Digital Commons Network^™

Eosinophils Protect Against Acetaminophen-Induced Liver Injury Through Cyclooxygenase-Mediated Il-4/Il-13 Production, Long Xu, Yang Yang, Jiali Jiang, Yankai Wen, Jong-Min Jeong, Christoph Emontzpohl, Constance L Atkins, Kangho Kim, Elizabeth A Jacobsen, Hua Wang, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: A better understanding of the underlying mechanism of acetaminophen (APAP)-induced liver injury (AILI) remains an important endeavor to develop therapeutic approaches. Eosinophils have been detected in liver biopsies of patients with APAP overdose. We recently demonstrated a profound protective role of eosinophils against AILI; however, the molecular mechanism had not been elucidated.

APPROACH AND RESULTS: In agreement with our previous data from experiments using genetic deletion of eosinophils, we found that depletion of eosinophils in wild-type (WT) mice by an anti-IL-15 antibody resulted in exacerbated AILI. Moreover, adoptive transfer of eosinophils significantly reduced liver injury and mortality …

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. …

State-Of-The-Art In Carbides/Carbon Composites For Electromagnetic Wave Absorption, Jingjing Huang, Hydia Puente, Nancy E Wareing, Minghua Wu, Maureen D Mayes, Harry Karmouty-Quintana, Shervin Assassi, Tingting W Mills

Faculty, Staff and Student Publications

Fibrosis of the skin and internal organs is a hallmark of systemic sclerosis (SSc). Although the pathogenesis of SSc is poorly understood, increasing evidence suggests that interleukins (IL)-4 and - 13 contribute to the pathogenesis of skin fibrosis by promoting collagen production and myofibroblast differentiation. Signal transducers and activators of transcription 6 (STAT6) is one of the most important downstream transcription factors activated by both IL-4 and IL-13. However, it is not completely understood whether STAT6 plays a role during the pathogenesis of skin fibrosis in SSc. In this study, we observed increased STAT6 phosphorylation in fibrotic skin samples collected …

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 …

Lichenoid Drug Eruption Induced By Erenumab, Meryl Musicante, Yamila Goenaga-Vázquez, Natasha Klimas

Faculty, Staff and Student Publications

No abstract provided.

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 …

Emergency Department Virtual Happy Hour: A Novel Approach To Peer Group Support During A Pandemic, Adeola A Kosoko, Shabana Walia, Ryan Huebinger

Faculty, Staff and Student Publications

Introduction Communities responded to the coronavirus disease 2019 (COVID-19) pandemic with mandatory social-distancing regulations. Pandemic and disaster research shows that social isolation can often cause negative emotions and medical provider burnout. The primary objective of this study was to create and evaluate a novel wellness program, the Happy Hour Wellness Initiative (HHWI), based on peer support group concepts to foster resilience for emergency healthcare providers in response to a novel disaster. Methods The study was performed at a large emergency department with physicians, advanced practice providers, and staff invited to attend weekly "virtual happy hour" sessions. Participants individually opted into …

Expression And Functions Of Transient Receptor Potential Channels In Liver Diseases, Wenhui Wang, Pengyu Liu, Yalin Zhang, Li Yan, Michael X Zhu, Jin Wang, Ye Yu

Faculty, Staff and Student Publications

Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental …

Percutaneous Revascularization For The Treatment Of Refractory Digital Ischemia In Systemic Sclerosis, Lily A Romero-Karam, Kevin A Honan, Salman A Arain, Maureen D Mayes

Faculty, Staff and Student Publications

OBJECTIVE: The objective of this study is to explore the role of adjunctive percutaneous revascularization of the hand in the management of patients with systemic sclerosis-associated refractory digital ischemia.

METHODS: We present our initial experience of using percutaneous upper extremity interventions to treat patients with systemic sclerosis and symptomatic Raynaud's phenomenon who presented with either refractory digital ischemia or non-healing ulcers. We discuss patient characteristics, procedural findings, and short-term clinical outcomes of these interventions.

RESULTS: We performed 14 interventions in 6 patients with non-healing digital ulcers or refractory ischemia secondary to systemic sclerosis. Angioplasty was performed at or below the …

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 …

Effects Of Subnormothermic Regulated Hepatic Reperfusion On Mitochondrial And Transcriptomic Profiles In A Porcine Model, Joohyun Kim, Michael A Zimmerman, Woo Young Shin, Brent T Boettcher, Ju-Seog Lee, Jong-In Park, Muhammed Ali, Meiying Yang, Jyotsna Mishra, Catherine E Hagen, Joseph E Mcgraw, Angela Mathison, Harvey J Woehlck, Gwen Lomberk, Amadou K S Camara, Raul A Urrutia, David F Stowe, Johnny C Hong

Faculty, Staff and Student Publications

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model.

SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation.

METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), …

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 …

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.

A Complete Methyl-Lysine Binding Aromatic Cage Constructed By Two Domains Of Phf2, John R Horton, Jujun Zhou, Qin Chen, Xing Zhang, Mark T Bedford, Xiaodong Cheng

Faculty, Staff and Student Publications

The N-terminal half of PHF2 harbors both a plant homeodomain (PHD) and a Jumonji domain. The PHD recognizes both histone H3 trimethylated at lysine 4 and methylated nonhistone proteins including vaccinia-related kinase 1 (VRK1). The Jumonji domain erases the repressive dimethylation mark from histone H3 lysine 9 (H3K9me2) at select promoters. The N-terminal amino acid sequences of H3 (AR2TK4) and VRK1 (PR2VK4) bear an arginine at position 2 and lysine at position 4. Here, we show that the PHF2 N-terminal half binds to H3 and VRK1 peptides containing K4me3, with dissociation constants (KD values) of 160 nM and 42 nM, …

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 …

Hetrombopag Plus Porcine Atg And Cyclosporine For The Treatment Of Aplastic Anaemia: Early Outcomes Of A Prospective Pilot Study, Wenrui Yang, Xin Zhao, Xu Liu, Youzhen Xiong, Huihui Fan, Li Zhang, Jianping Li, Lei Ye, Kang Zhou, Yuan Li, Yang Yang, Guangxin Peng, Liping Jing, Fengkui Zhang

Faculty, Staff and Student Publications

Hetrombopag, a small molecular thrombopoietin-receptor agonist, has shown encouraging efficiency in immunosuppressive therapy refractory or relapsed severe aplastic anaemia. To investigate the response rate of hetrombopag combined with IST as first-line treatment, we designed a prospective pilot study including 32 patients with SAA treated with anti-human T lymphocyte porcine immunoglobulin (p-ATG), cyclosporine, and hetrombopag. In addition, 96 patients with SAA treated with p-ATG and cyclosporine alone were matched as controls. In total, 21.9% of patients treated with hetrombopag achieved complete response (CR) at 3 months, while 5.2% of patients achieved CR in the control group (P = 0.005). At …

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 …

Vip152 Is A Selective Cdk9 Inhibitor With Pre-Clinical In Vitro And In Vivo Efficacy In Chronic Lymphocytic Leukemia, Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Katie Williams, Shelley Orwick, Janani Ravikrishnan, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J Johnson, Melanie M Frigault, Joy M Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C Byrd, Rosa Lapalombella

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in …