Author Interviews, Ovarian Cancer / 04.11.2024

MedicalResearch.com Interview with: Alessia Baccarini, PhD Assistant Professor Dept. of Immunology and Immunotherapy (DII) Icahn School of Medicine at Mount Sinai New York, New York 10029 MedicalResearch.com: What is the background for this study? Response: Ovarian cancer is characterized by a complex tumor microenvironment (TME) that significantly contributes to resistance against immunotherapy, particularly immune checkpoint blockade (ICB) therapies like anti-PD-1. Understanding the extracellular signals—such as cytokines and chemokines—that ovarian cancer cells utilize to create an immunosuppressive TME is critical for improving treatment outcomes. Our research focuses on elucidating how these signaling factors contribute to tumor growth and immune evasion. We utilized a novel genomic functional approach called Perturb-map to study intratumoral heterogeneity (ITH) in ovarian cancer within a mouse model, allowing us to investigate the communication between ovarian cancer cells and immune cells.  (more…)
Author Interviews, Cancer Research, Leukemia, Stem Cells / 01.11.2024

MedicalResearch.com Interview with: Eirini Papapetrou, MD, PhD Professor of Oncological Sciences Professor of Medicine, Hematology and Medical Oncology Director, Center for Advancement of Blood Cancer Therapies Co-Director, Stem Cell Engineering Core Icahn School of Medicine at Mount Sinai New York, NY 10029   MedicalResearch.com: What is the background for this study? What are the main findings? Response: RAS in the most commonly mutated oncogene in human cancers. Particularly in acute myeloid leukemia, about one third of cases have RAS mutations. We set out to understand the role of these mutations in the development of leukemia and in response to treatment. We found that RAS mutations happen late in the course of the disease as progression mutations because they are acquired by more mature leukemic cells coming from preexisting leukemia stem cells (LSCs). Importantly, these more mature cells, upon acquisition of RAS mutations, become leukemia stem cells (LSCs) with different properties than the previous LSCs. Most critically, they develop resistance to a recently FDA-approved drug for the treatment of leukemia, venetoclax (VEN). In addition, these RAS-mutated LSCs give rise to leukemia cells with monocytic differentiation. Both RAS mutations and monocytic differentiation of AML have previously been associated with VEN resistance in clinical studies. We show that it is the RAS mutations that cause both the monocytic differentiation and the VEN resistance. Thus, poor patient outcomes after VEN therapy are driven by RAS mutations and not by monocytic disease.  (more…)
Author Interviews, Genetic Research, Heart Disease, Nature / 14.06.2024

MedicalResearch.com Interview with: Ben Omega Petrazzini, B.Sc. Associate Bioinformatician Ron Do Laboratory Ron Do, Ph.D. Professor, Department of Genetics and Genomic Sciences Director, Center for Genomic Data Analytics Associate Director in Academic Affairs, The Charles Bronfman Institute for Personalized Medicine Charles Bronfman Professor in Personalized Medicine Icahn School of Medicine at Mount Sinai     MedicalResearch.com: What is the background for this study? Response: Rare coding variants directly affect protein function and can inform the role of a gene in disease. Discovery of rare coding variant associations for coronary artery disease (CAD) to date have only had limited success. Genetic studies typically use standard phenotyping approaches to classify cases versus controls for CAD. However, this phenotyping approach doesn’t capture disease progression or severity in individuals. We recently introduced an in-silico score for CAD (ISCAD) that tracks CAD progression, severity, underdiagnosis and mortality (Forrest et al. The Lancet, 2023, PMID 36563696). ISCAD was built using a machine learning model trained on clinical data from electronic health records (EHR). Importantly, ISCAD is a quantitative score that measures CAD on a spectrum. The quantitative nature of the score provides an opportunity to discover additional rare coding variant associations that may not have been detected with the standard case-control phenotyping approach. Here in this study, we performed a large-scale rare variant association study in the exome sequences of 604,915 individuals for ISCAD, a machine learning-based score for CAD. (more…)
ASCO, Author Interviews, Breast Cancer, Genetic Research / 05.06.2024

MedicalResearch.com Interview with: Rima Patel, MD Assistant Professor, Division of Hematology/Oncology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai   MedicalResearch.com: What is the background for this study? Response: The 21-gene Oncotype DX Recurrence Score (RS) and 70-gene MammaPrint (MP) assays provide prognostic information for distant recurrence and are used to guide chemotherapy use in hormone receptor (HR)-positive, HER2-negative early breast cancer (EBC). Previous reports have demonstrated racial differences in the prognostic accuracy of the RS. In both the TAILORx and RxPONDER trials, Black women with low genomic risk (RS 0-25) had a higher recurrence risk than White women. In another study using the NCDB database, Black race was associated with worse overall survival in multivariate models including RS. The impacts of race/ethnicity on the MammaPrint assay are unknown. (more…)
Author Interviews, Colon Cancer, Gastrointestinal Disease, Immunotherapy / 04.06.2024

MedicalResearch.com Interview with: Steven H. Itzkowitz, MD, FACP, FACG, AGAF Professor of Medicine and Oncological Sciences Director of the GI Fellowship Program Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study looked at patients with inflammatory bowel disease (IBD) who had a history of cancer in the past 5 years and asked whether the medications they received for their IBD might have affected their rates of getting future cancer (new or recurrent cancers). Because many of the medicines that are used to treat IBD can affect the immune system in various ways, there has been concern that the medicines might predispose to subsequent cancers. We found that patients who received immunosuppressive medications had a numerically increased risk of subsequent cancer, this was not statistically higher than those who had not been exposed to these medications. While previous studies have looked at this question retrospectively, this is the first report that analyzed this issue prospectively using individuals from the United States.  Moreover, this study represents a multi-institutional collaboration among gastroenterologists at most of the major NYC healthcare systems. (more…)
Author Interviews, Cancer Research, Prostate, Prostate Cancer, Urology, Vaccine Studies / 08.04.2024

MedicalResearch.com Interview with: Sujit Nair, PhD Director of GU Immunotherapy Research Department of Urology Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? How is the vaccine obtained? Response: https://classic.clinicaltrials.gov/ct2/show/NCT03262103 Dr. Tewari is the treating physician and clinical lead on the study.  This is a phase I, open-label, clinical trial (NCT03262103) using a dose escalation strategy in 12 patients diagnosed with clinically localized prostate cancer with plans for surgery. The investigational agent used in the trial is Poly-ICLC, an immune modulator developed by ONCOVIR. Poly-ICLC is a double-stranded RNA that mimics viral activity, thereby stimulating the immune response. (more…)
Author Interviews, OBGYNE / 19.03.2024

MedicalResearch.com Interview with: Chelsea A DeBolt, MD Assistant Professor, Obstetrics, Gynecology and Reproductive Science Division of Maternal-Fetal Medicine Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: Significant immunological shifts, systemically and at the maternal-fetal interface, are required for a successful pregnancy. Yet, there is a paucity of comprehensive data investigating the systemic immune changes within the same individual transitioning from the non-pregnant to pregnant state. (more…)
Author Interviews, Heart Disease / 06.11.2023

MedicalResearch.com Interview with: Prakriti Gaba, MD Cardiovascular Medicine Fellow Brigham and Women's Hospital Deepak L. Bhatt MD MPH Director of Mount Sinai Fuster Heart Hospital Dr. Valentin Fuster Professor of Cardiovascular Medicine Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study?  Response: Accurate classification of acute myocardial infarction is instrumental for the appropriate diagnosis and effective management of patients suffering from this widely prevalent cardiovascular condition. In the past, there have been a variety of clinical scores published to advise clinicians on the best classifications schemes for patients with acute MI. These have included the Thrombolysis in Myocardial Infarction (TIMI) risk score, the HEART score, and the Killip classification. The strength of these traditional scores includes their practicality, as they can be implemented at the bedside to rapidly assist with prognostication. Nonetheless, as technologic advancements have made imaging and tissue identification more accessible, national and international committees are looking to revise traditional classification schemes of acute MI with novel ones leveraging multimodal approaches. (more…)
Author Interviews, Eli Lilly, Gastrointestinal Disease, NEJM / 02.11.2023

MedicalResearch.com Interview with: Marla C. Dubinsky, MD Professor of Pediatrics and Medicine Icahn School of Medicine at Mount Sinai Co- director, Susan and Leonard Feinstein IBD Clinical Center Mount Sinai Health System MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of UC? Response: Lucent 1 and Lucent 2 were the induction and maintenance registration trials studying the efficacy and safety of mirikizumab in patients 18 years and older with moderate to severely active ulcerative colitis. Mirikizumab is a monoclonal antibody targeting the p19 subunit of IL23. Lucent-3 is the open label extension arm for those meeting inclusion criteria after completing Lucent 2. This study evaluated the long term efficacy and safety of mirikizumab in patients with ulcerative colitis who completed a total of 104 weeks of active mirikizumab treatment. Ulcerative colitis is a chronic incurable inflammatory condition of colon. Common symptoms include diarrhea, blood in the stool, abdominal cramping and bowel urgency. Bowel urgency is one of the most burdensome symptoms that a patient with you could experience. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Ovarian Cancer / 07.08.2023

MedicalResearch.com Interview with: Pei Wang, PhD Professor, Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Michael J. Birrer MD PhD Director, Winthrop P. Rockefeller Cancer Institute University of Arkansas for Medical Sciences Little Rock, AR 72205 Amanda G. Paulovich MD PhD Translational Science and Therapeutics Division Fred Hutchinson Cancer Center Seattle WA 98109 MedicalResearch.com: What is the background for this study? How common is serous ovarian cancer? Response: Epithelial ovarian cancer accounts for >185,000 deaths/year worldwide. The most common subtype, high-grade serous ovarian cancer (HGSOC), accounts for 60% of deaths. Despite improvements in surgical and chemotherapeutic approaches, HGSOC mortality has not changed in decades. Five-year survival remains ~30% for the majority of patients. Standard of care involves surgical debulking combined with adjuvant or neoadjuvant chemotherapy with carbo- or cisplatin in combination with a taxane. At diagnosis, HGSOC is among the most chemo-sensitive of all epithelial malignancies, with initial response rates of ~85%, presumably related to DNA repair defects. Platinum is thought primarily to drive the response rate, due to the lower single-agent response rate for taxanes. Unfortunately, 10-20% of HGSOC patients have treatment-refractory disease at diagnosis, fail to respond to initial chemotherapy, and have a dismal prognosis. The poor response to subsequent therapy and median overall survival of ~12 months for these patients has not changed in 40 years. Despite >30 years of literature studying platinum resistance in cancer, there currently is no way to distinguish refractory from sensitive HGSOCs prior to therapy. Consequently, patients with refractory disease experience the toxicity of platinum-based chemotherapy without benefit. Due to their rapid progression, they are commonly excluded from participating in clinical trials. Consequently, there is no ongoing clinical research that could identify effective therapeutic agents for these patients or provide insights into molecular mechanisms of refractory disease.  “Right now, we can’t identify drug-resistant ovarian cancer patients up front,” said co-senior author Michael Birrer, MD, PhD, who directs UAMS’ Winthrop J. Rockefeller Cancer Institute. “We find them by default: They get sick and pass away so quickly that they can’t even be put on new clinical trials.” To address this unmet clinical need, we performed proteogenomic analysis of treatment-naïve HGSOCs (chemo-sensitive and chemo-refractory) to identify molecular signatures of refractory HGSOC and to identify potential treatment targets. (more…)
Author Interviews, Gastrointestinal Disease, Immunotherapy / 17.05.2023

MedicalResearch.com Interview with: Marla Dubinsky, M.D. Professor of Pediatrics and Medicine Co-director of the Susan and Leonard Feinstein IBD Clinical Center Chief of the Division of Pediatric Gastroenterology and Nutrition Icahn School of Medicine at Mount Sinai     MedicalResearch.com: What is the background for this study? How does MIRIKIZUMAB differ from other medications for UC? Response: This is a phase 2 study to assess the PK (pharamcokinetics), safety and efficacy of mirikizumab in pediatric ulcerative colitis (UC). Mirikizumab is a humanized monoclonal antibody that specifically binds to the p19 subunit of interleukin-23, a key inflammatory mediator in inflammatory bowel disease. (more…)
Author Interviews, Genetic Research / 21.03.2023

MedicalResearch.com Interview with: Ernest Turro, PhD Associate Professor Genetics and Genomics Sciences The Turro group runs a research program on statistical genomics, with a dual focus on rare diseases and blood-related traits at the Icahn School of Medicine Mount Sinai Health System   MedicalResearch.com: What is the background for this study? Would you describe the Rareservoir database? Response:   The main motivation for our work is that only half of the approximately 10,000 catalogued rare diseases have a resolved genetic cause (or aetiology). Patients with these diseases are unable to obtain a genetic diagnosis which could otherwise inform prognosis, treatment for themselves and affected relatives. One route towards resolving the remaining aetiologies is to enroll large numbers of rare disease patients into research studies so that statistical analyses can be performed comparing the genetic with the clinical characteristics of the study participants. One major endeavour, the 100,000 Genomes Project (100KGP), sequenced the genomes and collected clinical phenotype data for 34,523 UK patients and 43,016 unaffected relatives across 29,741 families. The scale of this study is unprecedented, partly thanks to the ever-decreasing cost of DNA sequencing (25 years ago, it cost $1bn to sequence a whole genome, while now it costs only a few hundred dollars). Working with such large datasets is notoriously cumbersome. To overcome this, we developed a computational approach (the Rareservoir) that distills the most important information into a relatively small database, allowing us to apply our statistical methods nimbly. We noted that the "genetic variants" that cause rare diseases are typically kept rare in the human population by natural selection because affected individuals tend to have few children, if any. This meant that we could discard the genetic information corresponding to variants that are common in the human population without throwing away the key disease-causing variants. By focussing on these "rare variants", we were able to perform our analyses using a small database (a `Rareservoir’), only 5.5GB in size, hastening our progress significantly. (more…)
Allergies, Author Interviews, Dermatology / 09.03.2023

MedicalResearch.com Interview with: Nicholas Gulati, MD, PhD Director, Early Detection of Skin Cancer and Oncodermatology Clinic The Kimberly and Eric J. Waldman Department of Dermatology Mount Sinai Health System New York, New York MedicalResearch.com: What is the background for this study? What is dupilumab primarily used for? Response: Dupilumab is a monoclonal antibody that inhibits a specific part of the immune system known as Th2 cells, which are important in the development of various diseases including atopic dermatitis (eczema) and asthma. Therefore, dupilumab has become one of the major treatments for these conditions. Given the increasing use of this drug, it is important to understand the safety of it in terms of cancer development, as that is currently largely unknown. (more…)
Author Interviews, Dermatology, Lancet / 13.12.2022

MedicalResearch.com Interview with: Dr. Emma Guttman-Yassky, MD, PhD Waldman Professor and System Chair The Kimberly and Eric J. Waldman Department of Dermatology Director, Center of Excellence in Eczema Director, Laboratory of Inflammatory Skin Diseases Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background for this study are studies that show that OX40 is a pathway that is upregulated in patients with atopic dermatitis (or eczema). OX40 is involved in activation of immune molecules associated with allergy and atopy, and also with formation of memory immune cells that are required for disease recurrence. The hypothesis to the study was that giving an OX40 antagonist will not only ameliorate the disease but perhaps have a remittive effect in that the disease will not come back. Indeed all drug doses were significantly effective at week 16, the primary endpoint compared to placebo and continued to improve towards week 36, the secondary endpoint. In addition, the responders to treatment maintained their responses for an additional 20 weeks, which is unusual, suggesting a potential for disease modification. (more…)
Author Interviews, Environmental Risks, Hepatitis - Liver Disease, JAMA / 06.07.2022

MedicalResearch.com Interview with: Dania Valvi, MD MPH PhD Assistant Professor Department of Environmental Medicine and Public Health Co-Director, MS in Epidemiology Icahn School of Medicine at Mount Sinai Email: [email protected] MedicalResearch.com:  What is the background for this study?    Response: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children in the U.S., Europe and other world regions, currently affecting 1 in every 10 children, and 1 in every 3 children with obesity in the U.S. The rate of pediatric NAFLD has more than doubled in recent decades following the epidemic rates also noted for childhood obesity. There is increasing interest in the role that environmental chemical exposures may play in NAFLD etiology, since several animal studies have shown that prenatal exposures to endocrine-disrupting chemicals (EDCs) cause liver injury and damage; but, until now, the potential effects of prenatal EDC mixture exposures in pediatric NAFLD had not been studied. (more…)
Author Interviews, Cancer Research, COVID -19 Coronavirus, Lung Cancer, Surgical Research / 21.06.2022

MedicalResearch.com Interview with: Emanuela Taioli, MD, PhD Director, Institute for Translational Epidemiology Professor, Population Health Science and Policy Professor, Thoracic Surgery Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com:  What is the background for this study?  Response: NYC experienced a halt on all elective care from March 22 to June 8, 2020, provoking reduced cancer screening rates, and delayed cancer care and treatment. We wanted to quantify the effect of the “pause” on cancer stage at diagnosis using lung cancer as an example of a condition where early diagnosis can dramatically modify survival. (more…)
Author Interviews, Cancer Research, COVID -19 Coronavirus, Race/Ethnic Diversity, Radiation Therapy / 01.11.2021

MedicalResearch.com Interview with: Brianna M. Jones, MD Radiation Oncology Resident Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The COVID-19 pandemic has resulted in over 4 million deaths worldwide and, presently, there have been over 2 million cases diagnosed in New York. There have been numerous studies that demonstrate cancer patients are at increased risk of diagnosis and mortality to SARS-CoV-2 virus. Several studies have also noted socioeconomic status and race/ethnicity are associated with poorer outcomes. Within NYC, Elmhurst Hospital Center (EHC) emerged as an early epicenter in spring of 2020. The surrounding catchment area of EHC consists of a population that is 54% Latino, 33% Asian, 6% White, 4% Black, 1% Native American, and 1% other according to U.S. Census Bureau, making it one of the most racially and ethnically diverse populations in the country. Its residents are predominantly working-class immigrants with limited resources that work jobs now considered essential (e.g., delivery workers, grocery shops, et cetera). EHC continued to offer a range of cancer services throughout the pandemic. Given the high infection rate and diverse population at EHC, our study provides an opportunity to evaluate outcomes in one of the hardest hit communities to date. Therefore, our aim was to investigate patient characteristics, clinical outcomes, and predictors of COVID-19 diagnosis, severity, and mortality in patients with an active cancer diagnosis at EHC.  (more…)
Author Interviews, Cancer Research / 27.10.2021

MedicalResearch.com Interview with: Shoshana Rosenzweig Medical Student Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Would you briefly describe the Phantosmia phenomenon?  Response: Phantosmia is an olfactive disorder resulting in the perception of a foul-smelling odor without odorant stimulus. This study was spearheaded by Dr. Suzanne Wolden, a pediatric radiation oncologist and the senior author of the research. She noticed that patients receiving proton beam therapy were complaining of this phenomenon more than her patients receiving photon therapy. Through this research, the team hoped to characterize radiation treatment induced phantosmia in pediatric, adolescent and young adult patients treated with proton beam therapy and we hoped to identify potential clinical and treatment-related characteristics that may correlate with the development of phantosmia.  (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, Journal Clinical Oncology, Metabolic Syndrome, Race/Ethnic Diversity, Social Issues / 08.06.2021

MedicalResearch.com Interview with: Giampaolo Greco PhD MPH Assistant Professor Department of Population Health Science and Policy Icahn School of Medicine  at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The motivation for our study was to understand why mortality rate from breast cancer is much higher in African American women than in White women, despite the fact that these groups have similar incidence rate of breast cancer. Metabolic syndrome, a cluster of metabolic abnormalities that includes abdominal obesity, hypertension, hyperglycemia and dyslipidemia, is more prevalent among African American women and may be a risk factor for breast cancer. Subjective social status (SSS) is the perception of individuals of their own ranking in the social hierarchy and complements other parameters of socioeconomic status, such as income and education, that are considered more objective. Socioeconomic status is associated with cardiovascular and mental health. Although objective measures of social status are associated with worse breast cancer outcomes, the relationship of SSS to breast cancer is uncertain. (more…)
Author Interviews, Genetic Research, Ophthalmology / 08.06.2021

MedicalResearch.com Interview with: Louis Pasquale, MD, FARVO Professor of Ophthalmology Icahn School of Medicine at Mount Sinai. Site Chair of the Department of Ophthalmology Mt. Sinai Hospital and Vice Chair of Translational Ophthalmology Research Mount Sinai Healthcare System  MedicalResearch.com: What is the background for this study? Response: Studies on the relation between caffeine intake and glaucoma have been contradictory, although our work suggested an adverse association amongst people with a self-reported family history of glaucoma. (more…)
ASCO, Author Interviews, Cancer Research / 07.06.2021

MedicalResearch.com Interview with: Mai Takahashi MD MPH Mount Sinai Beth Israel - Resident Physician New York, New York MedicalResearch.com: What is the background for this study? Response: The incidence of head and neck cancer had been significantly increasing in North America and Europe driven by Human Papillomavirus-related cancer (HPV OPC) which account for more than 60% of total oropharyngeal cancer cases. Compared to environmentally related oropharyngeal cancer, the HPV OPC patient population is generally younger and has a much better prognosis. However, they will suffer from long-term deteriorations in quality of life (QoL) and the declines associated with treatment intensity. Hence multiple studies have focused on de-intensification therapy with reduced dose chemoradiotherapy (CRT).  (more…)
Author Interviews, Environmental Risks, Pediatrics, Toxin Research, Weight Research / 08.03.2021

MedicalResearch.com Interview with: Alison P. Sanders, PhD Pronouns:  She/Her Assistant Professor Icahn School of Medicine at Mount Sinai Department of Environmental Medicine and Public Health Department of Pediatrics Director, Interdisciplinary Environmental Health Postdoctoral Fellowship MedicalResearch.com: What is the background for this study? Response: My research group is dedicated to understanding environmental and early life risk factors that contribute to kidney function decline. While some of the pathobiology leading to chronic kidney disease remains unclear, we understand that the process is complex and, like many chronic diseases, begins long before clinical diagnosis. My research investigates how the environment and mixtures of environmental chemicals/toxicants interact with traditional risk factors such as obesity, preterm birth, and nutritional status to hasten or prevent chronic kidney disease. (more…)
Author Interviews, JAMA, Social Issues / 20.10.2020

MedicalResearch.com Interview with: Aaron Baum, PhD Assistant Professor, Department of Health System Design & Global Health Economist, Arnhold Institute for Global Health Icahn School of Medicine at Mount Sinai Health System MedicalResearch.com: What is the background for this study? Response: To what degree are geographic health disparities in the leading risk factors for morbidity and mortality in the United States – including elevated blood pressure and blood sugar, obesity, and poor mental health – driven by the place where people live versus by characteristics of the people who live in different places? For example, male adults in Mississippi are 33% more likely to have uncontrolled blood pressure and 54% more likely to be obese than male adults in Colorado. One explanation is that male adults who live in Mississippi are different is many other ways from male adults in Colorado, some of which can't be directly measured and adjusted for, and that those unobserved differences cause the health disparity. Another possibility is that the place where a person lives actually contributes to the health disparity. Using national electronic health records from the Veterans Health Administration, we conducted a retrospective cohort study of 5 million adults, including 1 million who moved zip codes exactly once between 2008-2018. Our goal was to isolate how a movers' likelihood of uncontrolled blood pressure, uncontrolled diabetes, obesity and depression changed in response to changes in the prevalence of each outcome in his or her environment. (more…)
Author Interviews, Cancer Research, Lancet, Nature / 19.05.2020

MedicalResearch.com Interview with: Matthew Galsky, MD Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: Standard first-line treatment for metastatic urothelial (bladder) cancer has been platinum-based chemotherapy for decades. In 2016, atezolizumab, an immunotherapy that inhibits PD-L1, received accelerated approval by the FDA for the treatment of metastatic urothelial cancer for patients progressing despite prior platinum-based chemotherapy and this was followed by approvals for 4 additional PD-1 or PD-L1 inhibitors in this setting over the next couple years. With this first new drug class approved, representing the first new drugs approved for metastatic urothelial cancer for decades, logical question arose (a) should we combine these drugs with platinum-based chemotherapy in the first-line metastatic treatment setting and (b) is there a role to replace first-line chemotherapy with atezolizumab monotherapy. The IMvigor 130 trial was designed to address these questions. The trial enrolled 1213 patients who were randomized to treatment with (a) atezolizumab plus platinum-based chemotherapy, (b) placebo + platinum-based chemotherapy, or (c) atezolizumab monotherapy. The trial employed a hierarchical analysis plan such that comparisons between arms for certain endpoints could only be formally tested if other the preceding comparisons demonstrated a significant improvement.  (more…)
Author Interviews, Biomarkers, Gastrointestinal Disease / 28.03.2020

MedicalResearch.com Interview with: Jean-Frederic Colombel MD The Henry D Janowitz Division of Gastroenterology Icahn School of Medicine at Mount Sina New York, NY 10029, USA MedicalResearch.com: What is the background for this study? Response: The goals of therapy in Crohn’s disease have shifted from mere control of symptoms also called clinical remission towards combination of clinical and endoscopic remission also called deep remission which is now considered as the new therapeutic “target”. However it has yet to be proven that targeting deep remission instead of clinical remission is able to stop the progression of Crohn’s disease towards bowel damage, complications and hospitalizations. This study is a post-hoc analysis of the CALM trial that was published in The Lancet in 2018 where newly diagnosed patients were randomized to escalate therapy based on symptoms only (control arm) or based on a combination of symptoms and two biomarkers namely C-reactive protein in blood and calprotectin in stools (tight control arm). (more…)
Author Interviews, JAMA, Ophthalmology, Rheumatology / 15.12.2019

MedicalResearch.com Interview with: Robert Ritch, MD, FACS, FARVO Shelley and Steven Einhorn Distinguished Chair Professor of Ophthalmology, Surgeon Director Emeritus Chief, Glaucoma Services Emeritus The New York Eye and Ear Infirmary of Mount Sinai New York, NY 10003 Founder, Medical Director and Chairman, Scientific Advisory Board The Glaucoma Foundation  MedicalResearch.com: What is the background for this study? Response: Nailfold capillaroscopy (NFC), long used in rheumatology is a new approach to investigation of glaucoma. Posterior to the nailbed and just anterior to the proximal nailfold is the cuticle, which has no structural elements visible to the naked eye. NFC is a non-invasive imaging modality that provides a highly magnified view of the capillaries at the nailfold of digits. It has also been used in ophthalmology to show morphological changes at the nailfold capillaries of POAG and XFG/XFS patients, helping to confirm the systemic nature of these diseases. With nailfold capillaroscopy, an extensive array of capillaries can be seen greatly enlarged on a monitor screen. Capillary loops can be imaged, stored, recorded with videoscopy, and blood flow actively imaged and measured.. The first series of papers on glaucoma were written by Prof Josef Flammer’s group at the turn of the 21st century, looking at vasospasm, blood flow in normal-tension and high-tension glaucoma, and relating ocular blood flow alterations to systemic vascular regulation and relating laser Doppler flowmetry to NFC. Studies from Korea later associated nailbed hemorrhages and loss of nailbed capillaries to the presence of optic disc hemorrhages and investigated correlation of of heart rate variability with visual field defects and nailfold capillaroscopy. Studies by our group began with the publication in 2015 of a paper by Pasquale et al (Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite Study. IOVS;56:7021) using NFC video microscopy, associating dilated capillaries, avascular zones, and hemorrhages with primary open-angle glaucoma. Successive manuscripts and presentations at conferences have indicated differences between capillary loop patterns in high-tension and normal-tension POAG and exfoliation syndrome/exfoliation glaucoma. Our goal in this paper was to compare nailfold peripheral blood flow in XFG, which had not previously been compared to control subjects using NFC. We explored the peripheral blood flow at the nailfold of patients with high-tension glaucoma, normal-tension glaucoma, exfoliation glaucoma (XFG) and compared it to control subjects further evaluate the possible differences between these glaucoma entities. We examined the morphology and extent of nailfold capillary loops, vascular tortuosity, blood flow, and nailfold hemorrhages. (more…)
Author Interviews, Biomarkers, Hematology, Transplantation / 09.12.2019

MedicalResearch.com Interview with: Hrishikesh Srinagesh MD The Tisch Cancer Institute at Mount Sinai MedicalResearch.com: What is the background for this study? Response: Graft-versus-host disease (GVHD) is the leading cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT). Acute GVHD occurs in approximately 50% of HCT patients and targets the skin, liver, and gastrointestinal tract primarily. The change in clinical symptoms (e.g. reduction in volume of diarrhea) is used as the primary endpoint in most trials of acute GVHD treatment, but more accurate metrics are needed to predict long-term survival. Over the past decade, the Mount Sinai Acute GVHD International Consortium (MAGIC) has studied two biomarkers important in GVHD pathogenesis: suppressor of tumorigenesis 2 (ST2) and regenerating islet-derived 3 alpha (REG3). These proteins are shed into the bloodstream when the gastrointestinal tract is damaged during GVHD, the most lethal form of acute GVHD. The concentrations of ST2 and REG3 can be used generate an individual’s estimated probability of 6 month NRM known as the MAGIC Algorithm Probability (MAP). Our study evaluated whether the MAP measured at the start of GVHD treatment and four weeks later could predict long-term survival and we compared the MAP to clinical response after four weeks, the gold standard of response.  (more…)
Author Interviews, Ophthalmology / 14.10.2019

MedicalResearch.com Interview with: Sumayya Ahmad, MD Assistant Professor of Ophthalmology Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The cornea is usually curved like a basketball or a globe. Roughly all of the edges are about equal distant from the center. With this shape, light enters the eye normally and the image is not distorted.  However, not all eyes are shaped that way. About 30% of eyes have  astigmatism, in which the cornea is shaped like a football, or elongated in one axis. If the longest diameter is up and down, we call that with the rule astigmatism, and if it is to the side, we call that against-the rule astigmatism. A lot of studies have been devoted to astigmatism over the years, but nobody has looked at it from a population perspective in the United States and tried to figure out the relationships it may have. Most studies are from one center or other country's databases, but not ours. The National Health and Nutrition Examination Survey, or NHANES, is a survey composed in the United States each year that looks at a representative sample of people from across the country. It's a great way to study the relationship between the environment and people. We tried to look at demographic factors (like age, gender, race) and ocular factors related to against and with the rule astigmatism. (more…)
Author Interviews, Heart Disease, JAMA, Stem Cells / 26.03.2019

MedicalResearch.com Interview with: Annetine C. Gelijns, PhD Professor and System Chair Population Health Science and Policy Icahn School of Medicine at Mount Sinai Alan J Moskowitz, MD Professor of Population Health Science and Policy Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Where do these mesenchymal cells come from?  Response: Implantable LVADs significantly improve the survival and quality of life of advanced heart failure patients. However, these devices are associated with substantial adverse events, including infection and thromboembolic events. Moreover, whereas these devices improve myocardial function, few patients recover sufficient function to be explanted from their LVAD. These observations have focused attention on stem cells as a possible adjunctive therapy to further augment cardiac recovery. Mesenchymal precursor cells (MPCs), which are obtained from healthy donors and culture-expanded, have been shown in animal and early human studies to improve cardiac function. Using temporary weaning as a signal of cardiac recovery, we conducted an exploratory trial in the Cardiothoracic Surgical Trials Network (CTSN), which found that MPCs increased the probability of temporary weaning from full LVAD support compared to sham-control patients. Therefore, this signal of efficacy led the CTSN to design our current follow-up trial evaluating the efficacy and safety of a higher dose of MPCs in LVAD patients. (more…)
Author Interviews, Endocrinology, Gender Differences, Hormone Therapy / 26.03.2019

MedicalResearch.com Interview with: Joshua Safer, MD, Executive Director Center for Transgender Medicine and Surgery Mount Sinai Health System Senior Faculty, Medicine, Endocrinology, Diabetes and Bone Disease Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? What are the main findings? Response: The standard trans feminizing hormone regimen includes estrogen both to suppress testosterone and so that the individual has sufficient circulating sex hormone in the body for good bone health. After orchiectomy, there is no need to suppress testosterone because the levels are very low and it is common to cut the estrogen dose in half.  Cis women with premature ovarian failure often take about 2 mg of estradiol daily so that dose has seemed reasonable for trans women without testes.  However, when my co-author Sira Korpaisarn and I checked estradiol levels and gonadotropins (pituitary hormones, LH and FSH) as a guide to dosing, we found that based on that testing, trans women may require higher doses of estrogens than the 2 mg that we expected. (more…)