Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Lifestyle & Health / 27.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23700" align="alignleft" width="138"]Dr. Céline Vetter Dr.Phil. Instructor in Medicine Harvard Medical School Associate Epidemiologist Channing Division of Network Medicine Brigham and Women's Hospital Boston, MA, 02115 Dr. Céline Vetter[/caption] Dr. Céline Vetter,  Dr.Phil. Instructor in Medicine Harvard Medical School Associate Epidemiologist Channing Division of Network Medicine Brigham and Women's Hospital Boston, MA, 02115 MedicalResearch.com: What is the background for this study? Response: Heart Disease is still the leading cause of death in the US, with 1 in every 4 deaths being attributed to heart disease. On the other hand, it is estimated that approximately 15 millions Americans work evening shifts, night shift, rotating shifts or any other kind of irregular schedule that is arranged by the employer. The link between shift work and coronary heart disease has been studied for decades now, but because shift work can take so many forms, results have not been consistent. Another contributing factor to this inconsistency might be that few studies could actually track individuals over long periods of time, so that some studies might have missed when participants did actually develop coronary heart disease. Our study was based on the Nurses' Health Studies I and II, where women about 189,000 registered female nurses completed every two years mailed questionnaires that comprise items about their health status, medical history, and known or suspected risk factors for cancer and heart disease. They also reported their lifetime history of rotating night shift work in 1988 and 1989, respectively. Across the 24 years of the study periods, we observed more than 10,000 cases of coronary heart disease (i.e. myocardial infarction, CHD death, angiogram-confirmed angina pectoris, and procedures related to coronary heart disease, i.e. angioplasty, coronary artery bypass graft surgery or stents).
AACR, Author Interviews, Brigham & Women's - Harvard, Weight Research / 20.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23635" align="alignleft" width="120"]Joao Incio MD Research Fellow in Radiation Oncology Harvard Medical School/MGH Boston, MA Dr. Joao Incio[/caption] Joao Incio MD Research Fellow in Radiation Oncology Harvard Medical School/MGH Boston, MA MedicalResearch.com: What is the background for this study? Dr. Incio: With  the  current  epidemic  of  obesity,  the  majority  of  pancreatic  cancer  patients  are  overweight  or  obese  at  diagnosis.  Importantly, obesity  worsens treatment  outcomes  in  pancreatic  cancer  patients.  Therefore,  understanding  the  mechanisms  that  underlie  the  poorer  prognosis  of  obese  cancer  patients  is  of  paramount importance.  Obesity  causes  inflammation  and  fibrosis  in  the  normal  pancreas  due  to  the  accumulation  of  dysfunctional  hypertrophic  adipocytes.  Importantly,  desmoplasia  -­  a fibroinflammatory  microenvironment  -­  is  a  hallmark  of  pancreatic  ductal  adenocarcinoma  (PDAC),  and  we  have  shown  that  activation  of  pancreatic  stellate  cells  (PSCs)  via angiotensin-­II  type  1  receptor  (AT1)  pathway  is  a  major  contribution  to  tumor  desmoplasia.  Whether  obesity  affects  desmoplasia  in  PDACs,  and  interferes  with  delivery  and response  of  chemotherapeutics,  was   the focus of our study.
Author Interviews, Autism, Brigham & Women's - Harvard, PLoS / 09.04.2016

MedicalResearch.com Interview with: Ya Wen PhD TRANSCEND Research, Neurology Department Massachusetts General Hospital, Charlestown, Massachusetts, Harvard Medical School, Harvard University, Boston, Massachusetts Higher Synthesis Foundation, Cambridge, Massachusetts MedicalResearch.com: What is the background for this study? Dr. Ya Wen: At the time of this study (December 2014), the SFARI (Simons Foundation Autism Research Initiative) Gene-Human Gene Module recorded 667 human genes implicated as relevant to Autism spectrum disorders (ASDs). Now the number is close to 800. We sought to address the challenge of making sense of this large list of genes by identifying coherent underlying biological mechanisms that link groups of these genes together. To do this, we used information from several existing and well established databases and created a “demographics” of autism genes and pathways. MedicalResearch.com: What are the main findings? Dr. Ya Wen: From these hundreds of autism genes, we first found the relatively most important pathways, and then we generated a pathway network by mapping the pathway-pathway interactions into an Autism Pathway Network. Our systems analyses of this network converged upon an important role in autism pathophysiology for two pathways: MAPK signaling and calcium signaling, and specifically the process where they overlap, “calcium-protein kinase C-Ras-Raf-MAPK/ERK”. Our study also illuminated genetic relationships between autism and several other kinds of illness, including cancer, metabolic and heart diseases. Many of the significant genes and pathways were associated with vulnerability in the processing of challenging environmental influences.
Author Interviews, Brain Cancer - Brain Tumors, Brigham & Women's - Harvard, PNAS / 06.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23151" align="alignleft" width="144"]Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA 02114 Dr. Rakesh Jain[/caption] Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114

MedicalResearch.com: What is glioblastoma and why is it difficult to treat?

Dr. Jain: Glioblastoma (GBM) is the most common malignant tumor of the brain, and remains highly lethal. The standard treatment consists of surgical removal followed by chemo-radiation and anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) antibody. Unfortunately, glioblastoma cells invade the brain far from the original tumor mass. Hence, even with the best surgical techniques it is not possible to remove all tumor cells, as they are embedded in vital parts of the brain at the time of the surgery. As a result, even after multimodal therapies, most  glioblastoma patients succumb to their disease within 2 years. New approaches are desperately needed.

MedicalResearch.com: What is anti-angiogenic therapy and why is it used for glioblastoma?

Dr. Jain: One key feature ofglioblastomas is their highly abnormal, leaky and ineffective vasculature. This leads to brain swelling around the tumor and poor tumor blood perfusion, which in turn can render the tumors more aggressive. These vascular abnormalities are due to the uncontrolled overproduction in GBMs of angiogenic factors such as VEGF. Anti-angiogenic therapies using anti-VEGF agents can transiently “normalize” the GBM vasculature structure and function and reduce brain swelling, increase blood perfusion, and impact morbidity and survival. Unfortunately, even when this therapy is added to the standard therapy with surgery and chemo-radiation, GBM patients typically do not survive on average more than 1.5 years.
Author Interviews, Brigham & Women's - Harvard, Heart Disease / 04.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23053" align="alignleft" width="116"]Jacob Joseph, MD, FACC, FAHA Associate Professor of Medicine, Harvard Medical School Cardiology Consortium Lead, VA Clinical Trial Network, Associate Physician, Brigham & Women's Hospital Dr. Jacob Joseph[/caption] Jacob Joseph, MD, FACC, FAHA Associate Professor of Medicine, Harvard Medical School Cardiology Consortium Lead, VA Clinical Trial Network, Associate Physician, Brigham & Women's Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Joseph: The background for this study is the fact that heart failure with preserved ejection fraction (HFPEF) continues to be a challenge for cardiology. Clinical trials have thus far failed to give us a treatment. One of the major issues in clinical care and research is the marked heterogeneity of this condition.  Is an 80 year old woman with HFPEF, chronic kidney disease, and atrial fibrillation the same as a 50 year old hypertensive with left ventricular hypertrophy and HFPEF? In fact the recently reported TOPCAT study showed that the outcomes in patients enrolled in North and South America were significantly different from patients enrolled from Russia and Georgia, an effect that may have partly affected the results of the entire trial. In this study we examined whether a simple clinical tool like QRS duration measured on ECG could help to identify a subgroup of HFPEF patients who are at risk of adverse outcomes. When we analyzed the patients enrolled in the TOPCAT trial, we did in fact find that prolonged QRS duration is associated with worse outcomes in HFPEF. This association was independent of the region of enrollment and traditional cardiac risk factors. We also found that the association was seen in different types of conduction blocks. Furthermore the risk of adverse events started at QRS duration of approximately 100ms.
Author Interviews, Brigham & Women's - Harvard / 01.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23069" align="alignleft" width="150"]Le Min, MD,PhD Brigham and Women's Hospital, Endocrinology Division Dr. Le Min[/caption] Le Min, MD,PhD Brigham and Women's Hospital, Endocrinology Division MedicalResearch.com: What is the background for this study? Dr. Min: As you know, immune checkpoint blockade therapies by anti-CTLA4 and Anti-PD1 have shown promising and durable anti-cancer effects on several advanced malignancies. Interestingly, endocrine disorders are among the most common adverse effects associated with immune checkpoint blockade therapies. More interestingly, it appears that hypophysitis, the inflammation of the pituitary is commonly related to anti-CTLA4 therapy while thyroid disorders are more commonly seen in anti-PD1 monotherapy and the combined therapy with anti-PD1 and anti-CTLA4. Anti-CTLA4-related hypophysitis has been well characterized but there is no study to characterize the thyroid disorders associated with anti-PD1 monotherapy and the combined therapy with anti-PD1 and anti-CTLA4. As an endocrinologist, I have been taking care of a population of such patients who received either monotherapy with anti-PD1 or combined therapy with anti-PD1 and anti-CTLA4 and developed thyroid disorders.
Addiction, Author Interviews, Brigham & Women's - Harvard, Gender Differences, JAMA, Sexual Health / 27.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22822" align="alignleft" width="149"]Dr. Sari L. Reisner PhD Research Fellow in the Department of Epidemiology Harvard T.H. Chan School of Public Health Associate Scientific Researcher in the Division of General Pediatrics Boston Children’s Hospital/ Harvard Medical School Dr. Sari Reisner[/caption] Dr. Sari L. Reisner PhD Research Fellow in the Department of Epidemiology Harvard T.H. Chan School of Public Health Associate Scientific Researcher in the Division of General Pediatrics Boston Children’s Hospital/ Harvard Medical School  MedicalResearch.com: What are the main findings? Dr. Reisner: Transgender youth—including adolescent and young adult transgender women assigned a male sex at birth who identify as girls, women, transgender women, transfemale, male-to-female, or another diverse gender identity on the transfeminine spectrum—represent a vulnerable population at-risk for negative mental health and substance use/abuse outcomes. Although community surveys of transgender people in the United States have found a high prevalence of depression, anxiety, and substance use relative to the general adult U.S. population, studies typically utilize screening instruments or sub-threshold symptom questions and do not use diagnostic interviews. Diagnostic interview data are scarce among young transgender women; such data are important to establish guidelines for diagnosis and treatment for this youth group given their complex life experiences. The aim of this study was to report the prevalence of mental health, substance dependence, and co-morbid psychiatric disorders assessed via a diagnostic interview in an at-risk community-recruited sample of young transgender women. This observational study reported baseline finding from a diverse sample of 298 sexually active, young transgender women ages 16-29 years (mean age 23.4; 49.0% Black, 12.4% Latina, 25.5% White, 13.1% other minority race/ethnicity) enrolled in Project LifeSkills, an ongoing randomized controlled HIV prevention intervention efficacy trial in Chicago and Boston, between 2012-2015 (NIMH-funded, multiple PIs: Rob Garofalo, MD, MPH & Matthew Mimiaga, ScD, MPH).
Accidents & Violence, Author Interviews, Brigham & Women's - Harvard, Obstructive Sleep Apnea / 21.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22418" align="alignleft" width="130"]Stefanos N. Kales, MD, MPH, FACP, FACOEM Associate Professor, Harvard Medical School & Harvard TH Chan School of Public Health Director, Occupational Medicine Residency Division Chief OEM, Cambridge Health Alliance Dr. Stefanos Kales[/caption] Stefanos N. Kales, MD, MPH, FACP, FACOEM  Associate Professor, Harvard Medical School & Harvard TH Chan School of Public Health Director, Occupational Medicine Residency Division Chief OEM, Cambridge Health Alliance MedicalResearch: What is the background for this study? Dr. Kales: Up to 20% of all large truck crashes are due to drowsy or fatigued driving, which would account for almost 9,000 fatalities and up to 220,000 serious injuries. OSA is the most common medical cause of excessive daytime sleepiness or fatigue, and has been linked with negative impacts on attention, working memory, vigilance, and executive functioning. Past studies primarily of passenger car drivers have linked untreated OSA with a several-fold increased risk of motor vehicle accidents. They have also shown that effective treatment with CPAP reduces this risk close to that of unaffected drivers. Although commercial truck drivers undergo a biennial examination to determine their medical fitness to safely operate a vehicle, there are currently no mandatory standards for OSA screening or diagnosis, in part because there have been no large-scale studies evaluating the crash risk of commercial drivers diagnosed with OSA. Our study examined the results of the first large-scale employer program to screen, diagnose, and monitor OSA treatment adherence in the U.S. trucking industry 
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JACC, Radiology / 10.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22547" align="alignleft" width="139"]Guillermo J. Tearney, MD PhD Mike and Sue Hazard Family MGH Research Scholar Professor of Pathology, Harvard Medical School Wellman Center for Photomedicine Massachusetts General Hospital Dr. Gary Tearney[/caption] Guillermo J. Tearney, MD PhD Mike and Sue Hazard Family MGH Research Scholar Professor of Pathology, Harvard Medical School Wellman Center for Photomedicine Massachusetts General Hospital MedicalResearch.com: What is the background for this study? Dr. Tearney: In this study, we investigated a new, advanced catheter-based imaging technology for identifying the coronary plaques that may potentially precipitate heart attack. The new technique combines intracoronary OCT, that provides images of tissue emicrostructure with near-infrared autofluorescence (NIRAF) that informs on the molecular/biological characteristics of plaque. MedicalResearch.com: What are the main findings? Dr. Tearney: Our main findings were that: 1) Intracoronary OCT-NIRAF is safe and feasible in patients 2) NIRAF was elevated focally in portions of the coronary artery that contained high risk OCT features, and 3) The findings are suggestive that NIRAF may be a new imaging feature that is indicative of inflammation in human coronary lesions in vivo.
Author Interviews, Brigham & Women's - Harvard, JAMA, Vitamin D / 08.03.2016

MedicalResearch.com Interview with: Kassandra Munger, Sc.D. Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? Dr. Munger: Previous work has shown that adequate vitamin D nutrition is associated with a lower risk of multiple sclerosis (MS).  Results from studies examining whether adequate vitamin D exposure during early-life are also associated with a lower risk of MS have been mixed.  One study reported that daughters of mothers with high dietary vitamin D intake during their pregnancy had a reduced risk of multiple sclerosis, while two studies measuring 25-hydroxy vitamin D either in a blood sample from the pregnant mother or from a sample taken from the neonate, were not associated with future multiple sclerosis risk in the child.
Author Interviews, Brigham & Women's - Harvard, Melanoma, Ophthalmology / 08.03.2016

MedicalResearch.com Interview with: Ines Laines MD and Deeba Husain MD Associate Professor Ophthalmology Harvard Medical School Investigator Angiogenesis Laboratory Retina Service Massachusetts Eye and Ear Infirmary Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Uveal melanoma (UM) is the most common malignant tumor of the eye in adults. More than half of the patients are long-term survivors. It is well established for other malignancies that cancer survivors are especially prone to developing independent second primary neoplasms (SPNs) and that their characteristics vary according to the site of the first primary tumor. Multifactorial causes seem to be involved, including environmental exposures and genetic risk factors. The relevance of the treatment modalities applied to the first tumor also seem to play a role, in particular radiation therapy, which is currently the gold-standard treatment for most uveal melanoma. This risk is most pronounced in the organs within the irradiated fields, but has also been described in sites not directly exposed to radiation. Despite growing knowledge about treatment-induced effects on the occurrence of SPNs in patients with other malignancies, data is insufficient for uveal melanoma. We present a population-based analysis of the Surveillance, Epidemiology, and End Results (SEER) database, which is a well-validated public database with a case ascertainment rate of 98%. In this study, we evaluated whether patients with UM demonstrate an increased incidence of  second primary neoplasms compared to the general population, including an analysis on whether radiation therapy is associated with a higher risk of thesesecond primary neoplasms.
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Hand Washing, Health Care Systems, JAMA, UCSF / 07.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22366" align="alignleft" width="133"]Dr. Andrew Auerbach MD Professor of Medicine in Residence Director of Research Division of Hospital Medicine UCSF Dr. Andrew Auerbach[/caption] Dr. Andrew Auerbach MD Professor of Medicine in Residence Director of Research Division of Hospital Medicine UCSF and [caption id="attachment_22367" align="alignleft" width="100"]Jeffrey L. Schnipper, MD, MPH Associate Physician, Brigham and Women's Hospital Associate Professor of Medicine, Harvard Medical School Department of Medicine Brigham and Women's Hospital Dr. Jeffrey Scnhipper[/caption] Jeffrey L. Schnipper, MD, MPH Associate Physician, Brigham and Women's Hospital Associate Professor of Medicine, Harvard Medical School Department of Medicine Brigham and Women's Hospital     MedicalResearch.com: What is the background for this study? Response: The Affordable Care Act required the Department of Health and Human Services to establish a program to reduce what has been dubbed a “revolving door of re-hospitalizations.” Effective October 2012, 1 percent of every Medicare payment was deducted for a hospital that was determined to have excessive readmissions. This percentage has subsequently increased to up to 3 percent. Penalties apply to readmitted Medicare patients with some heart conditions, pneumonia, chronic lung disease, and hip and knee replacements. Unfortunately, few data exist to guide us in determining how many readmissions are preventable, and in those cases how they might have been prevented. MedicalResearch.com: What are the main findings? Response: Our main findings were that 27 percent of readmissions were preventable, and that the most common contributors to readmission were being discharged too soon, poor coordination between inpatient and outpatient care providers, particularly in the Emergency Departments and in arranging post acute care.
Author Interviews, Brigham & Women's - Harvard, JAMA, Stroke / 04.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22178" align="alignleft" width="108"]Hakan Ay MD, FAHA Associate Professor of Neurology and Radiology Stroke Service, Department of Neurology Dr. Hakan Ay[/caption] Hakan Ay MD, FAHA Associate Professor of Neurology and Radiology Stroke Service, Department of Neurology Director of Stroke Research, A.A. Martinos Center, Department of Radiology Massachusetts General Hospital Harvard Medical School Boston MA, USA Medical Research: What is the background for this study? What are the main findings? Dr. Ay: Recurrent stroke is an important public health problem. One quarter of all strokes are recurrent strokes. Approximately one out of every 10 patients with stroke develops a second stroke within the next 2 years. The most critical period for recurrence after stroke is the first 90 days; approximately half of recurrent strokes that occur within 2 years occur within the first 90 days. The RRE tool was developed at the Massachusetts General Hospital in 2010 to assess the 90-day risk of recurrent stroke. The RRE was subsequently tested in a separate cohort of patients with transient stroke symptoms (mini strokes) admitted to the Massachusetts General Hospital in 2011. The current study expands upon prior two studies by showing that the RRE tool provides reliable risk estimates when tested in cohorts of patients recruited from different academic centers in various parts of the world. The study reports that the RRE can stratify approximately one-half of patients with stroke either at high-risk or at low-risk with a reasonable accuracy.
AHA Journals, Author Interviews, Brigham & Women's - Harvard, Heart Disease, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21826" align="alignleft" width="166"]Mercedes Sotos Prieto, PhD Research Associate, Department of Nutrition Harvard T.H. Chan School of Public Health 665 Huntington Ave Boston, MA, 02115 Dr. Mercedes Sotos Prieto[/caption] Mercedes Sotos Prieto, PhD Research Associate, Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MA, 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Sotos-Prieto: Given that CVD remains the leading cause of death in the US, the prevention of risk factor development through healthy lifestyle factors, or primordial prevention, is of paramount importance to minimize the long-term risk of CVD. However, the prevalence of these healthy behaviors among US adults remains low. The Healthy Heart Score is a 20-year CVD risk prediction model based on modifiable lifestyle factors and we have shown previously that this score effectively predicted the 20-year risk of CVD in mid-adulthood. Whether this risk score is associated with clinically-relevant CVD risk factors is unknown. Therefore, in this study we analyzed the association between the Healthy Heart Score and incidence of clinical CVD risk factors, including diabetes, hypertension, and hypercholesterolemia among 69,505 U.S women in the Nurses’ Health Study II during 20 years of follow-up. The Healthy Heart Score is based on the 9 most critical lifestyle factors that best estimate CVD risk including: current smoking, higher BMI, low physical activity, lack of moderate alcohol consumption, low intakes of fruits, vegetables, cereal fiber, and nuts, and high intakes of sugar-sweetened beverages and red and processed meats. The Healthy Heart Score estimates the 20 –year CVD risk, thus a higher score reflected a higher predictive CVD risk. Over 20 years, we documented 3,275 incident cases of diabetes, 17,420 of hypertension, and 24,385 of hypercholesterolemia. Our main findings showed that women with higher predicted CVD risk based on the Healthy Heart Score (highest quintile vs. lowest) had significantly greater risk of developing each clinical risk factor individually. Specifically, women with a higher predictive CVD risk had an 18-fold higher risk of type 2 diabetes, 5-fold higher risk of hypertension, and 3-fold higher risk of hypercholesterolemia over 20-years. Further, a higher predictive CVD risk was associated with a 53-fold greater risk of developing a high CVD risk profile (defined as the diagnosis of all 3 clinical risk factors) and this association was most pronounced among women who were younger, did not smoke, and had optimal weight
Author Interviews, Brigham & Women's - Harvard / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21963" align="alignleft" width="160"]Dr. Michelle Dossett Dr. Michelle Dossett[/caption] Michelle Dossett, MD, PhD, MPH Benson-Henry Institute for Mind Body Medicine Massachusetts General Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Dossett: In 2015 the FDA and FTC held public hearings on the regulation and advertising, respectively, of homeopathic drug products.  Among their questions, they were curious about the use and public perceptions of these products.  However, there is little data available to answer these questions.  Every 5 years, the National Center for Health Statistics at the CDC and the National Center for Complementary and Integrative Health (NCCIH) at the NIH team up to survey Americans about their use of complementary and integrative medicine (CIM) modalities.  We analyzed data from the 2012 survey to address some of the questions raised by the FDA and FTC. We found that 2.1% of U.S. adults had used homeopathic products within the past year, however, only 19% had seen a practitioner for homeopathic therapy.  The most common health complaints that homeopathic products were used to address included head and chest colds and other respiratory and otorhinolaryngology (ear, nose, and throat) complaints. The second most common category of conditions these products were used for was musculoskeletal pain such as muscle and joint pain.  Intriguingly, people who used homeopathic products were more likely to find them helpful for a health condition than supplement users found their use of supplements.  Moreover, homeopathy users who saw a practitioner were more likely to find that it helped their health problem “a great deal” than those who did not.
AHA Journals, Asthma, Author Interviews, Brigham & Women's - Harvard, Heart Disease / 15.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21625" align="alignleft" width="300"]Guo-Ping Shi, DSc and Dr. Cong-Lin Liu Cardiovascular Medicine Brigham and Women’s Hospital Boston, MA Guo-Ping Shi, ScD and Dr. Cong-Lin Liu
Cardiovascular Medicine
Brigham and Women’s Hospital
Boston, MA[/caption] Guo-Ping Shi, ScD and Dr. Cong-Lin Liu Cardiovascular Medicine Brigham and Women’s Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: Abdominal aortic aneurysm (commonly called AAA) is an aortic disease that affects 1~5% men above 50, depending on the countries and regions. There is currently no effective medication or prevention besides surgical repair. Fast growth or unstable AAA often leads to aortic rupture and sudden death. Although ultrasound can be used to monitor the size and growth of AAA, our current annual health examination system in the US does not include this service. We report that mast cells are essential to AAA (J Clin Invest. 2007;117:3359-68). These cells are predominant immune cells in allergic asthmatic lungs from humans and experimental animals. Plasma immunoglobulin E (IgE) level elevation is also a signature of allergic asthma. We report that IgE contributes to experimental AAA by activating mast cells, as well as other immune cells such as macrophages and T cells (EMBO Mol Med. 2014;6:952-69). Direct evidence from our recent study demonstrates that production of allergic asthma in mice doubles the AAA sizes in experimental mice (Arterioscler Thromb Vasc Biol. 2016;36:69-77). All these prior studies suggest a role of allergic asthma to the pathogenesis of AAA. In this human population-based nationwide case-control study (Arterioscler Thromb Vasc Biol. 2016 Feb 11. [Epub ahead of print]), we reported two major findings: First, among 15,942 Danish AAA patients selected from 1996 to 2012, compared to those who did not have asthma, patients who had hospital-diagnosed asthma within the past 12 months had 60% more risk to experience aortic rupture, and those who had hospital-diagnosed asthma within the past 6 months had greater than 100% more risk to experience aortic rupture. Further, patients who received anti-asthmatic treatment, as evidence of asthma, also had 20~50% more risk of experiencing aortic rupture than those who did not have record of anti-asthmatic treatment, depending on how recent the patients received the treatments. Second, among a general men population aged from 65 to 74, patients who used bronchodilating drugs to treat asthma or reversible obstructive pulmonary disease had 45% more risk to have AAA compared with those who never used bronchodilators. This risk was not affected by smoking or other major AAA risk factors.
Author Interviews, Brigham & Women's - Harvard, Macular Degeneration / 15.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21415" align="alignleft" width="133"]Demetrios Vavvas, M.D., Ph.D. Co-Director Ocular Regenerative Medical Institute Clinician scientist at Mass. Eye and Ear and Co-Director of the Ocular Regenerative Medicine Institute at Harvard Medical School Dr. Demetrios Vavvas[/caption] Demetrios Vavvas, M.D., Ph.D. Co-Director Ocular Regenerative Medical Institute Clinician scientist at Mass. Eye and Ear and Co-Director of the Ocular Regenerative Medicine Institute at Harvard Medical School Medical Research: What is the background for this study? Dr. Vavvas: There is a lack of effective therapies for dry age-related macular degeneration (AMD), one of the leading causes of blindness affecting millions. Although AMD shares similarities with atherosclerosis, prior studies on statins and AMD have failed to show improvement. A limitation of these studies has been the heterogeneity of  age-related macular degeneration disease and the lack of standardization in statin dosage. We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in age-related macular degeneration. Medical Research: What are the main findings? Dr. Vavvas: Here, we present for the first time evidence that treatment with high-dose atorvastatin (80mg) is associated with regression of lipid deposits and improvement in visual acuity, without atrophy or neovascularization, in high-risk age-related macular degeneration patients. Medical Research: What should clinicians and patients take away from your report? Dr. Vavvas:
  • High dose lipophilic statin administration was associated with regression of large soft drusen and vision gain in 10/23 age-related macular degeneration patients.
  • Duration of treatment before a positive response was observed was usually 1-1.5 years.
  • Patients on high-dose statin appeared to be protected from progression to “wet” neovascular-AMD.
Cholesterol reduction was similarly drastic in responders and non-responders, which suggests that genetic variation may be important in determine who will benefit and who may not. Age-related macular degeneration is a heterogeneous disease and that targeting the lipid pathway in the appropriate manner and to the appropriate populations we may have the potential not only to slow down or arrest the disease but all to reverse it.
Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, Lung Cancer, Radiology / 10.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21454" align="alignleft" width="172"]Phillip M. Boiselle, MD Professor of Radiology and Associate Dean for Academic and Clinical Affairs Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts Dr. Phillip Boiselle[/caption] Phillip M. Boiselle, MD Professor of Radiology and Associate Dean for Academic and Clinical Affairs Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts Medical Research: What is the background for this study? Dr. Boiselle: We surveyed leading academic medical centers in 2013 and found considerable variability in their practice patterns as well as a relatively small number of patients being screened for lung cancer at these sites. Considering landmark developments since that time, including favorable policy and payment decisions by USPSTF  and CMS  and development of radiology-specific nodule guidelines by the American College of Radiology, we were curious to see whether there would be greater conformity of practice patterns and increased patient volumes in response to these developments. Medical Research: What are the main findings? Dr. Boiselle: First, our finding of greater conformity of lung cancer screening practices at present compared to 2013 confirmed our hypothesis that the development of radiology-specific guidelines by ACR would contribute to greater uniformity. Second, we were surprised by the very modest level of increase in patient volumes for CT screening over time despite the favorable USPSTF and CMS decisions. We emphasize, however, that the timing of our survey occurred too early to determine the full impact of CMS coverage on patient volumes
Author Interviews, Blood Pressure - Hypertension, Brigham & Women's - Harvard, Nutrition / 05.02.2016

MedicalResearch.com Interview with: Lea Borgi, MD Joint Fellowship Program in Nephrology Brigham and Women’s/ Massachusetts General Medical Research: What is the background for this study? What are the main findings? Dr. Borgi: Hypertension is one of the most common diseases in the United States and in the world. It is a known risk factor for cardiovascular disease. Even when hypertension is well-controlled with anti-hypertensives, these individuals are at an increased cardiovascular risk. Therefore, a healthy lifestyle is critical for normotensive individuals. This usually includes dietary patterns. However, if we could restrict dietary patterns to specific foods, then we would be able to provide better advice to our patients. In this study, we analyzed the association of fruits and vegetables with the incidence of hypertension. We were also interested in studying the change in consumption of fruits and vegetables over time and the incidence of hypertension. We used data from 3 large prospective cohort studies: the Nurses’ Health Study, the Nurses’ Health Study II and the Health Professional Follow-up study (total of 187,453 participants). Information about health and food intake was updated every 2 and 4 years, respectively. We found that participants who consumed ≥4 servings/day of fruits (not including fruit juice) had a lower risk of developing hypertension (follow-up was more than 20 years), when compared to participants whose consumption was ≤4 servings/weeks (Hazard ratio=0.92; 95%CI= 0.87-0.97). However, the association of vegetable intake with hypertension was different; indeed, we found no significant association with a HR of 0.95(0.86-1.04). To better understand these associations, we further analyzed individual fruits and vegetables with the incidence of hypertension. We found lower risks of developing hypertension when these individual fruits and vegetables were consumed ≥4 servings/week as compared to <1 serving/month: broccoli, carrots, tofu or soybeans, raisins and apples. In contrast, we found that eating more string beans or brussel sprouts was associated with an increased risk of hypertension with HRs of 1.11(1.05-1.17) and 1.23(1.04-1.46), respectively. In all of our analyses, we adjusted for potential cofounders (such as age, gender, body mass index and more). Finally, we also found that increasing total fruit (but not total vegetable) consumption by ≥7servings/week in the preceding 8 years was associated with a lower risk of hypertension with a pooled HR 0.94(0.90-0.97).
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Lancet, Pediatrics, Radiation Therapy / 02.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21220" align="alignleft" width="120"]Dr. Torunn Yock, MD Director, Pediatric Radiation Oncology Associate Professor, Harvard Medical School Radiation Oncology Quality Assurance Massachusetts General Hospital, Proton Center Boston, MA Dr. Torunn Yock[/caption] Dr. Torunn Yock, MD Director, Pediatric Radiation Oncology Associate Professor, Harvard Medical School Radiation Oncology Quality Assurance Massachusetts General Hospital, Proton Center Boston, MA Medical Research: What is the background for this study? Dr. Yock: Proton radiotherapy is a highly targeted form of radiation therapy that can spare normal tissues better than standard x-ray/photon based radiotherapy. Because, all side effects from radiotherapy come from radiation dose to normal healthy tissues, it is widely believed that proton radiotherapy has great potential to mitigate the side effects of treatment, both acute and long term side effects. There have been many planning studies that show that proton radiation can achieve a more highly conformal dose distribution and appear to spare 50% or more normal tissue from unnecessary irradiation.  However, there have been only a handful of retrospective studies that report disease control and side effects of treatment. While the technology looked promising, the definitive clinical data has been lacking to date. Because of this lack of clinical outcome data, the role and benefit of proton radiotherapy has been a subject of great debate in the oncology community.  Critics assert that proton radiotherapy is expensive and unproven and therefore a leading culprit in escalating costs of oncologic health care. Proponents assert that when used in the appropriate patient setting, the margin of benefit in terms of improved health outcomes, outweighs the increased cost of treatment. We embarked on this study to answer help answer the call for prospectively collected clinical outcome data to better define the most appropriate role for proton radiotherapy. Importantly, this study addresses both disease control and side effects of treatment in a pediatric medulloblastoma cohort of children. Medical Research: What are the main findings? Dr. Yock: This study shows that disease control in the pediatric medulloblastoma population is very much the same as that which is achieved by photon based radiotherapy treatments. However, more importantly, late side effects commonly attributed to radiotherapy such as neurocognitive decline over time and hearing loss appear to be improved compared with published photon treated cohorts of pediatric medulloblastoma patients.  Additionally, adverse late side effects on the cardiopulmonary, GI, and reproductive systems were essentially eliminated.
Author Interviews, BMJ, Brigham & Women's - Harvard, Nutrition, Pediatrics / 02.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21216" align="alignleft" width="144"]Dr. Maryam S. Farvid, PhD Takemi Fellow Harvard T.H. Chan School of Public Health Dr. Maryam Farvid[/caption] Dr. Maryam S. Farvid, PhD Takemi Fellow Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Farvid: Previous studies of fiber intake and breast cancer have almost all been non-significant, but none of them examined diet during adolescence or early adulthood, a period when breast cancer risk factors appear to be particularly important. Current study supports protective role of dietary fiber intake on breast cancer. The women who reported the highest amount of fiber consumed during high school, about 28 grams daily, had a 16% lower risk of overall breast cancer compared with those who said they consumed an about 15 grams a day. Also highest verses lowest intake of fiber during early adulthood was associated with a 19% lower risk of overall breast cancer. The associations were more apparent for premenopausal breast cancer than postmenopausal breast cancer. Each 10 grams increase in adolescent fiber intake may lead to a 20% lower risk of premenopausal breast cancer, as was a 15% for overall breast cancer.
Author Interviews, Brigham & Women's - Harvard, Dermatology / 01.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21180" align="alignleft" width="120"]Victor Allen Neel, MD, PhD Director, Dermatologic Surgery Massachusetts General Hospital Dr. Victor Neel[/caption] Victor Allen Neel, MD, PhD Director, Dermatologic Surgery Massachusetts General Hospital Medical Research: What is the background for this study? Dr. Neel: Seborrheic keratoses (SKs) are the very common, warty brown skin lesions that are found on the face, chest and back of most people over forty. They affect every race and they increase in size and frequency with age. Although they are not dangerous, they can mimic dangerous conditions and are cosmetically unappealing. There is a high demand in the field of dermatology by both patients and physicians for a topical treatment. Currently there no FDA-approved drugs that have been shown to be effective at removing them. Medical Research: What are the main findings? Dr. Neel: Although seborrheic keratoses are the most common benign tumors in humans, very little was known about what causes them. Our paper was the first to study the biology of SKs in the laboratory, identify the key proteins controlling their abnormal growth and to pinpoint a potential treatment for commercial development. We found that the enzyme called Akt was activated in seborrheic keratoses. Inhibiting this enzyme with a compound called A44 caused the SK cells to undergo "apoptosis,"  or programmed cell death. Normal skin cells were unaffected by A44.
Author Interviews, Brigham & Women's - Harvard, UCSF, Zika / 31.01.2016

MedicalResearch.com Interview with: [caption id="attachment_21161" align="alignleft" width="180"]Mary E. Wilson, MD Visiting Professor of Epidemiology and Biostatistics School of Medicine, University of California San Francisco Adjunct Professor of Global Health and Population Harvard T.H. Chan School of Public Health Boston, Massachusetts Dr. Mary Wilson[/caption] Mary E. Wilson, MD Visiting Professor of Epidemiology and Biostatistics School of Medicine, University of California San Francisco Adjunct Professor of Global Health and Population Harvard T.H. Chan School of Public Health Boston, Massachusetts  Medical Research: What is the background for this study? Response: Zika virus infections are spreading explosively in the Americas. This flavivirus infection, spread by Aedes mosquitoes, is new to the Americas, so the majority clinicians have little knowledge of the infection and its potential complications. The country most affected so far is Brazil, where more than a million infections have been reported in less than a year. Infection has also spread to at least 20 other countries in the Americas (the Caribbean, Mexico, Central and South America). Prior to 2007 Zika virus was known to cause infections only in Africa and Asia. Since then, it has spread and caused epidemics in Micronesia, French Polynesia, Easter Island, and since 2015 in Brazil. Most of the movement of the virus from one region to another is via travelers who are infected and then are bitten by mosquitoes in a new region. In Brazil an increase in cases of infants born with microcephaly (small head) has been noted coincident with the Zika epidemic, and the virus has been recovered from amniotic fluid and from fetal tissue, suggesting that Zika infection during pregnancy may cause microcephaly in the developing fetus. An increase in cases of Guillain-Barre syndrome has also been observed during this and previous outbreaks. Studies are underway to determine if Zika virus is the cause of microcephaly and Guillain-Barre syndrome.In Brazil an increase in cases of infants born with microcephaly (small head) has been noted coincident with the Zika epidemic, and the virus has been recovered from amniotic fluid and from fetal tissue, suggesting that Zika infection during pregnancy may cause microcephaly in the developing fetus. An increase in cases of Guillain-Barre syndrome has also been observed during this and previous outbreaks. Studies are underway to determine if Zika virus is the cause of microcephaly and Guillain-Barre syndrome. Most countries in the Americas, including the United States, are infested with types of mosquitoes that are competent to transmit the virus, but weather conditions also have to be warm enough to permit the virus to disseminate in the mosquito so that it can be transmitted to another person. The symptoms of Zika virus infection are typically mild and self-limited  – fever, aches, rash, and conjunctivitis. In fact, the majority of those infected have no symptoms. Because the virus can enter the bloodstream even in asymptomatic infected persons, there is concern that the virus could be spread by blood transfusion, if a person donates blood during the short period (probably a few days at most) when virus is in the blood. Other reasons for the paper are to highlight what is known about some of the insect repellents and to point out important gaps in our knowledge of their use and urgent research needs.
Author Interviews, Brigham & Women's - Harvard, Johns Hopkins, Race/Ethnic Diversity, Surgical Research / 29.01.2016

MedicalResearch.com Interview with: Adil H. Haider, MD, MPH Kessler Director for the Center for Surgery and Public Health Brigham and Women's Hospital Harvard Medical School, and the Harvard T.H. Chan School of Public Health Deputy Editor of JAMA SurgeryAdil H. Haider, MD, MPH Kessler Director for the Center for Surgery and Public Health Brigham and Women's Hospital  Harvard Medical School, and the Harvard T.H. Chan School of Public Health Deputy Editor of JAMA Surgery  Medical Research: What is the background for this study? Dr. Haider: Racial/Ethnic disparities have been identified in multiple surgical fields. They are thought to be caused by a complex interplay of patient-, provider-, and systems-level factors. As healthcare professionals, providers play a key role in the care and outcomes that patients experience. However, despite published research about the existence of disparities, it remains unknown the extent to which surgeons perceive that racial/ethnic disparities exist. Medical Research: What are the main findings? Dr. Haider: In a pilot study designed to assess the extent to which US surgeons report awareness of racial/ethnic disparities, only 36.6% agreed that racial/ethnic disparities exist in healthcare. Even fewer, 11.6% acknowledged that disparities were present in their hospital or clinic, and a mere 4.7% reported disparities in their personal practice.
Author Interviews, Brigham & Women's - Harvard, Diabetes, Diabetologia, Sleep Disorders / 29.01.2016

MedicalResearch.com Interview with: Dr. Yanping Li Research Scientist Harvard T.H.Chan School of Public Health Boston, MA 02115

Medical Research: What is the background for this study? What are the main findings? Dr. Li: Sleeping difficulty is a common disorder but always lack of attention from both the patients and physicians. Our study finds that women with sleeping difficulty is associated with a higher risk of type 2 diabetes.
Author Interviews, Brigham & Women's - Harvard, End of Life Care, JAMA / 27.01.2016

MedicalResearch.com Interview with: Joel Weissman, PhD, Deputy Director and Zara Cooper, MD, MSc Associate Surgeon Center for Surgery and Public Health Brigham and Women’s Hospital Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Response: A major priority for providers of end-of-life care is balancing the intensity of a patient’s treatment with quality of life. Previous studies have looked at the intensity of end-of-life care for the general population, but not whether physicians, the group most familiar with end-of-life care, receive more or less intense end-of-life care compared to non-physicians. Research from the Center for Surgery and Public Health (CSPH) at Brigham and Women’s Hospital found that for 3 of 5 end-of-life care intensity measures, physicians received significantly less intensive end-of-life care than the general population.  The findings are published in the January 19, 2016 issue of JAMA, in a special themed issue focusing on end-of-life care. The analysis included non-health maintenance organization Medicare beneficiaries aged 65 years or older who died between 2004 and 2011 in Massachusetts, Michigan, Utah, and Vermont, and was based on availability of electronic death records and ability to link to Medicare. Researchers used data from these records to look at 5 validated measures of end-of-life care intensity during the last 6 months of life: surgery, hospice care, intensive care unit (ICU) admission, death in the hospital, and expenditures. They then compared these measures between physicians and the general population (excluding other health care workers and lawyers), physicians vs. lawyers, who are presumed to be socioeconomically and educationally similar, and lawyers vs. the general population. There were 2,396 deceased physicians, 2,081 lawyers, and 666,579 people included in the analysis. Overall, physicians were less likely to die in a hospital compared with the general population (27.9 percent vs. 32 percent, respectively), less likely to have surgery (25.1 percent vs. 27.4 percent), and less likely to be admitted to the ICU (25.8 percent vs. 27.6 percent). Physicians were less likely to die in a hospital compared to lawyers (27.9 percent vs. 32.7 percent, respectively), but did not differ significantly in other measures.
Asthma, Author Interviews, Brigham & Women's - Harvard, JAMA, Vitamin D / 26.01.2016

[caption id="attachment_20929" align="alignleft" width="120"]Augusto A. Litonjua, MD, MPH Associate Professor Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA 02115 USA Dr. Augusto Litonjua[/caption] MedicalResearch.com Interview with: Augusto A. Litonjua, MD, MPH Associate Professor Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA 02115 USA  Medical Research: What is the background for this study? What are the main findings? Response: Vitamin D deficiency has been hypothesized to contribute to the asthma and allergy epidemic.  Vitamin D has been shown to affect lung development in utero. However, observational studies have shown mixed results when studying asthma development in young children. Since most asthma cases start out as wheezing illnesses in very young children, we hypothesized that vitamin D supplementation in pregnant mothers might prevent the development of asthma and wheezing illnesses in their offspring.  We randomly assigned 881 pregnant women at 10 to 18 weeks' gestation and at high risk of having children with asthma to receive daily 4,000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D (n = 440), or a placebo plus a prenatal vitamin containing 400 IU vitamin D (n = 436). Eight hundred ten infants were born during the study period, and 806 were included in the analyses for the 3-year outcomes. The children born to mothers in the 4,400 IU group had a 20% reduction in the development of asthma or recurrent wheeze compared to the children born to mothers in the 400 IU group (24% vs 30%, respectively; an absolute reduction of 6%).  However, this reduction did not reach statistical significance (p=0.051).
Author Interviews, Brigham & Women's - Harvard, Multiple Sclerosis, Neurological Disorders, Stem Cells / 26.01.2016

MedicalResearch.com Interview with: Zhigang He, PhD, BM Professor of Neurology  and Michela Fagiolini, PhD Assistant Professor of Neurology F.M. Kirby Neurobiology Center, Department of Neurology Children’s Hospital, Harvard Medical School Boston, MA 02115, USA

Medical Research: What is the background for this study? Drs. Fagiolini and He: Brain or spinal cord injury is still a major medical problem and there is no effective treatment of promoting functional recovery. A key issue is the nerve fibers, or axons, connecting different brain regions are damaged and cannot be repaired. For example, the axons in the optic nerve are the only channels transmitting visual signals from eye to brain. If damaged, our brain will not be able to receive visual signals and be blinded. Thus, a logical therapy should be to stimulate damaged axons to regrow to the targets and reconnect the eyes and brain. Studies in the past from us and others revealed several approaches of promoting the regrowth of injured axons, but it was unknown whether these regenerated axons could form functional connections and mediate functional recovery. Medical Research: What are the main findings? Drs. Fagiolini and He:  What we discovered in this study is that these regenerated axons could form functional connections, synapses, in the brain targets, but surprisingly fail to mediate behavioral visual function recovery. In mammals, many long projecting axons are insulated by lipid-enriched myelin sheets which could significantly speed up nerve conduction and facilitate the functional coordination of different brain regions during behavior. Interestingly, we found that different from intact optic nerves, these regenerated axons fail to be myelinated and thus possess poor conductance. When we treat these mice with compounds that can improve nerve conduction, we do observe partial yet significant functional recovery. Thus, there are at least two pieces of information from this study:
  • First, axon regrowth might not enough for functional recovery, nerve conduction could be another hurdle;
  • Second, the combination of these manipulations could serve a proof-of-principle example for achieving functional recovery.
Author Interviews, Brigham & Women's - Harvard, Dermatology, JAMA, Melanoma, Transplantation / 20.01.2016

More on Dermatology from MedicalResearch.com  [caption id="attachment_20781" align="alignleft" width="115"]Pritesh S. Karia, MPH Manager-Dermatologic Oncology Research Program Mohs and Dermatologic Surgery Center Brigham and Women's Hospital Boston, MA 02130 Pritesh Karia[/caption] MedicalResearch.com Interview with: Pritesh S. Karia, MPH Manager-Dermatologic Oncology Research Program Mohs and Dermatologic Surgery Center Brigham and Women's Hospital Boston, MA 02130  Medical Research: What is the background for this study? Response: Several recent studies have shown a reduced incidence of skin cancer in organ transplant recipients (OTR) treated with sirolimus as first-time therapy and those converted from calcineurin inhibitors to sirolimus. Although cancer formation is one of the main reasons for conversion to sirolimus, studies examining the effect of sirolimus on the risk of subsequent cancer formation in organ transplant recipients who have already been diagnosed with a post-transplant cancer are limited.