genes), but has since been finding a more modern role in high throughput RNA-seq which can accurately depict the physiological status of a cell. Despite its critical role, an inherent flaw exists in all known reverse transcriptases. They make many errors while copying RNA - due to the lack of an error-checking (proofreading) domain. Consequently, the errors produced in reverse transcription are propagated into RNA sequencing potentially leading to corrupted data. The reason for the low fidelity of reverse transcriptases is due to their evolutionary heritage. All RTs are evolved from polymerase enzymes which lack the proofreading domain. This is in stark contrast to certain DNA polymerases which have extreme fidelity. The idea was, what if you could take a high fidelity DNA polymerase and transform it into a high fidelity RT. To do this we developed directed evolution techniques that would enrich these DNA polymerases for reverse transcriptase activity. After a monumental engineering effort, we were left with the world's first reverse transcriptase that could error-check during polymerization. We found that this increased the fidelity of RNA sequencing, in addition to a number of other interesting properties (for instance this single enzyme can do both reverse transcription and PCR). (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, MRI, Surgical Research / 24.06.2016

MedicalResearch.com Interview with: Eva C. Gombos, MD Assistant Professor, Radiology Harvard Medical School Brigham and Women’s Hospital MedicalResearch.com: What is the background for this study? Response: Treatment of early stage breast cancer, breast-conserving therapy (BCT), which consists of lumpectomy followed by whole-breast irradiation, requires re-excision 20 %–40% of patients due to positive margins. Breast MR is the imaging modality with the highest sensitivity to detect breast cancer. However, patients who undergo breast MR imaging have not experienced reduced re-excision or improved survival rates. Our hypothesis is that supine (performed with patient lying on her back) MR imaging within the operating room can be used to plan the extent of resection, to detect residual tumor immediately after the first attempt at definitive surgery, and to provide feedback to the surgeon within the surgical suite. The aim of this study was to use intraoperative supine MR imaging to quantify breast tumor deformation and displacement secondary to the change in patient positioning from imaging (prone performed the patient lying on her stomach) to surgery (supine) and to evaluate the residual tumor immediately after BCT. (more…)
Anesthesiology, Author Interviews, Cognitive Issues, NYU, Pediatrics, Science / 23.06.2016

MedicalResearch.com Interview with: Guang Yang, Ph.D. Assistant Professor NYU Langone School of Medicine Alexandria Center for Life Sciences New York, NY 10016 MedicalResearch.com: What is the background for this study? How common is the problem of long-lasting behavioral deficits after repeated anesthesia exposure in neonates? Response: Each year, in the United States alone, more than 1 million children under 4 years of age undergo surgical procedures that require anesthesia. Many lines of evidence from animal studies have shown that prolonged or repeated exposure to general anesthesia during critical stages of brain development leads to long-lasting behavioral deficits later in life. The results from human studies are less clear, although some studies suggest a higher incidence of learning disabilities and attention-deficit and hyperactivity disorders in children repeatedly exposed to procedures requiring general anesthesia. To date, there has been no effective treatment to mitigate the potential neurotoxic effects of general anesthesia. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Heart Disease, JAMA, Pharmacology / 22.06.2016

MedicalResearch.com Interview with: Thomas Andrew Gaziano, MD, MSc Department of Cardiology Assistant Professor Harvard Medical School MedicalResearch.com: What is the background for this study? Response: Heart failure (HF) is the leading cause of admissions to hospitals in the United States and the associated costs run between $24-47 billion annually. Targeting neurohormonal pathways that aggravate the disease has the potential to reduce admissions. Enalapril, an angiotensin converting enzyme-inhibitor (ACEI), is more commonly prescribed to treat HF than Sacubitril/Valsartan, an angiotensin-receptor/neprilysin inhibitor (ARNI). The latter was shown to reduce cardiovascular death and hospitalizations due to heart failure in a multi-country, randomized clinical (PARADIGM-HF), compared to Enalapril. In order to assess the cost-effectiveness of Sacubitril/Valsartan, compared to Enalapril, in the United States, we created a model population with population characteristics equivalent to the population in the PARADIGM-HF trial. Using a 2-state Markov model we simulated HF death and hospitalizations for patients with a left ventricular ejection fraction (LVEF) of 40% or less. (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, Nutrition, Prostate Cancer / 22.06.2016

MedicalResearch.com Interview with: Dr. Ying Bao Sc.D., M.D Assistant Professor of Medicine Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nuts are rich in bioactive macronutrients, micronutrients, tocopherols and phytochemicals. Current epidemiological evidence has consistently linked increased nut consumption to reduced risk of several chronic conditions including cardiovascular diseases, type 2 diabetes, and inflammation. In contrast, evidence on nut consumption and cancer risk has been insufficient and equivocal. Prostate cancer is the leading cancer among U.S. men, with approximately 220,800 new cases diagnosed in 2015. However, very few studies have investigated the association between nut intake and prostate cancer. Thus, in the current study, we followed 47,299 US men from 1986-2012, and examined (1) whether consuming more nuts prevents getting prostate cancer, and (2) whether consuming more nuts reduces death rates among non-metastatic prostate cancer patients. During 26 years of follow-up, 6,810 men were diagnosed with prostate cancer, and 4,346 of these patients were without metastasis at diagnosis. We found no association between nut intake and being diagnosed with prostate cancer. However, among non-metastatic prostate cancer patients, those who consumed nuts 5 or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month. (more…)
Author Interviews, MRI, Neurological Disorders, Neurology, NIH, Stroke / 22.06.2016

MedicalResearch.com Interview with: Dr. Richard Leigh MD Neuro Vascular Brain Imaging Unit National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients who suffer an ischemic stroke have limited treatment options. One of the reasons for this is that our treatments can sometimes make the stroke worse by transforming the ischemic stroke into a hemorrhagic stroke. In our study we identified a new piece of information that we can extract from the patient’s MRI scan that informs us on the risk of having a hemorrhage. (more…)
Author Interviews, Heart Disease, JACC, UCSD / 22.06.2016

MedicalResearch.com Interview with: Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS Assistant Professor Cardiac Electrophysiology, Division of Cardiology University of California, San Diego (UCSD) MedicalResearch.com: What is the background for this study? Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and imparts significant stroke risk. In patients with AF determined to be at intermediate to high risk for thromboembolism, anticoagulation with warfarin (a vitamin K antagonist) or the newer non-vitamin K antagonist oral anticoagulants clearly reduces morbidity and mortality compared to aspirin. We sought to evaluate practice patterns of cardiovascular specialists in the United states to determine how often AF patients at risk for stroke are prescribed aspirin over oral anticoagulation, and predictors of this practice. (more…)
Author Interviews, Heart Disease, JAMA, Race/Ethnic Diversity, UCSF / 22.06.2016

MedicalResearch.com Interview with: Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS Director of Clinical Research Division of Cardiology Endowed Professor of Atrial Fibrillation Research University of California, San Francisco MedicalResearch.com: What is the background for this study? What are the main findings? Response: We and others have previously demonstrated that, despite the observation that African Americans on average exhibit more risk factors for atrial fibrillation, they demonstrate a substantially reduced risk of the disease. This suggests that, if we could understand the mechanism underlying this apparent paradox, we might learn something fundamentally important to atrial fibrillation that would be relevant to treating or preventing the disease regardless of race. Building on our previous work demonstrating that, among African Americans, more European ancestry (determined by genomic testing) was a statistically significant predictor of atrial fibrillation, we sought to identify the gene(s) that might underlie this observation. The analysis took two forms. First, we examined if any differences among several well-established single nucleotide polymorphisms (SNP) associated with atrial fibrillation might mediate the race-atrial fibrillation relationship. One such SNP statistically mediated (rs10824026) up to about a third of the race-atrial fibrillation relationship. It’s important to mention that a causal relationship cannot be proven here. Perhaps more remarkable was the observation that the disease-associated alleles of the SNPs most closely associated with atrial fibrillation in multiple studies were actually significantly more common among African Americans, pointing to the complex nature of both the race-atrial fibrillation relationship as well as the genetics of atrial fibrillation. Finally, leveraging the ancestral relationships, we performed a genome wide admixture mapping study with the hope of reducing the penalty for multiple hypothesis testing incurred in conventional genome wide association studies. While several loci revealed associations with atrial fibrillation with small p values, none met our criteria for genome wide significance. (more…)
Author Interviews, Heart Disease, JAMA, Pharmacology, UCLA / 22.06.2016

MedicalResearch.com Interview with: Gregg C. Fonarow, MD, FACC, FAHA Eliot Corday Professor of Cardiovascular Medicine and Science Director, Ahmanson-UCLA Cardiomyopathy Center Co-Chief of Clinical Cardiology, UCLA Division of Cardiology Co-Director, UCLA Preventative Cardiology Program David Geffen School of Medicine at UCLA Los Angeles, CA, 90095-1679 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Fonarow: Angiotensin receptor neprilysin inhibitors (ARNI) have been demonstrated to reduce mortality in patients with heart failure with reduced ejection fraction. However, to date, the population level impact of optimal implementation of this therapy in the United States has not been evaluated. This new analysis estimates that as many 28,484 deaths in heart failure with reduced ejection fraction patients annually could be prevented or postponed with optimal use of angiotensin receptor neprilysin inhibitors (with sensitivity analyses demonstrating a range of 18,230 to 41,017). (more…)
Author Interviews, Journal Clinical Oncology, Karolinski Institute, Leukemia / 22.06.2016

MedicalResearch.com Interview with: Hannah Bower, MSc Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previously, if left untreated or with symptomatic treatment (up to the 1970’s), the median survival time of patients with chronic myeloid leukemia (CML) ranged between two and three years. Later, interferon alpha and allogeneic stem cell transplantation were introduced. However, improvements in survival were mainly seen in younger patients. Treatment with the tyrosine-kinase inhibitor (TKI) imatinib-mesylate (Glivec®, Gleevec®) began in Sweden in the early 2000 resulting in major survival improvements, with the exception of the old/very elderly. We investigated if these improvements continued to 2013 and if improvements are now observed in the elderly via the life expectancy and the loss in expectation of life; the latter of these quantifies the change in the life expectancy due to a diagnosis of CML. The great improvements in life expectancy, especially in the youngest patients, translate into great reductions in the loss in expectation of life. The major factor contributing to the improvement in the elderly is likely the increasing use of TKIs. (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA, Personalized Medicine, UCSF / 21.06.2016

MedicalResearch.com Interview with: Peter Ganz, MD Chief, Division of Cardiology Director, Center of Excellence in Vascular Research Zuckerberg San Francisco General Hospital Maurice Eliaser Distinguished Professor of Medicine University of California, San Francisco MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ganz:  The research described in the JAMA paper involved measuring 1,130 different proteins in nearly 2000 individuals with apparently stable coronary heart disease, who were followed up to 11 years. Initially, two hundred different proteins were identified whose blood levels could be related to the risk of heart attacks, strokes, heart failure and death, and ultimately a combination of nine proteins was selected for a risk prediction model, based on their combined accuracy and sensitivity. Application of these findings to samples of patients with stable coronary heart disease demonstrated that some of those who were deemed clinically stable instead had a high risk of adverse cardiovascular outcomes, while other patients with the same clinical diagnosis had a very low risk. Thus, individuals who all carried the same clinical diagnosis of stable coronary heart disease had a risk of an adverse cardiovascular event that varied by as much as 10-fold, as revealed by analysis of the levels of the nine proteins in their blood. Given such large differences in risk and outcomes, patients could reasonably opt to be treated differently, depending on their level of risk. We hope that in the future, management of patients with stable angina will at least in part rely on risk assessment based on levels of blood proteins. (more…)
Author Interviews, Heart Disease, Nature, University Texas, Weight Research / 21.06.2016

MedicalResearch.com Interview with: Mikhail Kolonin, PhD, Associate Professor Director, Center for Metabolic and Degenerative Diseases Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at Houston Houston, TX 77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Epidemiology studies have indicated that in obese patients progression of prostate, breast, colorectal, and other cancers is more aggressive. Adipose (fat) tissue, expanding and undergoing inflammation in obesity, directly fuels tumor growth. Adipose tissue is composed by adipocytes and stromal/vascular cells, which secrete tumor-trophic factors. Previous studies by our group have demonstrated that adipose stromal cells, which support blood vessels and serve as adipocyte progenitors, are recruited by tumors and contribute to cancer progression. Mechanisms underlying stromal cell trafficking from fat tissue to tumors have remained obscure. We discovered that in obesity a chemokine CXCL1, expressed by cancer cells, attracts adipose stromal cells to tumors. (more…)
Author Interviews, Brigham & Women's - Harvard, CT Scanning, JAMA, Stroke / 21.06.2016

MedicalResearch.com Interview with: Dr. Gregoire Boulouis MD MS Research Fellow at Massachusetts General Hospital / Harvard Med. School Boston, Massachusetts MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Boulouis: Hemorrhagic Stroke or Intracerebral hemorrhage (ICH) still has a poor prognosis. A substantial proportion of patients will experience ongoing intracranial bleeding and their hematomas will grow in size in the first hours following presentation, a phenomenon called 'hemorrhage epxansion'. Patients with hemorrhage expansion have been shown to have significantly worse clinical outcome. If all baseline ICH characteristics (location, initial hemorrhage volume, ..) are non modifiable at the time of diagnosis, hemorrhage expansion, however, represents one of the few potential targets to improve outcome in ICH patients. An accurate selection of patients at high risk of expansion is needed to optimize patients' selection in expansion targetted trials and, eventually, to help stratifying the level of care at the acute phase. In this study, we investigated whether the presence of non-contrast Computed Tomography hypodensities within the baseline hematoma, a very easily and reliably assessed imaging marker, was associated with more hemorrhage expansion. A total of 1029 acute phase ICH patients were included ; approximately a third of them demonstrated CT hypodensities at baseline. In this population, CT hypodensities were independently associated with hemorrhage expansion with an odds ratio of 3.42 (95% CI 2.21-5.31) for expansion in fully adjusted multivariable model. (more…)