Biomedical Informatics Commons^™

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 …

Cost Of Failure To Achieve Textbook Outcomes: Association Of Insurance Type With Outcomes And Cumulative Cost For Inpatient Surgery, Michael A Jacobs, Jeongsoo Kim, Jasmine C Tetley, Susanne Schmidt, Bradley B Brimhall, Virginia Mika, Chen-Pin Wang, Laura S Manuel, Paul Damien, Paula K Shireman

Faculty, Staff and Student Publications

Background: Surgical outcome/cost analyses typically focus on single outcomes and do not include encounters beyond the index hospitalization.

Study design: This cohort study used NSQIP (2013-2019) data with electronic health record and cost data risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status, and operative stress assessing cumulative costs of failure to achieve textbook outcomes defined as absence of 30-day Clavien-Dindo level III and IV complications, emergency department visits/observation stays (EDOS), and readmissions across insurance types (private, Medicare, Medicaid, uninsured). Return costs were defined as costs of all 30-day emergency department visits/observation stays and readmissions.

Results: Cases were performed …

Reply To J Widder, Steven J Chmura, Wendy A Woodward, Julia R White

Faculty, Staff and Student Publications

No abstract provided.

Optimized Decision Support For Selection Of Transoral Robotic Surgery Or (Chemo)Radiation Therapy Based On Posttreatment Swallowing Toxicity, Mehdi Hemmati, Carly Barbon, Abdallah S R Mohamed, Lisanne V Van Dijk, Amy C Moreno, Neil D Gross, Ryan P Goepfert, Stephen Y Lai, Katherine A Hutcheson, Andrew J Schaefer, Clifton D Fuller, Md Anderson Head And Neck Cancer Symptom Working Group Affiliations Expand

Faculty, Staff and Student Publications

BACKGROUND: A primary goal in transoral robotic surgery (TORS) for oropharyngeal squamous cell cancer (OPSCC) survivors is to optimize swallowing function. However, the uncertainty in the outcomes of TORS including postoperative residual positive margin (PM) and extranodal extension (ENE), may necessitate adjuvant therapy, which may cause significant swallowing toxicity to survivors.

METHODS: A secondary analysis was performed on a prospective registry data with low- to intermediate-risk human papillomavirus-related OPSCC possibly resectable by TORS. Decision trees were developed to model the uncertainties in TORS compared with definitive radiation therapy (RT) and chemoradiation therapy (CRT). Swallowing toxicities were measured by Dynamic Imaging …

Long-Term Effects Of Obstructive Sleep Apnea And Its Treatment On Open-Angle Glaucoma: A Big-Data Cohort Study, Tae-Eun Lee, Jong Seung Kim, Sang Woo Yeom, Min Gyu Lee, Jong Hwan Lee, Haeng-Jin Lee

Faculty, Staff and Student Publications

STUDY OBJECTIVES: The relationship between open-angle glaucoma (OAG) and obstructive sleep apnea (OSA) is unclear. The long-term risk for OAG after OSA diagnosis has not been investigated. Therefore, we assessed the risk for OAG among patients with OSA over a 12-year follow-up period using nationwide, population-based data.

METHODS: The OSA group was randomly selected from among 3.5 million individuals registered with the National Health Insurance Service. The non-OSA group was obtained through propensity score matching considering several variables. The primary endpoint was glaucoma diagnosis.

RESULTS: The OSA and non-OSA groups both included 6,369 individuals. The overall hazard ratio for OAG …

Pyridoxamine Treatment Ameliorates Large Artery Stiffening And Cerebral Artery Endothelial Dysfunction In Old Mice, Emily H Reeve, Elise K Kronquist, Julia R Wolf, Byron Lee, Aleena Khurana, Hanson Pham, Abigail E Cullen, Jessica A Peterson, Antonio Meza, R Colton Bramwell, Laura Villasana, Daniel R Machin, Grant D Henson, Ashley E Walker

Faculty, Staff and Student Publications

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old …

Dual Beam-Current Transformer Design For Monitoring And Reporting Of Electron Ultra-High Dose Rate (Flash) Beam Parameters, Kevin Liu, Allison Palmiero, Nitish Chopra, Brett Velasquez, Ziyi Li, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

PURPOSE: To investigate the usefulness and effectiveness of a dual beam-current transformer (BCTs) design to monitor and record the beam dosimetry output and energy of pulsed electron FLASH (eFLASH) beams in real-time, and to inform on the usefulness of this design for future eFLASH beam control.

METHODS: Two BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam …

E Pluribus Unum: Prospective Acceptability Benchmarking From The Contouring Collaborative For Consensus In Radiation Oncology Crowdsourced Initiative For Multiobserver Segmentation, Diana Lin, Kareem A Wahid, Benjamin E Nelms, Renjie He, Mohammed A Naser, Simon Duke, Michael V Sherer, John P Christodouleas, Abdallah S R Mohamed, Michael Cislo, James D Murphy, Clifton D Fuller, Erin F Gillespie

Faculty, Staff and Student Publications

Purpose: Contouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. An obstacle to artificial intelligence (AI) development is the paucity of multiexpert datasets; consequently, we sought to characterize whether aggregate segmentations generated from multiple nonexperts could meet or exceed recognized expert agreement.

Approach: Participants who contoured ≥1 region of interest (ROI) for the breast, sarcoma, head and neck (H&N), gynecologic (GYN), or gastrointestinal (GI) cases were identified as a nonexpert or recognized expert. Cohort-specific ROIs were combined into single simultaneous truth and performance level estimation (STAPLE) consensus segmentations. …

Gender Bias In The Evaluation Of Surgical Performance: Results Of A Prospective Randomized Trial, Mara B Antonoff, Hope Feldman, Jessica G Y Luc, Paula I Iaeger, M Laura Rubin, Liang Li, Ara A Vaporciyan

Faculty, Staff and Student Publications

Objective: The study aims to determine the influence of trainee gender on assessments of coronary anastomosis performance.

Summary of background data: Understanding the impact of gender bias on the evaluation of trainees may enable us to identify and utilize assessment tools that are less susceptible to potential bias.

Methods: Cardiothoracic surgeons were randomized to review the video performance of trainees who were described by either male or female pronouns. All participants viewed the same video of a coronary anastomosis and were asked to grade technique using either a Checklist or Global Rating Scale (GRS). Effect of trainee gender on scores …

American Radium Society (Ars) Appropriate Use Criteria (Auc) For Extrahepatic Cholangiocarcinoma, Leila T Tchelebi, Krishan R Jethwa, Anna T Levy, Christopher J Anker, Timothy Kennedy, Elliot Grodstein, Christopher L Hallemeier, Salma K Jabbour, Ed Kim, Rachit Kumar, Percy Lee, William Small, Vonetta M Williams, Navesh Sharma, Suzanne Russo

Faculty, Staff and Student Publications

Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic …

Predictors Of Oncologic Outcome In Patients Receiving Phase I Investigational Therapy For Recurrent Or Metastatic Cervical Cancer, Ji Son, Heather Y Lin, Siqing Fu, Amadeo B Biter, Ecaterina E Dumbrava, Daniel D Karp, Aung Naing, Shubham Pant, Sarina A Piha-Paul, Jordi Rodon, Vivek Subbiah, Apostolia M Tsimberidou, Timothy A Yap, Michael M Frumovitz, Amir A Jazaeri, Pedro T Ramirez, Shannon N Westin, Ying Yuan, Funda Meric-Bernstam, David S Hong

Faculty, Staff and Student Publications

INTRODUCTION: We aimed to identify clinical, pathologic, and treatment factors that are predictive of response and survival in patients with cervical cancer referred to phase I clinical trials.

METHODS: Patients with cervical cancer who received at least one dose of a phase I investigational agent at our institution between 2014 and 2022 were included. The log-rank test was used to analyze differences in progression-free survival (PFS) and overall survival (OS), and multivariable regression analysis was performed.

RESULTS: We included 65 patients with a median age of 41 years (range, 20-74), 3 prior therapies (range, 1-7), and 67.7% squamous carcinoma. The …

Retrospective Evaluation Of The Role Of Gemcitabine-Docetaxel In Well-Differentiated And Dedifferentiated Liposarcoma, Prapassorn Thirasastr, Heather Lin, Behrang Amini, Wei-Lien Wang, Jeffrey M Cloutier, Elise F Nassif, Emily Z Keung, Christina L Roland, Barry Feig, Dejka Araujo, Robert S Benjamin, Anthony P Conley, John A Livingston, Joseph Ludwig, Shreyaskumar Patel, Ravin Ratan, Vinod Ravi, Maria Alejandra Zarzour, Xiao Zhou, Neeta Somaiah

Faculty, Staff and Student Publications

OBJECTIVE: Well-differentiated (WDLPS) and dedifferentiated liposarcoma (DDLPS) account for the majority of liposarcomas. Although gemcitabine-docetaxel is used as second-line treatment in soft tissue sarcomas, its efficacy in WDLPS/DDLPS is not established. This study retrospectively analyzed the efficacy of gemcitabine regimens in WDLPS/DDLPS.

METHODS: All patients with WDLPS or DDLPS who received gemcitabine-based chemotherapy at our institution between September 2002 and January 2021 were included. Response was evaluated by an independent radiologist using RECIST 1.1. The Kaplan-Meier method was used to estimate distributions of survival outcomes and log-rank tests were used to compare survival outcomes between subgroups.

RESULTS: Sixty-five WDLPS/DDLPS patients …

Malignant Transformation By Oncogenic K-Ras Requires Idh2-Mediated Reductive Carboxylation To Promote Glutamine Utilization, Rui Liu, Panpan Liu, Huichang Bi, Jianhua Ling, Huiqin Zhang, Mingquan Zhang, Yumin Hu, Paul J Chiao, Peng Huang, Jinyun Liu

Faculty, Staff and Student Publications

No abstract provided.

Mental Health, War Trauma, And Migration: The Contribution Of Comprehensive Psychoneuroendocrinology, Robert Dantzer

Faculty, Staff and Student Publications

No abstract provided.

Automatic Diagnosis Of Late-Life Depression By 3d Convolutional Neural Networks And Cross-Sample Entropy Analysis From Resting-State Fmri, Chemin Lin, Shwu-Hua Lee, Chih-Mao Huang, Guan-Yen Chen, Wei Chang, Ho-Ling Liu, Shu-Hang Ng, Tatia Mei-Chun Lee, Shun-Chi Wu

Faculty, Staff and Student Publications

Resting-state fMRI has been widely used in investigating the pathophysiology of late-life depression (LLD). Unlike the conventional linear approach, cross-sample entropy (CSE) analysis shows the nonlinear property in fMRI signals between brain regions. Moreover, recent advances in deep learning, such as convolutional neural networks (CNNs), provide a timely application for understanding LLD. Accurate and prompt diagnosis is essential in LLD; hence, this study aimed to combine CNN and CSE analysis to discriminate LLD patients and non-depressed comparison older adults based on brain resting-state fMRI signals. Seventy-seven older adults, including 49 patients and 28 comparison older adults, were included for fMRI …

Clinical Features Associated With Outcomes And Biomarker Analysis Of Dabrafenib Plus Trametinib Treatment In Patients With Braf-Mutant Melanoma Brain Metastases, James S Wilmott, Hussein Tawbi, Johnathan A Engh, Nduka M Amankulor, Brindha Shivalingam, Hiya Banerjee, Ismael A Vergara, Hansol Lee, Peter A Johansson, Peter M Ferguson, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Lisa H Butterfield, Richard A Scolyer, John M Kirkwood, Georgina V Long, Michael A Davies

Faculty, Staff and Student Publications

PURPOSE: This study aimed to identify baseline clinical features associated with the outcomes of patients enrolled in the COMBI-MB phase II study of dabrafenib and trametinib treatment in patients with V600 BRAF-mutant metastatic melanoma with melanoma brain metastases (MBM). Exploratory biomarker analysis was also conducted as part of the synergistic COMBI-BRV trial (BRV116521), to identify molecular and immunologic changes associated with dabrafenib in MBMs and extracranial metastases (ECM).

PATIENTS AND METHODS: Post hoc analysis was performed for baseline features of patients (n = 125) enrolled in COMBI-MB. Analyses were performed to identify baseline clinical features associated with intracranial response rate …

Smart Start: Rituximab, Lenalidomide, And Ibrutinib In Patients With Newly Diagnosed Large B-Cell Lymphoma, Jason Westin, R Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Hun Ju Lee, Luis Fayad, Loretta Nastoupil, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy Mcdonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W Scott, Christopher R Flowers, Sattva Neelapu, Michael R Green

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset.

METHODS: We enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m

RESULTS: The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. …

A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci For Oral Cancer In Taiwan, Da-Tian Bau, Ting-Yuan Liu, Chia-Wen Tsai, Wen-Shin Chang, Jian Gu, Jai-Sing Yang, Liang-Chun Shih, Fuu-Jen Tsai

Faculty, Staff and Student Publications

Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The …

The Gdf15-Gfral Axis Mediates Chemotherapy-Induced Fatigue In Mice, Brandon Chelette, Chinenye L Chidomere, Robert Dantzer

Faculty, Staff and Student Publications

Cancer-related fatigue is defined as a distressing persistent subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning. This form of fatigue is highly prevalent during cancer treatment and in some patients, it can persist for years after treatment has ended. An understanding of the mechanisms that drive cancer-related fatigue is still lacking, which hampers the identification of effective treatment options. Various chemotherapeutic agents including cisplatin are known to induce mitochondrial dysfunction and this effect is known to mediate chemotherapy-induced peripheral …

Tissue-Resident Memory T Cells Trigger Rapid Exudation And Local Antibody Accumulation, Pamela C Rosato, Sahar Lotfi-Emran, Vineet Joag, Sathi Wijeyesinghe, Clare F Quarnstrom, Hanna N Degefu, Rebecca Nedellec, Jason M Schenkel, Lalit K Beura, Lars Hangartner, Dennis R Burton, David Masopust

Faculty, Staff and Student Publications

Adaptive immunity is didactically partitioned into humoral and cell-mediated effector mechanisms, which may imply that each arm is separate and does not function together. Here, we report that the activation of CD8+ resident memory T cells (TRM) in nonlymphoid tissues triggers vascular permeability, which facilitates rapid distribution of serum antibodies into local tissues. TRM reactivation was associated with transcriptional upregulation of antiviral signaling pathways as well as Fc receptors and components of the complement cascade. Effects were local, but evidence is presented that TRM in brain and reproductive mucosa are both competent to induce rapid antibody exudation. TRM reactivation in …

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 …

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.

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), …

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 …

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 …

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 …

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 …

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 …