Annals Internal Medicine, Asthma, Author Interviews, Pharmacology / 16.11.2015

MedicalResearch.com Interview with: Michael Miligkos, MD, MS Laboratory of Biomathematics, University of Thessaly School of Medicine Larissa, Greece Medical Research: What is the background for this study? What are the main findings? Dr. Miligkos: Asthma is one of the most common chronic diseases with and has considerable social and economic burdens. Although inhaled corticosteroids constitute the current gold standard of maintenance treatment, leukotriene-receptor antagonists (LTRAs) have the advantages of oral once- or twice- daily dosing and, apparent avoidance of the adverse effects associated with long-term corticosteroid therapy. In addition, their mechanisms of action theoretically predicts a good response in patients with specific asthma “phenotypes”. This systematic review investigated the use of all marketed LTRAs in usual licensed doses as asthma controller medications compared with placebo and found that administration of a LTRA to adults and adolescents with asthma significantly reduced the risk for an exacerbation. In trials of LTRA monotherapy, LTRAs significantly improved asthma control compared with placebo, whereas only some measures of asthma control were significantly improved in trials of LTRAs used as add-on use therapy to ICSs. (more…)
Author Interviews, Blood Clots, Orthopedics, PLoS / 16.11.2015

MedicalResearch.com Interview with: Banne Nemeth, MD and  Suzanne C. Cannegieter MD PhD Leiden University Medical Center The Einthoven Laboratory for Experimental Vascular Medicine Clinical Department of Epidemiology and Orthopedic Surgery Medical Research: What is the background for this study? What are the main findings? Dr. Nemeth: Clinicians cannot currently accurately predict who will develop venous thrombosis, but it would be very helpful to be able to identify individuals at high risk for venous thrombosis because the condition can be prevented by giving anticoagulants before a clot forms (thromboprophylaxis). The ability to predict venous thrombosis would be particularly useful in patients who have had a lower limb immobilized in a cast after, for example, breaking a bone. These patients have an increased risk of venous thrombosis compared to patients without cast immobilization. We developed and validated a prediction model to identify patients with plaster cast of the lower extremity who are at high risk to develop venous thrombosis. A clinical risk score named, L-TRIP(cast) score (Leiden Thrombosis Risk Prediction for patients with cast immobilization score), was developed containing 14 clinical risk factors such as age, sex, BMI, use of oral contraceptives and location of plaster cast. Patients that score 9 points or higher are classified as being at high risk for venous thrombosis. Clinicians may decide to prescribe thromboprophylaxis therapy for these patients. (more…)
Author Interviews, Personalized Medicine, Pharmacology / 16.11.2015

MedicalResearch.com Interview with: Diane Frenier Esq Reed Smith Corporate Partner Member of Corporate & Securities Group and Life Sciences Health Industry Group Background: Diane Frenier Esq discusses the M&A boom in the pharmaceutical and retail drug industry including a the "global study of 100 senior executives at life sciences companies by global law firm Reed Smith, in partnership with Mergermarket, reveals that 94% are planning to make an acquisition in the next year”. Medical Research: What are the main drivers behind the pursuit of cross-border life sciences deals? Ms Frenier: I think companies are trying to strengthen their capabilities in areas that are a core focus for them (e.g., in certain therapeutic areas, or for orphan drugs), and that includes adding products in those core focus areas and, in some cases, broadening geographically so they can market products in those core focus areas on a more global basis.  This will allow them to use their resources more efficiently and take advantage of saving from reducing redundancies. (more…)
Author Interviews, Columbia, Heart Disease, JACC, Transplantation / 14.11.2015

MedicalResearch.com Interview with: Raymond Givens MD PhD  Columbia University Medical Center  Medical Research: What is the background for this study? What are the main findings? Dr. Givens: Multiple listing- i.e., simultaneous placement on multiple organ transplant waiting lists- is allowed by the United Network for Organ Sharing (UNOS). Because insurance generally does not pay for the costs of transportation between multiple centers or of temporary housing, there has been concern that the multiple-listing policy gives an unfair advantage to wealthier patients. We examined the UNOS database from 2000-2013 and identified 33,928 patients who were listed for a first-time single-organ heart transplant, 2% of whom met our definition of multiple-listing. Compared to single-listed patients, multiple-listed patients lived in ZIP codes with significantly higher median incomes, and were more likely to have private insurance and less likely to be supported by Medicaid. They were also significantly more likely to have blood type O and to live in areas with higher predicted waiting times. Despite having lower listing priority at the start of the primary listing and lower predicted mortality, the multiple-listed patients were often upgraded at secondary listing and had a higher eventual transplant rate (74.4% vs 70.2%) and lower mortality rate while listed (8.1% vs 12.2%). When the multiple-listed cohort was compared against a propensity-score-matched single-listed subset the relative rare of transplant was 3.02. There were no differences in post-transplant survival. (more…)
AHA Journals, Author Interviews, Heart Disease / 14.11.2015

MedicalResearch.com Interview with: Susan Marzolini, R.Kin, PhD Scientific Associate, TRI-REPS Supervisor Toronto Rehab/UHN Cardiovascular Prevention and Rehabilitation Program Medical Research: What is the background for this study? What are the main findings? Dr. Marzolini: Coronary artery bypass graft (CABG) surgery is a leading revascularization procedure for treating coronary artery disease. Despite effective revascularization, cardiovascular risk factor control through intensive lifestyle and pharmacological treatment is essential to prevent graft deterioration and progression of atherosclerosis following surgery. Outpatient cardiac rehabilitation (CR) programs offer structured exercise, education, interdisciplinary support, counselling, and risk reduction to promote secondary prevention. These programs have been shown to improve fitness, psychosocial well-being, and significantly reduce morbidity and mortality after CABG surgery. However, while Canadian and international guidelines endorse “early” referral to CR post-cardiac event, actual practice is variable and delays are common_ENREF_9_ENREF_9_ENREF_7. Delayed entry is of concern, as there is emerging evidence that later referral and initiation of cardiac rehabilitation is associated with negative consequences on cardiovascular fitness, however this has not been examined in the post-CABG population. Therefore, we conducted a retrospective analysis of 6497 consecutively enrolled post CABG participants in a single cardiac rehabilitation program in Toronto, Canada from January 1995 to October 2012. Our objective was to examine the effects of later entry on CR outcomes (i.e., CR use, anthropometrics, and functional capacity) while accounting for demographic, environmental, and physiological correlates of longer wait-time. We found that longer wait-time to start a cardiac rehabilitation program was associated with poorer outcomes including less improvement in cardiopulmonary fitness and lower program attendance, which have been shown to confer a mortality disadvantage. Longer wait time was also associated with less improvement in body fat percentage as well as poorer completion rates. We identified that bypass patients predisposed to longer wait times, and subsequently poorer participation and outcomes, are women, those who are older, from a lower socioeconomic neighborhood, people with a more complex medical history, who are employed, have a longer drive-time to cardiac rehabilitation, and people with less social support. (more…)
AACR, Author Interviews, Duke, Immunotherapy / 14.11.2015

MedicalResearch.com Interview with: Jiayuh Lin, Ph.D. Associate Professor, College of Medicine, The Ohio State University Medical Research: What is the background for this study? What are the main findings? Dr. Jiayuh Lin: Pancreatic cancer is one of the most serious forms of cancer.  Because of the poor response to chemotherapy as conventionally used, patients with any stage of pancreatic cancer may appropriately be considered candidates for clinical trials using novel agents. IL-6 signaling plays an important role in oncogenesis and high serum IL-6 levels is a poor prognostic factor for overall survival in pancreatic cancer. Therefore, IL-6 is considered as a viable target for pancreatic cancer therapy.  We utilized a drug discovery method with Multiple Ligand Simultaneous Docking and drug repositioning to identify an existing FDA-approved drug Bazedoxifene with previously unknown biological function as an IL-6/GP130 inhibitor.  Bazedoxifene can inhibit cell viability of pancreatic cancer cells expressing IL-6 and suppressed pancreatic tumor growth in vivo. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA / 14.11.2015

MedicalResearch.com Interview with: Samuel Klempner, M.D. Assistant Professor Division of Hematology/Oncology UC Irvine Health Orange, CA 92868  Medical Research: What is the background for this study? What are the main findings? Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options.  This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types.  Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an EGFR mutation common to lung cancer could be treated similar to a lung cancer based on the genomic changes. In our study we found another way that the BRAF protein and its downstream signaling may become activated through duplicating part of the protein called the kinase domain.  This genetic event causes the pathway to be always "on" which is not normal, and likely drives cancer growth.  However, BRAF kinase domain duplication appears sensitive to currently available drugs that target the BRAF pathway, as evidenced by the response in our patient.  Thus, finding this change is important and may be able to guide a more personalized therapy choice.  Importantly, we found BRAF kinase domain duplication across multiple different tumor types, suggesting this may be a recurrent event in some cancers.  A very similar finding, involving duplication of the EGFR kinase domain, was also just reported (Cancer Discovery 2015;5:1155-1163) lending further validation to this mechanism of pathway activation in cancer. (more…)
AHA Journals, Author Interviews, McGill, Stroke / 14.11.2015

MedicalResearch.com Interview with: Sophie Vincent, Medical Student McGill University and Kristian Filion, PhD FAHA Assistant Professor of Medicine Division of Clinical Epidemiology Jewish General Hospital/McGill University Medical Research: What is the background for this study? What are the main findings? Response: Patients with carotid atherosclerosis causing vascular stenosis are at increased risk of stroke, which is the third leading cause of death in the United States and in Canada. Carotid artery stenting and carotid endarterectomy are the primary surgical options for the treatment of carotid stenosis. With the assumption that an endovascular approach would offer a more favorable safety profile than open surgical procedure, the use of stenting increased significantly following its entry into the market in the 1990s. However, despite this observed increase in use, the long-term safety and efficacy of stenting relative to endarterectomy remained unclear, which is why we decided to conduct this study. Although carotid artery stenting has more favorable periprocedural outcomes with respect to myocardial infarction, hematoma, and cranial nerve palsy, the observed increased risk of stroke throughout follow-up with stenting suggests that endarterectomy remains the treatment of choice for the management of carotid stenosis. (more…)
Author Interviews, Breast Cancer, Chemotherapy, MRI / 14.11.2015

MedicalResearch.com Interview with: Dr. Franca Podo, Dr Sci Former Director of the Molecular and Cellular Imaging Unit Department of Cell Biology and Neurosciences Istituto Superiore di Sanità Rome, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Podo: Population-based studies showed that triple negative breast cancers (TNBCs), i.e. those which are negative for estrogen and progesterone receptors without HER-2/neu overexpression, have a more aggressive clinical course and a 2-to-3 fold higher likelihood of distant recurrence and death from breast cancer within 5 years from diagnosis, compared with non-TNBCs. In a study published in Clinical Cancer Research (Online First 26 October 2015) Dr. F. Podo and Dr. F. Santoro (Istituto Superiore di Sanità, Rome) and Prof. F. Sardanelli (Università degli Studi di Milano, IRCCS Policlinico San Donato) in collaboration with other Italian co-authors, compared phenotype features and survival rates of invasive TNBCs versus non-TNBCs detected during the HIBCRIT-1 screening study of 501 asymptomatic women at high genetic-familial risk for breast cancer. The screening included BRCA1 and BRCA2 mutation carriers, as well as women with a strong family history of breast and/or ovarian cancer, enrolled between 2000 and 2008 in 18 centers. Data analysis from a median 9.7-year follow-up until June 2015 showed that, combining an annual screening including magnetic resonance imaging (MRI) with adequate treatment options, the mean 5-year overall survival of triple negative breast cancers was not significantly different from that of non-TNBCs (86% vs 93%), in spite of a 3-fold higher rate of cases of grade 3 invasive ductal carcinoma in the former subgroup (71% in TNBCs vs 23% in non-TNBCs). The mean disease-free survival rates were also very similar (77% vs 76%, respectively). (more…)
Aging, Author Interviews, Depression, Geriatrics / 13.11.2015

MedicalResearch.com Interview with: Helena Chui, Ph.D. CPsychol Lecturer Division of Psychology University of Bradford Bradford England  Medical Research: What is the background for this study? What are the main findings? Dr. Chui: It is debatable whether psychological well-being improves or declines with age. Findings of the age-related changes in psychological well-being, life satisfaction, and depressive symptoms, are not unequivocal. Some studies have found that people stay pretty stable in terms psychological well-being until late life. Other studies have found otherwise. My recent publication reports the findings using a 15-year longitudinal study from Australia. Results showed that as people get older, depressive symptoms increase. Both men and women reported increasingly more depressive symptoms as they aged, with women initially starting with more depressive symptoms than men. However, men showed a faster rate of increase in symptoms so that the difference in the genders was reversed at around the age of 80. (more…)
AACR, Author Interviews, NIH, Nutrition, Ovarian Cancer, Race/Ethnic Diversity / 13.11.2015

MedicalResearch.com Interview with: Bo (Bonnie) Qin, PhD Postdoctoral associate at Rutgers Cancer Institute of New Jersey Medical Research: What is the background for this study? What are the main findings? Response:  Ovarian cancer is among the top five causes of cancer death among women in the US. Compared to white women, African-American women tend to have a worse 5-year survival rate of ovarian cancer. It highlights a critical need for identifying preventive factors in African Americans, particularly through dietary modification, which is relatively low cost and low risk compared to medical treatments. We found that adherence to an overall healthy dietary pattern i.e. Alternate Healthy Eating Index (AHEI)-2010 may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal women. Adherence to the current Dietary Guidelines for Americans i.e. Healthy Eating Index-2010, were also strongly associated with reduced risk of ovarian cancer among postmenopausal African-American women. (more…)
Author Interviews, JAMA, Mental Health Research, Primary Care / 13.11.2015

Shahrzad Mavandadi, PhD Research Health Science Specialist and Investigator Veterans Integrated Services Network 4 Mental Illness Research, Education, and Clinical Center Corporal Michael J. Crescenz Veterans Affairs Medical Center Philadelphia, PennsylvaniaMedicalResearch.com Interview with: Shahrzad Mavandadi, PhD Research Health Science Specialist and Investigator Veterans Integrated Services Network 4 Mental Illness Research, Education, and Clinical Center Corporal Michael J. Crescenz Veterans Affairs Medical Center Philadelphia, Pennsylvania  Medical Research: What is the background for this study? Dr. Mavandadi: Mental health (MH) conditions are underidentified and undertreated in later life.  This is particularly true among subgroups of older adults who are more vulnerable to developing mental health issues, have poor access to specialty care, and are less responsive to treatment and therapy.  Thus, we sought to evaluate longitudinal MH outcomes among low-income, community-dwelling older adults enrolled in an evidence-based, collaborative mental health care management service (i.e., the SUpporting Seniors Receiving Treatment And INtervention (SUSTAIN) program).  The SUSTAIN program integrates mental health with primary care (which is where the majority of behavioral health conditions in later life are managed) and provides standardized, measurement-based, software-aided MH assessment and connection to community resources to older adults by telephone. While there is a strong evidence base for the efficacy of collaborative care models for me conditions, little is known about the amount or level of patient and provider support that is needed to achieve optimal behavioral health outcomes.  Thus, we specifically examined outcomes among older adults randomized to one of two program arms of varying intensity: MH symptom monitoring alone or mental health symptom monitoring plus MH care management.   MH care management involved care managers who provided education, counseling, and decision support to patients and their primary care providers, a licensed mental health clinician who supervised the care managers, and the use of an algorithm to help guide pharmacological and non-pharmacological treatment plans.  The sample consisted of 1018 older adults prescribed an antidepressant or anxiolytic by their non-behavioral health providers who presented with clinically significant symptoms at intake. (more…)
Author Interviews, CDC, Infections, OBGYNE, STD / 13.11.2015

MedicalResearch.com Interview with: Dr. Virginia Bowen PhD Epidemic Intelligence Service Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention,CDC  Medical Research: What is the background for this study? What are the main findings? Dr. Bowen: Congenital syphilis (CS) occurs when a mother infected with syphilis transmits the infection to her child during the course of pregnancy. Our study looked at recent trends in CS between 2008 and 2014. After four years of decline, Congenital syphilis rates increased by 38% from 2012 to 2014. The findings from this report show we are missing opportunities to screen and treat pregnant women for STDs. Syphilis in pregnant women can cause miscarriages, premature births, stillbirths, or death of newborn babies. We have effective tests and treatment for syphilis – there’s no excuse for allowing it to resurge. Every case of CS is one too many. (more…)
Author Interviews, Heart Disease, Lipids, Stanford / 13.11.2015

MedicalResearch.com Interview with: Liana Del Gobbo PhD Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and Life Sciences Research Organization, Bethesda, MD Medical Research: What is the background for this study? What are the main findings? Dr. Del Gobbo: Accumulating evidence suggests that nut intake lowers risk of cardiovascular disease. But the specific mechanisms by which nuts may exert beneficial effects (eg. through lowering blood cholesterol, blood pressure, inflammation, etc.) were not clear. Two prior reviews on this topic only evaluated one type of nuts, and only a few cardiovascular risk factors. To address these knowledge gaps, we performed a systematic review and meta-analysis of controlled trials to examine the effects of eating tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, Brazil nuts) on major cardiovascular risk factors including blood lipids (total cholesterol, LDL, HDL, triglycerides [TG]), lipoproteins (ApoA1, ApoB, ApoB100), blood pressure (systolic, SBP; diastolic, DBP), and inflammation (C-reactive protein, CRP) in adults 18 years or older without cardiovascular disease. A daily serving of nuts (1oz serving, or 28g per day) significantly lowered total cholesterol, LDL, ApoB, and triglycerides, with no significant effects on other risk factors, such as HDL cholesterol, blood pressure or inflammation. To give you an idea of a 1oz serving size of nuts, it is about 23 almonds, 18 cashews, 21 hazelnuts, 6 Brazil nuts, 12 macadamia nuts, 14 walnut halves, 20 pecan halves, 49 pistachios. We did not see any differences in cholesterol-lowering effects by nut type. (more…)
Author Interviews, JAMA, Mental Health Research, Pediatrics / 13.11.2015

MedicalResearch.com Interview with: Dr. Mai-Britt Guldin PhD Department of Public Health Aarhus University  Medical Research: What is the background for this study? Dr. Guldin: The background for this study is that death of a parent in childhood is experienced by 3-4% of children in Western societies, and we know such a loss is one of the most stressful and potentially harmful events in childhood. Therefore, we aimed to investigate how parental death may influence the long-term risk of suicide and how this risk differes by cause of parental death, age at loss, sex of child, socioeconomic factors and parental history of psychiatric illness.The sample size in this study is unparalleled by other studies on risk of suicide. Medical Research: What are the main findings? Dr. Guldin: The main findings were that in a population of 7.302,033 (in three Scandinavian countries), we identified 189,094 persons who lost a parent before the age of 18. Of these bereaved persons, 265 died from suicide. Compared to a control group of persons matched by age and sex, but who did not lose a parent before the age of 18, suicide was twice as common in the bereaved cohort (IRR = 2.02; 95% CI, 1.67-2.44). The risk remained high for at least 25 years of follow-up. The risk was particularly high for children who lost a parent due to suicide, but was also high for children who lost a parent due to other causes. The risk tended to be particularly high for boys who lost a mother and children losing a parent before the age of six. (more…)
Author Interviews, OBGYNE, Pediatrics, Toxin Research, Weight Research / 13.11.2015

MedicalResearch.com Interview with: Joseph M. Braun PhD Assistant Professor Department of Epidemiology in the Program in Public Health Brown University Medical Research: What is the background for this study? Dr. Braun:  Perfluoroalkyl substances are a class of chemicals used to produce stain/water repellent textiles, fire fighting foams, and non-stick coatings. Virtually all people in the US have measurable levels of several different perfluoroalkyl substances in their blood. There is concern that early life exposure to these chemicals can increase the risk of obesity by reducing fetal growth or promoting adipogenesis. What are the main findings? Dr. Braun:  Pregnant women in our study had perfluorooctanoic acid (PFOA) concentrations in their blood that were over 2-fold higher than pregnant women in the United States (median: 5.3 vs. 2.3 ng/mL) during the same time period (2003-2006). Children born to women with higher serum PFOA concentrations during pregnancy had a higher body mass index, greater waist circumference, and more body fat at 8 years of age compared to children born to women with lower serum PFOA concentrations. In addition, children born to women with higher serum PFOA concentrations during pregnancy gained more fat mass between 2 and 8 years of age than children born to women with lower PFOA concentrations. (more…)
Author Interviews, FASEB, Metabolic Syndrome, Nutrition, Weight Research / 13.11.2015

MedicalResearch.com Interview with: Suzan Wopereis, Ph.D. TNO, Microbiology and Systems Biology Group Zeist, The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Wopereis: For the first time we could demonstrate the very subtle start of negative health effects caused by a high calorie snack diet in healthy men. We already knew about the negative consequences of such diets from so called epidemiologic studies. In such studies, scientists compare large populations (thousands of people) to better understand disease development. For example, by comparing  obese populations to a lean population, scientists could define various steps in the disease development related to obesity, like high cholesterol, onset of inflammation, high blood pressure, high glucose, etc. Yet, the early deviations from health  were difficult to study because human metabolism (the way we digest and metabolize our meals from a biochemical viewpoint)  is very flexible and able to efficiently deal with all kinds of daily stressors, such as a meal or intensive exercise. So, at TNO we decided to exploit  this flexibility by giving our healthy volunteers a ‘challenge test’, in the form of a high-fat milkshake. Next, we studied how multiple aspects of their metabolism react to such a challenge test. We showed that a snack diet for 4 weeks reduced many aspects of  flexibility of our healthy men, thus indicating very early changes in health. Both the high-fat challenge test and the integral study of many different outcomes form a novel approach of what “healthy” really means. In the study we used two groups of male volunteers. One group of 10 healthy male volunteers and one group of 9 male volunteers with Metabolic Syndrome, who had a combination of 2 or more risk factors that raises your risk for heart disease and other health problems (unhealthy cholesterol levels, high blood pressure, high blood sugar, high blood lipids, and abdominal fat). In other words, subjects with Metabolic Syndrome have a suboptimal health condition. Both groups received a high-fat milk-shake, and before and up to 8 hours after consumption of this metabolic challenge-test, blood samples were taken. In these blood samples, 61 different biomarkers were measured, such as cholesterol and blood sugar. These 61 biomarkers were used for a thorough health assessment of these 2 groups in response to the challenge test. We noted that biochemical processes related to sugar metabolism, fat metabolism and inflammation function abnormal in subjects with Metabolic Syndrome. The next step was to provide the 10 healthy male volunteers with a snack diet for 4 weeks. On top of their normal diet they had to consume an additional 1300 kcal per day, in the form of sweets and savory products such as candy bars, tarts, peanuts, and crisps. After these 4 weeks the response of the same 61 biomarkers to the challenge test was evaluated. Here, we observed that signaling molecules such as hormones regulating the control of sugar and fat metabolism and inflammation were changed, resembling the very subtle start of negative health effects. Without the use of the challenge test, we would not have been able to observe that even this short period of overfeeding induces changes in the metabolism of healthy people that resemble what happens in people with metabolic syndrome. (more…)
Author Interviews, Dermatology, Melanoma, NEJM, UCSF / 13.11.2015

MedicalResearch.com Interview with: Boris C. Bastian, MD, PhD Professor of Dermatology and Pathology Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research University of California, San Francisco Medical Research: What is the background for this study? What are the main findings? Dr. Bastian:  The cost of DNA sequencing has dropped substantially since the initial sequencing of the human genome in 2001. As a result, the most common cancer subtypes have now been sequenced, revealing the pathogenic mutations that drive them. A typical cancer is driven by 5-10 mutations, but we still do not understand the order in which these mutations occur for most cancers. Determining the order in which mutations occur is challenging for cancers that are detected at a late stage. Melanomas, however, lend themselves to this type of analysis because they are pigmented and found on the surface of the skin, allowing them to be identified early. Sometimes, melanomas are even found adjacent to their remnant precursor neoplasms, such as benign nevi (also known as common moles). We performed detailed genetic analyses of 37 cases of melanomas that were adjacent to their intact precursor neoplasms. We microdissected and sequenced the surrounding uninvolved normal tissue, the precursor neoplasm, and the descendent neoplasm. By comparing the genetic abnormalities in each of the microdissected areas, we were able to decipher the order of genetic alterations for each case. Our work reveals the stereotypic pattern of mutations as they occur in melanoma. Mutations in the MAPK pathway, usually affecting BRAF or NRAS, occur earliest, followed by TERT promoter mutations, then CDKN2Aalterations, and finally TP53 and PTEN alterations. Benign nevi typically harbor a single pathogenic alteration, whereas fully evolved melanomas harbor three or more pathogenic alterations. We also identified an intermediate stage of neoplasia with some but not all of the pathogenic mutations required for fully evolved melanoma. There has been a longstanding debate whether morphologically intermediate lesions, such as dysplastic nevi, truly constitute biological intermediates or whether they simply represent a gray zone of histopathological assessment. Our data indicates that these neoplasms are genuine biological entities. Finally, we observe evidence of UV-radiation-induced DNA damage at all stages of pathogenesis, implicating UV radiation in both the initiation and progression of melanoma. (more…)
Author Interviews, Rheumatology, Smoking / 13.11.2015

Jasvinder Singh MD MPH Professor of Medicine UAB Division of Clinical Immunology and Rheumatology MedicalResearch.com Interview with: Jasvinder Singh MD MPH Professor of Medicine UAB Division of Clinical Immunology and Rheumatology  Medical Research: What is the background for this study? What are the main findings? Dr. Singh: A systematic review of the effect of smoking on outcomes after total joint replacement showed that current smoking increased the risk of overall post-operative complications but that there were scarce data for smoking and specific surgical outcomes of arthroplasty. We performed a study using data from an institutional Total Joint Registry to answer this question.   In a study of for 7,926 patients who underwent hip or knee arthroplasty, 7% were current tobacco users. We found that compared to current non-users, current tobacco users had higher hazard ratios (95% CI) for deep infection, 2.37 (1.19, 4.72; p=0.01) and implant revision, 1.78 (1.01, 3.13; p=0.04) after total hip or knee arthroplasty. No significant differences were noted for periprosthetic fractures or superficial infections. (more…)
Author Interviews, Biomarkers, Rheumatology / 13.11.2015

MedicalResearch.com Interview with: Ron Rogers Executive Vice President, Corporate Communications Spokesman, Myriad Genetics, Inc. Salt Lake City, Utah 84108 Medical Research: What is the background for the MBDA test? What types of biomarkers are included in the score? Response: Vectra DA is an advanced blood test for adults with rheumatoid arthritis (RA). It helps you and your doctor better understand your rheumatoid arthritis disease activity.  Vectra DA blood test for RA gives physicians a more complete look at your disease activity by measuring 12 markers of RA disease activity. Some other tests, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR or “sed rate”), only measure one marker. Vectra DA test scores can help track your disease activity over time with an objective measure that complements your doctor’s exam and your own assessment.  Patients with high Vectra DA scores have 7-fold higher risk for rheumatoid arthritis-related joint damage than patients with low or moderate Vectra DA scores. You can learn more about the specific biomarkers at: http://vectrada.com/health-care-professionals/biomarkers/ (more…)
Author Interviews, Bone Density, Mineral Metabolism, Nutrition, Pediatrics / 13.11.2015

MedicalResearch.com Interview with: Audry H. Garcia PhD Scientist Department of Epidemiology Erasmus MC, University Medical Center Rotterdam Rotterdam, The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Garcia: Mild and chronic metabolic acidosis as a result of a diet rich in acid-forming nutrients, such as cheese, fish, meat and grain products, may interfere with optimal bone mineralization and indirectly increase the risk of osteoporosis later in life. Previous observational studies in adults have reported inverse associations between dietary acid load and bone mass. However, the evidence in younger populations is scarce; only a few studies have been performed in healthy children and adolescents with inconsistent results, and not much is known on the effects of dietary acid load on bone mass in younger children or in children with a non-European background. In a prospective multiethnic population-based cohort study of 2,850 children from the city of Rotterdam, the Netherlands, we found that dietary acid load estimated as dietary potential renal acid load (dPRAL), and as protein intake to potassium intake ratio (Pro:K) at 1 year of age, was not consistently associated with childhood bone health. Furthermore, associations did not differ by sex, ethnicity, weight status, or vitamin D supplementation. (more…)
Author Interviews, Compliance, Heart Disease / 13.11.2015

MedicalResearch.com Interview with: Dr. Tracy Wang MD MHS MSc Assistant Dean, Continuing Medical Education Director, Center for Educational Excellence Fellowship Associate Program Director Associate Professor of Medicine, Cardiology Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Response: Medication non-adherence is a known challenge in the management of patients with coronary artery disease. Barriers to adherence are multifactorial, attributed to patient, healthcare provider, and social determinants. However, whether patient medication adherence varies across different hospitals is unknown. In this study, we sought to determine whether inter-hospital differences exist in the degree of patient adherence to secondary prevention medications after discharge. Moreover, we assessed whether these hospital-specific variations in medication adherence, if any, correspond to downstream patient outcomes. We observed that the majority of post-MI patients were prescribed guideline-recommended secondary prevention medications at discharge. However, among those prescribed, we see a significant decline in the use of these medications within just 90 days after discharge. Medication adherence rates varied markedly across U.S. hospitals, with the widest variation seen for post-discharge use of beta-blockers. Hospitals with high post-discharge  medication adherence were associated with significantly lower risk of major adverse cardiovascular events and death or all-cause readmissions when compared with hospitals with low adherence rates, even after adjustment for differences in patient case-mix. (more…)
AHA Journals, Author Interviews, Blood Pressure - Hypertension, Brigham & Women's - Harvard, Heart Disease / 12.11.2015

MedicalResearch.com Interview with: Carrie C. Lubitz, MD, MPH Assistant Professor of Surgery, Harvard Medical School Senior Scientist, Institute for Technology Assessment Attending Surgeon, Mass General/North Shore Center for Outpatient Care Danvers, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Lubitz: Given reported estimates of resistant hypertension and the proportion of resistant hypertensive patients  with primary hyperaldosteronism (PA) - the most common form of secondary hypertension caused by a nodule or hyperplasia of the adrenal glands – we estimate over a million Americans have undiagnosed PA. Furthermore, it has been shown that patients with PA with the same blood pressure as comparable patients with primary hypertension have worse outcomes. In our study, we found that identifying and appropriately treating patients with PA can improve long-term outcomes in patients in a large number of patients who have resistant hypertension. (more…)
AACR, Author Interviews, Lymphoma, MD Anderson / 12.11.2015

MedicalResearch.com Interview with: Dr. Jatin J. Shah, MD Associate Professor, Department of Lymphoma/Myeloma Assistant Professor, Lymphoma/Myeloma Division of Cancer Medicine The University of Texas, MD Anderson Cancer Center Houston, TX  Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells. The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma. (more…)
Author Interviews, Sugar, Weight Research / 12.11.2015

MedicalResearch.com Interview with: Prof. Peter J. Rogers PhD School of Experimental Psychology University of Bristol, Bristol, UK Medical Research: What is the background for this study? Prof. Rogers: In recent years low-calorie sweeteners have been in the headlines because of concern that they may undermine rather than help with healthy weight management. That concern is based on selective reporting of studies and outright speculation. Our aim was to review the totality of evidence on this subject, which included results from human and animal (mouse and rat) studies. Medical Research: What are the main findings? Prof. Rogers: We found that randomised, controlled intervention trials in humans showed consistently that low-calorie sweeteners versus sugar consumption reduced energy intake and body weight, with no effect or even reduced body weight compared with consumption of water. These types of studies provide the strongest form of evidence – superior to animal and observational studies. In the animal studies, exposure to low-calorie sweeteners was mostly not representative of how people consume low-calorie sweeteners. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, JAMA, Neurological Disorders, Schizophrenia / 12.11.2015

MedicalResearch.com Interview with: Frederick W. Vonberg, MA, MBBS Research Fellow in Neurocritical Care Boston Children's Hospital and Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Response: An association between schizophrenia and epilepsy has long been suspected, ever since people noticed similarities in some aspects of the presentation of the two conditions, and in their epidemiology. For example, people with epilepsy are thought to be more at risk of developing schizophrenia. Furthermore, a psychosis resembling schizophrenia can characterize some forms of epilepsy. Whether this link reflected an overlap in the genetics of the two conditions has remained a mystery, however. In this study, we used a recently developed computational technique to show that there is a significant positive correlation between the genetic variants that are associated with epilepsy and with those that are associated with schizophrenia. (more…)
Author Interviews, BMJ, Diabetes / 12.11.2015

MedicalResearch.com Interview with: Prof. Julia Hippisley-Cox PhD Professor of Clinical Epidemiology & General Practice Faculty of Medicine & Health Sciences The University of Nottingham  Medical Research: What is the background for this study? What are the main findings? Prof. Hippisley-Cox:          Patients with type 1 or type 2 diabetes are at increased risk of blindness and amputation but generally do not have an accurate assessment of the magnitude of their individual risk. There are currently no tools available to calculate risk of other complications such as amputation or blindness. This is important since these are the complications which patients with diabetes fear most and which most impair quality of life. They are also the complications for which patients are most likely to over-estimate their risk and over-estimate the benefits of intensive treatment.          We have developed and externally validated new risk prediction algorithms which calculates absolute risk of developing these complications over a 10 year period in patients with diabetes, taking account of their individual risk factors. (more…)
Author Interviews / 12.11.2015

MedicalResearch.com Interview with: Aouatef Bellamine, Ph.D Lonza Inc Medical Research: What is the background for this study? What are the main findings? Dr. Bellamine: About two years ago, Robert Koeth and his colleagues (Nat Med. 2013 May;19(5):576-85) published a paper linking atherosclerosis and increased cardiac disease risks to Trimethylamine N-oxide (TMAO), a degradation product of dietary quaternary ammonium compounds such as L-Carnitine, Betaine and Choline. When these compounds are not completely absorbed into the intestine, bacterial gut metabolizes them to TMA (Trimethylamine) which is absorbed to the blood and further metabolized by the liver flavin-containing mono-oxygenases (FMOs) to TMAO. This is why some people use injectable l carnitine products. Koeth’s observation was based on
  • 1- clinical association between L-Carnitine levels increased incidence of major cardiac events,
  • 2- on increased lesion formation in ApoE-/- mouse, a disease model used to study atherosclerosis.The conclusion was that TMAO promotes atherosclerosis. Although the association is established, the cause to effect cannot be clarified given the lack of dose response in this mouse model (a single dose has been used) and the small number of animals in the treatment group making the difference between treatments (3 out of 11 animals). In addition, TMAO has been described to play the role of a molecular chaperone, preventing the protein unfolding. TMAO is also found in fish where it plays an important role in maintaining a normal osmolality. Fish is reported otherwise to be a healthy food source and its consumption is not linked to atherosclerosis occurrence.
Lonza decided to investigate the mechanism (s) behind these observations (Bellamine et al., Experimental Biology meeting, San Diego, 28 April 2014, Bellamine et al., Atherosclerosis in press). First, we showed that increasing TMAO levels up to 10-fold the Cmax as reported in humans, did not affect the foam cell formation in vitro, an obligatory step in the atherosclerosis disease progression. Second, we used an improved version of the ApoE-/- mouse model, expressing the cholesteryl ester transport protein (CETP) lacking normally in rodents. The CETP plays a major role in the cholesterol re-cycling in humans and its inhibition has been studied as a target for atherosclerosis treatment. Further, we used different doses of dietary L-Carnitine, leading to different levels of TMAO in an attempt to establish a dose-response curve. We found that TMAO levels inversely correlated with the lesion size. Significantly reduced aortic lesion size was observed at high levels of TMAO. These effects were independent from lipid changes. These observations suggest that TMAO may play a protective role in atherosclerosis disease development by reducing the lesion formation. When the lesions start developing, the TMAO levels would be up-regulated by a compensatory mechanism (possibly by increasing FMOs expression levels). (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, PNAS / 12.11.2015

MedicalResearch.com Interview with: Lei Xu, MD, PhD Steele Laboratory of Tumor Biology Radiation Oncology Department Massachusetts General Hospital Medical Research: What is the background for this study? Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing. Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves. (more…)
Author Interviews, Diabetes, Kidney Disease / 12.11.2015

MedicalResearch.com Interview with: Charuhas Thakar, MD Director, Division of Nephrology and Hypertension Professor of Medicine University of Cincinnati Medical Research: What is the background for this study? What are the main findings? "Diabetes is the major contributor to the growing burden of end-stage renal disease,” says Charuhas Thakar, MD, professor and director of the Division of Nephrology and Hypertension at the UC College of Medicine. "Acute kidney injury is a common problem among diabetic patients who require admissions to hospitals. Approximately one-third of patients who develop AKI also have diabetes mellitus.” Dr. Thakar along with a team of researchers have looked at a cohort of about 3,700 patients with Type 2 diabetes longitudinally followed for a five-year period to determine AKI’s impact. AKI is a rapid loss of kidney function, which is common in hospitalized patients. It has many causes that include low blood volume, exposure to substances or interventions harmful to the kidney and obstruction of the urinary tract. (more…)