Author Interviews, Cancer, Cancer Research, Chemotherapy / 10.07.2015

MedicalResearch.com Interview with: Junichi Nishimura MD, PhD Assistant professor Osaka University in Japan Medical Research: What is the background for this study? What are the main findings? Dr. Nishimura: Oxaliplatin is classified as moderately emetogenic chemotherapy and 2-drug combination antiemetic therapy is recommended for Oxaliplatin based chemotherapy including FOLFOX and XELOX in all guidelines for antiemesis. Nausea and vomiting are still frequent adverse events which decrease the patient’s QOL. However, there was no study investigating whether 3-drug combination antiemetic therapy (5HT3 receptor antagonist+dexamethasone+aprepitant) reduce chemotherapy-induced nausea and vomiting. In this study, we conducted a multicentre, randomized phase III study to evaluate the usefulness of the combined use of aprepitant in colorectal cancer patients treated with Oxaliplatin based chemotherapy. In this phase III study, 3-drug combination therapy significantly increased the inhibition rate of vomiting which was the primary endpoint of this study. Moreover, the inhibition rate of nausea, complete response (no vomiting and no rescue medication use), and complete protection (no vomiting , no rescue medication use and no moderate or worsened nausea) was significantly higher in aprepitant group in overall and delayed phase. We, next, compared the inhibition of vomiting and nausea between males and females in delayed phase. When patients were grouped by sex regardless of the assigned treatment group, females were more affected by nausea and vomiting than males. Finally, in female, aprepitant did significantly prevent nausea and vomiting as well as increased chance of complete protection.
Author Interviews, Cancer Research, Colon Cancer / 10.07.2015

Howard S. Hochster, MD Associate Director, Yale Cancer Center Professor of Medicine, Yale School of Medicine New Haven, CT 06520MedicalResearch.com Interview with: Howard S. Hochster, MD Associate Director, Yale Cancer Center Professor of Medicine, Yale School of Medicine New Haven, CT 06520 Medical Research: What is the background for this study? What are the main findings? Dr. Hochster: TAS-102 is a novel anti-metabolite, recently combined with a metabolic inhibitor to make it orally bioavailable and active in the treatment of cancer.  In pre-clinical studies, it is non-cross reactive with 5FU.  What this means practically is that we have another chemotherapy agent that can be used for patients with colon cancer.  This drug will be an addition to the approved chemotherapy agents 5FU, oxaliplatin and irinotecan.  It may be combinable with these and with targeted agents to provide new active regimens. The main findings of the study were published in NEJM, May 15, 2015.  The study enrolled 800 patients randomized (2:1 ratio) to drug vs placebo.  Patients with advanced colon cancer who had been treated with all the previously approved drugs were eligible.  The drug was active in reducing time to tumor growth (Progression Free Survival) by 50% and improved overall survival for treated patients by about 25%. The data I presented at ESMO included a further analysis on specific genomic subsets of patients within the 800 patient study.  All patients were tested locally for RAS mutations and about 50% had such mutations (as expected).  There was no differences in benefit or toxicity for those with RAS wild-type tumors or RAS mutated tumors.  We also looked at those with BRAF mutations, but only 15% of patients were tested and this mutation occurs in about 8% of colon cancer, so we had very few patients with BRAF mutation.  Given this limitation, it appeared that this did not make a difference for benefit or toxicity either.
Author Interviews, Depression, Mental Health Research, Pediatrics / 10.07.2015

MedicalResearch.com Interview with: Katie Burkhouse, Graduate Student and Dr. Brandon Gibb Ph.D Professor of Psychology Director of the Mood Disorders Institute and Center for Affective Science Binghamton University Medical Research: What is the background for this study? What are the main findings? Dr. Gibb:  One of the strongest risk factors for depression is a family history of the disorder.  However, even among this at-risk group, the majority of children of depressed parents do not develop depression themselves.  For those who do become depressed, the depression can severely and negatively affect their social and academic functioning, become chronic or recurrent over the lifespan, and increase risk for suicide.  What is needed therefore, is a good indicator of which children may be at greatest risk for depression so that interventions can be targeted to these individuals.  We believe that pupil dilation may represent one such marker.  Changes in pupil dilation are associated with activity in the brain’s emotional circuits and have been linked in previous research to the presence of depression.  What my graduate student Katie Burkhouse found is that, even among children who are not currently experiencing symptoms of depression, the degree to which their pupil dilates when they look at pictures of sad faces predicts their risk for developing clinically significant episodes of depression over the next two years.  The findings were specific to pupil responses to sad faces and were not observed when children looked at happy or angry faces suggesting that there is something specific to how the children were processing sad images.
Author Interviews, Cancer Research, End of Life Care, JAMA / 10.07.2015

MedicalResearch.com Interview with: Jennifer Mack, MD, MPH Pediatric oncologist Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Medical Research: What is the background for this study? What are the main findings? Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern California patients who died between the ages of 15 and 39 between the years 2001 and 2010. We found that more than two-thirds of adolescents and young adults received at least one form of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit care in the last month of life (22%), and hospitalization in the last month of life (62%). Medical Research: What should clinicians and patients take away from your report? Dr. Mack: A majority of dying young people with cancer receive intensive measures at the end of life. Older patients who know they are dying usually do not want to receive intensive measures, which are associated with a poorer quality of life near death. High rates of intensive measures raise the concern that young people may experience unnecessary suffering at the end of life. However, it is also important to recognize that adolescents and young adult patients may have different priorities than older patients, and may be more willing to accept intensive measures in order to live as long as possible. Clinicians, patients, and family members should talk about what is most important to patients at the end of life so that their values can be upheld, whether patients prioritize doing everything possible to live as long as possible or focus on quality of life. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Mack: Future research should further examine end-of-life decision-making for adolescents and young adults, including the reasons for receipt of intensive measures. Citation: JAMA Oncology irene.sege@childrens.harvard.edu MedicalResearch.com Interview with: Jennifer Mack, MD, MPH Pediatric oncologist Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Medical Research: What is the background for this study? What are the main findings? Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern California patients who died between the ages of 15 and 39 between the years 2001 and 2010. We found that more than two-thirds of adolescents and young adults received at least one form of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit care in the last month of life (22%), and hospitalization in the last month of life (62%).
Author Interviews, Education, Outcomes & Safety, Surgical Research / 10.07.2015

Judy A. Tjoe, MD, FACS Breast Oncology Surgeon Aurora Health Care Milwaukee, WIMedicalResearch.com Interview with: Judy A. Tjoe, MD, FACS Breast Oncology Surgeon Aurora Health Care Milwaukee, WI Medical Research: What is the background for this study? What are the main findings? Dr. Tjoe: Numerous national health organizations have confirmed minimally invasive breast biopsy (MIBB), which uses a percutaneous core needle as opposed to open surgical techniques, as the biopsy procedure of choice when a patient’s diagnostic test reveals a breast lesion suggestive of malignancy. Unfortunately, despite the overwhelming evidence supporting use of MIBB, open breast biopsy rates in the United States remain as high as 24-39%. Our study was designed to determine if measuring individual practice patterns and providing subsequent feedback to surgeons across a large, multihospital healthcare system would improve their adherence to the quality metric of using minimally invasive breast biopsy to diagnose indeterminate breast lesions. We found that the proportion of studied surgeons (n=46) appropriately adhering to the MIBB quality metric in every instance (i.e. those who achieved 100% adherence) significantly improved from 80.4% to 95.7% (p=0.0196) after receiving feedback on not only their own practice patterns, but those of their blinded peers. As might be expected, the handful of breast-dedicated surgeons (n=4) who cared for nearly half of the analyzed patient population achieved perfect adherence throughout the study, but interestingly, the gains made in total adherence were driven by the general surgeons (n=42), showing that the study’s direct educational efforts were effective in changing practice patterns for the better. These efforts included sending letters describing adherence to the quality metric to individual surgeons and organizational leadership.
Author Interviews, Cancer Research, End of Life Care, JAMA, Johns Hopkins / 10.07.2015

Amol Narang MD Radiation Oncology Resident Johns Hopkins MedicineMedicalResearch.com Interview with: Amol Narang MD Radiation Oncology Resident Johns Hopkins Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Narang: The care provided to cancer patients at end-of-life can be intense, including frequent ER visit, hospitalizations, and ICU stays in the last month of life, administration of chemotherapy in last two weeks of life, and late referrals to hospice. Providing high-intensity treatments at end-of-life has been associated with reduced patient quality-of-life and increased caregiver bereavement. Advance care planning represents an opportunity for patients to indicate their preferences for end-of-life care to try to ensure that the care that they receive at end-of-life is consistent with their values, and has been endorsed by oncologic professional societies, such as ASCO and the NCCN. As such, we wanted to assess if oncologists’ long-standing recognition of the merits of advance care planning has translated into increased participation in advance care planning by cancer patients, and to determine which forms of advance care planning are associated with intensity of care given at end-of-life. From 2000-12, we found that the only type of advance care planning that increased was the assignment of a power of attorney (52% in 2000 to 74% in 2012). However, having a power of attorney was not associated with receiving less aggressive end-of-life care. On the other hand, having a living wills and engaging in a discussion with a provider or loved one about preferences for end-of-life care were both associated with reduced treatment intensity. However, the frequency with which cancer patients created a living or discussed their preferences for end-of-life care did not increase over the study period; importantly, 40% of patients dying of cancer never communicated their preferences for care at end-of-life with anyone.
Author Interviews, Clots - Coagulation, JAMA, Surgical Research / 10.07.2015

Robert J. Lewandowski, MD FSIRAssociate Professor of Radiology Director of Interventional Oncology Department of Radiology Northwestern University Feinberg School of MedicineMedicalResearch.com Interview with: Robert J. Lewandowski, MD FSIR Associate Professor of Radiology Director of Interventional Oncology Department of Radiology Northwestern University Feinberg School of Medicine Medical Research: What is the background for this study? What are the main findings? Response: Retrievable inferior vena cava filters (rIVCF) were designed to provide temporary prevention from pulmonary embolism and then be removed when no longer needed. With permanent United States Food and Drug Administration (FDA) indication, these devices now account for the majority of IVC filters placed. Most rIVCFs placed are never removed because of poor clinical follow up, failed retrieval procedures, or patients not being offered the opportunity for filter removal secondary to prolonged dwell time; the latter has previously been correlated with retrieval failure. Retrievable IVCFs appear to be subject to greater device related complications (e.g., filter penetration of the IVC, filter migration, filter fracture) relative to permanent devices; furthermore, the rates of these complications appear to increase with filter dwell time. This prompted the FDA to issue a 2010 safety alert urging removal of rIVCFs once they are deemed no longer necessary. In the present study, we sought to determine whether rIVCF dwell time affects technical success of the retrieval procedure. Over a six-year period, 648 retrieval procedures were performed at our institution, with filter dwell times ranging from 0-108 months. We found that filter dwell time did not negatively impact IVC filter retrieval success nor did it increase our adverse events from the retrieval procedure. With advanced, adjunctive IVC filter retrieval techniques, rIVCFs can be safely and reliably removed despite long dwell times.
Author Interviews, Blood Pressure - Hypertension, BMJ, Kidney Disease / 10.07.2015

Gijs Van Pottelbergh, MD, PhD Department of Health and Technology Leuven University College Leuven, BelgiumMedicalResearch.com Interview with: Gijs Van Pottelbergh, MD, PhD Department of Health and Technology Leuven University College Leuven, Belgium Medical Research: What is the background for this study? What are the main findings? Response: Earlier research identified arterial hypertension as a cause of chronic kidney disease but in older persons the relation between blood pressure and kidney function is little investigated.This study analyses the relation between dynamic blood pressure measurements and kidney function over time. A decline in blood pressure over time turned out to be a strong risk factor for kidney function decline in all age strata.
Author Interviews, Dengue / 10.07.2015

MedicalResearch.com Interview with: Dr. Eng Eong Ooi BMBS PhD FRCPath Associate Professor & Deputy Director Program in Emerging Infectious Diseases Duke-NUS Graduate Medical School Singapore Medical Research: What is the background for this study? What are the main findings? Response: Dengue prevention continues to rely exclusively on vector control guided by disease and virologic surveillance. The latter has focused on detecting changes in the prevalence of the four antigenically distinct viral serotypes as, in general terms, herd immunity depends on long-lived serotype-specific antibodies.  However, epidemiological observations have indicated that a small number of changes within the viral genome have also been associated with several major outbreaks, without any change in viral serotype.  Identifying the genetic changes that alter viral fitness epidemiologically would thus be important to differentiate strains that have a greater potential of causing epidemics and targeted for control. Using the 1994 outbreak in Puerto Rico as a case in point, we identified nucleotide substitutions in the 3’ untranslated region (3’UTR) of the viral genome as critical determinants of dengue virus’ epidemiological fitness.  Mechanistically, mutations in the 3’UTR altered secondary viral RNA structures and changed the relative proportion of genomic to subgenomic RNA of the virus in infected cells.  The epidemiologically fitter viruses produced larger amounts of subgenomic to genomic RNA.  This subgenomic RNA then binds a host protein, TRIM25, which is a E3 ubiquitin ligase that polyubiquitylates RIG-I to amplify and sustain signalling for type-I interferon expression.  By binding to TRIM25, the subgenomic RNA of dengue virus inhibits the activation and thus enzymatic function of TRIM25.  We suggest that with reduced interferon expression, the virus was thus able to spread more effectively from cell to cell within the infected individuals to reach viremia levels for further subsequent mosquito-borne transmission.
Author Interviews, BMJ, CDC, OBGYNE / 10.07.2015

Jennita Reefhuis, PhD Epidemiologist with CDC National Center on Birth Defects and Developmental DisabilitiesMedicalResearch.com Interview with: Jennita Reefhuis, PhD Epidemiologist with CDC National Center on Birth Defects and Developmental Disabilities Medical Research: What is the background for this study? Dr. Reefhuis: There are previous reports on the link between birth defects and SSRIs. However, the results across some of these studies conflicted. It is not clear whether one SSRI might be safer than other SSRIs. Medical Research: What are the main findings? Dr. Reefhuis: Reassuringly, we found that the five earlier reported links between specific birth defects and sertraline were not found again. We did find that some birth defects occur two to three times more frequently among babies born to mothers who took paroxetine and fluoxetine in early pregnancy.
Author Interviews, Dermatology, NEJM / 10.07.2015

Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg 07.04.2009 | Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg, Germany, 07.04.2009 | [© (c) Martin Zitzlaff, Emilienstr.78, 20259 Hamburg, Germany, Tel. +491711940261, http://www.zitzlaff.com, martin@zitzlaff.com, Postbank Hamburg BLZ 20010020 Kto.-Nr. 10204204, MwSt. 7%, Veroeffentlichung nur gegen Honorar (MFM) und Belegexemplar, mit Namensnennung] MedicalResearch.com Interview with: Prof. Dr. med. Kristian Reich DERMATOLOGIKUM HAMBURG Hamburg Medical Research: What is the background for this study? What are the main findings? Prof. Reich: The Phase 2b X-PLORE study compared a new generation biologic therapy, guselkumab - an inhibitor of IL–23, with the anti–tumor necrosis factor (TNF)–alpha agent adalimumab (Humira®) and placebo in the treatment of moderate-to-severe plaque-type psoriasis. It showed that up to 86 percent of patients treated with guselkumab achieved a Physician’s Global Assessment (PGA) score of cleared psoriasis or minimal psoriasis at week 16, the study’s primary endpoint.  Interestingly, levels of efficacy were higher for several guselkumab doses through week 16 when compared to adalimumab. Improvements with guselkumab continued through week 40 with every eight- or twelve-week maintenance treatment.  
Author Interviews, Heart Disease, JAMA / 09.07.2015

MedicalResearch.com Interview with: Dr Emanuele Di Angelantonio FESC FAHA University Lecturer | University of Cambridge Director | MPhil in Public Health, University of Cambridge Deputy Director | NIHR Biomedical Research Unit in Donor Health and Genomics Honorary Consultant | NHS Blood and Transplant Department of Public Health and Primary Care Strangeways Research Laboratory Cambridge, UK Medical Research: What is the background for this study? What are the main findings? Response: Previous research as mainly focused on individual with one cardiometabolic condition alone and, despite it could be expected that having more than one condition poses a greater risk, this is the first study that is able to precisely quantify how much is worst. Furthermore, given that the conditions we study (diabetes, heart attack, and stroke) share several risk factors, it could be expected that the combination of these will not be  multiplicative. We were somewhat surprised to find that participants who had 1 condition had about twice the rate of death; 2 conditions, about 4 times the rate of death; and all 3 conditions, about 8 times the rate of death. We  estimated that at the age of 60 years, men with any two of the cardiometabolic conditions studied would on average have 12 years of reduced life expectancy, and men with all three conditions would have 14 years of reduced life expectancy. For women at the age of 60 years, the corresponding estimates were 13 years and 16 years. The figures were even more dramatic for patients at a younger age. At the age of 40 years, men with all three cardiometabolic conditions would on average have 23 years of reduced life expectancy; for women at the same age, the corresponding estimate was 20 years.
Author Interviews, Biomarkers, Melanoma / 09.07.2015

MedicalResearch.com Interview with: Mario Mandalà, MD Department of Oncology and Haematology Papa Giovanni XXIII Hospital Bergamo, Italy Medical Research: What is the background for this study? Dr. Mandalà: In addition to their established molecular mechanism of action, growing evidence suggests that the therapeutic efficacy of BRAFi relies on additional factors that affect the tumor–host interactions, including the enhancement of melanoma antigen expression and the increase in immune response against tumor cells.  Preclinical data show that oncogenic BRAF contributes to immune evasion, and that targeting this mutation may increase the melanoma immunogenicity. Data in vitro or from animal models propose PD-L1 as a potential mechanism that favors BRAFi resistance through the modulation of host immune responses. However, demonstration of this hypothesis in the clinical setting is lacking. Medical Research: What are the main findings? Dr. Mandalà: In the present study, we have evaluated, in a homogeneous series of MMP treated with BRAFi, the association of tumoral PD-L1 IHC expression and the density of TIMC with RR, PFS and OS. Results provide the first proof-of-principle clinical evidence of the predictive and prognostic relevance of PD-L1 IHC expression and density of immune cell infiltration in BRAFV600 mutated MMP receiving BRAFi.
Author Interviews, Biomarkers, Infections / 09.07.2015

Yingfu Li, PhDProfessor, Dept of Biochemistry and Biomedical Sciences and Dept of Chemistry and Chemical Biology McMaster University, Hamilton, CanadaMedicalResearch.com Interview with: Yingfu Li, PhD Professor, Dept of Biochemistry and Biomedical Sciences and Dept of Chemistry and Chemical Biology McMaster University, Hamilton, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Li: Simple, accurate and sensitive diagnostic tests are highly sought-after in modern medicine. Take bacterial infection as an example. Many microbial pathogens pose serious threats to public health and are responsible for many annual outbreaks that result in numerous human illnesses and deaths. Early and accurate detection of specific pathogens has long been recognized as a crucial strategy in the control of infectious diseases because such a measure can provide timely care of patients, prevent potential outbreaks, and minimize the impact of on-going epidemics. To detect the infection early, we need highly sensitive tests. We have developed a molecular device made of DNA that can be turned on by a molecule of choice, such as a biomarker for a disease. When it gets switched on, the system will undergo massive signal amplification allowing for extremely sensitive detection of the target molecule. The test has the best sensitivity ever reported for a detection system of this kind – it is as much as 10,000 times more sensitive than other detection systems. The scientific report can be found at http://onlinelibrary.wiley.com/doi/10.1002/anie.201503182/abstract
Author Interviews, Nature, OBGYNE / 08.07.2015

Shawn L. Chavez, Ph.D Assistant Scientist/Professor Oregon National Primate Research Center OHSU | Oregon Health & Science UniversityMedicalResearch.com Interview with: Shawn L. Chavez, Ph.D Assistant Scientist/Professor Oregon National Primate Research Center OHSU | Oregon Health & Science University Medical Research: What is the background for this study? Dr. Chavez: This study builds upon a previous study also published in Nature Communications in 2012, which demonstrated that chromosomally normal and abnormal 4-cell human embryos can be largely distinguished by combining the timing intervals of the first three cell divisions with the presence or absence of a dynamic process called cellular fragmentation. The current study further combines time-lapse imaging of embryo development and full chromosome analysis with high throughout single-cell gene expression profiling to assess the chromosomal status of human embryos up to the 8-cell stage. Medical Research: What are the main findings? Dr. Chavez: The key findings of this research were that by measuring the duration of the first cell division, one can identify which embryos are chromosomally normal versus abnormal even earlier in development. By examining gene expression at a single-cell level, we were able to correlate the chromosomal make-up of an embryo to a subset of 12 genes that are activated prior to the first cell division. These genes likely came from either the egg or sperm and can be used to predict whether an embryo will be chromosomally normal or abnormal within the first 30 hours of development.
Author Interviews, Education, Johns Hopkins, Outcomes & Safety, Surgical Research / 08.07.2015

Judy Huang, M.D. Professor of Neurosurgery Program Director, Neurosurgery Residency Program Fellowship Director, Cerebrovascular Neurosurgery Johns Hopkins HospitalMedicalResearch.com Interview with: Judy Huang, M.D. Professor of Neurosurgery Program Director, Neurosurgery Residency Program Fellowship Director, Cerebrovascular Neurosurgery Johns Hopkins Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Huang: Residents are medical school graduates who are in training programs working alongside and under supervision of more senior physicians, known as attendings. Patients are sometimes wary of having residents assist in their operations, but an analysis of 16,098 brain and spine surgeries performed across the United States finds that resident participation does not raise patient risks for postoperative complications or death.
Author Interviews, Cancer Research, JNCI / 08.07.2015

Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 AustraliaMedicalResearch.com Interview with: Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 Australia Medical Research: What is the background for this study? Response: At least 1 in 1,000 people in the population have a mutation in one of the mismatch repair genes that causes Lynch syndrome. These people have a very high risk of bowel cancer (colorectal cancer): if nothing is done, about half would develop the disease. The main risk reduction method for these people is to have regular colonoscopy screening every year. Almost nothing is known whether or not lifestyle factors and medications can modify the risk of bowel cancer for people with Lynch syndrome. A study was conducted to investigate the associations between aspirin and ibuprofen intake and the risk of bowel cancer, by studying 1,858 people with Lynch syndrome who were recruited into the Colon Cancer Family Registry from Australia, New Zealand, Canada and the USA. This is the largest study to date investigating the associations between aspirin, ibuprofen and bowel cancer risk for people with Lynch syndrome.
Author Interviews, Cancer Research, Genetic Research, JAMA / 08.07.2015

Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 AustraliaMedicalResearch.com Interview with: Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 Australia Medical Research: What is the background for this study? What are the main findings? Response: About 2-5% of uterine cancer are associated with an underlying genetic condition mainly Lynch syndrome. Lynch syndrome is caused by a mutation in one of the mismatch repair genes. At least 1 in 1000 people in the population have a mutation that causes Lynch syndrome and these people have a very high risk of cancers mainly bowel and uterine cancers. One in three women with a mutation in one of the mismatch repair genes are likely to develop a uterine cancer in their lifetime. The only way to reduce the risk of uterine cancer for these women is to remove the uterus. There is no current recommendation for screening method to detect uterine cancer early. Almost nothing is known about if and how lifestyle factors and hormonal factors can modify their risk of uterine cancer. By studying 1128 women with a mutation that causes Lynch syndrome who were recruited from Australia, New Zealand, Canada and the USA, we found that later age at first menstrual cycle, having one or more live births, and using hormonal contraceptive use for one year or longer were associated with a lower risk of uterine cancer.
Author Interviews, Breast Cancer, Endocrinology, Lancet, Menopause / 08.07.2015

MedicalResearch.com Interview with: Dr. Jürg Bernhard Ph.D. International Breast Cancer Study Group Coordinating Center and Bern University Hospital, Inselspital, Bern, Switzerland Medical Research: What is the background for this study? What are the main findings? Response: In the combined analysis of the SOFT and TEXT trials, the aromatase inhibitor exemestane was more effective than tamoxifen in preventing breast cancer recurrence in young women (premenopausal) who also receive ovarian function suppression (OFS) as adjuvant (post-surgery) treatment for hormone-sensitive early breast cancer, providing a new treatment option for these women. These trials were conducted by the International Breast Cancer Study Group (IBCSG) and involved more than 4700 patients of over 500 centers in 27 countries. Now we present patient-reported quality of life outcomes from these trials. In the TEXT and SOFT trials, patients assigned exemestane+OFS reported more detrimental effects of bone or joint pain, vaginal dryness, greater loss of sexual interest and difficulties becoming aroused, while patients assigned tamoxifen+OFS were more affected by hot flushes and sweats. Global quality of life domains (mood, ability to cope and physical well-being) were similar between the randomized treatment groups.
Author Interviews, Diabetes, Weight Research / 08.07.2015

Subhadra Gunawardana DVM, Ph.D Research Associate Professor Department of Molecular Physiology & Biophysics Vanderbilt University Medical Center Nashville, TN 37232MedicalResearch.com Interview with: Subhadra Gunawardana DVM, Ph.D Research Associate Professor Department of Molecular Physiology & Biophysics Vanderbilt University Medical Center Nashville, TN 37232 Medical Research: What is the background for this study? What are the main findings? Response: For many years the general consensus has been that insulin replacement is essential for treating type 1 diabetes. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Our work on mouse models show that type 1 diabetes can be effectively reversed without insulin, through subcutaneous transplantation of embryonic brown adipose tissue (BAT). BAT transplantation leads to replenishment of recipients' white adipose tissue; dramatic decrease of inflammation; secretion of a number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin-independent glucose homeostasis is established physiologically, through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue. Medical Research: What should clinicians and patients take away from your report? Response: If translated to human patients, this approach could provide a cure for type 1 diabetes that does not require regular exogenous administration of insulin or any other compound, and would thus avoid the many inherent difficulties with such therapies.
AHA Journals, Author Interviews, Connective Tissue Disease, Heart Disease, NYU/NYMC / 08.07.2015

Mohamed Boutjdir, PhD, FAHADirector of the Cardiovascular Research Program VA New York Harbor Healthcare System Professor, Depts of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center and NYU School of Medicine, New York, NYMedicalResearch.com Interview with: Mohamed Boutjdir, PhD, FAHA Director of the Cardiovascular Research Program VA New York Harbor Healthcare System Professor, Depts of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center and NYU School of Medicine, New York, NY Medical Research: What is the background for this study? What are the main findings? Dr. Boutjdir: Patients with autoimmune diseases including Sjogren’s syndrome, systemic lupus erythematosus and other connective tissue diseases who are seropositive for anti-SSA/Ro antibodies may present with corrected QTc prolongation on the surface ECG. This QTc prolongation can be arrhythmogenic and lead to Torsades de Pointes fatal arrhythmia. In our study, we established for the first time an animal model for this autoimmune associated QTc prolongation that is reminiscent of the clinical long QT2 syndrome. We also demonstrated the functional and molecular mechanisms by which the presence of the anti-SSA/Ro antibodies causes QTc prolongation by a direct cross-reactivity and then block of the hERG channel (Human ether-a-go-go-related gene). This hERG channel is responsible for cardiac repolarization and its inhibition causes QTc prolongation. We were able to pinpoint to the target epitope at the extracellular pore forming loop between segment 5 and segment 6 of the hERG channel.
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JACC, Lifestyle & Health / 08.07.2015

Liana C. Del Gobbo, PhDPostdoctoral Research Fellow Friedman School of Nutrition Science & Policy Tufts University Boston MAMedicalResearch.com Interview with: Liana C. Del Gobbo, PhD Postdoctoral Research Fellow Friedman School of Nutrition Science & Policy Tufts University Boston MA Medical Research: What is the background for this study? What are the main findings? Dr. Del Gobbo: Heart failure most commonly develops in adults over 65 years old- the most rapidly growing portion of the US population. The condition greatly reduces the quality of life of older adults. Heart failure is the leading cause of hospitalizations in the US among those on Medicare, and is associated with large  health care costs. Prevention is key for reducing the burden of this disease. A detailed analysis of factors that might help prevent heart failure, such as a person's pattern of eating (as well as individual foods), in addition to other lifestyle factors (eg. smoking, physical activity, etc), had not been previously examined all together, in the same study. To get a fuller picture of how to prevent this condition, this study examined the relative importance of dietary habits and other lifestyle factors for development of heart failure. Our paper shows that older adults can cut their risk in half by adhering to a few healthy lifestyle factors, including moderate physical activity, modest alcohol consumption (eg. more than one drink/week, but not more than 1-2 drinks/day), not smoking, and maintaining a healthy weight.
Author Interviews, Infections, Surgical Research / 08.07.2015

Paul M. Sethi, MD Orthopaedic & Neurosurgery Specialists Greenwich, CT MedicalResearch.com Interview with: Paul M. Sethi, MD Orthopaedic & Neurosurgery Specialists Greenwich, CT MedicalResearch: What is the background for this study? Dr. Sethi: Propionibacterium acnes is one of the most significant pathogens in shoulder surgery; the cost of a single infection after shoulder arthroplasty may be upwards $50,000. Residual P. acnes may be found on the skin 29% of the time immediately after surgical skin preparation and in 70% of dermal biopsy specimens. Identifying more ideal skin preparation may help reduce the risk of infection. MedicalResearch: What is the purpose of this study? Dr. Sethi: The purpose of this study was to evaluate the ability of topical benzoyl peroxide (BPO) cream, along with chlorhexidine skin preparation, to reduce the chance of identifying residual bacteria after skin preparation. Our hypothesis was that adding topical benzoyl peroxide to our skin preparation would reduce the number of positive P. acnes cultures identified during surgery.
Author Interviews, Insomnia, JAMA, Mental Health Research / 07.07.2015

Jason Ong, Ph.D., CBSM Associate Professor, Department of Behavioral Sciences Director, Behavioral Sleep Medicine Training Program Rush University Medical CenterMedicalResearch.com Interview with: Jason Ong, Ph.D., CBSM Associate Professor, Department of Behavioral Sciences Director, Behavioral Sleep Medicine Training Program Rush University Medical Center Medical Research: What is the background for this study? What are the main findings? Response: Insomnia is a very common sleep problem that was previously thought to be related to another medical or psychiatric condition.  Evidence now supports the notion that insomnia can emerge as a disorder distinct from the comorbid condition.  In this study, we evaluated the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), the most widely used nonpharmacologic treatment for insomnia, in the context of medical and psychiatric comorbidities. We conducted a systematic review and meta-analysis of 37 studies and found that 36% of patients who received cognitive behavioral therapy for insomnia were in remission at post-treatment compared to 17% who received a control or comparison condition.  CBT-I had medium to large effects for improving sleep quality and reducing the amount of time awake in bed.  Positive findings were also found on the comorbid condition, with greater improvements in psychiatric conditions compared to medical conditions.
Author Interviews, Heart Disease, Nature / 07.07.2015

Dr. Gary K OwensRobert M. Berne Cardiovascular Research Center University of Virginia, Charlottesville, VirginiaMedicalResearch.com Interview with: Dr. Gary K Owens Ph.D Robert M. Berne Cardiovascular Research Center University of Virginia, Charlottesville, Virginia Medical Research: What is the background for this study? Dr. Owens: The leading cause of death in the USA and worldwide is cardiovascular disease with many of the clinical consequences including heart attacks (myocardial infarctions) and strokes being secondary consequences of atherosclerosis, commonly referred to as hardening of the arteries. Importantly, a heart attack is not caused by gradual narrowing of a large coronary artery by the atherosclerotic plaque, but rather is caused by acute rupture of a plaque that results in a catastrophic thrombotic event that can completely occlude a major coronary artery shutting off blood supply to a major heart region. Similarly, rupture of a plaque can result in formation of a thrombus that breaks off and circulates to a cerebral vessel where it can occlude blood flow to a brain region leading to a stroke. As such, it is critical to understand the mechanisms that regulate the stability of plaques, and the likelihood of plaque rupture. The general dogma among clinicians and cardiovascular researchers has been that atherosclerotic plaques that have an abundance of macrophages and macrophage-derived foam cells relative to smooth muscle cells (SMC), the cells that normally line all of your blood vessels, are less stable and more prone to rupture with subsequent clinical consequences. However, the evidence for this is based on use of methods that are unreliable in identifying which cells within the plaque are truly derived from macrophages versus SMC, and even more importantly, what mechanisms regulate phenotypic transitions of these cells that are critical in the pathogenesis of this disease. Indeed, results of studies in cultured smooth muscle cells and macrophages have shown that each cell can express markers of the other cell type in response to stimuli likely to be present within advanced atherosclerotic lesions while down-regulating expression of their typical cell selective markers. As such, previous studies in the field have likely mis-identified which cell is which in many cases. The goals of our studies were to clearly identify which cells within advanced atherosclerotic lesions are derived from SMC, to determine the various phenotypes exhibited by these cells and their functional role in lesion pathogenesis,  and to determine what regulates these phenotypic transitions.
Author Interviews, Cancer Research, Dermatology / 07.07.2015

Wen-Qing Li Ph.D Department of Dermatology Warren Alpert Medical School Department of Epidemiology, School of Public Health, Brown University, Providence, RIMedicalResearch.com Interview with: Wen-Qing Li Ph.D Department of Dermatology Warren Alpert Medical School Department of Epidemiology, School of Public Health, Brown University, Providence, RI Medical Research: What is the background for this study? Response: Rosacea is a chronic inflammatory cutaneous disorder and may be an end-organ response in a systemic disorder. We systemically examined the association between personal history of rosacea and risk of cancer based on 75088 whites in the Nurses’ Health Study II, during a follow-up of 20 years. Medical Research: What are the main findings? Response: We suggest possible associations between personal history of rosacea and an increased risk of thyroid cancer and Basal Cell Cancer. Analyses did not find significant associations for other individual cancer types. 
Author Interviews, Diabetes, Lipids, Ophthalmology / 06.07.2015

Dr Ruth Hogg, Lecturer Centre for Experimental Medicine (formerly Centre for Vision and Vascular Science) Institute of Clinical Science Block Belfast Northern IrelandMedicalResearch.com Interview with: Dr Ruth Hogg, Lecturer Centre for Experimental Medicine (formerly Centre for Vision and Vascular Science) Institute of Clinical Science Block Belfast Northern Ireland Medical Research: What is the background for this study? What are the main findings? Dr. Hogg: The development of Diabetic macular edema (DME) in patients with diabetes can result in severe visual loss.  Understanding the factors driving the development of these conditions is important for developing effective treatments.  The role of lipids has been suggested by previous studies however as the evidence overall appeared to have significant uncertainty we decided to undertake a systematic review and where possible perform a meta-analysis or results. The study revealed that the evidence of a relationship between blood lipid levels and Diabetic macular edema from cohort and case control studies was strong but evidence from the randomised control trials (RCTs) was weak.  The RCTS evaluated however were often not designed to look at Diabetic macular edema as an primary outcome, and this was often part of a secondary analysis leaving uncertainty over the power to detect the association.