Internal Medicine Commons^™

Trβ Activation Confers At2-To-At1 Cell Differentiation And Anti-Fibrosis During Lung Repair Via Klf2 And Cebpa, Xin Pan, Lan Wang, Juntang Yang, Yingge Li, Min Xu, Chenxi Liang, Lulu Liu, Zhongzheng Li, Cong Xia, Jiaojiao Pang, Mengyuan Wang, Meng Li, Saiya Guo, Peishuo Yan, Chen Ding, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the …

Syntaxin 3b: A Snare Protein Required For Vision, Himani Dey, Mariajose Perez-Hurtado, Ruth Heidelberger

Faculty, Staff and Student Publications

Syntaxin 3 is a member of a large protein family of syntaxin proteins that mediate fusion between vesicles and their target membranes. Mutations in the ubiquitously expressed syntaxin 3A splice form give rise to a serious gastrointestinal disorder in humans called microvillus inclusion disorder, while mutations that additionally involve syntaxin 3B, a splice form that is expressed primarily in retinal photoreceptors and bipolar cells, additionally give rise to an early onset severe retinal dystrophy. In this review, we discuss recent studies elucidating the roles of syntaxin 3B and the regulation of syntaxin 3B functionality in membrane fusion and neurotransmitter release …

Pparγ/Etv2 Axis Regulates Endothelial-To-Mesenchymal Transition In Pulmonary Hypertension, Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

A Virtual Breakthrough Series Collaborative For Missed Test Results: A Stepped-Wedge Cluster-Randomized Clinical Trial, Lisa Zubkoff, Andrew J Zimolzak, Ashley N D Meyer, Jennifer Sloane, Umber Shahid, Traber Giardina, Sahar A Memon, Taylor M Scott, Daniel R Murphy, Hardeep Singh

Faculty, Staff and Students Publications

IMPORTANCE: Missed test results, defined as test results not followed up within an appropriate time frame, are common and lead to delays in diagnosis and treatment.

OBJECTIVE: To evaluate the effect of a quality improvement collaborative, the Virtual Breakthrough Series (VBTS), on the follow-up rate of 2 types of test results prone to being missed: chest imaging suspicious for lung cancer and laboratory findings suggestive of colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted between February 2020 and March 2022 at 12 Department of Veterans Affairs (VA) medical centers, with a predefined 3-cohort roll-out. Each …

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Beom-Jun Kim, Aparna Mitra, Craig T Vollert, Jonathan T Lei, Diana Fandino, Meenakshi Anurag, Matthew V Holt, Xuxu Gou, Jacob B Pilcher, Matthew P Goetz, Donald W Northfelt, Susan G Hilsenbeck, C Gary Marshall, Marc L Hyer, Robert Papp, Shou-Yun Yin, Carmine De Angelis, Rachel Schiff, Suzanne A W Fuqua, Cynthia X Ma, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Thrombectomy For Stroke With Large Infarct On Noncontrast Ct: The Tesla Randomized Clinical Trial, Writing Committee For The Tesla Investigators, Albert J Yoo, Osama O Zaidat, Sunil A Sheth, Ansaar T Rai, Santiago Ortega-Gutierrez, Curtis A Given, Syed F Zaidi, Ramesh Grandhi, Hugo Cuellar, Maxim Mokin, Jeffrey M Katz, Amer Alshekhlee, Muhammad A Taqi, Sameer A Ansari, Adnan H Siddiqui, Nobl Barazangi, Joey D English, Alberto Maud, Jawad Kirmani, Rishi Gupta, Dileep R Yavagal, Jason Tarpley, Dhruvil J Pandya, Marshall C Cress, Sushrut Dharmadhikari, Kaiz S Asif, Tareq Kass-Hout, Ajit S Puri, Nazli Janjua, Aniel Q Majjhoo, Aamir Badruddin, Randall C Edgell, Rakesh Khatri, Larry Morgan, Anmar Razak, Alicia Zha, Priyank Khandelwal, Nils Mueller-Kronast, Dennis J Rivet, Thomas Wolfe, Brian Snelling, Ali Sultan-Qurraie, Shao-Pow Lin, Rajkamal Khangura, Alejandro M Spiotta, Parita Bhuva, Sergio Salazar-Marioni, Eugene Lin, Abdul R Tarabishy, Edgar A Samaniego, Murali K Kolikonda, Mouhammad A Jumaa, Vivek K Reddy, Pankaj Sharma, Olvert A Berkhemer, Pieter-Jan Van Doormaal, Adriaan C G M Van Es, Wim H Van Zwam, Bart J Emmer, Ludo F Beenen, Charles B L M Majoie, Nancy Buderer, Michelle A Detry, Anna Bosse, Todd L Graves, Christina Saunders, Lucas Elijovich, Ashutosh Jadhav, Mary Patterson, Hannah Slight, Kristine Below, Sami Al Kasab, Tesla Investigators

Faculty, Staff and Student Publications

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset.

Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset.

Design, setting, and participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at …

Mesenchymal Stromal Cells Protect Combined Oncolytic And Helper-Dependent Adenoviruses From Humoral Immunity, Ada Irmak Özcan, Arianexys Aquino Lόpez, Alexandra N Wolff, Audrey Ma, Amanda Rosewell Shaw, Masataka Suzuki, Malcolm K Brenner, Mary K Mckenna

Faculty, Staff and Students Publications

Systemic delivery of oncolytic and immunomodulatory adenoviruses may be required for optimal effects on human malignancies. Mesenchymal stromal cells (MSCs) can serve as delivery systems for cancer therapeutics due to their ability to transport and shield these agents while homing to tumors. We now use MSCs to deliver a clinically validated binary oncolytic and helper-dependent adenovirus combination (CAdVEC) to tumor cells. We show successful oncolysis and helper-dependent virus function in tumor cells even in the presence of plasma from adenovirus-seropositive donors. In both two- and three-dimensional cultures, CAdVEC function is eliminated even at high dilutions of seropositive plasma but is …

A Smart Water Bottle And Companion App (Hidratespark 3) To Improve Bladder-Filling Compliance In Patients With Prostate Cancer Receiving Radiotherapy: Nonrandomized Trial Of Feasibility And Acceptability, William Jin, Christopher Montoya, Benjamin James Rich, Crystal Seldon Taswell, Miguel Noy, Deukwoo Kwon, Benjamin Spieler, Brandon Mahal, Matthew Abramowitz, Raphael Yechieli, Alan Pollack, Alan Dal Pra

Faculty, Staff and Student Publications

Background: Patients with prostate cancer undergoing radiation therapy (RT) need comfortably full bladders to reduce toxicities during treatment. Poor compliance is common with standard of care written or verbal instructions, leading to wasted patient value (PV) and clinic resources via poor throughput efficiency (TE).

Objective: Herein, we assessed the feasibility and acceptability of a smartphone-based behavioral intervention (SBI) to improve bladder-filling compliance and methods for quantifying PV and TE.

Methods: In total, 36 patients with prostate cancer were enrolled in a single-institution, closed-access, nonrandomized feasibility trial. The SBI consists of a fully automated smart water bottle and smartphone app. Both …

Traumatic Brain Injury And Variants Of Shock Index, Sai Doppalapudi, Muhammad Adrish

Faculty, Staff and Students Publications

Traumatic Brain Injury is a major cause of death and long-term disability. The early identification of patients at high risk of mortality is important for both management and prognosis. Although many modified scoring systems have been developed for improving the prediction accuracy in patients with trauma, few studies have focused on prediction accuracy and application in patients with traumatic brain injury. The shock index (SI) which was first introduced in the 1960s has shown to strongly correlate degree of circulatory shock with increasing SI. In this editorial we comment on a publication by Carteri et al wherein they perform a …

Reimagining Critical Care: Trends And Shifts In 21st Century Medicine, Sai Doppalapudi, Bilal Khan, Muhammad Adrish

Faculty, Staff and Students Publications

Critical care medicine has undergone significant evaluation in the 21st century, primarily driven by advancements in technology, changes in healthcare delivery, and a deeper understanding of disease processes. Advancements in technology have revolutionized patient monitoring, diagnosis, and treatment in the critical care setting. From minimally invasive procedures to advances imaging techniques, clinicians now have access to a wide array of tools to assess and manage critically ill patients more effectively. In this editorial we comment on the review article published by Padte S et al wherein they concisely describe the latest developments in critical care medicine.

Social Vulnerability And Sickle Cell Disease Mortality In The Us, Jia Yi Tan, Boon Jian San, Yong-Hao Yeo, Kok Hoe Chan, Hamid S Shaaban, Daniel E Ezekwudo, Modupe Idowu

Faculty, Staff and Student Publications

Importance: Social determinants of health (SDOH) influence health outcomes, including those of sickle cell disease (SCD), despite advancements in treatments like disease-modifying therapies.

Objective: To investigate the association of SDOH with SCD mortality rates from 2016 to 2020.

Design, setting, and participants: This cross-sectional study combined county-level data from the Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI) with SCD mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1, 2016, to December 31, 2020. US counties were divided into …

Imprecise Clinical Assessments And Inaccurate Grades: Family Medicine Clerkship Director Perspectives, Arindam Sarkar, Joel J Heidelbaugh, Gage Hallbauer, Nital Appelbaum

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: As application to residency programs becomes increasingly competitive, educational leaders face growing student concern about imprecise clinical assessments and clerkship grades.

METHODS: As part of a large annual survey of family medicine clerkship directors (FMCDs), 10 questions were disseminated in May 2023 about perceived levels of imprecise assessments by faculty. We aimed to determine to what extent respondents felt their institution's evaluation system propagated inaccurate grading.

RESULTS: A total of 52% of 169 FMCDs responded to the survey. Of these, 7% of respondents were completely confident that their preceptors would give two students of identical competence the …

Multicenter, Phase 1 Study Of Etavopivat (Ft-4202) Treatment For Up To 12 Weeks In Patients With Sickle Cell Disease, Santosh L Saraf, Robert Hagar, Modupe Idowu, Ifeyinwa Osunkwo, Kimberly Cruz, Frans A Kuypers, R Clark Brown, James Geib, Maria Ribadeneira, Patricia Schroeder, Eric Wu, Sanjeev Forsyth, Patrick F Kelly, Theodosia A Kalfa, Marilyn J Telen

Faculty, Staff and Student Publications

Etavopivat is an investigational, once daily, oral, selective erythrocyte pyruvate kinase (PKR) activator. A multicenter, randomized, placebo-controlled, double-blind, 3-part, phase 1 study was conducted to characterize the safety and clinical activity of etavopivat. Thirty-six patients with sickle cell disease (SCD) were enrolled into 4 cohorts: 1 single-dose, 2 multiple ascending doses, and 1 open-label (OL). In the OL cohort, 15 patients (median age 33.0 years [range, 17-55]) received 400 mg etavopivat once daily for 12 weeks; 14 patients completed treatment. Consistent with the mechanism of PKR activation, increases in adenosine triphosphate and decreases in 2,3-diphosphoglycerate were observed and sustained over …

Clearing New Frontiers: Sinonasal Health And The Future Of Spaceflight, Faizaan I Khan, Isuru Somawardana, Roshan Dongre, Najm S Khan, Keyvon Rashidi, Samuel Razmi, David Hilmers, Omar G Ahmed, Masayoshi Takashima

Faculty, Staff and Students Publications

No abstract provided.

Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana

Faculty, Staff and Students Publications

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of …

Safety Of Treating Acute Pulmonary Embolism At Home: An Individual Patient Data Meta-Analysis, Dieuwke Luijten, Delphine Douillet, Kim Luijken, Cecile Tromeur, Andrea Penaloza, Olivier Hugli, Drahomir Aujesky, Stefano Barco, Joseph R Bledsoe, Kyle E Chang, Francis Couturaud, Paul L Den Exter, Carme Font, Menno V Huisman, David Jimenez, Christopher Kabrhel, Jeffrey A Kline, Stavros Konstantinides, Thijs Van Mens, Remedios Otero, W Frank Peacock, Olivier Sanchez, William B Stubblefield, Luca Valerio, David R Vinson, Philip Wells, Maarten Van Smeden, Pierre-Marie Roy, Frederikus A Klok

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis.

METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events …

Influence Of Pathophysiologic Patterns Of Coronary Artery Disease On Immediate Percutaneous Coronary Intervention Outcomes, Carlos Collet, Daniel Munhoz, Takuya Mizukami, Jeroen Sonck, Hitoshi Matsuo, Toshiro Shinke, Hirohiko Ando, Brian Ko, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Ketina Arslani, Antonio Maria Leone, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Stephane Fournier, Liyew Desta, Andy Yong, Julien Adjedj, Javier Escaned, Masafumi Nakayama, Ashkan Eftekhari, Frederik M Zimmermann, Koshiro Sakai, Tatyana Storozhenko, Bruno R Da Costa, Gianluca Campo, Nick E J West, Tom De Potter, Ward Heggermont, Dimitri Buytaert, Jozef Bartunek, Colin Berry, Damien Collison, Thomas Johnson, Tetsuya Amano, Divaka Perera, Allen Jeremias, Ziad Ali, Nico H J Pijls, Bernard De Bruyne, Nils P Johnson

Faculty, Staff and Student Publications

Background: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes.

Methods: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI.

Results: A total of …

Patient And Family Contributions To Improve The Diagnostic Process Through The Ourdx Electronic Health Record Tool: A Mixed Method Analysis, Sigall K Bell, Kendall Harcourt, Joe Dong, Catherine Desroches, Nicholas J Hart, Stephen K Liu, Long Ngo, Eric J Thomas, Fabienne C Bourgeois

Faculty, Staff and Student Publications

Background: Accurate and timely diagnosis relies on sharing perspectives among team members and avoiding information asymmetries. Patients/Families hold unique diagnostic process (DxP) information, including knowledge of diagnostic safety blindspots-information that patients/families know, but may be invisible to clinicians. To improve information sharing, we co-developed with patients/families an online tool called 'Our Diagnosis (OurDX)'. We aimed to characterise patient/family contributions in OurDX and how they differed between individuals with and without diagnostic concerns.

Method: We implemented OurDX in two academic organisations serving patients/families living with chronic conditions in three subspecialty clinics and one primary care clinic. Prior to each visit, patients/families …

Inhalational Drug Devices: Revisiting The Linchpin Of Asthma Management, Damini Saxena, Neveda Murugesan, Uyioghosa D Evbayiro, Marina K Ngassa, Muhammad Adrish

Faculty, Staff and Students Publications

Asthma remains a prevalent condition among all age groups globally. First-line treatment requires the delivery of medications into the distal respiratory tract via inhalers. Using appropriate inhaler techniques is a significant challenge in achieving disease control. A variety of inhalers are available for treating asthma, and selecting the appropriate inhaler type for any given patient is crucial to achieving and maintaining symptomatic control. This review will discuss the anatomy and physiology behind drug delivery via inhalers, the types of inhalers currently available for use, nebulizers, and future directions in the delivery of inhaled medications for asthma.

The Sod1 Inhibitor, Lcs-1, Oxidizes H2s To Reactive Sulfur Species, Directly And Indirectly, Through Conversion Of Sod1 To An Oxidase, Kenneth R Olson, Tsuyoshi Takata, Kasey J Clear, Yan Gao, Zhilin Ma, Ella Pfaff, Karthik Mouli, Thomas A Kent, Prentiss Jones, Jon Fukuto, Gang Wu, Karl D Straub

Faculty, Staff and Student Publications

LCS-1, a putative selective inhibitor of SOD1, is a substituted pyridazinone with rudimentary similarity to quinones and naphthoquinones. As quinones catalytically oxidize H2S to biologically active reactive sulfur species (RSS), we hypothesized LCS-1 might have similar attributes. Here, we examine LCS-1 reactions with H2S and SOD1 using thiol-specific fluorophores, liquid chromatography–mass spectrometry, electron paramagnetic resonance (EPR), UV–vis spectrometry, and oxygen consumption. We show that LCS-1 catalytically oxidizes H2S in buffer solutions to form RSS, namely per- and polyhydrosulfides (H2Sn, n = 2–6). These reactions consume oxygen and produce hydrogen peroxide, but they do not have an EPR signature, nor do …

Dual Inhibition Of The Trka And Jak2 Pathways Using Entrectinib And Pacritinib Suppresses The Growth And Metastasis Of Her2-Positive And Triple-Negative Breast Cancers, Angelina T Regua, Shivani Bindal, Mariana K Najjar, Chuling Zhuang, Munazza Khan, Austin B J Arrigo, Anneliese O Gonzalez, Xinhai R Zhang, Jay-Jiguang Zhu, Kounosuke Watabe, Hui-Wen Lo

Faculty, Staff and Student Publications

HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness …

Bispecific Antibodies And Autologous Chimeric Antigen Receptor T Cell Therapies For Treatment Of Hematological Malignancies, Samer Al Hadidi, Helen E Heslop, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

In recent years, the therapeutic landscape for hematological malignancies has markedly advanced, particularly since the inaugural approval of autologous chimeric antigen receptor T cell (CAR-T) therapy in 2017 for relapsed/refractory acute lymphoblastic leukemia (ALL). Autologous CAR-T therapy involves the genetic modification of a patient's T cells to specifically identify and attack cancer cells, while bispecific antibodies (BsAbs) function by binding to both cancer cells and immune cells simultaneously, thereby triggering an immune response against the tumor. The subsequent approval of various CAR-T therapies and BsAbs have revolutionized the treatment of multiple hematological malignancies, highlighting high response rates and a subset …

Population-Level Trends In Self-Reported Healthcare Utilization Among Older Adults In Mexico With And Without Cognitive Impairment, José Eduardo Cabrero Castro, Rebeca Wong, Rafael Samper Ternent, Brian Downer

Faculty, Staff and Student Publications

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico.

METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and …

Gastrocnemius Electrical Stimulation Increases Ankle Dorsiflexion Strength In Patients With Post-Acute Sequelae Of Sars-Cov-2 (Pasc): A Double-Blind Randomized Controlled Trial, Myeounggon Lee, Alejandro Zulbaran-Rojas, Miguel Bargas-Ochoa, Bernardo Martinez-Leal, Rasha Bara, Areli Flores-Camargo, M G Finco, Ram Kinker Mishra, Jaewon Beom, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

Post-Acute sequelae of SARS-CoV-2 (PASC) is a multisystem disorder causing persistent musculoskeletal deconditioning and reduced lower extremity strength. Electrical stimulation (E-Stim) to the gastrocnemius muscle can enhance strength outcomes by increasing the frequency of muscle fiber activation. We investigated its effect on individuals with PASC. Participants were randomized into intervention (IG) or control (CG) groups. The IG self-administered daily one-hour E-Stim to both their gastrocnemius muscles using a functional device over 4-week, while the CG used a sham device. Primary outcomes were ankle dorsiflexion strength assessed via dynamometry during maximum voluntary contractions, and gastrocnemius voluntary activation (GVA) via surface electromyography. …

Effect Of Semaglutide On Regression And Progression Of Glycemia In People With Overweight Or Obesity But Without Diabetes In The Select Trial, Steven E Kahn, John E Deanfield, Ole Kleist Jeppesen, Scott S Emerson, Trine Welløv Boesgaard, Helen M Colhoun, Robert F Kushner, Ildiko Lingvay, Bartolome Burguera, Grzegorz Gajos, Deborah Bade Horn, Irene M Hramiak, Ania M Jastreboff, Alexander Kokkinos, Michael Maeng, Ana Laura S A Matos, Francisco J Tinahones, A Michael Lincoff, Donna H Ryan, Select Trial Investigators

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes.

RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c

RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference …

Assessing The State Of Obesity Care: Quality, Access, Guidelines, And Standards, Lee M Kaplan, Caroline M Apovian, Jamy D Ard, David B Allison, Louis J Aronne, Rachel L Batterham, Luca Busetto, Dror Dicker, Deborah B Horn, Aaron S Kelly, Jeffrey I Mechanick, Jonathan Q Purnell, Ximena Ramos-Salas, Assessing The State Of Obesity Care Writing Group

Faculty, Staff and Student Publications

BACKGROUND: An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence.

AIMS: The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity.

METHODS: The panel was held in Leesburg, Virginia in September 2019.

RESULTS: The panelists recommended addressing these unmet needs in obesity medicine through research, education, evaluation of delivery and payment of care, and updating clinical practice …

Association Between Intravenous Fluids During Labor And Primary Postpartum Hemorrhage: A Retrospective Cohort Study, Belinda R Bruce, Heather L Shepherd, Saleem Ahmed Khan, Charlotte R Haunton, Julie Leask, Bradley S De Vries

Faculty, Staff and Student Publications

INTRODUCTION: There is a major research gap relating to the impact of intravenous (IV) fluids administration during labor on maternal and neonatal outcomes. It is biologically plausible that a relationship between volume of IV fluids and primary postpartum hemorrhage (PPH) exists. The primary objective of this study was to evaluate whether the administration of high-volume IV fluids during labor (≥ 2500 mL) increases the risk of primary PPH and other adverse outcomes for women with a term, singleton pregnancy, in comparison to low-volume IV fluids during labor (<2500 >mL).

MATERIAL AND METHODS: A retrospective cohort study was conducted at a …

Vertebrate And Invertebrate Animal Infection Models Of Candida Auris Pathogenicity, Melissa Martinez, Danielle A Garsin, Michael C Lorenz

Faculty, Staff and Student Publications

Candida auris is an emerging fungal pathogen with several concerning qualities. First recognized in 2009, it has arisen in multiple geographically distinct genomic clades nearly simultaneously. C. auris strains are typically multidrug resistant and colonize the skin much better than most other pathogenic fungi; it also persists on abiotic surfaces, enabling outbreaks due to transmission in health care facilities. All these suggest a biology substantially different from the 'model' fungal pathogen, Candida albicans and support intensive investigation of C. auris biology directly. To uncover novel virulence mechanisms in this species requires the development of appropriate animal infection models. Various studies …

Practice For Real Life: Diversifying Cases In Educational Conferences, Erin H Yang, Zaven Sargsyan, Stephanie V Sherman, Prathit A Kulkarni

Faculty, Staff and Students Publications

No abstract provided.

Cognitive Behavioral Therapy Factors Related To Outcomes In Depression Among Youth With Hiv, Betsy D Kennard, Larry K Brown, Kristin Baltrusaitis, Miriam Chernoff, Graham J Emslie, Jessica Jones, Sarah Buisson, Jaime Deville, Megan Wilkins, Amber Bunch, Chivon Mcmullen Jackson, Christy Beneri, David E Shapiro

Faculty, Staff and Students Publications

PURPOSE: This is a secondary analysis of a multi-site, cluster (site) randomized trial of the efficacy of a combined Health and Wellness Cognitive Behavior Therapy (H&W CBT) and medication management approach for depression in youth with HIV (YWH) compared to standard care. In this study, we explored the association between H&W CBT factors and depression outcomes after 24 weeks of treatment to discover treatment elements associated with symptom reduction.

METHODS: Participants (12-24 years of age) were YWH in the United States (US) diagnosed with moderate to severe depression [Quick Inventory of Depressive Symptomatology (QIDS), Clinician-Rated score ≥ 11]. Thirteen US …