Medical Specialties Commons^™

Qt Interval And Short-Term Outcome In Acute Heart Failure, Òscar Miró, Oriol Aguiló, Joan Carles Trullàs, Víctor Gil, Begoña Espinosa, Javier Jacob, Pablo Herrero-Puente, Josep Tost, María Luísa López-Grima, Pere Comas, Carlos Bibiano, Lluís Llauger, Enrique Martin Mojarro, María Pilar López-Díez, Julio Núñez, Zubaid Rafique, Kelly R Keene, Frank Peacock, Pedro Lopez-Ayala, Christian Mueller, Manuel Montero Pérez-Barquero, Lluís Mont, Pere Llorens

Faculty, Staff and Students Publications

Objective: To investigate the association of corrected QT (QTc) interval duration and short-term outcomes in patients with acute heart failure (AHF).

Methods: We analyzed AHF patients enrolled in 11 Spanish emergency departments (ED) for whom an ECG with QTc measurement was available. Patients with pace-maker rhythm were excluded. Primary outcome was 30-day all-cause mortality and secondary outcomes were need of hospitalization, in-hospital mortality and prolonged hospitalization (> 7 days). Association between QTc and outcomes was explored by restricted cubic spline (RCS) curves. Results were expressed as odds ratios (OR) and 95%CI adjusted by patients baseline and decompensation characteristics, using a …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Jeffrey V Lazarus, Vlad Ratziu, Sven M Francque, Arun J Sanyal, Fasiha Kanwal, Diana Romero, Manal F Abdelmalek, Quentin M Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D Byrne, Graciela E Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D Guy, Stephen A Harrison, Seung Up Kim, Bart G Koot, Marko Korenjak, Kris V Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R Morgan, Elisabeth E Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C Sookoian, C Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N Newsome, Nafld Nomenclature Consensus Group

Faculty, Staff and Students Publications

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 …

Nonsense Variant Prdm16-Q187x Causes Impaired Myocardial Development And Tgf-Β Signaling Resulting In Noncompaction Cardiomyopathy In Humans And Mice, Bo Sun, Omid M T Rouzbehani, Ryan J Kramer, Rajeshwary Ghosh, Robin M Perelli, Sage Atkins, Amir Nima Fatahian, Kathryn Davis, Marta W Szulik, Michael A Goodman, Marissa A Hathaway, Ellenor Chi, Tarah A Word, Hari Tunuguntla, Susan W Denfield, Xander H T Wehrens, Kevin J Whitehead, Hala Y Abdelnasser, Junco S Warren, Mingfu Wu, Sarah Franklin, Sihem Boudina, Andrew P Landstrom

Faculty, Staff and Students Publications

BACKGROUND: PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans.

METHODS: Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR-mediated knock-in mouse model hosting the Prdm16Q187X allele was generated …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Jeffrey V Lazarus, Vlad Ratziu, Sven M Francque, Arun J Sanyal, Fasiha Kanwal, Diana Romero, Manal F Abdelmalek, Quentin M Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D Byrne, Graciela E Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D Guy, Stephen A Harrison, Seung Up Kim, Bart G Koot, Marko Korenjak, Kris V Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R Morgan, Elisabeth E Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C Sookoian, C Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N Newsome, Nafld Nomenclature Consensus Group

Faculty, Staff and Students Publications

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 …

Neonatal Cholestasis In Children With Alpha-1-At Deficiency Is A Risk For Earlier Severe Liver Disease With Male Predominance, Jeffrey Teckman, Philip Rosenthal, Rosalinda V Ignacio, Cathie Spino, Lee M Bass, Simon Horslen, Kasper Wang, John C Magee, Saul Karpen, Akihiro Asai, Jean P Molleston, Robert H Squires, Binita M Kamath, Stephen L Guthery, Kathleen M Loomes, Benjamin L Shneider, Ronald J Sokol, Children (Childhood Liver Disease Research Network)

Faculty, Staff and Students Publications

BACKGROUND: Our objective was to better understand the natural history and disease modifiers of Alpha-1-antitrypsin deficiency (AATD), a common genetic liver disease causing hepatitis and cirrhosis in adults and children. The clinical course is highly variable. Some infants present with neonatal cholestasis, which can resolve spontaneously or progress to cirrhosis; others are well in infancy, only to develop portal hypertension later in childhood.

METHODS: The Childhood Liver Disease Research Network has been enrolling AATD participants into longitudinal, observational studies at North American tertiary centers since 2004. We examined the clinical courses of 2 subgroups of participants from the several hundred …

Effect Of Aerobic Exercise On Erectile Function: Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Mohit Khera, Samir Bhattacharyya, Larry E Miller

Faculty, Staff and Students Publications

Background: The health benefits of regular aerobic exercise are well established, although there is limited high-quality evidence regarding its impact on erectile function.

Aim: To determine the effect of aerobic exercise on erectile function in men and to identify factors that may influence this effect.

Methods: This systematic review and meta-analysis included randomized controlled trials that evaluated the effects of aerobic exercise on erectile function via the Erectile Function domain of the International Index of Erectile Function (IIEF-EF). The mean difference in IIEF-EF scores between the aerobic exercise and nonexercising control groups was estimated by a random-effects meta-analysis. Meta-regression was …

Rcc2 Promotes Prostate Cancer Cell Proliferation And Migration Through Hh/Gli1 Signaling Pathway And Cancer Stem-Like Cells, Shenghan Wang, Zhentao Lei, Wei Liu, Jie Xiong, Yuqiang Shi, Lin Yang, Qiang Gao, Kai Le, Bao Zhang

Faculty, Staff and Student Publications

BACKGROUND: Regulator of chromosome condensation 2 (RCC2) was a telophase disk-binding protein on mitosis, and functions as an oncogene in many human cancers. However, its role on prostate cancer (PCa) was unknown. The goal of this study is to explore the function of RCC 2 on PCa development.

METHODS: The expression of RCC2 and its methylation level, its correlation with lymph node metastasis or disease-free survival (DFS) was analyzed using TCGA database. The effect of RCC2 on PCa cell proliferation, migration and invasion were detected using CCK-8, cell colony formation, Transwell and wood healing assays. RNA-seq and GSEA analysis were …

Case Of New-Onset Scleromyxoedema-Scleroedema Spectrum Disorder In A Patient With Cll, Yuanteng Jeff Li, Victor G Prieto, Jean Tayar

Faculty, Staff and Student Publications

No abstract provided.

Glial Cell Adhesion Molecule (Glialcam) Determines Proliferative Versus Invasive Cell States In Glioblastoma, Arpan De, John M Lattier, John E Morales, Jack R Kelly, Xiaofeng Zheng, Zhihua Chen, Sumod Sebastian, Zahra Nassiri Toosi, Jason T Huse, Frederick F Lang, Joseph H Mccarty

Faculty, Staff and Student Publications

The malignant brain cancer glioblastoma (GBM) contains groups of highly invasive cells that drive tumor progression as well as recurrence after surgery and chemotherapy. The molecular mechanisms that enable these GBM cells to exit the primary mass and disperse throughout the brain remain largely unknown. Here we report using human tumor specimens and primary spheroids from male and female patients that glial cell adhesion molecule (GlialCAM), which has normal roles in brain astrocytes and is mutated in the developmental brain disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC), is differentially expressed in subpopulations of GBM cells. High levels of GlialCAM promote …

Early And Empirical High-Dose Cryoprecipitate For Hemorrhage After Traumatic Injury: The Cryostat-2 Randomized Clinical Trial, Ross Davenport, Nicola Curry, Erin E Fox, Helen Thomas, Joanne Lucas, Amy Evans, Shaminie Shanmugaranjan, Rupa Sharma, Alison Deary, Antoinette Edwards, Laura Green, Charles E Wade, Jonathan R Benger, Bryan A Cotton, Simon J Stanworth, Karim Brohi, Cryostat-2 Principal Investigators

Faculty, Staff and Student Publications

IMPORTANCE: Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.

OBJECTIVE: To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.

DESIGN, SETTING, AND PARTICIPANTS: CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US …

Mechanism Of Stepwise Electron Transfer In Six-Transmembrane Epithelial Antigen Of The Prostate (Steap) 1 And 2, Kehan Chen, Lie Wang, Jiemin Shen, Ah-Lim Tsai, Ming Zhou, Gang Wu

Faculty, Staff and Student Publications

Six transmembrane epithelial antigen of the prostate (STEAP) 1-4 are membrane-embedded hemoproteins that chelate a heme prosthetic group in a transmembrane domain (TMD). STEAP2-4, but not STEAP1, have an intracellular oxidoreductase domain (OxRD) and can mediate cross-membrane electron transfer from NADPH via FAD and heme. However, it is unknown whether STEAP1 can establish a physiologically relevant electron transfer chain. Here, we show that STEAP1 can be reduced by reduced FAD or soluble cytochrome b5 reductase that serves as a surrogate OxRD, providing the first evidence that STEAP1 can support a cross-membrane electron transfer chain. It is not clear whether …

The Role Of Vitamin D In Patients With Inflammatory Bowel Disease Treated With Vedolizumab, Bincy P Abraham, Christopher Fan, Theresa Thurston, Joshua Moskow, Hoda M Malaty

Faculty, Staff and Students Publications

BACKGROUND: Many clinical factors can contribute to the efficacy of medical therapy in Inflammatory Bowel Disease (IBD). We assessed their effects on the efficacy of vedolizumab therapy in a cohort of patients with IBD.

METHODS: We conducted a retrospective study on patients between 18 and 80 years of age with ulcerative colitis (UC) or Crohn's disease (CD) who were seen in the IBD program at Houston Methodist in Houston, TX and treated with vedolizumab for at least 6 months from 2018 to 2022. We investigated factors prior to the initiation of therapy that best predicted treatment response, with an emphasis …

Molecular Basis Of Retinal Remodeling In A Zebrafish Model Of Retinitis Pigmentosa, Abirami Santhanam, Eyad Shihabeddin, Haichao Wei, Jiaqian Wu, John O'Brien

Faculty, Staff and Student Publications

A hallmark of inherited retinal degenerative diseases such as retinitis pigmentosa (RP) is progressive structural and functional remodeling of the remaining retinal cells as photoreceptors degenerate. Extensive remodeling of the retina stands as a barrier for the successful implementation of strategies to restore vision. To understand the molecular basis of remodeling, we performed analyses of single-cell transcriptome data from adult zebrafish retina of wild type AB strain (WT) and a P23H mutant rhodopsin transgenic model of RP with continuous degeneration and regeneration. Retinas from both female and male fish were pooled to generate each library, combining data from both sexes. …

Gonadotropin-Secreting And Thyrotropin-Secreting Pituitary Adenomas: A Single-Center Experience, Manjiri Karlekar, Chakra Diwaker, Vijaya Sarathi, Anurag Lila, Anima Sharma, Saba Samad Memon, Virendra Patil, Tushar Bandgar

Faculty, Staff and Student Publications

OBJECTIVE: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India.

MATERIALS AND METHODS: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical(inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas.

RESULTS: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, …

Circulating Metabolites May Illustrate Relationship Of Alcohol Consumption With Cardiovascular Disease, Yi Li, Mengyao Wang, Xue Liu, Jian Rong, Patricia Emogene Miller, Roby Joehanes, Tianxiao Huan, Xiuqing Guo, Jerome I Rotter, Jennifer A Smith, Bing Yu, Matthew Nayor, Daniel Levy, Chunyu Liu, Jiantao Ma

Faculty, Staff and Student Publications

BACKGROUND: Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.

METHODS: Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, …

Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 …

Targeting The Αvβ3/Ngr2 Pathway In Neuroendocrine Prostate Cancer, Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin E Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in …

Counts, Incidence Rates, And Trends Of Pediatric Cancer In The United States, 2003–2019, David A Siegel, Jessica B King, Philip J Lupo, Eric B Durbin, Eric Tai, Kathi Mills, Elizabeth Van Dyne, Natasha Buchanan Lunsford, S Jane Henley, Reda J Wilson

Faculty, Staff and Students Publications

BACKGROUND: Cancer is a leading cause of death by disease among children and adolescents in the United States. This study updates cancer incidence rates and trends using the most recent and comprehensive US cancer registry data available.

METHODS: We used data from US Cancer Statistics to evaluate counts, age-adjusted incidence rates, and trends among children and adolescents younger than 20 years of age diagnosed with malignant tumors between 2003 and 2019. We calculated the average annual percent change (APC) and APC using joinpoint regression. Rates and trends were stratified by demographic and geographic characteristics and by cancer type.

RESULTS: With …

Identification Of Blood Protein Biomarkers Associated With Prostate Cancer Risk Using Genetic Prediction Models: Analysis Of Over 140,000 Subjects, Hua Zhong, Jingjing Zhu, Shuai Liu, Dalia H Ghoneim, Praveen Surendran, Tao Liu, Sarah Fahle, Adam Butterworth, Md Ashad Alam, Hong-Wen Deng, Herbert Yu, Chong Wu, Lang Wu

Faculty, Staff and Student Publications

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. We developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant …

Multimodal Analysis Of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury, Finian Keleher, Hannah M Lindsey, Rebecca Kerestes, Houshang Amiri, Robert F Asarnow, Talin Babikian, Brenda Bartnik-Olson, Erin D Bigler, Karen Caeyenberghs, Carrie Esopenko, Linda Ewing-Cobbs, Christopher C Giza, Naomi J Goodrich-Hunsaker, Cooper B Hodges, Kristen R Hoskinson, Andrei Irimia, Marsh Königs, Jeffrey E Max, Mary R Newsome, Alexander Olsen, Nicholas P Ryan, Adam T Schmidt, Dan J Stein, Stacy J Suskauer, Ashley L Ware, Anne L Wheeler, Brandon A Zielinski, Paul M Thompson, Ian H Harding, David F Tate, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Student Publications

Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning.

Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function.

Design, setting, and participants: This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or …

Cardioprotective Effects Of Sodium-Glucose Cotransporter 2 Inhibitors And Their Possible Association With Normalization Of The Circadian Index Of Heart Rhythm, Nazile Bilgin Dogan, Hamiyet Yilmaz Yasar, Baris Kilicaslan

The Texas Heart Institute Journal

Background

Updated recommendations for the treatment of heart failure with reduced ejection fraction (HFrEF) include sodium-glucose cotransporter 2 (SGLT2) inhibitors and other long-established HFrEF therapies. These drugs’ mechanisms of action have yet to be fully clarified.

Objective

This study evaluated the effects of SGLT2 inhibitors on the modulation of autonomic function at 1 month beyond conventional HF therapy.

Methods

This single-center, observational, prospective study was conducted from January 2020 to December 2022. Patients with type 2 diabetes who had ischemic HFrEF and met the study criteria were considered for SGLT2 inhibitor treatment with empagliflozin or dapagliflozin. Changes in the circadian …

Clonal Hematopoiesis Of Indeterminate Potential (Chip) And Incident Type 2 Diabetes Risk, Deirdre K Tobias, Alisa K Manning, Jennifer Wessel, Sridharan Raghavan, Kenneth E Westerman, Alexander G Bick, Daniel Dicorpo, Eric A Whitsel, Jason Collins, Adolfo Correa, L Adrienne Cupples, Josée Dupuis, Mark O Goodarzi, Xiuqing Guo, Barbara Howard, Leslie A Lange, Simin Liu, Laura M Raffield, Alex P Reiner, Stephen S Rich, Kent D Taylor, Lesley Tinker, James G Wilson, Peitao Wu, April P Carson, Ramachandran S Vasan, Myriam Fornage, Bruce M Psaty, Charles Kooperberg, Jerome I Rotter, James Meigs, Joann E Manson

Faculty, Staff and Student Publications

OBJECTIVE: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in atherosclerotic coronary heart disease (CHD) and all-cause mortality, but its association with incident type 2 diabetes (T2D) is unknown. We hypothesized that CHIP is associated with elevated risk of T2D.

RESEARCH DESIGN AND METHODS: CHIP was derived from whole-genome sequencing of blood DNA in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) prospective cohorts. We performed analysis for 17,637 participants from six cohorts, without prior T2D, cardiovascular disease, …

Time To Endoscopy Or Colonoscopy Among Adults Younger Than 50 Years With Iron-Deficiency Anemia And/Or Hematochezia In The Vha, Joshua Demb, Lin Liu, Caitlin C Murphy, Chyke A Doubeni, Maria Elena Martinez, Samir Gupta

Faculty, Staff and Student Publications

IMPORTANCE: to date, the diagnostic test completion rate and the time to diagnostic endoscopy or colonoscopy among adults with iron-deficiency anemia (IDA) and/or hematochezia have not been well characterized.

OBJECTIVE: to evaluate the diagnostic test completion rate and the time to diagnostic testing among veterans younger than 50 years with IDA and/or hematochezia.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted within the Veterans Health Administration between October 1, 1999, and December 31, 2019, among US veterans aged 18 to 49 years from 2 separate cohorts: those with a diagnosis of IDA (n = 59 169) and those with …

Resilience Of Patients Undergoing Knee And Shoulder Arthroscopy Procedures, Jillian Mazzocca, Natalie Lowenstein, Connor Crutchfield, Jamie Collins, Elizabeth Matzkin

Student Papers, Posters & Projects

INTRODUCTION: Resilience is a person's capacity to overcome adversity. The purpose was to determine what patient factors correlate with resilience using the Brief Resilience Score. We hypothesize that characteristics of female sex, younger age, Workers' Compensation status, and preoperative opioid use are predictors of a lower preoperative resilience score and that patients with positive psychosocial factors would have higher resilience scores.

METHODS: Eight hundred nine patients undergoing knee or shoulder arthroscopy were preoperatively categorized into low, normal, and high-resilience groups. Preoperative patient-reported outcome measures (PROMs) and demographics were assessed. Statistical analyses evaluated differences in demographics and PROMs between resilience groups. …

Iron Overload Induces Cerebral Endothelial Senescence In Aged Mice And In Primary Culture In A Sex-Dependent Manner, Brian Noh, Maria Pilar Blasco-Conesa, Syed Mushfiqur Rahman, Sheelu Monga, Rodney Ritzel, Gary Guzman, Yun-Ju Lai, Bhanu Priya Ganesh, Akihiko Urayama, Louise D Mccullough, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age-related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence-associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived …

Ramipril For The Treatment Of Covid-19: Ramic, A Randomized, Double-Blind, Placebo-Controlled Clinical Trial, Daniel Q Huang, Veeral Ajmera, Christian Tomaszewski, Andrew Lafree, Ricki Bettencourt, Wesley K Thompson, Davey M Smith, Atul Malhotra, Ravindra L Mehta, Vaishal Tolia, Jeffrey Yin, Paul A Insel, Stone Leachman, Jinho Jung, Summer Collier, Lisa Richards, Kristin Woods, Maral Amangurbanova, Archana Bhatt, Xinlian Zhang, Oana M Penciu, Stuart Zarich, Tamrat Retta, Michelle S Harkins, J Pedro Teixeira, Brian Chinnock, Netanya S Utay, Jordan E Lake, Rohit Loomba

Faculty, Staff and Student Publications

Introduction: Retrospective studies report that angiotensin-converting enzyme inhibitors (ACEIs) may reduce the severity of COVID-19, but prospective data on de novo treatment with ACEIs are limited. The RAMIC trial was a randomized, multicenter, placebo-controlled, double-blind, allocation-concealed clinical trial to examine the efficacy of de novo ramipril versus placebo for the treatment of COVID-19.

Methods: Eligible participants were aged 18 years and older with a confirmed diagnosis of SARS-CoV-2 infection, recruited from urgent care clinics, emergency departments, and hospital inpatient wards at eight sites in the USA. Participants were randomly assigned to daily ramipril 2.5 mg or placebo orally in a …

Elevated Blood Pressure Accelerates White Matter Brain Aging Among Late Middle-Aged Women: A Mendelian Randomization Study In The Uk Biobank, Li Feng, Zhenyao Ye, Chen Mo, Jingtao Wang, Song Liu, Si Gao, Hongjie Ke, Travis A Canida, Yezhi Pan, Marleen M J Van Greevenbroek, Alfons J H M Houben, Kai Wang, Kathryn S Hatch, Yizhou Ma, David K Y Lei, Chixiang Chen, Braxton D Mitchell, L Elliot Hong, Peter Kochunov, Shuo Chen, Tianzhou Ma

Faculty, Staff and Student Publications

BACKGROUND: Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear.

METHODS: In this study, we focused on N  = 228 473 individuals of European ancestry who had genotype data and clinical BP measurements available (103 929 men and 124 544 women, mean age = 56.49, including 16 901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity …

Regional Vulnerability Indices In Youth With Persistent And Distressing Psychoticlike Experiences, Nicole R Karcher, Hailey Modi, Peter Kochunov, Si Gao, Deanna M Barch

Faculty, Staff and Student Publications

IMPORTANCE: Distressing and persistent psychoticlike experiences (PLEs) in youth are associated with greater odds of developing psychiatric conditions in adulthood. Despite this risk, it is unclear whether early PLEs show similar brain patterns compared with adults with psychiatric and neurologic conditions.

OBJECTIVE: To examine the degree to which persistent and distressing PLEs exhibit neural metrics that show similarity to adults with chronic psychiatric and neurologic conditions.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Adolescent Brain Cognitive Development (ABCD) Study examining the persistence and distress associated with PLEs across the first 3 waves of data with baseline structural magnetic resonance …

Pancreatic Replacement Therapy For Maladaptive Behaviors In Preschool Children With Autism Spectrum Disorder, Deborah A Pearson, Robert L Hendren, Matthew F Heil, William R Mcintyre, Shane R Raines

Faculty, Staff and Student Publications

IMPORTANCE: There is an urgent unmet need for a treatment addressing the core symptoms and associated maladaptive symptoms of autism spectrum disorder (ASD), especially in preschool populations.

OBJECTIVES: To evaluate whether treatment of children with ASD aged 3 to 6 years treated with high-protease pancreatic therapy produces long- and short-term improvements in autism-associated maladaptive behaviors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study at 32 sites across the US used a double-blind parallel group, delayed-start design comprising a 2-week blinded placebo run-in, and a double-blind, randomized, placebo-controlled segment (12 weeks). Children were recruited into the study in 2015, with data collection …

Texas Youth Depression And Suicide Research Network (Tx-Ydsrn) Research Registry And Learning Healthcare Network: Rationale, Design, And Baseline Characteristics, Madhukar H Trivedi, Abu Minhajuddin, Holli Slater, Regina Baronia, Joseph C Blader, Jamon Blood, Ryan Brown, Cynthia Claassen, Melissa Defilippis, David Farmer, Cynthia Garza, Jennifer L Hughes, Beth D Kennard, Israel Liberzon, Sarah Martin, Taryn L Mayes, Jair C Soares, Cesar A Soutullo, Eric A Storch, Sarah M Wakefield

Faculty, Staff and Student Publications

Background: American youth are seriously impacted by depression and suicide. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) Participant Registry Study was initiated in 2020 to develop predictive models for treatment outcomes in youth with depression and/or suicidality. This report presents the study rationale, design and baseline characteristics of the first 1000 participants.

Methods: TX-YDSRN consists of the Network Hub (coordinating center), 12 medical school "Nodes" (manage/implement study), each with 1-5 primary care, inpatient, and/or outpatient Sub-Sites (recruitment, data collection). Participants are 8-20-year-olds who receive treatment or screen positive for depression and/or suicidality. Baseline data include mood and suicidality …