Diseases Commons^™

Invasive Therapies For Acute Coronary Syndromes In The Covid-19 Era, Sanket Borgaonkar, Joshua Hahn, Marilyne Daher, Waleed Kayani, Hani Jneid

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: To identify and address the challenges associated with the care of ACS patients during the coronavirus 2019 pandemic.

RECENT FINDINGS: The COVID-19 pandemic has had a considerable global impact with over 2.0 million deaths worldwide so far. There has been considerable evidence suggesting that COVID-19 increases the risk of acute coronary syndromes (ACS). We propose characterizing ACS patients into 3 distinct categories to better assist in appropriate triage and management: critically ill patients, non-critically ill ST elevation myocardial infarction (STEMI) patients, and non-critically ill non-ST elevation myocardial infarction (NSTEMI)/unstable angina (UA) patients. We thoroughly review treatments strategies, …

Breast Cancer Risk For Female Relatives Of Male Breast Cancer Patients With Negative Brca1/2 Testing, Emily Martin

Dissertations and Theses (Open Access)

Risk models exist to estimate a female’s lifetime risk of breast cancer in the absence of a hereditary predisposition to cancer, namely Hereditary Breast and Ovarian Cancer syndrome. These risk models consider various factors such as reproductive history and family history, but few models take a family history of male breast cancer into account. This study aims to evaluate if prevalence of breast cancer among female relatives is higher when there is a family history of male breast cancer in the context of uninformative BRCA1 and BRCA2 testing. This information may aid in the process of risk assessments for patients …

Imaging Based Prediction Of Pathology In Adult Diffuse Glioma With Applications To Therapy And Prognosis, Evan Gates

Dissertations and Theses (Open Access)

The overall aggressiveness of a glioma is measured by histologic and molecular analysis of tissue samples. However, the well-known spatial heterogeneity in gliomas limits the ability for clinicians to use that information to make spatially specific treatment decisions. Magnetic resonance imaging (MRI) visualizes and assesses the tumor. But, the exact degree to which MRI correlates with the actual underlying tissue characteristics is not known.

In this work, we derive quantitative relationships between imaging and underlying pathology. These relations increase the value of MRI by allowing it to be a better surrogate for underlying pathology and they allow evaluation of the …

Investigating Diffusion Tensor Imaging Correlates Of Cognitive Impairment In Idiopathic Normal Pressure Hydrocephalus And Alzheimer's Disease, Omar Hasan, Omar Hasan

Dissertations and Theses (Open Access)

Modest expansion of the human brain cerebrospinal fluid (CSF)-filled ventricles is normal with aging, and because of this, it can be difficult for physicians to accurately diagnose and treat enlarged ventricles (ventriculomegaly), called hydrocephalus¹ (fluid or water in the brain) Ventriculomegaly occurs due to an obstruction (such as a blood clot or tumor), or a change in CSF absorption². Primary hydrocephalus, also called idiopathic normal pressure hydrocephalus (iNPH), is non-obstructive and may be comorbid with other neurodegenerative diseases such as Alzheimer’s disease (AD) or frontotemporal dementia (FTD). Clinically, it can be difficult to tell whether the pathophysiological …

Mitophagy Deficiency Increases Nlrp3 To Induce Brown Fat Dysfunction In Mice, Myoung Seok Ko, Ji Young Yun, In-Jeoung Baek, Jung Eun Jang, Jung Jin Hwang, Seung Eun Lee, Seung-Ho Heo, David A Bader, Chul-Ho Lee, Jaeseok Han, Jong-Seok Moon, Jae Man Lee, Eun-Gyoung Hong, In-Kyu Lee, Seong Who Kim, Joong Yeol Park, Sean M Hartig, Un Jung Kang, David D Moore, Eun Hee Koh, Ki-Up Lee

Faculty, Staff and Students Publications

Although macroautophagy/autophagy deficiency causes degenerative diseases, the deletion of essential autophagy genes in adipocytes paradoxically reduces body weight. Brown adipose tissue (BAT) plays an important role in body weight regulation and metabolic control. However, the key cellular mechanisms that maintain BAT function remain poorly understood. in this study, we showed that global or brown adipocyte-specific deletion of pink1, a Parkinson disease-related gene involved in selective mitochondrial autophagy (mitophagy), induced BAT dysfunction, and obesity-prone type in mice. Defective mitochondrial function is among the upstream signals that activate the NLRP3 inflammasome. NLRP3 was induced in brown adipocyte precursors (BAPs) from pink1 …

Temporal Changes And Institutional Variation In Use Of Percutaneous Coronary Intervention For St-Elevation Myocardial Infarction With Multivessel Coronary Artery Disease In The United States: An Ncdr Research To Practice Project, Eric A Secemsky, Neel Butala, Aishwarya Raja, Rohan Khera, Yongfei Wang, Jeptha P Curtis, Thomas M Maddox, Salim S Virani, Ehrin J Armstrong, Kendrick A Shunk, Ralph G Brindis, Deepak Bhatt, Robert W Yeh

Faculty, Staff and Students Publications

IMPORTANCE: After disparate results from observational and small randomized studies, the COMPLETE trial demonstrated superiority of multivessel (MV) percutaneous coronary intervention (PCI) over culprit-only PCI for ST-elevation myocardial infarction (STEMI).

OBJECTIVE: To describe temporal trends and institutional variation of MV PCI use for STEMI in the United States to inform how new evidence may influence clinical practice.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included STEMI admissions involving MV disease from 1598 institutions in the National Cardiovascular Data Registry CathPCI Registry from the third quarter of 2009 to the first quarter of 2018. An MV PCI was defined as a …

Genetics Of Atrial Fibrillation, Jitae A Kim, Mihail G Chelu, Na Li

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained cardiac arrhythmia. In addition to traditional risk factors, it is increasingly recognized that a genetic component underlies atrial fibrillation development. This review aims to provide an overview of the genetic cause of atrial fibrillation and clinical applications, with a focus on recent developments.

RECENT FINDINGS: Genome-wide association studies have now identified around 140 genetic loci associated with atrial fibrillation. Studies into the effects of several loci and their tentative gene targets have identified novel pathways associated with atrial fibrillation development. However, further validations of causality are still needed for many …

Enabling Precision Medicine In Cancer Care Through A Molecular Data Warehouse: The Moffitt Experience, Steven A Eschrich, Jamie K Teer, Phillip Reisman, Erin Siegel, Chandan Challa, Patricia Lewis, Katherine Fellows, Everin Malpica, Rodrigo Carvajal, Guillermo Gonzalez, Scott Cukras, Miguel Betin-Montes, Garrick Aden-Buie, Melissa Avedon, Daniel Manning, Aik Choon Tan, Brooke L Fridley, Travis Gerke, Mattias Van Looveren, Amilcar Blake, Jennifer Greenman, Dana E Rollison

Faculty, Staff and Students Publications

PURPOSE: The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research.

METHODS: Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse …

Prospective Patient-Reported Symptom Profiles Associated With Pediatric Acute Lymphoblastic Leukemia Relapse, Austin L Brown, Kimberly P Raghubar, Olga A Taylor, Melanie Brooke Bernhardt, Lisa S Kahalley, Wei Pan, Philip J Lupo, Marilyn J Hockenberry, Michael E Scheurer

Faculty, Staff and Students Publications

PURPOSE: Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention.

METHODS: Pediatric patients with ALL (age 2-18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2). Symptom clusters for co-occurring fatigue, pain, sleep disruptions, and nausea were defined using latent profile analysis. Hazard ratios (HR) and 95% …

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, And Function, And Cardiovascular Events (From The Atherosclerosis Risk In Communities Study), Aliza Hussain, Olive Tang, Caroline Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron Folsom, Gerardo Heiss, Faiez Zannad, Thomas Mosley, Salim S Virani, Josef Coresh, Eric Boerwinkle, Bing Yu, Jonathan W Cunningham, Amil M Shah, Scott D Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne

Faculty, Staff and Students Publications

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels …

Acetyl-Coa And Metabolite Fluxes Regulate White Adipose Tissue Expansion, Jessica B Felix, Aaron R Cox, Sean M Hartig

Faculty, Staff and Students Publications

White adipose tissue (WAT) depends on coordinated regulation of transcriptional and metabolic pathways to respond to whole-body energy demands. We highlight metabolites that contribute to biosynthetic reactions for WAT expansion. Recent studies have precisely defined how byproducts of carbohydrate and lipid metabolism affect physiological and endocrine functions in adipocytes. We emphasize the critical emerging roles of short-chain fatty acids (SCFAs) and tricarboxylic acid (TCA) cycle metabolites that connect lipogenesis to WAT energy balance and endocrine functions. These insights address how adipocytes use small molecules generated from central carbon metabolism to measure responses to nutritional stress.

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Type 2 Diabetes Subgroups, Risk For Complications, And Differential Effects Due To An Intensive Lifestyle Intervention, Michael P Bancks, Haiying Chen, Ashok Balasubramanyam, Alain G Bertoni, Mark A Espeland, Steven E Kahn, Scott Pilla, Elizabeth Vaughan, Lynne E Wagenknecht

Faculty, Staff and Students Publications

OBJECTIVE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.

RESEARCH DESIGN AND METHODS: In the Look AHEAD trial, 5,145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data on age …

Patient-Reported Barriers Are Associated With Receipt Of Hepatocellular Carcinoma Surveillance In A Multicenter Cohort Of Patients With Cirrhosis, Amit G Singal, Jasmin A Tiro, Caitlin C Murphy, James-Michael Blackwell, Jennifer R Kramer, Aisha Khan, Yan Liu, Song Zhang, Jessica L Phillips, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt.

METHODS: We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration.

RESULTS: Of 2871 patients …

Associations Of Abdominal Pain And Psychosocial Distress Measures With Health-Related Quality-Of-Life In Pediatric Healthy Controls And Irritable Bowel Syndrome, John M Hollier, Danita I Czyzewski, Mariella M Self, Yan Liu, Erica M Weidler, Miranda A L Van Tilburg, James W Varni, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: Children with irritable bowel syndrome (IBS) have lower health-related quality-of-life (HRQOL) than healthy controls (HC). Abdominal pain and psychosocial distress are negatively associated with HRQOL, although their relative effect is unclear.

AIM: The aim of this study was to compare the relative associations of abdominal pain and psychosocial distress with HRQOL in HC and IBS.

STUDY: Baseline abdominal pain, psychosocial distress, and HRQOL measures were obtained from HC and IBS pediatric clinical trial participants. Regression assessed which measures were most strongly associated with Physical and Psychosocial HRQOL separately by group. Interaction analyses examined group differences in the associations of …

Dietary Factors And Gastric Intestinal Metaplasia Risk Among Us Veterans, Mimi C Tan, Niharika Mallepally, Quynh Ho, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Studies on diet and gastric intestinal metaplasia (GIM) risk are lacking in US populations.

AIM: To determine the associations of dietary factors and risk of GIM among a US population with typical American diet.

METHODS: We analyzed data from a cross-sectional study of veterans attending primary care and endoscopy clinics at the Houston VA Medical Center. Patients completed a 110-item Block Food Frequency Questionnaire then underwent upper endoscopy with gastric mapping biopsies. We compared cases defined by GIM on ≥ 1 non-cardia gastric biopsy to controls without GIM. Associations of dietary factors and GIM were estimated using logistic regression …

Proteomic Investigation Of Glyceraldehyde-Derived Intracellular Ages And Their Potential Influence On Pancreatic Ductal Cells, Lakmini Senavirathna, Cheng Ma, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

Glyceraldehyde-derived advanced glycation end products (AGEs) play an important role in the pathogenesis of many diseases including cancer. Accumulation of intracellular AGEs could stimulate cancer induction and facilitate cancer progression. We evaluated the toxic effect of glyceraldehyde-derived intracellular AGEs on normal and malignant pancreatic ductal cells by assessing the cell viability, toxicity, and oxidative stress, followed by proteomic analysis. Our functional studies showed that pancreatic cancer cells (PANC-1 and MIA PaCa-2) were more resistant to glyceraldehyde treatment compared to normal pancreatic ductal epithelial cells (HPDE), while cytotoxicity effects were observed in all cell types. Furthermore, using 13C isotopic labeled glyceraldehyde, …

In Men With Obesity, T2dm Is Associated With Poor Trabecular Microarchitecture And Bone Strength And Low Bone Turnover, Francesca Vigevano, Giulia Gregori, Georgia Colleluori, Rui Chen, Vimlin Autemrongsawat, Nicola Napoli, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

INTRODUCTION: Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

METHODS: Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically …

Tocilizumab In Hospitalized Patients With Severe Covid-19 Pneumonia, Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S Aziz, Nichola Cooper, Ivor S Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants …

Decade-Long Nationwide Trends And Disparities In Use Of Comfort Care Interventions For Patients With Ischemic Stroke, Kristie M Chu, Erica M Jones, Jennifer R Meeks, Alan P Pan, Kathryn L Agarwal, George E Taffet, Farhaan S Vahidy

Faculty, Staff and Students Publications

Background Stroke remains one of the leading causes of disability and death in the United States. We characterized 10-year nationwide trends in use of comfort care interventions (CCIs) among patients with ischemic stroke, particularly pertaining to acute thrombolytic therapy with intravenous tissue-type plasminogen activator and endovascular thrombectomy, and describe in-hospital outcomes and costs. Methods and Results We analyzed the National Inpatient Sample from 2006 to 2015 and identified adult patients with ischemic stroke with or without thrombolytic therapy and CCIs using validated

Conditional Survival Among Patients With Oropharyngeal Cancer Treated With Radiation Therapy And Alive Without Recurrence 5 Years After Diagnosis, Kristina R Dahlstrom, Juhee Song, Peter F Thall, Clifton D Fuller, Katherine A Hutcheson, Faye M Johnson, G Brandon Gunn, Jack Phan, Steven J Frank, William H Morrison, Renata Ferrarotto, David I Rosenthal, Erich M Sturgis, Adam S Garden

Faculty, Staff and Students Publications

BACKGROUND: Risk of recurrence among patients with oropharyngeal cancer (OPC) who survive 5 years is low. The goal of this study was to assess long-term survival of patients with OPC alive without recurrence 5 years after diagnosis.

METHODS: This study included newly diagnosed patients with OPC, who had been treated with radiation and were alive without recurrence 5 years after diagnosis. Overall survival (OS) probabilities beyond 5 years were estimated using the Kaplan-Meier method. Factors associated with OS were determined using Bayesian piecewise exponential survival regression. Standardized mortality ratios for all-cause death were estimated controlling for study year, age, and …

Structure, Function And Inhibition Of Critical Protein-Protein Interactions Involving Mixed Lineage Leukemia 1 And Its Fusion Oncoproteins, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master regulator for transcription of important genes (e.g., Hox genes) for embryonic development and hematopoiesis. However, it is largely dispensable in matured cells. Dysregulation of MLL1 leads to overexpression of certain Hox genes and eventually leukemia initiation. Chromosome translocations involving MLL1 cause ~ 75% of acute leukemia in infants and 5-10% in children and adults with a poor prognosis. Targeted therapeutics against oncogenic fusion MLL1 (onco-MLL1) are therefore needed. Onco-MLL1 consists of the N-terminal DNA-interacting domains …

Regional Variations In Heart Failure Quality And Outcomes: Get With The Guidelines-Heart Failure Registry, Luke C Cunningham, Gregg C Fonarow, Clyde W Yancy, Shubin Sheng, Roland A Matsouaka, Adam D Devore, Hani Jneid, Anita Deswal

Faculty, Staff and Students Publications

Background

Regional patient characteristics, care quality, and outcomes may differ based on a variety of factors among patients hospitalized for heart failure (HF). Regional disparities in outcomes of cardiovascular disease have been suggested across various regions in the United States. This study examined whether there are significant differences by region in quality of care and short‐term outcomes of hospitalized patients with HF across the United States.

Methods and Results

We examined regional demographics, quality measures, and short‐term outcomes across 4 US Census Bureau regions in patients hospitalized with HF and enrolled in the GWTG‐HF (Get With The Guidelines–Heart Failure) registry …

Late Gadolinium Enhancement Magnetic Resonance Imaging Evaluation Of Post-Atrial Fibrillation Ablation Esophageal Thermal Injury Across The Spectrum Of Severity, Qussay Marashly, Chaitra Gopinath, Alex Baher, Madan Acharya, Mobin Kheirkhahan, Benjamin Hardisty, Mossab Aljuaid, Ibrahim Tawhari, Mark Ibrahim, Alan K Morris, Eugene G Kholmovski, Brent D Wilson, Nassir F Marrouche, Mihail G Chelu

Faculty, Staff and Students Publications

Background Esophageal thermal injury (ETI) is a byproduct of atrial fibrillation (AF) ablation using thermal sources. The most severe form of ETI is represented by atrioesophageal fistula, which has a high mortality rate. Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) allows identification of ETI. Hence, we sought to evaluate the utility of LGE-MRI as a method to identify ETI across the entire spectrum of severity. Methods and Results All AF radiofrequency ablations performed at the University of Utah between January 2009 and December 2017 were reviewed. Patients with LGE-MRI within 24 hours following AF ablation as well as patients …

A Phase Ii Study Of Autologous Mesenchymal Stromal Cells And C-Kit Positive Cardiac Cells, Alone Or In Combination, In Patients With Ischaemic Heart Failure: The Cctrn Concert-Hf Trial, Roberto Bolli, Raul D Mitrani, Joshua M Hare, Carl J Pepine, Emerson C Perin, James T Willerson, Jay H Traverse, Timothy D Henry, Phillip C Yang, Michael P Murphy, Keith L March, Ivonne H Schulman, Sohail Ikram, David P Lee, Connor O'Brien, Joao A Lima, Mohammad R Ostovaneh, Bharath Ambale-Venkatesh, Gregory Lewis, Aisha Khan, Ketty Bacallao, Krystalenia Valasaki, Bangon Longsomboon, Adrian P Gee, Sara Richman, Doris A Taylor, Dejian Lai, Shelly L Sayre, Judy Bettencourt, Rachel W Vojvodic, Michelle L Cohen, Lara Simpson, David Aguilar, Catalin Loghin, Lem Moyé, Ray F Ebert, Barry R Davis, Robert D Simari

Faculty, Staff and Student Publications

AIMS: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy.

METHODS AND RESULTS: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association …

Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun

Faculty, Staff and Students Publications

Systemic insulin sensitivity shows diurnal rhythm with a peak at wakening1,2. The molecular mechanism underlying such a temporal pattern is unclear. Here we demonstrate that nuclear receptors Rev-erbα/β in the GABAergic neurons in the suprachiasmatic nucleus (SCNGABA) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviors under the regular light-dark cycles. Rev-erb regulates the rhythmic expression of genes involved in neurotransmission in the SCN and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at wakening causes glucose intolerance, while restoration …

Clinical And Economic Burden Of Stroke Among Young, Midlife, And Older Adults In The United States, 2002-2017, Safi U Khan, Muhammad Zia Khan, Muhammad U Khan, Muhammad Shahzeb Khan, Mamas A Mamas, Muhammad Rashid, Ron Blankstein, Salim S Virani, Michelle C Johansen, Michael D Shapiro, Michael J Blaha, Miguel Cainzos-Achirica, Farhaan S Vahidy, Khurram Nasir

Faculty, Staff and Students Publications

OBJECTIVE: To assess trends of stroke hospitalization rates, inpatient mortality, and health care resource use in young (aged ≤44 years), midlife (aged 45-64 years), and older (aged ≥65 years) adults.

PATIENTS AND METHODS: We studied the National Inpatient Sample database (January 1, 2002 to December 31, 2017) to analyze stroke-related hospitalizations. We identified data using the

RESULTS: Of 11,381,390 strokes, 79% (n=9,009,007) were ischemic and 21% (n=2,372,383) were hemorrhagic. Chronic diseases were more frequent in older adults; smoking, alcoholism, and migraine were more prevalent in midlife adults; and coagulopathy and intravenous drug abuse were more common in young patients with …

Single-Cell Transcriptomics Identifies Limbal Stem Cell Population And Cell Types Mapping Its Differentiation Trajectory In Limbal Basal Epithelium Of Human Cornea, De-Quan Li, Sangbae Kim, Jin-Miao Li, Qianmiao Gao, Jongsu Choi, Fang Bian, Jiaoyue Hu, Yun Zhang, Jin Li, Rong Lu, Yumei Li, Stephen C Pflugfelder, Hongyu Miao, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution.

METHODS: Single cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis. Tissue RNA in situ hybridization with RNAscope, immunofluorescent staining and multiple functional assays were performed using human corneas and limbal epithelial culture models.

RESULTS: Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters belonging to three lineages. …

Automated Software-Assisted Diagnosis Of Esophageal Squamous Cell Neoplasia Using High-Resolution Microendoscopy, Mimi C Tan, Sheena Bhushan, Timothy Quang, Richard Schwarz, Kalpesh H Patel, Xinying Yu, Zhengqi Li, Guiqi Wang, Fan Zhang, Xueshan Wang, Hong Xu, Rebecca R Richards-Kortum, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm.

METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) …