Internal Medicine Commons^™

Dengue Outbreak Response During Covid-19 Pandemic, Key Largo, Florida, Usa, 2020, Devin Rowe, Catherine Mcdermott, Ysla Veliz, Alison Kerr, Mark Whiteside, Mikki Coss, Chad Huff, Andrea Leal, Edgar Kopp, Alexis Lacrue, Lea A Heberlein, Laura E Adams, Gilberto A Santiago, Jorge L Munoz-Jordan, Gabriela Paz-Bailey, Andrea M Morrison

Faculty, Staff and Student Publications

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Hernia Prevention Using Biologic Mesh And/Or Small Bites: A Multispecialty 2 × 2 Factorial Randomized Controlled Trial, Rainna Coelho, Naila H Dhanani, Nicole B Lyons, Karla Bernardi, Erik P Askenasy, Stefanos Millas, Julie L Holihan, Zuhair Ali, Mike K Liang

Faculty, Staff and Student Publications

BACKGROUND: Ventral incisional hernias are the most common complication after abdominal operation. Randomized trials have shown efficacy of prophylactic synthetic mesh and small bites. Adoption of these practices has been limited due to concerns with placement of synthetic mesh in contaminated cases and small bites in an overweight population. We sought to assess the efficacy of prophylactic biologic mesh and small bites to prevent postoperative major complications: ventral incisional hernias, surgical site infection, reoperation, and death.

STUDY DESIGN: High-risk patients (overweight/obese, current smoker) undergoing abdominal operation with a midline incision (5 cm or greater) were randomized (2 × 2 factorial …

Encephalitis In Hiv-Infected Adults In The Antiretroviral Therapy Era, Melissa Reimer-Mcatee, Denisse Ramirez, Casey Mcatee, Alejandro Granillo, Rodrigo Hasbun

Faculty, Staff and Student Publications

Introduction: Encephalitis presents with high morbidity and mortality in both HIV-infected and HIV-negative patients. There are currently no studies comparing HIV-infected and HIV-negative patients admitted to the hospital with acute encephalitis.

Methods: We conducted a multicenter, retrospective study of adults admitted to the hospital with a diagnosis of encephalitis in Houston, Texas between 2005 and 2020. We describe the clinical manifestations, etiology, and outcomes of these patients with a focus on those infected with HIV.

Results: We identified 260 patients with encephalitis, 40 of whom were infected with HIV. Viral etiology was identified in 18 of the 40 HIV-infected patients …

Outcomes Of Induction Vs Prelabor Cesarean Delivery At <33 Weeks For Hypertensive Disorders Of Pregnancy, Elisa T Bushman, William A Grobman, Jennifer L Bailit, Uma M Reddy, Ronald J Wapner, Michael W Varner, John M Thorp, Steve N Caritis, Mona Prasad, George R Saade, Yoram Sorokin, Dwight J Rouse, Sean C Blackwell, Jorge E Tolosa

Faculty, Staff and Student Publications

BACKGROUND: Hypertensive disorders of pregnancy are the leading cause of indicated preterm birth; however, the optimal delivery approach for pregnancies complicated by preterm hypertensive disorders of pregnancy remains uncertain.

OBJECTIVE: This study aimed to compare maternal and neonatal morbidity in patients with hypertensive disorders of pregnancy who either went induction of labor or prelabor cesarean delivery at <33 >weeks' gestation. In addition, we aimed to quantify the length of induction of labor and rate of vaginal delivery in those who underwent induction of labor.

STUDY DESIGN: This is a secondary analysis of an observational study which included 115,502 patients in 25 …

Monocyte-Derived Macrophages Orchestrate Multiple Cell-Type Interactions To Repair Necrotic Liver Lesions In Disease Models, Dechun Feng, Xiaogang Xiang, Yukun Guan, Adrien Guillot, Hongkun Lu, Chingwen Chang, Yong He, Hua Wang, Hongna Pan, Cynthia Ju, Sean P Colgan, Frank Tacke, Xin Wei Wang, George Kunos, Bin Gao

Faculty, Staff and Student Publications

The liver can fully regenerate after partial resection, and its underlying mechanisms have been extensively studied. The liver can also rapidly regenerate after injury, with most studies focusing on hepatocyte proliferation; however, how hepatic necrotic lesions during acute or chronic liver diseases are eliminated and repaired remains obscure. Here, we demonstrate that monocyte-derived macrophages (MoMFs) were rapidly recruited to and encapsulated necrotic areas during immune-mediated liver injury and that this feature was essential in repairing necrotic lesions. At the early stage of injury, infiltrating MoMFs activated the Jagged1/notch homolog protein 2 (JAG1/NOTCH2) axis to induce cell death-resistant SRY-box transcription factor …

Neutrophil Cd64 Index As A Good Biomarker For Early Diagnosis Of Bacterial Infection In Pregnant Women During The Flu Season, Lifei Yu, Panpan Cen, Linjian Zhang, Jianfei Ke, Xiangfei Xu, Jiexia Ding, Jie Jin, Jianhang Leng, Yunsong Yu

Faculty, Staff and Student Publications

BACKGROUND: Pregnant women are at high risk of developing febrile illness during the flu season. Early identification of a viral or bacterial infection is crucial in the management of febrile pregnant patients. Neutrophil CD64 (nCD64) has been shown to have more important diagnostic value in sepsis than traditional inflammatory indicators.

METHODS: The pregnant women enrolled were divided into three groups according to disease: influenza A infection, bacterial infection and healthy controls. Peripheral blood CD64, leukocyte, C-reactive protein (CRP), procalcitonin (PCT) and human Th1/Th2-related cytokines levels were routinely measured. The correlation between and diagnostic value of the nCD64 index and other …

The Association Of Race And Ethnicity With Severe Maternal Morbidity Among Individuals Diagnosed With Hypertensive Disorders Of Pregnancy, Ashok Krishnaswami, Michael W Rich, Min Ji Kwak, Parag Goyal, Daniel E Forman, Abdulla A Damluji, Matthew Solomon, Jamal S Rana, Deborah M Kado, Michelle C Odden

Faculty, Staff and Student Publications

AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 >mmHg) to standard (<140 >mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial.

METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality …

Deprescribing Statins, Considerations For Informed Decision Making, Craig Thomas, Henry Ellison, George E Taffet

Faculty, Staff and Students Publications

No abstract provided.

Effective Methods For Bulk Rna-Seq Deconvolution Using Scnrna-Seq Transcriptomes, Francisco Avila Cobos, Mohammad Javad Najaf Panah, Jessica Epps, Xiaochen Long, Tsz-Kwong Man, Hua-Sheng Chiu, Elad Chomsky, Evgeny Kiner, Michael J Krueger, Diego Di Bernardo, Luis Voloch, Jan Molenaar, Sander R Van Hooff, Frank Westermann, Selina Jansky, Michele L Redell, Pieter Mestdagh, Pavel Sumazin

Faculty, Staff and Students Publications

Background: RNA profiling technologies at single-cell resolutions, including single-cell and single-nuclei RNA sequencing (scRNA-seq and snRNA-seq, scnRNA-seq for short), can help characterize the composition of tissues and reveal cells that influence key functions in both healthy and disease tissues. However, the use of these technologies is operationally challenging because of high costs and stringent sample-collection requirements. Computational deconvolution methods that infer the composition of bulk-profiled samples using scnRNA-seq-characterized cell types can broaden scnRNA-seq applications, but their effectiveness remains controversial.

Results: We produced the first systematic evaluation of deconvolution methods on datasets with either known or scnRNA-seq-estimated compositions. Our analyses revealed …

Disparities In Antifibrotic Medication Utilization Among Veterans With Idiopathic Pulmonary Fibrosis, Bhavika Kaul, Joyce S Lee, Laura A Petersen, Charles Mcculloch, Ivan O Rosas, Venkata D Bandi, Ning Zhang, Alison M Dedent, Harold R Collard, Mary A Whooley

Faculty, Staff and Students Publications

BACKGROUND: Two antifibrotic medications, pirfenidone and nintedanib, are approved for the treatment of idiopathic pulmonary fibrosis (IPF). Little is known about their real-world adoption.

RESEARCH QUESTION: What are the real-world antifibrotic utilization rates and factors associated with uptake among a national cohort of veterans with IPF?

STUDY DESIGN AND METHODS: This study identified veterans with IPF who received care either provided by the Veterans Affairs (VA) Healthcare System or non-VA care paid for by the VA. Patients who had filled at least one antifibrotic prescription through the VA pharmacy or Medicare Part D between October 15, 2014, and December 31, …

Clinical Outcomes Associated With Overestimation Of Oxygen Saturation By Pulse Oximetry In Patients Hospitalized With Covid-19, Ashraf Fawzy, Tianshi David Wu, Kunbo Wang, Kenneth E Sands, Arielle M Fisher, Shanna A Arnold Egloff, Jeffrey D Dellavolpe, Theodore J Iwashyna, Yanxun Xu, Brian T Garibaldi

Faculty, Staff and Students Publications

IMPORTANCE: Many pulse oximeters have been shown to overestimate oxygen saturation in persons of color, and this phenomenon has potential clinical implications. The relationship between overestimation of oxygen saturation with timing of COVID-19 medication delivery and clinical outcomes remains unknown.

OBJECTIVE: To investigate the association between overestimation of oxygen saturation by pulse oximetry and delay in administration of COVID-19 therapy, hospital length of stay, risk of hospital readmission, and in-hospital mortality.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients hospitalized for COVID-19 at 186 acute care facilities in the US with at least 1 functional arterial oxygen saturation (SaO2) …

Androgen-Regulated Stromal Complement Component 7 (C7) Suppresses Prostate Cancer Growth, Zhicheng Zhou, Deyong Jia, Ohjoon Kwon, Shan Li, Huiyun Sun, Martine P Roudier, Daniel W Lin, Lawrence True, Colm Morrissey, Chad J Creighton, John K Lee, Li Xin

Faculty, Staff and Students Publications

The complement system is a major component of the innate immune system that works through the cytolytic effect of the membrane attack complex (MAC). Complement component 7 (C7) is essential for MAC assembly and its precisely regulated expression level is crucial for the cytolytic activity of MAC. We show that C7 is specifically expressed by the stromal cells in both mouse and human prostates. The expression level of C7 inversely correlates with clinical outcomes in prostate cancer. C7 is positively regulated by androgen signaling in the mouse prostate stromal cells. The androgen receptor directly transcriptionally regulates the mouse and human …

Prescribing Patterns Of Fall Risk-Increasing Drugs In Older Adults Hospitalized For Heart Failure, Esther Liu, Musarrat Nahid, Mahad Musse, Ligong Chen, Sarah N Hilmer, Andrew Zullo, Min Ji Kwak, Mark Lachs, Emily B Levitan, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: Older adults hospitalized for heart failure (HF) are at risk for falls after discharge. One modifiable contributor to falls is fall risk-increasing drugs (FRIDs). However, the prevalence of FRIDs among older adults hospitalized for HF is unknown. We describe patterns of FRIDs use and examine predictors of a high FRID burden.

METHODS: We used the national biracial REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort recruited from 2003-2007. We included REGARDS participants aged ≥ 65 years discharged alive after a HF hospitalization from 2003-2017. We determined FRIDs -cardiovascular (CV) and non-cardiovascular (non-CV) medications - …

Impact Of Type Of Induction Therapy On Outcomes In Older Adults With Aml After Allogeneic Stem Cell Transplantation, Nicholas J Short, Faustine Ong, Farhad Ravandi, Graciela Nogueras-Gonzalez, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Marina Konopleva, Gautam Borthakur, Betul Oran, Gheath Al-Atrash, Rohtesh Mehta, Elias J Jabbour, Musa Yilmaz, Ghayas C Issa, Abhishek Maiti, Richard E Champlin, Hagop Kantarjian, Elizabeth J Shpall, Uday Popat

Faculty, Staff and Student Publications

Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC; n = 44), lower-intensity therapy (LIT) without venetoclax (n = 29), or LIT with venetoclax (n = 54) and who underwent allogeneic HSCT in the first remission. The 2-year relapse-free survival …

The Neutralization Of The Eosinophil Peroxidase Antibody Accelerates Eosinophilic Mucin Decomposition, Panagiotis Doukas, Jan Paul Frese, Thorsten Eierhoff, Gabriel Hellfritsch, Ben Raude, Michael J Jacobs, Andreas Greiner, Alexander Oberhuber, Alexander Gombert

Faculty, Staff and Student Publications

Acute kidney injury (AKI) is a common complication after complex aortic procedures and it is associated with relevant mortality and morbidity. Biomarkers for early and specific AKI detection are lacking. The aim of this work is to investigate the reliability of the NephroCheck bedside system for diagnosing stage 3 AKI following open aortic surgery. In this prospective, multicenter, observational study,- https://clinicaltrials.gov/ct2/show/NCT04087161 -we included 45 patients undergoing open thoracoabdominal aortic repair. AKI risk (AKIRisk-Index) was calculated from urine samples at 5 timepoints: baseline, immediately postoperatively and at 12, 24, 48, and 72 h post-surgery. AKIs were classified according to the KDIGO …

Clinical And Demographic Factors Associated With Covid-19, Severe Covid-19, And Sars-Cov-2 Infection In Adults: A Secondary Cross-Protocol Analysis Of 4 Randomized Clinical Trials, Deborah A Theodore, Angela R Branche, Lily Zhang, Daniel S Graciaa, Madhu Choudhary, Timothy J Hatlen, Raadhiya Osman, Tara M Babu, Samuel T Robinson, Peter B Gilbert, Dean Follmann, Holly Janes, James G Kublin, Lindsey R Baden, Paul Goepfert, Glenda E Gray, Beatriz Grinsztejn, Karen L Kotloff, Cynthia L Gay, Brett Leav, Jacqueline Miller, Ian Hirsch, Jerald Sadoff, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Ann R Falsey, Hana M El Sahly, Magdalena E Sobieszczyk, Yunda Huang

Faculty, Staff and Student Publications

IMPORTANCE: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders.

OBJECTIVE: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network. Individual-level data from participants randomized to receive placebo within each trial were combined and analyzed. Enrollment began July 2020 and the last data cutoff was in July 2021. Participants included adults in stable health, at risk for SARS-CoV-2, and assigned to the placebo group …

Disparities In The Operative Experience Between Female And Male General Surgery Residents: A Multi-Institutional Study From The Us Rope Consortium, Leah K Winer, Sarah Kader, Jonathan S Abelson, Austin C Hammaker, Chukwuma N Eruchalu, James C Etheridge, Nancy L Cho, Darci C Foote, Felicia A Ivascu, Savannah Smith, Lauren M Postlewait, Kathriena Greenwell, Katherine M Meister, Kelsey B Montgomery, Polina Zmijewski, Samuel E Byrd, Mary K Kimbrough, Stephen J Stopenski, Jeffry T Nahmias, Jalen Harvey, Deborah Farr, Zachary M Callahan, Joshua A Marks, Christopher C Stahl, Motaz Al Yafi, Jeffrey M Sutton, Ali Elsaadi, Samuel J Campbell, Shah-Jahan M Dodwad, Sasha D Adams, Matthew R Woeste, Robert C G Martin, Purvi Patel, Michael J Anstadt, Bilal Waqar Nasim, Ross E Willis, Jitesh A Patel, Melisa R Newcomb, Brian C George, Ralph C Quillin, Alexander R Cortez

Faculty, Staff and Student Publications

OBJECTIVE: To examine differences in resident operative experience between male and female general surgery residents.

BACKGROUND: Despite increasing female representation in surgery, sex and gender disparities in residency experience continue to exist. The operative volume of male and female general surgery residents has not been compared on a multi-institutional level.

METHODS: Demographic characteristics and case logs were obtained for categorical general surgery graduates between 2010 and 2020 from the US Resident OPerative Experience Consortium database. Univariable, multivariable, and linear regression analyses were performed to compare differences in operative experience between male and female residents.

RESULTS: There were 1343 graduates from …

Immunotherapy-Related Pneumonitis And The Synergic Impact Of Thoracic Radiation And Preexisting Interstitial Lung Disease, Maria Azhar, Rodeo Abrencillo, Saumil Gandhi, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICIs) are the frontline of therapy for most cancers. Although ICIs are sometimes considered to be less harmful than systemic chemotherapies, ICIs may cause immune-related adverse events, which are cases of off-target inflammation in healthy tissues. Pneumonitis, an immune-related adverse event, is the leading cause of therapy-related mortality with ICIs. The aim of this review is to discuss how preexisting interstitial lung disease (ILD) and thoracic radiation increase the risk for ICI-pneumonitis. We discuss potential mechanisms of lung injury and how pneumonitis may impact cancer treatments.

RECENT FINDINGS: Preexisting ILD and thoracic radiation are …

Extracorporeal Carbon Dioxide Removal With The Hemolung In Patients With Acute Respiratory Failure: A Multicenter Retrospective Cohort Study, Ravindranath Tiruvoipati, Bindu Akkanti, Kha Dinh, Nicholas Barrett, Alexandra May, Jeremy Kimmel, Steven A Conrad

Faculty, Staff and Student Publications

Objectives: Extracorporeal carbon dioxide removal (ECCO 2 R) devices are effective in reducing hypercapnia and mechanical ventilation support but have not been shown to reduce mortality. This may be due to case selection, device performance, familiarity, or the management. The objective of this study is to investigate the effectiveness and safety of a single ECCO 2 R device (Hemolung) in patients with acute respiratory failure and identify variables associated with survival that could help case selection in clinical practice as well as future research.

Design: Multicenter, multinational, retrospective review.

Setting: Data from the Hemolung Registry between April 2013 and June …

Steroids For The Treatment Of Viral Encephalitis: A Systematic Literature Review And Meta-Analysis, Emira Hodzic, Rodrigo Hasbun, Alejandro Granillo, Anna R Tröscher, Helga Wagner, Tim J Von Oertzen, Judith N Wagner

Faculty, Staff and Student Publications

Background: Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE.

Methods: We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1.

Results: We screened 378 studies and included 50. 155 patients were …

Association Of Trauma Molecular Endotypes With Differential Response To Transfusion Resuscitation Strategies, Matthew R Thau, Ted Liu, Neha A Sathe, Grant E O'Keefe, Bryce R H Robinson, Eileen Bulger, Charles E Wade, Erin E Fox, John B Holcomb, W Conrad Liles, Ian B Stanaway, Carmen Mikacenic, Mark M Wurfel, Pavan K Bhatraju, Eric D Morrell

Faculty, Staff and Student Publications

IMPORTANCE: It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies.

OBJECTIVE: To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies.

DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe …

Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez

Faculty, Staff and Student Publications

AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.

METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping …

Extracellular Vesicle-Packaged Ilk From Mesothelial Cells Promotes Fibroblast Activation In Peritoneal Fibrosis, Qiang Huang, Yuxiang Sun, Long Peng, Juan Sun, Zixin Sha, Hongchun Lin, Yongjie Li, Canming Li, Huiqun Li, Hongli Shang, Yanxu Chen, Xianrui Dou, Zhaoyong Hu, Zengchun Ye, Hui Peng

Faculty, Staff and Students Publications

Progressive peritoneal fibrosis and the loss of peritoneal function often emerged in patients undergoing long-term peritoneal dialysis (PD), resulting in PD therapy failure. Varieties of cell-cell communications among peritoneal cells play a significant role in peritoneal fibrogenesis. Extracellular vesicles (EVs) have been confirmed to involve in intercellular communication by transmitting proteins, nucleic acids or lipids. However, their roles and functional mechanisms in peritoneal fibrosis remain to be determined. Using integrative analysis of EV proteomics and single-cell RNA sequencing, we characterized the EVs isolated from PD patient's effluent and revealed that mesothelial cells are the main source of EVs in PD …

Predictors, Disparities, And Facility-Level Variation: Sglt2 Inhibitor Prescription Among Us Veterans With Ckd, L Parker Gregg, David J Ramsey, Julia M Akeroyd, Shehrezade A Jafry, Michael E Matheny, Salim S Virani, Sankar D Navaneethan

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are recommended for type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease (CKD) or atherosclerotic cardiovascular disease (ASCVD). We evaluated factors associated with SGLT2 inhibitor prescription, disparities by race and sex, and facility-level variation in prescription patterns.

STUDY DESIGN: Retrospective cohort.

SETTING & PARTICIPANTS: A national sample of US veterans with comorbid T2DM, CKD, and ASCVD with a primary care visit between January 1 and December 31, 2020.

EXPOSURE: Race, sex, and individual Veterans Affairs (VA) location.

OUTCOME: SGLT2 inhibitor prescription.

ANALYTICAL APPROACH: Multivariable logistic regression assessed associations of race …

Current Programs And Incentives To Overcome Rural Physician Shortages In The United States: A Narrative Review, Kelley Arredondo, Hilary N Touchett, Sundas Khan, Matthew Vincenti, Bradley V Watts

Faculty, Staff and Students Publications

Access to healthcare continues to be a top priority and prominent challenge in rural communities, with 20% of the total U.S. population living in rural areas while only 10% of physicians practice in rural areas. In response to physician shortages, a variety of programs and incentives have been implemented to recruit and retain physicians in rural areas; however, less is known about the types and structures of incentives that are offered in rural areas and how that compares to physician shortages. The purpose of our study is to conduct a narrative review of the literature to identify and compare current …

Allogeneic, Off-The-Shelf, Sars-Cov-2-Specific T Cells (Alvr109) For The Treatment Of Covid-19 In High-Risk Patients, Spyridoula Vasileiou, Laquisa Hill, Manik Kuvalekar, Aster G Workineh, Ayumi Watanabe, Yovana Velazquez, Suhasini Lulla, Kimberly Mooney, Natalia Lapteva, Bambi J Grilley, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, Todd N Eagar, George Carrum, Kevin A Grimes, Ann M Leen, Premal Lulla

Faculty, Staff and Students Publications

Defects in T-cell immunity to SARS-CoV-2 have been linked to an increased risk of severe COVID-19 (even after vaccination), persistent viral shedding and the emergence of more virulent viral variants. To address this T-cell deficit, we sought to prepare and cryopreserve banks of virus-specific T cells, which would be available as a partially HLA-matched, off-the-shelf product for immediate therapeutic use. By interrogating the peripheral blood of healthy convalescent donors, we identified immunodominant and protective T-cell target antigens, and generated and characterized polyclonal virus-specific T-cell lines with activity against multiple clinically important SARS-CoV-2 variants (including 'delta' and 'omicron'). The feasibility of …

Systemic Adverse Events Among Patients With Diabetes Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections, Sidra Zafar, Annette Walder, Salim Virani, Kristin Biggerstaff, Silvia Orengo-Nania, Jonathan Chang, Roomasa Channa

Faculty, Staff and Students Publications

IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) agents are currently the mainstay of treatment for diabetic retinopathy (DR). Although effective, data on their systemic safety remains inconclusive, particularly in high-risk patient groups.

OBJECTIVE: To explore the systemic safety of intravitreal anti-VEGF agents among patients with diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, longitudinal population-based analysis of the Corporate Data Warehouse, a large-scale database of patients within the US Veteran Health Affairs. All patients 18 years and older with type 2 diabetes who were seen at any Veterans Affairs health care facility in the US between January 1, 2011, and …

Gata6-As1 Regulates Intestinal Epithelial Mitochondrial Functions, And Its Reduced Expression Is Linked To Intestinal Inflammation And Less Favourable Disease Course In Ulcerative Colitis, Katya E Sosnovski, Tzipi Braun, Amnon Amir, Danielle Moshel, Marina Benshoshan, Kelli L Vandussen, Nina Levhar, Haya Abbas-Egbariya, Katia Beider, Rakefet Ben-Yishay, Syed Asad Ali, Sean R Moore, Subra Kugathasan, Ifat Abramovich, Efrat Glick Saar, Batya Weiss, Iris Barshack, Eyal Gottlieb, Tamar Geiger, Shomron Ben-Horin, Igor Ulitsky, Jeffrey S Hyams, Lee A Denson, Yael Haberman

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Widespread dysregulation of long non-coding RNAs [lncRNAs] including a reduction in GATA6-AS1 was noted in inflammatory bowel disease [IBD]. We previously reported a prominent inhibition of epithelial mitochondrial functions in ulcerative colitis [UC]. However, the connection between reduction of GATA6-AS1 expression and attenuated epithelial mitochondrial functions was not defined.

METHODS: Mucosal transcriptomics was used to conform GATA6-AS1 reduction in several treatment-naïve independent human cohorts [n=673]. RNA pull-down followed by mass spectrometry was used to determine the GATA6-AS1 interactome. Metabolomics and mitochondrial respiration following GATA6-AS1 silencing in Caco-2 cells were used to elaborate on GATA6-AS1 functions.

RESULTS: GATA6-AS1 …

Transmembrane Stem Factor Nanodiscs Enhanced Revascularization In A Hind Limb Ischemia Model In Diabetic, Hyperlipidemic Rabbits, Eri Takematsu, Miles Massidda, Gretchen Howe, Julia Goldman, Patricia Felli, Lei Mei, Gregory Callahan, Andrew Sligar, Richard Smalling, Aaron Baker

Faculty, Staff and Student Publications

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. …

Troponin In Acute Chest Pain To Risk Stratify And Guide Effective Use Of Computed Tomography Coronary Angiography (Target-Ctca): A Randomised Controlled Trial, Kuan Ken Lee, David Lowe, Rachel O'Brien, Ryan Wereski, Anda Bularga, Caelan Taggart, Matthew T H Lowry, Amy V Ferry, Michelle C Williams, Giles Roditi, John Byrne, Chris Tuck, Denise Cranley, Praveen Thokala, Steve Goodacre, Catriona Keerie, John Norrie, David E Newby, Alasdair J Gray, Nicholas L Mills

Faculty, Staff and Student Publications

BACKGROUND: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death.

METHODS: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. …