Medicine and Health Sciences Commons^™

Effect Of Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease And Risk Factors For Rapid Progression, Dinesh Khanna, Toby M Maher, Elizabeth R Volkmann, Yannick Allanore, Vanessa Smith, Shervin Assassi, Michael Kreuter, Anna-Maria Hoffmann-Vold, Masataka Kuwana, Christian Stock, Margarida Alves, Steven Sambevski, Christopher P Denton

Faculty, Staff and Student Publications

Objective: To investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC.

Methods: The SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (< 18 months since first non-Raynaud symptom), elevated inflammatory markers (C reactive protein ≥6 mg/L and/or platelets ≥330×109/L) or significant skin fibrosis (modified Rodnan skin score (mRSS) 15-40 or mRSS ≥18) at baseline.

Results: In the placebo group, the rate of decline in FVC was numerically greater in subjects with < 18 months since first non-Raynaud symptom (-167.8 mL/year), elevated inflammatory markers (-100.7 mL/year), mRSS 15-40 (-121.7 mL/year) or mRSS ≥18 (-131.7 mL/year) than in all subjects (-93.3 mL/year). Nintedanib reduced the rate of FVC decline across subgroups, with a numerically greater effect in patients with these risk factors for rapid FVC decline.

Conclusion: In the …

Telehealth Trials To Address Health Equity In Stroke Survivors, Anjail Z Sharrief, Amy K Guzik, Erica Jones, Munachi Okpala, Mary F Love, Tamra Ishan Jayenda Ranasinghe, Cheryl Bushnell

Faculty, Staff and Student Publications

Telehealth has seen rapid expansion into chronic care management in the past 3 years because of the COVID-19 pandemic. Telehealth for acute care management has expanded access to equitable stroke care to many patients over the past two decades, but there is limited evidence for its benefit for addressing disparities in the chronic care of patients living with stroke. In this review, we discuss advantages and disadvantages of telehealth use for the outpatient management of stroke survivors. Further, we explore opportunities and potential barriers for telehealth in addressing disparities in stroke outcomes related to various social determinants of health. We …

First- Or Second-Trimester Sars-Cov-2 Infection And Subsequent Pregnancy Outcomes, Brenna L Hughes, Grecio J Sandoval, Torri D Metz, Rebecca G Clifton, William A Grobman, George R Saade, Tracy A Manuck, Monica Longo, Amber Sowles, Kelly Clark, Hyagriv N Simhan, Dwight J Rouse, Hector Mendez-Figueroa, Cynthia Gyamfi-Bannerman, Jennifer Bailit, Maged M Costantine, Harish M Sehdev, Alan T N Tita, George A Macones

Faculty, Staff and Student Publications

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy.

OBJECTIVE: This study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness.

STUDY DESIGN: A retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation …

Assistive Artificial Intelligence For Ultrasound Image Interpretation In Regional Anaesthesia: An External Validation Study, James S Bowness, David Burckett-St Laurent, Nadia Hernandez, Pearse A Keane, Clara Lobo, Steve Margetts, Eleni Moka, Amit Pawa, Meg Rosenblatt, Nick Sleep, Alasdair Taylor, Glenn Woodworth, Asta Vasalauskaite, J Alison Noble, Helen Higham

Faculty, Staff and Student Publications

BACKGROUND: Ultrasonound is used to identify anatomical structures during regional anaesthesia and to guide needle insertion and injection of local anaesthetic. ScanNav Anatomy Peripheral Nerve Block (Intelligent Ultrasound, Cardiff, UK) is an artificial intelligence-based device that produces a colour overlay on real-time B-mode ultrasound to highlight anatomical structures of interest. We evaluated the accuracy of the artificial-intelligence colour overlay and its perceived influence on risk of adverse events or block failure.

METHODS: Ultrasound-guided regional anaesthesia experts acquired 720 videos from 40 volunteers (across nine anatomical regions) without using the device. The artificial-intelligence colour overlay was subsequently applied. Three more experts …

Hyaluronan In The Pathogenesis Of Acute And Post-Acute Covid-19 Infection, Henry W Barnes, Sally Demirdjian, Naomi L Haddock, Gernot Kaber, Hunter A Martinez, Nadine Nagy, Harry Karmouty-Quintana, Paul L Bollyky

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients long after the resolution of viral replication. There is therefore great interest in understanding the host factors that contribute to COVID-19 pathogenesis. In this review, we address the role of hyaluronan (HA), an extracellular matrix polymer with roles in inflammation and cellular metabolism, in COVID-19 and critically evaluate the hypothesis that HA promotes COVID-19 pathogenesis. We first provide a brief overview of COVID-19 infection. …

Inter-Observer Variability Of Expert-Derived Morphologic Risk Predictors In Aortic Dissection, Martin J Willemink, Domenico Mastrodicasa, Mohammad H Madani, Marina Codari, Leonid L Chepelev, Gabriel Mistelbauer, Kate Hanneman, Maral Ouzounian, Daniel Ocazionez, Rana O Afifi, Joan M Lacomis, Luigi Lovato, Davide Pacini, Gianluca Folesani, Ricarda Hinzpeter, Hatem Alkadhi, Arthur E Stillman, Anna M Sailer, Valery L Turner, Virginia Hinostroza, Kathrin Bäumler, Anne S Chin, Nicholas S Burris, D Craig Miller, Michael P Fischbein, Dominik Fleischmann

Faculty, Staff and Student Publications

OBJECTIVES: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning.

METHODS: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a …

A Method Using Longitudinal Laboratory Data To Predict Future Intestinal Complication In Patients With Crohn's Disease, James Irwin, Anton Lord, Emma Ferguson, Lisa A Simms, Katherine Hanigan, Carlos A Montoya, Graham Radford-Smith

Faculty, Staff and Student Publications

Background

Stenosis, fistulization, and perforation of the bowel are severe outcomes which can occur in patients with Crohn’s disease. Accurate prediction of these events may enable clinicians to alter treatment strategies and avoid these outcomes.

Aims

To study the correlation between longitudinal laboratory testing and subsequent intestinal complications in patients with Crohn’s disease.

Methods

An observational cohort of patients with Crohn’s disease at a single center were analyzed between 01/01/1994 and 06/30/2016. A complication was defined as the development of an intestinal fistula, stenosis, or perforation. Exploratory analysis using Cox regression was performed to select the best statistical method to …

Association Of Endovascular Thrombectomy Vs Medical Management With Functional And Safety Outcomes In Patients Treated Beyond 24 Hours Of Last Known Well, Amrou Sarraj, Timothy J Kleinig, Ameer E Hassan, Pere Cardona Portela, Santiago Ortega-Gutierrez, Michael G Abraham, Nathan W Manning, James E Siegler, Nitin Goyal, Laith Maali, Spiros Blackburn, Teddy Y Wu, Jordi Blasco, Arturu Renú, Navdeep S Sangha, Juan F Arenillas, Margy E Mccullough-Hicks, Adam Wallace, Daniel Gibson, Deep K Pujara, Faris Shaker, Mercedes De Lera Alfonso, Marta Olivé-Gadea, Mudassir Farooqui, Juan S Vivanco Suarez, Zachary Iezzi, Jane Khalife, Colleen G Lechtenberg, Syed K Qadri, Rami B Moussa, Mohammad A Abdulrazzak, Tareq S Almaghrabi, Osman Mir, James Beharry, Balaji Krishnaiah, Megan Miller, Najwa Khalil, Gagan J Sharma, Aristeidis H Katsanos, Ali Fadhil, Kelsey R Duncan, Yin Hu, Sheryl B Martin-Schild, Georgios K Tsivgoulis, Dennis Cordato, Anthony Furlan, Leonid Churilov, Peter J Mitchell, Adam S Arthur, Mark W Parsons, James C Grotta, Clark W Sitton, Marc Ribo, Gregory W Albers, Bruce C V Campbell

Faculty, Staff and Student Publications

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.

OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or …

Identification Of Bradycardia Following Remdesivir Administration Through The Us Food And Drug Administration American College Of Medical Toxicology Covid-19 Toxic Pharmacovigilance Project, Jason M Devgun, Rongmei Zhang, Jeffrey Brent, Paul Wax, Keith Burkhart, Alison Meyn, Sharan Campleman, Stephanie Abston, Kim Aldy

Faculty, Staff and Student Publications

IMPORTANCE: The rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion-associated AE listed in the US Food and Drug Administration-approved prescribing information.

OBJECTIVE: To evaluate the magnitude and duration of bradycardic events following remdesivir administration.

DESIGN, SETTING, AND PARTICIPANTS: A multicenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 …

Association Of Frailty And The Expanded Operative Stress Score With Preoperative Acute Serious Conditions, Complications, And Mortality In Males Compared To Females: A Retrospective Observational Study, Qi Yan, Jeongsoo Kim, Daniel E Hall, Myrick C Shinall, Katherine Moll Reitz, Karyn B Stitzenberg, Lillian S Kao, Elizabeth L George, Ada Youk, Chen-Pin Wang, Jonathan C Silverstein, Elmer V Bernstam, Paula K Shireman

Faculty, Staff and Student Publications

OBJECTIVE: The aim of this study was to expand Operative Stress Score (OSS) increasing procedural coverage and assessing OSS and frailty association with Preoperative Acute Serious Conditions (PASC), complications and mortality in females versus males.

SUMMARY BACKGROUND DATA: Veterans Affairs male-dominated study showed high mortality in frail veterans even after very low stress surgeries (OSS1).

METHODS: Retrospective cohort using NSQIP data (2013-2019) merged with 180-day postoperative mortality from multiple hospitals to evaluate PASC, 30-day complications and 30-, 90-, and 180-day mortality.

RESULTS: OSS expansion resulted in 98.2% case coverage versus 87.0% using the original. Of 82,269 patients (43.8% male), 7.9% …

Prospective Evaluation Of The Fungitell® (1-->3) Beta-D-Glucan Assay As A Diagnostic Tool For Invasive Fungal Disease In Pediatric Allogeneic Hematopoietic Cell Transplantation: A Report From The Children’S Oncology Group, William R Otto, Christopher C Dvorak, Craig L K Boge, Luis Ostrosky-Zeichner, Adam J Esbenshade, Michael L Nieder, Sarah Alexander, William J Steinbach, Ha Dang, Doojduen Villaluna, Lu Chen, Micah Skeens, Theoklis E Zaoutis, Lillian Sung, Brian T Fisher

Faculty, Staff and Student Publications

BACKGROUND: Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non-invasive biomarkers, such as the beta-D-glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta-D-glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post-HCT period.

METHODS: Weekly surveillance blood testing with the Fungitell® BDG assay was performed during the early post-HCT period in the context of a randomized trial of children, adolescents, and young adults undergoing allogeneic HCT allocated to triazole or caspofungin prophylaxis. Positivity was defined at …

Assessment Of Symptom, Disability, And Financial Trajectories In Patients Hospitalized For Covid-19 At 6 Months, Andrew J Admon, Theodore J Iwashyna, Lee A Kamphuis, Stephanie J Gundel, Sarina K Sahetya, Ithan D Peltan, Steven Y Chang, Jin H Han, Kelly C Vranas, Kirby P Mayer, Aluko A Hope, Sarah E Jolley, Ellen Caldwell, Max L Monahan, Katrina Hauschildt, Samuel M Brown, Neil R Aggarwal, B Taylor Thompson, Catherine L Hough

Faculty, Staff and Student Publications

IMPORTANCE: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited.

OBJECTIVE: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization.

DESIGN, SETTING, AND PARTICIPANTS: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization …

Profiling Human Pathogenic Repeat Expansion Regions By Synergistic And Multi-Level Impacts On Molecular Connections, Cong Fan, Ken Chen, Yukai Wang, Edward V Ball, Peter D Stenson, Matthew Mort, Albino Bacolla, Hildegard Kehrer-Sawatzki, John A Tainer, David N Cooper, Huiying Zhao

Faculty, Staff and Student Publications

Whilst DNA repeat expansions cause numerous heritable human disorders, their origins and underlying pathological mechanisms are often unclear. We collated a dataset comprising 224 human repeat expansions encompassing 203 different genes, and performed a systematic analysis with respect to key topological features at the DNA, RNA and protein levels. Comparison with controls without known pathogenicity and genomic regions lacking repeats, allowed the construction of the first tool to discriminate repeat regions harboring pathogenic repeat expansions (DPREx). At the DNA level, pathogenic repeat expansions exhibited stronger signals for DNA regulatory factors (e.g. H3K4me3, transcription factor-binding sites) in exons, promoters, 5'UTRs and …

Fucosylation Of Hla-Drb1 Regulates Cd4+ T Cell-Mediated Anti-Melanoma Immunity And Enhances Immunotherapy Efficacy, Daniel K Lester, Chase Burton, Alycia Gardner, Patrick Innamarato, Krithika Kodumudi, Qian Liu, Emma Adhikari, Qianqian Ming, Daniel B Williamson, Dennie T Frederick, Tatyana Sharova, Michael G White, Joseph Markowitz, Biwei Cao, Jonathan Nguyen, Joseph Johnson, Matthew Beatty, Andrea Mockabee-Macias, Matthew Mercurio, Gregory Watson, Pei-Ling Chen, Susan Mccarthy, Carlos Moransegura, Jane Messina, Kerry L Thomas, Lancia Darville, Victoria Izumi, John M Koomen, Shari A Pilon-Thomas, Brian Ruffell, Vincent C Luca, Robert S Haltiwanger, Xuefeng Wang, Jennifer A Wargo, Genevieve M Boland, Eric K Lau

Faculty, Staff and Student Publications

Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs); thus, effective strategies to safely increase itICs are needed. We report that dietary administration of l-fucose induces fucosylation and cell surface enrichment of the major histocompatibility complex (MHC)-II protein HLA-DRB1 in melanoma cells, triggering CD4+ T cell-mediated increases in itICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance …

A 24-Month Updated Analysis Of The Comparative Effectiveness Of Zuma-5 (Axi-Cel) Vs Scholar-5 External Control In Relapsed/Refractory Follicular Lymphoma, M Lia Palomba, Paola Ghione, Anik R Patel, Myrna Nahas, Sara Beygi, Anthony J Hatswell, Steve Kanters, Eve H Limbrick-Oldfield, Sally W Wade, Markqayne D Ray, Jessica Owen, Sattva S Neelapu, John Gribben, John Radford, Sabela Bobillo

Faculty, Staff and Student Publications

Background: In the ZUMA-5 trial (Clinical trials identification: NCT03105336), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data.

Research design and methods: The SCHOLAR-5 cohort is comprised of r/r FL patients who initiated ≥3rd line of therapy after July 2014 and meeting ZUMA-5 eligibility criteria. Groups were balanced for patient characteristics through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. The overall response …

Sox17: A Highly Sensitive And Specific Immunomarker For Ovarian And Endometrial Carcinomas, Xudong Zhang, Jun Yao, Na Niu, Xiaoran Li, Yan Liu, Lei Huo, Elizabeth D Euscher, Huamin Wang, Diana Bell, Anil K Sood, Guoliang Wang, Barrett C Lawson, Preetha Ramalingam, Anais Malpica, Aysegul A Sahin, Qingqing Ding, Jinsong Liu

Faculty, Staff and Student Publications

PAX8 is the most commonly used immunomarker to link a carcinoma to the gynecologic tract; however, it lacks specificity. Through mining The Cancer Genome Atlas mRNA expression profile data, we identified SOX17 as a potential specific marker at the mRNA level for gynecologic tumors. To evaluate the utility of this marker in the identification of the gynecologic origin of a given carcinoma, we performed immunochemical staining in a large cohort of ovarian and endometrial cancer cases (n = 416), together with a large cohort of solid tumors from other organs (n = 1544) in tissue microarrays. Similar to PAX8, SOX17 …

Erratum: "Aapm Task Group Report 303 Endorsed By The Abs: Mri Implementation In Hdr Brachytherapy-Considerations From Simulation To Treatment", Joann Prisciandaro, Jacqueline Esthappan Zoberi, Gil'ad Cohen, Yusung Kim, Perry Johnson, Eric Paulson, William Song, Ken-Pin Hwang, Beth Erickson, Sushil Beriwal, Christian Kirisits, Firas Mourtada

Faculty, Staff and Student Publications

No abstract provided.

Hematopoietic Cell Transplantation In The Management Of Myelodysplastic Syndrome: An Evidence-Based Review From The American Society For Transplantation And Cellular Therapy Committee On Practice Guidelines, Zachariah Defilipp, Stefan O Ciurea, Corey Cutler, Marie Robin, Erica D Warlick, Ryotaro Nakamura, Andrew M Brunner, Bhagirathbhai Dholaria, Alison R Walker, Nicolaus Kröger, Nelli Bejanyan, Ehab Atallah, Roni Tamari, Melhem M Solh, Mary-Elizabeth Percival, Marcos De Lima, Bart Scott, Betul Oran, Guillermo Garcia-Manero, Mehdi Hamadani, Paul Carpenter, Amy E Dezern

Faculty, Staff and Student Publications

The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and critically evaluated in the context of the evidence. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of MDS experts comprising transplantation and nontransplantation physicians developed consensus treatment recommendations. This review summarizes the standard MDS indications for HCT and addresses areas of controversy. Recent prospective trials have confirmed that allogeneic HCT confers survival benefits in patients with advanced or high-risk MDS …

Structural Valve Deterioration After Self-Expanding Transcatheter Or Surgical Aortic Valve Implantation In Patients At Intermediate Or High Risk., Daniel O'Hair, Steven J Yakubov, Kendra J Grubb, Jae K Oh, Saki Ito, G Michael Deeb, Nicolas M Van Mieghem, David H Adams, Tanvir Bajwa, Neal S Kleiman, Stanley Chetcuti, Lars Søndergaard, Hemal Gada, Mubashir Mumtaz, John Heiser, William M Merhi, George Petrossian, Newell Robinson, Gilbert H L Tang, Joshua D Rovin, Stephen H Little, Renuka Jain, Sarah Verdoliva, Tim Hanson, Shuzhen Li, Jeffrey J Popma, Michael J Reardon

Heart and Vascular Articles

IMPORTANCE: The frequency and clinical importance of structural valve deterioration (SVD) in patients undergoing self-expanding transcatheter aortic valve implantation (TAVI) or surgery is poorly understood.

OBJECTIVE: To evaluate the 5-year incidence, clinical outcomes, and predictors of hemodynamic SVD in patients undergoing self-expanding TAVI or surgery.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis pooled data from the CoreValve US High Risk Pivotal (n = 615) and SURTAVI (n = 1484) randomized clinical trials (RCTs); it was supplemented by the CoreValve Extreme Risk Pivotal trial (n = 485) and CoreValve Continued Access Study (n = 2178). Patients with severe aortic valve …

Energy Intake At The Intersection Of The Clock And Ageing, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

Adverse Pregnancy Outcomes And Long Term Risk Of Ischemic Heart Disease In Mothers: National Cohort And Co-Sibling Study, Casey Crump, Jan Sundquist, Mary Ann Mclaughlin, Siobhan M Dolan, Usha Govindarajulu, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

OBJECTIVE: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers.

DESIGN: National cohort study.

SETTING: Sweden.

PARTICIPANTS: All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015.

MAIN OUTCOME MEASURES: The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy …

Spatiotemporal View Of Malignant Histogenesis And Macroevolution Via Formation Of Polyploid Giant Cancer Cells, Xiaoran Li, Yanping Zhong, Xudong Zhang, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand how malignant tumors develop, we tracked cell membrane, nuclear membrane, spindle, and cell cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single cells underwent traditional mitosis to generate tissue with uniform nuclear size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, nuclear fusion, and karyokinesis without cytokinesis. PGCCs underwent restitution multipolar endomitosis, nuclear fragmentation, and micronuclei formation to increase nuclear contents and heterogeneity. At the cellular level, the development of PGCCs was associated with forming transient intracellular cells, termed fecundity cells. The fecundity cells …

The Ra-Be-Real Multinational, Prospective, Observational Study In Patients With Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, Or Biologic Disease-Modifying Therapies: A 6-Month Interim Analysis, Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Pedro Lopez-Romero, Walid Fakhouri, Inmaculada De La Torre, Liliana Zaremba-Pechmann, Thorsten Holzkämper, Bruno Fautrel

Faculty, Staff and Student Publications

INTRODUCTION: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment.

METHODS: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any …

Incidence Of Postoperative Complications Following Pancreatectomy For Pancreatic Cystic Lesions Or Pancreatic Cancer, Eileen C Donovan, Laura R Prakash, Yi-Ju Chiang, Morgan L Bruno, Jessica E Maxwell, Naruhiko Ikoma, Ching-Wei D Tzeng, Matthew H G Katz, Jeffrey E Lee, Michael P Kim

Faculty, Staff and Student Publications

Background: In contrast to pancreatic ductal adenocarcinoma (PDAC), the risks of pancreatectomy for mucinous pancreatic cysts (MCs) are balanced against the putative goal of removing potentially malignant tumors. Despite undergoing similar operations, different rates of perioperative complications and morbidity between MC and PDAC patient populations may affect recommendations for resection. We therefore sought to compare the rates of postoperative complications between patients undergoing pancreatectomies for MCs or PDAC.

Methods: A prospectively maintained institutional database was used to identify patients who underwent surgical resection for MCs or PDAC from July 2011 to August 2019. Patient demographics, complications, and perioperative data were …

Phase Ii Trial Of Weekly Erlotinib Dosing To Reduce Duodenal Polyp Burden Associated With Familial Adenomatous Polyposis, N Jewel Samadder, Nathan Foster, Ryan P Mcmurray, Carol A Burke, Elena Stoffel, Priyanka Kanth, Rohit Das, Marcia Cruz-Correa, E Vilar, Gautam Mankaney, Navtej Buttar, Selvi Thirumurthi, Danielle K Turgeon, Michael Sossenheimer, Michelle Westover, Ellen Richmond, Asad Umar, Gary Della'zanna, Luz M Rodriguez, Eva Szabo, David Zahrieh, Paul J Limburg

Faculty, Staff and Student Publications

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate.

Objective: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP.

Design, setting and participants: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres.

Exposures: Participants self-administered 350 mg of erlotinib …

Paxlovid-Induced Tacrolimus Toxicity In The Treatment Of Covid-19: A Case Report., Stephanie Michael, Rachel Heilbronner, Christopher M Lloyd, Howard W Levitin

Pharmacy Articles

Paxlovid^TM (nirmaltrelvir/ritonavir) received emergency use authorization from the Food and Drug Administration (FDA) in December 2021 to treat coronavirus disease 2019 (COVID-19). Given the actions of Paxlovid on cytochrome P450-3A4 (CYP3A4) enzymes, it is imperative to check for potential drug-drug interactions before prescribing. We describe a case in which the common emergency department presentation of generalized weakness was found to be caused by interactions between Paxlovid and a patient's home medications resulting in tacrolimus toxicity.

Outpatient Therapies For Covid-19., Michelle Boysel, Christian Vaflor, Dan Sheridan

Pharmacy Articles

The world's healthcare systems were forced to evaluate evolving evidence regarding the COVID-19 pandemic quickly. The technology used to improve patient outcomes and survival is rapidly evolving along with the virus. This article discusses new therapies developed to treat and prevent COVID-19 in qualifying patients.

Recruitment In Acute Stroke Trials: Challenges And Potential Solutions, Joseph P Broderick, Yasmin N Aziz, Opeolu M Adeoye, James C Grotta, Andrew M Naidech, Andrew D Barreto, Colin P Derdeyn, Heidi J Sucharew, Jordan J Elm, Pooja Khatri

Faculty, Staff and Student Publications

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of …

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …

Why Does The X Chromosome Lag Behind Autosomes In Gwas Findings?, Ivan P Gorlov, Christopher I Amos

Faculty, Staff and Students Publications

The X-chromosome is among the largest human chromosomes. It differs from autosomes by a number of important features including hemizygosity in males, an almost complete inactivation of one copy in females, and unique patterns of recombination. We used data from the Catalog of Published Genome Wide Association Studies to compare densities of the GWAS-detected SNPs on the X-chromosome and autosomes. The density of GWAS-detected SNPs on the X-chromosome is 6-fold lower compared to the density of the GWAS-detected SNPs on autosomes. Differences between the X-chromosome and autosomes cannot be explained by differences in the overall SNP density, lower X-chromosome coverage …