Author Interviews, Biomarkers, Cancer Research / 02.07.2015

MedicalResearch.com Interview with: Chao Cheng, Ph.D. Assistant Professor Department of Genetics Institute for Quantitative Biomedical Sciences Geisel School of Medicine at Dartmouth Hanover NH, 03755 Medical Research: What is the background for this study? Dr. Cheng: Bladder cancer is a common tumor type, with non-muscle-invasive bladder cancer (NMIBC) representing the majority of cases. Bacillus Calmette-Guerin (BCG) treatment is an effective immunotherapy that is commonly used to treat cancers of this subtype. However, this treatment fails to suppress tumor recurrence in up to 40% of patients. For this reason, biomarkers that predict the recurrence/progression of bladder cancer and patient response to BCG therapy are needed to tailor treatment strategies to individual patients. Medical Research: What are the main findings? Dr. Cheng: We had previously developed an E2F4 signature that consisted of the E2F4 transcription factor and its target genes identified by ChIP-seq and ChIP-chip experiments. Here, we found that the E2F4 signature is predictive of the progression of both non-muscle-invasive and muscle-invasive bladder cancer. Furthermore, this signature is also predictive of patient responsiveness to intravesical BCG immunotherapy. Our results suggest that patients with positive E2F4 scores (indicating high E2F4 activity) benefit significantly from BCG therapy, while the progression of patients with negative E2F4 scores (indicating low E2F4 activity) does not show significant difference from untreated patients. (more…)
Author Interviews, Cancer Research, JNCI, NIH, OBGYNE / 02.07.2015

MedicalResearch.com Interview with: Ashley S. Felix, PhD Bethesda, MD MedicalResearch: What is the background for this study? What are the main findings? Dr. Felix: Endometrial cancer prognosis is strongly affected by disease stage, or the extent of spread from the primary site. Endometrial cancers can spread via the lymph nodes, blood vessels, through the uterine wall, or through the fallopian tube into the peritoneal cavity. The last of these mechanisms is poorly understood, but appears to be a more common mode of spread for aggressive histologic subtypes of endometrial cancer. We hypothesized that women who previously underwent tubal ligation (TL) and later developed endometrial cancer would have lower stage disease, possibly by blocking passage of tumor cells along the fallopian tubes. Further, we hypothesized that TL would be associated with better prognosis, due to its relationship with lower stage. We found that women in our study who previously had tubal ligation were more likely to have lower stage endometrial cancer compared with women who did not report a previous tubal ligation. Specifically, tubal ligation was inversely associated with stage III and stage IV cancer across all subtypes of the disease, including aggressive histologic subtypes. Further, in statistical models of tubal ligation, tumor stage, and mortality, we observed no independent association with improved survival, suggesting that tubal ligation impacts mortality mainly through its effects on stage. (more…)
Author Interviews, Ebola, Lancet / 02.07.2015

MedicalResearch.com Interview with: Jana Broadhurst, MD, PhD Stanford University Nira R Pollock MD PhD Boston Children's Hospital, Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: At present, diagnosis of Ebola virus disease (EVD) in west Africa requires transport of venipuncture blood to field laboratories for testing by real-time RT-PCR, resulting in delays that complicate patient care and infection control efforts. Therefore, an urgent need exists for a point-of-care rapid diagnostic test (RDT) for this disease. In this study, we performed a field validation of the Corgenix ReEBOV Antigen Rapid Test kit, the only Ebola RDT authorized for emergency use by the WHO and FDA. This test is a dipstick lateral flow immunoassay designed to detect the Ebola virus VP40 protein in whole blood (collected by either fingerstick or whole blood) or plasma. We performed the rapid diagnostic test at the point-of-care on fingerstick blood samples from 106 individuals with suspected EVD presenting at two Ebola clinical centers in Sierra Leone. Separately, we performed the RDT on 284 venous whole blood samples submitted to the Public Health England field reference laboratory for clinical testing. Two readers independently scored each RDT as positive, negative, or invalid, with any disagreements resolved by a third. RDT results were compared with clinical real-time RT-PCR results obtained with the RealStar Filovirus RT-PCR kit 1.0 (altona Diagnostics GmBH). In point-of-care testing of fingerstick blood, the RDT had 100% sensitivity (95% CI 87.7-100) and 92% specificity (95% CI 83.8-97.1). Similarly, in venipuncture blood tested in the reference laboratory the rapid diagnostic test had 100% sensitivity (95% CI 92.1-100) and 92% specificity (95% CI 88.0-95.3). The two independent readers agreed for 95.2% of point-of-care and 98.6% of reference laboratory RDT results. The maximum cycle threshold (Ct) value was 26.3 in PCR-positive samples tested from both point-of-care (mean Ct 22.6) and reference laboratory (mean Ct 21.5) cohorts. Six of 16 banked plasma samples from RDT-positive and altona-negative patients were positive by an alternative real-time RT-PCR assay (the Trombley assay); 3 of 18 samples from individuals who were negative by both the RDT and altona test were also positive by Trombley. (more…)
Author Interviews, Heart Disease, JAMA, University of Pittsburgh, Weight Research / 02.07.2015

Anita P. Courcoulas M.D., M.P.H., F.A.C.S Professor of Surgery Director, Minimally Invasive Bariatric & General Surgery University of Pittsburgh Medical CenterMedicalResearch.com Interview with: Anita P. Courcoulas M.D., M.P.H., F.A.C.S Professor of Surgery Director, Minimally Invasive Bariatric & General Surgery University of Pittsburgh Medical Center Medical Research: What is the background for this study? Dr. Courcoulas: This study is a randomized clinical trial that was originally funded through the American Recovery and Reinvestment Act of 2009 (ARRA) as a high priority comparative effectiveness topic; the goal of which was to better understand the role of surgical versus non-surgical treatments for Type 2 diabetes mellitus (T2DM) in people with lower Body Mass Index (BMI) between 30 and 40 kg/m2. This report highlights longer-term outcomes at 3 years following random assignment to either an intensive lifestyle weight loss intervention for 1 year followed by a low-level lifestyle intervention for 2 years or surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) followed by low-level lifestyle intervention in years 2 and 3. (more…)
Author Interviews, CDC, Dermatology, JAMA / 02.07.2015

Dr Gery GuyMedicalResearch.com Interview with: Gery P. Guy Jr., PhD, MPH Health Economist Division of Cancer Prevention and Control Centers for Disease Control and Prevention Medical Research: What is the background for this study? What are the main findings? Dr. Guy: Indoor tanning exposes users to intense ultraviolet radiation, which damages the skin and can cause skin cancer, including melanoma (the deadliest type of skin cancer), basal cell carcinoma, and squamous cell carcinoma. Previous research has demonstrated that indoor tanning is common among adults in the United States. This study examined the changes in prevalence and frequency of indoor tanning among adults in the United States. Our study found significant reductions in indoor tanning among all adults, women, and men. From 2010 to 2013, 1.6 million fewer women and 400,000 fewer men indoor tanned. While these reductions are encouraging, nearly 10 million adults continue to indoor tan at least once a year. These individuals are trading a tan for an increased risk of skin cancer. While the tan is temporary, the risk for skin cancer is permanent. (more…)
Author Interviews, Biomarkers, Chemotherapy, Nature, Pancreatic / 01.07.2015

Dr. Janaiah Kota Assistant Professor, Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis, IN,MedicalResearch.com Interview with: Dr. Janaiah Kota Assistant Professor, Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis, IN, Medical Research: What is the background for this study? Dr. Kota: Pancreatic cancer tumors are surrounded by a thick fibrotic shell known as “stroma” which protects the cancer cells from anticancer drugs such as chemotherapy. However, complete depletion of tumor stroma leads to more aggressive disease and decreases survival. The stromal abundance needs to be appropriately moderated (i.e. not too much nor too little) in pancreatic tumors. None of the current anti-stromal therapies have been effective enough to resolve this problem. Unless we understand the molecular signatures associated with tumor stroma, it will be challenging to develop an effective therapeutic strategy. There is a desperate need to develop new therapies for pancreatic cancer as only 7 percent of people with the disease survive more than 5 years after diagnosis. According to the National Cancer Institute, there will be an estimated 48,960 new cases of pancreatic cancer and 40,560 deaths from the disease in 2015. Medical Research: What are the main findings? Dr. Kota: We found that the loss of microRNA-29 (miR-29) is a common phenomenon of pancreatic cancer stromal cells, and that by restoring it, the viability and growth of the cancerous cells and stromal accumulation was reduced. The use of miR-29 as a therapeutic agent may be more effective in targeting reactive stroma, as a single miRNA regulates the expression of several genes associated with disease mechanisms. We expect that this novel approach has the potential to overcome the problems associated with current anti-stromal drugs and could lead to improved therapeutic strategies, enhanced drug delivery to the tumor bed, and, in the future, improved patient survival. (more…)
Author Interviews, Lancet, Leukemia, Lymphoma, Occupational Health / 01.07.2015

MedicalResearch.com Interview with: Dr Klervi Leuraud, Epidemiologist Institute for Radiological Protection and Nuclear Safety Cedex, France MedicalResearch: What is the background for this study? What are the main findings? Dr. Leuraud: INWORKS was performed to quantify the risk of cancer mortality associated to protracted low doses of ionizing radiation typical of occupational or environmental exposures, as well as of diagnostic medical exposures. While such risks are well known for acute exposures as those experienced by the Japanese survivors of the A-bombs, there is still a lack of information for exposures experienced by the workers and the public. Our study confirms the existence of an association between leukemia mortality and chronic exposure to low doses received by nuclear workers. (more…)
Author Interviews, Dermatology / 01.07.2015

MedicalResearch.com Interview with: Jennifer Latimer PhD Department of Dermatology at Newcastle University Newcastle, UK MedicalResearch: What is the background for this study? Dr. Latimer: There is extensive knowledge of the wavelength effects of UV on the skin to the nuclear DNA level. However the effects on mitochondrial DNA were unknown. The mitochondria have important links with aging and skin cancer and therefore knowing the individual UV wavelength effects is important. MedicalResearch: What are the main findings? Dr. Latimer: The main findings of this study were that the shorter and more energetic UVB wavelengths of UV were the most damaging to mitochondrial DNA. Furthermore we found that the skin fibroblast cells – those predominant in the deeper dermis layers of the skin were more sensitive to UV than keratinocytes, the main cells within the upper epidermis layer of the skin. (more…)
Author Interviews, Health Care Systems, Yale / 01.07.2015

MedicaIngrid Nembhard, PhD, MS Associate Professor, Yale School of Public Health & Yale School of Management Associate Director, Health Care Management Program YalelResearch.com Interview with: Ingrid M. Nembhard PhD MS Yale University New Haven, CT Medical Research: What is the background for this study? What are the main findings? Dr. Nembhard: Many health care organizations (hospital, medical groups,  etc.) have sought to address well-documented quality problems by implementing evidence-based innovations, that is, practices, policies, or technologies that have been proven to work in other organizations. The benefits of these innovations are often not realized because adopting organizations experience implementation failure—lack of skillful and consistent use of innovations by intended users (e.g., clinicians). Past research estimates that implementation failure occurs at rates greater than 50% in health care. The past work also shows organizational factors expected to be facilitators of implementation are not always helpful. In this work, we examined a possible explanation for the mixed results: different innovation types have distinct enabling factors. Based on observation and statistical analyses, we differentiated role-changing innovations, altering what workers do, from time-changing innovations, altering when tasks are performed or for how long. We then examined our hypothesis that the degree to which access to groups that can alter organizational learning—staff, management, and external network— facilitates implementation depends on innovation type. Our longitudinal study of 517 hospitals’ implementation of evidence-based practices for treating heart attack confirmed our thesis for factors granting access to each group: improvement team’s representativeness (of affected staff), senior management engagement, and network membership. Although team representativeness and network membership were positively associated with implementing role-changing practices, senior management engagement was not. In contrast, senior management engagement was positively associated with implementing time-changing practices, whereas team representativeness was not, and network membership was not unless there was limited management engagement. (more…)
Author Interviews, Breast Cancer, Radiation Therapy, UCLA / 01.07.2015

Dr. Mitchell Kamrava MD Department of Radiation Oncology University of California Los Angeles Los Angeles, CAMedicalResearch.com Interview with: Dr. Mitchell Kamrava MD Department of Radiation Oncology University of California Los Angeles Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Kamrava: Breast conservation (lumpectomy followed by radiation) is known, based on multiple randomized trials with over 20 years of follow-up, to provided equivalent outcomes as mastectomy.  The radiation component of breast conservation has standardly been delivered to the whole breast.  Studies show that the majority of breast recurrences occur near the lumpectomy cavity causing some to ask whether it is necessary to treat the whole breast in order to reduce the risk of a recurrence. Partial breast radiation delivers treatment just to the lumpectomy cavity with a small margin of 1-2 cm.  It’s delivered in a shorter time of 1 week compared with about 6 weeks for standard whole breast radiation and 3-4 weeks for hypofractionated whole breast radiation. The original method developed to deliver partial breast radiation is interstitial tube and button brachytherapy.  This uses multiple small little tubes that are placed through the lumpectomy cavity to encompass the area at risk.  One end of these tubes can be connected to a high dose rate brachytherapy machine that allows a motorized cable with a very small radiation source welded to the end of it to be temporarily pushed in and out of each of the tubes so that the patient can be treated from “inside out”.  This helps concentrate the radiation to the area of the lumpectomy cavity while limiting exposure to normal tissues.  This treatment is most commonly delivered as an out-patient two times per day for a total of 10 treatments. The main finding from our paper is that in reviewing the outcomes on over 1,000 women treated with this technique with an average follow-up of 6.9 years that the 10 year actuarial local recurrence rate was 7.6% and in women with more than 5 years of follow-up physician reported cosmetic outcomes were excellent/good in 84% of cases. (more…)
Author Interviews, Heart Disease, Statins / 01.07.2015

dr-duk-woo-park.pngMedicalResearch.com Interview with: Duk-Woo Park, MD, PhD. Professor, Division of Cardiology Asan Medical Center, University of Ulsan College of Medicine Seoul, Korea Medical Research: What is the background for this study? What are the main findings? Response: The applicability and potential clinical effects of the 2013 ACC/AHA cholesterol guidelines on major cardiovascular outcomes in the “real-world” population remains uncertain and also should also be evaluated in multiple groups of various ethnic backgrounds. We determined the proportions of adult persons eligible for statin therapy by changes of 2013 ACC/AHA cholesterol guidelines using a nationally representative sample from an Asian country (South Korea) and also we evaluated the potential clinical effects of this cholesterol guideline on future cardiovascular outcomes using an external validation cohort from the Korean National Health Examination. Similar to findings from the United States and the European cohort, our study showed that the 2013 ACC/AHA guidelines would substantially increase the number of adults who would be potentially eligible for statin therapy in Korean population. In addition, the 2013 ACC/AHA guidelines would have identified more cases with higher events of cardiovascular disease (CVD) for statin treatment than the ATP-III guidelines. (more…)
Asthma, Author Interviews, Nature, Nutrition / 01.07.2015

Dr. Alison Thorburn Ph.D. School of Medical and Applied Sciences, Central Queensland University Rockhampton, Queensland 4702, AustraliaMedicalResearch.com Interview with: Dr. Alison Thorburn Ph.D. Department of Immunology Monash University Victoria, Australia Medical Research: What is the background for this study? Dr. Thorburn: Asthma is a highly prevalent disease in the Western World. The prevailing explanation for this has been the hygiene hypothesis, which proposes that a decline in family size and improved hygiene has decreased exposure to infectious agents and therefore resulted in dysregulated immune responses that lead to asthma. However, recently there has been more attention on the role of diet and the gut microbiota in explaining the prevalence of inflammatory diseases in Western World. Indeed, many studies implicate obesity, as well as a high fat, low fruit and vegetable diet with higher prevalence of asthma. On the other hand, a Mediterranean diet, which is high in fruit and vegetables, is associated with lower prevelance of asthma. Interestingly, the consumption of dietary fiber is reduced in severe asthmatics. These and other data suggest that the diet (particularly dietary fibre) and the gut microbiota may play an important role in the development of asthma. Medical Research: What are the main findings? Dr. Thorburn: The main findings of this study are that: -        In mice: A high-fiber diet promotes a gut microbiota that produces high levels of anti-inflammatory short-chain fatty acids (SCFAs), particularly acetate. Acetate (alkaline form of vinegar) suppressed the development of allergic airways disease (AAD, a model for human asthma) in adult mice and the offspring of pregnant mice. -        In humans: High dietary fiber intake during late pregnancy is associated with higher acetate levels in the serum and a decrease in the percentage of infants showing predictors for asthma development in later life. -        The mechanism underlying these findings involves increasing T regulatory cell number and function through epigenetic mechanisms, which enhance immune regulation to prevent inflammation. (more…)
Aging, Author Interviews, Exercise - Fitness / 30.06.2015

MedicalResearch.com Interview with: Andreas Vigelsø PhD, research assistant University of Copenhagen Faculty of Health Sciences Center for Healthy Aging Dept. of Biomedical Sciences Copenhagen Denmark Medical Research: What is the background for this study? Response: According to the UN, the number of individuals more than 60 years old is expected to more than double, from 841 million worldwide today to more than 2 billion in 2050. Furthermore, the aging process is associated with a reduction in muscle mass, strength and fitness level. Collectively, this may contribute to frailty and may limit independent living. In addition, disease or injuries that can cause short-term immobilization are a further threat to independent living for older individuals. Despite its clinical importance for an increasing population of older individuals, few studies have examined older individuals after immobilization. Thus, our aim was to determine the effect of aerobic retraining as rehabilitation after short-term leg immobilization on leg strength, leg work capacity, and leg muscle mass in young and older men. Medical Research: What are the main findings? Response: Interestingly, our study reveals that inactivity affects the muscular strength in young and older men equally. Having had one leg immobilized for two weeks, young people lose up to a third of their muscular strength, while older people lose approx. one fourth. A young man who is immobilized for two weeks loses muscular strength in his leg equivalent to ageing by 40 or 50 years. Moreover, short-term leg immobilization had marked effects on leg strength, and work capacity and 6 weeks’ retraining was sufficient to increase, but not completely rehabilitate, muscle strength, and to rehabilitate aerobic work capacity and leg muscle mass. (more…)
Author Interviews, BMJ, Gastrointestinal Disease, Surgical Research / 30.06.2015

John Maret-Ouda MD, PhD candidateMedicalResearch.com Interview with: John Maret-Ouda  MD,  PhD candidate Upper Gastrointestinal Surgery Department of Molecular medicine and Surgery Karolinska Institutet Stockholm, Sweden MedicalResearch: What is the background for this study? What are the main findings? Dr. Maret-Ouda : This review is part of the BMJ series “Uncertainties pages”, where clinically relevant, but debated, medical questions are highlighted and discussed. The present study is assessing treatment of severe gastro-oesophageal reflux disease, where the current treatment options are medical (proton-pump inhibitors) or surgical (laparoscopic antireflux surgery). The clinical decision-making is often left to the clinician and local guidelines. We evaluated the existing literature to compare the two treatment options regarding reflux control, complications, future risk of oesophageal adenocarcinoma, health related quality of life, and cost effectiveness. The main findings were that surgery might provide slightly better reflux control and health related quality of life, but is associated with higher risks of complications compared to medication. A possible preventive effect regarding oesophageal adenocarcinoma remains uncertain. Regarding cost effectiveness, medication seems more cost effective in the short term, but surgery might be more cost effective in the longer term. Since medication provides good treatment of severe gastro-oesophageal reflux disease, but with lower risks of complications, this remains the first line treatment option. (more…)
Author Interviews, Microbiome, Weight Research / 30.06.2015

Dr. Karine Clément M.D., Ph.D. Assistant Professor, Nutrition Department Hotel-Dieu hospital ParisMedicalResearch.com Interview with: Prof. Karine Clément MD, PhD Director ICAN - Institute of Cardiometabolism And Nutrition Hôpital La Pitié-Salpêtrière, Paris www.ican.paris [email protected] Medical Research: What is the background for this study? What are the main findings? Dr. Clément: Obesity, associated with insulin resistance, is a chronic inflammatory disease revealed by a moderate but long-term increase in the levels of inflammatory molecules in the blood. Our groups and others have shown that several organs such as adipose tissues, liver, pancreas and muscles are also sites of inflammation with accumulation of immune cells such as macrophages and lymphocytes. This low-grade inflammatory state perturbs the tissue biology and contributes to the development and/or maintenance of insulin resistance and diabetes. In addition our teams and others showed that the intestinal functions are altered in obesity such as sugar and lipid absorption of and enteroendocrine nutrient signaling to the whole body. Our teams showed modifications of immunity in the obese intestine, and particularly in the jejunum part where most of sugar and lipid absorption takes place. Obesity increases the absorptive surface of the intestine and the colonization of the epithelium by CD8αβ T lymphocytes not affecting tissue integrity, thus differing from IBD inflammation. The cytokines secreted by the CD8 T cells of obese, but not lean subjects, are able to inhibit insulin action in enterocytes. In these patients, the increase of intestinal CD8 T cell density correlates with sugar absorption capacity and with the level of obesity and associated complications such as liver disease (NASH – Non-Alcoholic SteatoHepatitis) and dyslipidemia. (more…)
Author Interviews, Columbia, JACC, PTSD, Women's Heart Health / 30.06.2015

Jennifer A. Sumner, Ph.D.MedicalResearch.com Interview with: Jennifer A. Sumner, Ph.D. Columbia University Mailman School of Public Health New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Dr. Sumner: Cardiovascular disease, which includes conditions like heart attack and stroke, is the leading cause of death worldwide. Stress has long been thought to increase risk of cardiovascular disease, and posttraumatic stress disorder (PTSD) is the quintessential stress-related mental disorder. Some individuals who are exposed to traumatic events, such as unwanted sexual contact, the sudden unexpected death of a loved one, and physical assault, develop PTSD, which is characterized by symptoms of re-experiencing the trauma (e.g., nightmares), avoidance of trauma reminders (e.g., avoiding thinking about the trauma), changes in how one thinks and feels (e.g., feeling emotionally numb), and increased physiological arousal and reactivity (e.g., being easily startled). PTSD is twice as common in women as in men; approximately 1 in 10 women will develop PTSD in their lifetime. Research has begun to suggest that rates of cardiovascular disease are higher in people with PTSD. However, almost all research has been done in men. My colleagues and I wanted to see whether PTSD was associated with the development of cardiovascular disease in a large sample of women from the general public. We looked at associations between PTSD symptoms and new onsets of heart attack and stroke among nearly 50,000 women in the Nurses’ Health Study II over 20 years, beginning in 1989. Women with the highest number of PTSD symptoms (those reporting 4+ symptoms on a 7-item screening questionnaire) had 60% higher rates of developing cardiovascular disease (both heart attack and stroke) compared to women who were not exposed to traumatic events. Unhealthy behaviors, including lack of exercise and obesity, and medical risk factors, including hypertension and hormone replacement use, accounted for almost 50% of the association between elevated PTSD symptoms and cardiovascular disease. We also found that trauma exposure alone (reporting no PTSD symptoms on the screening questionnaire) was associated with elevated cardiovascular disease risk compared to no trauma exposure. Our study is the first to look at trauma exposure and PTSD symptoms and new cases of cardiovascular disease in a general population sample of women. These results add to a growing body of evidence suggesting that trauma and PTSD have profound effects on physical health as well as mental health. (more…)
Author Interviews, Cleveland Clinic, JAMA, Prostate Cancer / 30.06.2015

Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch.com Interview with: Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch: Tell me a little bit about the impetus for this study. What gap in knowledge were you trying to fill?  Dr. Zhu: Prostate cancer is a very challenging disease to understand and manage. For the minority of men, prostate cancer is a lethal disease, and in fact, it is the second leading cause of cancer death in American men, behind only lung cancer. However, for the majority of men, prostate cancer poses little risk of death. In fact, about 1 man in 7 will be diagnosed with prostate cancer during his lifetime, but only 1 man in 38 will die from prostate cancer. In an effort to avoid suffering and death from prostate cancer for those men with the lethal form, the early detection of prostate cancer (before the disease has reached a stage when it is no longer curable) through widespread prostate cancer screening was instituted in the late 1980s and early 1990s. As a result, prostate cancer diagnosis increased substantially, and most prostate cancers were detected at an early, treatable stage. Screening successfully reduced the risk of death from prostate cancer by 20%. Unfortunately, our best available screening tests, i.e. prostate-specific antigen (PSA) testing and the digital rectal exam, do not differentiate well between lethal and nonlethal prostate cancer. Consequently, screening is associated with a high risk of overdiagnosis of nonlethal prostate cancer. As a result, about 800 men must be screened and about 30 men must be diagnosed and treated to avoid one death from the prostate cancer, according to recent results from the largest prostate cancer screening trial. Since the natural history of newly diagnosed screen-detected prostate cancer is difficult to predict (i.e. lethal or nonlethal), most prostate cancers have been treated aggressively, leading to overtreatment of many nonlethal cancers. Aside from receiving unnecessary treatment, these men are exposed to the potential side effects and complications of treatment, including erectile dysfunction and urinary incontinence. In response to the harms associated with screening and treatment, the US Preventative Services Task Force issued a statement in 2011 (formalized in 2012) recommending against prostate cancer screening in all men. Unfortunately, while minimizing the risks of overdiagnosis and overtreatment for men with nonlethal prostate cancer, this solution eliminates any of the potential benefits of screening for those men with the lethal form of the disease. As urologists, our solution is different. Rather than throw the baby out with the bathwater, we prefer to preserve PSA screening and its benefits by addressing and hopefully minimizing its associated risks. To achieve this, our goal is to better distinguish between those men who have lethal vs. nonlethal prostate cancer, limiting treatment only to those men who have the lethal form of the disease at an early stage when it is still curable. The dilemma is that our currently available diagnostic tests are unable to accurately differentiate lethal from nonlethal prostate cancer with 100% certainty at the time of initial diagnosis. The solution, or at least part of the solution, is active surveillance. In men who appear to have nonlethal (“low risk”) cancer at the time of diagnosis, it now appears to be safe to observe these cancers, at least initially. This is the concept behind active surveillance. Active surveillance entails carefully monitoring men with low-risk prostate cancer using serial testing and reserving the option of treatment for those men with prostate cancers that exhibit lethal characteristics. In this way, active surveillance preserves the benefits of screening while minimizing the harms of overdiagnosis and overtreatment. Active surveillance was first introduced in the early 2000s, but its efficacy and safety have only been elucidated recently over the last 5 years. Given that active surveillance may be one solution to the screening dilemma, we wanted to evaluate contemporary active surveillance utilization, which is the impetus for our study. Based on the most recent data available to us, we chose the years 2010-2011, which coincide to the time immediately before and during the release of the US Preventative Services Task Force statement against PSA screening. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, JNCI / 30.06.2015

Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114MedicalResearch.com Interview with: Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114 MedicalResearch: What is the background for this study? What are the main findings? Dr. Padera: Systemic therapy benefits cancer patients with lymph node metastases; however all phase III clinical trials to date of antiangiogenic therapy have failed in the adjuvant setting. We have previously reported the lack of efficacy of antiangiogenic therapies in pre-clinical models of spontaneous lymphatic metastasis, however there were no mechanistic data to explain these observations. Here, we developed a novel chronic lymph node window model to facilitate new discoveries in the mechanisms of growth and spread of lymph node metastases. Our new data provide pre-clinical evidence along with supporting clinical evidence that angiogenesis does not occur in the growth of metastatic lesions in the lymph node. These results reveal a mechanism of treatment resistance to antiangiogenic therapy in adjuvant setting, particularly those involving lymph node metastases. (more…)
Author Interviews, OBGYNE / 29.06.2015

Frank Vandekerckhove, MD, PhD Clinical Head, Centre for Reproductive Medicine University Hospital Ghent BelgiumMedicalResearch.com Interview with: Frank Vandekerckhove, MD, PhD Clinical Head, Centre for Reproductive Medicine University Hospital Ghent Belgium Medical Research: What is the background for this study? What are the main findings? Dr. Vandekerckhove: Several retrospective studies have evaluated seasonal variations in the outcome of IVF treatment. Some also included weather conditions, mostly temperature and hours of daylight. The results were conflicting. We focused on individual variables provided as monthly results by our national meteorological institute. We shifted the results in IVF outcome to the weather results of one month earlier, as we supposed that the selection of good quality oocytes may start in the weeks before. Between January 2007 and December 2013, the IVF outcome of all Belgian patients treated in our university center was compared to the quarter of the year and monthly mean values of temperature, rain fall, rainy days and sunshine hours during the month when gonadotropins were started or the month before. 11494 patients started an IVF cycle and were included. Firstly bivariate correlation was performed by linear modelling between monthly weather conditions and IVF results. Secondly the same IVF outcome variables were plotted against the weather results stratified per quartile for each individual meteorological variable. There was no relationship between IVF outcome and the quarter of the year. When looking for a linear correlation between IVF results and the mean monthly values for the weather, the results were inconsistent. However, when the same analysis was repeated with the weather results of 1 month earlier, there was a clear trend towards better IVF outcome with higher temperature, less rain and more sunshine hours. The live birth rate per cycle was significantly different (p 0.019) between different groups (Q=quartile) of mean number of sunshine hours (Q1=60.75, Q2=136.00, Q3=174.50). (more…)
Author Interviews, Flu - Influenza, Vaccine Studies, Wistar / 29.06.2015

Scott E. Hensley, Ph.D. Assistant Professor Wistar Institute Philadelphia, PA 1910MedicalResearch.com Interview with: Scott E. Hensley, Ph.D. Assistant Professor Wistar Institute Philadelphia, PA 1910   Medical Research: What is the background for this study? What are the main findings? Response: Previous studies documented that the the 2014-2015 H3N2 flu vaccine strain was antigenically distinct compared to most recent H3N2 flu strains.  Recent H3N2 strains possess several mutation and it was previously unknown which of these mutations contributed to the 2014-2015 vaccine mismatch.  We used a reverse-genetic engineering approach to identify specific viral mutations that contributed to the 2014-2015 vaccine mismatch. (more…)
Author Interviews, Infections, Microbiome, Urinary Tract Infections / 29.06.2015

MedicalResearch.com Interview with: Jeffrey P. Henderson, M.D., Ph.D. Assistant Professor of Medicine and Molecular Microbiology Center for Women's Infectious Diseases Research Division of Infectious Diseases and Robin Shields-Cutler, Ph.D Ph.D. Student, Molecular Microbiology and Microbial Pathogenesis Washington University School of Medicine St. Louis, Missouri Medical Research: What is the background for this study? Response: Increasing antibiotic resistance, together with an appreciation that many patients are particularly susceptible to recurrent Urinary Tract Infections UTIs following antibiotic therapy, motivated interest in the events that occur during early stages of UTI pathogenesis. Abundant evidence suggests that uropathogenic E.coli must obtain iron from human hosts in order to cause a clinical infection. Early in infection, human cells secrete a protein called siderocalin that is known to limit bacterial growth by sequestering iron. This protein is detectable in the urine of Urinary Tract Infections patients. Medical Research: What are the main findings? Response: We obtained urine from a diverse panel of healthy volunteers, inoculated them individually with a uropathogenic E.coli strain, and monitored growth in the presence and absence of a fixed amount of siderocalin. Siderocalin exhibited a remarkably wide range of activity between individuals. We traced this variation back to differences in urinary pH and to phenolic urinary metabolites. We could significantly facilitate siderocalin’s antibacterial activity in urine by alkalinizing it above 6.5 and adding phenolic metabolites. The metabolites that potentiate siderocalin’s antibacterial effect have been linked to dietary sources such as coffee, tea, and berries. Some of these compounds may further derive from the actions of gut microbes on dietary phenols. The functional basis for these compounds’ properties seems to arise from siderocalin’s ability to use them as molecular grips that chelate iron ions in a form that is difficult for bacteria to access. From the pathogen perspective, we found that enterobactin, a molecule secreted by E.coli, acts as a microbial countermeasure to urinary siderocalin. Adding a drug-like inhibitor to urine that blocks enterobactin biosynthesis greatly increased siderocalin’s antibacterial effect. (more…)
AHRQ, Author Interviews, Hospital Acquired, Outcomes & Safety / 27.06.2015

Ann Scheck McAlearney, Sc.D., M.S. Professor, Family Medicine Vice Chair for Research, Department of Family Medicine College of Medicine Ohio State University Columbus, OhioMedicalResearch.com Interview with: Ann Scheck McAlearney, Sc.D., M.S. Professor, Family Medicine Vice Chair for Research, Department of Family Medicine College of Medicine Ohio State University Columbus, Ohio MedicalResearch: What is the background for this study? What are the main findings? Dr. McAlearney: In this study, we sought to explore the potential role high-performance work practices (HPWPs) may play in explaining differences in the success of central line-associated blood stream infection (CLABSI) reduction efforts involving otherwise similar organizations and approaches. We analyzed data from 194 key informant interviews across eight hospitals participating in the federally funded ‘‘On the CUSP: Stop BSI’’ initiative. We found evidence that at sites more successful at reducing central line-associated blood stream infection, HPWPs facilitated the adoption and consistent application of practices known to prevent CLABSIs; these HPWPs were virtually absent at lower performing sites. In this paper we present examples of management practices and illustrative quotes categorized into four HPWP subsystems: (a) staff engagement, (b) staff acquisition/development, c) frontline empowerment, and (d) leadership alignment/development. (more…)
Author Interviews, BMJ, Infections, Vaccine Studies / 26.06.2015

MedicalResearch.com Interview with: Siv Klevar, DVM,PhD. Norwegian Veterinary Institute Department of Diagnostics Section of Immunology Oslo Medical Research: What is the background for this study? Dr. Klevar:  Border control veterinary officers reported a surge in the number of imported dogs after the pet travel regulations were relaxed in 2012. At the same time rescue groups, through social media advertisement, encouraged and facilitated the adoption of dogs from shelters in Eastern Europe. The removal of the requirement regarding individual serological testing for antibodies to rabies before importing pets into UK, Ireland, Sweden, Malta and Norway, made it much easier to import pets into these countries. Previously import required several months of preparation and additional costs whereas under the new regulations it could be done after a single vaccination and a 3 week wait. The Norwegian Food Authority initiated a project to look at exotic pathogens in these re-homed dogs. This study reports the rabies antibody levels detected in some of the rehomed stray dogs entering Norway during 2012. The Norwegian Veterinary Institute and National Veterinary Institute in Sweden carried out the study. Medical Research: What are the main findings? Dr. Klevar: Our results showed that a high proportion of stray dogs, compared to a control group of pet dogs from Sweden, didn’t have sufficient protection against rabies virus after vaccination. Although we do not know exactly why this was the case, the exceedingly low levels of antibodies detected in some of the stray animals would suggest that they were not properly vaccinated, even though all the paperwork showed they were fully compliant with Pet Travel Regulations. The main issue highlighted by this study is that the current regulations are not sufficient to prevent rabies introduction when importing rescue dogs from countries where the virus is present to countries free from the disease. The reason for this is that the current regulations do not require a check to see if the pet has been properly vaccinated (by testing the animal’s blood for antibodies). In addition to this, the 21 day waiting period after vaccination isn’t long enough for rabies to develop if the dog had been infected prior to vaccination. (more…)
Author Interviews, Biomarkers, Cancer Research, Johns Hopkins / 26.06.2015

Nishant Agrawal M.D. Associate Professor of Otolaryngology Johns Hopkins University School of MedicineMedicalResearch.com Interview with: Nishant Agrawal M.D. Associate Professor of Otolaryngology Johns Hopkins University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Agrawal: The idea of the study really arose from the specificity of genetic changes that characterize and are the hallmark of cancer cells.  Only cancer cells contain these mutations so their detection in bodily fluids was a reasonable expectation.  The current study builds on previous work from our group that tumor DNA can be detected in the bodily fluids of patients with many different types of solid malignancies.  The main findings of the study are that tumor DNA in saliva and plasma provides a non-invasive biomarker for head and neck cancer.  The take home message is that tumor DNA has potential to be used as a biomarker for screening, early detection, monitoring during treatment, and surveillance after cancer treatment is completed. (more…)
Author Interviews, BMC, Colon Cancer, Microbiome / 26.06.2015

Michael B. Burns, Ph.D. HHMI Post-Doctoral Fellow Dept. of Genetics, Cell Biology and Development Dept. of Ecology, Evolution, and Behavior Masonic Cancer Center Dept. of Biology Teaching and Learning University of Minnesota, Twin Cities St. Paul, MN 55108MedicalResearch.com Interview with: Michael B. Burns, Ph.D. HHMI Post-Doctoral Fellow Dept. of Genetics, Cell Biology and Development Dept. of Ecology, Evolution, and Behavior Masonic Cancer Center Dept. of Biology Teaching and Learning University of Minnesota Twin Cities St. Paul, MN 55108 Medical Research: What is the background for this study? Dr. Burns: Recent technological advances have made it possible to survey all the of microbes that are in, on, and around us. One of the surprising things is the sheer quantity and diversity of the bacteria in our environments and our microbiomes. Many researchers have begun the systematic characterization of the microbes that are associated with specific disease states, including cancer. With regard to colorectal cancer, there have been numerous studies that have identified specific bacteria that are linked to the presence of the disease. There have been many reports that have identified particular potentially important microbes that may be causing the cancer, driving the cancer, or some combination of the two. Among these microbes, one of the best studied so far is a group of bacteria called Fusobacterium. Medical Research: What are the main findings? Dr. Burns: In our work, we set out to perform another characterization of the bacteria in the gut microbiome that are specifically associated with colorectal tumors. We used samples of normal colon tissue from the same individuals as controls, which allowed us to account for much of the variability in the different bacteria we found that might have been simply the result of, for instance, diet. In our analysis, we confirmed the previous results related to Fusobacterium, and additionally discovered a new potential culprit in colorectal cancer, a group of bacteria named Providencia. The finding of another new set of microbes that might be causing or driving cancer is not surprising. As indicated above, there are many groups who have found other potential candidate microbes that could be implicated in the disease. Our next question was to determine if there was some reason why there might be so many different bacteria that are linked with the disease and what it might be able to tell us about what these bacteria are doing. To that end, we used computational approaches to assess what these two groups of bacteria might be doing at a functional level and if there were any similarities. We found that there was a great deal in common between Fusobacterium and Providencia, including a finding that one of the common functions was related to a large group of virulence genes. (more…)
Author Interviews, PLoS / 26.06.2015

MedicalResearch.com Interview with: Jose A. Garcia Salcedo, PhD. Unidad de Enfermedades Infecciosas Hospital Universitario San Cecilio Instituto de Investigación Biosanitaria de Granada Granada Spain Medical Research: What is the background for this study? Response: Drug resistance is complicating the treatment of parasitic diseases including African trypanosomiasis, a fatal disease if left untreated. Development of a vaccine is unlikely due to parasite antigenic variation. Current chemotherapy relies primarily on four drugs. Three of these drugs access the cell’s interior through surface transporters and resistance mechanisms are largely associated with loss-of-function mutations in the involved surface drug transporters. (more…)
Author Interviews, Heart Disease, Technology / 26.06.2015

Dr. Carsten Lennerz Deutsches Herzzentrum München MedicalResearch.com Interview with: Dr. Carsten Lennerz Deutsches Herzzentrum München Medical Research: What is the background for this study? What are the main findings? Response: The number of cardiovascular implantable electronic devices (CIEDs) is increasing. Worldwide more than 4 million people rely on an implanted pacemaker (PM) or implantable cardioverter defibrillator ICD. Sensing intrinsic cardiac electrical activity is the core principle of all CIED devices, however in case of electromagnetic interference (EMI) exogenous electric and magnetic fields can be picked up by the sensing circuit and mistakenly interpreted as a cardiac signal by the CIED. PM can respond to EMI with pacing-inhibition, leading to bradycardia or asystole and resulting in syncope. In ICDs EMI may be detected as a life threatening ventricular arrhythmia with the subsequent delivery of inappropriate shocks. Early studies on EMI, run more than 10 years ago, have identified mobile phones as a source of EMI with pacemakers. Based on these pacemaker studies the CIED manufacturer and the regulatory authorities (e.g. Food and Drug Administration [FDA]) currently recommend a safety distance, i.e. hold the phone to the contra-lateral ear and avoid placing a turned-on phone next to the generator pocket. In the meantime telecommunication and the CIED techniques have dramatically evolved. The classic mobile phone has been replaced by modern smartphones, furthermore the network standards have changed from GSM to UMTS (3G) and LTE (4G). New cardiac devices are now in use including more devices for cardiac resynchronisation therapy (CRT) or for the protection from sudden cardiac death (ICD); some of them are even compatible for MRI diagnostics. With the use of a hemertic titanium shell, new filtering properties of the feed-throughs, sense amplifiers and noise protection algorhythms as well as the predominant use of bipolar leads the CIED may be better shielded against external influences and adverse effects of EMI. In light of the above, the purpose of our study was to evaluate if previous precautions recommended to cardiovascular implantable electronic devices recipients are still up-to-date or if they can be abandoned. By today there are neither studies focusing on EMI between modern smartphones and modern CIEDs nor on newer mobile network standards (UMTS or LTE). In a cross-sectional study we enrolled 308 patients and exposed them to the electromagnetic field of three smartphones (Samsung Galaxy 3, Nokia Lumia, HTC One XL) by placing the handhelds directly over the pulse generator. Installing an own base mobile network station we ensured that each smartphone went through a standardized protocol that included the entire calling process (connecting, ringing, talking), the handovers between all current network standards (GSM, UMTS, LTE where applicable) and operation at maximal transmission power. More than 3.400 tests on electromagnetic interference were performed. One out of 308 patients (0.3%) was repeatedly affected by EMI caused by smartphones. The patient’s MRI compatible CRT-defibrillator malfunctioned with short-term ventricular and atrial oversensing when exposed to Nokia or HTC smartphones operating at GSM and UMTS. (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, Menopause, Orthopedics / 26.06.2015

MedicalResearch.com Interview with: Dr Matthew Miller Department of Health Science Northeastern University Department of Health Policy and Management, Harvard T.H. Chan School of Public Health Harvard University Boston, Massachusetts and Yi-Han Sheu Department of Epidemiology Harvard T.H. Chan School of Public Health Harvard University Boston, Massachusetts Medical Research: What is the background for this study? Response: Selective serotonin reuptake inhibitors (SSRIs) were recently approved by the FDA to treat vasomotor symptoms associated with menopause. No prior study has directly examined whether fracture risk is increased among perimenopausal women who initiate SSRIs or among a population of women without mental disorders more generally.. Medical Research: What are the main findings? Response: We found that SSRIs treatment for non-psychiatric conditions at doses customarily used to treat depression is, all else equal, associated with higher rates of fractures -- an effect that first became evident several months after beginning treatment and, importantly, persisted over the five year study period. (more…)