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Author Interviews, Biomarkers, Kidney Disease, University of Michigan / 07.12.2015

MedicalResearch.com Interview with: Wenjun Ju, Ph.D., M.S. Research Assistant Professor, Internal Medicine Matthias Kretzler, M.D. Professor, Internal Medicine, Nephrology Research Professor, Computational Medicine and Biology University of Michigan Health System  Medical Research: What is the background for this study? What are the main findings? Response: Chronic kidney disease (CKD) is a global health issue that affects approximately 15% of the global population.. While not all patients with CKD will progress to end-stage kidney disease (ESKD), those that do tend to advance quickly and require dialysis or kidney transplant. They are also at an increased risk of death from cardiovascular disease. According to the International Society of Nephrology, treatment of CKD, including medical management, dialysis and kidney transplant, is very costly.  In the U.S. alone, therapy for CKD is likely to exceed $48 billion per year, and the ESKD program consumes 6.7 percent of the total Medicare budget to care for less than 1 percent of the covered population. In China, the disease will cost the economy the equivalent of $558 billion in the U.S. over the next decade. Early identification of patients that are more likely to experience end-stage kidney disease is an urgent, unmet clinical need. Currently, kidney biopsy is required to determine diagnosis and prognosis of kidney disease. This procedure is costly, carries a low, but significant health risk, and has limited ability to predict the future course of kidney disease. Together with the European Renal cDNA Bank and the Peking University Institute of Nephrology, the University of Michigan team identified epidermal growth factor (EGF) as a promising candidate for prediction of kidney function loss while analyzing transcriptomic data derived from kidney tissue biopsies of CKD patients across Europe and the U.S. We then validated the findings in urine samples from more than 940 patients in North America, Europe and China, and found that a decrease in urinary EGF protein concentration is an early sign of diminishing kidney function and pinpoints the at-risk patient population. (more…)
Author Interviews, Breast Cancer, Cancer, Genetic Research / 07.12.2015

MedicalResearch.com Interview with: Dr. Jane E. Churpek, MD Assistant Professor of Medicine Co-Director, Comprehensive Cancer Risk and Prevention Program The University of Chicago Medicine Chicago, IL 6063 Medical Research: What is the background for this study? What are the main findings? Dr. Churpek:   We designed this study to try to understand whether damaging, inherited changes in genes known to cause an increased risk of breast cancer are common in those who develop leukemia after getting chemotherapy and/or radiation for treatment of breast cancer. Leukemias that occur in this setting are called “therapy-related.” This means that chemotherapy or radiation, or both, may have been involved in causing the leukemia.  This is an uncommon but serious complication of cancer treatment, and the factors that put women at risk for this complication are not well understood. We looked at the clinical histories of 88 such women. We found that most of them have relatives who also had cancer, suggesting they may be cancer-prone to begin with. Because we did not have a group of women who had similar breast cancer treatment and who did not get a therapy-related leukemia, we cannot definitively prove that more women with therapy-related leukemia than expected had these mutations. However, this study gives us reason to further study the role of these genes in therapy-related leukemia. (more…)
Author Interviews, Multiple Sclerosis / 07.12.2015

MedicalResearch.com Interview with: Dr. Vittorio Gallo PhD Center for Neuroscience Research Children’s Research Institute Children’s National Medical Center Washington, DC 20010 Medical Research: What is the background for this study? What are the main findings? Dr. Gallo: Astrocytes are cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, and help maintain homeostasis. In many neurodegenerative disorders – including multiple sclerosis  (MS) –astrocytes undergo a cellular and biochemical transformation called reactive gliosis. This process significantly impacts – both positively and negatively – neural regeneration. Reactive astrocytes (RAs) synthesize and release a peptide called Endothelin-1 (ET-1). Gallo and his team previously demonstrated that ET-1 is expressed at high levels by RAs in multiple sclerosis (MS) lesions and that – in animal models of MS – this peptide inhibits repair by delaying oligodendrocyte maturation and remyelination.  The main finding of the study published in Cell Reports is the identification of the cellular and molecular pathway that mediates the inhibitory effects of ET-1 on oligodendrocyte regeneration and remyelinaton in demyelinated lesions. In particular - by using pharmacological and genetic approaches - the study demonstrates that the ET-1 acts selectively through the ET-receptor B (ENDRB) on astrocytes - and not oligodendrocytes - to indirectly inhibit remyelination. (more…)
Author Interviews, Lancet, Multiple Sclerosis, Pharmacology, UCLA / 07.12.2015

MedicalResearch.com Interview with: Professor Rhonda Voskuhl, M.D. Jack H. Skirball Chair in MS Research Director of the UCLA MS Program David Geffen School of Medicine University of California, Los Angeles Medical Research: What is the background for this study? What are the main findings? Dr. Voskuhl: It had been known for decades that relapses were reduced during pregnancy in women with Multiple Sclerosis (MS), psoriasis and rheumatoid arthritis. We viewed this as a major clue to help find new disease modifying treatments. Focusing on MS, we investigated treatment with estriol, an estrogen that is made by the fetus/placenta during pregnancy. Preclinical studies and a pilot clinical trial at UCLA showed good results leading to the current Phase 2 clinical trial at 16 sites across the U.S. It showed that treatment with estriol pills compared to placebo pills, each in combination with standard of care (glatirmar acetate) injections, reduced relapses by one third to one half over and above standard of care treatment. (more…)
Author Interviews, Rheumatology, UCSF, Weight Research / 07.12.2015

MedicalResearch.com Interview with: Alexandra S. Gersing, MD Department of Radiology and Biomedical Imaging University of California, San Francisco Medical Research: What is the background for this study? What are the main findings? Dr. Gersing:  This study is part of a larger NIH-funded project focusing on the effects of weight change in individuals at risk for and with osteoarthritis. Our group has previously shown that weight gain causes substantial worsening of knee joint degeneration in patients with risk factors for osteoarthritis and now we aimed to show that weight loss could protect the knee joint from degeneration and osteoarthritis. Osteoarthritis is one of the major causes of pain and disability worldwide; and cartilage plays a central role in the development of joint degeneration. Since cartilage loss is irreversible, we wanted to assess whether lifestyle interventions, such as weight loss, could make a difference at a very early, potentially reversible stage of cartilage degradation and whether a certain amount of weight loss is more beneficial to prevent cartilage deterioration. To measure these early changes we used a novel Magnetic Resonance Imaging (MRI) technique, called T2 mapping, which allows us to evaluate biochemical cartilage degradation in the patient on a molecular level. The most relevant finding of this study is that patients with more that 10% of weight loss benefited significantly more from losing weight compared to the obese controls that did not lose weight or only lost little weight. (more…)
Author Interviews, Genetic Research, Weight Research / 06.12.2015

MedicalResearch.com Interview with: Ida Donkin MD, PhD Postdoc, Medical Doctor, PhD University of Copenhagen Faculty Of Health Sciences Copenhagen, Denmark Medical Research: What is the background for this study? Dr. Donkin: We know that children of obese fathers are more prone to develop obesity themselves – regardless of the weight of the mother. We also know that obesity and diabetes are diseases with a very big inheritable components in their aetiology. If your parents are obese, you have a risk of about 75% percent of developing obesity yourself. But we do not know how the disease is inherited from one generation to the next. Despite exhaustive research trying to investigate genes potentially responsible for this, and more than 125 genetic mutations have been discovered to associate to the development of obesity, all the genetic mutations put together cannot explain more than about 10% of the actual inheritance. So how is obesity inherited from parents to children? One explanation could be the transfer of epigenetic information from one generation to the next. Epigenetic information is established in our body’s cells in response to our lifestyle and the environment around us. We discovered that the epigenetic factors of semen cells also responds to changes in our lifestyle, and we speculated whether these might be the key to understand how obesity in dads can lead to obesity in children. Medical Research: What are the main findings? Dr. Donkin: In this study we discovered that the information kept in our semen cells responds dynamically to changes in our lifestyle. If you are obese, your semen cells will contain a different epigenetic pattern than if you are lean. Weight loss induced by gastric bypass surgery will dynamically change these epigenetic patterns, meaning that by changing our lifestyle, we can actively change the epigenetic information we pass on to our children. Other research groups have created solid evidence showing us that most these epigenetic marks kept in the sperm cells will be passed on to the embryo at fertilization. The epigenetic information can affect the development of the embryo, and thereby change the health – and the risk of disease – of our children. Our study thus provides a likely explanation for the mechanism of the inheritance of acquired traits and diseases through generations, and gives us a likely explanation as to why children of obese fathers are more prone to develop obesity themselves. (more…)
Author Interviews, Colon Cancer, Cost of Health Care, Health Care Systems, Outcomes & Safety, Surgical Research / 06.12.2015

MedicalResearch.com Interview with: Johannes Govaert MD Department of Surgery Leiden University Medical Center Leiden, The Netherlands Medical Research: What is the background for this study? Dr. Govaert: The Value Based Health Care agenda ofPprof. Porter (Harvard Business School) suggests that focus in healthcare should shift from reducing costs to improving quality: where quality of healthcare improves, cost reduction will follow. One of the cornerstones of potential cost reduction, as mentioned by Porter, could be availability of key clinical data on processes and outcomes of care. Despite the important societal and economical role the healthcare system fulfils, it still lags behind when it comes to standardised reporting processes. With the introduction of the Dutch Surgical Colorectal Audit (DSCA) in 2009, robust quality information became available enabling monitoring, evaluation and improvement of surgical colorectal cancer care in the Netherlands. Since the introduction of the DSCA postoperative morbidity and mortality declined. Primary aim of this study was to investigate whether improving quality of surgical colorectal cancer care, by using a national quality improvement initiative, leads to a reduction of hospital costs. Detailed clinical data was obtained from the 2010-2012 population-based Dutch Surgical Colorectal Audit. Costs at patient-level were measured uniformly in all 29 participating hospitals and based on Time-Driven Activity-Based Costing. Medical Research: What are the main findings? Dr. Govaert: Over three consecutive years (2010-2012) severe complications and mortality after colorectal cancer surgery respectively declined with 20% and 29%. Simultaneously, costs during primary admission decreased with 9% without increase in costs within the first 90 days after discharge. Moreover, an inverse relationship (at hospital level) between severe complication rate and hospital costs was identified among the 29 participating hospitals. Hospitals with increasing severe complication rates (between 2010 and 2012) were associated with increasing costs whereas hospitals with declining severe complication rates were associated with cost reduction. (more…)
Accidents & Violence, Author Interviews / 06.12.2015

MedicalResearch.com Interview with: Professor Ajai Singh Department of Orthopaedic Surgery King George's Medical University India  Medical Research: What is the background for this study? Prof. Singh: Road traffic accidents (RTAs), in the current scenario, have taken the form of an epidemic. Developing countries are presently showing an increasing trend with respect to the number of vehicles and population. Personality characteristics are becoming a significant contributor in RTAs, owing to rising stress levels and varying circumstances. In developing countries, most of the RTAs occur in urban regions and pedestrians, passengers, and motorcyclists collectively constitute around 90% of deaths. We, therefore, conducted this study in order to evaluate the patterns of various personality characteristics in patients suffering from nonfatal orthopedic injuries as a result of Road traffic accidents and attending a tertiary care center, with special focus on motorcyclists. Medical Research: What are the main findings? Prof. Singh: Most of the accidental injuries are faced by motorized two wheeler drivers of younger age. This is probably due to the fact that we are a developing nation with a huge population having motorized two wheeler vehicles as a major means of private transport. Also, these motorized two wheelers have a low safety profile that makes their riders more prone to accident. Amongst all the motorcyclists encountering road traffic accidents, impulsive personality trait is found in 85.19% and histrionic trait was found in 82.72% of cases. (more…)
Author Interviews, Lifestyle & Health, PLoS / 06.12.2015

MedicalResearch.com Interview with: Ding Ding (Melody), Ph.D., MPH NHMRC Early Career Senior Research Fellow Sydney University Postdoctoral Research Fellow Prevention Research Collaboration Sydney School of Public Health The University of Sydney  Medical Research: What is the background for this study? What are the main findings? Response:  The study followed a large sample (around 200,000) of Australian adults aged 45 or older. Participants reported their lifestyle behaviours (smoking, excessive alcohol use, physical inactivity, unhealthy diet, prolonged sitting, short/long sleep duration) at baseline (2006-2009) and were followed up for around 6 years (up to June 2014). Based on linked administrative data (death records), we found a clear relationship between the total number of lifestyle risk behaviours and the risk of mortality---the more risk behaviours, the higher risk for mortality. This pattern of associations was consistent in men and women, participants in different age groups, of different socioeconomic status, and with and without major chronic disease. Certain behavioural risk factors have synergistic associations with mortality and appear more harmful together than individually. For example, if people only sit for long hours (defined as >7 hours a day), without having other co-occurring risk behaviours, the risk for mortality was only elevated by 15%, and if people are only physically inactive without having other co-occurring risk behaviours, the risk for mortality was elevated by 60%. However when the two risk factors were combined, say if one is not physically active AND sit for long hours, the combined risk has become much larger (increased by 140%, compared with those with zero risk behaviours).  Similarly, the combination of smoking and excessive alcohol use appeared a lot more “deadly” than the two risk factors alone. (more…)
Author Interviews, Heart Disease, JAMA, Kidney Disease / 05.12.2015

MedicalResearch.com Interview with: Girish N. Nadkarni, MD, MPH Division of Nephrology, Department of Medicine Icahn School of Medicine at Mount Sinai New York, New York MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Nadkarni: Cardiovascular disease is one of the major causes of morbidity and mortality in patients with kidney disease. Moreover, there is a lack of good quality evidence in kidney disease patients. In addition, previous studies have shown that cardiovascular trials exclude patients with kidney disease. We wanted to analyze all of the clinical trials on acute myocardial infarctions and heart failure in the last decade and see if they continued excluding patients with kidney disease. We discovered that in 371 trials including close to six hundred thousand patients, the majority (57%) excluded patients with kidney disease. A large proportion of the trials excluded patients for non-specific reasons, rather than a prespecified threshold of kidney function and did not report kidney function at baseline. Finally, in trials that did include kidney patients and reported outcomes by kidney function, only 13% showed an interaction or suggestion of harm. (more…)
Author Interviews, Cancer Research, Cleveland Clinic, Heart Disease / 05.12.2015

MedicalResearch.com Interview with: Sadeer G Al-Kindi, MD Fellow, Harrington Heart and Vascular Institute Onco-Cardiology Program, Advanced Heart Failure and Transplant Center, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center Cleveland, OH Medical Research: What is the background for this study? Dr. Al-Kindi: Cardiovascular disease and cancer are the most common causes of death in the United States. They often have the same risk factors (for example, smoking, advancing age, obesity). Many cancers are treated with drugs that can have detrimental effect on the heart thus limiting their use. Some studies have suggested that cardiovascular diseases can worsen outcomes in patients with cancer. The emergence of onco-cardiology programs led to multidisciplinary care of patients with cancer and heart disease. Given this tight relationship between cancers and cardiovascular disease, we hypothesized that heart disease and its risk factors are very common in patients diagnosed with cancer. Medical Research: What are the main findings? Dr. Al-Kindi: Using a very large clinical database of 1/8th of the US population, we identified patients with most common cancers that are treated with cardiotoxic medications and identified the prevalence of cardiovascular diseases. Overall, prevalence was 33% for hematologic malignancies (leukemia and lymphoma), 43% for lung cancers, 17% for breast cancers, 26% for colon cancers, 35% for renal cancers, and 26% for head and neck cancers. Peripheral artery disease, coronary artery disease and cerebrovascular diseases were the most common, followed by heart failure, and carotid artery disease. Despite the high prevalence, only about a half of these patients were on the cardiovascular medicines and half were referred to cardiologists. (more…)
Author Interviews, Genetic Research, Heart Disease, Neurological Disorders, NIH, Science / 05.12.2015

MedicalResearch.com Interview with: Jonathan Kaltman, MD Chief, Heart Development and Structural Diseases Branch Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute Medical Research: What are the main findings? Dr. Kaltman:  Congenital heart disease (CHD) is the most common birth defect but the cause for most defects is unknown.  Surgery and clinical care of patients with congenital heart disease has improved survival but now we are learning that many patients have neurodevelopmental abnormalities, including learning disability and attention/behavioral issues. Medical Research:  What are the main findings?
  • Using exome sequencing we found that patients with  congenital heart disease have a substantial number of de novo mutations.  This finding is especially strong in patients with CHD and another structural birth defect and/or neurodevelopmental abnormalities.
  • Many of the genes identified are known to be expressed in both the heart and the brain, suggesting a single mutation may contribute to both congenital heart disease and neurodevelopmental abnormalities.
(more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Mental Health Research / 05.12.2015

MedicalResearch.com Interview with: Dr. Jamie Stagl, PhD Was a Ph.D. student in Psychology at University of Miami during the research period Currently, a post-doctoral fellow in Psychiatric Oncology Massachusetts General Hospital Cancer Center in Boston Medical Research: What is the background for this study? What are the main findings? Dr. Stagl: This is a newly published finding from a randomized trial funded by the National Cancer Institute that showed that women with breast cancer who received stress management skills early on in their treatment had longer survival and longer time without breast cancer recurrence at eight to 15 years after their initial diagnosis. This secondary analysis is published online and in the November 2015 issue of Breast Cancer Research and Treatment. The study was conducted by senior investigator, Michael Antoni, Ph.D., Survivorship Theme Leader of the Cancer Control research program at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and Professor of Psychology and Psychiatry and Behavioral Sciences, and his research team, including lead author Jamie Stagl, Ph.D., currently a postdoctoral fellow at Massachusetts General Hospital Cancer Center in Psychiatric Oncology and Behavioral Sciences. In this trial, women received an intervention called Cognitive-Behavioral Stress Management, which was created by Dr. Michael Antoni at the University of Miami. After surgery for breast cancer, women received 10 weekly, group-based sessions of skills to manage stress based in cognitive-behavioral strategies and relaxation training. Women learned muscle relaxation, mindfulness meditation, and breathing exercises to promote relaxation. Women also learned strategies for altering negative thoughts, worries, and improve coping. Previous studies by Dr. Antoni and his research team have shown that women who received these stress management skills had better psychological adjustment, less distress, and less anxiety through treatment. Dr. Stagl recently published findings showing that these women had less depressive symptoms and better quality of life during survivorship. The current study shows that these women may also benefit from stress management in terms of risk of disease progression and mortality. (more…)
Author Interviews, Breast Cancer, Lancet, Mammograms, Radiology / 05.12.2015

MedicalResearch.com Interview with: Prof Stephen Duffy BSc MSc CStat Professor Of Cancer Screening Wolfson Institute Of Preventive Medicine Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Prof. Duffy: There is debate on the value of diagnosing and treating ductal carcinoma in situ (DCIS) of the breast, depending mainly on different theories about the risk of progression to invasive breast cancer if DCIS were untreated. No-one asserts that no DCIS is progressive and no-one asserts that all DCIS is progressive. There is, however, a range of opinions on the proportion of progressive disease. We found that those mammography screening units in the UK with higher detection rates of DCIS had lower subsequent rates of invasive cancers in the three years after screening. (more…)
Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, CT Scanning, Gender Differences, Lung Cancer / 04.12.2015

MedicalResearch.com Interview with: Phillip Boiselle, M.D. Staff, Cardiothoracic Imaging Beth Israel Deaconess Medical Center Associate Dean for Academic and Clinical Affairs Professor of Radiology, Harvard Medical School Boston, Mass Medical Research: What is the background for this study? What are the main findings? Dr. Boiselle: Previous studies have shown that women have a greater mortality benefit from lung cancer screening then men, and that this test (CT screening) is more cost-effective for women than men. Our purpose was to determine whether the relative risk of lung cancer for women and men differed depending on the specific type of lung nodule that was discovered at screening. Such differences could potentially help to influence a more personalized approach to patient management in lung cancer screening. (more…)
Abuse and Neglect, Author Interviews, JAMA, OBGYNE / 04.12.2015

MedicalResearch.com Interview with: Alex Haynes, MD, MPH Assistant Professor of Surgery, Harvard Medical School Assistant in Surgery, Massachusetts General Hospital Division of Surgical Oncology Associate Program Director, Safe Surgery, Ariadne Labs Research Associate Harvard School of Public Health and George Molina, MD, MPH Surgical Research Resident Massachusetts General Hospital  Medical Research: What is the background for this study? What are the main findings? Response: We have previously done work looking at the global volume of operations, and in particular the surgical volume at a country level. This work was based on the hypothesis that a certain level of surgical care is necessary for healthy populations. In doing this work, we found that cesarean delivery makes up a large proportion of all operations that happen globally. In the mid-1980’s, based on existing data the World Health Organization made the recommendation that at a country-level, the cesarean delivery rate should not exceed 10 to 15 per 100 live births. We wanted to see if this recommendation was still applicable using current data. In order to answer this question, we used multiple imputation to estimate country-level cesarean delivery rates for all 194 countries in the world in 2012 to investigate the association between country-level cesarean delivery rates and maternal and neonatal mortality. We found that at a population level, as the cesarean delivery rate increased up to about 19 per 100 live births, there was a decrease in country-level maternal and neonatal mortality. However, as country-level cesarean delivery rates rose above this level there were no associated changes in maternal or neonatal mortality. (more…)
Author Interviews, HIV, Immunotherapy, PLoS / 04.12.2015

MedicalResearch.com Interview with: Andreas Meyerhans, PhD ICREA Research Professor at the University Pompeu Fabra Infection Biology Group Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain Medical Research: What is the background for this study? What are the main findings? Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion. We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds. (more…)
Author Interviews, Psychological Science, Sexual Health / 04.12.2015

MedicalResearch.com Interview with: Tess M. Gemberling, M.A. Social Psychology Ph.D. Student Co-Principal Investigator University of Alabama Medical Research: What is the background for this study? Response: Many stereotypes of BDSM (bondage and discipline [B&D], dominance and submission [D/s], sadomasochism [SM],) that can be seen on websites similar to fucked gay xxx, exist; however, research with practitioners suggests these stereotypes are largely unfounded. Preliminary evidence implies BDSM practitioners are psychologically healthy individuals. This study was conducted to further evaluate these results. Medical Research: What are the main findings? Response: Along with other findings, the majority of results indicates practitioners are well functioning. Overall, participants are healthy in the mental, emotional, and interpersonal aspects of their lives. In addition, practitioners are often victims of violence but are not perpetrators of violence. (more…)
Author Interviews, BMC, BMJ, Genetic Research / 03.12.2015

MedicalResearch.com Interview with: Hatem A. Azim MD PhD Breast Cancer Translational Research Laboratory Institut Jules Bordet Université Libre de Bruxelles Brussels, Belgium Medical Research: What is the background for this study? What are the main findings? Dr. Azim: As at breast cancer diagnosis is known to impact prognosis, with young patients having worse outcome. On the other hand, elderly patients are less studies in general and little is known on their tumor characteristics. In this study, we aimed to define the pattern of genomic aberrations in different age groups. This can result in identifying if key potentially targetable genomic alterations are more specific to particular age groups and thus could open the door to design particular studies targeting these aberrations in these age groups. We found that  age is associated with unique biological features at the DNA level, independent of tumor stage, histology and breast cancer molecular subtype. Of particular mention, the higher prevalence of GATA3 mutation in younger patient, a known driver mutation associated with endocrine resistance. In addition, age at diagnosis appears to impact the tumor transcriptome confirming previous observations, but also highlighting novel findings, of particular relevance the higher expression of stem cell related genes in young patients. (more…)
Author Interviews, Karolinski Institute, Lancet, OBGYNE, Weight Research / 03.12.2015

MedicalResearch.com Interview with: Professor Sven Cnattingius Professor in reproductive epidemiology Clinical Epidemiology Unit, Department of Medicine Karolinska University Hospital Karolinska Institutet, Stockholm, Sweden  Medical Research: What is the background for this study? Prof. Cnattingius: Maternal overweight and obesity are associated with increased risks of stillbirth and infant mortality. Weight gain between pregnancies increases risks of other obesity-related complications, including preeclampsia, gestational diabetes, and preterm birth. Weight gain appear to increase these risks especially in women who start off with normal weight. As these complications increases risks of stillbirth and infant mortality, we wanted to study the associations between weight change between successive pregnancies and risks of stillbirth and infant mortality (deaths during the first year of life). Medical Research: What are the main findings? Prof. Cnattingius: The main findings include:
  • Weight gain increases risk of stillbirth in a dose-response manner.
  • In women starting off with normal weight (BMI <25), weight gain  increases risk of infant mortality in a dose-response manner.
  • In women starting off with overweight or obesity (BMI >25), weight loss reduces the risk of neonatal mortality (deaths during the first four weeks of life).
(more…)
Alzheimer's - Dementia, Author Interviews, Nature, UCSF / 03.12.2015

MedicalResearch.com Interview with: Elsa Suberbielle, DVM, PhD Research Scientist Gladstone Institute of Neurological Diseases San Francisco, CA 94158 Medical Research: What is the background for this study? Dr. Suberbielle: BRCA1 is a key protein involved in DNA repair, and mutations that impair its function increase the risk for breast and ovarian cancer. Research into DNA repair mechanisms in dividing cells recently was recently rewarded by the Nobel Prize in Chemistry. In such cells, BRCA1 helps repair a type of DNA damage known as double-strand breaks that can occur when cells are injured. In neurons, though, such breaks can occur even under normal circumstances, for example, after increased brain activity, as shown by the team of Gladstone scientists in an earlier study. The researchers speculated that in brain cells, cycles of DNA damage and repair facilitate learning and memory, whereas an imbalance between damage and repair disrupts these functions. Medical Research: What are the main findings? Dr. Suberbielle In a new study published in Nature Communications, Researchers from the Gladstone Institutes demonstrates that Alzheimer’s disease is associated with a depletion of BRCA1 in neurons and that BRCA1 depletion can cause cognitive deficits. The researchers experimentally reduced BRCA1 levels in the neurons of mice. Reduction of the DNA repair factor led to an accumulation of DNA damage and to neuronal shrinkage. It also caused learning and memory deficits. Because Alzheimer’s disease is associated with similar neuronal and cognitive problems, the scientists wondered whether they might be mediated by depletion of BRCA1. They therefore analyzed neuronal BRCA1 levels in post-mortem brains of Alzheimer’s patients. Compared with non-demented controls, neuronal BRCA1 levels in the patients were reduced by 65-75%. To determine the causes of this depletion, the investigators treated neurons grown in cell culture with amyloid-beta proteins, which accumulate in Alzheimer brains. These proteins depleted BRCA1 in the cultured neurons, suggesting that they may be an important cause of the faulty DNA repair seen in Alzheimer brains. Further supporting this conclusion, the researchers demonstrated that accumulation of amyloid-beta in the brains of mice also reduced neuronal BRCA1 levels. They are now testing whether increasing BRCA1 levels in these mouse models can prevent or reverse neurodegeneration and memory problems. (more…)
Author Interviews, CDC, Gender Differences, HIV / 03.12.2015

MedicalResearch.com Interview with: Dr. Andrew Auld MD, MSc Medical Epidemiologist Division of Global HIV & TB CDC MedicalResearch: What is the background for this study? Dr. Auld: Equitable access to antiretroviral therapy for men and women living with HIV is a principle endorsed by most countries and funding bodies, including the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). This analysis, including more than 765,000 adult patients starting antiretroviral therapy in 12 countries (10 African countries, Haiti, and Vietnam), is the most up-to-date and comprehensive assessment of differences in HIV treatment access among men and women with HIV in developing countries. MedicalResearch: What are the main findings? Dr. Auld: Investigators showed that in all 10 African countries and Haiti, women with HIV were far more likely to be on treatment than men. In these 11 countries, women were 23%–83% more likely to access antiretroviral therapy than men with HIV. In addition, in six African countries and Haiti, gender imbalance in HIV treatment access appears to be getting worse over time. (more…)
Author Interviews, Blood Pressure - Hypertension, Coffee / 03.12.2015

MedicalResearch.com Interview with: Wenji Li, MMed, PhD Postdoc Associate Department of Pharmaceutics Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey Medical Research: What is the background for this study? What are the main findings? Dr. Li: Hypertension is a vital risk factor for many serious disorders. Male and age ≥40 years were found to be highly associated with more severe hypertension. In Singapore, the prevalence of hypertension increased markedly from age 40 years onwards. Tea, a popular beverage in Chinese people, has been approved to possess many beneficial pharmacological effects including antihypertension. However, no clinical studies on the correlation between tea drinking and its effect on lowering blood pressure among Singaporeans have been conducted. To find out the potential link, we are the first to investigate the correlation of hypertension and consumption of tea, health supplements, living habits and socio-demographic factors among Singaporean Chinese residents. By the large scale cross-sectional epidemiology study (N = 1184), we found the prevalence of hypertension among the whole investigated population was 49.73% and the prevalence increased to 66.47% in the sub-population aged ⩾60 years. High risk of hypertension was associated with age ⩾60 years, obesity, family history of hypertension, diabetes history, hyperlipidemia history, male and coffee intake. In contrast, drinking green tea at least 150 ml per week was associated with lower hypertension risk. Drinking combination of green tea and British tea was associated with higher reduction in the risk of hypertension. This study suggests that consumption of tea, especially green tea and British tea, is beneficial for lowering the risk of hypertension while the consumption of coffee may have the opposite effect.  (more…)
Author Interviews, Breast Cancer, Depression, JNCI, Kaiser Permanente / 03.12.2015

MedicalResearch.com Interview with: Reina Haque, PhD, MPH Research scientist Department of Research & Evaluation Kaiser Permanente Southern California Pasadena Calif Medical Research: What is the background for this study? What are the main findings? Dr. Haque: Tamoxifen is a commonly prescribed generic drug taken by women with breast cancer to reduce their chances of developing a recurrence. Tamoxifen is recommended for five years, but has notable side effects, including hot flashes, night sweats and depression. Since hormone replacement therapy is not recommended to alleviate these symptoms in breast-cancer survivors, antidepressants have been increasingly prescribed for relief. Almost half of the 2.4 million breast-cancer survivors in the U.S. take antidepressants. However, previous studies have suggested that antidepressants reduce tamoxifen's effectiveness in lowering subsequent breast-cancer risk. This study was conducted to determine whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer. (more…)
ASCO, Author Interviews, Immunotherapy, Ovarian Cancer / 02.12.2015

MedicalResearch.com Interview with: Junzo Hamanishi  M.D., Ph.D. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine Assistant Professor Kyoto Japan Medical Research: What is the background for this study? Dr. Hamanishi: More than 70% of patients with advanced ovarian cancer who achieve remission ultimately relapse and there are few effective treatments for these patients. Because the development of new treatment strategies for these patients is urgently required, we have focused on and studied the potential of cancer cells to escape from host immunity with PD-1/PD-L1 immunosuppressive signal in the tumor microenvironment to find new treatment strategies to overcome this phenomenon, collaborating with Professor Honjo who discovered PD-1 since 2006. Therefore, we conducted a phase II clinical trial in 20 platinum-resistant, recurrent ovarian cancer patients to evaluate the safety and anti-tumor efficacy of anti-PD-1 antibody (nivolumab) with 2 cohort at a dose of 1 or 3 mg/kg (constituting two 10-patient cohorts). Medical Research: What are the main findings? Dr. Hamanishi: This study is the first investigator-initiated phase II clinical trial testing the safety and efficacy of nivolumab against platinum-resistant ovarian cancer. In the 20 patients in whom responses could be evaluated, the best overall response was 15%, including two patients with a durable complete response (3mg/kg cohort). The disease control rate in all 20 patients was 45%. The median progression-free survival was 3.5 months, with a median overall survival of 20.0 months. Especially in the 3 mg/kg cohort, two patients achieved a complete response, and disease stabilized in another two patients. The objective response rate in 3mg/kg cohort cohort was 20% and disease was controlled in 40% of the higher-dose group. In the four patients who demonstrated an antitumor response, responses were durable and evident. Grade 3 or 4 treatment-related adverse events (AE) occurred in eight out of 20 patients or 40% overall. However, the frequency of AEs were not different in 2 cohorts. (more…)
Author Interviews, Infections, Nature / 02.12.2015

MedicalResearch.com Interview with: Professor Søren Riis Paludan DMSc, PhD Department of Biomedicine Aarhus University Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Paluden: We were interested in understanding the first immune reactions that occur when an organism meets an infectious agent (virus or bacteria). The main finding is that we have identified an immune reaction that is activated as the microbe disturbed the mucus layer at mucosal surfaces. This is an immune reaction occuring earlier than what has been thought previously, and may represent a mechanism that enables the organism to fight most microbes that we meet without mounting strong immune responses. This is important, since strong immune reactions - in addition to contributing to elimination of microbes - also have negative effects such as fever, etc. (more…)
Author Interviews, Cognitive Issues, Exercise - Fitness, JAMA, Lifestyle & Health / 02.12.2015

MedicalResearch.com Interview with: Tina Hoang MSPH Staff Research Associate Northern California Institute for Research and Education, Veterans Affairs Medical Center Dr. Kristine Yaffe MD Professor of Psychiatry, Neurology, and Epidemiology University of California San Francisco, CA  94121 Medical Research: What is the background for this study? What are the main findings? Response: We assessed physical activity and TV watching in young adults over 25 years to see if there was an association with cognitive function in middle age.  Most previous studies have only considered this association in older adults. We found that both low physical activity and high TV watching over time were associated with worse cognitive function. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, MRI, Yale / 02.12.2015

MedicalResearch.com Interview with: Shiyi Wang, MD, PhD Assistant Professor of Epidemiology (Chronic Diseases) Yale School of Public Health Medical Research: What is the background for this study? Dr. Wang: As magnetic resonance imaging (MRI) of the breast has become part of medical care, there is increasing concern that this highly sensitive test might identify health problems that otherwise would not have had an impact on the patient – so called “overdiagnosis”. However, even if MRI use leads to overdiagnosis, the main “theoretical” benefit of early detection by MRI is to prevent future advanced diseases, the prognosis of which is deleterious. A systematic literature review found that, compared to mammography and/or ultrasound, MRI had a 4.1% incremental contralateral breast cancer (breast cancer in the opposite breast) detection rate. At this point, the impact of MRI on long-term contralateral breast cancer outcomes remains unclear.  Medical Research: What are the main findings? Dr. Wang: Analyzing the Surveillance, Epidemiology, and End Results-Medicare dataset, we compared two groups of women who had breast cancer (one group receiving an MRI, and the other not) in terms of stage-specific contralateral breast cancer occurrences. We found that after five years, the MRI group had a higher detection rate of cancer in the opposite breast than the non-MRI group (7.2 % vs. 4.0%). Specifically, MRI use approximately doubles the detection rate of early stage contralateral breast cancer, but does not decrease the incidence of advanced stage contralateral breast cancer occurrences after a 5-year follow-up. Our results indicate that nearly half of additional breast cancers detected by the preoperative MRI were overdiagnosed, which means that many of these occult cancers not detected by MRI would not have become clinically evident over the subsequent 5 years. There was no evidence that MRI use was benefiting women because the rate of advanced cancer was similar in the MRI and the non-MRI groups. (more…)