Author Interviews, HIV, NEJM, University of Pennsylvania / 24.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29950" align="alignleft" width="148"]Katharine J Bar, MD Assistant Professor of Medicine Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania Physician, International Travel Medicine, Perelman Center for Advanced Medicine Director, Penn CFAR Viral and Molecular Core Dr. Katharine J Bar[/caption] Katharine J Bar, MD Assistant Professor of Medicine Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania Physician, International Travel Medicine, Perelman Center for Advanced Medicine Director, Penn CFAR Viral and Molecular Core MedicalResearch.com: What is the background for this study? What are the main findings? Response: The passive administration of monoclonal antibodies has revolutionized many fields of medicine. Anti-HIV monoclonal antibodies are being explored as components of novel therapeutic and curative strategies, as they can both neutralize free virus and kill virus-infected cells. We sought to determine whether passive administration of an anti-HIV monoclonal antibody, VRC01, to chronically HIV-infected individuals on antiretroviral medications (ART) would be safe and well tolerated and could delay virus rebound after discontinuation of their ART.
Author Interviews, BMJ, Cost of Health Care, Nursing, Outcomes & Safety, University of Pennsylvania / 16.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29710" align="alignleft" width="200"]Dr Linda H Aiken PhD, FAAN, FRCN, RN Claire M. Fagin Leadership Professor in Nursing Professor of Sociology, School of Arts & Sciences Director, Center for Health Outcomes and Policy Research University of Pennsylvania School of Nursing Center for Health Outcomes and Policy Research Philadelphia, PA 19104 Dr Linda H Aiken[/caption] Dr Linda H Aiken PhD, FAAN, FRCN, RN Claire M. Fagin Leadership Professor in Nursing Professor of Sociology, School of Arts & Sciences Director, Center for Health Outcomes and Policy Research University of Pennsylvania School of Nursing Center for Health Outcomes and Policy Research Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? Response: The idea that adding lower skilled and lower wage caregivers to hospitals instead of increasing the number of professional nurses could save money without adversely affecting care outcomes is intuitively appealing to mangers and policymakers but evidence is lacking on whether this strategy is safe or saves money.
Author Interviews, Heart Disease, Pediatrics, University of Pennsylvania / 14.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29595" align="alignleft" width="150"]Maryam Y. Naim, MD Pediatric Cardiac Intensive Care Physician The Cardiac Center The Children’s Hospital of Philadelphia Perelman School of Medicine The University of Pennsylvania, Philadelphia Dr. Maryam Y. Naim[/caption] Maryam Y. Naim, MD Pediatric Cardiac Intensive Care Physician The Cardiac Center The Children’s Hospital of Philadelphia Perelman School of Medicine The University of Pennsylvania, Philadelphia MedicalResearch.com: What is the background for this study?  Response: In adults bystander compression only CPR has similar outcomes to bystander conventional COR therefore the The American Heart Association recommends untrained lay rescuers perform compression only CPR in adults that have an out of hospital cardiac arrest. In children respiratory arrests are more common therefore conventional CPR with chest compressions and rescue breaths are recommended for out of hospital cardiac arrest.
Author Interviews, Biomarkers, Cancer, Cancer Research, University of Pennsylvania / 28.10.2016

MedicalResearch.com Interview with: [caption id="attachment_29147" align="alignleft" width="112"]Eric Ojerholm, MD Resident, Radiation Oncology Hospital of the University of Pennsylvania Dr. Eric Ojerholm[/caption] Eric Ojerholm, MD Resident, Radiation Oncology Hospital of the University of Pennsylvania MedicalResearch.com: What is the background for this study? Response: Multiple studies reported that a blood test —the neutrophil-to-lymphocyte ratio (NLR)—might be a helpful biomarker for bladder cancer patients. If this were true, NLR would be very appealing because it is inexpensive and readily available. However, previous studies had several methodological limitations. MedicalResearch.com: What did you do in this study Response: We therefore put NLR to the test by performing a rigorous “category B” biomarker study—this is a study that uses prospectively collected biomarker data from a clinical trial. We used data from SWOG 8710, which was a phase III randomized trial that assessed surgery with or without chemotherapy for patients with muscle-invasive bladder cancer. We tested two questions. First, could NLR tell us how long a bladder cancer patient would live after curative treatment? Second, could NLR predict which patients would benefit from chemotherapy before surgery?
Alzheimer's - Dementia, Author Interviews, Hormone Therapy, JAMA, Prostate Cancer, University of Pennsylvania / 15.10.2016

MedicalResearch.com Interview with: Kevin T. Nead, MD, MPhil Resident, Radiation Oncology Perelman School of Medicine Hospital of the University of Pennsylvania. MedicalResearch.com: What is the background for this study? Response: Androgen deprivation therapy is a primary treatment for prostate cancer and works by lowering testosterone levels. There is a strong body of research suggesting that low testosterone can negatively impact neurovascular health and function. We were therefore interested in whether androgen deprivation therapy is associated with dementia through an adverse impact on underlying neurovascular function.
Author Interviews, Biomarkers, Lung Cancer, Personalized Medicine, University of Pennsylvania / 13.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27877" align="alignleft" width="132"]Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania Dr. Erica Carpenter[/caption] Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients' tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy. Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn's Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently.
Author Interviews, Sleep Disorders, University of Pennsylvania / 12.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25138" align="alignleft" width="148"]Richard J. Schwab, MD Professor, Department of Medicine Division of Sleep Medicine Pulmonary, Allergy and Critical Care Division Co-Director, Penn Sleep Center University of Pennsylvania Medical Center Philadelphia, PA 19104 Dr. Richard Schwab[/caption] Richard J. Schwab, MD Professor, Department of Medicine Division of Sleep Medicine Pulmonary, Allergy and Critical Care Division Co-Director, Penn Sleep Center University of Pennsylvania Medical Center Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Schwab: Hypoglossal nerve stimulation is a pacemaker (a tiny generator and a sensing lead) placed in the right side of the chest, but instead of using electrical pulses to control the heart, the device stimulates the hypoglossal nerve which is the nerve that controls the motion of the tongue. Patients use a remote control to turn on the device before going to sleep and turn it off upon waking up. Stimulation of the tongue moves the tongue forward which enlarges the upper airway.
Author Interviews, HIV, University of Pennsylvania / 06.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24043" align="alignleft" width="200"]Robert Bonacci MPH, MD Candidate’16 University of Pennsylvania School of Medicine Robert Bonacci[/caption] Robert Bonacci MPH, MD Candidate’16  University of Pennsylvania School of Medicine MedicalResearch.com: What is the background for this study? Response: During the mid-2000’s, the HIV incidence rate stubbornly persisted around 50,000 infections per year. Responding to this trend, President Obama released the first comprehensive US National HIV/AIDS Strategy (NHAS) in 2010. The NHAS hoped to spur a more coordinated national response and set ambitious targets for reducing HIV incidence (25 percent) and the transmission rate (30 percent), among other goals, by 2015. To evaluate whether the U.S. achieved the NHAS goals by 2015, we used mathematical models drawing on data from the U.S. Centers for Disease Control and Prevention (CDC) on HIV prevalence and mortality for 2007 to 2012, and our own previously published incidence estimates from 2008-2012. Changes seen from 2010 through 2012 were extrapolated for the time period 2013 through 2015.
Author Interviews, Gender Differences, Kidney Disease, Transplantation, University of Pennsylvania / 22.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23696" align="alignleft" width="180"]Matthew Levine, MD, PhD Associate professor of Transplant Surgery Perelman School of Medicine University of Pennsylvania Dr. Mathew Levine[/caption] Matthew Levine, MD, PhD Assistant Professor of Transplant Surgery Perelman School of Medicine University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Levine: This work stemmed from a known finding that female mice tolerate kidney injury better than males and this is true of mice that share exactly the same genes.  Therefore, the gender difference was the driving factor.  My basic science laboratory works at the intersection between scientific discovery and clinical application and this led us to question whether the same phenomenon was true in humans and whether we could identify a way in which this could be used to improve injury tolerance above what is seen in untreated subjects.  What we found was that the hormonal environment seems to impact ischemia tolerance, with female environment being protective and the male environment worsening injury tolerance in ischemia models where blood flow is interrupted and then restored.  The kidneys seemed to adapt to take on the injury response of the host after transplantation, indicating that the differences were not forged into the kidney itself and therefore could be altered.  We then found that estrogen therapy improved kidney injury tolerance when given to female mice in advance of injury, but no effect was seen in male mice.  And most importantly, we found that in a large cohort of transplant recipients that female recipients had better injury tolerance after transplant than male recipients, as shown by ability to avoid dialysis in the first week after transplant, otherwise known as delayed graft function (DGF). This is a fairly major finding since it has not been observed in the literature despite several decades of transplant data being carefully studied.
Author Interviews, Heart Disease, Lipids, Pharmacology, University of Pennsylvania / 03.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22305" align="alignleft" width="111"]Dr. Richard L. Dunbar MD MS Assistant Professor of Medicine, Attending Physician, Preventive Cardiovascular Medicine Clinic, Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of MedicineMember, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine Dr. Richard Dunbar[/caption] Dr. Richard L. Dunbar MD MS Assistant Professor of Medicine, Attending Physician, Preventive Cardiovascular Medicine Clinic, Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of MedicineMember, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine and [caption id="attachment_22306" align="alignleft" width="90"]Dr. Harsh Goel WellSpan Academic Hospitalists Department of Medicine, York Hospital, PA Dr. Harsh Goel[/caption] Dr. Harsh Goel WellSpan Academic Hospitalists Department of Medicine, York Hospital, PA  MedicalResearch.com: What is the background for this analysis? Response: Niacin is the first cholesterol lowering treatment to prevent heart attacks and lower long term mortality. It thus provided the first proof that lowering cholesterol reduces cardiovascular risk. However, it is generally poorly tolerated due to almost universal flushing, limiting use. The better-tolerated statin drugs overshadowed niacin, rightly dominating hyperlipidemia therapy. Despite their advantages, statins are far from perfect, leaving important gaps. Firstly, at least 10% of patients simply don’t tolerate statins. Secondly, about 40% of patients have insufficient cholesterol lowering, leaving them far from their target LDL-cholesterol levels. Finally, even though statins lower cardiovascular risk, they by no means eliminate it and significant residual risk remains even in patients who respond to them. The relatively poor tolerance of niacin motivated development of an extended-release alternative which was dosed very differently from the established cardioprotective regimen used in the Coronary Drug Project (CDP) and the Stockholm Ischemic Heart Disease Study (SIHDS), the two landmark trials that proved niacin's benefits. These trailblazing trials used 3 grams of niacin divided throughout the fed portion of the day as 1 gram thrice daily with meals. In sharp contrast, the alternative regimen was severely handicapped by a profoundly lower dose of only 2 grams per day. Perhaps worse, the alternative regimen dosed all of the niacin at one sitting, at bedtime before the overnight fast, rather than three times a day before meals. We believe these were critical departures from the established cardioprotective niacin regimen, insofar as they severely undermined the alternative regimen’s efficacy. Accordingly, when added to statins, the alternative regimen failed to recapitulate the benefits seen with the established cardioprotective regimen in two recent large clinical trials, the AIM-HIGH trial and the HPS2-THRIVE trial. Besides the inherent flaws of the alternative regimen, there were also major issues with the trial designs which likely contributed to null results. From a practice standpoint, this is worrisome, because clinicians may draw erroneous conclusions from the trials of the alternative regimen, and thereby deny a significant population of hyperlipidemic patients the benefits of a well-proven cardioprotective therapy, i.e. the population which does not tolerate or does not respond adequately to statins (almost 50% of at risk patients). Hence, we embarked on a critical analysis and review of the alternative regimen with a special focus on the AIM-HIGH and HPS2-THRIVE trials to bring to light the pitfalls of comparing radically different regimens of what is nominally the same drug.
AHA Journals, Author Interviews, Heart Disease, PAD, Surgical Research, University of Pennsylvania / 26.02.2016

[caption id="attachment_20701" align="alignleft" width="180"]Dr. Grace Wang MD FACS Assistant Professor of Surgery Division of Vascular and Endovascular Surgery Hospital of the University of Pennsylvania Dr. Grace Wang[/caption] MedicalResearch.com Interview with: Dr. Grace Wang MD FACS Assistant Professor of Surgery Division of Vascular and Endovascular Surgery Hospital of the University of Pennsylvania Medical Research: What is the background for this study? Dr. Wang: PAD is a major source of morbidity and mortality resulting in functional impairment, limb loss, as well as death. Despite epidemiologic studies which have contributed to our understanding of PAD prevalence and its association with traditional atherosclerotic risk factors, there have been conflicting studies published on the incidence of PAD and differences in treatment outcomes in women versus men. Patients with chronic kidney disease (CKD) are at particularly high risk for PAD. We set out to to define how the incidence of peripheral arterial disease (PAD) in chronic kidney disease (CKD) differs according to sex and age.
AHA Journals, Author Interviews, Gender Differences, Heart Disease, University of Pennsylvania, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21844" align="alignleft" width="148"]Dr. Robert L. Wilensky MD Director, Interventional Cardiology Research Director, Interventional Cardiology Training Program Professor of Medicine Hospital of the University of Pennsylvania Dr. Robert Wilensky[/caption] Dr. Robert L. Wilensky MD Director, Interventional Cardiology Research Director, Interventional Cardiology Training Program Professor of Medicine Hospital of the University of Pennsylvania Medical Research: What is the background for this study? Dr. Wilensky: We wanted to evaluate whether young women, under the age of 50 years, had an increased risk for recurrent ischemic events after percutaneous coronary intervention (PCI) compared to young men or older women. Medical Research: What are the main findings?  Dr. Wilensky: Despite having less severe coronary artery disease,  had an increased risk of repeated events, generally need for repeat PCI in either the exact location of the original procedure or within the artery that underwent the procedure. This despite the finding that young women were treated with the same medications as young men.
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, Pediatrics, University of Pennsylvania / 04.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21295" align="alignleft" width="112"]Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia Dr. Adam Resnick[/caption] Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia   [caption id="attachment_21297" align="alignleft" width="150"]Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania Payal Jain[/caption] Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania   Medical Research: What is the background for this study? What are the main findings? Response: This study originates from our long-standing interest in studying pediatric low-grade gliomas (PLGGs), which are the most commonly diagnosed brain tumor in children. While several PLGGs have been found to harbor mutations/gene fusions driving the mitogen-associated protein kinase (MAPK) pathway leading to clinical trials testing MAPK inhibitors, these tumors remain poorly categorized and not enough is known about specific genetic mutations driving different tumor sub-types and the potential for specific targeted therapeutics. Our current study encompasses analysis of the largest combined genomic dataset of pediatric low-grade gliomas samples.  In doing this we, identified the MYB-QKI gene fusion, a non-MAPK related event, as the common genetic event driving a rare PLGG sub-type, called angiocentric gliomas. We have reported a novel tri-partite mechanism by which MYB-QKI mediates its oncogenic effect, this being the first report of a single gene rearrangement utilizing three different paths to cause cancer.
  • First, this gene rearrangement activates MYB, which is a proto-oncogene that is normally not expressed in the developed brain.
  • Second, we found that the rearrangement leads to translocation of QKI-related enhancers close to MYB’s promoters, thereby driving MYB-QKI expression in these tumors. Furthermore, MYB-QKI can also regulate its expression in a positive feedback loop.
  • Third, the tumor suppressor activities of QKI are disrupted in MYB-QKI. Such collaboration of genetic and epigenetic dysregulation in a single genetic rearrangement has previously not been reported.
Author Interviews, JAMA, Nursing, Outcomes & Safety, Surgical Research, University of Pennsylvania / 20.01.2016

More on Nursing Research on MedicalResearch.com MedicalResearch.com Interview with: [caption id="attachment_20725" align="alignleft" width="178"]Jeffrey H. Silber, M.D., Ph.D. The Nancy Abramson Wolfson Professor of Health Services Research The Children's Hospital of Philadelphia Professor of Pediatrics and Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine Professor of Health Care Management, The Wharton School Director, Center for Outcomes Research The Children's Hospital of Philadelphia Philadelphia, PA 19104 Dr. Jeffrey Silber[/caption] Jeffrey H. Silber, M.D., Ph.D. The Nancy Abramson Wolfson Professor of Health Services Research Professor of Pediatrics and Anesthesiology & Critical Care,  The University of Pennsylvania Perelman School of Medicine Professor of Health Care Management The Wharton School Director, Center for Outcomes Research The Children's Hospital of Philadelphia Philadelphia, PA 19104  Medical Research: What is the background for this study? Response: We wanted to test whether hospitals with better nursing work environments displayed better outcomes and value than those with worse nursing environments, and to determine whether these results depended on how sick patients were when first admitted to the hospital. Medical Research: What are the main findings? Response: Hospitals with better nursing work environments (defined by Magnet status), and staffing that was above average (a nurse-to-bed ratio greater than or equal to 1), had lower mortality than those hospitals with worse nursing environments and below average staffing levels. The mortality rate in Medicare patients undergoing general surgery was 4.8% in the hospitals with the better nursing environments versus 5.8% in those hospitals with worse nursing environments. Furthermore, cost per patient was similar. We found that better nursing environments were also associated with lower need to use the Intensive Care Unit. The greatest mortality benefit occurred in patients in the highest risk groups.
Alzheimer's - Dementia, Author Interviews, Journal Clinical Oncology, Prostate Cancer, Testosterone, University of Pennsylvania / 10.12.2015

[caption id="attachment_19976" align="alignleft" width="180"]Kevin T. Nead, MD, MPhil Dept. of Radiation Oncology Perelman School of Medicine University of Pennsylvania Dr. Kevin Nead[/caption] MedicalResearch.com Interview with: Kevin T. Nead, MD, MPhil Dept. of Radiation Oncology Perelman School of Medicine University of Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Nead: There are a growing number of studies suggesting that the use of  Androgen Deprivation Therapy (ADT)  may be associated with cognitive changes and some of these changes overlap with characteristic features of Alzheimer’s disease. In addition, low testosterone levels have been associated with Alzheimer’s disease risk and ADT lowers testosterone levels. Despite these findings, we could not identify any studies examining the association between ADT and Alzheimer’s disease risk. We therefore felt this study could make an important contribution in guiding future research to fully understand the relative risks and benefits of ADT. We examined electronic medical record data from Stanford University and Mt. Sinai hospitals to identify a cohort of 16,888 patients with prostate cancer. We found that men with prostate cancer who received Androgen Deprivation Therapy were more likely to develop Alzheimer’s disease than men who did not receive  Androgen Deprivation Therapy. We also found that this risk increased with a longer duration of ADT. These results were consistent using multiple statistical approaches and separately at both Stanford and Mr. Sinai.
Author Interviews, Smoking, University of Pennsylvania, Weight Research / 16.10.2015

[caption id="attachment_18458" align="alignleft" width="150"]Dr. Samuel H. Preston Ph.D Professor, Department of Sociology and Population Studies Center University of Pennsylvania Philadelphia, Pennsylvania Dr. Samuel Preston[/caption] MedicalResearch.com Interview with: Dr. Samuel H. Preston Ph.D Professor, Department of Sociology and Population Studies Center University of Pennsylvania Philadelphia, Pennsylvania  Medical Research: What is meant by the Obesity Paradox? Is it reported more in some groups? Dr. Preston: The obesity paradox is a term that is used when a study finds that obese people have lower mortality than non-obese people. The finding is considered paradoxical because the obese do not have lower mortality in cross-sections of the general population. The paradox is, however, commonly observed among people who suffer from a particular illness such as heart disease or diabetes.  Medical Research: What are the main findings of your study? What is reverse causation and how does it affect obesity studies? Dr. Preston: We find in a nationally representative sample that, among people suffering from cardiovascular disease, mortality is indeed lower for people who are overweight or obese than for people of normal weight. So the paradox appears among this group. However, when we study people's mortality according to their maximum lifetime weight, the paradox disappears. We attribute its disappearance primarily to the fact that many  people who have lost weight from their maximum are doing so because they are ill. This phenomenon is referred to as "reverse causation" because illness is affecting weight rather than weight affecting illness and mortality.
Author Interviews, Personalized Medicine, Transplantation, University of Pennsylvania / 05.10.2015

MedicalResearch.com Interview with: Brendan J. Keating, DPhil Assistant professor of Transplant Surgery Penn Medicine Medical Research: What is the background for this study? What are the main findings? Response: Genetic studies in transplantation have been plagued by small samples and very complex phenotypes/outcomes of patients. Transplanted individuals are typically on potent immunosuppression drugs for the rest of their lives, as they have 3.5 million to 10 million variants difference from an unrelated transplanted donor organ. Such populations would certainly benefit from large well-powered genetic studies but only 3 transplant genome-wide genotyping studies comprising a few hundred individuals have been published. The papers outline the resources in hand for the International Genetics & Translational Research in Transplantation Network, comprising 22 studies to date (since the publication it has now expanded to 25 studies and > 32,000 subjects with genome-wide genotyping data). We show significant statistical power in iGeneTRAiN to detect main effect association signals across regions such as the MHC region (which harbors the HLA Class I/II regions which are well established to associate with transplantation outcomes). We also show strong genome-wide power to detect transplant outcomes that span all solid organs including graft survival, acute rejection, new onset of diabetes after transplantation (fast becoming the most common comorbidity post-transplantation), and delayed graft function (to date we have looked at this in kidney transplant patients only). We show that iGeneTRAiN is statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The transplant specific GWAS array that we designed (described in depth in the Genome Medicine paper) show that the coverage in key transplant associated regions is much higher than conventional arrays, and we describe the ‘imputation’ pipeline to expand the 780,000 or so variants examined in any given individual to > 15 millions of variants using whole genome sequencing reference datasets.
Author Interviews, Infections, University of Pennsylvania, Vaccine Studies / 22.08.2015

David B. Weiner, Ph.D. Professor, Department of Pathology and Laboratory Medicine Chair, Gene Therapy and Vaccine Program, CAMB Co-Leader Tumor Virology Program, Abramson Cancer Program University of Pennsylvania, Perelman School of MedicineMedicalResearch.com Interview with: David B. Weiner, Ph.D. Professor, Department of Pathology and Laboratory Medicine Chair, Gene Therapy and Vaccine Program, CAMB Co-Leader Tumor Virology Program, Abramson Cancer Program University of Pennsylvania, Perelman School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Weiner: MERS, like the Severe Acute Respiratory Syndrome (SARS), is characterized by high fever and severe cough from pneumonia. MERS is caused by an emerging human coronavirus, which is distinct from the SARS coronavirus. Since its identification in 2012, MERS has been linked to over 1,300 infections and close to 400 deaths. It has occurred in the Arabian Peninsula, Europe, and in the US and in Asia. It can be spread in a hospital setting. Scientists now report that a novel synthetic DNA vaccine can, for the first time, induce protective immunity against the Middle EastRespiratory Syndrome (MERS) coronavirus in animal species.   Researchers from the Perelman School of Medicine at the University of Pennsylvania. The NIH, the Public Health agency of Canada, and from a leading company in the development of synthetic DNA vaccine technology, Inovio described the results in a paper  published their work in Science Translational Medicine (STM) this week.  The experimental, preventive vaccine, given six weeks before exposure to the MERS virus, fully protects rhesus macaques from disease. The vaccine also generated potentially protective antibodies in blood drawn from camels, the purported source of MERS transmission in the Middle East.
Author Interviews, Biomarkers, Dermatology, JAMA, Pulmonary Disease, University of Pennsylvania / 12.08.2015

Misha A. Rosenbach, MD Assistant Professor of Dermatology at the Hospital of the University of Pennsylvania Assistant Professor of Dermatology in MedicineMedicalResearch.com Interview with: Misha A. Rosenbach, MD Assistant Professor of Dermatology at the Hospital of the University of Pennsylvania Assistant Professor of Dermatology in Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Rosenbach: Sarcoidosis is an inflammatory disease of unknown etiology where genetically susceptible patients develop multi-organ granulomatous inflammation in response to an as-yet unidentified stimulus.  Patients with sarcoidosis typically have granulomatous inflammation in their lungs, but the second most commonly affected organ is the skin; the eyes, lymph nodes, liver, heart, brain, and other organs can be affected as well.  Patients with sarcoidosis can experience a few disease trajectories; some spontaneously recover, while others have persistent, active inflammation, whereas another group can experience inflammation which leads to scarring and fibrosis.  It can be challenging to distinguish these cohorts of patients based on their lungs alone. The skin is much easier to evaluate, as it is right there on the surface, and can be examined by physicians without resorting to invasive tests or radiography.  At Penn, we developed a novel cutaneous sarcoidosis assessment tool, called the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI), which is designed to accurately measure how inflamed skin sarcoid lesions are in a given patient, as well as describing which type of cutaneous lesion patients’ have.  The CSAMI has in previously studies been shown to be reliable when used by dermatologists, with excellent inter-rater and intra-rater reproducibility. In this study, we had a group of Pulmonologists, Rheumatologists, and Dermatologists (representing the groups of physicians who most commonly care for patients with sarcoidosis, especially if there is skin involvement) evaluate a group of patients with cutaneous sarcoidosis, using the CSAMI and another sarcoidosis activity instrument, the SASI, which has also previously been used to measure skin sarcoidosis activity in a number of settings.  We were able to demonstrate that these cutaneous scoring tools are reliable and reproducible and able to accurately measure cutaneous sarcoidosis disease activity in a variety of patients with a range of skin disease severity.  We also compared the physician scores to patients’ own evaluations of their disease, and showed that the CSAMI (physician impression of disease) correlated well with patients’ own perception of their disease activity and severity.
Author Interviews, Inflammation, Lipids, University of Pennsylvania / 04.08.2015

Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of PennsylvaniaMedicalResearch.com Interview with: Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Medical Research: What is the background for this study? What are the main findings? Dr. Skarke: A growing body of publications suggests anti-inflammatory actions of fish oils. These health benefits are proposed to emerge from lipids called specialized pro-resolving mediators, (SPMs), which can be formed from omega-3 polyunsaturated fatty acids found in fish. A limitation to date, though, in this field is that there is little evidence of their formation in humans. And the cases where presence of these lipids is reported in humans, less rigorous analytical approaches, such as enzyme immunoassay (EIA), radioimmunoassay (RIA) or mass spectrometry without internal authentic standards, have been used. Thus, the specific aim for our study was to use state-of-the-art mass spectrometry to identify and quantify these specialized pro-resolving mediators. Several aspects of our study design set us apart from what was done in previous studies.
  • First, we biased our ability to detect SPMs formed in healthy volunteers by giving fish oil in high doses which had been previously shown to influence blood pressure and platelet aggregation under placebo-controlled conditions.
  • Second, we also looked at lower doses of fish oil, those more commonly consumed by the general public, for the formation of SPMs during an acute inflammatory response and its resolution.
  • Third, we relied in our measurements of SPMs on authentic internal standards. These deuterated lipids, d4-resolvin E1 for example, facilitate distinct identification of the naturally formed lipid.
  • And fourth, we achieved very low limit of detection levels, below 10 pg/ml for resolvin E1, for example.
The surprising finding of our studies is that we failed to detect a consistent signal of SPM formation in urine or plasma of healthy volunteers who had taken fish oil. Even more surprising was that we found no alteration in the formation of SPMs during the resolution of inflammation. These results let us question the relevance of endogenous specialized pro-resolving mediators to the putative anti-inflammatory effects of fish oils in humans.
Author Interviews, PLoS, Toxin Research, University of Pennsylvania / 17.07.2015

Reynold A. Panettieri, Jr., M.D. Robert L. Mayock and David A. Cooper Professor of Medicine Pulmonary, Allergy & Critical Care Division Director, Airways Biology Initiative Deputy Director, Center of Excellence in Environmental Toxicology Adjunct Professor, Wistar Institute Philadelphia, PA 19104-3413MedicalResearch.com Interview with: Reynold A. Panettieri, Jr., M.D. Robert L. Mayock and David A. Cooper Professor of Medicine Pulmonary, Allergy & Critical Care Division Director, Airways Biology Initiative Deputy Director, Center of Excellence in Environmental Toxicology Adjunct Professor, Wistar Institute Philadelphia, PA  19104-3413 Medical Research: What is the background for this study? What are the main findings? Dr. Panettieri: Over the past ten years in the US, unconventional gas and oil drilling (hydraulic fracturing) to generate natural gas has markedly increased.  In areas with hydraulic fracturing, there is a large increase in truck traffic, noise and potential air and water pollution.  Accordingly, residents may experience health consequences from such exposures.  We questioned whether proximity to active wells increases hospitalization rates in residents.  To address this question, we reviewed all hospitalizations in two counties in Pennsylvania, namely, Bradford and Susquehanna Counties, that experienced a meteoric increase in active wells.  In comparison, Wayne County, where there is a moratorium on hydraulic fracturing, is demographically identical to Bradford and Susquehanna Counties and served as a control population.  Having examined the 25 most common reasons for admission to the hospital, we determined that cardiovascular hospitalizations as well as neurologic, dermatologic and cancer hospitalizations were associated with living closer to active wells.  These data represent some of the first studies to associate active well drilling with hospitalizations in the United States.
Author Interviews, OBGYNE, Technology, University of Pennsylvania / 24.06.2015

Dan Dongeun Huh, Ph.D. Wilf Family Term Chair & Assistant Professor Department of Bioengineering University of Pennsylvania Philadelphia, PA 19104MedicalResearch.com Interview with: Dan Dongeun Huh, Ph.D. Wilf Family Term Chair & Assistant Professor Department of Bioengineering University of Pennsylvania Philadelphia, PA 19104 Medical Research: What is the background for this study? What are the main findings? Response: The placenta is a temporary organ central to pregnancy and serves as a major interface that tightly regulates transport of various endogenous and exogenous materials between mother and fetus.  The placental barrier consisting of the closely apposed trophoblast epithelium and fetal capillary endothelium is responsible for maintaining this critical physiological function, and its dysfunction leads to adverse pregnancy outcomes.  Despite its importance, barrier function of the placenta has been extremely challenging to study due to a lack of surrogate models that faithfully recapitulate the key features of the placental barrier in humans.  Our study aims to directly address this long-standing technical challenge by providing a microengineered in vitro system that replicates architecture, microenvironment, and physiological function of the human placenta barrier.  This “placenta-on-a-chip” device consists of microfabricated upper and lower cell culture chambers separated by a thin semipermeable membrane, and the placental barrier is generated by culturing human trophoblasts and fetal endothelial cells on either side of the membrane with steady flows of culture media in both chambers.  This microfluidic cell culture condition allowed the cells to form confluent monolayers on the membrane surface and to create a bi-layer tissue that resembled the placental barrier in vivo.  Moreover, the microengineered barrier enabled transport of glucose from the maternal chamber to the fetal compartment at physiological rates.
Author Interviews, Gastrointestinal Disease, Transplantation, University of Pennsylvania / 11.05.2015

MedicalResearch.com Interview with: Dr. David Goldberg MD, MSCE Assistant Professor of Medicine LDI Fellow, Leonard Davis Institute, University of Pennsylvania Medical Director for Living Donor Liver Transplantation, Hospital of the University of Pennsylvania Senior Scholar, Center for Clinical Epidemiology and Biostatistics MedicalResearch: What is the background for this study? What are the main findings? Dr. Goldberg: While there are data that demonstrate differences in authorization (consent) rates for deceased donation among racial and ethnic minorities, it is unknown how these differences contribute to geographic differences in the number of deceased organ donors.  It has been postulated that geographic differences in the distribution of racial and ethnic minorities may contribute to differences in the deceased organ supply, yet there have been no empiric data to support this.  Using data on “eligible deaths,” defined as potential brain-dead organ donors <=70 years of age, we demonstrated that even after accounting for differences in the racial/ethnic demographics of the potential donor population, there are dramatic differences in authorization (consent) rates across geographic areas that are not explained by demographics alone. If the source of these differences could be identified, then there could be large increases in the number of organ donors, and lifesaving transplants, in areas with lower authorization rates.
Author Interviews, Heart Disease, JACC, Stroke, University of Pennsylvania / 25.04.2015

Jay Giri, MD MPH Director, Peripheral Intervention Assistant Professor of Clinical Medicine University of PennsylvaniaMedicalResearch.com Interview with Jay Giri, MD MPH Director, Peripheral Intervention Assistant Professor of Clinical Medicine University of Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Giri: Carotid artery stents are placed by vascular surgeons or interventional cardiologists to decrease the risk of long-term stroke in patients with severe atherosclerotic disease of the carotid artery.  When these procedures are performed, there is a risk of releasing small amounts of debris into the brain’s circulation, causing a stroke around the time of the procedure (peri-procedural stroke).  In order to mitigate this issue, embolic protection devices (EPD) have been developed to decrease the chances of small debris reaching the brain. Two types of EPD exist.  The first is a small filter meant to catch the debris released by placement of the carotid stent (distal filter EPD). The second is a more complex device type that leads to transient halting of blood flow to the brain in the carotid artery being stented (proximal EPD). Debris-containing blood is removed from the body prior to allowing normal blood flow to proceed back to the brain after stent placement. Our prior research has shown that nearly all (>95%) of domestic carotid stenting procedures are performed with utilization of one of these devices.  We sought to compare important clinical outcomes of stroke and death between these 2 device types within a large national sample of patients undergoing carotid stenting. Some small prior studies have investigated whether the total amount of debris reaching the brain is less with proximal embolic protection devices.  These studies have shown mixed results.  However, no prior study has investigated important clinical outcomes of stroke and death in relation to these devices. We found that overall uptake of proximal embolic protection devices utilization in America has not been robust.  Less than 7% of all domestic CAS procedures are performed with this technology.   Our analysis showed that in-hospital and 30-day stroke/death rates with proximal EPD and distal filter EPD were similar (1.6% vs. 2.0%, p = 0.56 and 2.7% vs. 4.0%, p = 0.22, respectively).
Author Interviews, HIV, JAMA, Pediatrics, University of Pennsylvania / 02.04.2015

Elizabeth Lowenthal, MD MSCE Assistant Professor of Pediatrics Children's Hospital of PhiladelphiaMedicalResearch.com Interview with: Elizabeth Lowenthal, MD MSCE Assistant Professor of Pediatrics Children's Hospital of Philadelphia Medical Research: What is the background for this study? What are the main findings? Dr. Lowenthal: Between 2005 and 2012, HIV related deaths declined by 30% worldwide. However, during the same time period, HIV related deaths increased 50% among adolescents. Over 90% of HIV-infected children and adolescents live in sub-Saharan Africa and HIV is the leading cause of death among adolescents in Africa. Treatment is available that can allow babies born with HIV to live to be healthy adults. However, strict adherence to these medicines is necessary and often becomes a great challenge during adolescence. In our study of 300 adolescents (ages 10-19) in Botswana, my team found that adolescents who come to clinic without a parent or guardian have a 4.5X greater odds of failing their HIV treatment.
Author Interviews, Mental Health Research, Pediatrics, University of Pennsylvania / 04.03.2015

Courtney Benjamin Wolk, Ph.D. Postdoctoral Researcher Center for Mental Health Policy and Services Research Perelman School of Medicine Department of Psychiatry University of Pennsylvania Philadelphia, PA 19104MedicalResearch.com Interview with: Courtney Benjamin Wolk, Ph.D. Postdoctoral Researcher Center for Mental Health Policy and Services Research Perelman School of Medicine Department of Psychiatry University of Pennsylvania Philadelphia, PA 19104 Medical Research: What is the background for this study? What are the main findings? Response: Previous research investigating the relationship between anxiety and suicidality has been mixed. An ongoing question in the field has been whether anxiety disorders independently increase risk for suicidal ideation and behavior or if the high co-occurrence of anxiety and mood symptoms or other shared demographic factors are driving relationships that have been observed between anxiety and suicidality. We examined the relationship between response to treatment for an anxiety disorder in childhood and suicidal ideation, plans, and attempts 7 to 19 years after treatment with cognitive-behavioral therapy, more commonly referred to as CBT. Our results indicated that participants who responded favorably to cognitive-behavioral therapy during childhood had lower rates of lifetime, past month, and past two-week suicidal ideation endorsement than treatment non-responders. This was the case across both self-report and interview-report of suicidal ideation. Treatment response was not significantly associated with suicide plans or attempts, though plans and attempts were infrequently endorsed in our sample, limiting the ability to detect findings.
AHA Journals, Author Interviews, Gender Differences, Heart Disease, University of Pennsylvania, Women's Heart Health / 26.02.2015

Dawn Pedrotty, MD, PhD Cardiovascular Medicine Fellowship University of PennsylvaniaMedicalResearch.com Interview with: Dawn Pedrotty, MD, PhD Cardiovascular Medicine Fellowship University of Pennsylvania MedicalResearch: What is the background for this review? What are the main findings? Dr. Pedrotty: Heart failure (HF) is the most common cause for hospitalization among patients 65 years and older, affecting approximately 6 million Americans; at 40 years of age, American males and females have a one in five lifetime risk of developing heart failure. There are two distinct heart failure phenotypes: a syndrome with normal or near-normal left ventricular ejection fraction (LVEF) referred to as HF with preserved ejection fraction (HFpEF), and the phenotype associated with poor cardiac contractility or heart failure with reduced ejection fraction (HFrEF). Risk factors associated with HFpEF include female gender, especially women with diabetes, higher body mass index, smoking, hypertension, concentric left ventricular hypertrophy (LVH), and atrial fibrillation (AF). There has been a growing interest in the development of criteria for specific subsets of HFpEF, a syndromal disease where multiple cardiac and vascular abnormalities exist. One approach is to implement phenomapping, identifying phenotypically distinct HFpEF categories and developing a classification system to group together pathophysiologically similar individuals who may respond in a more homogeneous, predictable way to intervention. Another option would be to focus on a known physiologic differences which might shed light on pathologic mechanisms e.g. gender and the influences of obesity and atrial fibrillation.
Author Interviews, Education, Outcomes & Safety, Surgical Research, University of Pennsylvania / 25.02.2015

Samuel D. Pimentel Doctoral student Statistics Department Wharton School of the University of PennsylvaniaMedicalResearch.com Interview with: Samuel D. Pimentel Doctoral student Statistics Department Wharton School of the University of Pennsylvania   MedicalResearch: What is the background for this study? What are the main findings? Response: Surgical training has undergone major changes in recent years – including a reduction of six to twelve months of training time – and there is controversy about whether these changes have been good or bad for patient outcomes.   Our work partially addresses the issue by asking whether newly-trained surgeons perform better or worse than experienced surgeons.  We compared surgical patients treated by new surgeons to a similar group of patients treated by experienced surgeons using a new statistical technique called large, sparse optimal matching.  Our analysis found no significant differences in mortality rates between the two groups.