Medicine and Health Sciences Commons^™

Association Of Puberty Stage And Weight Status With Cardiometabolic Risk In Children And Adolescents Living On The Texas-Mexico Border, Ee Vien Low, Miryoung Lee, Cici Bauer, Susan P Fisher-Hoch, Joseph B Mccormick, Susan Abughosh, Ekere J Essien, Jessica Rodriguez, Hua Chen

Faculty, Staff and Student Publications

Background: This retrospective cohort study aimed to examine the interaction effect between puberty stage and weight status on individual and clustering of cardiometabolic risk factors (CMRFs) among Mexican American children and adolescents. A total of 333 children and adolescents (aged 8-18 years) enrolled in the Cameron County Hispanic Cohort (CCHC) from 2014 to 2020 were included in the study.

Methods: CCHC is a longitudinal, randomly recruited cohort based on the United States Census tracts/blocks of Mexican Americans living on the Texas-Mexico border. Individual CMRFs, including high blood pressure, central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and insulin resistance (IR) were …

Longitudinal Change In Blood Dna Epigenetic Signature After Smoking Cessation, Amena Keshawarz, Roby Joehanes, Weihua Guan, Tianxiao Huan, Dawn L Demeo, Megan L Grove, Myriam Fornage, Daniel Levy, George O'Connor

Faculty, Staff and Student Publications

Cigarette smoking is associated with epigenetic changes that may be reversible following smoking cessation. Whole blood DNA methylation was evaluated in Framingham Heart Study Offspring (n = 169) and Third Generation (n = 30) cohort participants at two study visits 6 years apart and in Atherosclerosis Risk in Communities (ARIC) study (n = 222) participants at two study visits 20 years apart. Changes in DNA methylation (delta β values) at 483,565 cytosine-phosphate-guanine (CpG) sites and differentially methylated regions (DMRs) were compared between participants who were current, former, or never smokers at both visits (current-current, former-former, never-never, respectively), versus those who …

Maternal Occupational Exposure To Chemicals And Child Cognitive Function, Jennifer Ish, Elaine Symanski, David Gimeno Ruiz De Porras, Maribel Casas, George L Delclos, Mònica Guxens, Jesús M Ibarluzea, Carmen Iñiguez, Aitana Lertxundi, Marisa Rebagliato, Michael D Swartz, Kristina W Whitworth

Faculty, Staff and Student Publications

BACKGROUND: Limited data exist regarding child neurodevelopment in relation to maternal occupational exposure to endocrine-disrupting chemicals (EDCs).

METHODS: We included 1058 mother-child pairs from the INfancia y Medio Ambiente (INMA) project (2003-2008). Using a job-exposure matrix, exposure probability scores for ten EDC groups were assigned to each mother based on her longest held job during pregnancy. At the child's 5-year visit, the McCarthy Scales of Children's Abilities was administered, yielding the general cognitive index and scales for specific cognitive domains. We analyzed region-specific associations between EDC exposures and each outcome separately using adjusted linear regression and combined region-specific effect estimates …

Effectiveness And Feasibility Of The Workout On Wheels Internet Intervention (Wowii) For Individuals With Spinal Cord Injury: A Randomized Controlled Trial, Katherine Froehlich-Grobe, Jaehoon Lee, Christa Ochoa, Amber Lopez, Erina Sarker, Simon Driver, Ross Shegog, Suh-Jen Lin

Faculty, Staff and Student Publications

STUDY DESIGN: Randomized-controlled trial (RCT) with immediate intervention (IMM) and wait-list control (WLC) groups; WLC participants received the intervention during delivery to subsequent cohorts.

OBJECTIVES: Investigate the effectiveness and feasibility of a virtually-delivered exercise intervention.

SETTING: Home and community.

METHODS: A total of 168 middle-aged (49.6 [12.3] years old) men (57%) and women (43%) who lived an average 15.5 (12.3) years with spinal cord injury (SCI) participated. The 16-week program provides users (a) website access with exercise information, resources, and 16 skill-building modules; (b) virtual 60-minute, group-based weekly meetings; and (c) a starter package of exercise equipment. Primary outcomes included …

First-In-Human Study Of An Ox40 (Ivuxolimab) And 4-1bb (Utomilumab) Agonistic Antibody Combination In Patients With Advanced Solid Tumors, Omid Hamid, Alberto A Chiappori, John A Thompson, Toshihiko Doi, Siwen Hu-Lieskovan, Ferry A L M Eskens, Willeke Ros, Adi Diab, Jean-Philippe Spano, Naiyer A Rizvi, Jeffrey S Wasser, Eric Angevin, Patrick A Ott, Alison Forgie, Wenjing Yang, Cen Guo, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

Background: Ivuxolimab (PF-04518600) and utomilumab (PF-05082566) are humanized agonistic IgG2 monoclonal antibodies against OX40 and 4-1BB, respectively. This first-in-human, multicenter, open-label, phase I, dose-escalation/dose-expansion study explored safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ivuxolimab+utomilumab in patients with advanced solid tumors.

Methods: Dose-escalation: patients with advanced bladder, gastric, or cervical cancer, melanoma, head and neck squamous cell carcinoma, or non-small cell lung cancer (NSCLC) who were unresponsive to available therapies, had no standard therapy available or declined standard therapy were enrolled into five dose cohorts: ivuxolimab (0.1-3 mg/kg every 2 weeks (Q2W)) intravenously plus utomilumab (20 or 100 mg every …

Comprehensive Multiplexed Immune Profiling Of The Ductal Carcinoma In Situ Immune Microenvironment Regarding Subsequent Ipsilateral Invasive Breast Cancer Risk, Mathilde M Almekinders, Tycho Bismeijer, Tapsi Kumar, Fei Yang, Bram Thijssen, Rianne Van Der Linden, Charlotte Van Rooijen, Shiva Vonk, Baohua Sun, Edwin R Parra Cuentas, Ignacio I Wistuba, Savitri Krishnamurthy, Lindy L Visser, Iris M Seignette, Ingrid Hofland, Joyce Sanders, Annegien Broeks, Jason K Love, Brian Menegaz, Lodewyk Wessels, Alastair M Thompson, Karin E De Visser, Erik Hooijberg, Esther Lips, Andrew Futreal, Jelle Wesseling

Faculty, Staff and Student Publications

Background: Ductal carcinoma in situ (DCIS) is treated to prevent subsequent ipsilateral invasive breast cancer (iIBC). However, many DCIS lesions will never become invasive. To prevent overtreatment, we need to distinguish harmless from potentially hazardous DCIS. We investigated whether the immune microenvironment (IME) in DCIS correlates with transition to iIBC.

Methods: Patients were derived from a Dutch population-based cohort of 10,090 women with pure DCIS with a median follow-up time of 12 years. Density, composition and proximity to the closest DCIS cell of CD20+ B-cells, CD3+CD8+ T-cells, CD3+CD8- T-cells, CD3+FOXP3+ regulatory T-cells, CD68+ cells, and CD8+Ki67+ T-cells was assessed with …

Tumor Treating Fields With Radiation For Glioblastoma: A Narrative Review, Ryan C. Miller, Muneeb Khan Niazi, Olga Russial, Spencer Poiset, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Background and objective: With a phase 3 clinical trial (EF-32, ClinicalTrials.gov: NCT04471844) currently underway examining the potential benefit of concurrent chemoradiation and tumor treating fields (TTFields) for patients with glioblastoma (GBM), we present the following narrative review to highlight the current evidence that supports this approach. The current management paradigm for GBM includes maximal safe surgical resection followed by concurrent chemoradiation with further temozolomide (TMZ) and TTFields used as maintenance therapy. Despite several treatment advances over the past few decades, the overall prognosis remains poor and new strategies are currently under investigation, including the use of chemoradiation concurrently with …

Atrial Fibrillation Induced By Anticancer Drugs And Underling Mechanisms., Alexander Burashnikov

Division of Cardiology Faculty Papers

Cancer therapy has made major progress in the past several decades, but treatments are often accompanied by significant side effects. Arrhythmias are a widespread complication of some antineoplastic drugs, with atrial fibrillation (AF) being the most often encountered drug-associated arrhythmia. Preexisting AF risk factors are commonly present in cancer patients who develop drug-associated AF, and active cancer itself may cause or promote AF. Although anticancer drugs may induce AF in cancer patients without AF risk factors, it appears that most drug-associated AF develop when cancer drugs add or aggravate precancer-existing and/or cancer-related pro-AF factors/alterations, additively or synergistically producing AF. Abnormalities …

Young Transposable Elements Rewired Gene Regulatory Networks In Human And Chimpanzee Hippocampal Intermediate Progenitors, Sruti Patoori, Samantha M Barnada, Christopher Large, John I Murray, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

The hippocampus is associated with essential brain functions, such as learning and memory. Human hippocampal volume is significantly greater than expected compared with that of non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced pluripotent stem cells into TBR2 (or EOMES)-positive hippocampal intermediate progenitor cells (hpIPCs). We found that the gene networks active in hpIPCs …

Response To Brentuximab Vedotin By Cd30 Expression In Non-Hodgkin Lymphoma, Deepa Jagadeesh, Steve Horwitz, Nancy L Bartlett, Youn Kim, Eric Jacobsen, Madeleine Duvic, Meredith Little, William Trepicchio, Keenan Fenton, Matthew Onsum, Julie Lisano, Ranjana Advani

Faculty, Staff and Student Publications

BACKGROUND: The safety and efficacy of brentuximab vedotin (BV), an antibody-drug conjugate directed to the CD30 antigen, has been assessed in several trials in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell non-Hodgkin lymphoma (NHL). The objective of this research was to examine the relationship between CD30 expression level and clinical response to BV.

PATIENTS AND METHODS: We analyzed response in patients treated with BV monotherapy in 5 prospective clinical studies in relapsed or refractory PTCL, CTCL, or B-cell NHL. CD30 expression was assessed by immunohistochemistry (IHC) using the Ber H2 antibody for 275 patients.

RESULTS: …

Clinical And Pathological Characteristics And Outcomes Among Patients With Subcutaneous Panniculitis-Like T-Cell Lymphoma And Related Adipotropic Lymphoproliferative Disorders, Joan Guitart, Aaron R Mangold, Maria Estela Martinez-Escala, Christina J Walker, Nneka I Comfere, Mellissa Pulitzer, Kerri E Rieger, Carlos A Torres-Cabala, Laura B Pincus, Erica S Kumar, Erica Bo Kyung Wang, Katherine E Park, Maria L Espinosa, Madeleine Duvic, Youn H Kim, Steven Horwitz

Faculty, Staff and Student Publications

IMPORTANCE: There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date.

OBJECTIVE: To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort …

Mismatch Repair And Microsatellite Instability Testing For Immune Checkpoint Inhibitor Therapy: Guideline From The College Of American Pathologists In Collaboration With The Association For Molecular Pathology And Fight Colorectal Cancer, Angela N Bartley, Anne M Mills, Eric Konnick, Michael Overman, Christina B Ventura, Lesley Souter, Carol Colasacco, Zsofia K Stadler, Sarah Kerr, Brooke E Howitt, Heather Hampel, Sarah F Adams, Wenora Johnson, Cristina Magi-Galluzzi, Antonia R Sepulveda, Russell R Broaddus

Faculty, Staff and Student Publications

Context.—: The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status.

Objective.—: To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy.

Design.—: The College of American Pathologists convened an expert panel to perform a systematic review …

Clinical Relevance Of Proteomic Profiling In De Novo Pediatric Acute Myeloid Leukemia: A Children’S Oncology Group Study, Fieke W Hoff, Anneke D Van Dijk, Yihua Qiu, Chenyue W Hu, Rhonda E Ries, Andrew Ligeralde, Gaye N Jenkins, Robert B Gerbing, Alan S Gamis, Richard Aplenc, E Anders Kolb, Todd A Alonzo, Soheil Meshinchi, Amina A Qutub, Eveline S J M De Bont, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

Pediatric acute myeloid leukemia (AML) remains a fatal disease for at least 30% of patients, stressing the need for improved therapies and better risk stratification. As proteins are the unifying feature of (epi)genetic and environmental alterations, and are often targeted by novel chemotherapeutic agents, we studied the proteomic landscape of pediatric AML. Protein expression and activation levels were measured in 500 bulk leukemic patients' samples and 30 control CD34+ cell samples, using reverse phase protein arrays with 296 strictly validated antibodies. The multistep MetaGalaxy analysis methodology was applied and identified nine protein expression signatures (PrSIG), based on strong recurrent protein …

First-In-Human Phase 1/1b Study To Evaluate Sitravatinib In Patients With Advanced Solid Tumors, Todd Bauer, Byong Chul Cho, Rebecca Heist, Lyudmila Bazhenova, Theresa Werner, Sanjay Goel, Dong-Wan Kim, Douglas Adkins, Richard D Carvajal, Ajjai Alva, Keith Eaton, Judy Wang, Yong Liu, Xiaohong Yan, Jamie Christensen, Saskia Neuteboom, Richard Chao, Shubham Pant

Faculty, Staff and Student Publications

Sitravatinib (MGCD516), a spectrum-selective receptor tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MERTK) and split kinase family receptors, has demonstrated preclinical anti-tumor activity and modulation of tumor microenvironment. This first-in-human phase 1/1b study included sitravatinib dose exploration and anti-tumor activity evaluation in selected patients with advanced solid tumors. Primary objectives included assessment of safety, pharmacokinetics and clinical activity of sitravatinib. Secondary objectives included identifying doses for further investigation and exploring molecular markers for patient selection. In phase 1, 32 patients received 10-200 mg, while phase 1b dose expansion comprised 161 patients (150 mg n = 99, 120 mg n = …

T1 Signal Intensity Ratio Of The Pancreas As An Imaging Biomarker For The Staging Of Chronic Pancreatitis, Temel Tirkes, Anil K Dasyam, Zarine K Shah, Evan L Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Stephanie T Chang, Carlos A Farinas, Joseph R Grajo, Kareem Mawad, Naoki Takahashi, Sudhakar K Venkatesh, Ashley Wachsman, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Stephen K Van Den Eeden, Yunlong Yang, Mark Topazian, Dana K Andersen, Jose Serrano, Darwin L Conwell, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Purpose: Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study.

Methods: The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0-6) based on their …

Brequinar And Dipyridamole In Combination Exhibits Synergistic Antiviral Activity Against Sars-Cov-2 In Vitro: Rationale For A Host-Acting Antiviral Treatment Strategy For Covid-19, James F Demarest, Maryline Kienle, Ruthmabel Boytz, Mary Ayres, Eun Jung Kim, J J Patten, Donghoon Chung, Varsha Gandhi, Robert A Davey, David B Sykes, Nadim Shohdy, John C Pottage, Vikram S Kumar

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the associated global pandemic resulting in >400 million infections worldwide and several million deaths. The continued evolution of SARS-CoV-2 to potentially evade vaccines and monoclonal antibody (mAb)-based therapies and the limited number of authorized small-molecule antivirals necessitates the need for development of new drug treatments. There remains an unmet medical need for effective and convenient treatment options for SARS-CoV-2 infection. SARS-CoV-2 is an RNA virus that depends on host intracellular ribonucleotide pools for its replication. Dihydroorotate dehydrogenase (DHODH) is a ubiquitous host …

Effect Of Dexamethasone On Dyspnoea In Patients With Cancer (Abcd): A Parallel-Group, Double-Blind, Randomised, Controlled Trial, David Hui, Veronica Puac, Zeena Shelal, Rony Dev, Sandra K Hanneman, Kristofer Jennings, Hilary Ma, Diana L Urbauer, Sanjay Shete, Frank Fossella, Zhongxing Liao, George Blumenschein, Joe Y Chang, Michael O'Reilly, Saumil J Gandhi, Anne Tsao, Donald A Mahler, Eduardo Bruera

Faculty, Staff and Student Publications

BACKGROUND: Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea.

METHODS: This double-blind, multi-site, parallel group randomized trial enrolled ambulatory patients with cancer, age ≥18, average dyspnea intensity over the past week ≥4/10 in a 0–10 point numeric rating scale and randomly assigned them to receive dexamethasone 8 mg orally every 12 hours for 7 days followed by 4 mg orally every 12 hours for 7 days or matching placebo capsules. Pharmacists conducted permuted block …

Adhering To Eat And Exercise Status During Radiotherapy For Oropharyngeal Cancer For Prevention And Mitigation Of Radiotherapy-Associated Dysphagia, Carly E A Barbon, Christine B Peterson, Amy C Moreno, Stephen Y Lai, Jay P Reddy, Ariana Sahli, Rosemary Martino, Faye M Johnson, Clifton David Fuller, Katherine A Hutcheson

Faculty, Staff and Student Publications

IMPORTANCE: Previously published work reported independent benefit of maintenance of oral intake (eat) and swallowing exercise adherence (exercise) during radiotherapy (RT) on diet and functional outcomes. The current study seeks to validate the authors' previously published findings in a large contemporary cohort of patients with oropharynx cancer (OPC) and address limitations of the prior retrospective study using prospective, validated outcome measures.

OBJECTIVE: To examine the longitudinal association of oral intake and swallowing exercise using validated, clinician-graded and patient-reported outcomes.

DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a prospective OPC registry including patients who underwent primary RT/chemoradiotherapy (CRT) or primary transoral …

An Elisa-Based Platform For Rapid Identification Of Structure-Dependent Nucleic Acid-Protein Interactions Detects Novel Dna Triplex Interactors, Nicholas G Economos, Upasna Thapar, Nanda Balasubramanian, Georgios I Karras, Peter M Glazer

Faculty, Staff and Student Publications

Unusual nucleic acid structures play vital roles as intermediates in many cellular processes and, in the case of peptide nucleic acid (PNA)-mediated triplexes, are leveraged as tools for therapeutic gene editing. However, due to their transient nature, an understanding of the factors that interact with and process dynamic nucleic acid structures remains limited. Here, we developed snapELISA (structure-specific nucleic acid-binding protein ELISA), a rapid high-throughput platform to interrogate and compare up to 2688 parallel nucleic acid structure-protein interactions in vitro. We applied this system to both triplex-forming oligonucleotide-induced DNA triplexes and DNA-bound PNA heterotriplexes to describe the identification of previously …

223ra Induces Transient Functional Bone Marrow Toxicity, Maria Parlani, Francesco Boccalatte, Anna Yeaton, Feng Wang, Jianhua Zhang, Iannis Aifantis, Eleonora Dondossola

Faculty, Staff and Student Publications

223Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety of clinical trials for primary and metastatic cancers to bone. Clinical evaluation of 223Ra hematologic safety showed a significantly increased rate of neutropenia and thrombocytopenia in patients, hinting at myelosuppression as a side effect. Methods: In this study, we investigated the consequences of 223Ra treatment on bone marrow biology by combining flow cytometry, single-cell RNA sequencing, three-dimensional multiphoton microscopy and bone marrow transplantation analyses. Results: 223Ra accumulated in bones and induced zonal radiation damage confined to …

Netbce: An Interpretable Deep Neural Network For Accurate Prediction Of Linear B-Cell Epitopes, Haodong Xu, Zhongming Zhao

Faculty, Staff and Student Publications

Identification of B-cell epitopes (BCEs) plays an essential role in the development of peptide vaccines and immuno-diagnostic reagents, as well as antibody design and production. In this work, we generated a large benchmark dataset comprising 124,879 experimentally supported linear epitope-containing regions in 3567 protein clusters from over 1.3 million B cell assays. Analysis of this curated dataset showed large pathogen diversity covering 176 different families. The accuracy in linear BCE prediction was found to strongly vary with different features, while all sequence-derived and structural features were informative. To search more efficient and interpretive feature representations, a ten-layer deep learning framework …

Artificial Intelligence For Radiation Oncology Applications Using Public Datasets, Kareem A Wahid, Enrico Glerean, Jaakko Sahlsten, Joel Jaskari, Kimmo Kaski, Mohamed A Naser, Renjie He, Abdallah S R Mohamed, Clifton D Fuller

Faculty, Staff and Student Publications

Artificial intelligence (AI) has exceptional potential to positively impact the field of radiation oncology. However, large curated datasets - often involving imaging data and corresponding annotations - are required to develop radiation oncology AI models. Importantly, the recent establishment of Findable, Accessible, Interoperable, Reusable (FAIR) principles for scientific data management have enabled an increasing number of radiation oncology related datasets to be disseminated through data repositories, thereby acting as a rich source of data for AI model building. This manuscript reviews the current and future state of radiation oncology data dissemination, with a particular emphasis on published imaging datasets, AI …

Self-Expanding Transcatheter Vs Surgical Aortic Valve Replacement In Intermediate-Risk Patients: 5-Year Outcomes Of The Surtavi Randomized Clinical Trial, Nicolas M Van Mieghem, G Michael Deeb, Lars Søndergaard, Eberhard Grube, Stephan Windecker, Hemal Gada, Mubashir Mumtaz, Peter S Olsen, John C Heiser, William Merhi, Neal S Kleiman, Stanley J Chetcuti, Thomas G Gleason, Joon Sup Lee, Wen Cheng, Raj R Makkar, Juan Crestanello, Barry George, Isaac George, Susheel Kodali, Steven J Yakubov, Patrick W Serruys, Rüdiger Lange, Nicolo Piazza, Mathew R Williams, Jae K Oh, David H Adams, Shuzhen Li, Michael J Reardon

Faculty, Staff and Student Publications

IMPORTANCE: In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited.

OBJECTIVE: To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial.

DESIGN, SETTING, AND PARTICIPANTS: SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. …

Preventive And Therapeutic Reduction Of Amyloid Deposition And Behavioral Impairments In A Model Of Alzheimer’S Disease By Whole Blood Exchange, Akihiko Urayama, Ines Moreno-Gonzalez, Diego Morales-Scheihing, Vineetkumar Kharat, Sandra Pritzkow, Claudio Soto

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the major form of dementia in the elderly population. The main neuropathological changes in AD patients are neuronal death, synaptic alterations, brain inflammation, and the presence of cerebral protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Compelling evidence suggests that the misfolding, aggregation, and cerebral deposition of amyloid-beta (Aβ) plays a central role in the disease. Thus, prevention and removal of misfolded protein aggregates is considered a promising strategy to treat AD. In the present study, we describe that the development of cerebral amyloid plaques in a transgenic mice model of AD (Tg2576) …

The Impact Of Intraoperative Glucagon On The Diagnostic Accuracy Of Intraoperative Cholangiogram For The Diagnosis Of Choledocholithiasis: Experience From A Large Tertiary Care Center, Artem Boyev, Srinivas Sanjeevi, Martha M Estrada, Tien C Ko, Curtis J Wray

Faculty, Staff and Student Publications

INTRODUCTION: In response to the COVID-19 pandemic, hospitals reported decreased admissions for acute surgical diagnoses, but scant data was available to quantify the decrease and its consequences. The objective of this study was to examine the incidence of acute care surgery encounters before and during the COVID-19 pandemic.

MATERIALS AND METHODS: A retrospective cohort study was performed at a single, urban, United States safety-net hospital. Emergency room encounters, admissions, non-elective surgical procedures, patient acuity, and surgical complications were compared before and after the start of the COVID-19 pandemic. The primary outcome of the study was the incidence rate (IR) and …

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

DESIGN: A cross-sectional observational study.

SETTING: A scientific laboratory.

POPULATION: Chronic stroke.

METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …

Development Of The International Spinal Cord Injury Basic Data Set For Informal Caregivers, Carol Haywood, Rebecca Martin, Kathryn Dent, M J Mulcahey

Faculty, Staff and Student Publications

STUDY DESIGN: Mixed-methods, including expert consensus for initial development and a multi-center repeated measures design for field testing.

OBJECTIVES: To develop an International Spinal Cord Injury Basic Data Set for caregivers of individuals with spinal cord injury/disorder (SCI/D) for use in research and clinical care settings.

SETTING: International, multi-disciplinary working group with field testing in five North American pediatric rehabilitation hospitals.

METHODS: The data set was developed iteratively through meetings and online surveys with a working group of experts in pediatric and adult SCI/D rehabilitation and caregivers of individuals with SCI/D. Initial reliability was examined through repeat administration of a …

Rumination As A Mediator Of The Association Between Racial Discrimination And Depression Among Black Youth, Donte L Bernard, Colleen A Halliday, Funlola Are, Devin E Banks, Carla Kmett Danielson

Faculty, Staff and Student Publications

BACKGROUND: Racial discrimination constitutes a significant risk factor for depressive symptoms among Black youth. Rumination, a maladaptive self-regulatory stress response, is a notable pathway by which racial discrimination contributes to depressive symptoms among racial/ethnic minority adults. Yet, examinations of the mechanistic nature of rumination in the context of racial discrimination among racial/ethnic minority youth remain limited. The present study investigated rumination as a mediator of the association between racial discrimination and depressive symptoms among Black youth.

METHODS: Data for the current study were drawn from baseline questionnaire responses of community recruited Black pre-and-early adolescents (N = 158, 53% female, M …

Genetics And Epigenetics Of Self-Injurious Thoughts And Behaviors: Systematic Review Of The Suicide Literature And Methodological Considerations, Salahudeen Mirza, Anna R Docherty, Amanda Bakian, Hilary Coon, Jair C Soares, Consuelo Walss-Bass, Gabriel R Fries

Faculty, Staff and Student Publications

Suicide is a multifaceted and poorly understood clinical outcome, and there is an urgent need to advance research on its phenomenology and etiology. Epidemiological studies have demonstrated that suicidal behavior is heritable, suggesting that genetic and epigenetic information may serve as biomarkers for suicide risk. Here we systematically review the literature on genetic and epigenetic alterations observed in phenotypes across the full range of self-injurious thoughts and behaviors (SITB). We included 577 studies focused on genome-wide and epigenome-wide associations, candidate genes (SNP and methylation), noncoding RNAs, and histones. Convergence of specific genes is limited across units of analysis, although pathway-based …

Concerns About The Use Of Polygenic Embryo Screening For Psychiatric And Cognitive Traits, Todd Lencz, Maya Sabatello, Anna Docherty, Roseann E Peterson, Takahiro Soda, Jehannine Austin, Laura Bierut, David Crepaz-Keay, David Curtis, Franziska Degenhardt, Laura Huckins, Gabriel Lazaro-Munoz, Manuel Mattheisen, Bettina Meiser, Holly Peay, Marcella Rietschel, Consuelo Walss-Bass, Lea K Davis

Faculty, Staff and Student Publications

Private companies have begun offering services to allow parents undergoing in-vitro fertilisation to screen embryos for genetic risk of complex diseases, including psychiatric disorders. This procedure, called polygenic embryo screening, raises several difficult scientific and ethical issues, as discussed in this Personal View. Polygenic embryo screening depends on the statistical properties of polygenic risk scores, which are complex and not well studied in the context of this proposed clinical application. The clinical, social, and ethical implications of polygenic embryo screening have barely been discussed among relevant stakeholders. To our knowledge, the International Society of Psychiatric Genetics is the first professional …