Author Interviews, Brigham & Women's - Harvard, Infections, Vaccine Studies / 11.05.2015

Manoj Duraisingh Ph.D. John LaPorte Given Professor of Immunology and Infectious Diseases Harvard T.H. Chan School of Public Health Department of Immunology and Infectious DiseasesBoston, MassachusettsMedicalResearch.com Interview with: Manoj Duraisingh Ph.D. John LaPorte Given Professor of Immunology and Infectious Diseases Harvard T.H. Chan School of Public Health Department of Immunology and Infectious Diseases Boston, Massachusetts MedicalResearch: What is the background for this study? What are the main findings? Dr. Duraisingh: The malaria parasite P. falciparum is one of the most important pathogens of humans, with enormous mortality resulting from blood-stage infections, when parasites replicate exponentially in red blood cells. Although anti-Plasmodial drugs are in clinical use, widespread and increasing parasite drug-resistance has contributed to an ongoing public health crisis, and we urgently need to find novel approaches to prevent and treat disease. Targeting host red blood cell molecules presents an unexploited alternative. However, the highly differentiated and enucleated red blood cell poses a significant technical hurdle for genetic experimentation, due to the lack of a nucleus. Here we have developed a novel, forward genetic screen to identify critical factors of malaria infection of red blood cells in an unbiased fashion. Our screen takes advantage of recent advances in human stem cell biology that enable the ex vivo culture of red blood cells from nucleated hematopoietic precursors which are amenable to in vitro genetics. We have now identified a surface molecule CD55 (alias Decay-Accelerating Factor, DAF) as an essential host factor required for the invasion of red blood cells by P. falciparum. We demonstrate that this protein is required by all P. falciparum strains tested (laboratory and field) for invasion. Furthermore, we demonstrate that CD55 acts at the initial stage of invasion when the P. falciparum parasite attaches to the surface of the red blood cell. Collectively, our findings indicate that CD55 is an ideal target for the development of new host-directed and vaccine therapeutics for malaria.
Author Interviews, Brigham & Women's - Harvard, Electronic Records, JACC, Stroke / 11.05.2015

Dr. Karen E. Joynt, MD MPH Cardiovascular Division Brigham and Women's Hospital and VA Boston Healthcare System Department of Health Policy and Management, Harvard School of Public HealthMedicalResearch.com Interview with: Karen E. Joynt, MD MPH Cardiovascular Division, Brigham and Women's Hospital and VA Boston Healthcare System Department of Health Policy and Management Harvard T.H. Chan School of Public Health MedicalResearch: What is the background for this study?  What are the main findings? Dr. Joynt: While there is a great deal of optimism about the potential of Electronic Health Records (EHRs) to improve health care, there is little national data examining whether hospitals that have implemented EHRs have higher-quality care or better patient outcomes.  We used national data on 626,473 patients with ischemic stroke to compare quality and outcomes between hospitals with versus without EHRs.  We found no difference in quality of care, discharge home (a marker of good functional status), or in-hospital mortality between hospital with versus without EHRs.  We did find that the chances of having a long length of stay were slightly lower in hospitals with EHRs than those without them.
Author Interviews, Biomarkers, UCSF / 10.05.2015

Alan H.B. Wu, PhD, DABCC Professor Laboratory Medicine Chief, Clinical Chemistry Laboratory University of California San Francisco, CAMedicalResearch.com Interview with: Alan H.B. Wu, PhD, DABCC Professor Laboratory Medicine Chief, Clinical Chemistry Laboratory University of California San Francisco, CA Medical Research: What is the background for this study? What are the main findings? Response: Clinical trials are conducted for validation of novel biomarkers.  There is considerable heterogeniety in the quality design and documentation of findings. This can have a major impact on the conclusions rendered.
Author Interviews, Diabetes, General Medicine, Statins, UT Southwestern / 08.05.2015

Ishak Mansi, MD Staff Internist, VA North Texas Health System. Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TXMedicalResearch.com Interview with: Ishak Mansi, MD Staff Internist, VA North Texas Health System. Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Mansi:  Statin use is associated with increased incidence of diabetes, and possibly increased body weight, and less exercise capacity. Data on the long-term effects of these associations in healthy adults are very limited. Additionally, the effects of these associations on diabetic complications have not been adequately studied. Dr. Mansi at VA North Texas Health System, Dallas and Professor of Medicine and Clinical Sciences at the University of Texas Southwestern, Dallas, TX and his colleagues found that among generally healthy individuals, statin-users in comparison to non-users had a higher odds of being diagnosed with new onset diabetes, diabetes with complications, and overweight/obesity. The researchers examined the records of tens of thousands of Tricare beneficiaries, during the period from 10/1/2003 to 3/1/2012. After excluding patients who had at baseline a preexisting cardiovascular diseases or severe chronic diseases that may be life-limiting (including diabetes mellitus), they identified a cohort of 25,970 patients as “healthy cohort”. They, further, matched 3,351 statins-users and 3,351 nonusers on several baseline characteristics to ensure comparability. There are 3 main important findings for our study:
  1. Statin use was associated with significantly higher risk of new onset diabetes even in a very healthy population. Whereas the risk of diabetes with statins is known, it was thought that this may be due to the overall multiple risks of statin-users (that caused them to receive statins as a therapy).
  2. Statin use was associated with very high risk of diabetes complications in this healthy population: this was never shown before.
  3. Statin use is associated with higher risk of obesity: this also is widely unknown. However, few studies have noted this (one study using patient survey noted this, another study using Mendelian randomization showed it, and post-hoc analysis of a clinical trial showed that statin user gained more weight). Our study, which used a different methodology (retrospective cohort study) add another piece of evidence. Obesity is at endemic level in the US and treatment options are limited.
High-intensity statins was associated with greater risks of all outcomes. This article is published in the Journal of General Internal Medicine (JGIM). JGIM is the official journal of the Society of General Internal Medicine.
Author Interviews, Genetic Research, Infections, Inflammation, NYU / 07.05.2015

Dr. Ludovic Desvignes. PhD. Assistant Professor, Departments of Medicine and Pathology NYU Langone Medical CenterMedicalResearch.com Interview Dr. Ludovic Desvignes PhD. Assistant Professor, Departments of Medicine and Pathology NYU Langone Medical Center MedicalResearch: What is the background for this study? Dr. Desvignes: This study is the result of a collaboration at NYU Langone Medical Center, between the laboratories of Dr. Stefan Feske and Dr. Joel Ernst, my mentor. Dr. Feske and colleagues had developed a mouse model of rare, inherited mutations he had identified in infants. These mutations occur in the genes for STIM1 and ORAI1, which are crucial for calcium flux in cells of the immune system. The young patients affected by these mutations suffer from severe, recurrent and chronic infections that often cause death before their first birthday. In particular, some of these patients cannot control infection with BCG, which is a normally innocuous strain of mycobacteria administered to protect against tuberculosis (TB). TB is a chronic infection and one of the leading causes of infection-related death worldwide. Going into this study, Dr. Feske and colleagues knew that without functional calcium channels, immune cells do not function properly. However, they did not fully understand how these channels contribute to immune responses to infectious pathogens in a living organism and in particular, for pathogens that cause chronic infections such as TB. This is why Dr. Ernst and I collaborated with Dr. Feske and provided him with our clinical and research expertise in TB. MedicalResearch: What are the main findings? Dr. Desvignes: Dr. Feske’s mice are genetically engineered to lack STIM1 in a certain type of immune cells, known as T cells or T lymphocytes. We infected these mice with Mycobacterium tuberculosis, the bacterium causing TB. Mycobacterium tuberculosis causes chronic infection by manipulating the immune system even in healthy people. The first very surprising result of our study was that mice lacking calcium flux in T cells handled acute TB fairly well. Only during the chronic phase of infection did they become unable to control mycobacterial growth and developed a strong inflammation in their lungs, which was due to an infiltration by different types of immune cells, including T cells. We discovered that the accumulation of STIM1-deficient T cells in the lungs resulted from the cells’ inability to die, which is a normal mechanism to limit an immune response and prevent excessive inflammation. Another immune control mechanism that failed in the absence of STIM1 is mediated by a subset of T cells called induced regulatory T cells, or iTreg cells. These cells are essential to prevent normal immune responses from going “overboard” by suppressing the functions of other immune cells, including T cells. We found that calcium signals are required for the development of iTreg cells and that their numbers were strongly reduced in the lungs of infected STIM1-deficient mice. We therefore think that the lack of iTreg cells in the absence of STIM1 contributes to the severe lung inflammation in chronic TB. The third finding that really surprised us was that T cells accumulating in the lungs of STIM1-deficient mice produced large amounts of a protein called interferon gamma. While interferon gamma is required to control Mycobacterium tuberculosis, it is also a very potent promoter of inflammation and too much of it can lead to tissue damage. Dr. Feske and colleagues had previously observed that calcium fluxes promote the production of interferon gamma in T cells cultured in vitro and we expected the STIM1-deficient T cells to be defective in the production of that protein. During chronic TB, however, calcium signaling turned out to be not only dispensable for the production of interferon gamma by T cells but it was actually required to limit its production and thus, to control inflammation.
Author Interviews, Breast Cancer, Case Western, Genetic Research / 07.05.2015

Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with: Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of Medicine MedicalResearch: What is the background for this study? What are the main findings? Dr. Khalil: This study aimed to identify other genes that work synergistically with the oncogene HER2 in HER2positive (HER+) breast cancer. The gene HER2 is amplified in those patients, which results in excess activities that promote uncontrolled cell growth. There are drugs that target HER2 and diminish its activity. However, these drugs can work initially, but patients relapse; or sometimes, the drugs don't work at all in some patients. Thus, by identifying other genes that work synergistically with the HER2 gene, we now have more genes to target by various drugs or compounds to destroy the tumor. The challenge was how to identify the key genes that work synergistically with HER2, especially in human subjects. To that end, we used clinical samples from a clinical trial of a drug that is known to inhibit HER2 activity to identify those genes. To further refine our list, we used cell culture models of the disease to also inhibit HER2. By combining those data sets, we identified 44 protein-coding genes. Next, we wanted to make sure that those genes stand a third independent filter. For that part, we interrogated those 44 genes in HER2+ tumors vs matched normal tissues from The Cancer Genome Atlas database — a collection of hundreds of tumors and normal tissues. Of the 44 genes, 35 genes passed this third filter. By examining the known functions of those genes, we can deduce that those genes work cooperatively with HER2 to promote carcinogenesis. There are currently known drugs that target some of those genes. We will use these drugs in combination with a drug that target HER2 to determine if the combination works better at destroying the tumor entirely. Lastly, we found that a special type of genes that we previously discovered, called lincRNAs, could also affect the oncogenic activity of HER2. These lincRNAs can also be targeted with HER2 to eliminate the tumor.
Author Interviews, OBGYNE, UCLA / 06.05.2015

Anita L. Nelson, MD Professor, Department of Obstetrics and Gynecology at Harbor-UCLA Medical Center Los Angeles BioMedical Research Institute Harbor-UCLA Medical Center Torrance, California MedicalResearch.com Interview with: Anita L. Nelson, MD Professor, Department of Obstetrics and Gynecology at Harbor-UCLA Medical Center Los Angeles BioMedical Research Institute Harbor-UCLA Medical Center Torrance, California Medical Research: What is the background for this study? What are the main findings? Dr. Nelson: The clinical impact heavy menstrual bleeding has often been expressed in terms of quality of life issues, but many women have heavy and prolonged bleeding that can lead to serious medical problems. The frequency with which women were treated at Harbor-UCLA Medical Center with profoundly low hemoglobin levels prompted us to do a comprehensive review of such women during a recent five year period to remind readers that even in the 21st century, this is not an uncommon problem. Overall 149 woman were treated 168 times for severe anemia (hemoglobin < 5.0 g/dL); 40% had previously been transfused (but not effectively treated). Over a quarter had reactive thrombocytosis which placed them at high risk for thrombosis (DVT, PE, and stroke). Over a third were discharged without therapy to prevent recurrence.
Author Interviews, Education, Vanderbilt / 06.05.2015

Candace McNaughton, MD MPH Assistant Professor Department of Emergency Medicine Vanderbilt University, Nashville, TNMedicalResearch.com Interview with: Candace McNaughton, MD MPH Assistant Professor Department of Emergency Medicine Vanderbilt University, Nashville, TN Medical Research: What is the background for this study? Dr. McNaughton: Heart failure affects more than 5 million Americans, is a frequent cause of hospitalization, and by 2030 is projected to cost as much $70 billion, so there is a lot of interest in helping patients with heart failure manage their condition. Health literacy, or the ability to use and understand healthcare information, is important for all patients, but the stakes are very high for patients with heart failure. Some people who are highly literate or highly educated in other areas may have difficulty reading and understanding healthcare information. Patients with lower health literacy skills may have difficulty communicating with healthcare providers, navigating the healthcare system, recognizing signs of health decline, and knowing when and who to contact when they do become ill. Medical Research: What are the main findings? Dr. McNaughton: To our knowledge, this is the first study in which health literacy was measured by nurses when patients were admitted to the hospital for heart failure. Nurses asked patients three questions about whether they have problems learning about their medical condition, their confidence filling out medical forms, and how often they have someone help them read hospital materials. With these three questions, information about the health literacy level of individual patients can be made easily available their healthcare providers. We found that among 1,379 patients hospitalized for acute heart failure, those with low health literacy had 32% greater risk of death compared to patients with a literacy score of 10 or higher, even after adjusting age, sex, race, insurance status, education, other medical conditions, and how long they were in the hospital. 
Author Interviews, Cancer Research, End of Life Care, Surgical Research, UC Davis / 04.05.2015

Robert J Canter MD Associate Professor of Clinical Surgery Division of Surgical Oncology University of California at DavisMedicalResearch.com Interview with: Robert J Canter MD Associate Professor of Clinical Surgery Division of Surgical Oncology University of California at Davis Medical Research: What is the background for this study? Dr. Canter: Our data suggest that surgeons are improving in their ability to select patients for surgical intervention in cancer patients near their end of life. Our research suggests that surgeons may be operating on healthier patients who are anticipated to have a better recover from a palliative operation. These are patients who can perform activities of daily living without assistance, for example. Our interest in the appropriate surgical care of people with late-stage cancer grew from observing terminally ill patients whose acute problems were addressed through surgery, and who then suffered complications resulting in lengthy stays in intensive care units, and even in death. Unfortunately, it is quite common that this group of disseminated malignancy patients end up dying in the intensive care unit instead of being managed with less invasive interventions with hopes of returning home with their families, including with hospice care.
Author Interviews, Compliance, Emory, Heart Disease / 04.05.2015

Andre Paixao, MD Division of Cardiology Emory University Atlanta, GA, 30322.MedicalResearch.com Interview with: Andre Paixao, MD Division of Cardiology Emory University Atlanta, GA, 30322. Medical Research: What is the background for this study? Dr. Paixao: Despite advances in cardiovascular prevention, coronary heart disease remains a major cause of morbidity and mortality. Understanding risk factor burden and control as well as perceived risk prior to acute myocardial infarction (MI) presentation may identify opportunities for system-based interventions to promote adherence to evidence based recommendations and improve overall cardiovascular health. Medical Research: What are the main findings? Dr. Paixao: Our study assessed predicted risk and risk factor control prior to Myocardial Infarction (MI) presentation in 443,117 patients included in the NCDR ACTION Registry-GWTG. Only 36.1% of patients met all assessed risk factor control metrics (i.e. LDL cholesterol, non-HDL cholesterol, nonsmoking status and aspirin use among those with prior cardiovascular disease). Risk factor control was suboptimal in the primary and secondary prevention groups. Prior cardiovascular disease was present in 41.6% of patients presenting with an acute MI. Among those without prior cardiovascular disease or diabetes, only 13.4% were classified as high risk based on the Framingham Risk Score.
AACR, Author Interviews, Breast Cancer, NIH, Ovarian Cancer / 03.05.2015

Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer InstituteMedicalResearch.com interview with Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers. We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population.
Author Interviews, Cancer Research, Nature, UT Southwestern / 03.05.2015

Dr. Alec (Chengcheng) Zhang Michael L. Rosenberg Scholar in Medical Research Associate Professor of Physiology and Developmental Biology Member of the Harold C. Simmons Comprehensive Cancer Center UT Southwestern Medical CenterMedicalResearch.com Interview with: Dr. Alec (Chengcheng) Zhang Michael L. Rosenberg Scholar in Medical Research Associate Professor of Physiology and Developmental Biology, Member of the Harold C. Simmons Comprehensive Cancer Center UT Southwestern Medical Center Medical Research: What is the background for this study? What are the main findings? Response: Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. Treatments for AML yield poor outcomes, especially for the typical senior patients. The medical need for new therapies for AML is underscored by the fact that no new therapies for AML have been approved in over 30 years. There are over 50 experimental agents in clinical trials for the treatment of AML today, although only a few agents have promising data to date. New molecular targets and therapeutic strategies are needed for AML treatment. In 2012, we published a paper showing that we cloned the human leukocyte immunoglobulin-like receptor B2 (LILRB2) as a receptor for several angiopoietin-like proteins (Angptls) (Zheng et al 2012 Nature 485:656-660). The LILRB family receptors contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and are classified as inhibitory receptors because ITIM motifs can recruit phosphatases SHP-1, SHP-2, or SHIP to negatively regulate immune cell activation. Surprisingly, in that work, we showed that PirB, the mouse ortholog of LILRB2, is expressed by AML stem cells (AML-SCs) and supports AML development. Although counterintuitive, this result is consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. In the current paper, we continued the research and report that a number of receptors containing the ITIMs are crucial for the development of AML. We mainly focus on studying the function and downstream signaling of LAIR1 as a representative ITIM-containing receptor. We found that the deletion of LAIR1 does not affect normal hematopoiesis but abolishes leukemia development in several different mouse leukemia models. We also identified a mechanism by which LAIR1 supports AML development, showing that the LAIR1/SHP-1/CAMK1/CREB pathway sustains the survival and self-renewal of AML cells. Importantly, our findings are well supported by bioinformatics analysis of AML patient databases and experimental results of human leukemia cells. Since certain ITIM-containing receptors are essential for AML cells but not critical for normal hematopoiesis, and blocking their signaling can boost immunity, these ITIM-containing receptors including LAIR1 represent ideal targets for treating AML.
Author Interviews, Heart Disease, Mayo Clinic, Psychological Science / 01.05.2015

Shannon M. Dunlay, M.D. M.S. Advanced Heart Failure and Cardiac Transplantation Assistant Professor of Medicine and Health Care Policy and Research Mayo Clinic RochesterMedicalResearch.com Interview with: Shannon M. Dunlay, M.D. M.S. Advanced Heart Failure and Cardiac Transplantation Assistant Professor of Medicine and Health Care Policy and Research Mayo Clinic Rochester MedicalResearch: What is the background for this study? What are the main findings? Dr. Dunlay: Left ventricular assist devices (LVAD) are increasingly utilized as destination therapy (DT) in patients that are not candidates for heart transplantation. Optimal patient selection is essential in improving outcomes, but many of the factors associated with favorable outcomes remain poorly understood. It is important for us to better understand the role that psychosocial factors may play in outcomes after DT LVAD. Unlike transplant, where the limited organ supply requires choosing candidates with optimal psychosocial characteristics, DT LVAD therapy is more readily available as it does not rely on organ donors. There are no clear guidelines on what constitutes an acceptable psychosocial risk prior to DT LVAD. As a result, many programs will offer DT LVAD to candidates despite psychosocial concerns if it is felt they will otherwise benefit. Data are needed to inform programs about whether such candidates are truly at elevated risk of adverse outcomes. In our single-center study including 131 patients, we found that several psychosocial characteristics are predictive of readmission after DT LVAD. A history of illegal drug use and depression are associated with a higher risk of readmission, while tobacco use is associated with lower readmission risk. Psychosocial characteristics were not significant predictors of death after DT LVAD.
Author Interviews, Cancer Research, Gastrointestinal Disease, Genetic Research, NIH / 30.04.2015

Dr. Steven Wank MDMedicalResearch.com Interview with: Dr. Stephen Wank MD Digestive Diseases Branch, NIDDK National Institutes of Health, Bethesda, Maryland MedicalResearch: What is the background for this study? Dr. Wank: Small intestinal carcinoids are rare and difficult to diagnose because symptoms may be absent or mistaken for more common diseases. Because carcinoids usually grow slowly over several years before spreading or causing symptoms, patients often seek medical attention late with advanced, incurable disease. However, when diagnosed at an early stage, carcinoid can be surgically cured. Presently, there are no long-term effective therapies for surgically non-resectable disease. Although carcinoids occur sporadically, there have been reports of family clusters (more than one blood relative with carcinoid). Hereditary small intestinal carcinoid has not been recognized as a disease and causative genetic factors have not been identified in either sporadic cases or families with multiple affected members. If small intestinal carcinoid occurs in families on a hereditary basis, we hypothesized that asymptomatic relatives in families with carcinoid are at a high risk of harboring an undiscovered tumor. To test this, we established a clinical research protocol at the National Institutes of Health in Bethesda, Maryland to screen asymptomatic relatives in families with at least two cases of small intestinal carcinoid in the hope of detecting their tumors at an early surgically curable stage. If successful in our endeavor, we would improve the outcome of the disease in these asymptomatic relatives and position ourselves to discover the genetic basis for their disease. Understanding the gene mutations causing small intestinal carcinoid would allow us to screen for the disease with a blood test, help us understand what causes the disease, and treat the disease with specific targeted therapies.
Author Interviews, Columbia, Opiods / 30.04.2015

Silvia S. Martins, MD, PHDAssociate Professor of Epidemiology Department of Epidemiology Mailman School Of Public Health Columbia University New York, NY 10032MedicalResearch.com Interview with Silvia S. Martins, MD, PHD Associate Professor of Epidemiology Department of Epidemiology Mailman School Of Public Health Columbia University New York, NY 10032 MedicalResearch: What is the background for this study? What are the main findings? Dr. Martins: The background for this study is former studies showing links between nonmedical use of prescription opioids and transition to heroin and other illegal substances, prescription opioid-related and heroin-related fatal overdoses . In addition, a particular public health concern is that the transition to heroin and further injecting heroin may increase the risk of bloodborne infections. We used data from the National Survey on Drug Use and Health, a large nationally representative household sample of 67,500 people, and self-reported heroin use within the last 12 months, the researchers examined the change in patterns of past-year non-prescription drug and heroin use between 2002-2005 and 2008-2011 across racial and ethnic groups. The most significant rise in heroin use was among Hispanics and non-Hispanic whites, where the rate of heroin use for the latter group increased by 75 percent in 2008-2011 compared to earlier years. Regarding frequency of use, for Hispanics, increases were significant only among those using opioids about 1-29 days in the past year. Among blacks and whites, significant increases in the rate of heroin use were observed among those using prescription opioids more frequently (100-365 days) in the past year.
Addiction, Author Interviews, Case Western, Psychological Science / 29.04.2015

Maria Pagano, PhD Case Western Reserve University School of Medicine Department of Psychiatry, Division of Child Psychiatry Cleveland, OHMedicalResearch.com Interview with: Maria Pagano, PhD Case Western Reserve University School of Medicine Department of Psychiatry, Division of Child Psychiatry Cleveland, OH MedicalResearch: What is the background for this study? Dr. Pagano: Socially anxious adolescents quickly figure out that alcohol and drugs can provide ease and comfort in social situations that are anxiety provoking.  Reaching for a substance to change how you feel can quickly become a knee-jerk reaction, can develop into an addiction, and robs youths of learning how to tolerate interpersonal differences and uncomfortable feelings, developing emotional maturity, and cultivating self acceptance. Adolescents who fear being criticized by their peers are likely to not speak up in group therapies during treatment, which can limit their benefit from treatment.  There is a lot of healing that comes sharing your insides with others. Socially anxious patients may not get this healing nor let others really get to know who they are and give input to their lives Higher peer helping in AA during treatment means getting active in low intensity tasks like putting away chairs, or making coffee at a 12-step meeting.  It is less about needing peer assistance or expecting praise or recognition from giving service.  It is more about adopting the attitude of "how can I be helpful?"
Author Interviews, Brigham & Women's - Harvard, CHEST, Sleep Disorders / 29.04.2015

dr-matthias-eikermann.jpgMedicalResearch.com Interview with: Matthias Eikermann, MD, PhD Associate Professor of Anaesthesia, Harvard Medical School Director of Research, Critical Care Division Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Eikermann: Obstructive sleep apnea occurs in about 5% of pregnant women, worsens as pregnancy progresses and is likely to persist into the early postpartum period. A main cause of anesthesia-related maternal death is postpartum airway obstruction. We observed among early postpartum women, that 45° upper body elevation increased upper airway diameter and mitigated sleep apnea, without adverse effects on quality of sleep after delivery.
Author Interviews, Pediatrics, UCSD, Weight Research / 28.04.2015

Mark D. DeBoer, MD, MSc, MCR Associate Professor of Pediatrics Division of Pediatric Endocrinology, University of VirMedicalResearch.com Interview with: Mark D. DeBoer, MD, MSc, MCR Associate Professor of Pediatrics Division of Pediatric Endocrinology, University of Virginia Medical Research: What is the background for this study? What are the main findings? Dr. DeBoer: The American Academy of Pediatrics recommends that children watch no more than 2 hours of TV daily. We wanted to see if children watching shorter amounts of TV were more likely to have higher weight status. We found that children in kindergarten who watched 1-2 hours a day were more than 40% more likely to be overweight and obese and gained more unhealthy weight over the next year.
Author Interviews, Brigham & Women's - Harvard, Hematology / 28.04.2015

MedicalResearch.com Interview with: John M. Higgins, MD MGH Center for Systems Biology Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Higgins: Hundreds of studies over the past 8 years have shown that increased variation in the size of red blood cells (RBCs) is associated with increased risk for a very wide range of common diseases, like heart disease, many types of cancer, infection, many autoimmune diseases, and lots of other conditions.  The size of red blood cells (RBCs) in the circulation of a healthy person usually varies by about 12-14%, meaning that if you took a sample of the cells, most of the bigger cells would be about 14% larger than the smaller cells.  People whose red blood cells show more variation in size have a greater risk of developing a wide range of diseases.  Also, among patients already diagnosed with many common diseases like heart disease or cancer, those with higher RBC size variation have worse outcomes.  It is unknown how all of these different diseases could be connected to variation in the size of red blood cells.  The study explains a major cause for this connection.  We find that the human body seems to slow down the production and destruction of RBCs in just about every major disease very slightly.  Since red blood cells gradually become smaller as they age, a delay in destruction will increase the fraction of small cells, and the overall variation in size increases.  The study also describes a method to estimate a patient’s RBC clearance rate.
AACR, Author Interviews, HPV, University Texas, Vaccine Studies / 27.04.2015

Jacqueline Hirth, PhD, MPH Assistant Professor andMedicalResearch.com Interview with: Jacqueline Hirth, PhD, MPH Assistant Professor and Dr. Abbey B. Berenson MD, MMS, PhD Center for Interdisciplinary Research in Women's Health Obstetrics and Gynecology The University of Texas Medical Branch at Galveston TexasDr. Abbey B. Berenson MD, MMS, PhD Center for Interdisciplinary Research in Women's Health Obstetrics and Gynecology The University of Texas Medical Branch at Galveston Texas

Medical Research: What is the background for this study? What are the main findings? Response: In this sample of young women, vaccination was effective at reducing prevalence of vaccine-type HPV (6,11,16,18) compared to women who were unvaccinated. We also found a dose response, with young women who received at least 2 doses of the 3 dose vaccine series having a lower rate of vaccine-type HPV compared to those who only received one dose (8.6% compared to 16.9%, respectively).
Author Interviews, Cancer Research, Hepatitis - Liver Disease, UCSD / 27.04.2015

Lisa M. Nyberg, MD, MPH Transplant Hepatologist Director, Hepatology Research Kaiser Permanente, Garfield Specialty Center San Diego, CA 92111MedicalResearch.com Interview with: Lisa M. Nyberg, MD, MPH Transplant Hepatologist Director, Hepatology Research Kaiser Permanente, Garfield Specialty Center San Diego, CA  92111 Medical Research: What is the background for this study? What are the main findings? Dr. Nyberg: The overall cancer rates were higher in patients with Hepatitis C (HCV) vs those without HCV. Of note, though, the HCV cohort had higher rates of alcohol abuse, tobacco use, cirrhosis and diabetes mellitus (DM). However, even after stratification for the variables alcohol abuse, tobacco use, body mass index (BMI) and DM; the increased cancer rates remained significant for total cancer sites, liver cancer and NHL. Note that this study does not establish a cause and effect relationship between Hepatitis C and cancer. A strength of this study is that it is an evaluation of a large patient population (n=35,712 with HCV and 5,297,191 without HCV). Limitations of the study are those inherent in epidemiological studies using large databases. For example, confounders may not be accurately recorded in automated databases (smoking and alcohol abuse may be under-recorded).
Author Interviews, Heart Disease, JACC, Stroke, University of Pennsylvania / 25.04.2015

Jay Giri, MD MPH Director, Peripheral Intervention Assistant Professor of Clinical Medicine University of PennsylvaniaMedicalResearch.com Interview with Jay Giri, MD MPH Director, Peripheral Intervention Assistant Professor of Clinical Medicine University of Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Giri: Carotid artery stents are placed by vascular surgeons or interventional cardiologists to decrease the risk of long-term stroke in patients with severe atherosclerotic disease of the carotid artery.  When these procedures are performed, there is a risk of releasing small amounts of debris into the brain’s circulation, causing a stroke around the time of the procedure (peri-procedural stroke).  In order to mitigate this issue, embolic protection devices (EPD) have been developed to decrease the chances of small debris reaching the brain. Two types of EPD exist.  The first is a small filter meant to catch the debris released by placement of the carotid stent (distal filter EPD). The second is a more complex device type that leads to transient halting of blood flow to the brain in the carotid artery being stented (proximal EPD). Debris-containing blood is removed from the body prior to allowing normal blood flow to proceed back to the brain after stent placement. Our prior research has shown that nearly all (>95%) of domestic carotid stenting procedures are performed with utilization of one of these devices.  We sought to compare important clinical outcomes of stroke and death between these 2 device types within a large national sample of patients undergoing carotid stenting. Some small prior studies have investigated whether the total amount of debris reaching the brain is less with proximal embolic protection devices.  These studies have shown mixed results.  However, no prior study has investigated important clinical outcomes of stroke and death in relation to these devices. We found that overall uptake of proximal embolic protection devices utilization in America has not been robust.  Less than 7% of all domestic CAS procedures are performed with this technology.   Our analysis showed that in-hospital and 30-day stroke/death rates with proximal EPD and distal filter EPD were similar (1.6% vs. 2.0%, p = 0.56 and 2.7% vs. 4.0%, p = 0.22, respectively).
AHA Journals, Author Interviews, Depression, Duke, Heart Disease, Race/Ethnic Diversity / 24.04.2015

Dr. Robert J. Mentz MD Assistant Professor of Medicine Director, Duke University Cooperative Cardiovascular Society Advanced Heart Failure and Cardiac Transplantation Duke University Medical Center Duke Clinical Research InstituteMedicalResearch.com Interview with: Dr. Robert J. Mentz MD Assistant Professor of Medicine Director, Duke University Cooperative Cardiovascular Society Advanced Heart Failure and Cardiac Transplantation Duke University Medical Center Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Mentz: Previous studies have shown that depression is associated with worse outcomes in heart failure patients; however, most of these prior studies were conducted in primarily white patient populations. The impact of depressive symptoms on outcomes specifically in blacks with heart failure has not been well studied. We used data from the HF-ACTION trial of exercise training in heart failure patients, which collected data on depressive symptoms via the Beck Depression Inventory (BDI-II), to assess the association between depressive symptoms and outcomes in black patients as compared with white patients. We found that in blacks with heart failure, baseline symptoms of depression and worsening of symptoms over time were both associated with increased all-cause mortality/hospitalization.
AACR, Author Interviews, Cancer Research, NIH, Vaccine Studies / 22.04.2015

Daniel C. Beachler, PhD, Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) MedicalResearch.com Interview with: Daniel C. Beachler, PhD Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) Medical Research: What is the background for this study? What are the main findings? Dr. Beachler: HPV is a common sexually transmitted infection. Individuals can acquire HPV infections in the epithelium of their cervical, anal and oral sites, and occasionally these infections lead to cancer. There are three prophylactic HPV vaccines on the market that can protect against HPV at these sites among those not been previously exposed to HPV. This study examined the effect of HPV vaccination of 18-25 year old women at all three anatomic sites. The combined multi-site HPV vaccine efficacy has not been reported previously. It was unknown whether the vaccine may protect non-infected sites against HPV infection or re-infection in women exposed to HPV prior to vaccination. We observed that the HPV vaccine provides the strongest protection at all three sites among women unexposed to HPV before vaccination. Additionally, we observed some protection at the non-infected sites in women who were previously infected with HPV.
Author Interviews, Brigham & Women's - Harvard, Mental Health Research, Stroke, Toxin Research / 22.04.2015

Elissa Hope Wilker, Sc.D. Beth Israel Deaconess Medical Center Cardiovascular Epidemiology Research Harvard Medical SchoolMedicalResearch.com Interview with: Elissa Hope Wilker, Sc.D. Beth Israel Deaconess Medical Center Cardiovascular Epidemiology Research Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Wilke: Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but the impact on structural changes in the brain is not well understood. We studied older adults living in the greater Boston area and throughout New England and New York and we looked at the air pollution levels and how far they lived from major roads. We then linked this information to findings from MRI studies of structural brain images. Although air pollution levels in this area are fairly low compared to levels observed in other parts of the world, we found that people who lived in areas with higher levels of air pollution had smaller brain volumes, and higher risk of silent strokes. The magnitude of association that we observed for a 2 µg/m3 increase in fine particulate matter (PM2.5) (a range commonly observed across urban areas) was approximately equivalent to one year of brain aging. The association with silent strokes is of concern, because these are associated with increased risk of overt strokes, walking problems, and depression.
Author Interviews, Autism, Education, Emory, JAMA, Pediatrics / 22.04.2015

MedicalResearch.com Interview with: Lawrence Scahill, MSN, PhD and Karen Bearss, PhD Department of Pediatrics, Marcus Autism Center Children’s Healthcare of Atlanta and Emory University Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Autism spectrum disorder (ASD) affects an estimated 0.6 to 1% of children worldwide. In young children with ASD (e.g. 3 to 7 years of age) up to 50% also have disruptive behaviors such as tantrums, aggression, self-injury and noncompliance. When present, these disruptive behaviors interfere with the child’s readiness to make use of educational and other supportive services. The presence of disruptive behaviors also hinders the acquisition of routine daily living skills. Parent Training has been shown to be effective for young children with disruptive behaviors who do not have Autism spectrum disorder – but it has not be well-studied in children with ASD. The current multisite study shows that parent training is effective in reducing serious behavioral problems in young children with ASD. This is the largest randomized trial of a behavioral intervention in children with ASD.  180 children were randomly assigned to parent training or parent education. Both treatments were delivered individually to parents over 24 weeks. Serious behavioral problems were reduced by almost 50% in the parent-training group compared to about 30% for parent education. A clinician who was blind to treatment assignment rated positive response in 69% of children in the parent training group compared to 40% for parent education. In addition, 79% of children who showed a positive response to parent training at the end of the 24-week trial maintained benefit at 6 months post treatment. Parent training provided parents with specific strategies on how to manage tantrums, aggression, self-injury and noncompliance in children with autism spectrum disorder. Parent education provided up-to-date and useful information about ASD, but no instruction on how to address behavioral problems. Parents were engaged in the study treatments as evidenced by the low drop-out rate of 10% .
Author Interviews, Heart Disease, JACC, NYU, Obstructive Sleep Apnea, Sleep Disorders / 22.04.2015

Dr. Larry Chinitz MD Professor of Medicine and Director, Cardiac Electrophysiology NYU Langone Medical CenterMedicalResearch.com Interview with: Dr. Larry Chinitz MD Professor of Medicine and Director, Cardiac Electrophysiology NYU Langone Medical Center MedicalResearch: What is the background for this study? What are the main findings? Dr. Chinitz: The treatment algorithms proposed currently for maintenance of sinus rhythm in patients with atrial fibrillation focus on use of anti-arrhythmic drugs and catheter ablation. Data available to evaluate the effect of modification of known adverse clinical factors on atrial fibrillation recurrence is scant. Obstructive sleep apnea in a known factor associated with both new onset atrial fibrillation as well as its recurrence after catheter ablation. Through a meta-analysis of available data we found that use of continuous positive airway pressure in patients with sleep apnea was associated with a 42% relative risk reduction in recurrence of atrial fibrillation. This effect was similar across patient groups irrespective of whether they were medically managed or with catheter ablation.
AACR, Author Interviews, Genetic Research, Melanoma, NYU, Personalized Medicine, Wistar / 21.04.2015

Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NYMedicalResearch.com Interview with: Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NY Medical Research: What is the background for this study? What are the main findings? Dr. Wilson: Metastatic cutaneous melanoma is an extremely aggressive form of skin cancer.  Traditionally, it has been characterized by clinicopathologic characteristics.  More recently, melanoma tumors have also been stratified by common somatic mutations for which targeted therapies have been developed or are under investigation, including BRAF, NRAS and KIT.  In addition to somatic mutations, aberrant intracellular signaling pathways and cell cycle disruption contribute to melanoma pathogenesis.  Indeed, recent next generation sequencing studies have identified a number of new genes involved in melanomagenesis.  A comprehensive evaluation and understanding of concurrent and mutually exclusive mutations in tumors has been lacking.  Therefore, we developed a comprehensive custom targeted capture of 108 genes previously implicated in melanoma pathogenesis.  We used the targeted panel to perform massively parallel sequencing on 94 well-established human melanoma cell lines, 67 patient-derived xenografts (PDX), and 5 cell lines made from PDX, all untreated. Samples were clustered based on deleterious mutations.  Eighty-three percent of samples had deleterious mutations in the MAPK signaling pathway (including BRAF, RAS) and NF1.  Ten percent of samples had PI3K pathway mutations which were predominantly associated with BRAF mutations.  TP53 was found to be mutated in 24% of the samples and were also associated with mutations in the MAPK pathway.  Mutations in chromatin remodeling genes were mutually exclusive with each other, but were associated with BRAF and NRAS mutations.  Of particular interest, five of the 10 NF1mutated samples harbored likely deleterious mutations in MAP3K5 or MAP3K9, suggesting the potential involvement of JNK signal transduction pathway in a cohort of samples.
AACR, Author Interviews, Breast Cancer, UCSD / 21.04.2015

Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New YorMedicalResearch.com Interview with: Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New York Medical Research: What is the background for this study? This year, breast cancer will claim the lives of nearly 40,000 women in the United States, and up to half of these women will have a disease that is driven by the estrogen receptor.
  • Although medicines have been approved for the treatment of hormone receptor-positive breast cancer for decades, more treatment options are needed.
  • Resistance to endocrine therapies causes morbidity and mortality for women with metastatic estrogen receptor-positive (ER+) breast cancer as many patients relapse or develop resistance to available hormonal agents via estrogen-dependent and estrogen-independent mechanisms.
  • Dual-acting investigational Selective Estrogen Receptor Degrader (SERDs) could potentially lead to a new treatment option for people with hormone receptor-positive breast cancer and may help overcome resistance to current anti-hormonal medicines.
  • GDC-0810 is a dual-acting investigational next-generation oral SERD that works in a number of ways to prevent estrogen fueling tumor growth. It is not only designed to target the estrogen receptor (ER) as an antagonist, but also to cause degradation of the ER protein. In preclinical studies, GDC-0810 was shown to induce tumor regressions in both tamoxifen sensitive and tamoxifen resistant tumor models in vivo.
Medical Research: What are the main findings?
  • Clinical data from the dose-escalation portion of a Phase I/IIa study evaluating GDC-0810 appears to have an acceptable safety profile with encouraging anti-tumor activity in postmenopausal women with advanced breast cancer positive for the estrogen receptor (ER), all of whom were previously treated with standard endocrine therapy.
  • Promising anti-tumor activity was observed in 38% of patients on study for six months or longer. At all doses tested, there was robust engagement of the estrogen receptor by GDC-0810 as demonstrated by fluoroestradiol (FES) PET scans.  Overall, the most common adverse events of any grade related to GDC-0810 were diarrhea, nausea and fatigue.