Digital Commons Network^™

Evaluation Of The Efficacy Of The Anti-Ulcer Oral Mucosal Protective Agent Radoralex® In The Prevention And Treatment Of Radiation-Induced Oral Mucosal Reactions Induced During Treatment Of Nasopharyngeal Carcinoma, Jun Yin, Jirui Xie, Jiawei Lin, Chengyin Weng, Shun Lu, Peng Xu, Shuo Zhang, Cheng Luo, Yecai Huang, Lu Li, Jinyi Lang, Mei Feng

Student and Faculty Publications

The aim of this study was to evaluate the efficacy and safety of antiulcer oral mucosal protectant-RADoralex® in the prevention and treatment of radiation-induced oral mucosal reactions elicited during intensity-modulated radiation therapy (IMRT). for locally advanced nasopharyngeal carcinoma (NPC). A total of 90 patients with locally advanced NPC who developed post-treatment grade 1 oral mucositis were selected for this study. They were randomly assigned to the experimental group (n = 44) treated by mouth rinsing with the RADoralex® during radiochemotherapy and the control group (n = 43) treated by mouth rinsing with sodium bicarbonate solution, and the patients’ oral mucosal …

The Impact Of Vitamin A Deficiency On Tuberculosis Progression, Brendan K Podell, Omowunmi Aibana, Chuan-Chin Huang, James E Dilisio, Macallister C Harris, David F Ackart, Kody Armann, Alexander Grover, Patrice Severe, Marc Antoine Jean Juste, Kathryn Dupnik, Randall J Basaraba, Megan B Murray

Faculty and Staff Publications

BACKGROUND: Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression.

METHODS: We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of …

High-Frequency Ultrasound In Patients With Seronegative Rheumatoid Arthritis, Junkui Wang, Miao Wang, Qinghua Qi, Zhibin Wu, Jianguo Wen

Student and Faculty Publications

This study aimed to investigate the value of high-frequency ultrasound (HFUS) in differentiation of the seronegative rheumatoid arthritis (SNRA) and osteoarthritis (OA) and in the diagnosis of SNRA. 83 patients diagnosed with SNRA (SNRA group) and 40 diagnosed with OA (OA group) who received HFUS were retrospectively analyzed. The grayscale (GS) scores, power Doppler (PD) scores, and bone erosion (BE)scores were recorded, and added up to calculate the total scores of US variables. The correlations of the total scores of US variables with the 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were analyzed. The …

Fulminant Lung Fibrosis In Non-Resolvable Covid-19 Requiring Transplantation, Soma S K Jyothula, Andrew Peters, Yafen Liang, Weizhen Bi, Pooja Shivshankar, Simon Yau, Puneet S Garcha, Xiaoyi Yuan, Bindu Akkanti, Scott Collum, Nancy Wareing, Rajarajan A Thandavarayan, Fernando Poli De Frias, Ivan O Rosas, Bihong Zhao, L Maximilian Buja, Holger K Eltzschig, Howard J Huang, Harry Karmouty-Quintana

Student and Faculty Publications

BACKGROUND: Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19.

METHODS: Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We …

Consensus Subtypes Of Hepatocellular Carcinoma Associated With Clinical Outcomes And Genomic Phenotypes, Sung Hwan Lee, Sun Young Yim, Yun Seong Jeong, Qi-Xiang Li, Sang-Hee Kang, Bo Hwa Sohn, Shwetha V Kumar, Ji-Hyun Shin, You Rhee Choi, Jae-Jun Shim, Hayeon Kim, Ji Hoon Kim, Shin Kim, Sheng Guo, Randy L Johnson, Ahmed Kaseb, Koo Jeong Kang, Yun Shin Chun, Hee Jin Jang, Byoung Gill Lee, Hyun Goo Woo, Min Jin Ha, Rehan Akbani, Lewis R Roberts, David A Wheeler, Ju-Seog Lee

Student and Faculty Publications

BACKGROUND AND AIMS: Although many studies revealed transcriptomic subtypes of HCC, concordance of the subtypes are not fully examined. We aim to examine a consensus of transcriptomic subtypes and correlate them with clinical outcomes.

APPROACH AND RESULTS: By integrating 16 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes. STM (STeM) is characterized by high stem cell features, vascular invasion, and poor prognosis. CIN (Chromosomal INstability) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity. BCM (Beta-Catenin with high Male …

Liver Injury After Sars-Cov-2 Vaccination: Features Of Immune-Mediated Hepatitis, Role Of Corticosteroid Therapy And Outcome, Cumali Efe, Anand V Kulkarni, Benedetta Terziroli Beretta-Piccoli, Bianca Magro, Albert Stättermayer, Mustafa Cengiz, Daniel Clayton-Chubb, Craig Lammert, Christine Bernsmeier, Özlem Gül, Fatima Higuera-De La Tijera, Margarita Anders, Ellina Lytvyak, Mete Akın, Tugrul Purnak, Rodrigo Liberal, Mirta Peralta, Berat Ebik, Serkan Duman, Nurhan Demir, Yasemin Balaban, Álvaro Urzua, Fernando Contreras, Maria Grazia Venturelli, Yılmaz Bilgiç, Adriana Medina, Marcos Girala, Fulya Günşar, Maria-Carlota Londoño, Theodoros Androutsakos, Ayelen Kisch, Alper Yurci, Fatih Güzelbulut, Yasir Furkan Çağın, Enver Avcı, Murat Akyıldız, Emine Kübra Dindar-Demiray, Murat Harputluoğlu, Rahul Kumar, Sanjaya K Satapathy, Manuel Mendizabal, Marcelo Silva, Stefano Fagiuoli, Stuart K Roberts, Neşe Karadağ Soylu, Ramazan Idilman, Eric M Yoshida, Aldo J Montano-Loza, George N Dalekos, Ezequiel Ridruejo, Thomas D Schiano, Staffan Wahlin

Faculty and Staff Publications

BACKGROUND AND AIMS: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series.

APPROACH AND RESULTS: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) …

A Cluster-Randomized Controlled Trial Of Automated Internet Weight-Loss Programs In Primary Care: Role Of Automated Provider Feedback, Deborah F Tate, Jennifer L Kraschnewski, Caitlin Martinez, Molly Diamond, Susan Veldheer, Kevin O Hwang, Erik B Lehman, Chengwu Yang, Christopher N Sciamanna

Faculty and Staff Publications

OBJECTIVE: Despite the high prevalence of obesity and associated health risks in the United States adult population, few primary care providers (PCPs) have time and training to provide weight-management counseling to their patients. This study aims to compare the effect of referral to a comprehensive automated digital weight-loss program, with or without provider email feedback, with usual care on weight loss in patients with overweight or obesity.

METHODS: A total of 550 adults (mean [SD], 51.4 [11.2] years, BMI = 35.1 [5.5] kg/m

RESULTS: Weight changes (mean [SE]) at 12 months were -0.92 (0.46), -3.68 (0.46), and -3.58 (0.48) kg …

Further Evidence That Arih1 Rare Variants Predispose To Thoracic Aortic Disease, Maura L Boerio, Nicole M Engelhardt, Sanmati Cuddapah, Jessica I Gold, Isabella C Marin, Amélie Pinard, Dongchuan Guo, Siddharth K Prakash, Dianna M Milewicz

Faculty and Staff Publications

No abstract provided.

Using Single Molecule Molecular Inversion Probes As A Cost-Effective, High-Throughput Sequencing Approach To Target All Genes And Loci Associated With Macular Diseases, Rebekkah J Hitti-Malin, Claire-Marie Dhaenens, Daan M Panneman, Zelia Corradi, Mubeen Khan, Anneke I Den Hollander, G Jane Farrar, Christian Gilissen, Alexander Hoischen, Maartje Van De Vorst, Femke Bults, Erica G M Boonen, Patrick Saunders, Susanne Roosing, Frans P M Cremers

Faculty and Staff Publications

Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 …

Patient Identification Of Diagnostic Safety Blindspots And Participation In "Good Catches" Through Shared Visit Notes, Sigall K Bell, Fabienne Bourgeois, Joe Dong, Alex Gillespie, Long H Ngo, Tom W Reader, Eric J Thomas, Catherine M Desroches

Faculty and Staff Publications

UNLABELLED: Policy Points Patients and families can identify clinically relevant errors, including "blindspots"-safety hazards that are difficult for clinicians or organizations to see. Health information transparency, including patient access to electronic visit notes, now federally mandated in the US and the subject of policy debate worldwide, creates a new opportunity to engage patients in diagnostic safety. However, not all patients access notes. Patient identification of blindspots in their notes underscores the need to systematically and equitably engage willing patients in safety, promote patient "good catches," and establish routine systems for patient feedback to help avoid preventable diagnostic errors and delays. …

Reproducing Statistics Performed In Published Randomized Controlled Trials, Naila H Dhanani, Oscar A Olavarria, Cynthia S Bell, Julie L Holihan, Mike K Liang

Student and Faculty Publications

INTRODUCTION: Randomized controlled trials (RCT) represent evidence at the lowest potential risk for bias. Clinicians in all specialties depend upon RCTs to guide patient care. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. Our aim was to confirm the statistical reproducibility of published RCTs.

METHODS: PubMed was searched using "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. The reproduced p-value from our analysis and the published p-value were compared. …

Association Of Patient Belief About Success Of Antibiotics For Appendicitis And Outcomes: A Secondary Analysis Of The Coda Randomized Clinical Trial, Writing Group For The Coda Collaborative, Irene Y Zhang, Emily C Voldal, Giana H Davidson, Joshua M Liao, Callie M Thompson, Wesley H Self, Lillian S Kao, Jill Cherry-Bukowiec, Krishnan Raghavendran, Amy H Kaji, Daniel A Deugarte, Eva Gonzalez, Katherine A Mandell, Kristen Ohe, Nicole Siparsky, Thea P Price, David C Evans, Jesse Victory, William Chiang, Alan Jones, Matthew E Kutcher, Hailie Ciomperlik, Mike K Liang, Heather L Evans, Brett A Faine, Miriam Neufeld, Sabrina E Sanchez, Anusha Krishnadasan, Bryan A Comstock, Patrick J Heagerty, Sarah O Lawrence, Sarah E Monsell, Erin E C Fannon, Larry G Kessler, David A Talan, David R Flum

Student and Faculty Publications

IMPORTANCE: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials.

OBJECTIVE: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial.

DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive …

Anti-Diabetic Effects Of Glp1 Analogs Are Mediated By Thermogenic Interleukin-6 Signaling In Adipocytes, Absalon D Gutierrez, Zhanguo Gao, Vala Hamidi, Liang Zhu, Karla Bermudez Saint Andre, Kayla Riggs, Monika Ruscheinsky, Hongyu Wang, Yongmei Yu, Charles Miller, Hernan Vasquez, Heinrich Taegtmeyer, Mikhail G Kolonin

Student and Faculty Publications

Mechanisms underlying anti-diabetic effects of GLP1 analogs remain incompletely understood. We observed that in prediabetic humans exenatide treatment acutely induces interleukin-6 (IL-6) secretion by monocytes and IL-6 in systemic circulation. We hypothesized that GLP1 analogs signal through IL-6 in adipose tissue (AT) and used the mouse model to test if IL-6 receptor (IL-6R) signaling underlies the effects of the GLP1-IL-6 axis. We show that liraglutide transiently increases IL-6 in mouse circulation and IL-6R signaling in AT. Metronomic liraglutide treatment resulted in AT browning and thermogenesis linked with STAT3 activation. IL-6-blocking antibody treatment inhibited STAT3 activation in AT and suppressed liraglutide-induced …

Effect Of Selective Decontamination Of The Digestive Tract On Hospital Mortality In Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial, The Suddicu Investigators For The Australian And New Zealand Intensive Care Society Clinical Trials Group, John A Myburgh, Ian M Seppelt, Fiona Goodman, Laurent Billot, Maryam Correa, Joshua S Davis, Anthony C Gordon, Naomi E Hammond, Jon Iredell, Qiang Li, Sharon Micallef, Jennene Miller, Jayanthi Mysore, Colman Taylor, Paul J Young, Brian H Cuthbertson, Simon R Finfer

Student and Faculty Publications

IMPORTANCE: Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain.

OBJECTIVE: To determine whether SDD reduces in-hospital mortality in critically ill adults.

DESIGN, SETTING, AND PARTICIPANTS: A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021.

INTERVENTIONS: ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a …

Self-Guided Smartphone Application To Manage Chronic Musculoskeletal Pain: A Randomized, Controlled Pilot Trial, Chao Hsing Yeh, Jennifer Kawi, Lauren Grant, Xinran Huang, Hulin Wu, Robin L Hardwicke, Paul J Christo

Faculty and Staff Publications

Objective: The goal of this study is to evaluate the feasibility and efficacy of an auricular point acupressure smartphone app (mAPA) to self-manage chronic musculoskeletal pain. Methods: A prospective, longitudinal, randomized, controlled pilot trial was conducted using a three-group design (self-guided mAPA (n = 14); in-person mAPA (n = 12); and control (n = 11)). The primary outcomes included physical function and pain intensity. Results: After a 4-week APA intervention, participants in the in-person mAPA group had improved physical function of 32% immediately post-intervention and 29% at the 1M follow-up. Participants in the self-guided mAPA group had …

Targeting The Eif2ak1 Signaling Pathway Rescues Red Blood Cell Production In Sf3b1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts, Vera Adema, Feiyang Ma, Rashmi Kanagal-Shamanna, Natthakan Thongon, Guillermo Montalban-Bravo, Hui Yang, Scott A Peslak, Feng Wang, Pamela Acha, Francesc Sole, Pamela Lockyer, Margherita Cassari, Jaroslaw P Maciejewski, Valeria Visconte, Irene Gañán-Gómez, Yuanbin Song, Carlos Bueso-Ramos, Matteo Pellegrini, Tuyet M Tan, Rafael Bejar, Jennifer S Carew, Stephanie Halene, Valeria Santini, Gheath Al-Atrash, Karen Clise-Dwyer, Guillermo Garcia-Manero, Gerd A Blobel, Simona Colla

Student and Faculty Publications

SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks of a specific MDS subtype, MDS with ringed sideroblasts (MDS-RS), which is characterized by the accumulation of erythroid precursors in the bone marrow and primarily affects the elderly population. Here, using single-cell technologies and functional validation studies of primary SF3B1-mutant MDS-RS samples, we show that SF3B1 mutations lead to the activation of the EIF2AK1 pathway in response to heme deficiency and that targeting this pathway rescues aberrant erythroid differentiation and enables the red blood cell maturation of MDS-RS erythroblasts. These data support the development of …

The Multiple Waves Of Covid-19 In Patients With Inflammatory Bowel Disease: A Temporal Trend Analysis, Gilaad G Kaplan, Fox E Underwood, Stephanie Coward, Manasi Agrawal, Ryan C Ungaro, Erica J Brenner, Richard B Gearry, Michele Kissous-Hunt, James D Lewis, Siew C Ng, Jean-Francois Rahier, Walter Reinisch, Flavio Steinwurz, Xian Zhang, Michael D Kappelman, Jean-Frederic Colombel

Faculty and Staff Publications

BACKGROUND: Cases of coronavirus disease 2019 (COVID-19) have emerged in discrete waves. We explored temporal trends in the reporting of COVID-19 in inflammatory bowel disease (IBD) patients.

METHODS: The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry of IBD patients diagnosed with COVID-19. The average percent changes (APCs) were calculated in weekly reported cases of COVID-19 during the periods of March 22 to September 12, September 13 to December 12, 2020, and December 13 to July 31, 2021.

RESULTS: Across 73 countries, 6404 cases of COVID-19 were reported in IBD patients. COVID-19 …

Ovarian Steroid Cell Tumors, Not Otherwise Specified: Analysis Of Nine Cases With A Literature Review, Mengyan Lin, Kechun Bao, Lingjia Lu, Shuhang Xu, Yun Liang, Xiaodong Cheng, Fenfen Wang

Student and Faculty Publications

BACKGROUND: Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS), are rare, with few large studies. The purpose of this study was to analyze the clinical features, prognosis, and treatment choices for these patients of different age groups.

METHODS: This was a retrospective study. We identified nine cases of ovarian steroid cell tumor, not otherwise specified, confirmed by post-operative histopathological examination, and analyzed clinical features, surgical procedures, and follow up outcomes. We also reviewed cases reports of ovarian steroid cell tumors, not otherwise specified.

RESULTS: A total of nine cases were included. The age range was 9-68 years (mean, 41.89 …

Stroke Genetics Informs Drug Discovery And Risk Prediction Across Ancestries, Aniket Mishra, Rainer Malik, Tsuyoshi Hachiya, Tuuli Jürgenson, Shinichi Namba, Daniel C Posner, Frederick K Kamanu, Masaru Koido, Quentin Le Grand, Mingyang Shi, Yunye He, Marios K Georgakis, Ilana Caro, Kristi Krebs, Yi-Ching Liaw, Felix C Vaura, Kuang Lin, Bendik Slagsvold Winsvold, Vinodh Srinivasasainagendra, Livia Parodi, Hee-Joon Bae, Ganesh Chauhan, Michael R Chong, Liisa Tomppo, Rufus Akinyemi, Gennady V Roshchupkin, Naomi Habib, Yon Ho Jee, Jesper Qvist Thomassen, Vida Abedi, Jara Cárcel-Márquez, Marianne Nygaard, Hampton L Leonard, Chaojie Yang, Ekaterina Yonova-Doing, Maria J Knol, Adam J Lewis, Renae L Judy, Tetsuro Ago, Philippe Amouyel, Nicole D Armstrong, Mark K Bakker, Traci M Bartz, David A Bennett, Joshua C Bis, Constance Bordes, Sigrid Børte, Anael Cain, Paul M Ridker, Kelly Cho, Zhengming Chen, Carlos Cruchaga, John W Cole, Phil L De Jager, Rafael De Cid, Matthias Endres, Leslie E Ferreira, Mirjam I Geerlings, Natalie C Gasca, Vilmundur Gudnason, Jun Hata, Jing He, Alicia K Heath, Yuk-Lam Ho, Aki S Havulinna, Jemma C Hopewell, Hyacinth I Hyacinth, Michael Inouye, Mina A Jacob, Christina E Jeon, Christina Jern, Masahiro Kamouchi, Keith L Keene, Takanari Kitazono, Steven J Kittner, Takahiro Konuma, Amit Kumar, Paul Lacaze, Lenore J Launer, Keon-Joo Lee, Kaido Lepik, Jiang Li, Liming Li, Ani Manichaikul, Hugh S Markus, Nicholas A Marston, Thomas Meitinger, Braxton D Mitchell, Felipe A Montellano, Takayuki Morisaki, Thomas H Mosley, Mike A Nalls, Børge G Nordestgaard, Martin J O'Donnell, Yukinori Okada, N Charlotte Onland-Moret, Bruce Ovbiagele, Annette Peters, Bruce M Psaty, Stephen S Rich, Jonathan Rosand, Marc S Sabatine, Ralph L Sacco, Danish Saleheen, Else Charlotte Sandset, Veikko Salomaa, Muralidharan Sargurupremraj, Makoto Sasaki, Claudia L Satizabal, Carsten O Schmidt, Atsushi Shimizu, Nicholas L Smith, Kelly L Sloane, Yoichi Sutoh, Yan V Sun, Kozo Tanno, Steffen Tiedt, Turgut Tatlisumak, Nuria P Torres-Aguila, Hemant K Tiwari, David-Alexandre Trégouët, Stella Trompet, Anil Man Tuladhar, Anne Tybjærg-Hansen, Marion Van Vugt, Riina Vibo, Shefali S Verma, Kerri L Wiggins, Patrik Wennberg, Daniel Woo, Peter W F Wilson, Huichun Xu, Qiong Yang, Kyungheon Yoon, Compass Consortium, Invent Consortium, Dutch Parelsnoer Initiative (Psi) Cerebrovascular Disease Study Group, Estonian Biobank, Precise4q Consortium, Finngen Consortium, Ninds Stroke Genetics Network (Sign), Megastroke Consortium, Siren Consortium, China Kadoorie Biobank Collaborative Group, Va Million Veteran Program, International Stroke Genetics Consortium (Isgc), Biobank Japan, Charge Consortium, Gigastroke Consortium, Iona Y Millwood, Christian Gieger, Toshiharu Ninomiya, Hans J Grabe, J Wouter Jukema, Ina L Rissanen, Daniel Strbian, Young Jin Kim, Pei-Hsin Chen, Ernst Mayerhofer, Joanna M M Howson, Marguerite R Irvin, Hieab Adams, Sylvia Wassertheil-Smoller, Kaare Christensen, Mohammad A Ikram, Tatjana Rundek, Bradford B Worrall, G Mark Lathrop, Moeen Riaz, Eleanor M Simonsick, Janika Kõrv, Paulo H C França, Ramin Zand, Kameshwar Prasad, Ruth Frikke-Schmidt, Frank-Erik De Leeuw, Thomas Liman, Karl Georg Haeusler, Ynte M Ruigrok, Peter Ulrich Heuschmann, W T Longstreth, Keum Ji Jung, Lisa Bastarache, Guillaume Paré, Scott M Damrauer, Daniel I Chasman, Jerome I Rotter, Christopher D Anderson, John-Anker Zwart, Teemu J Niiranen, Myriam Fornage, Yung-Po Liaw, Sudha Seshadri, Israel Fernández-Cadenas, Robin G Walters, Christian T Ruff, Mayowa O Owolabi, Jennifer E Huffman, Lili Milani, Yoichiro Kamatani, Martin Dichgans, Stephanie Debette

Student and Faculty Publications

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary …

Nab-Paclitaxel, Capecitabine, And Radiation Therapy After Induction Chemotherapy In Treating Patients With Locally Advanced And Borderline Resectable Pancreatic Cancer: Phase 1 Trial And Imaging-Based Biomarker Validation., Eugene J Koay, Mohamed Zaid, Maureen Aliru, Polycarpe Bagereka, Arie Van Wieren, Maria Jovie Rodriguez, Galia Jacobson, Robert A Wolff, Michael Overman, Gauri Varadhachary, Shubham Pant, Huamin Wang, Ching-Wei Tzeng, Naruhiko Ikoma, Michael Kim, Jeffrey E Lee, Matthew Hg Katz, Eric Tamm, Priya Bhosale, Cullen M Taniguchi, Emma B Holliday, Grace L Smith, Ethan B Ludmir, Bruce D Minsky, Christopher H Crane, Albert C Koong, Prajnan Das, Xuemei Wang, Milind Javle, Sunil Krishnan

Student and Faculty Publications

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.

METHODS AND MATERIALS: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m

RESULTS: Twenty-three patients started and finished …

Association Of Atrial Septal Aneurysm And Shunt Size With Stroke Recurrence And Benefit From Patent Foramen Ovale Closure, Jean-Louis Mas, Jeffrey L Saver, Scott E Kasner, Jason Nelson, John D Carroll, Gilles Chatellier, Geneviève Derumeaux, Anthony J Furlan, Howard C Herrmann, Peter Jüni, Jong S Kim, Benjamin Koethe, Pil Hyung Lee, Benedicte Lefebvre, Heinrich P Mattle, Bernhard Meier, Mark Reisman, Richard W Smalling, Lars Sondergaard, Jae-Kwan Song, David E Thaler, David M Kent

Faculty and Staff Publications

IMPORTANCE: The Patent Foramen Ovale (PFO)-Associated Stroke Causal Likelihood classification system combines information regarding noncardiac patient features (vascular risk factors, infarct topography) and PFO features (shunt size and presence of atrial septal aneurysm [ASA]) to classify patients into 3 validated categories of responsiveness to treatment with PFO closure. However, the distinctive associations of shunt size and ASA, alone and in combination, have not been completely delineated.

OBJECTIVE: To evaluate the association of PFO closure with stroke recurrence according to shunt size and/or the presence of an ASA.

DESIGN, SETTING, AND PARTICIPANTS: Pooled individual patient data from 6 randomized clinical trials …

Optical Molecular Imaging And Theranostics In Neurological Diseases Based On Aggregation-Induced Emission Luminogens, Peili Cen, Youyou Zhou, Chunyi Cui, Yen Wei, Zhen Cheng, Shuizhu Wu, Hong Zhang, Mei Tian

Faculty and Staff Publications

Optical molecular imaging and image-guided theranostics benefit from special and specific imaging agents, for which aggregation-induced emission luminogens (AIEgens) have been regarded as good candidates in many biomedical applications. They display a large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. Neurological diseases are becoming a substantial burden on individuals and society that affect over 50 million people worldwide. It is urgently needed to explore in more detail the brain structure and function, learn more about pathological processes of neurological diseases, and develop more efficient approaches for theranostics. Many AIEgens have been successfully designed, synthesized, and further …

Medication Complexity Among Older Adults With Hf: How Can We Assess Better?, Min Ji Kwak, Monica Cheng, Parag Goyal, Dae Hyun Kim, Scott L Hummel, Abhijeet Dhoble, Ashish Deshmukh, Rajender Aparasu, Holly M Holmes

Faculty and Staff Publications

Medical management of heart failure (HF) has evolved and has achieved significant survival benefits, resulting in highly complex medication regimens. Complex medication regimens create challenges for older adults, including nonadherence and increased adverse drug events, especially associated with cognitive impairment, physical limitations, or lack of social support. However, the association between medication complexity and patients' health outcomes among older adults with HF is unclear. The purpose of this review is to address how the complexity of HF medications has been assessed in the literature and what clinical outcomes are associated with medication regimen complexity in HF. Further, we aimed to …

Meaningful Improvement In General Health Outcomes With Guselkumab Treatment For Psoriatic Arthritis: Patient-Reported Outcomes Measurement Information System-29 Results From A Phase 3 Study, Ana-Maria Orbai, Laura C Coates, Atul Deodhar, Philip S Helliwell, Christopher T Ritchlin, Evan Leibowitz, Alexa P Kollmeier, Elizabeth C Hsia, Xie L Xu, Shihong Sheng, Yusang Jiang, Yan Liu, Chenglong Han

Faculty and Staff Publications

OBJECTIVE: The Phase 3 DISCOVER-1 study of guselkumab is the first randomized controlled trial to use Patient-Reported Outcomes Measurement Information System (PROMIS) measures to assess the effects of treatment on general health outcomes in patients with psoriatic arthritis (PsA).

METHODS: Patients (N = 381) with active PsA were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week 0, Week 4, then every 8 weeks (Q8W); or placebo with Week 24 crossover to guselkumab Q4W. The PROMIS-29 Profile contains four items for each of seven domains (anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, …

Prevalent Multimorbidity Combinations Among Middle-Aged And Older Adults Seen In Community Health Centers, Ana R Quiñones, Steele H Valenzuela, Nathalie Huguet, Maria Ukhanova, Miguel Marino, Jennifer A Lucas, Jean O'Malley, Teresa D Schmidt, Robert Voss, Katherine Peak, Nathaniel T Warren, John Heintzman

Student and Faculty Publications

BACKGROUND: Multimorbidity (≥ 2 chronic diseases) is associated with greater disability and higher treatment burden, as well as difficulty coordinating self-management tasks for adults with complex multimorbidity patterns. Comparatively little work has focused on assessing multimorbidity patterns among patients seeking care in community health centers (CHCs).

OBJECTIVE: To identify and characterize prevalent multimorbidity patterns in a multi-state network of CHCs over a 5-year period.

DESIGN: A cohort study of the 2014-2019 ADVANCE multi-state CHC clinical data network. We identified the most prevalent multimorbidity combination patterns and assessed the frequency of patterns throughout a 5-year period as well as the demographic …

Same Day Discharge Following Elective, Minimally Invasive, Colorectal Surgery : A Review Of Enhanced Recovery Protocols And Early Outcomes By The Sages Colorectal Surgical Committee With Recommendations Regarding Patient Selection, Remote Monitoring, And Successful Implementation, Elisabeth C Mclemore, Lawrence Lee, Traci L Hedrick, Laila Rashidi, Erik P Askenasy, Daniel Popowich, Patricia Sylla

Student and Faculty Publications

BACKGROUND: As enhanced recovery programs (ERPs) have continued to evolve, the length of hospitalization (LOS) following elective minimally invasive colorectal surgery has continued to decline. Further refinements in multimodal perioperative pain management strategies have resulted in reduced opioid consumption. The interest in ambulatory colectomy has dramatically accelerated during the COVID-19 pandemic. Severe restrictions in hospital capacity and fear of COVID transmission forced surgical teams to rethink strategies to further reduce length of inpatient stay.

METHODS: Members of the SAGES Colorectal Surgery Committee began reviewing the emergence of SDD protocols and early publications for SDD in 2019. The authors met at …

Assessing Urinary Phenol And Paraben Mixtures In Pregnant Women With And Without Gestational Diabetes Mellitus: A Case-Control Study, Wei-Jen Chen, Candace Robledo, Erin M Davis, Jean R Goodman, Chao Xu, Jooyeon Hwang, Amanda E Janitz, Tabitha Garwe, Antonia M Calafat, Jennifer D Peck

Student and Faculty Publications

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable …

Association Of Social Needs And Healthcare Utilization Among Medicare And Medicaid Beneficiaries In The Accountable Health Communities Model, Jennifer Holcomb, Linda Highfield, Gayla M Ferguson, Robert O Morgan

Student and Faculty Publications

BACKGROUND: Integration of health-related social needs (HRSNs) data into clinical care is recognized as a driver for improving healthcare. However, few published studies on HRSNs and their impact are available. CMS sought to fill this gap through the Accountable Health Communities (AHC) Model, a national RCT of HRSN screening, referral, and navigation. Data from the AHC Model could significantly advance the field of HRSN screening and intervention in the USA.

OBJECTIVE: to present data from the Greater Houston AHC (GH-AHC) Model site on HRSN frequency and the association between HRSNs, sociodemographic factors, and self-reported ED utilization using a cross-sectional design. …

Risk Factors For The Development Of Retinopathy In Prediabetes And Type 2 Diabetes: The Diabetes Prevention Program Experience, Neil H White, Qing Pan, William C Knowler, Emily B Schroeder, Dana Dabelea, Emily Y Chew, Barbara Blodi, Ronald B Goldberg, Xavier Pi-Sunyer, Christine Darwin, Mathias Schlögl, David M Nathan

Faculty and Staff Publications

OBJECTIVE: To determine glycemic and nonglycemic risk factors that contribute to the presence of diabetic retinopathy (DR) before and after the onset of type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: During the Diabetes Prevention Program (DPP) and DPP Outcome Study (DPPOS), we performed fundus photography over time in adults at high risk for developing T2D, including after they developed diabetes. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, with DR defined as typical lesions of DR (microaneurysms, exudates, hemorrhage, or worse) in either eye.

RESULTS: By DPPOS year 16 (∼20 years after random …

Chemotherapy-Induced Toxicities And Their Associations With Clinical And Non-Clinical Factors Among Breast Cancer Patients In Vietnam, Sang M Nguyen, Anh T Pham, Lan M Nguyen, Hui Cai, Thuan V Tran, Xiao-Ou Shu, Huong T T Tran

Faculty and Staff Publications

Understanding the burden and factors related to chemotherapy-induced toxicity is important in treatment planning for breast cancer patients. We conducted a prospective study among 396 newly diagnosed and chemotherapy-treated breast cancer patients recruited in two major cancer hospitals in northern Vietnam. Toxicities were captured through medical chart reviews and patient self-reports and graded using NCI CTCAE classification. Associations for sociodemographic and clinical factors with chemotherapy-induced toxicities during first-line chemotherapy were evaluated via multivariable logistic regression. Severe (i.e., grade ≥ 3) hematological (38.6%), and gastrointestinal (12.9%) toxicities were common. A pre-existing nephrological condition was significantly associated with the risk of severe …