Medical Specialties Commons^™

Molecular Mechanisms Of Resistance To Kinase Inhibitors And Redifferentiation In Thyroid Cancers, Marie-Claude Hofmann, Muthusamy Kunnimalaiyaan, Jennifer R Wang, Naifa L Busaidy, Steven I Sherman, Stephen Y Lai, Mark Zafereo, Maria E Cabanillas

Faculty, Staff and Student Publications

Protein kinases play critical roles in cell survival, proliferation and motility. Their dysregulation is therefore a common feature in the pathogenesis of a number of solid tumors, including thyroid cancers. Inhibiting activated protein kinases has revolutionized thyroid cancer therapy, offering a promising strategy in treating tumors refractory to radioactive iodine treatment or cytotoxic chemotherapies. However, despite satisfactory early responses, these drugs are not curative and most patients inevitably progress due to drug resistance. This review summarizes up-to-date knowledge on various mechanisms that thyroid cancer cells develop to bypass protein kinase inhibition and outlines strategies that are being explored to overcome …

A Semi-Mechanistic Dose-Finding Design In Oncology Using Pharmacokinetic/Pharmacodynamic Modeling, Xiao Su, Yisheng Li, Peter Müller, Chia-Wei Hsu, Haitao Pan, Kim-Anh Do

Faculty, Staff and Student Publications

While a number of phase I dose-finding designs in oncology exist, the commonly used ones are either algorithmic or empirical model-based. We propose a new framework for modeling the dose-response relationship, by systematically incorporating the pharmacokinetic (PK) data collected in the trial and the hypothesized mechanisms of the drug effects, via dynamic PK/PD modeling, as well as modeling of the relationship between a latent cumulative pharmacologic effect and a binary toxicity outcome. This modeling framework naturally incorporates the information on the impact of dose, schedule and method of administration (e.g., drug formulation and route of administration) on toxicity. The resulting …

Development And Validation Of A Population-Based Anatomical Colorectal Model For Radiation Dosimetry In Late Effects Studies Of Survivors Of Childhood Cancer, Constance A Owens, Bastien Rigaud, Ethan B Ludmir, Aashish C Gupta, Suman Shrestha, Arnold C Paulino, Susan A Smith, Christine B Peterson, Stephen F Kry, Choonsik Lee, Tara O Henderson, Gregory T Armstrong, Kristy K Brock, Rebecca M Howell

Faculty, Staff and Student Publications

Purpose: The purposes of this study were to develop and integrate a colorectal model that incorporates anatomical variations of pediatric patients into the age-scalable MD Anderson Late Effects (MDA-LE) computational phantom, and validate the model for pediatric radiation therapy (RT) dose reconstructions.

Methods: Colorectal contours were manually derived from whole-body non-contrast computed tomography (CT) scans of 114 pediatric patients (age range: 2.1-21.6 years, 74 males, 40 females). One contour was used for an anatomical template, 103 for training and 10 for testing. Training contours were used to create a colorectal principal component analysis (PCA)-based statistical shape model (SSM) to extract …

Molecular Map Of Chronic Lymphocytic Leukemia And Its Impact On Outcome, Binyamin A Knisbacher, Ziao Lin, Cynthia K Hahn, Ferran Nadeu, Martí Duran-Ferrer, Kristen E Stevenson, Eugen Tausch, Julio Delgado, Alex Barbera-Mourelle, Amaro Taylor-Weiner, Pablo Bousquets-Muñoz, Ander Diaz-Navarro, Andrew Dunford, Shankara Anand, Helene Kretzmer, Jesus Gutierrez-Abril, Sara López-Tamargo, Stacey M Fernandes, Clare Sun, Mariela Sivina, Laura Z Rassenti, Christof Schneider, Shuqiang Li, Laxmi Parida, Alexander Meissner, François Aguet, Jan A Burger, Adrian Wiestner, Thomas J Kipps, Jennifer R Brown, Michael Hallek, Chip Stewart, Donna S Neuberg, José I Martín-Subero, Xose S Puente, Stephan Stilgenbauer, Catherine J Wu, Elias Campo, Gad Getz

Faculty, Staff and Student Publications

Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the 'CLL map,' we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. …

Comparison Of Pulmonary Function Changes Between Patients Receiving Neoadjuvant Chemotherapy And Chemoradiotherapy Prior To Minimally Invasive Esophagectomy: A Randomized And Controlled Trial, Xiaosang Chen, Mingjun Du, Han Tang, Hao Wang, Yong Fang, Miao Lin, Jun Yin, Lijie Tan, Yaxing Shen

Faculty, Staff and Student Publications

PURPOSE: Adequate pulmonary function is important for patients undergoing surgical resection of esophageal cancer, especially those that received neoadjuvant therapy. However, it is unknown if pre-operative radiation affects pulmonary function differently compared to chemotherapy. The purpose of this study was to compare changes in pulmonary function between patients undergoing minimally invasive esophagectomy (MIE) who received neoadjuvant chemotherapy or chemoradiotherapy.

METHODS: Between March 2017 and March 2018, esophageal cancer patients requiring neoadjuvant therapy were prospectively enrolled and randomly assigned to receive chemotherapy (CT) or chemoradiotherapy (CRT) before MIE. All patients received pulmonary function testing before and after the neoadjuvant therapy. Changes …

Flow Cytometry Immunophenotypic Features Of Pure Erythroid Leukemia And The Distinction From Reactive Erythroid Precursors, Hong Fang, Sa A Wang, M James You, Shimin Hu, Roberto N Miranda, Zhenya Tang, Pei Lin, Jeffrey L Jorgensen, Jie Xu, Beenu Thakral, Ellen J Schlette, Siba El Hussein, Carlos Bueso-Ramos, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

BACKGROUND: The immunophenotype of pure erythroid leukemia (PEL) as determined by flow cytometry immunophenotypic analysis is not well characterized. The immunophenotypic difference between PEL and reactive conditions is under-explored.

METHODS: We assessed and compared the immunophenotype of 24 PEL cases and 28 reactive cases containing early erythroid precursors by flow cytometry.

RESULTS: The neoplastic erythroid cells in all PEL cases were positive for CD36 and CD71. CD45 was also positive in all cases, but the expression level was often dimmer than granulocytes. CD117 expression ranged from partial to uniform, and CD235a was often only positive in the CD117-dim to negative …

Aortic Root Dissection Due To An Automated Fastener Device, Ismael A Salas De Armas, L Maximilian Buja, Manish K Patel, Jayeshkumar Patel, Mehmet H Akay, Emre Gok, Igor D Gregoric

Faculty, Staff and Student Publications

Minimally invasive aortic valve replacement through a right thoracotomy is frequently performed in patients with aortic valve disease. The Cor-Knot Device (LSI Solutions) is an automated fastener that secures valve sutures. This case report is for a patient who developed postcardiotomy shock during a minimally invasive aortic valve surgery. The patient was found to have an aortic root dissection involving 90% of the aortic root circumference, including bilateral coronary ostia. The autopsy revealed that the aortic damage could be explained by a direct aortic intimal tear from the distal tip of the device shaft. The device was most likely not …

Active Vs Traditional Methods Of Recruiting Children For A Clinical Trial In Rural Primary Care Clinics: A Cluster-Randomized Clinical Trial, Paul M Darden, Ann M Davis, Jeannette Y Lee, Milan Bimali, Alan E Simon, Andrew M Atz, Crystal S Lim, Thao-Ly Phan, James R Roberts, Russell J Mcculloh, Lee Pyles, Michelle Shaffer, Jessica N Snowden

Department of Pediatrics Faculty Papers

Importance: To our knowledge, there are no published randomized clinical trials of recruitment strategies. Rigorously evaluated successful recruitment strategies for children are needed.

Objective: To evaluate the feasibility of 2 recruitment methods for enrolling rural children through primary care clinics to assess whether either or both methods are sufficiently effective for enrolling participants into a clinical trial of a behavioral telehealth intervention for children with overweight or obesity.

Design, setting, and participants: This cluster-randomized clinical trial of 2 recruitment methods was conducted at 4 primary care clinics in 4 separate states. Each clinic used both recruitment methods in random order. …

A Case Of Isolated Cardiac Burkitt Lymphoma Causing Right-Sided Heart Failure, Graham Rector, Stephanie J Koh, Rashed Tabbaa

The Texas Heart Institute Journal

Primary cardiac tumors are rare, as the most common cause of cardiac masses is from metastatic disease. In this article, a unique case of isolated cardiac Burkitt lymphoma causing right-sided heart failure in a 70-year-old man who presented to the emergency department with abdominal distension and lower-extremity swelling is described. The right ventricular mass was initially identified via computed tomographic scans of the abdomen and pelvis. Further workup included transthoracic echocardiogram and cardiac magnetic resonance imaging that showed extension of the mass into the right atrium and pericardium. Staging imaging and bone marrow biopsy revealed no evidence of metastatic disease. …

Dilated Cardiomyopathy With Multiple Left Ventricular Thrombi And Embolic Stroke After Mild Covid-19, Radhapriya Yalamanchi, Madhan Kumar Murugan, Krishnaswamy Chandrasekharan, Refai Showkathali

The Texas Heart Institute Journal

COVID-19 is a novel disease with multisystem involvement, but most patients have pulmonary and cardiovascular involvement in the acute stages. The cardiovascular impact of acute COVID-19 is well recognized and ranges from myocarditis, arrhythmias, and thrombotic occlusion of coronary arteries to spontaneous coronary artery dissection and microthrombi in small coronary vessels on autopsy. We report a case of a 37-year-old man who recovered from mild COVID-19 only to present a few weeks later with devastating cardiovascular involvement that included severe left ventricular impairment resulting from nonischemic cardiomyopathy, multiple left ventricular thrombi, and embolic stroke.

Magnetic Resonance Imaging Based Superficial Femoral Artery Velocity Measurements In Peripheral Artery Disease, Ankita Sinharoy, Neeti Reddy, John Kent Lin, Vijay Nambi, Eric Y Yang, Panagiotis Kougias, Addison A Taylor, Alan B Lumsden, Christie M Ballantyne, Joel D Morrisett, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. In this study, we analyzed how non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) measured velocity markers of the distal superficial femoral artery (SFA) are associated with clinical and functional characteristics of PAD. A total of 70 (27 diabetic and 43 non-diabetic) PAD patients were included in this secondary analysis of data collected from the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically (ECG)-gated 2D-PC-MRI was performed at a proximal and a distal imaging location of …

Myocarditis Mimicking Stress-Induced (Takotsubo) Cardiomyopathy, Arzu Canan, Ryan C Van Woerkom, Prabhakar Shantha Rajiah

The Texas Heart Institute Journal

No abstract provided.

Butyrate-Producing Bacteria And Insulin Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Jinrui Cui, Gautam Ramesh, Martin Wu, Elizabeth T Jensen, Osa Crago, Alain G Bertoni, Chunxu Gao, Kristi L Hoffman, Patricia A Sheridan, Kari E Wong, Alexis C Wood, Yii-Der I Chen, Jerome I Rotter, Joseph F Petrosino, Stephen S Rich, Mark O Goodarzi

Faculty, Staff and Students Publications

Gut microbiome studies have documented depletion of butyrate-producing taxa in type 2 diabetes. We analyzed associations between butyrate-producing taxa and detailed measures of insulin homeostasis, whose dysfunction underlies diabetes in 224 non-Hispanic Whites and 129 African Americans, all of whom completed an oral glucose tolerance test. Stool microbiome was assessed by whole-metagenome shotgun sequencing with taxonomic profiling. We examined associations among 36 butyrate-producing taxa (n = 7 genera and 29 species) and insulin sensitivity, insulin secretion, disposition index, insulin clearance, and prevalence of dysglycemia (prediabetes plus diabetes, 46% of cohort), adjusting for age, sex, BMI, and race. The genus Coprococcus …

Clinical And Molecular Features Of Pediatric Cancer Patients With Lynch Syndrome, Sarah Scollon, Mohammad K Eldomery, Jacquelyn Reuther, Frank Y Lin, Samara L Potter, Lauren Desrosiers, Kenneth L Mcclain, Valeria Smith, Jack Meng-Fen Su, Rajkumar Venkatramani, Jianhong Hu, Viktoriya Korchina, Neda Zarrin-Khameh, Richard A Gibbs, Donna M Muzny, Christine Eng, Angshumoy Roy, D Williams Parsons, Sharon E Plon

Faculty, Staff and Students Publications

BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD).

PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies.

RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second …

Nurturing Children’S Development Through Healthy Eating And Active Living: Time For Policies To Support Effective Interventions In The Context Of Responsive Emotional Support And Early Learning, Helen Skouteris, Rachael Green, Alexandra Chung, Heidi Bergmeier, Lisa H Amir, Sukhpreet Kaur Baidwan, Angel Marie Chater, Catherine Chamberlain, Ruth Emond, Kay Gibbons, Michelle Gooey, Kostas Hatzikiriakidis, Emma Haycraft, Andrew P Hills, Daryl J Higgins, Oliver Hooper, Sue-Anne Hunter, Pam Kappelides, Sue Kleve, Jacynta Krakouer, Julie C Lumeng, Yannis Manios, Athar Mansoor, Michael Marmot, Louise C Mâsse, Karen Matvienko-Sikar, Zandile June-Rose Mchiza, Caroline Meyer, George Moschonis, Emily R Munro, Teresia Margareta O'Connor, Adrienne O'Neil, Thomas Quarmby, Rachel Sandford, Janet U Schneiderman, Simone Sherriff, Doug Simkiss, Alison Spence, Elizabeth Sturgiss, Dave Vicary, Rebecca Wickes, Luke Wolfenden, Mary Story, Maureen M Black

Faculty, Staff and Students Publications

Fostering the growth, development, health, and wellbeing of children is a global priority. The early childhood period presents a critical window to influence lifelong trajectories, however urgent multisectoral action is needed to ensure that families are adequately supported to nurture their children's growth and development. With a shared vision to give every child the best start in life, thus helping them reach their full developmental potential, we have formed the International Healthy Eating Active Living Matters (HEALing Matters) Alliance. Together, we form a global network of academics and practitioners working across child health and development, and who are dedicated to …

Analysis Of Insppire-2 Cohort: Risk Factors And Disease Burden In Children With Acute Recurrent Or Chronic Pancreatitis, Aliye Uc, Gretchen A Cress, Fuchenchu Wang, Maisam Abu-El-Haija, Kate M Ellery, Douglas S Fishman, Cheryl E Gariepy, Tanja Gonska, Tom K Lin, Quin Y Liu, Megha Mehta, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP).

METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP.

RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR …

Trends, Predictors, And Outcomes Of Transcatheter Aortic Valve Implantation In Patients With Bicuspid Aortic Valve Related Disease: Insights From The Nationwide Inpatient Sample And Nationwide Readmission Database, Waqas Ullah, Salman Zahid, Hamza Muhammadzai, Fouad Khalil, Arnav Kumar, Abdul Mannan Khan Minhas, Muhammad Zia Khan, Salim S Virani, David L Fischman, Pinak Shah, Deepak L Bhatt

Faculty, Staff and Students Publications

Background: Transcatheter aortic valve implantation (TAVI) has increasingly been utilized in patients with bicuspid aortic valve (BAV) related aortic stenosis (AS) with insufficient large-scale data on its safety.

Methods: The Nationwide Inpatient Sample and Nationwide Readmission Database (2011-2018) were queried to identify patients undergoing TAVI for BAV versus trileaflet aortic valve (TAV) associated AS. The in-hospital, 30- and 180-day odds of outcomes were assessed using a propensity-matched analysis (PSM) to calculate adjusted odds ratios (aOR) with its 95% confidence interval (CI).

Results: A total of 216,723 TAVI (TAV: 214,050 and BAV: 2,673) crude and 5,347 matched population (TAV: 2,674 and …

Race, Racism, And Antiracism In Emergency Medicine: A Scoping Review Of The Literature And Research Agenda For The Future, Anna Darby, Emily C Cleveland Manchanda, Hannah Janeway, Shamsher Samra, Marquita Norman Hicks, Ruby Long, Katrina A Gipson, Anita N Chary, Brenda A Adjei, Kajal Khanna, Ava Pierce, Sheri-Ann O Kaltiso, Sophia Spadafore, Jennifer Tsai, Annette Dekker, Molly E Thiessen, Jordan Foster, Rose Diaz, Mikaela Mizuno, Elizabeth Schoenfeld

Faculty, Staff and Students Publications

Objectives: The objective was to conduct a scoping review of the literature and develop consensus-derived research priorities for future research inquiry in an effort to (1) identify and summarize existing research related to race, racism, and antiracism in emergency medicine (EM) and adjacent fields and (2) set the agenda for EM research in these topic areas.

Methods: A scoping review of the literature using PubMed and EMBASE databases, as well as review of citations from included articles, formed the basis for discussions with community stakeholders, who in turn helped to inform and shape the discussion and recommendations of participants in …

Looking On The Horizon; Potential And Unique Approaches To Developing Radiation Countermeasures For Deep Space Travel, Rihana S Bokhari, Afshin Beheshti, Sarah E Blutt, Dawn E Bowles, David Brenner, Robert Britton, Lawrence Bronk, Xu Cao, Anushree Chatterjee, Delisa E Clay, Colleen Courtney, Donald T Fox, M Waleed Gaber, Sharon Gerecht, Peter Grabham, David Grosshans, Fada Guan, Erin A Jezuit, David G Kirsch, Zhandong Liu, Mirjana Maletic-Savatic, Kyle M Miller, Ruth A Montague, Prashant Nagpal, Sivan Osenberg, Luke Parkitny, Niles A Pierce, Christopher Porada, Susan M Rosenberg, Paul Sargunas, Sadhana Sharma, Jamie Spangler, Daniel Naveed Tavakol, Dilip Thomas, Gordana Vunjak-Novakovic, Chunbo Wang, Luke Whitcomb, Damian W Young, Dorit Donoviel

Faculty, Staff and Students Publications

Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human health and performance on future missions beyond low Earth orbit. This paper will describe three funded and complementary avenues for reducing the risk to humans from radiation exposure experienced in deep space. The first focus is on identifying new therapeutic targets to reduce the damaging effects of radiation by focusing on high throughput genetic screens in accessible, sometimes called lower, organism models. The second focus …

Re-Examining The Widespread Policy Of Stopping Sodium-Glucose Cotransporter-2 Inhibitors During Acute Illness: A Perspective Based On The Updated Evidence, Kamlesh Khunti, Vanita R Aroda, Deepak L Bhatt, Biykem Bozkurt, John B Buse, Hiddo L Heerspink, Silvio E Inzucchi, Carolyn S P Lam, Nikolaus Marx, John J V Mcmurray, Scott D Solomon, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now seen as an integral part of therapy in type 2 diabetes to control not only blood glucose but to improve cardiovascular and kidney outcomes. Diabetic ketoacidosis (DKA) is an uncommon but serious complication of type 2 diabetes, which has a high case fatality rate. The absolute risk of DKA in large, prospective randomized clinical trials in people with type 2 diabetes using SGLT2 inhibitors has been low, although the relative risk is higher in those assigned to SGLT2 inhibitors compared with placebo. In those without diabetes but prescribed SGLT2 inhibitors for heart failure or …

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R Deshotels, Caroline Sun, Vijay Nambi, Salim S Virani, Kunihiro Matsushita, Bing Yu, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Students Publications

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.

Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …

Rare Variants In Genes Encoding Subunits Of The Epithelial Na+ Channel Are Associated With Blood Pressure And Kidney Function, Brandon M Blobner, Annet Kirabo, Ossama B Kashlan, Shaohu Sheng, Donna K Arnett, Lewis C Becker, Eric Boerwinkle, Jenna C Carlson, Yan Gao, Richard A Gibbs, Jiang He, Marguerite R Irvin, Sharon L R Kardia, Tanika N Kelly, Charles Kooperberg, Stephen T Mcgarvey, Vipin K Menon, May E Montasser, Take Naseri, Susan Redline, Alexander P Reiner, Muagututi'a S Reupena, Jennifer A Smith, Xiao Sun, Dhananjay Vaidya, Karine A Viaud-Martinez, Daniel E Weeks, Lisa R Yanek, Xiaofeng Zhu, Ryan L Minster, Thomas R Kleyman

Faculty, Staff and Students Publications

Background: The epithelial Na+ channel (ENaC) is intrinsically linked to fluid volume homeostasis and blood pressure. Specific rare mutations in SCNN1A, SCNN1B, and SCNN1G, genes encoding the α, β, and γ subunits of ENaC, respectively, are associated with extreme blood pressure phenotypes. No associations between blood pressure and SCNN1D, which encodes the δ subunit of ENaC, have been reported. A small number of sequence variants in ENaC subunits have been reported to affect functional transport in vitro or blood pressure. The effects of the vast majority of rare and low-frequency ENaC variants on blood pressure are …

Optimal Cardiometabolic Health And Risk Of Heart Failure In Type 2 Diabetes: An Analysis From The Look Ahead Trial, Kershaw V Patel, Muhammad Shahzeb Khan, Matthew W Segar, Judy L Bahnson, Katelyn R Garcia, Jeanne M Clark, Ashok Balasubramanyam, Alain G Bertoni, Muthiah Vaduganathan, Michael E Farkouh, James L Januzzi, Subodh Verma, Mark Espeland, Ambarish Pandey

Faculty, Staff and Students Publications

Aims: To evaluate the contribution of baseline and longitudinal changes in cardiometabolic health (CMH) towards heart failure (HF) risk among adults with type 2 diabetes (T2D).

Methods and results: Participants of the Look AHEAD trial with T2D and without prevalent HF were included. Adjusted Cox models were used to create a CMH score incorporating target levels of parameters weighted based on relative risk for HF. The associations of baseline and changes in the CMH score with risk of overall HF, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) were assessed using Cox models. Among the 5080 participants, 257 incident …

Aging-Associated Regγ Proteasome Decline Predisposes To Tauopathy, Jialu Tu, Haiyang Zhang, Ting Yang, Yun Liu, Solomon Kibreab, Yunpeng Zhang, Liangcai Gao, Robb E Moses, Bert W O'Malley, Jianru Xiao, Xiaotao Li

Faculty, Staff and Students Publications

The REGγ-20S proteasome is an ubiquitin- and ATP-independent degradation system, targeting selective substrates, possibly helping to regulate aging. The studies we report here demonstrate that aging-associated REGγ decline predisposes to decreasing tau turnover, as in a tauopathy. The REGγ proteasome promotes degradation of human and mouse tau, notably phosphorylated tau and toxic tau oligomers that shuttle between the cytoplasm and nuclei. REGγ-mediated proteasomal degradation of tau was validated in 3- to 12-month-old REGγ KO mice, REGγ KO;PS19 mice, and PS19 mice with forebrain conditional neuron-specific overexpression of REGγ (REGγ OE) and behavioral abnormalities. Coupled with tau accumulation, we found …

Predicting The Disease Severity In Male Individuals With Ornithine Transcarbamylase Deficiency, Svenja Scharre, Roland Posset, Sven F Garbade, Florian Gleich, Marie J Seidl, Ann-Catrin Druck, Jürgen G Okun, Andrea L Gropman, Sandesh C S Nagamani, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka, Urea Cycle Disorders Consortium (Ucdc) And The European Registry And Network For Intoxication Type Metabolic Diseases (E-Imd) Consortia Study Group

Faculty, Staff and Students Publications

Objective: Ornithine transcarbamylase deficiency (OTC-D) is an X-linked metabolic disease and the most common urea cycle disorder. Due to high phenotypic heterogeneity, ranging from lethal neonatal hyperammonemic events to moderate symptoms and even asymptomatic individuals, the prediction of the disease course at an early disease stage is very important to individually adjust therapies such as medical treatment or liver transplantation. In this translational study, we developed a severity-adjusted classification system based on in vitro residual enzymatic OTC activity.

Methods: Applying a cell-based expression system, residual enzymatic OTC activities of 71 pathogenic OTC variants were spectrophotometrically determined and subsequently correlated with …

Choosing And Switching Biological Agents In Severe Asthma, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Clinical Characteristics And Associated Factors Of Colonic Polyps In Acromegaly, Guiliang Peng, Xing Li, Yuanyuan Zhou, Jianying Bai, Pian Hong, Weixing Li, Yuling Zhang, Lei Zhang, Qian Liao, Mingyu Liao, Ling Zhou, Zheng Sun, Rufei Shen, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

PURPOSE: To investigate the clinical characteristics and associated factors of colonic polyps in patients with acromegaly.

METHODS: Clinical characteristics and colonoscopy findings of 86 acromegaly patients who received treatment were retrospectively reviewed, and colonoscopy findings and the correlation with growth hormone (GH)-secreting pituitary adenoma (GHPA) volume and hormonal/metabolic levels were analyzed.

RESULTS: The prevalence of colonic polyps in acromegaly patients was 40.7% and increased significantly with advanced age, especially in those ≥50 years. Multiple polyps (62.8%) and colonic polyps in the left colon (54.2%) were detected more frequently. Compared to acromegaly patients without polyps, those with polyps displayed higher insulin-like …

Cardiac Size, Shape, And Ventricular Contractility In Fetuses At Sea Level With An Estimated Weight Less-Than 10th Centile, Wesley Lee, Lauren M Mack, Roxanna Miremadi, Betul Yilmaz Furtun, Haleh Sangi-Haghpeykar, Greggory R Devore

Faculty, Staff and Students Publications

OBJECTIVES: To investigate cardiac size, shape, and ventricular contractility in fetuses with estimated fetal weight (EFW)(Houston).

METHODS: A prospective ultrasound study examined 37 fetuses with EFWsize, shape, and contractility of both ventricles were analyzed with speckle tracking methods. Z scores were calculated using the mean ± standard deviation (SD) derived from normal controls. Measurements were abnormal if their Z score values were+1.65. The proportion of small fetuses with abnormal parameters was compared to normal reference ranges. Results were compared to a similar published study of small fetuses at higher altitude in Denver.

RESULTS: About one-third of Houston fetuses with EFW(RV) …

Management Of Upper Gastrointestinal Symptoms In Patients With Autoimmune Gastritis, Juan D Gomez Cifuentes, Jordan Sparkman, David Y Graham

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Autoimmune gastritis is characterized by atrophy of acid secreting parietal cells resulting in achlorhydria. Upper gastrointestinal symptoms are common in autoimmune gastritis and frequently result in prescriptions for acid suppressant medications despite the inability of the stomach to secrete acid. Evidence-based recommendations for management of gastrointestinal symptoms in autoimmune gastritis are lacking.

RECENT FINDINGS: The most common symptoms in patients with autoimmune gastritis are dyspepsia, heartburn, and regurgitation. Gastroesophageal reflux should be confirmed by pH-impedance testing and is typically weakly acid or alkaline. Therapy for reflux focuses on mechanical prevention of reflux (i.e., elevation of the head …

Participation In A Longitudinal Seminar Series Increases Medical Student Engagement With The Covid-19 Pandemic, Katherine M Naeger, Kaelyn C Cummins, Prathit A Kulkarni

Faculty, Staff and Students Publications

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic required a multifaceted response by healthcare professionals. Medical students played only a limited role in the early response, resulting in feelings of disengagement. The authors developed a discussion-based elective course reviewing the COVID-19 response to address this gap in medical student education.

METHODS: Preclinical medical students enrolled in this elective participated in weekly virtual interactive seminars led by expert faculty members. Students completed a final survey quantifying their understanding of the overall COVID-19 response, knowledge of its individual facets, and their feelings of personal engagement on a Likert scale from 1 to 5, …