Author Interviews, Brigham & Women's - Harvard, Hepatitis - Liver Disease, Technology / 01.01.2017

MedicalResearch.com Interview with: Prof. David A. Weitz Mallinckrodt Professor of Physics and Applied Physics School of Engineering and Applied Sciences Harvard University MedicalResearch.com: What is the background for this technology study? What are the main findings? Response: Currently, it is very time-consuming and expensive to develop new drugs. One reason is that many drugs fail in clinical trials after animal studies, simply because animals are very different from humans. One promising means of solving this problem is to replace animal experiments with artificial human tissues that can be used to directly screen a drug. However, it is a challenge to construct artificial human tissues, as almost all human tissues are composed of multiple types of cells and extracellular matrices in 3D structures. In our studies, we have successfully developed a droplet-based microfluidic technique to fabricate large numbers of monodisperse, portable microtissues. We spatially assemble different types of cells in a 3D core-shell structure and construct an artificial human microtissue in each individual drop. The specific structures we create in the microdoplets are designed to mimic the behavior of the liver, and hence we call these structures a ‘liver in a drop.’  (more…)
Author Interviews, Brigham & Women's - Harvard, Gender Differences, Hospital Readmissions, JAMA / 20.12.2016

MedicalResearch.com Interview with: Yusuke Tsugawa, MD, MPH, PhD Department of Health Policy and Management Harvard T. H. Chan School of Public Health, Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Boston, Massachusetts  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We analyzed a 20% sample of Medicare beneficiaries hospitalized with a medical condition in 2011-2014, and found that patients treated by female doctors have lower mortality and readmission rates than those cared for by male doctors. (more…)
Author Interviews, Brigham & Women's - Harvard, Endocrinology, Infections / 18.12.2016

MedicalResearch.com Interview with: Flaminia Catteruccia PhD Associate Professor of Immunology and Infectious Diseases Department of Immunology and Infectious Diseases Boston, Massachusetts 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mosquito control via lethal insecticides is a key method for reduction of malaria transmission. As insecticide resistance is spreading, new intervention methods are urgent. Our study demonstrates that studies on mosquito biology can provide novel, much needed tools for malaria control. We show how key aspects of mosquito physiology and Plasmodium development can be significantly disrupted in the female Anopheles mosquito by agonists of the insect steroid hormone 20-hydroxyecdysone (20E). Modeling of the data predicts that the integration of 20E agonists in malaria control programs would significantly reduce malaria prevalence to a similar extent as insecticides, but without imposing severe costs to mosquito populations (more…)
Author Interviews, Brigham & Women's - Harvard, Dental Research, Infections, Rheumatology, Science / 17.12.2016

MedicalResearch.com Interview with: Maximilian F. Konig, MD Division of Rheumatology, Johns Hopkins University School of Medicine Current affiliation: Department of Medicine Massachusetts General Hospital Harvard Medical School MedicalResearch.com: What is the background for this study? Response:The idea that rheumatoid arthritis (RA), an autoimmune disease that leads to chronic joint inflammation and destruction, may be initiated by a bacterial infection is not novel, but has been posited for more than a century. Based on the clinical observation that patients with RA frequently have severe periodontal disease (gum disease), gum inflammation has long been thought to contribute to disease development in RA. However, limited understanding of the mechanisms that fuel and sustain the autoimmune attack in RA made it difficult to pinpoint a specific bacterial trigger. In recent years, our understanding of the abnormal immune response that attacks the joints in patients with RA has grown exponentially, and we now know that disease-specific autoantibodies (ACPAs) target modified self-proteins (this modification is known as citrullination). It is this abnormal immune response against citrullinated proteins that appears to drive the joint (and sometimes lung) inflammation seen in rheumatoid arthritis. Recent studies from our laboratory at The Johns Hopkins University (led by principle investigator Felipe Andrade, MD, PhD) suggested that an immune cell called the neutrophil, which normally protects us from infection at sites like the oral cavity or anywhere else in the body, also appears to be the source of the proteins attacked in RA. We were therefore interested to understand what drives the association of gum disease, an inflammation commonly triggered by bacteria, with RA. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Primary Care / 09.12.2016

MedicalResearch.com Interview with: Dr. Ateev Mehrotra MD Associate professor, Department of Health Care Policy Harvard Medical School and a hospitalist at Beth Israel Deaconess Medical Center Boston, Massachusetts MedicalResearch.com: What is the background for this study? What are the main findings? Response: More people in the US are using price transparency websites to shop for care. Some have wondered whether using the information on these websites to choose a doctor will help them actually save money. A relatively small difference in price for visits on the website translated into hundreds of dollars. (more…)
Author Interviews, Brigham & Women's - Harvard, ENT, Neurological Disorders / 30.11.2016

MedicalResearch.com Interview with: Daniel M. Merfeld, Ph.D. Professor of Otolaryngology Harvard Medical School Massachusetts Eye and Ear Director, Jenks Vestibular Physiology Laboratory Senior Scientist MedicalResearch.com: What is the background for this study? Response: Nearly half of the population will see a clinician at some point in their lives with symptoms related to the vestibular system (e.g., dizziness, vertigo, imbalance and blurred vision). The vestibular system, made up of tiny fluid-filled membranes in the inner ear, is responsible for receiving information about motion, balance and spatial orientation. With the goal of determining whether age affected the function of the vestibular system, our research team administered balance and motion tests to 105 healthy people ranging from 18 to 80 years old and measured their vestibular thresholds (“threshold” refers to the smallest possible motion administered that the subject is able to perceive correctly). (more…)
Artificial Sweeteners, Author Interviews, Brigham & Women's - Harvard, Metabolic Syndrome, Weight Research / 28.11.2016

MedicalResearch.com Interview with: Richard Hodin, MD Gastrointestinal and Endocrine Surgery Professor of Surgery, Harvard Medical School Chief of Academic Affairs, Department of Surgery, Massachusetts General Hospital Boston, Mass 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Sugar substitutes like Aspartame are widely used and supposed to make people lose weight and have less diabetes, heart disease, etc. However, a number of studies indicate that theses substitutes don’t work very well. The reasons for them not working have not been clear. Our study found that the most common sugar substitute (aspartame) blocks an enzyme in our gut called Intestinal Alkaline Phosphatase (IAP). By blocking IAP, Aspartame prevents the beneficial effects of IAP which normally works to prevent obesity, diabetes, and other aspects of the metabolic syndrome. So, we now have an explanation for why Aspartame may make obesity and the metabolic syndrome worse, rather than better. (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, Heart Disease, Nutrition / 25.11.2016

MedicalResearch.com Interview with: Dr. Qi Sun Sc.D, M.D., M.M.S. Assistant Professor in the Department of Nutrition Harvard T.H. Chan School of Public Heath Boston MedicalResearch.com: What is the background for this study? What are the main findings? Response: Interpretation of existing human study data regarding saturated fat intake in relation to heart disease risk is quite confusing and distorted in certain publications. It is a fact that, depending on data analysis strategies, the effects of saturated fats may depend on which macronutrients they replace. For example, substituting saturated fats for refined carbohydrates will not lead to an elevated risk of heart disease because both nutrients are harmful whereas replacing saturated fats with good polyunsaturated fats results in risk reduction. In our current analysis, we clearly demonstrated that when total saturated fatty acids were replaced by polyunsaturated fatty acids, monounsaturated fatty acids, whole grain carbohydrates, and plant-based proteins, the diabetes risk would decrease. Furthermore, we showed that major individual saturated fatty acids were all associated with an elevated heart disease risk. (more…)
Author Interviews, Brigham & Women's - Harvard, Kidney Disease, Nutrition / 20.11.2016

MedicalResearch.com Interview with: Dr. Teodor G. Paunescu PhD Assistant Professor of Medicine Harvard Medical School Boston MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with kidney disease frequently report food aversion and poor dietary intake leading to malnutrition, a complication associated with high morbidity and mortality. However, there are no effective treatments currently available to address this complication, and the mechanisms underlying anorexia and food aversion in these patients remain unclear. Because of the critical role of olfaction in flavor appreciation and dietary intake, we decided to quantify olfactory (smelling) deficits in advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. We found that patients with kidney disease have significant olfactory deficits that need objective assessments for accurate characterization. Our results also indicate that olfactory deficits likely attribute to nutritional impairment in patients with kidney disease. (more…)
Author Interviews, Brigham & Women's - Harvard, Kidney Disease, Stem Cells / 20.11.2016

MedicalResearch.com Interview with: Dr. Ryuji Morizane MD, PhD Associate Biologist, Renal Division Brigham and Women’s Hospital Affiliated Faculty, Harvard Stem Cell Institute Instructor, Harvard Medical School MedicalResearch.com: What is the background for this study? Response: Polycystic kidney disease (PKD) accounts for 10% of end-stage kidney disease (ESKD), and there is currently no curable treatment available for patients with PKD. The adult onset form of PKD, the most common type of PKD, takes 30 years to form cysts in humans; therefore, it is difficult to study mechanisms of PKD to find novel therapeutics for patients. (more…)
Author Interviews, Brigham & Women's - Harvard, OBGYNE, Pediatrics / 18.11.2016

MedicalResearch.com Interview with: Melissa C. Bartick, MD, MSc Department of Medicine Cambridge Health Alliance Harvard Medical School Cambridge, MA MedicalResearch.com: What is the background for this study? Response: This is the first study ever to combine maternal and pediatric health outcomes from breastfeeding into a single model. We had published a cost analysis of suboptimal breastfeeding for pediatric disease in 2010, which found that suboptimal breastfeeding cost the US $13 billion in costs of premature death costs and medical expenses, and 911 excess deaths. We followed that up with a maternal cost analysis which found about $18 billion in premature death costs and medical expenses. In both these studies, most of the costs were from premature death. We were unable to combine the results of these two studies because their methodologies were different, and both of them, especially the pediatric portion needed to be updated. (more…)
Author Interviews, Brigham & Women's - Harvard, Compliance, Gastrointestinal Disease, Pharmacology, Technology / 18.11.2016

MedicalResearch.com Interview with: C. Giovanni Traverso, MB, BChir, PhD Gastroenterologist and biomedical engineer Division of Gastroenterology at BWH Instructor of medicine at Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: We developed a drug delivery system capable of safely residing in the stomach for 2 weeks. Furthermore we demonstrated the capacity of the novel dosage form, in the shape of a star, to protect the drug from the acidic stomach environment and also slowly release drug over the course of 14 days. We applied this new technology towards efforts targeting the elimination of malaria. Specifically, we focused on a drug called ivermectin that has been used to treat parasites but also has the benefit of being toxic to malaria-carrying mosquitos when they bite someone who has ivermectin in their system. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, NEJM, Surgical Research / 17.11.2016

MedicalResearch.com Interview with: Mandeep R. Mehra, MD, FACC, FESC, FHFSA, FRCP Medical Director, Brigham and Women’s Hospital Heart and Vascular Center Executive Director, Center for Advanced Heart Disease Professor of Medicine, Harvard Medical School Editor in Chief, The Journal of Heart and Lung Transplantation Brigham and Women's Hospital Boston, MA Mandeep R. Mehra, MD, FACC, FESC, FHFSA, FRCP Medical Director, Brigham and Women’s Hospital Heart and Vascular Center Executive Director, Center for Advanced Heart Disease Professor of Medicine, Harvard Medical School Editor in Chief, The Journal of Heart and Lung Transplantation Brigham and Women's Hospital Boston, MA MedicalResearch.com: What is the background for this study? Response: 10% of patients with heart failure and a reduced ejection fraction transition into Advanced Stages of disease where they become unresponsive to life prolonging traditional medications. Such patients typically require intravenous inotropic therapy to preserve cardiac function but most remain profoundly limited in their quality of life. In such cases a heart transplant is desirable but this is an option for only a few patients. Left Ventricular Assist Devices (LVADs) have become the mainstay for treating such patients either while they await a transplant or as a permanent option. However, there are challenges leading to infections, strokes, bleeding and most importantly pump malfunction due to thrombosis of the LVAD itself. The HeartMate 3 LVAD is a centrifugal pump that is designed to overcome the problem of pump thrombosis by virtue of 3 engineering attributes: (a) A frictionless rotor that is based on a fully magnetically levitated platform (b) wide blood flow passages that reduce red cell destruction and (c) an artificial intrinsic pulse that prevents stasis of blood within the pump. (more…)
Author Interviews, Brigham & Women's - Harvard, Neurological Disorders / 17.11.2016

MedicalResearch.com Interview with: Michael D. Fox, MD, PhD Assistant Professor in Neurology Berenson-Allen Center for Noninvasive Brain Stimulation Division of Cognitive Neurology, Department of Neurology Beth Israel Deaconess Medical Center Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Consciousness is thought to be composed of arousal plus awareness, but no one knows where these processes live in the human brain. We took a unique approach to this question by studying human brain lesions that disrupt consciousness and cause coma. We found one small spot in the brainstem that was specific for coma (i.e. lesions that hit this spot caused coma while lesions that didn’t hit the spot did not cause coma). In other words, there was one spot in the human brainstem that, when lesioned, disrupted arousal and caused coma We then looked at the connectivity of that brainstem spot, and found that it was connected to two cortical regions previously implicated in awareness. These cortical regions also contained a unique type of brain cell thought only to be present in higher order mammals that are self-aware. To confirm our findings, we looked at the integrity of our network in patients with disorders of consciousness (e.g. persistent vegetative state) and found selective disruption of this network. (more…)
Author Interviews, Brigham & Women's - Harvard, Gender Differences, Memory, Menopause / 12.11.2016

MedicalResearch.com Interview with: Jill M. Goldstein, Ph.D. Director of Research for the Connors Center for Women's Health and Gender Biology Brigham and Women's Hospital and Professor of Psychiatry and Medicine at Harvard Medical School MedicalResearch.com: What is the background for this study? Response: Maintaining intact memory function as we age is one of the primary public health challenges of our time. In fact, women are at almost twice the risk for Alzheimer's disease and it is not only because women live longer. Thus, it is incumbent upon us to understand this sex difference and incorporate the knowledge into the development of sex-dependent therapeutics. Our study focused on beginning this investigation by understanding how memory circuitry and memory function change over the menopausal transition, when we believe that sex differences in memory aging emerge. By understanding healthy aging, we will better understand how the brain goes awry with age differently in men and women and who might be at highest risk for Alzheimer's disease later in life. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, JAMA / 24.10.2016

MedicalResearch.com Interview with: Anna D. Sinaiko, PhD, MPP Research Scientist Department of Health Policy & Management Harvard T.H. Chan School of Public Health Boston, MA 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response: One strategy for reducing health care spending in the U.S. is to increase transparency in health care pricing for patients. The idea is that patients can learn about and anticipate the prices they would pay for health care before they receive care, and incorporate that information into their choices about whether and where to receive care. When patients incorporate price information into their decisions, it gives providers an incentive to compete on price and quality. There has been a dramatic increase in the availability of health care price information over the last few years for patients who have commercial health insurance, primarily through web-based tools. In this study, we examined the impact of this information on patient choice of health care facility. We find that a small number of enrollees with commercial health insurance through Aetna, 3% overall, accessed price information through their transparency tool. Among users of the tool, patients who viewed price information for imaging services and for sleep studies before they had the service chose facilities with lower prices, and incurred lower spending (of 12%) for imaging services. We found no effect on patient choices for patients who viewed price information for 6 other health care services (carpal tunnel release, cataract/lens procedures, colonoscopy, echocardiogram, mammograms, and upper gastrointestinal endoscopy). (more…)
AHA Journals, Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, Clots - Coagulation, Heart Disease / 18.10.2016

MedicalResearch.com Interview with: Eric A. Secemsky, MD MSc Interventional Cardiology Fellow Massachusetts General Hospital Harvard Medical School Fellow, Smith Center for Outcomes Research in Cardiology Beth Israel Deaconess Medical Center MedicalResearch.com: What is the background for this study? Response: Use of oral anticoagulant (OAC) therapy prior to coronary stenting is a significant predictor of post-procedural bleeding events. Previous studies have estimated that the frequency of chronic OAC use among patients undergoing percutaneous coronary intervention (PCI) is between 3% to 7%. Yet many of these analyses examined select patient populations, such as those admitted with acute myocardial infarction or atrial fibrillation, and preceded the market approval of non-vitamin K antagonist oral anticoagulants (NOACs). As such, the contemporary prevalence of OAC use among all-comers undergoing PCI, as well as associated risks of adverse events, are currently unknown. Therefore, we used PCI data from a large, integrated healthcare system to determine current use of  oral anticoagulant use among all-comers undergoing coronary stenting and the related short- and long-term risks of therapy. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Technology / 12.10.2016

MedicalResearch.com Interview with: Ateev Mehrotra, M.D. Associate Professor Department of Health Care Policy Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prior research has highlighted that physicians make diagnostic errors roughly 10 to 15 percent of the time. Over the last two decades, computer-based checklists and other “fail-safe” digital apps have been increasingly used to reduce medication errors or streamline infection-prevention protocols. Lately, experts have wondered whether computers might also help reduce diagnostic errors. In the study, 234 internal medicine physicians were asked to evaluate 45 clinical cases, involving both common and uncommon conditions with varying degrees of severity. For each case, physicians had to identify the most likely diagnosis along with two additional possible diagnoses. Each clinical vignette was solved by at least 20 physicians. The same cases were also evaluated using 19 symptom checkers, websites or apps that use computers that help patients determine potential diagnoses for what is wrong based on their symptoms. The physicians vastly outperformed the symptom-checker apps, listing the correct diagnosis 72 percent of the time, compared with 34 percent of the time for the digital platforms. Eighty-four percent of clinicians listed the correct diagnosis in the top three possibilities, compared with 51 percent for the digital symptom-checkers. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, JAMA, Outcomes & Safety / 10.10.2016

MedicalResearch.com Interview with: Jared Conley, MD, PhD, MPH Department of Emergency Medicine Massachusetts General Hospital Harvard Medical School Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: As the U.S. healthcare system seeks to improve the health of populations and individual patients, there is increasing interest to better align healthcare needs of patients with the most appropriate setting of care—particularly as it relates to hospital-based care (accounting for 1/3 of total U.S. healthcare costs). Avoiding hospitalization—as long as safety and quality are not compromised—is often preferred by patients and the added benefit of potentially making care more affordable further promotes such care redesign efforts. There is a growing body of research studying alternative management strategies to hospitalization; we sought to comprehensively review and analyze this work. Alternative management strategies reviewed include outpatient management, quick diagnostic units, observation units, and hospital-at-home. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Surgical Research / 06.10.2016

MedicalResearch.com Interview with: Diego Lopez Harvard medical student and Dr. Andrew Loehrer MD former surgical resident at MGH senior author: David C. Chang, PhD, MPH, MBA Associate Professor of Surgery Director of Healthcare Research and Policy Development Department of Surgery Massachusetts General Hospital Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: Income inequality in the United States has been increasing in recent decades, and has become an important in this election cycle. Although income inequality is often framed in terms of its effects on politics and the economy, little attention has been paid to its effect on the healthcare system. In our study, we set out to evaluate the way in which counties with differing levels of income inequality made use of the healthcare system while controlling for the overall income (as well as other demographic variables). We found that areas with higher income inequality were associated with higher Medicare expenditures.  And these effects are independent of – meaning they are in addition to – the known effect of poverty on healthcare utilization. (more…)
Author Interviews, Blood Pressure - Hypertension, Brigham & Women's - Harvard, Heart Disease, JACC, Salt-Sodium / 06.10.2016

MedicalResearch.com Interview with: Nancy Cook ScD Professor of Medicine, Harvard Medical School Professor in the Department of Epidemiology Harvard T.H. Chan School Public Health Brigham & Women’s Hospital Division of Preventive Medicine Boston, MA 02215 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The association of sodium intake with later mortality has been controversial. While there is a well-accepted effect on blood pressure, the effects of sodium on later cardiovascular disease, and particularly mortality, have been subject to dispute. While the adverse effects of high sodium are now widely accepted, effects at lower levels of sodium intake are less clear. Some recent studies have found a J-shaped relationship, with increased disease rates among those consuming lower levels of sodium, contrary to the effects on blood pressure. In contrast, we found a direct linear relationship of usual intake of sodium with later mortality over 20 years of follow-up. Those with the lowest sodium intake experienced the lowest mortality. Our measure of intake was based on the average over 1-3 years of several measures of 24hr urine sodium excretion, the gold standard of sodium measurement. This is much more precise than measurements based on a single 24hr sodium excretion or especially on a spot urine sample, which is used in many publications that found the J-shaped curve. Our data were assessed in a healthy cohort of men and women without hypertension or cardiovascular disease, so had less potential bias due to these factors. We thus believe that our results showing the lowest mortality among those consuming the lowest levels of sodium are more accurate. (more…)
Author Interviews, Brigham & Women's - Harvard, Depression, JCEM, Menopause, Sleep Disorders / 28.09.2016

MedicalResearch.com Interview with: Hadine Joffe, MD, MSc Associate Professor of Psychiatry, Harvard Medical School Vice Chair for Psychiatry Research Director of Division of Women's Mental Health / Dept of Psychiatry / Brigham and Women’s Hospital Director of Psycho-Oncology Research / Dept of Psychosocial Oncology and Palliative Care /Dana Farber Cancer Institute www.brighamwharp.org MedicalResearch.com: What is the background for this study? Response: We conducted this study to advance our understanding about causes of mood disturbance in the menopause transition that are specifically related to menopause. We used an experimental model to dissect out the contributions of hot flashes and sleep disturbance from contribution of changing levels of estrogen because hot flashes, sleep problems, and estrogen fluctuations co-occur and are difficult to distinguish from one another. Understanding whether hot flashes and/or sleep disturbance are causally related to mood disturbance will help us identify who is at risk for mood changes during the menopause transition. This is incredibly important now that we are finding effective non-hormonal treatments for hot flashes and sleep disruption. (more…)
Annals Internal Medicine, Author Interviews, Brigham & Women's - Harvard, Colon Cancer, Geriatrics / 27.09.2016

MedicalResearch.com Interview with: Xabier Garcia-De-Albeniz MD PhD Research Associate Department of Epidemiology Harvard T.H. Chan School of Public Health Mongan Institute for Health Policy Massachusetts General Hospital MedicalResearch.com: What is the background for this study? Response: Randomized controlled trials are considered the gold standard to inform health care delivery. Unfortunately, no randomized controlled trials of screening colonoscopy have been completed. Ongoing trials exclude persons aged 75 or older, and will not have mature results before 2025. However, healthy persons older than 75 may live long enough to benefit from colorectal cancer (CRC) screening. The Medicare program reimburses screening colonoscopy without an upper age limit since the year 2001. We used the extensive experience of Medicare beneficiaries to evaluate the effectiveness and safety of screening colonoscopy. (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Nature, Technology / 23.09.2016

MedicalResearch.com Interview with: Natalie Artzi PhD principal research scientist MIT's Institute for Medical Engineering and Science and Assistant professor of medicine Brigham and Women's Hospital With co-authors: Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Noam Shomron MedicalResearch.com: What is the background for this study? What are the main findings? Response: Metastases are the primary cause for mortality in breast cancer, the most common cancer in women regardless of ethnicity. Recent studies show that germline sequence variants, such as single-nucleotide polymorphisms (SNPs) in miRNA-binding sites, can disrupt the downregulation by miRNAs, with a profound effect on gene expression levels and consequentially on the phenotype, including increased risk for cancer. In the current study, we aimed to determine the potential effect of SNPs within miRNA-binding sites on metastatic breast cancer progression and their potential use as suppression targets to prevent metastasis. Our collaborators at Tel-Aviv Universityin a research led by Dr. Noam Shomron found that the SNP, rs1071738, located in a target site for miR-96 and miR-182 on the 3’-UTR of the PALLD gene, encodes the Palladin actin-associated protein, which is a documented player in breast cancer motility. In vitro experiments revealed a functional downregulation of Palladin levels by miR-96 and miR-182, which subsequently reduces migration and invasion abilities of breast cancer cells. My lab then showed in an in vivo experiment that the use of nanoparticles embedded in a hydrogel scaffold as a miRNA delivery vehicle enables an efficient and specific delivery of miR-96/miR-182 directly to breast tumours, which results in marked reduction of breast cancer metastasis. We then proceeded to study the effect of combination therapy in which we will use a chemotherapy drug to shrink the primary tumor and the miRNAs to prevent metastasis. The intercalation of a chemotherapy drug, cisplatin, to the miR-conjugated nanoparticles further improved the effect, leading to significant reduction in both primary tumour growth and metastasis. Our study highlights the therapeutic potential of miRNAs, and specifically miR-96 and miR-182, and support the importance of Palladin regulation in breast cancer metastasis. (more…)
AHA Journals, Author Interviews, Brigham & Women's - Harvard, Endocrinology, Heart Disease, Thyroid Disease / 17.09.2016

MedicalResearch.com Interview with: Layal Chaker, MD, MSc PhD candidate Department of Endocrinology and Epidemiology Erasmus Medical Center Rotterdam, The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: The association of thyroid function with coronary heart disease is well–established but not much was known about the association of thyroid function with sudden cardiac death. We conducted the study with the hypothesis that thyroid hormone levels affect cardiovascular risk factors and therefore could also affect the risk of sudden cardiac death (SCD). We were surprised to see that when we control our analyses for these cardiovascular risk factors, the association of high and high-normal thyroid function with SCD remained similar, suggesting that other pathways could play a role. Thyroid hormone has different effects on the cardiovascular systems and future studies should identify which pathway could be responsible for the increased risk of sudden cardiac death with higher thyroid hormone levels. This could lead to better assessment of individual risk and identify possible prevention targets. (more…)
Author Interviews, Brigham & Women's - Harvard, Infections, JAMA, Ophthalmology / 17.09.2016

MedicalResearch.com Interview with: Dr. Daria Van Tyne, PhD The Gilmore Lab Department of Ophthalmology Harvard Medical School Massachusetts Eye and Ear Infirmary Boston, Massachusetts MedicalResearch.com: What is the background for this study? What are the main findings? Response: A specific clone of E. coli, type ST131, which produces an extended-spectrum beta-lactamase (ESBL – an enzyme that inactivates many penicillin-type antibiotics), has rapidly spread around the globe to become the leading cause of multidrug-resistant, non-intestinal E. coli infection. Despite this, E. coli is a rare cause of infection of the cornea. A patient was recently seen at the Massachusetts Eye and Ear Infirmary with a severe E. coli infection of the cornea, and the large number of antibiotic resistances of this strain tipped us off to the possibility that it might be the highly virulent ST131 ESBL type. By sequencing the DNA of its genome, we found that it was indeed ST131 ESBL E. coli. Moreover, we discovered a new mutation in this strain that allows it to produce a slimy outer coating on its surface. This slime layer, or capsule, makes the bacteria more resistant to removal by phagocytic cells of the immune system. The slime layer also makes these particular colonies appear different on a special type of agar that contains the dye Congo Red. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Colon Cancer, End of Life Care, Lung Cancer / 09.09.2016

MedicalResearch.com Interview with: Joseph A. Greer, Ph.D. Program Director, Center for Psychiatric Oncology & Behavioral Sciences Associate Director, Cancer Outcomes Research Program, Massachusetts General Hospital Cancer Center Yawkey Center, Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many patients with advanced cancer have a high symptom burden, increased depression symptoms, misperceptions about their prognosis, and difficulties in making decisions about care at the end of life. To address these challenges and improve care for this vulnerable population, our research team initially conducted a small, single-group pilot study of early palliative care integrated with standard oncology care for patients with advanced lung cancer. This study showed that the model of integrated care was feasible and acceptable to patients and their families. Specifically, the majority of patients in the study were able to meet with a palliative care clinician at least monthly from the time of diagnosis of metastatic lung cancer, in order to receive help with managing symptoms as well as support for coping with the disease and making decisions about treatment. We then conducted a follow-up randomized controlled trial of early, integrated palliative care in a sample of approximately 150 patients with metastatic non-small cell lung cancer. This study was published in the New England Journal of Medicine in 2010 and showed that those patients who received early palliative care reported significantly improved quality of life, mood, prognostic awareness, and end-of-life care compared to those who received standard oncology care alone. To confirm the findings of our prior research and to determine whether the benefits of early integrated palliative care would apply to a larger sample of patients with diverse malignancies, we recently completed another randomized trial of this same model of care in a sample of 350 patients with incurable lung and gastrointestinal cancers. In this trial, we observed that patients who received the early palliative care intervention reported higher quality of life and improved mood by 24 weeks but not at the primary end-point of 12 weeks. Our team was surprised to find that the trajectory of quality of life and depression symptoms over time was different for individuals with incurable lung versus gastrointestinal cancers in this study. As expected, the palliative care intervention positively buffered the decline in quality of life by 12 weeks for patients with incurable lung cancer, as we had seen in our prior trial. However, the group of patients with gastrointestinal cancers reported an improvement in their quality of life by the 12-week time point regardless of whether they received the palliative care intervention. We are still exploring possible reasons for this difference, such as whether changes in cancer therapy may have reduced symptoms and improved quality of life in the group of patients with gastrointestinal cancer. In addition, we were pleased to learn that the early integrated palliative care intervention led to improvements in how patients cope with their illness. For example, compared to patients in the usual oncology care group, those who received early, integrated palliative care were more likely to learn ways to accept their diagnosis and to take positive actions to make their lives better. So, in addition to treating patients’ symptoms, the palliative care clinicians in this study were bolstering people’s adaptive coping skills. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JACC, Outcomes & Safety, Surgical Research / 04.09.2016

MedicalResearch.com Interview with: Senthil Selvaraj, MD, MA and Deepak L. Bhatt, MD, MPH Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: There has been significant controversy in the effect of off-hours presentation in ST-elevation myocardial infarction (STEMI). Off-hours presentation has been associated with longer treatment time, an independent predictor of worse outcomes in STEMI, though a number of other studies have shown no difference as well. Moreover, little data has been generated from clinical trials, which has the advantage of comprehensive and adjudicated outcomes. In our analysis of nearly 2,000 STEMI patients from the CHAMPION PHOENIX study (a randomized, controlled trial of cangrelor in percutaneous coronary intervention), we found that off-hours presentation was not associated with worse efficacy or safety outcomes at 48 hours or 30 days. More specifically, outcomes not typically reported in registry data, such as ischemia-driven revascularization and stent thrombosis, were not significantly different between the groups. Interestingly, treatment times were actually faster in the “off-hours” group as well. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JACC, Pharmacology / 31.08.2016

MedicalResearch.com Interview with: Aaron S. Kesselheim, M.D., J.D., M.P.H. Associate Professor of Medicine at Harvard Medical School Director, Program On Regulation, Therapeutics, And Law (PORTAL) Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women's Hospital Boston MA 02120 MedicalResearch.com: What is the background for this study? What are the main findings? Response: It has been previously reported that the number of new cardiovascular drugs approved by the U.S. Food and Drug Administration (FDA) has declined in recent years. So we sought to empirically assess trends in the development of new cardiovascular therapeutics. (more…)