Digital Commons Network^™

Association Between Parathyroid Hormone Concentration And Incident Atrial Fibrillation In Older Persons With Kidney Failure Initiating Dialysis, Pascale Khairallah, Sai Liu, Maria E Montez-Rath, Kevin F Erickson, Tara I Chang, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Introduction: Atrial fibrillation (AF) is common in persons with kidney failure on hemodialysis. In the general population, higher intact parathyroid hormone (iPTH) levels were found to be associated with presence of AF. Whether iPTH associates with AF in patients on hemodialysis is unknown.

Methods: Using merged USRDS-DaVita data (2006-2011), we selected persons aged 67+ years who initiated hemodialysis and survived 120 days. Eligible persons had continuous Medicare A + B coverage from 2 years prior to kidney failure and no diagnosis of AF. Sociodemographic, comorbidity, and clinical information were abstracted from Medicare forms, billing claims, and electronic health records. iPTH …

Association Of Insulin Resistance With Radiographic Lung Abnormalities And Incident Lung Disease: The Framingham Offspring Study, Sarath Raju, Paula Sierra, Vickram Tejwani, Kristen A Staggers, Meredith Mccormack, Dennis T Villareal, Ivan O Rosas, Nicola A Hanania, Tianshi David Wu

Faculty, Staff and Students Publications

Objective: Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study.

Research design and methods: Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident …

Refinement Of A Published Gene-Physical Activity Interaction Impacting Hdl-Cholesterol: Role Of Sex And Lipoprotein Subfractions, Kenneth E Westerman, Tuomas O Kilpeläinen, Magdalena Sevilla-Gonzalez, Margery A Connelly, Alexis C Wood, Michael Y Tsai, Kent D Taylor, Stephen S Rich, Jerome I Rotter, James D Otvos, Amy R Bentley, Samia Mora, Hugues Aschard, D C Rao, Charles Gu, Daniel I Chasman, Alisa K Manning

Faculty, Staff and Students Publications

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C). We explored this GxE in the Women’s Genome Health Study (WGHS; N=23,294; the strongest cohort-specific signal in the original meta-analysis), the UK …

Follow-Up Adherence After Teleretinal Screening For Diabetic Retinopathy, Paul D Chamberlain, Rishabh C Date, Kevin L Shen, Giovanni A Campagna, Linda B Piller, Yvonne I Chu, Christina Y Weng

Faculty, Staff and Students Publications

Aim: Determine the follow-up rate for patients referred following an abnormal teleretinal imaging (TRI) screening and examine patient characteristics predictive of follow-up nonadherence.

Materials and methods: A cross-sectional study of patients screened between August 2014 and July 2016 in the Harris Health System (HHS) in Houston, TX. All diabetic patients referred for in-person examination, who had data for all study variables, and who did not have established ophthalmic care in the HHS within the previous 2 years were included. Data collected included TRI findings, clinic location, age, race, gender, hemoglobin A1C (HbA1c), and insulin use. The primary outcome was whether …

Impact Of An Electronic Medical Record Quality Improvement Intervention On Helicobacter Pylori Treatment And Eradication Rates In A U.S. Hospital System, Shivani Kastuar, Samanthika Devalaraju, Juan Gomez Cifuentes, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

Background: In this pre- and post-intervention quality improvement (QI) study, the impact of an electronic medical record (EMR) order set for Helicobacter pylori treatment was assessed. We evaluated changes in optimal treatment regimen usage, eradication testing, and successful eradication rates based on the intervention.

Materials and methods: Data were collected from patients within the Harris Health System (Houston, TX) with H. pylori infection. The pre-intervention cohort included patients with a positive H. pylori test from January to February 2022. An EMR order set for H. pylori treatment implemented in May 2022 included optimal treatment recommendations using local antibiotic resistance patterns …

Epidemiology And Longitudinal Course Of Chylomicronemia: Insights From Nhanes And A Large Health Care System, Seyedmohammad Saadatagah, Mohammadreza Naderian, Miriam Larouche, Daniel Gaudet, Iftikhar J Kullo, Christie M Ballantyne

Faculty, Staff and Students Publications

Background: Chylomicronemia is characterized by fasting triglyceride (TG) ≥1000 mg/dL; its longitudinal course is not well studied.

Methods: Using National Health and Nutrition Examination Survey (NHANES) data (1999-2018; n = 21,998), we determined chylomicronemia prevalence and temporal trend. Using Mayo Clinic data (4,524,506 TG measurements for 1,294,044 individuals), we studied the longitudinal course and ascertained persistent chylomicronemia (PC), defined as TG ≥1000 mg/dL in more than half the measurements for individuals with ≥3 measurements. We used logistic regression to assess factors associated with PC.

Results: In NHANES, the prevalence of chylomicronemia was 0.20% overall, with higher prevalence in men (0.32%) …

"How Can I Get Out Of This?": A Qualitative Study Of The Phenomenology And Functional Impact Of Misophonia In Youth And Families, Andrew Giles Guzick, Catherine Elizabeth Rast, Brenna Burns Maddox, Servando Rodriguez Barajas, Jane Clinger, Joseph Mcguire, Eric A Storch

Faculty, Staff and Students Publications

Introduction: Misophonia is an increasingly recognized disorder characterized by negative emotional and sensory reactions to specific noises. Although misophonia most often begins in childhood, there has been minimal research on its clinical presentation in youth. This qualitative study explored cognitive behavioral processes that are involved in misophonia and its associated functional impairment in young people and their families.

Methods: Focused interviews were conducted with 20 youth with misophonia (ages 10-17) and their parents. Thematic analyses of these interviews using a cognitive behavioral theoretical framework were conducted.

Results: A number of themes were identified, which included internalizing and externalizing cognitive behavioral …

Goldenbraid20 E Coli: A Comprehensive And Characterized Toolkit For Enterics, Matthew B Cooke, Kobie T Welch, Laura D Ramirez, Alice X Wen, David C Marciano, Christophe Herman

Faculty, Staff and Students Publications

Modular cloning systems streamline laboratory workflows by consolidating genetic 'parts' into reusable and modular collections, enabling researchers to fast-track strain construction. The GoldenBraid 2.0 modular cloning system utilizes the cutting property of type IIS restriction enzymes to create defined genetic 'grammars', which facilitate the reuse of standardized genetic parts and assembly of genetic parts in the right order. Here, we present a GoldenBraid 2.0 toolkit of genetic parts designed to accelerate cloning in the model bacterium

No Evidence Of Mmr Induced Trained Immunity To Prevent Sars Cov2: Results From A Multi-Centre Rct, Sinead Delany-Moretlwe, George Kyei, Erik Dubberke, Linda Yun, Leon Du Toit, Mary Politi, Ben Swan, Anne Deschryver, Sherry Mckinnon, Ananya Gupta, Shabaana Khader, Michael S Avidan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Measles-containing vaccines (MCV), by training innate immune cells, are hypothesized to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19).

METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned adults, 18 years and older, to receive MCV or saline. The primary outcome was polymerase chain reaction (PCR) confirmed symptomatic COVID-19, up to 60 days after intervention. Secondary outcomes were PCR-confirmed symptomatic COVID-19 and serologically confirmed SARS-CoV-2 infection, up to 150 days after intervention.

RESULTS: Of 3411 randomised participants, the modified intention-to-treat population included 1607 in the MCV and 1545 in the saline group. …

Barriers And Facilitators To Implementing A Task-Sharing Mental Health Intervention For Sickle Cell Disease Populations In Low- And Middle-Income Countries: A Qualitative Analysis Using The Consolidated Framework For Implementation Research (Cfir), John Patena, Leah Elster, Tania Hameed, Sumedha Kulkarni, Alden Yuanhong Lai, Annika C Sweetland, Joyce Gyamfi, Temitope Ojo, Angela Odoms-Young, Charmaine Royal, Emmanuel Peprah

2020-Current year OA Pubs

BACKGROUND: People living with Sickle Cell Disease (SCD) experience higher rates of common mental disorders (CMD). There is an alarming treatment gap in the provision of adequate mental health services for CMDs in low- and middle-income countries (LMIC). One solution is the implementation of task-sharing interventions such as the Friendship Bench which utilizes concepts of problem-solving therapy (PST). This investigation uses a qualitative study design to evaluate the acceptability and feasibility of implementing a PST-based task-sharing mental health intervention for SCD populations in LMICs using the Consolidated Framework for Implementation Research (CFIR).

METHODS: Purposive, convenience, and snowball sampling strategies were …

Outcomes In Pediatric Cholesteatoma, Katherine M Miller, Yi-Chun Carol Liu, Jaqueline E Weinstein, Michael S Cohen, David H Chi, Samantha Anne

Faculty, Staff and Students Publications

OBJECTIVE: The objective of the study is to evaluate the outcomes of surgical management options for cholesteatoma using a national database.

STUDY DESIGN: Database analysis of the Pediatric Health Information System database to identify children undergoing surgical intervention for cholesteatoma from October 2015 to December 2022.

METHODS: Patients were categorized by initial surgical modality: tympanoplasty (TM), tympanoplasty with canal wall-up tympanomastoidectomy (TM-CWU), and tympanoplasty with canal wall-down tympanomastoidectomy (TM-CWD). Group comparisons were done on number of surgical revisions and number of patients identified with recommendations for hearing aids.

RESULTS: A total of 6304 patients were identified in the database who …

The Pointer Imaging Baseline Cohort: Associations Between Multimodal Neuroimaging Biomarkers, Cardiovascular Health, And Cognition, Theresa M Harrison, Tyler Ward, Jacinda Taggett, Pauline Maillard, Samuel N Lockhart, Youngkyoo Jung, Laura C Lovato, Robert Koeppe, William J Jagust, Danielle Harvey, Joseph C Masdeu, Hwamee Oh, Darren R Gitelman, Neelum T Aggarwal, Mark A Espeland, Maryjo L Cleveland, Rachel Whitmer, Sarah Tomaszewski Farias, Stephen Salloway, Valory Pavlik, Melissa Yu, Christine Tangney, Heather Snyder, Maria Carrillo, Laura D Baker, Prashanthi Vemuri, Charles Decarli, Susan M Landau

Staff and Researcher Publications

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study.

Methods: Participants underwent health and cognitive assessments and neuroimaging with multimodal positron emission tomography (PET) (beta-amyloid [Aβ] and tau) and magnetic resonance imaging (MRI). Framingham risk score (FRS) was used to quantify cardiovascular disease (CVD) risk.

Results: A total of 1052 participants (31% from underrepresented ethnoracial groups) were enrolled. Compared to Aβ-, Aβ+ (29%) participants were older, …

The Infected Diabetic Foot: Risk Factors For Re-Infection After Treatment For Diabetic Foot Osteomyelitis, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index < 0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure < 40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Effective Thrombectomy For Biventricular Thrombosis With An Endoscope Via The Aortic And Tricuspid Heart Valves, Yuki Endo, Yoshiei Shimamura, Chizuo Kikuchi, Hiroshi Niinami

The Texas Heart Institute Journal

The simultaneous formation of thrombi in the left and right ventricles is extremely rare, and this condition's clinical characteristics and prognosis remain unknown. Therefore, treatment methods are still controversial. This case highlights the potential for endoscopic thrombectomy as a viable option for the treatment of giant floating biventricular thrombi in a patient with restricted cardiac function. This approach via the aortic and tricuspid heart valves allowed for effective and complete removal of the thrombi, thereby preventing further embolic complications.

Navigating The Complexities Of Mitral Valve Clipping: Early Severe Mitral Valve Stenosis After Mitral Valve Clipping, Wassim Abouzeid, Ahmad Haddad, Chrystina Kiwan, Ahsan Khan, Addi Suleiman

The Texas Heart Institute Journal

This case study explores the journey of an 80-year-old male patient with a history of hypertension, diabetes, coronary artery disease after coronary artery bypass grafting, atrial fibrillation, and heart failure. Nine months before he presented to the emergency department, he had undergone mitral valve clipping for severe mitral valve regurgitation. Despite initial improvement, the patient experienced return of symptoms, including dyspnea at rest and lower limb edema. The results of this case-discovery of the need for mitral valve replacement-provides insights into the management of complications from mitral valve clipping and emphasizes that management requires a nuanced, meticulous approach.

Long-Term Health-Related Quality Of Life In Kawasaki Disease-Related Coronary Artery Aneurysm: A Large Single-Center Assessment In Nanjing, China, Yun Zhou, Mei Chen, Wenting Gao, Yu Chen, Ying Meng

The Texas Heart Institute Journal

BACKGROUND: The impact of coronary artery aneurysms (CAAs) caused by Kawasaki disease (KD) on long-term health-related quality of life (HRQOL) in children has not been well documented.

METHODS: This study investigated long-term HRQOL in a large sample of children diagnosed with KD-related CAAs. A case-control, retrospective study included 66 patients with KD-related CAAs. A total of 98 hospitalized patients were matched as controls based on age and sex: 49 patients were allocated to a group with pneumonia and 49 patients were allocated to a group with arterio-arterial fistula. Both child-reported and parent-proxy-reported Pediatric Quality of Life Inventory surveys were collected. …

Talking About Suffering In The Intensive Care Unit, Brent M Kious, Judith B Vick, Peter A Ubel, Olivia Sutton, Jennifer Blumenthal-Barby, Christopher E Cox, Deepshikha Ashana

Center for Medical Ethics and Health Policy Staff Publications

Background: Some have hypothesized that talk about suffering can be used by clinicians to motivate difficult decisions, especially to argue for reducing treatment at the end of life. We examined how talk about suffering is related to decision-making for critically ill patients, by evaluating transcripts of conversations between clinicians and patients' families.

Methods: We conducted a secondary qualitative content analysis of audio-recorded family meetings from a multicenter trial conducted in the adult intensive care units of five hospitals from 2012-2017 to look at how the term "suffering" and its variants were used. A coding guide was developed by consensus-oriented discussion …

Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Faculty, Staff and Students Publications

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used …

Biallelic Variation In The Choline And Ethanolamine Transporter Flvcr1 Underlies A Severe Developmental Disorder Spectrum, Daniel G Calame, Jovi Huixin Wong, Puravi Panda, Dat Tuan Nguyen, Nancy C P Leong, Riccardo Sangermano, Sohil G Patankar, Mohamed S Abdel-Hamid, Lama Alabdi, Sylvia Safwat, Kyle P Flannery, Zain Dardas, Jawid M Fatih, Chaya Murali, Varun Kannan, Timothy E Lotze, Isabella Herman, Farah Ammouri, Brianna Rezich, Stephanie Efthymiou, Shahryar Alavi, David Murphy, Zahra Firoozfar, Mahya Ebrahimi Nasab, Amir Bahreini, Majid Ghasemi, Nourelhoda A Haridy, Hamid Reza Goldouzi, Fatemeh Eghbal, Ehsan Ghayoor Karimiani, Amber Begtrup, Houda Elloumi, Varunvenkat M Srinivasan, Vykuntaraju K Gowda, Haowei Du, Shalini N Jhangiani, Zeynep Coban-Akdemir, Dana Marafi, Lance Rodan, Sedat Isikay, Jill A Rosenfeld, Subhadra Ramanathan, Michael Staton, Kerby C Oberg, Robin D Clark, Catharina Wenman, Sam Loughlin, Ramy Saad, Tazeen Ashraf, Alison Male, Shereen Tadros, Reza Boostani, Ghada M H Abdel-Salam, Maha Zaki, Ali Mardi, Farzad Hashemi-Gorji, Ebtesam Abdalla, M Chiara Manzini, Davut Pehlivan, Jennifer E Posey, Richard A Gibbs, Henry Houlden, Fowzan S Alkuraya, Kinga Bujakowska, Reza Maroofian, James R Lupski, Long N Nguyen

Faculty, Staff and Students Publications

Purpose: FLVCR1 encodes a solute carrier protein implicated in heme, choline, and ethanolamine transport. Although Flvcr1-/- mice exhibit skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia (DBA), biallelic FLVCR1 variants in humans have previously only been linked to childhood or adult-onset ataxia, sensory neuropathy, and retinitis pigmentosa.

Methods: We identified individuals with undiagnosed neurodevelopmental disorders and biallelic FLVCR1 variants through international data sharing and characterized the functional consequences of their FLVCR1 variants.

Results: We ascertained 30 patients from 23 unrelated families with biallelic FLVCR1 variants and characterized a novel FLVCR1-related phenotype: severe developmental disorders with profound developmental delay, microcephaly …

Targeted Analysis Of Dyslexia-Associated Regions On Chromosomes 6, 12 And 15 In Large Multigenerational Cohorts, Nicola H Chapman, Patrick A Navas, Michael O Dorschner, Michele Mehaffey, Karen G Wigg, Kaitlyn M Price, Oxana Y Naumova, Elizabeth N Kerr, Sharon L Guger, Maureen W Lovett, Elena L Grigorenko, Virginia Berninger, Cathy L Barr, Ellen M Wijsman, Wendy H Raskind

Faculty, Staff and Students Publications

Dyslexia is a common learning impairment with a genetic basis that affects word reading and spelling. An increasing list of loci and genes have been implicated, but analyses to-date have investigated only limited genomic variation within each locus with no confirmed pathogenic variants identified. Our study is the first to comprehensively sequence both coding and cis-acting regulatory regions of such genes in a large study sample. In a collection of >2000 participants in families from three independent sites, we performed targeted capture and comprehensive sequencing of all exons and some regulatory elements of five candidate risk genes (DNAAF4, CYP19A1, DCDC2, …

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu

Faculty, Staff and Students Publications

Rationale: Atherosclerotic cardiovascular disease (ASCVD) represents the predominant cause of mortality and morbidity globally. Given the established role of hypercholesterolemia as a significant risk factor for ASCVD, the discovery of new lipid-lowering medications is of paramount importance. ATP citrate lyase (ACLY) is a crucial enzyme in cellular metabolism, providing acetyl-CoA as the building block for the biosynthesis of fatty acids and cholesterol. Consequently, it has emerged as a promising drug target for innovative treatments of lipid metabolic disorders.

Methods: Virtual screening of a natural product library was performed to identify small-molecule ACLY inhibitors, leading to the discovery of isoginkgetin (ISOGK). …

Tobacco Exposure Linked To Warthin’S Tumor Being The Most Common Benign Parotid Neoplasm In Veterans: A Retrospective Cohort Study, Louis Abarca, Linda K Green, Ray Y Wang, Vlad C Sandulache, David J Hernandez

Faculty, Staff and Students Publications

Objective: Parotid gland neoplasms account for a large proportion of benign salivary gland tumors, with pleomorphic adenomas (PA) being the most common in the civilian population, followed by Warthin's tumor (WT). However, the distinct risk profiles of Veterans significantly influence the incidence and prevalence of salivary gland neoplasms. We investigated the diagnostic and management algorithms for benign parotid gland neoplasms in Veterans.

< >Methods: Retrospective cohort study. Descriptive statistics were calculated using Microsoft Excel. Categorical variables were compared using chi square tests, and were reported with 95% confidence intervals, with statistical significance set at P <  .05.

Results: The study included 158 patients …

Relationships Of Personality Traits With The Taxonomic Composition Of The Gut Microbiome Among Psychiatric Inpatients, William Orme, Sandra L Grimm, Divya S N Vella, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

Objective: Through the brain-gut-microbiome axis, myriad psychological functions that affect behavior share a dynamic, bidirectional relationship with the intestinal microbiome. Little is known about the relationship between personality-a stable construct that influences social- and health-related behaviors-and the bacterial ecosystem. The authors of this exploratory study examined the relationship between general and maladaptive personality traits and the composition of the gut microbiome.

Methods: In total, 105 psychiatric inpatients provided clinical data and fecal samples. Personality traits were measured with the five-factor model of personality, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Personality Inventory for DSM-5; 16S …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, O'Jay Stewart, Conor Gruber, Haley E Randolph, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Real-World Experiences With Vmat2 Inhibitors In Pediatric Hyperkinetic Movement Disorders, Sujal Manohar, Jennifer Jacobe, Rebecca Berger, Joseph Jankovic, Mariam Hull

Faculty, Staff and Students Publications

Background: Vesicular monoamine transporter 2 (VMAT2) inhibitors are often prescribed for the treatment of hyperkinetic movement disorders such as tics, stereotypy, tardive dyskinesia and chorea. These dopamine depleters have been FDA approved in adults for the treatment of chorea in Huntington's disease and tardive dyskinesia. Use of VMAT2 inhibitors in pediatric hyperkinetic movement disorders, however, is limited due to lack of pediatric FDA approval. We review the real-world prescribing practices and patient experiences with VMAT2 inhibitors in children.

Methods: We performed a retrospective chart review of patients treated with VMAT2 inhibitors at a pediatric movement disorders clinic from 2011 to …

Prognostic Value Of The Monocyte-To-High-Density Lipoprotein-Cholesterol Ratio In Acute Coronary Syndrome Patients: A Systematic Review And Meta-Analysis, Michał Pruc, Jacek Kubica, Maciej Banach, Damian Świeczkowski, Zubaid Rafique, William Frank Peacock, Zbigniew Siudak, Stanisław Surma, Prabath Nanayakkara, Krzysztof Kurek, Anne Lepetit, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Globally, diseases of the cardiovascular system stand as principal contributors to mortality and are expected to show an upward trajectory. The occurrence of acute coronary syndrome (ACS) has been linked to underlying inflammatory processes. The monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) has garnered significant attention as a prognostic biomarker, encapsulating the synergistic roles of inflammation and lipid metabolism in the pathophysiology of cardiovascular diseases, including ACS.

Aims: This meta-analysis examines the prognostic MHR ratio in ACS patients.

Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases to identify the relevant meta-analyses published before February 26, …

Design And Rationale Of Myoflame-19 Randomised Controlled Trial: Myocardial Protection To Reduce Post-Covid Inflammatory Heart Disease Using Cardiovascular Magnetic Resonance Endpoints, Valentina O Puntmann, Dietrich Beitzke, Andreas Kammerlander, Inga Voges, Dominik D Gabbert, Marcus Doerr, Bishwas Chamling, Biykem Bozkurt, Juan Carlos Kaski, Erica Spatz, Eva Herrmann, Gernot Rohde, Philipp Deleuw, Lenka Taylor, Christine Windemuth-Kieselbach, Cornelia Harz, Marta Santiuste, Laura Schoeckel, Juliana Hirayama, Peter C Taylor, Colin Berry, Eike Nagel

Faculty, Staff and Students Publications

Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement before development of myocardial injury and impairment is missing.

Methods: Prospective multicenter randomized placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodeling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no pre-existing significant comorbidities or structural …

Effects Of Dialysate Potassium Concentration Of 30 Mmol/Leffects Of Dialysate Potassium Concentration Of 30 Mmol/L With Sodium Zirconium Cyclosilicate On Dialysis-Free Days Versus Dialysate Potassium Concentration Of 20 Mmol/L Alone On Rates Of Cardiac With Sodium Zirconium Cyclosilicate On Dialysis-Free Days Versus Dialysate Potassium Concentration Of 20 Mmol/L Alone On Rates Of Cardiac Arrhythmias In Hemodialysis Patients With Hyperkalemia Arrhythmias In Hemodialysis Patients With Hyperkalemia, David M Charytan, Wolfgang C Winkelmayer, Christopher B Granger, John P Middleton, Charles A Herzog, Glenn M Chertow, James M Eudicone, Jeremy D Whitson, James A Tumlin

Faculty, Staff and Students Publications

The optimal approach towards managing serum potassium (sK+) and hemodialysate potassium concentrations is uncertain. To study this, adults receiving hemodialysis for three months or more with hyperkalemia (pre-dialysis sK+ 5.1-6.5 mmol/l) had cardiac monitors implanted and were randomized to either eight weeks of 2.0 mmol/l potassium/1.25 mmol/l calcium dialysate without sodium zirconium cyclosilicate (SZC) (2.0 potassium/noSZC) or 3.0 mmol/l potassium/1.25 mmol/l calcium dialysate combined with SZC (3.0 potassium/SZC) on non-dialysis days to maintain pre-dialysis sK+ 4.0-5.5 mmol/l, followed by treatment crossover for another eight weeks. The primary outcome was the rate of adjudicated atrial fibrillation (AF) episodes of at least …

Healthcare Utilization Unchanged In The Control Arm Of A Randomized Clinical Trial, Pratik Gongloor, Saad Nadeem, Xiaoying Yu, Mukaila Raji, Kristina D Mena, Elizabeth M Vaughan

Faculty, Staff and Students Publications

including among control groups. Increased access to care and heightened health awareness during trial enrollment could lead to altered behaviors, a phenomenon known as the Hawthorne effect, which may obscure true intervention impacts; however, this effect remains poorly studied in low-income environments.

Aim: To conduct a secondary exploratory analysis of healthcare utilization among control participants of a randomized clinical trial (RCT).

Methods: We retrospectively analyzed electronic medical records from the control arm (n = 26) of an RCT involving low-income Hispanic adults with type 2 diabetes receiving care at a community clinic. Before randomization to a 12-month diabetes education intervention …