Abuse and Neglect, Author Interviews, Pediatrics, University of Pennsylvania / 16.12.2016

MedicalResearch.com Interview with: Joanne N. Wood, MD, MSHP Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Research Director, SafePlace Faculty, PolicyLab The Children’s Hospital of Philadelphia  MedicalResearch.com: What is the background for this study? Response: Each year the U.S. Army Family Advocacy program (FAP) investigates between 6000 to 9000 reports of alleged abuse or neglect involving children of Army service members.   In approximately 48% of reported cases FAP determines a child was a victim of maltreatment, substantiates the report, and collaborates with local civilian child protection service (CPS) agencies in providing services and ensuring safety. Thus, FAP plays a key role in supporting Army families and protecting children.  But FAP can only investigate and respond to cases of child abuse and neglect about which they are aware. (more…)
AHA Journals, Author Interviews, Lipids, Pharmacology / 16.12.2016

MedicalResearch.com Interview with: Dr. Eli M. Roth MD, FACC President, Medical Director Sterling Research Group Cincinnati, OH MedicalResearch.com: What is the background for this study? What are the main findings? Response: At this year’s AHA 2016, we presented a pharmacodynamics analysis of ODYSSEY CHOICE I, which evaluated the effects of Praluent 300 mg administered every four weeks (Q4W) for 24 weeks in hypercholesterolemia patients at moderate to very high cardiovascular risk who were on maximally tolerated statin or no statin and/or other lipid-lowering therapies. The pharmacodynamic analysis of CHOICE I in patients on statins supports the use of Praluent 300 mg Q4W as an alternative starting dose for patients who prefer a Q4W dosing regimen and demonstrates the value of LDL-C based dosing interval adjustment. The findings from this analysis were consistent with prior ODYSSEY Phase 3 studies, showing that Praluent substantially reduced circulating free PCSK9 concentration, resulting in significant LDL-C reductions. Additionally, Praluent was generally well tolerated. (more…)
Aging, Author Interviews, Cancer Research, Genetic Research / 16.12.2016

MedicalResearch.com Interview with: Jerry W. Shay PhD Professor Department of Cell Biology, UT Southwestern Medical Center MedicalResearch.com: What did you find? Response: Telomeres are the ends of chromosomes and they gradually shortened with every cell division. There have been multiple studies proposing that shortened telomeres correlate with human aging. Most cancers overcome the shortening of telomeres and aging by activating the enzyme, telomerase. Surprisingly, the human telomerase gene (hTERT) is very close to the telomere on chromosome 5p. During human development telomerase is active until about 18 weeks of gestation. It has been a mystery until this present work of what actually causes telomerase to become silenced. We found in this current work that when telomeres are long during development the telomere loops over and helps to silence the telomerase gene. However, as we age and telomeres get progressively shorter, then telomerase becomes permissive for activation and possibly initiation of cancer. This study in part explain why most cancers are in the 65 and older segment of the population. (more…)
Author Interviews, Genetic Research, JAMA / 16.12.2016

MedicalResearch.com Interview with: C. Anthony Blau, M.D. Professor of Medicine, Division of Hematology University of Washington School of Medicine Co-Director, University of Washington Institute for Stem Cell and Regenerative Medicine Director, Center for Cancer Innovation MedicalResearch.com: What is the background for this study? What are the main findings? Response: Matching cancer treatment to the molecular composition of a patient’s tumor holds promise for making cancer therapies more effective, and molecular testing for cancer patients has become widespread in recent years. Recently molecular testing of tumor samples has been complemented by blood tests that characterize tumor DNA that has been shed into the bloodstream.  Blood tests are attractive because they are much less invasive than obtaining tumor tissue via biopsies. (more…)
Author Interviews, Cost of Health Care, Johns Hopkins, Weight Research / 16.12.2016

MedicalResearch.com Interview with: Ruchi Doshi, MPH MD Candidate 2017 | Johns Hopkins University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Current guidelines recommend that physicians collaborate with non-physician health professionals to deliver weight management care. While several studies have looked at barriers physicians face in providing these services, few studies have looked at the barriers that the non-physician health professionals face. Ultimately, we found that one quarter of these health professionals found insurance coverage to be a current challenge to providing weight management care, and that over half of them felt improved coverage would help facilitate weight loss. These findings were consistent regardless of the income level of the patient populations. (more…)
Author Interviews, Cost of Health Care, Geriatrics / 16.12.2016

MedicalResearch.com Interview with: Leigh Purvis, MPA AARP PPI Director of Health Services Research MedicalResearch.com: What is the background for this study? What are the main findings? Response: This report is part of an ongoing series that AARP has been publishing since 2004. The report focuses on brand name prescription drugs that are widely used by older Americans and found that, on average, their retail prices increased almost 130 times faster than general inflation in 2015. The report also found that the average annual cost for one brand name medication used on a chronic basis was more than $5,800 in 2015, almost $1,000 higher than the average annual cost of therapy in 2014. (more…)
Author Interviews, Infections, Nature / 16.12.2016

MedicalResearch.com Interview with: Professor Alistair J P Brown  DSc FSB FAAM FRSE Aberdeen Fungal Group, MRC Centre for Medical Mycology, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen UK  MedicalResearch.com: What is the background for this study? Response: Most of us harbor the yeast Candida albicans, and most of the time it does us no harm.  However, under certain circumstances it can break out to cause nasty infections of the mouth or genitalia (thrush), or potentially fatal infections in vulnerable intensive care patients.  Indeed, over half of women will suffer at least one episode of vulvovaginal candidiasis in their lifetime, and over 5% of women suffer recurrent episodes (four or more episodes per annum).  Also, it has been estimated that there are over 400,000 life-threatening systemic Candida infections worldwide per annum, of which over 40% are fatal (see Science Translational Medicine (2012) vol. 4, 165rv13).  A key to this is the potency of our immunological defenses: the weaker our defenses the more vulnerable we are to fungal infection.  Therefore, we in the Medical Research Council (MRC) Centre for Medical Mycology – and other groups worldwide – are studying the mechanisms by which our immune cells recognize and kill invading Candida cells, thereby protecting us from infection. (more…)
Author Interviews, Nature, Neurological Disorders, Technology / 16.12.2016

MedicalResearch.com Interview with: Bin He, Ph.D. Director, Institute for Engineering in Medicine Director, Center for Neuroengineering Distinguished McKnight University Professor of Biomedical Engineering Medtronic-Bakken Endowed Chair for Engineering in Medicine University of Minnesota, Minneapolis, MN 55455 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This work is aimed at developing a noninvasive brains-computer interface to allow disabled patients to control their environment by just thinking about it. We found 8 human subjects were able to accomplish 3D reach and grasp tasks without using any muscle activities but just thinking about it. (more…)
Author Interviews, Memory, Sleep Disorders / 16.12.2016

MedicalResearch.com Interview with: Roi Levy The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, The Mina and Everard Goodman Faculty of Life Sciences Bar Ilan University Ramat Gan, Israel

MedicalResearch.com: What is the background for this study? Response: Long-term memory after an experience takes many hours to be reach its final form. During the consolidation period, the nascent memory is labile: the consolidation can be interrupted by new experiences, or new experiences that are too insignificant to be remembered can capture the consolidation process, and thereby be remembered. To avoid potentially maladaptive interactions between a new experience and consolidation, a major portion of the consolidation is deferred to the time in which we sleep, when new experiences are unlikely. For over 100 years, studies have demonstrated that sleep improves memory formation. More recent studies have shown that consolidation occurs during sleep, and that consolidation depends on the synthesis of products that support memory formation. Consolidation is unlikely to be shut off immediately when we are awakened from sleep. At this time, even a transient experience could capture the consolidation, leading to a long-lasting memory of an event that should not be remembered, or could interfere with the consolidation. We have identified a mechanism that prevents long-term memories from being formed by experiences that occur when awakened from sleep. (more…)
Author Interviews, Gastrointestinal Disease, HIV, Inflammation / 15.12.2016

MedicalResearch.com Interview with: Prof. Jamal Tazi Director, Institute for Molecular Genetics CNRS and University of Montpellier and Executive Committee Member ABIVAX MedicalResearch.com: What is the background for this study? Response: Its long been established that people with HIV, even those treated successfully with antiretroviral treatment, exhibit significantly higher levels of chronic inflammation than HIV-negative people. The causes of this inflammation are many – ongoing viral replication, often in the so-called viral reservoirs, leaky gut syndrome, concomitant viral infections (eg CMV, hepatitis etc). (more…)
Author Interviews, Cancer Research, Dermatology, Surgical Research / 15.12.2016

MedicalResearch.com Interview with: Hywel C. Williams DSc, FMedSci, NIHR Senior Investigator Director of the NIHR Health Technology Assessment Programme http://www.nets.nihr.ac.uk/programmes/hta Professor of Dermato-Epidemiology and Co-Director of the Centre of Evidence-Based Dermatology, http://www.nottingham.ac.uk/research/groups/cebd/index.aspx University of Nottingham, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our clinical trial of 5% imiquimod cream versus surgery for low risk basal carcinoma (BCC) of the skin was first prompted by a shocking lack of randomised controlled clinical trials for what is the commonest form of human cancer. We had conducted a Cochrane systematic review prior to starting the study and found very few long term studies. An emerging literature on imiquimod cream at the time suggested that it might have a clinically useful effect for low risk BCC. All the studies were short term and industry supported, so with the support of Cancer Research UK (UK largest cancer charity), we undertook a large independent study to see how the cream compared to the reference standard of excision surgery with a 4mm margin for low risk superficial and nodular BCC. Our three year results, published in Lancet Oncology, showed that surgery is clearly superior to imiquimod cream, with a success rate (absence of initial failure and no signs of recurrence at 3 years) of 98.4% compared to 83.6% for imiquimod. Nevertheless, the 83.6% success rate is still potentially useful, so we wanted to see whether these 3 year results were sustained. So we followed up your study participants for a total of 5 years and found that the response rates at 5 years were almost the same as those at 3 years (97.7% and 82.5% for surgery and imiquimod respectively). Most treatment failures with imiquimod occurred early on ie in the first year of treatment. Our study shows that if initial treatment works, the benefits are sustained. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, JAMA, Pediatrics, Pulmonary Disease / 15.12.2016

MedicalResearch.com Interview with: Kristin N. Ferguson, BSc The Royal Women’s Hospital and Deakin University Melbourne, Victoria, Australia MedicalResearch.com: What is the background for this study? Response: Weaning preterm infants from mechanical ventilation, thereby minimising the risks of having an endotracheal tube in situ which may further damage their fragile lungs, is something all neonatal clinicians are keen to do. We provide clinicians with a straightforward list of safe and effective strategies to help them in this task, as well as pointing out some treatments to either avoid or use with caution. (more…)
Author Interviews, Education, JAMA, Surgical Research / 15.12.2016

MedicalResearch.com Interview with: Mohammed Al-Omran, MD, MSc, FRCSC Head, Division of Vascular Surgery St. Michael’s Hospital Professor, Department of Surgery University of Toronto MedicalResearch.com: What is the background for this study? What are the main findings? Response: General surgery residency is among the most demanding clinical training programs in medicine. Several studies have suggested surgical residents have a relatively high attrition rate; however, no study has systematically reviewed the overall prevalence and causes of attrition among general surgery residents. We included over 20 studies representing 19,821 general surgery residents in our review. Most studies were from the US. We found the pooled estimate of attrition prevalence among general surgery residents was 18%. Female residents were more likely to leave than male (25% versus 15%), and residents were most likely to leave after their first training year (48%). Departing residents most commonly switched to another medical specialty (such as anaesthesia, plastic surgery, radiology or family medicine) or relocated to another general surgery program. The most common causes of attrition were uncontrollable lifestyle (range of 18% to 88%) and transferring to another specialty (range of 18% to 39%). (more…)
Author Interviews, Dermatology, Education, JAMA, Melanoma / 15.12.2016

MedicalResearch.com Interview with: June K. Robinson, MD Research Professor of Dermatology Northwestern University Feinberg School of Medicine Department of Dermatology Chicago, IL 60611 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This is a secondary finding from a randomized controlled trial of a structured skills training program for melanoma patients and their skin check partners. The pairs learned and performed skin self-examination for the early detection of melanoma. They continued to perform skin checks for 2 years and trained pairs identified more early melanoma (melanoma in situ and Stage 1A melanoma) than controls. (more…)
Author Interviews, Pain Research, Pediatrics, Vaccine Studies / 13.12.2016

MedicalResearch.com Interview with:

Dr. Anna Taddio PhD Professor in the Leslie Dan Faculty of Pharmacy University of Toronto Adjunct senior scientist and clinical pharmacist at SickKids MedicalResearch.com: What is the background for this study? Response: We do not know enough about how well different pain interventions work over time and when combined together. In this study, we compared the effectiveness of interventions when layered together, starting from simplest to most complicated in terms of implementation, in the first year of life in infants undergoing routine vaccinations. We compared 4 different treatments: 1. placebo (sham), 2. Educational video for parents about how to soothe their infants, 3) video and sucrose (sugar water), 4) video and sucrose and liposomal lidocaine cream. (more…)
Author Interviews, Leukemia, Nature, Pediatrics, UT Southwestern, Weight Research / 13.12.2016

MedicalResearch.com Interview with: Chengcheng (Alec) Zhang, Ph.D. Associate Professor Hortense L. and Morton H. Sanger Professorship in Oncology Michael L. Rosenberg Scholar for Medical Research Department of Physiology UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? Response: New therapeutic targets and approaches are needed to effectively treat leukemia. Acute myeloid leukemia (AML) is the most common form of adult acute leukemia whereas acute lymphoblastic leukemia (ALL) is the most common form of cancer in children; ALL also occurs in adults. Although treatment of pediatric ALL is highly effective, a sizeable number of patients are non-responders who succumb to this disease. The outcome of ALL in adults is significantly worse than for pediatric ALL. Additionally, some types of ALL have a much poorer prognosis than others. Dietary restriction, including fasting, delays aging and has prolonged effects in a wide range of organisms and has been considered for cancer prevention. In certain types of solid tumor,_ENREF_1 dietary restriction regimens are able to promote T cell-mediated tumor cytotoxicity and enhance anticancer immunosurveillance, and coordinate with chemotherapy to promote the anti-cancer effects. However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown. Furthermore, whether dietary restriction alone can inhibit cancer development is not clear. (more…)
Author Interviews, Lipids, Nutrition, Weight Research / 13.12.2016

MedicalResearch.com Interview with: Dr. Koji Ishiguro National Agriculture and Food Research Organization Japan MedicalResearch.com: What is the background for this study? Response: -Sweet potato (Ipomoea batatas L.) roots are not only used for human consumption, they are used to make starch materials, processed foods, and distilled spirits in Japan. Starch use accounts for about 15% (131,500 tons) of total sweet potato production. Starch residues are discharged during starch production and are mainly used in animal feed and compost. Large amounts of the wastewater, which can cause serious environmental problems, are discarded after clarification. Investigation into the uses of the by-products of the sweet potato starch industry would benefit both the environment and industry. (more…)
Author Interviews, Boehringer Ingelheim, Cancer Research / 12.12.2016

MedicalResearch.com Interview with: Professor Giorgio V. Scagliotti Chair of the Department of Oncology University of Torino,Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: LUME-Meso II is an international study designed to evaluate the safety and efficacy of nintedanib plus pemetrexed/cisplatin, followed by nintedanib versus placebo plus pemetrexed/cisplatin, followed by placebo, for the treatment of patients with unresectable malignant pleural mesothelioma (MPM). MPM is a rare cancer that affects the cells that make up the mesothelium of the pleura – the lining or membrane that covers and protects the lungs. It represents less than 1% of all cancers and is often related to long-term asbestos exposure with some suffering from malignant mesothelioma. A significant improvement in progression-free survival (PFS), the study’s primary endpoint, was observed for patients receiving nintedanib plus chemotherapy compared to patients receiving placebo plus chemotherapy. (more…)
Alzheimer's - Dementia, Annals Internal Medicine, Author Interviews, Critical Care - Intensive Care - ICUs, Health Care Systems, University of Pittsburgh / 12.12.2016

MedicalResearch.com Interview with: Joshua M. Thorpe, PhD, MPH From the Center for Health Equity Research and Promotion Veterans Affairs Pittsburgh Healthcare System Pittsburgh Pennsylvania, and Center for Health Services Research in Primary Care Department of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy MedicalResearch.com: What is the background for this study? Response: Care coordination for persons with dementia is challenging for health care systems under the best of circumstances. These coordination challenges are exacerbated in Medicare-eligible veterans who receive care through both Medicare and the Department of Veterans Affairs (VA). Recent Medicare and VA policy changes (e.g., Medicare Part D, Veteran’s Choice Act) expand veterans’ access to providers outside the VA. While access to care may be improved, seeking care across multiple health systems may disrupt care coordination and increase the risk of unsafe prescribing - particularly in veterans with dementia. To see how expanded access to care outside the VA might influence medication safety for veterans with dementia, we studied prescribing safety in Veterans who qualified for prescriptions through the VA as well as through the Medicare Part D drug benefit. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Mammograms, MD Anderson, Surgical Research / 12.12.2016

MedicalResearch.com Interview with: Henry M. Kuerer, MD, PhD, FACS Executive Director, Breast Network Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Research Department of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program MedicalResearch.com: What is the background for this study? Response: Worldwide, triple negative and HER2 positive breast cancers, combined, account for about 370,000 women diagnosed annually. With recent advances in neoadjuvant systemic therapy (NST, chemotherapy and targeted therapy given before surgery) for both subsets, the pCR (pathologic complete response- when no residual cancer is found) rates found at the time of surgery in these populations can be as high as 60 percent. This high rate of pCR naturally raises the question of whether surgery is required for all patients, particularly those who will receive adjuvant radiation. We believe surgery may potentially be redundant – at least for these two subtypes of breast cancer – because of such a high chance for no evidence of disease at the time of pathological review. If there’s no cancer left after the patient has received chemotherapy and the patient is going to receive local radiation therapy, is surgery actually needed? The challenge has been that standard breast imaging methods cannot accurately predict residual disease after NST. However, by doing the same image-guided percutaneous needle biopsies after neoadjuvant systemic therapy that we do at time of diagnosis, our preliminary research reveals that we may be able to accurately predict which women will have cancer or not. (more…)
Addiction, Author Interviews, Opiods, Pediatrics / 12.12.2016

MedicalResearch.com Interview with: Nicole Villapiano, MD, MSc Robert Wood Johnson Clinical Scholar Internal Medicine/Pediatrics Institute for Healthcare Policy & Innovation University of Michigan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Over the past few years, research has highlighted that the opioid epidemic is accelerating at a rapid pace across the United States, including in rural areas. What we don’t know is how the opioid crisis is affecting rural moms and their infants. As a doctor that takes care of kids, I was concerned about this. So our team took on this study to explore the differences in rates of maternal opioid use and neonatal abstinence syndrome in rural and urban areas of the US from 2004-2013. Neonatal abstinence syndrome is what happens to babies who are exposed to opioids in their mothers’ womb. When these babies are born and no longer have opioid exposure from mom, they go through a period of opioid withdrawal. These babies can have symptoms that range from difficulty taking a bottle, jitteriness, difficulty sleeping, irritability, and discomfort to more serious problems like prematurity, difficulty breathing, and seizures. Symptoms can last several days to many weeks. Babies with neonatal abstinence syndrome are in the hospital longer than the average newborn, and sometimes require special treatment to help control their symptoms. (more…)
Author Interviews, Education, JAMA, Outcomes & Safety, UCSF / 12.12.2016

MedicalResearch.com Interview with: Charlie M. Wray, DO, MS Assistant Clinical Professor of Medicine University of California, San Francisco Department of Medicine San Francisco VA Medical Center MedicalResearch.com: What is the background for this study? Response: Since the establishment of residency duty hour regulations in 2010, which subsequently lead to increased discontinuity of inpatient care and more resident shift work, educators and researchers have attempted to establish which shift handoff technique(s) or strategies work best. National organizations, such as the ACGME, AHRQ, and the Joint Commission have made specific recommendations that are considered "best practice". In our study, using an annual national survey given to Internal Medicine Program Directors, we examined the degree of implementation of these recommended handoff strategies and the proportion of Program Director satisfaction with each of the respective strategies. (more…)
Author Interviews, Diabetes, Diabetes Care, Exercise - Fitness, Lifestyle & Health / 12.12.2016

MedicalResearch.com Interview with: Bernard M Duvivier  Department of Human Biology and Movement Science NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre Maastricht, the Netherlands MedicalResearch.com: What is the background for this study?  What are the main findings? Response: The health benefits of exercise have been well established but sitting is a risk factor for health, independent of exercise. As many people with type 2 diabetes don’t like to exercise we investigated whether replacing sitting time with light-intensity activities (standing and light walking) is equally effective to exercise when energy expenditure is comparable. Our results suggest that for people with type 2 diabetes, light-intensity activities (light walking and standing) can be an alternative to exercise to improve glucose regulation. In addition we showed that too much sitting has negative effects on insulin sensitivity which could not be fully compensated by 1 hour of exercise per day. (more…)
Author Interviews, BMJ, Dermatology, Herpes Viruses, HIV, Infections, STD / 12.12.2016

MedicalResearch.com Interview with: E. Charles Osterberg, M.D. Assistant Professor of Surgery Genitourinary Reconstruction and Trauma University of Texas- Dell Medical School Dell-Seton Medical Center / University Hospital MedicalResearch.com: What is the background for this study? Response: Pubic hair grooming has become an increasingly common practice among men and women. Perceptions of genital normalcy have changed as modern society’s definition of attractiveness and feelings of femininity and masculinity have changed. Pubic hair grooming has been shown to increase morbidity such as genital injuries, however little is known about the relationship between grooming practices and sexually transmitted infections. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 12.12.2016

MedicalResearch.com Interview with: Dr. Adrian Lee PhD Professor, Department of Pharmacology and Chemical Biology Director, Women's Cancer Research Center University of Pittsburgh Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The goal of this study was to understand molecular changes which occur when breast cancers metastasize to the brain, with the eventual of identifying new therapeutic strategies. Brain metastases occur in 10-15% of patients with metastatic breast cancer and are a major clinical challenge. Limited therapeutic options exist for patients with brain metastases. We analyzed molecular changes in pairs of patient-matched primary breast cancers and brain metastases. We found that brain metastases tended to have the same intrinsic subtype as the primary breast cancer, however, there were many genes which changes in gene expression and may represent therapeutic targets. The most common change was an increase in ErbB2/HER2 which can be targeted clinically. (more…)
Author Interviews, Biomarkers, Infections, JAMA, Neurological Disorders / 12.12.2016

MedicalResearch.com Interview with: Zanusso Gianluigi M.D.Ph.D. Department of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona, Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: To determine RT-QuIC assay sensitivity and specificity in cerebrospinal fluid and olfactory mucosa in a large group of patients with a clinical diagnosis of probable, possible or suspect Creutzfeldt–Jakob disease (CJD) and controls. In these patients, RT-QuIC testing of CSF and olfactory mucosa provided a specificity and sensitivity of 100%. A softer swab for olfactory mucosa sampling provided the same sensitivity as using a brush . (more…)
Author Interviews, Genetic Research, Leukemia, NYU / 11.12.2016

MedicalResearch.com Interview with: Jason Saliba PhD Perlmutter Cancer Center New York University Langone Medical Center New York, NY MedicalResearch.com: What is the background for this study? What are the main findings? Response: The outcome for children with acute lymphoblastic leukemia (ALL) has improved dramatically over the last four decades, but the prognosis for those who relapse remains dismal, especially for those who relapse while on therapy. In fact, relapsed disease remains a leading cause of cancer related mortality in children. To date, various studies have discovered a number of somatic alterations that contribute to driving relapse and have provided profound insight into the selective forces that lead to clonal outgrowth of drug resistant populations. However, the timing of the initial emergence of the driving mutations along with the speed of clonal outgrowth is unknown. Whole exome sequencing (WES) was run on available diagnosis, germline (remission), and relapse samples collected from thirteen pediatric ALL patients treated according to Nordic NOPHO ALL protocols. Analyses were then performed to find somatic missense mutations enriched in the relapse samples versus their patient matched diagnosis and/or germline samples. Candidate relapse driving missense mutations were identified as present at high levels (>20%) in the relapse sample, but were undetectable in germline or low to absent in the diagnosis sample. Eight of the thirteen patients contained mutations in genes previously reported to be enriched at relapse. Interestingly, a majority of the patients contained novel candidate relapse specific genes involved in a wide array of cellular processes such as cell adhesion/migration, RNA polymerase II/transcription, circadian rhythm, the unfolded protein response, RNA transport, epigenetic regulation, DNA methylation, and kinases. (more…)