Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, Melanoma, Prostate Cancer / 23.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56034" align="alignleft" width="97"]Saud H AlDubayan, M.D. Instructor in Medicine, Harvard Medical School Attending Physician, Division of Genetics, Brigham and Women's Hospital
 Computational Biologist, Department of Medical Oncology,  Dana-Farber Cancer Institute Associate Scientist, The Broad Institute of MIT and Harvard Dr. AlDubayan[/caption] Saud H AlDubayan, M.D. Instructor in Medicine, Harvard Medical School Attending Physician, Division of Genetics, Brigham and Women's Hospital Computational Biologist, Department of Medical Oncology, Dana-Farber Cancer Institute Associate Scientist, The Broad Institute of MIT and Harvard  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The overall goal of this study was to assess the performance of the standard method currently used to detect germline (inhered) genetic variants in cancer patients and whether we could use recent advances in machine learning techniques to further improve the detection rate of clinically relevant genetic alterations. To investigate this possibility, we performed a head to head comparison between the current gold-standard method for germline analysis that has been universally used in clinical and research laboratories and a new deep learning analysis approach using germline genetic data of thousands of patients with prostate cancer or melanoma. This analysis showed that across all different gene sets that were tested, the deep learning-based framework was able to identify additional cancer patients with clinically relevant germline variants that went undetected by the standard method. For example, several patients in our study also had germline variants that are associated with an increased risk of ovarian cancer, for which the surgical removal of the ovaries (at a certain age) is highly recommended. However, these genetic alterations were only identified by the proposed deep learning framework.    
Aging, Author Interviews, Genetic Research, McGill / 22.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56017" align="alignleft" width="111"]Richard C. Austin, PhD Professor and Career Investigator of the Heart and Stroke Foundation of Ontario Amgen Canada Research Chair in Nephrology McMaster University and St. Joseph’s Healthcare Hamilton, Ontario, Canada Dr. Austin[/caption] Richard C. Austin, PhD Professor and Career Investigator of the Heart and Stroke Foundation of Ontario Amgen Canada Research Chair in Nephrology McMaster University and St. Joseph’s Healthcare Hamilton, Ontario, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: A previous study published in 2011 by my collaborator, Dr. Michel Chretien at the IRCM, identified a rare mutation in the PCSK9, termed Q152H. Individuals harboring this mutation demonstrated dramatic reductions in their LDL cholesterol levels and had a significantly lower risk of CVD. Furthermore, individuals harboring the Q152H mutation showed increases in longevity with no evidence of other diseases such as liver disease, cancer and chronic kidney disease. This Q152H mutation was unique with only 4 families in Quebec shown to harbor this genetic variant. In terms of its effect on PCSK9 expression/activity, the mutation at Q152H was precisely at the cleavage site in PCSK9 necessary for its activation. As a result, the Q152H mutation fails to be cleaved and activated, thereby blocking its secretion into the circulation. This is why the Q152H mutation is considered a loss-of-function PCSK9 mutant. Given our lab's interest in endoplasmic reticulum (ER) stress and ER storage diseases, we began to collaborate with Drs. Chretien and Seidah at the IRCM to investigate whether this Q152H mutant, when overexpressed in liver cells, would cause ER stress and liver cell injury. This was based on the findings that the Q152H mutant does not undergo autocatalytic cleavage and its subsequent secretion from liver cells. It is well known in the literature that the accumulation of misfolded or inactive proteins in the ER gives rise to ER stress and cell injury/dysfunction. As a result, we initially showed to our surprise that overexpression of the Q152H mutant in liver cells failed to cause ER stress BUT increased the protein levels of several important ER chaperones, GRP78 and GRP94, known to PROTECT against liver cell injury/dysfunction. As part of our JCI study, we furthered these studies to examine the effect of the Q152H mutant when overexpressed in the livers of mice. This is where we demonstrated that the Q152H mutation showed protection against ER stress-induced liver injury/dysfunction.
Author Interviews, Dermatology, Genetic Research / 20.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56009" align="alignleft" width="134"]Jillian F. Rork, MD Assistant Professor of Dermatology Dartmouth-Hitchcock Medical Center at Manchester and The Geisel School of Medicine Dr. Rork[/caption] Jillian F. Rork, MD Assistant Professor of Dermatology Dartmouth-Hitchcock Medical Center at Manchester and The Geisel School of Medicine Society for Pediatric Dermatology Member MedicalResearch.com: What is the background for this study? Would you briefly explain the genetic condition of Down syndrome? Response:  Down syndrome is the most common chromosomal abnormality, occurring in approximately 1 in 700 newborns in the United States.  Trisomy of chromosome 21 can result in multisystem involvement such as hearing loss, heart defects, autoimmune conditions and dementia. This study focuses on how trisomy 21 affects one of the body’s largest organs, the skin. Current literature addressing dermatologic conditions associated with Down syndrome is limited. There is often emphasis on rare skin conditions such as elastosis perforans serpiginosa, milia-like idiopathic calcinosis cutis, and eruptive syringomas. There is lack of consensus on incidence of more common disorders. We performed a retrospective chart review of 101 patients with Down syndrome in our dermatology practice at the University of Massachusetts to better describe associated skin conditions.
Author Interviews, Dermatology, Genetic Research, Melanoma / 19.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55999" align="alignleft" width="142"]Sarah I. Estrada, M.D., FCAP  Laboratory Director Affiliated Dermatology® www.affderm.com Dr. Estrada[/caption] Sarah I. Estrada, M.D., FCAP  Laboratory Director Affiliated Dermatology® www.affderm.com MedicalResearch.com: What is the background for this study? What are the main findings? Response: As a dermatopathologist who makes diagnoses on lesions that may be melanoma, I’m faced with the reality that my accurate interpretation of biopsy tissue is key for the patient to be treated most effectively. Often histopathological evaluation is straightforward but not as often as I would like. The study presented here offers a new test that can be used in conjunction with my evaluation to determine if a questionable lesion is in fact melanoma. The test was developed to take into account the gene expression of the lesion which may factor in characteristics that I cannot visually observe. The test was validated and has shown very promising accuracy metrics.
Author Interviews, Blood Pressure - Hypertension, Heart Disease, Pediatrics, USPSTF / 19.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56002" align="alignleft" width="133"]Martha Kubik, Ph.D., R.N. Professor and director of the School of Nursing College of Health and Human Services at George Mason University USPSTF Task Force Member Dr. Kubik[/caption] Martha Kubik, Ph.D., R.N. Professor and director of the School of Nursing College of Health and Human Services at George Mason University USPSTF Task Force Member MedicalResearch.com: What is the background for this study? What are the main findings? Has the recommendation changed over the last decade? Response: High blood pressure is becoming more common among children and teens in the United States and can have serious negative health effects in childhood and adulthood, such as kidney and heart disease. However, there is not enough research to know whether treating high blood pressure in young people improves cardiovascular health in adulthood. The Task Force continued to find that there is not enough evidence to recommend for or against screening for high blood pressure in children and teens who do not have signs or symptoms.
AHA Journals, Author Interviews, COVID -19 Coronavirus, Race/Ethnic Diversity, Stanford / 19.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55996" align="alignleft" width="200"]Fatima Rodriguez, MD, MPH, FACC, FAHA Assistant Professor, Cardiovascular Medicine Stanford University School of Medicine Palo Alto, CA 94304 Dr. Rodriguez[/caption] Fatima Rodriguez, MD, MPH, FACC, FAHA Assistant Professor, Cardiovascular Medicine Stanford University School of Medicine Palo Alto, CA 94304 MedicalResearch.com: What is the background for this study? Response: The COVID-19 pandemic has magnified existing racial/ethnic disparities in the United States. The goal of this study was to leverage new data collected from the American Heart Association’s COVID-19 Cardiovascular Disease Registry to understand racial/ethnic differences in presentation and outcomes for hospitalized patients.
Author Interviews, BMJ, Brigham & Women's - Harvard, Fertility, OBGYNE / 19.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55925" align="alignleft" width="200"]Jennifer Yland, MS Department of Epidemiology Boston University School of Public Health Jennifer Yland[/caption] Jennifer Yland Doctoral Student in Epidemiology Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? Response: Worldwide, about 22% of reproductive-aged women used hormonal contraception last year. Long-acting reversible contraceptive (LARC) methods, which include intrauterine devices (IUDs), implants, patches, and injectable contraceptives, have become increasingly popular. However, little is known about the return to fertility after use of different contraceptives, particularly LARC methods.
Alzheimer's - Dementia, Author Interviews, Lipids, Mental Health Research, Microbiome / 18.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55988" align="alignleft" width="200"]Moira Marizzoni, PhD Researcher, Fatebenefratelli Center in Brescia  Dr. Marizzoni[/caption] Moira Marizzoni, PhD Researcher, Fatebenefratelli Center in Brescia  MedicalResearch.com: What is the background for this study? Response: Alzheimer’s disease is the most common cause of dementia. Still incurable, it directly affects nearly one million people in Europe, and indirectly millions of family members as well as society as a whole. The gut microbiota could play a role in brain diseases including Alzheimer’s disease. Some gut bacteria components or products can reach the brain via the blood and might promote brain amyloidosis (one of the main pathological features in Alzheimer’s disease).   MedicalResearch.com: What are the main findings?  Response: This study evaluated a cohort of 89 people between 65 and 85 years of age composed of subjects suffering from Alzheimer’s disease or other neurodegenerative diseases causing similar memory problems, and of subjects with no memory problems. The study revealed that elevated levels of microbiota-products with known pro-inflammatory properties (i.e. lipopolysaccharides and the short chain fatty acids acetate and valerate) were associated with greater cerebral amyloid pathology while elevated levels of those with anti-inflammatory properties (i.e. the short chain fatty acid butyrate) were associated with lower amyloid pathology.
Author Interviews, Orthopedics, Radiology, Rheumatology, UCSF, Weight Research / 18.11.2020

MedicalResearch.com Interview with: Silvia Schirò MD Department of Radiology and Biomedical Imaging University of California, San Francisco MedicalResearch.com: What is the background for this study?  Response: Knee osteoarthritis (OA) is worldwide the second most frequent cause of lower extremity disability, and it has a global incidence of 199 cases per 100.000, including over 14 million people with symptomatic knee OA in the US. Overweight and obese individuals have a higher incidence of knee OA due to excessive knee joint load. The association between physical activity and knee OA, has not been systematically addressed in overweight and/or obese subjects and its association seems to be controversial. On the one hand, mild to non-weight-bearing physical activities have been found to be beneficial in the management knee homeostasis, the physiologic knee joint load providing an optimized environment for the joint tissues. On the other hand, excessive fast-paced physical activity with high load-joint torsion such as racquet sports, ball sports and running have been found to have an increased incidence of knee injury compared to mild-moderate exercise such as swimming, bicycling and low-impact aerobics independent of body weight.
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Social Issues / 18.11.2020

MedicalResearch.com Interview with: David-Dan Nguyen, MPH Research Fellow | Center for Surgery and Public Health Brigham and Women's Hospital Medical Student | McGill University  MedicalResearch.com: What is the background for this study? Response: In 2017, the US Preventive Services Task Force updated its recommendation for PSA screening for prostate cancer from a grade D to a grade C for men aged 55 to 69 years. This updated recommendation endorsed shared decision making and harmonizes with the guidelines of the American Urological Association and the American Cancer Society which also recommend shared decision making for PSA screening. Shared decision making is a meaningful dialogue between the physician and the patient that namely includes a review of risks and expected outcomes of screening as well as the patient’s preferences and values. Understandably, the patient’s ability to critically assess the medical information provided (i.e. their health literacy) likely influences this process. We sought to characterize the effect of health literacy on shared decision making for PSA screening. We used data from 2016 when PSA screening for prostate cancer was not recommended by the US Preventive Services Task Force — in other words, we also sought to understand how health literacy impacted screening rates in the context of countervailing guidelines on PSA screening.
Author Interviews, Brain Injury, Exercise - Fitness, JAMA / 17.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55977" align="alignleft" width="142"]Tara L Sharma DO Clinical Assistant Professor of Neurology at UWMC Seattle, WA 98133 Dr. Sharma[/caption] Tara L Sharma DO Clinical Assistant Professor of Neurology at UWMC Seattle, WA 98133 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Flying can lead to reduced oxygen partial pressures and cerebral blood flow causing worsening clinical outcome in cases of moderate to severe TBI; however, not much is known regarding the clinical consequences of flying in individuals with concussion or mild TBI. Because many athletes suffer concussions during games, it is necessary to know if flying afterward may potentially hinder their ability to return to play. Overall, we found no associated between air travel and increased symptom severity in both our entire cohort and the subset of football players.
AHA Journals, Author Interviews, Heart Disease, University of Michigan / 17.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55974" align="alignleft" width="125"]Sara Saberi, MD, MS Assistant Professor Inherited Cardiomyopathy Program Frankel Cardiovascular Center University of Michigan Hospital Michigan Medicine Dr. Saberi[/caption] Sara Saberi, MD, MS Assistant Professor Inherited Cardiomyopathy Program Frankel Cardiovascular Center University of Michigan Hospital Michigan Medicine MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by HCM? How common is it and whom does it affect? Response: HCM is short for hypertrophic cardiomyopathy, the most common genetic myocardial disorder. It occurs in 1:500 people worldwide and because it is inherited in an autosomal dominant fashion, it affects men and women equally. HCM is characterized by unexplained left ventricular (LV) hypertrophy, hypercontractility, myofibrillar disarray and myocardial fibrosis with associated abnormalities in LV compliance and diastolic function. In some patients, there is progressive adverse cardiac remodeling, associated with chronic heart failure and atrial fibrillation as a result of diastolic dysfunction, left ventricular outflow tract (LVOT) obstruction, or less commonly, LV systolic dysfunction. Current medical management of obstructive HCM (oHCM) is limited to the use of beta blockers and non-dihydropyridine calcium channel blockers, or disopyramide, none of which have been shown to modify disease expression or outcomes after onset. Mavacamten is a first-in-class, small molecule, selective inhibitor of cardiac myosin specifically developed to target the underlying pathophysiology of HCM by reducing actin–myosin cross-bridge formation. The phase 3 EXPLORER-HCM trial showed that mavacamten improved exercise capacity, LVOT gradients, symptoms, and health status compared with placebo in patients with symptomatic oHCM. At selected study sites, participants were enrolled in a cardiac magnetic resonance (CMR) imaging substudy. CMR is the gold standard for measurement of ventricular mass, volumes and noninvasive tissue characterization, making it an ideal imaging modality to assess the effect of mavacamten on cardiac structure and function in patients with HCM.
Author Interviews / 17.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55967" align="alignleft" width="166"]Franco Vazza. PhD Associate Professor. Department of Physics and Astronomy University of Bologna, Italy Dr. Vazza
University of Bologna image[/caption] Franco Vazza. PhD Associate Professor. Department of Physics and Astronomy University of Bologna, Italy MedicalResearch.com: What is the background for this study? Response: We are an astrophysicist and a neurosurgeon, and we realised we had access, from our disciplines, to quantitative datasets to test the (long lived) idea that the two systems are very similar. So we designed simple experiments in which we can analyse both systems in an homogenous way. MedicalResearch.com: What are the main findings? Response:  If this work has any value, this is probably to be searched into the way it exposes the way in which such different systems (indeed sitting at the opposite extremes of cosmic scales) may evolve according to similar “macro” laws , i.e. not newer physical laws in any sense, but complex ways in which physical laws combine to evolve macro objects, or in this case networks of event. We hope this will trigger new research in this sense in the near future! 
Author Interviews, COVID -19 Coronavirus, Heart Disease / 17.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55944" align="alignleft" width="200"]Benjamin D. Horne, PhD Cardiovascular and Genetic Epidemiologist Intermoumtain Health Dr. Horne[/caption] Benjamin D. Horne, PhD Cardiovascular and Genetic Epidemiologist Intermoumtain Health MedicalResearch.com: What is the background for this study? Response: The Intermountain Mortality Risk Score (IMRS) is a risk prediction tool developed in 2009 and repeatedly validated over the last decade to predict death, major adverse health events such as heart attack and stroke, and the onset of major chronic diseases. IMRS is computed using sex-specific weightings of parameters from the complete blood count (CBC) and basic metabolic profile (BMP), and age. The CBC and BMP are commonly-ordered clinical laboratory panels that include hemoglobin, white blood cell count, glucose, creatinine, sodium, calcium, and other factors whose testing is standardized and the results are objective and quantitative with no need to know what diagnoses a patient may have. IMRS is known to be a superior predictor of death compared to comorbidity-based risk scores and has been found to predict health outcomes in people with no chronic disease diagnoses as well as patients with coronary heart disease, atrial fibrillation, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and various other diagnoses. IMRS has not been evaluated as a predictor of health outcomes for people with COVID-19, but if it does it could be useful for people to use to evaluate their own risk of poor outcomes if they are infected with SARS-CoV-2, for clinical personnel to guide the care of patients with COVID-19, and for public health professionals to use to determine who among those never diagnosed with COVID-19 is at higher risk of poor health outcomes and should be the first to receive a COVID-19 immunization. 
Author Interviews, Heart Disease, JACC / 17.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55919" align="alignleft" width="200"]Simon Winther, MD, PhD Associate professor Department of Cardiology, Gødstrup Hospital Herning, Denmark Dr. Winther[/caption] Simon Winther, MD, PhD Associate professor Department of Cardiology, Gødstrup Hospital Herning, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Both European and American guidelines have traditionally recommended estimating the pre-test probability (PTP) of CAD based on the classic Diamond-Forrester approach using sex, age, and type of chest complaints. However, The European Society of Cardiology (ESC) has recently suggested a novel concept of Clinical Likelihood of CAD as a more comprehensive assessment of CAD probability but no strategy has been proposed. I this study, we improve the estimation of the likelihood of obstructive coronary artery disease (CAD) by combining the classic pre-test probability model (Diamond–Forrester approach using sex, age, and symptoms) with clinical risk factors and coronary artery calcium score in symptomatic patients with suspected CAD. Hence, we propose a simple clinical tool for the individual estimation of clinical likelihood of CAD. The tool was developed by stepwise simplification of advanced machine learning models without significant loss of accuracy and the model were validated the both European and North American cohorts. 
Allergies, Author Interviews, Dermatology / 17.11.2020

MedicalResearch.com Interview with: Yashu Dhamija MD Dr. Thomas Schmidlin, MD Cleveland Clinic Akron General  MedicalResearch.com: What is the background for this study? Response: We are seeing an increased use of face masks in the COVID-19 pandemic and while that is encouraged and necessary to limit the spread of disease in the general publication, it can mean challenges for some individuals. Patients with known sensitizations to allergens contained in face masks may experience rash or irritation with commonly used face coverings. It is also possible for patients without a history of contact dermatitis to become sensitized to allergens after wearing facial coverings more regularly, thus leading to new cases of contact dermatitis (CD) in individuals with no known prior history of contact dermatitis.
Author Interviews, Brigham & Women's - Harvard, Dermatology, JAMA, McGill, Mental Health Research / 17.11.2020

Editor's note: This piece discusses suicide. If you have experienced suicidal thoughts or have lost someone to suicide and want to seek help, you can contact the Crisis Text Line by texting "START" to 741-741 or call the Suicide Prevention Lifeline at 800-273-8255.  MedicalResearch.com Interview with: David-Dan Nguyen, MPH Research Fellow | Center for Surgery and Public Health, Brigham and Women's Hospital Medical Student | McGill University MedicalResearch.com: What is the background for this study? Response: There is ongoing concern about the side-effects of finasteride, a drug used for the management of alopecia and benign prostatic hyperplasia. These concerns have led to the coining of the “post-finasteride syndrome” which remains controversial. Indeed, there is conflicting evidence on the post-finasteride syndrome/adverse events associated with finasteride. We wanted to contribute to this conflicting body of evidence by examining suicidality, depression, and anxiety reports linked to finasteride use using the WHO’s pharmacovigilance database, VigiBase. Such pharmacovigilance databases are useful for the study of rare adverse events that are suspected to be associated with medication use.
Author Interviews, Melanoma, Vaccine Studies / 16.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56006" align="alignleft" width="130"]Dr-Nina Bhardwaj Dr. Bhardwaj[/caption] Nina Bhardwaj MD, PhD Professor of Medicine (Hematology and Medical Oncology) and Urology Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? What types of cancer may be amenable to this vaccine? Response: The goal was to determine if vaccine responses could be improved by increasing special white cell numbers, namely dendritic cells, which are key for jumpstarting an immune response. MedicalResearch.com: What are the main findings?  Response: We found that the agent flt3-L mobilized these dendritic cells which help to improve the vaccine’s ability to prime the immune system. 
Author Interviews, COVID -19 Coronavirus, Occupational Health / 16.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55952" align="alignleft" width="200"]Emily Barrett, PhD  Associate Professor Department of Biostatistics and Epidemiology Rutgers School of Public Health Dr. Barrett[/caption] Emily Barrett, PhD Associate Professor Department of Biostatistics and Epidemiology Rutgers School of Public Health MedicalResearch.com: What is the background for this study? Response: We started this study in the very early stages of the pandemic to look at SARS-CoV-2 viral transmission and disease severity in health care workers as compared to non-health care workers.  There was a tremendous amount of fear and uncertainty about the virus and the early anecdotal reports coming out of China and Italy highlighted the plight of many frontline health care workers who had been infected on the job. We knew that our U.S. health care workers would soon be facing this tremendous challenge. We started this study to examine risks of infection in our vulnerable frontline health care workers and a comparison group of non-health care workers. Our results are from the early stages of the U.S. pandemic in March-April 2020.
Author Interviews, Genetic Research / 16.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55947" align="alignleft" width="130"]Philippe M Soriano, PhD Professor,  Cell, Developmental & Regenerative Biology and Oncological Sciences Icahn School of Medicine at Mount Sinai Dr. Soriano[/caption] Philippe M Soriano, PhD Professor,  Cell, Developmental & Regenerative Biology and Oncological Sciences Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The study was performed primarily to help understand how signals sent from growth factors to their receptors on the cell surface (see reply to the following question) initiate a cascade of events within the cells that lead to proliferation, survival, or other biological responses. This is important to know because deregulation of many of these pathways can lead to cancers. MedicalResearch.com: Would you explain what is meant by FGFs and their interaction with RTKs? Response: FGFs are cell signaling proteins that are also known as growth factors because they often lead to cell proliferation. They act by binding to receptors on the cell surface that are part of a family of receptor tyrosine kinases (RTKs). These RTKs are transmembrane proteins that have a domain outside of the cell that binds to the growth factor and a domain within the cell that has tyrosine kinase activity, hence the name “receptor tyrosine kinase (RTK).” This enzymatic activity adds a phosphate to a tyrosine residue of target proteins and starts a typical signal transduction pathway (referred to in the paper as “canonical”) leading to the usual biological responses (proliferation, survival, migration, etc.)
Author Interviews, Cancer Research, JAMA, Prostate Cancer, Technology / 13.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55940" align="alignleft" width="200"]Dave Steiner MD PhD Clinical Research Scientist Google Health, Palo Alto, California Dr. Steiner[/caption] Dave Steiner MD PhD Clinical Research Scientist Google Health, Palo Alto, California MedicalResearch.com: What is the background for this study? Response: For prostate cancer patients, the grading of cancer in prostate biopsies by pathologists is central to risk stratification and treatment decisions. However, the grading process can be subjective, often resulting in variability among pathologists. This variability can complicate diagnostic and treatment decisions. As an initial step towards addressing this problem, we and others in the field have recently developed artificial intelligence (AI) algorithms that perform on-par with expert pathologists for prostate cancer grading. Such algorithms have the potential to improve the quality and efficiency of prostate biopsy grading, but the impact of these algorithms when used by pathologists has not been well studied. In the current study, we developed and evaluated an AI-based assistant tool for use by pathologists while reviewing prostate biopsies.
Author Interviews, Gout, Rheumatology / 12.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55936" align="alignleft" width="150"]MedicalResearch.com Interview with: Jeffrey D. Kent, M.D., FACG, FACP Executive Vice President, Medical Affairs and Outcomes Research Horizon MedicalResearch.com: What is the background for this study? What is the marker for reduced immunogenicity with Pegloticase? Response: Pegloticase is a recombinant, pegylated uricase that is used for treatment of chronic gout in patients who fail oral urate lowering therapy (uncontrolled gout) and has a demonstrated impact on the serum uric acid (sUA) level. As with other biologics, in some people the body’s immune system develops anti-drug antibodies and reduces the effectiveness of the biologic therapy. Recent case series and open-label trials have suggested that using an immunomodulator with pegloticase has the potential to increase the durability of response so patients can receive a full course of therapy. Researchers in the RECIPE trial sought to examine whether the co-administration of disease-modifying antirheumatic drugs (DMARDs), specifically mycophenolate mofetil, may mitigate this loss of efficacy and increase in response rates for people living with uncontrolled gout MedicalResearch.com: Are symptoms of gout improved as well as reduced infusion reactions? Response Results from this trial indicated that short-term concomitant use of mycophenolate mofetil with pegloticase was generally well tolerated. It was also associated with a statistically significant and clinically meaningful impact on the proportion of patients achieving and maintaining an sUA ≤6 mg/dL at 24 weeks. No infusion reactions were reported in the pegloticase/mycophenolate mofetil arm (0 or 22 patients) compared to 30 percent (3 of 10) of patients reporting infusion reactions in the pegloticase/placebo arm. It’s been well established that in patients receiving pegloticase with persistent urate lowering, they experience relatively rapid resolution of tophi indicating significant reductions in their urate burden. MedicalResearch.com: What are the main findings? Response: This is the first randomized controlled trial evaluating pegloticase co-prescribed with an immunomodulator compared to pegloticase with placebo. Data showed that 86.4 percent of patients (19 of 22) receiving co-therapy of pegloticase with mycophenolate mofetil achieved an sUA ≤ 6 mg/dL through Month 3, the primary study endpoint, compared to 40.0 percent of patients (4 of 10) receiving pegloticase monotherapy. After Month 3, all patients received pegloticase only and at Month 6 a sustained response was shown in 68.2 percent (15 of 22) of patients who had received pegloticase with mycophenolate mofetil versus 30.0 percent (3 of 10) of patients who received pegloticase and placebo. This data adds to the growing body of evidence on the concomitant use of pegloticase with an immunomodulator to ultimately help more patients receive a full course of therapy and improve outcomes and may help shift the treatment paradigm in uncontrolled gout. MedicalResearch.com: What should readers take away from your report? Response: While rheumatologists are familiar with and may use DMARDs for other autoimmune conditions to minimize the development of anti-drug antibodies and increase response to therapies, data shows that the use of an immunomodulating therapy in patients with uncontrolled gout can improve response rates. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: There is a consistent pattern demonstrating that the concomitant use of pegloticase and an immunomodulator can improve patient outcomes without introducing additional toxicities. As clinicians we understand the immense burden gout places on our patients. Future research should continue exploring options to maximize the benefit of effective treatments to improve patient outcomes. MedicalResearch.com: Is there anything else you would like to add? Response: Uncontrolled gout is a chronic, systemic inflammatory condition and we continue to see data linking it to many comorbid conditions. Horizon is evaluating the use of methotrexate to improve response rates for pegloticase. We are committed to exploring various immunotherapy co-treatment options to allow both patients and clinicians to address elevated sUA levels to minimize urate burden and avoid lasting damage to the body. RECIPE is an investigator-initiated trial led by Puja Khanna, M.D., M.P.H. and Kenneth Saag, M.D., M.Sc. Citation: Khanna P, Khanna D, Cutter G, Foster J, Melnick J, Jaafar S, Biggers S, Rahman A, Kuo H, Feese M, Saag K. Reducing Immunogenicity of Pegloticase (RECIPE) with Concomitant Use of Mycophenolate Mofetil in Patients with Refractory Gout—a Phase II Double Blind Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/reducing-immunogenicity-of-pegloticase-recipe-with-concomitant-use-of-mycophenolate-mofetil-in-patients-with-refractory-gout-a-phase-ii-double-blind-randomized-controlled-trial/. Accessed November 12, 2020. [subscribe] Last Modified: [last-modified] The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. Dr. Kent[/caption]Jeffrey D. Kent, M.D., FACG, FACP Executive Vice President, Medical Affairs and Outcomes Research Horizon MedicalResearch.com: What is the background for this study? What is the marker for reduced immunogenicity with Pegloticase?   Response: Pegloticase is a recombinant, pegylated uricase that is used for treatment of chronic gout in patients who fail oral urate lowering therapy (uncontrolled gout) and has a demonstrated impact on the serum uric acid (sUA) level. As with other biologics, in some people the body’s immune system develops anti-drug antibodies and reduces the effectiveness of the biologic therapy.  Recent case series and open-label trials have suggested that using an immunomodulator with pegloticase has the potential to increase the durability of response so patients can receive a full course of therapy. Researchers in the RECIPE trial sought to examine whether the co-administration of disease-modifying antirheumatic drugs (DMARDs), specifically mycophenolate mofetil, may mitigate this loss of efficacy and increase in response rates for people living with uncontrolled gout
Author Interviews, COVID -19 Coronavirus, JAMA / 12.11.2020

MedicalResearch.com Interview with: Brunella Posteranno PhD Associate Professor of Microbiology Department of Medical and Surgical Sciences Rome, Italy MedicalResearch.com: What are the main findings? Response: This study arises from an attempt to clarify some recent evidences of positive real-time PCR (RT-PCR) test results among patients who recovered from COVID-19 with prior negative results. Retesting positive for SARS-CoV-2 RNA, in the absence of any symptoms suggestive of new infection, poses questions regarding not only the SARS-CoV-2 infection course but also, most importantly, the infectivity status of recovered COVID-19 patients. In other words, it is unknown whether such patients are infectious and whether they should be quarantined. Detecting genetic sequences (i.e., RNA) of SARS-CoV-2 in respiratory samples (e.g., nasal/oropharyngeal swab samples) by RT-PCR assays enable us to identify persons suffering from COVID-19 along with those who have been exposed and able to transmit virus to others even if they are asymptomatic. It is not hyperbole to say that without RT-PCR testing an effective fight against the virus would be impossible. However, RT-PCR assays are not a viral culture and do not allow to determine whether the virus is viable and, consequently, transmissible. In this study, we investigated RT-PCR retested positive nasal/oropharyngeal swab (NOS) samples from recovered COVID-19 patients for the presence of replicative SARS-CoV-2 RNA to assess active virus replication. 
Annals Internal Medicine, Author Interviews, Kidney Disease, Pediatrics / 12.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55860" align="alignleft" width="150"]Prof. Dr. Hans Pottel Professeur Invité (titre honorifique) Faculté de Médecine Université de Liège Prof. Pottel[/caption] Prof. Dr. Hans Pottel PhD Professeur Invité (titre honorifique) Faculté de Médecine Université de Liège KULeuven-KULAK, Kortrijk, Belgium  MedicalResearch.com: What is the background for this study? Why do we need a new GFR? Response: The currently recommended equations have flaws, mainly because there is one equation (CKiD) recommended for children, and one recommended (CKD-EPI) for adults (by KDIGO). When transitioning from pediatric nephrology care to adult nephrology care, the switch from CKiD to CKD-EPI causes implausible jumps (of more than 50%), mainly because CKD-EPI largely overestimates GFR in young adults (18-30 years). The new equation overcomes this problem as it applies for all ages (for children and adults) and overcomes the known flaws of the currently most used equations. The new equation is less biased and more precise across the full age spectrum and for the full range of serum creatinine concentrations. The equation was developed in 11 251 participants from 7 cohorts (development and internal validation datasets) and validated in 8 378 participants from 6 cohorts (external validation dataset). Data were coming from European and American nephrology centers. No patients of African-American ancestry were included. Actually, the previously published FAS-equation served as the basic mathematical form for the equation, but we adjusted the power coefficients for serum creatinine (very much like it was done in the CKD-EPI equation). You could say that we used properties of both the FAS and CKD-EPI equation to come to an improved equation to estimate GFR.
Author Interviews, COVID -19 Coronavirus, Depression, Mental Health Research, Occupational Health, Pediatrics, UCSF / 11.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55915" align="alignleft" width="120"]Kyle T. Ganson, PhD, MSW Assistant Professor, Factor-Inwentash Faculty of Social Work University of Toronto Toronto, Canada Dr. Ganson[/caption] Kyle T. Ganson, PhD, MSW Assistant Professor, Factor-Inwentash Faculty of Social Work University of Toronto Toronto, Canada [caption id="attachment_55902" align="alignleft" width="132"]Jason M Nagata M.D., M.Sc Assistant Professor of Pediatrics Division of Adolescent and Young Adult Medicine Department of Pediatrics, University of California San Francisco, San Francisco, CA Dr. Nagata[/caption]   Jason Nagata, MD, MSc Assistant Professor of Pediatrics University of California, San Francisco San Francisco, California, USA     MedicalResearch.com: What is the background for this study? Response: A quarter of young adults in the US have reported being unemployed during the COVID-19 pandemic. Young adults may be especially affected by employment loss as they often work in industries most adversely affected by social distancing. MedicalResearch.com: What are the main findings? Response: Among a sample of nearly 5,000 young adults age 18 to 26 in the US, we found that since March 2020, young adults who lost their job or were part of a household that experienced employment loss were more likely than those with secure employment to experience four common symptoms of anxiety and depression. This was also true of young adults who expected an employment loss in the next four weeks. The study also found that symptoms of anxiety and depression were common among the sample of young adults. In the seven days prior to the survey, 75% reported being nervous, anxious or on edge, 68% reported not being able to stop or control worrying, 67% reported having little interest or pleasure in doing things, and 64% reported feeling down, depressed, or hopeless.
Author Interviews, Baylor College of Medicine Houston, Smoking, Tobacco Research / 11.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55912" align="alignleft" width="120"]Dr-Mahmoud Al Rifai Dr. Al Rifai[/caption] Mahmoud Al Rifai, MD, MPH Cardiovascular Disease Fellow Baylor College of Medicine Houston, TX [caption id="attachment_55680" align="alignleft" width="150"]Salim S. Virani, MD, PhD Section of Cardiology Michael E. DeBakey Veterans Affairs Medical Center Dr. Virani[/caption] Salim S. Virani, MD, PhD, FACC, FAHA, FASPC Professor, Section of Cardiovascular Research Director, Cardiology Fellowship Training Program Baylor College of Medicine Staff Cardiologist, Michael E. DeBakey Veterans Affairs Medical Center Co-Director, VA Advanced Fellowship in Health Services Research & Development at the Michael E. DeBakey VA Medical Center Investigator, Health Policy, Quality and Informatics Program Michael E. DeBakey Veterans Affairs Medical Center HSR&D Center of Innovation Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: E-cigarettes have gained popularity since their introduction in the U.S. market nearly 20 years ago and their use has increased especially among younger adults. On the other hand, public health efforts aimed at curbing tobacco use over the past few decades have resulted in a decrease in cigarette use. However, state-specific laws and regional cultural differences with regards to perception of these products may result in variability in tobacco use patterns. We therefore evaluate temporal changes in e-cigarette and cigarette use in each U.S. state between the years 2016 to 2018.
Aging, Author Interviews, Geriatrics, Heart Disease, Lancet, Lipids / 11.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55907" align="alignleft" width="128"]Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital Herlev, Denmark Dr. Nordestgaard[/caption] Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital Herlev, Denmark  MedicalResearch.com: What is the background for this study? Response: Previous studies have yielded mixed results regarding the association between elevated cholesterol levels and increased risk of atherosclerotic cardiovascular disease in individuals above age 70 years; with some studies showing no association and others only minimal association. However, these previous studies were based on cohorts recruiting individuals decades ago where life-expectancy were shorter and where treatment of comorbidities were very different from today
Author Interviews, COVID -19 Coronavirus, Nutrition, Pediatrics, UCSF / 11.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55902" align="alignleft" width="132"]Jason M Nagata M.D., M.Sc Assistant Professor of Pediatrics Division of Adolescent and Young Adult Medicine Department of Pediatrics, University of California San Francisco, San Francisco, CA Dr. Nagata[/caption] Jason M Nagata M.D., M.Sc Assistant Professor of Pediatrics Division of Adolescent and Young Adult Medicine Department of Pediatrics, University of California San Francisco, San Francisco, CA MedicalResearch.com: What is the background for this study? Response: During the COVID-19 pandemic, food insecurity is expected to rise given economic uncertainty and job losses. Vulnerable and marginalized populations are disproportionately affected by both COVID-19 and food insecurity.  
Author Interviews, Cancer Research / 10.11.2020

MedicalResearch.com Interview with: Brianna M. Jones, MD Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: Oral tongue cancer has traditionally been a diagnosis associated with older age and habitual tobacco or alcohol use. However, in the past few decades there has been a disproportionate increase in oral tongue cancer in young patients, particularly in those without a prior history of significant alcohol or tobacco use. In the literature, these young patients without traditional risk factors seem to represent a distinct clinical entity with worse oncologic outcomes. The purpose of this study was to compare young patients (age ≤45) to older patients (>45) with oral tongue squamous cell carcinoma (OTSCC) without habitual smoking or drinking history. 
Author Interviews, BMJ, Breast Cancer, Cancer Research, Radiation Therapy / 10.11.2020

MedicalResearch.com Interview with: Professor Jayant S Vaidya MBBS MS DNB FRCS PhD Professor of Surgery and Oncology University College London MedicalResearch.com: What is the background for this study? What type of single dose radiation is used?  [caption id="attachment_55895" align="alignleft" width="500"]Prof Jeffrey S Tobias, Prof Jayant S Vaidya, Prof Max Bulsara and Prof Michael Baum Prof Jeffrey S Tobias, Prof Jayant S Vaidya, Prof Max Bulsara.                             and Prof Michael Baum[/caption] Response: The findings of the large international randomised trial (TARGIT-A trial), published in the British Medical Journal (BMJ 2020;370:m2836), confirm the long-term effectiveness of Targeted Intraoperative Radiotherapy (TARGIT-IORT): a breast cancer treatment which is increasingly available throughout the world. For most women with early breast cancer, a single dose of targeted radiotherapy during surgery is just as effective as conventional radiotherapy, which requires several visits to hospital after surgery. Conventional external beam radiotherapy (EBRT) is delivered from outside the body via a radiotherapy machine (linear accelerator), and consists of a daily treatment session (known as fractions) to the whole breast, over a period between three to six weeks. Each of these treatments is given over a few minutes, but requires 15 to 30 hospital visits, which could be a significant distance from where the patient lives. TARGIT-IORT is delivered immediately after lumpectomy (tumour removal), via a small ball-shaped device placed inside the breast, directly where the cancer had been. The single-dose treatment lasts for around 20 to 30 minutes and replaces the need for extra hospital visits, benefiting both patient safety and well-being. The device used is called INTRABEAM. More details are described on the BMJ and UCL webpages: https://www.bmj.com/company/newsroom/single-dose-radiotherapy-as-good-as-conventional-radiotherapy-for-most-women-with-early-breast-cancer/ https://www.ucl.ac.uk/news/2020/aug/single-dose-radiotherapy-effective-treating-breast-cancer https://blogs.bmj.com/bmj/2020/08/20/targeted-intraoperative-radiotherapy-for-early-breast-cancer-new-evidence/