Author Interviews, JAMA, Social Issues / 04.12.2020

MedicalResearch.com Interview with: Amal Trivedi, MD, MPH Professor of Health Services, Policy & Practice Director of Graduate Studies, Health Services Research Brown University School of Public Health MedicalResearch.com: What is the background for this study? Response: Nearly all hospitals in the United States, including all Veterans Affairs Medical Centers (VAMCs), report mortality rates for patients hospitalized for common medical and surgical conditions. But these mortality rates do not adjust for socioeconomic factors that are associated with worse outcomes following hospitalization. (more…)
Author Interviews, COVID -19 Coronavirus, Hematology / 04.12.2020

MedicalResearch.com Interview with: George Sakoulas, MD Sharp Memorial Hospital and Sharp Rees-Stealy Medical Group Associate Adjunct Professor UC San Diego School of Medicine San Diego MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by IVIG?   Response: IVIG stands for intravenous immunoglobulin. It is a preparation from pooled blood donors isolating antibodies in their blood and highly concentrated for use. It's uses are to either replace immunoglobulins in patients who do not produce enough of them because of some underlying immunodeficiency or, as in the case of COVID, they take advantage of the immune signaling properties of the non-variable part of the antibodies. Many immune cells have receptors that bind the non-variable (also called the Fc-gamma region), and when bound, the activity of these activated immune cells is modulated. IVIG is used in many immunologic complications of infections like Guillan-Barre, Kawasaki's disease, immune mediated encephalitis from mycoplasma, just to name a few. We decided to study IVIG because:
  1. Our anecdotal yet successful use of IVIG in treating ARDS due to influenza and other viruses.
  2. Our very definitive successful use of IVIG in a very sick patient with COVID early in the pandemic.
  3. The weak yet positive retrospective data from China of IVIG in COVID.
  4. The mechanism of IVIG inhibiting neutrophil extracellular trap (or NETS) thought to play an important role in COVID severe disease.
  5. IVIG has been around to 4 decades and many physicians have a level of prescribing comfort.
It is worth clarifying that the benefit here is NOT from neutralizing antibodies against SARS-CoV-2 virus but rather the immunomodulatory effect. It will be very interesting to see if the effect/benefit changes over time as pooled blood donors feeding the IVIG supply do develop more antibodies against SARS-CoV-2, but this is not yet known.  (more…)
Author Interviews, Kidney Disease / 03.12.2020

MedicalResearch.com Interview with: Khurram Jamil, MD Vice President, Clinical Research in Hepatology Critical Care Division, Mallinckrodt MedicalResearch.com: What is the background for the new data of terlipressin presented during Kidney Week 2020 Reimagined? Would you briefly describe hepatorenal syndrome type 1? Whom does it affect and how frequently does it progress to ESRD? Response:  Results from two post-hoc analyses of terlipressin, an investigational agent in the U.S. for adults with hepatorenal syndrome type 1 (HRS-1), were presented at Kidney Week 2020 Reimagined, the annual meeting of the American Society of Nephrology. The first was an oral presentation titled, “Terlipressin Improves Renal Replacement Therapy–Free Survival in Hepatorenal Syndrome Type 1” and included a pooled post-hoc analysis to assess the incidence of renal replacement therapy (RRT) and its impact on survival among patients from three Phase 3 trials. The second was a poster presentation titled, “Treatment of Hepatorenal Syndrome Type 1 with Terlipressin Reduces Need for Renal Replacement Therapy After Liver Transplantation,” which focused on a post-hoc analysis of the CONFIRM study and evaluated the need for RRT among patients who had liver transplantation within 90 days of HRS treatment. HRS-1 is an acute and life-threatening syndrome involving acute kidney failure in people with cirrhosis.[i] HRS-1 can progress to life-threatening renal failure within days,i and has a median survival time of approximately two weeks and greater than 80 percent mortality within three months if left untreated.[ii],[iii] It is often a challenge to effectively diagnose in a timely manner due to its diagnosis of exclusion.iii In general, the average patient with hepatorenal syndrome (HRS type 1 or type 2) is in their 50s,[iv] and up to 73 percent of HRS patients are men.[v]  HRS-1 is estimated to affect between 30,000 and 40,000 patients in the U.S. annually.[vi],[vii] (more…)
Author Interviews, COVID -19 Coronavirus, JAMA, Pediatrics, Smoking, Stanford, Tobacco, Tobacco Research / 03.12.2020

MedicalResearch.com Interview with: Bonnie Halpern-Felsher, PhD, FSAHM (pronouns: she/her) Professor of Pediatrics Taube Endowed Research Faculty Scholar Professor (by courtesy), Epidemiology and Population Health Professor (by courtesy), Psychiatry and Behavioral Sciences Director of Fellows’ Scholarship, Department of Pediatrics Director of Research, Division of Adolescent Medicine Co-leader, Scholarly Concentrations, Pediatrics Residency Program MedicalResearch.com: What is the background for this study? What are the main findings? Response: To examine adolescent and young adult e-cigarette use during the COVID-19 pandemic. There were 4 main findings:
  • About 2/3 of adolescent and young adult ever-e-cigarette users reported either quitting or cutting back on e-cigarette use since COVID-19 began.
  • Users least likely to quit or cut back e-cigarette use were those showing higher levels of nicotine dependence and those who had used e- cigarettes a large number of times.
  • Adolescent and young adult e-cigarette users found it harder to access e-cigarettes, but unlike studies before COVID-19, the dominant source of purchasing e-cigs was online instead of brick-and-mortar during COVID-19 pandemic.
  • Youth below 21 years were able to purchase e-cigarettes without any age verification, and those whose age was verified were asked to physically show ID or provided an email, which are less effective means to prevent underage youth use.
(more…)
Addiction, Author Interviews, COVID -19 Coronavirus, JAMA, Opiods, UCLA / 03.12.2020

MedicalResearch.com Interview with: Joseph Friedman, MD/PhD student David Geffen School of Medicine UCLA MedicalResearch.com: What is the background for this study? Response: Numerous researchers, clinicians, officials, harm reduction agencies, and people who use drugs have sounded the alarm that the COVID-19 pandemic is exacerbating the United States overdose crisis. However, data sources typically used to track overdoses in the US often have long lags that impede timely monitoring and response. For example, the CDC released preliminary overdose figures for 2019 in July 2020, and even these numbers may change. As they are available in near real-time, emergency medical services (EMS) data have increasingly been used as a source of up-to-date information to monitor epidemiological shifts during the COVID-19 pandemic. In this study, we used data from the National EMS Information System (NEMSIS), a large registry of over 10,000 EMS agencies in 47 states that represented over 80% of all EMS activations nationally in 2020. We used the data to track shifts in overdose-related cardiac arrests observed by EMS.   (more…)
Aging, Author Interviews, Cognitive Issues / 03.12.2020

MedicalResearch.com Interview with: Susanna Rosi, Ph.D.  Lewis and Ruth Cozen Chair II Professor, Brain and Spinal Injury Center Weill Institute for Neuroscience Kavli Institute of Fundamental Neuroscience Departments of Physical Therapy Rehabilitation Science, Neurological Surgery University of California San Francisco MedicalResearch.com: What is the background for this study? Response: Everybody has experienced a “senior moment” forgetting where the car keys are, or where you put your glasses. These forgetful moments are not always indicative of a disease, but rather can be a consequence of normal aging. Normal aging is associated with decline of cognitive abilities, such as memory, spatial orientation, problem solving and executive functioning. Investigating what changes happen in the brain with age, can help us to understand why these ‘senior moments’ occur. When we understand what causes these moments, we can design therapeutics with the hopes of preventing or reversing them.  With increased life expectancy age-associatedmemory decline becomes a growing concern. We wanted to investigate (i) What causes memory decline with age? (ii) Are there ways to reverse it?  (more…)
Author Interviews, Weight Research / 03.12.2020

MedicalResearch.com Interview with: Gurmukh Singh, MD, PhD, MBA Department of Pathology, Section of Clinical Pathology Walter Shepeard Professor of Pathology Section Chief, Clinical Pathology. Associate Medical Director, Clinical Laboratory GRMC and Children's Hospital of Georgia MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by the obesity paradox? Response: Obese people tend to get more diseases, such as hypertension, diabetes, cancer etc. However, when they get seriously ill, e.g., sick enough to require admission to intensive care treatment unit (ICU), obese people tend to have better outcomes than normal weight people. (more…)
Author Interviews, Heart Disease, JAMA, Lifestyle & Health, USPSTF / 03.12.2020

MedicalResearch.com Interview with: Dr. John Epling, M.D., M.S.Ed Professor of family and community medicine Virginia Tech Carilion School of Medicine in Roanoke, VA. Medical director of research for family and community medicine Medical director of employee health and wellness for the Carilion Clinic Dr. Epling joined the U.S. Preventive Services Task Force in January 2016. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cardiovascular disease, which includes heart disease and stroke, is one of the leading causes of death in the United States. Nearly half of all adults have at least one risk factor for cardiovascular disease. Evidence shows that counseling aimed at helping people improve their diet and increase their physical activity can help prevent cardiovascular disease. This typically involves a trained counselor who provides education, helps people set goals, shares strategies, and stays in regular contact.  The Task Force recommends behavioral counseling interventions that promote a healthy diet and physical activity to help people at risk for cardiovascular disease stay healthy. (more…)
Author Interviews, Mental Health Research, Psychological Science / 01.12.2020

MedicalResearch.com Interview with: Gert Martin Hald, PhD Head of Section (Environmental Health), Associate Professor Department of Public Health, University of Copenhagen Copenhagen, Denmark MedicalResearch.com: What is the background for this study? Response: Basically, much of previous research has investigated mental and physical health of divorcees only after extensive separation periods, which is mandatory in most countries before juridical divorce unless infidelity or violence is involved in the divorce. During the time of data collection (2016-2019), Denmark where data was collected did not require separation periods before granting divorce. This means that as a first, we could investigate the mental and physical health of divorcees within days of them filling for divorce and perhaps better and more accurately pick up well-known adverse effects of mental- and physical health states of divorcees at the time of their divorce.   (more…)
Author Interviews / 01.12.2020

MedicalResearch.com Interview with: Daniel Maloney, Ph.D Farrar Lab Smurfit Institute of Genetics Trinity College Dublin MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of Dominant optic atrophy? Response: Dominant Optic Atrophy (DOA) is a progressive blinding disorder that affects roughly 1:10,000 to 1:30,000 people. It is primarily caused by mutations in the OPA1 gene, which plays a pivotal role in the maintenance of the mitochondrial network. There is currently no way to prevent or cure DOA. We sought to build upon previous work to test if OPA1 could be delivered as a potential gene therapy intervention.  (more…)
Asthma, AstraZeneca, Author Interviews / 01.12.2020

MedicalResearch.com Interview with: Frank Trudo, MD MBA Vice President, US Medical, Respiratory & Immunology AstraZeneca  MedicalResearch.com: What is the background for this study? Response: PONENTE is a multicenter, open-label, single-arm, Phase IIIb trial to evaluate the efficacy and safety of reducing daily oral corticosteroids (OCS) use after initiation of 30 mg dose of FASENRA (benralizumab) administered subcutaneously in adult patients with severe eosinophilic asthma on high-dose inhaled corticosteroids plus long-acting beta2-agonist and long-term use of OCS therapy with or without additional asthma controller(s). The trial expands on OCS-sparing data previously seen in the ZONDA Phase III trial by using a faster steroid tapering schedule in patients who did not experience adrenal insufficiency to reduce OCS use from higher doses. Compared to published trials of other biologics, PONENTE has a personalized OCS tapering schedule that allows for more rapid OCS tapering from higher OCS doses, followed by an assessment of the adrenal function as part of decision-making to manage the risk of adrenal insufficiency. PONENTE also has a longer maintenance phase (approximately 24-32 weeks), allowing assessment of the durability of OCS reduction. FASENRA is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis (programmed cell death). MedicalResearch.com: How is it administered?  Response: FASENRA is injected under your skin (subcutaneously) one time every 4 weeks for the first 3 doses, and then every 8 weeks. In 2019, FASENRA was approved in the US for self-administration in a single dose prefilled autoinjector, the FASENRA pen. (more…)
Alzheimer's - Dementia, Author Interviews, Medical Imaging, Mental Health Research / 01.12.2020

MedicalResearch.com Interview with: Maria Vittoria Spampinato, MD Neuroradiology Division Director Department of Radiology and Radiological Science Medical University of South Carolina Charleston, SC 29425-3230 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Alzheimer’s disease (AD) represents a major public health crisis worldwide. More than 5 million people currently have AD in the United States. AD is a slowly progressing neurodegenerative brain disorder with a long preclinical phase. Many people with AD first suffer from mild cognitive impairment (MCI), a decline in cognitive abilities like memory and thinking skills that is greater than that associated with normal aging. A person with MCI is at an increased risk of developing AD or another dementia, although some individuals with MCI remain cognitively stable or improve. Anxiety is frequently observed in individuals with MCI. The reported prevalence of anxiety in MCI patients varies between 10 and 50%.  In this study we evaluated a cohort of 339 individuals with MCI participating in the Alzheimer’s Disease Neuroimaging Initiative study (ADNI2). During the five years of study participation, 72 patients experienced cognitive decline and were diagnosed with AD. We did not find difference in age, gender and education among patients with and without AD conversion. Patients who progressed had greater atrophy of the hippocampi and entorhinal cortex on their MRI scan, as expected (hippocampal atrophy is often used as a marker of neurodegeneration in AD), as well as greater prevalence of APOE4 is the strongest known genetic risk factor for AD.   Patients who progressed to Alzheimer’s disease also had greater severity of anxiety during the study, as measured using the Neuropsychiatric Inventory-Questionnaire. Next we determined the effect of the MRI findings (hippocampal and entorhinal cortex atrophy), of the genetic risk factor (APOE4) and of the severity of anxiety on the time to progression to AD. We found that higher levels of anxiety were associated with faster progression from MCI to AD, independently of whether they had a genetic risk factor for Alzheimer’s disease or brain volume loss. We still need to understand better the association between anxiety disorders and cognitive decline. We do not know whether increased levels of anxiety are a consequence of cognitive decline or if anxiety exacerbates to cognitive decline. If we were able to find in the future that anxiety is actually contributing to cognitive decline, then we should more aggressively screen for anxiety disorders in the elderly population.  (more…)
Author Interviews, Cancer Research, Genetic Research / 01.12.2020

MedicalResearch.com Interview with: Nina Bhardwaj MD PhD Director of Immunotherapy Tisch Cancer Institute Icahn School of Medicine at Mt Sinai Ward-Coleman Chair in Cancer Research Professor of Hematology and Oncology MedicalResearch.com: What is the background for this study? Response: Neoantigens are novel antigens expressed by tumors as a result of somatic mutations or frame shift mutations. They can be very immunogenic and consequently they are being incorporated into cancer vaccine platforms. In most cases it is necessary to determine each patient’s individual mutations and customize their vaccine antigens accordingly. We sought to identify shared mutations in cancer antigens which are deficient in DNA repair mechanisms namely microsatellite unstable tumors. These tumors have mutations in genes that normally are responsible for ensuring that DNA is properly replicated. Because these genes encode proteins that ensure proper repair around micro-satellite areas (which contain short repeated sequences of DNA and are present in similar regions from one person’s genome to the next), when they are mutated, these regions may not be repaired. Consequently due to nucleotide deletions and insertions one gets frame shift mutations which result in new protein expression which can be shared across tumors, as has been observed for a few regions. We therefore did a comprehensive study of a subset of tumors to determine the breadth of shared frame shift mutations. (more…)
Author Interviews, COVID -19 Coronavirus, Inflammation, JAMA, Pediatrics, Race/Ethnic Diversity / 30.11.2020

MedicalResearch.com Interview with: Ellen H. Lee, MD Incident Command System Surveillance and Epidemiology Section New York City Department of Health and Mental Hygiene Long Island City, New York  MedicalResearch.com: What is the background for this study? Response: Published reports of the COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) have described higher proportions of cases among Black and Hispanic children. However, case series are limited by the lack of population-level data, which could help provide context for the racial/ethnic distribution of cases described in these reports. The New York City (NYC) Department of Health and Mental Hygiene required reporting of all possible cases of MIS-C among NYC residents, and for cases meeting MIS-C criteria, applied population denominators to calculate MIS-C incidence rates stratified by race/ethnicity. To help characterize the burden of severe COVID-19 disease in NYC, we also calculated COVID-19 hospitalization rates stratified by race/ethnicity. (more…)
AHA Journals, Author Interviews, Heart Disease, Women's Heart Health / 30.11.2020

MedicalResearch.com Interview with: Justin A. Ezekowitz, MBBCh, MSc Professor, Department of Medicine Co-Director, Canadian VIGOUR Centre Director, Cardiovascular Research, University of Alberta Cardiologist, Mazankowski Alberta Heart Institute MedicalResearch.com: What is the background for this study? What are the main findings? Are women older, sicker when they experience heart disease? Response: Previous research looking at sex-differences in heart health has often focused on recurrent heart attack or death, however, the vulnerability to heart failure between men and women after heart attack remains unclear. Our study includes all patients from an entire health system of over 4 million people and includes information not usually available in other analyses. Women were nearly a decade older and more often had a greater number of other medical conditions when they presented to hospital for their first heart attack, and were at greater risk for heart failure after the more severe type of heart attack (also known as a ST-elevation MI). This gap between men and women has started to narrow over time. (more…)
Author Interviews, Infections, OBGYNE, Pediatrics / 26.11.2020

MedicalResearch.com Interview with: Jessica Miller PhD Postdoc Fellow Murdoch Childrens Research Institute  MedicalResearch.com: What is the background for this study? Response: Cesarean section (CS) may be a lifesaving intervention for women and babies. However, the global proportion of CS births is rapidly increasing and may not be medically justified. As CS has implications for both mother and child, the increasing rates warrant population-level analyses of potential risks. Many suggested long-term outcomes in CS-born children relate to altered immune development. It is possible that differences in the newborn microbiome by mode of birth contribute to the development of early immune responses which may influence the risk of immune-related outcomes, including infection. CS has been associated with an increased risk for specific infection-related hospitalisations, mainly lower respiratory tract and gastrointestinal infections, but it remains unclear whether CS is associated with increased risk of overall infection-related hospitalisation or only certain infection types, and whether risk differs for emergency versus elective/pre-labour CS. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, JAMA, Yale / 26.11.2020

MedicalResearch.com Interview with: Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director, Breast Cancer Translational Research Co-Director, Yale Cancer Center Genetics and Genomics Program Yale Cancer Center Yale School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: In HER2-positive early stage (stage I-II) breast cancer, several different preoperative (also called neoadjuvant) chemotherapy options exist, each of these is associated with a different rate of complete eradication of cancer from the breast and lymph nodes (called pathologic complete response or pCR). Patients who experience pCR have excellent long term survival. The complete response rates range from 20% to 80%, the rates are higher with regimens that include several different chemotherapy drugs and dual HER2 blockade. Unfortunately, these highly effective multi-drug treatment regimens are also more toxic and more expensive.  We also learned that patients who do not achieve pCR after preoperative therapy, have high rates of recurrence, but the recurrence rate can be improved by administering postoperative adjuvant therapy. These two observations together, (1) different regimens with different toxicities and costs resulting in different pCR rates, and (2) existence of effective postoperative therapies for patients with residual cancer after preoperative therapy, sets the stage for combining various pre- and post-operative treatment strategies. Starting with a shorter, less toxic and less expensive neoadjuvant regimen would allow a substantial minority (20-45%) of patients who archive pCR to be spared of longer and more toxic regimens, whereas those with residual disease could receive the remaining part of the currently most effective regimens post-operatively as adjuvant therapy. In this study we examined the cost effectiveness of different neoadjuvant followed by adjuvant treatment strategies from a healthcare payer perspective. (more…)
Accidents & Violence, Author Interviews, Pediatrics, Race/Ethnic Diversity / 26.11.2020

MedicalResearch.com Interview with: Dr. Monika K. Goyal, MD Associate Division Chief, Emergency Medicine Children’s National Hospital Department of Pediatrics, School of Medicine and Health Sciences The George Washington University Washington, District of Columbia MedicalResearch.com: What is the background for this study? Response: There has been growing attention to the disproportionate use of police force in communities of color. Therefore, we sought to investigate whether Black and Hispanic teenagers have higher rates of death due to police shootings when compared to white youth. (more…)
Author Interviews, Education, Pediatrics / 26.11.2020

MedicalResearch.com Interview with: Lukas D. Lopez Doctoral Candidate Psychological Sciences, Developmental Psychology University of California, Merced MedicalResearch.com: What is the background for this study? What are the main findings? Response: "This study is unique because it uses LENA recording devices which are small recording devices that infants wear in the pocket of a vest that record all infant babbles and caregiver responses in the home. We then had trained listeners annotate infant-adult vocal exchanges within sections of those recordings focusing on the specific types of sounds infants made and specific types of adult responses to those sounds. Using this combination of methods is distinctive because it allowed us to capture a more natural picture of a family's language environment in the home context, whereas most research on this topic is conducted in the laboratory. We then related this information to caregivers' reports of their infant's vocabulary. Our study finds that the caregivers who scaffold and elaborate on their infant’s babbling report that their infants can say more words." (more…)
Author Interviews, Heart Disease, JAMA, Pediatrics, Surgical Research / 25.11.2020

MedicalResearch.com Interview with: Michael R. Flaherty, DO Attending, Pediatric Critical Care Medicine Co-Director, Trauma and Injury Prevention Outreach Program, MGH Instructor in Pediatrics, Harvard Medical School Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings?   Response: This study was a joint collaboration between Massachusetts General Hospital and Boston Children’s Hospital. The Consumer Product Safety Commission (CPSC) found an increasing incidence of rare earth magnet ingestions by children causing serious injury; Injuries are particularly serious when a child ingests two of these small magnets, or a magnet with another metal object – this can lead to bowel walls becoming attached and kinked, leading to catastrophic bowel injury and/or death. The Consumer Product Safety Commission initiated campaigns to limit sales in 2012 with voluntary recalls and safety standards, as well as public awareness campaigns, legislative advocacy, and lawsuits. In October 2014, the CPSC published their final rule, “Safety Standard for Magnet Sets,” which prohibited the sale of magnets based on a pre-specified size and power scale, essentially eliminating the ability to sell SREMs. This rule was appealed by largest manufacturer of these magnets, Zen Magnets, LLC., and in November 2016 this rule was legally reversed by the U.S. Court of Appeals Tenth Circuit resulting in a resurgence of these magnets on the market. (more…)
Author Interviews / 24.11.2020

MedicalResearch.com Interview with: Ventura Simonovich Jefe. Sección Farmacología Clínica. Servicio de Clínica Médica Coordinador Operativo. Investigación Patrocinada. Departamento de Investigación Hospital Italiano de Buenos Aires Vicepresidente. Asociación Argentina de Farmacología Experimental (AAFE) MedicalResearch.com: What is the background for this study? What are the main findings? Response: The convalescent plasma is something that was used almost since the beginning of this pandemic, but all the information came at the beginning from cohort studies. We decided to run this trial to evaluate the efficacy of the convalescent plasma in patients with severe Covid 19 pneumonia, which was the main indication in our country. Our findings show that convalescent plasma is equal to placebo except in patients younger than 65, in that population placebo is better than plasma.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, Melanoma, Prostate Cancer / 23.11.2020

MedicalResearch.com Interview with: 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.     (more…)
Aging, Author Interviews, Genetic Research, McGill / 22.11.2020

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Dermatology, Genetic Research / 20.11.2020

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Dermatology, Genetic Research, Melanoma / 19.11.2020

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Blood Pressure - Hypertension, Heart Disease, Pediatrics, USPSTF / 19.11.2020

MedicalResearch.com Interview with: 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. (more…)
AHA Journals, Author Interviews, COVID -19 Coronavirus, Race/Ethnic Diversity, Stanford / 19.11.2020

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, Fertility, OBGYNE / 19.11.2020

MedicalResearch.com Interview with: 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. (more…)
Alzheimer's - Dementia, Author Interviews, Lipids, Mental Health Research, Microbiome / 18.11.2020

MedicalResearch.com Interview with: 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. (more…)
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. (more…)