Medicine and Health Sciences Commons^™

Relationship Between Obstructive Sleep Apnea And Balance On Computerized Dynamic Posturography, Meha G Fox, Helen S Cohen, Haleh Sangi-Haghpeykar, Masayoshi Takashima

Faculty, Staff and Students Publications

BACKGROUND: Obstructive sleep apnea (OSA) leads to chronic sleep deprivation. The relationship between OSA and balance is poorly understood.

AIM/OBJECTIVE: This study aimed to determine if OSA adversely affects standing balance.

MATERIAL AND METHODS: Adults with a clinically indicated polysomnogram (PSG) diagnostic of OSA, who were not on therapy, were recruited from an academic tertiary care referral clinic. Subjects completed the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), and the STOP-BANG questionnaire (SBQ). Their balance was tested with the Sensory Organization Test (SOT) of computerized dynamic posturography (CDP).

RESULTS: Sixteen subjects participated in the study, including three with …

Validation Of Atovaquone Plasma Levels By Liquid Chromatography-Tandem Mass Spectrometry For Therapeutic Drug Monitoring In Pediatric Patients, Thomas D Horvath, Izmarie Poventud-Fuentes, Lily Olayinka, Asha James, Sigmund J Haidacher, Kathleen M Hoch, Alexandra M Stevens, Anthony M Haag, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.

METHODS: Atovaquone was extracted from a 10 µL volume of K

RESULTS: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min …

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 …

Histone-Stimulated Platelet Adhesion To Mouse Cremaster Venules In Vivo Is Dependent On Von Willebrand Factor, Justin A Courson, Fong W Lam, Kimberly W Langlois, Rolando E Rumbaut

Faculty, Staff and Students Publications

Objective: Extracellular histones are known mediators of platelet activation, inflammation, and thrombosis. Von Willebrand Factor (vWF) and Toll-like receptor 4 (TLR4) have been implicated in pro-inflammatory and prothrombotic histone responses. The objective of this study was to assess the role of vWF and TLR4 on histone-induced platelet adhesion in vivo.

Methods: Intravital microscopy of the mouse cremaster microcirculation, in the presence of extracellular histones or saline control, was conducted in wild-type, vWF-deficient, and TLR4-deficient mice to assess histone-mediated platelet adhesion. Platelet counts following extracellular histone exposure were conducted. Platelets were isolated from vWF-deficient mice and littermates to assess the role …

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 …

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 …

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 …

Development Of A Novel Mouse Model Of Menopause-Associated Asthma, William P Pederson, Laurie M Ellerman, Estevan C Sandoval, Scott Boitano, Jennifer B Frye, Kristian P Doyle, Heddwen L Brooks, Francesca Polverino, Julie G Ledford

Faculty, Staff and Students Publications

No abstract provided.

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 …

Clearance Of Hiv-1 Or Siv Reservoirs By Promotion Of Apoptosis And Inhibition Of Autophagy: Targeting Intracellular Molecules In Cure-Directed Strategies, Min Chen, Min Li, Marietta M Budai, Andrew P Rice, Jason T Kimata, Mahesh Mohan, Jin Wang

Faculty, Staff and Students Publications

The reservoirs of the HIV display cellular properties resembling long-lived immune memory cells that could be exploited for viral clearance. Our interest in developing a cure for HIV stems from the studies of immunologic memory against infections. We and others have found that long-lived immune memory cells employ prosurvival autophagy and antiapoptotic mechanisms to protect their longevity. Here, we describe the rationale for the development of an approach to clear HIV-1 by selective elimination of host cells harboring replication-competent HIV (SECH). While reactivation of HIV-1 in the host cells with latency reversing agents (LRAs) induces viral gene expression leading to …

Steroid Receptor Coactivator-3 Inhibition Generates Breast Cancer Antitumor Immune Microenvironment, Sang Jun Han, Nuri Sung, Jin Wang, Bert W O'Malley, David M Lonard

Faculty, Staff and Students Publications

BACKGROUND: The tumor immune microenvironment (TIME) generated by cancer-infiltrating immune cells has a crucial role in promoting or suppressing breast cancer progression. However, whether the steroid receptor coactivator-3 (SRC-3) modulates TIME to progress breast cancer is unclear. Therefore, the present study evaluates whether SRC-3 generates a tumor-promoting TIME in breast tumors using a syngeneic immune-intact mouse model of breast cancer.

METHODS: We employed E0771 and 4T1 breast cancer in immune-intact syngeneic female C57BL/6 and BALB/c mice, respectively. SI-2, a specific small-molecule inhibitor of SRC-3, was administered daily (2.5 mg/kg) to E0771 and 4T1 breast tumor-bearing immune-intact mice. In addition, SRC-3 …

Implementation Of The Texas Community-Engaged Statewide Consortium For The Prevention Of Covid-19, Erika L Thompson, Bettina M Beech, Robert L Ferrer, Lorna H Mcneil, Jasmine J Opusunju, Rebecca A Seguin-Fowler, Emily E Spence, Luis Torres-Hostos, Christopher I Amos, Palak Desai, Jamboor K Vishwanatha

Faculty, Staff and Students Publications

The Community Engagement Alliance (CEAL) Against COVID-19 Disparities aims to conduct community-engaged research and outreach. This paper describes the Texas CEAL Consortium's activities in the first year and evaluates progress. The Texas CEAL Consortium comprised seven projects. To evaluate the Texas CEAL Consortium's progress, we used components of the RE-AIM Framework. Evaluation included estimating the number of people reached for data collection and education activities (reach), individual project goals and progress (effectiveness), partnerships established and partner engagement (adoption), and outreach and education activities (implementation). During the one-year period, focus groups were conducted with 172 people and surveys with 2107 people …

14-3-3Τ Drives Estrogen Receptor Loss Via Erα36 Induction And Gata3 Inhibition In Breast Cancer, Lidija A Wilhelms Garan, Yang Xiao, Weei-Chin Lin

Faculty, Staff and Students Publications

About one-fourth of recurrent estrogen receptor-positive (ER+) breast cancers lose ER expression, leading to endocrine therapy failure. However, the mechanisms underlying ER loss remain to be fully explored. We now show that 14-3-3τ, up-regulated in ∼60% of breast cancer, drives the conversion of ER+ to ER- and epithelial-to-mesenchymal transition (EMT). We identify ERα36, an isoform of ERα66, as a downstream effector of 14-3-3τ. Overexpression of 14-3-3τ induces ERα36 in xenografts and tumor spheroids. The regulation is further supported by a positive correlation between ERα36 and 14-3-3τ expression in human breast cancers. ERα36 can antagonize ERα66 and inhibit ERα66 expression. Isoform-specific …

A Cop1-Gata2 Axis Suppresses Ar Signaling And Prostate Cancer, Tao Shen, Bingning Dong, Yanling Meng, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Androgen receptor (AR) signaling is crucial for driving prostate cancer (PCa), the most diagnosed and the second leading cause of death in male patients with cancer in the United States. Androgen deprivation therapy is initially effective in most instances of AR-positive advanced or metastatic PCa. However, patients inevitably develop lethal castration-resistant PCa (CRPC), which is also resistant to the next-generation AR signaling inhibitors. Most CRPCs maintain AR expression, and blocking AR signaling remains a main therapeutic approach. GATA2 is a pioneer transcription factor emerging as a key therapeutic target for PCa because it promotes AR expression and activation. While directly …

Interferon Signaling In The Endometrium And In Endometriosis, Yuri Park, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is an estrogen-dependent inflammatory disease that develops in reproductive-aged women who experience pelvic pain and infertility. Even though endometriosis is not a new disease, its molecular etiology has not been clearly elucidated. Defects in the immune system might be one of the factors that promote endometriosis progression. For example, elevated levels of proinflammatory cytokines are associated with endometriosis. Interferon is one of the cytokines that is elevated in endometriotic tissues compared with normal endometrium. Therefore, high interferon levels play a crucial role in endometriosis progression. In addition to endometriosis, however, interferon has a critical role in endometrial function, particularly …

Loss Of Non-Motor Kinesin Kif26a Causes Congenital Brain Malformations Via Dysregulated Neuronal Migration And Axonal Growth As Well As Apoptosis, Xuyu Qian, Ellen M Degennaro, Maya Talukdar, Shyam K Akula, Abbe Lai, Diane D Shao, Dilenny Gonzalez, Jack H Marciano, Richard S Smith, Norma K Hylton, Edward Yang, J Fernando Bazan, Lee Barrett, Rebecca C Yeh, R Sean Hill, Samantha G Beck, Aoi Otani, Jolly Angad, Tadahiro Mitani, Jennifer E Posey, Davut Pehlivan, Daniel Calame, Hatip Aydin, Osman Yesilbas, Kendall C Parks, Emanuela Argilli, Eleina England, Kiho Im, Ajay Taranath, Hamish S Scott, Christopher P Barnett, Peer Arts, Elliott H Sherr, James R Lupski, Christopher A Walsh

Faculty, Staff and Students Publications

Kinesins are canonical molecular motors but can also function as modulators of intracellular signaling. KIF26A, an unconventional kinesin that lacks motor activity, inhibits growth-factor-receptor-bound protein 2 (GRB2)- and focal adhesion kinase (FAK)-dependent signal transduction, but its functions in the brain have not been characterized. We report a patient cohort with biallelic loss-of-function variants in KIF26A, exhibiting a spectrum of congenital brain malformations. In the developing brain, KIF26A is preferentially expressed during early- and mid-gestation in excitatory neurons. Combining mice and human iPSC-derived organoid models, we discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and …

Associations Of Warfarin Use With Risks Of Ischemic Cerebrovascular Events And Major Bleeding In Patients With Hyperthyroidism-Related Atrial Fibrillation, Sian-De Liu, Shwu-Jiuan Lin, Chin-Ying Ray, Fang-Tsyr Lin, Weei-Chin Lin, Li-Hsuan Wang

Faculty, Staff and Students Publications

The use of oral anticoagulants for patients with new-onset hyperthyroidism-related atrial fibrillation (AF) is controversial. We aimed to evaluate the clinical benefits of warfarin therapy in this population. This retrospective cohort study used a data-cut of Taiwan Health and Welfare Database between 2000 and 2016. We compared warfarin users and nonusers among AF patients with hyperthyroidism. We used 1:2 propensity score matching to balance covariates and Cox regression model to calculate hazard ratios (HRs). The primary outcome was risk of ischemic stroke/transient ischemic attack (TIA), and the secondary outcome was major bleeding. After propensity score matching, we defined 90 and …

Cgas-Sting Activation Contributes To Podocyte Injury In Diabetic Kidney Disease, Nan Zang, Chen Cui, Xinghong Guo, Jia Song, Huiqing Hu, Mengmeng Yang, Mingyue Xu, Lingshu Wang, Xinguo Hou, Qin He, Zheng Sun, Chuan Wang, Li Chen

Faculty, Staff and Students Publications

Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway is activated in podocytes at the early stage of kidney dysfunction, which is associated with the activation of STING downstream effectors TBK1 and NF-κB but not IRF3. Lipotoxicity induces mitochondrial damage and mtDNA leakage to the cytosol through Bcl-2 associated X protein (BAX) in podocytes. BAX-mediated mtDNA cytosolic leakage can activate the cGAS-STING pathway in the absence of lipotoxicity and is sufficient to cause podocyte injury. Depletion of cytosolic mtDNA, genetic STING knockdown, or pharmacological inhibition of STING or …

Sensitive Image-Based Chromatin Binding Assays Using Inducible Erα To Rapidly Characterize Estrogenic Chemicals And Mixtures, Adam T Szafran, Maureen G Mancini, Fabio Stossi, Michael A Mancini

Faculty, Staff and Students Publications

The United States Environmental Protection Agency (EPA) has been pursuing new high throughput in vitro assays to characterize endocrine disrupting chemicals (EDCs) that interact with estrogen receptor signaling. We characterize two new PRL-HeLa cell models expressing either inducible C-terminal (iGFP-ER) or N-terminal (iER-GFP) tagged estrogen receptor-α (ERα) that allows direct visualization of chromatin binding. These models are an order of magnitude more sensitive, detecting 87 - 93% of very weak estrogens tested compared to only 27% by a previous PRL-HeLa variant and compares favorably to the 73% detected by an EPA-developed computational model using in vitro data. Importantly, the chromatin …

Genetic Inhibition Of Nuclear Factor Of Activated T-Cell C2 Prevents Atrial Fibrillation In Crem Transgenic Mice, Li Ni, Satadru K Lahiri, Jiali Nie, Xiaolu Pan, Issam Abu-Taha, Julia O Reynolds, Hannah M Campbell, Haihao Wang, Markus Kamler, Wilhelm Schmitz, Frank Ulrich Müller, Na Li, Xiang Wei, Dao Wen Wang, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

AIMS: Abnormal intracellular calcium (Ca2+) handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signalling pathway contributes to atrial remodelling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models.

METHODS AND RESULTS: Expression levels of NFATc1-c4 isoforms were assessed by quantitative reverse transcription-polymerase chain reaction in right atrial appendages from patients with chronic AF (cAF). NFATc1 and NFATc2 mRNA levels were elevated in cAF patients compared with those in normal sinus …

Control Of Ribosomal Rna Synthesis By Hematopoietic Transcription Factors, Charles Antony, Subin S George, Justin Blum, Patrick Somers, Chelsea L Thorsheim, Dexter J Wu-Corts, Yuxi Ai, Long Gao, Kaosheng Lv, Michel G Tremblay, Tom Moss, Kai Tan, Jeremy E Wilusz, Austen R D Ganley, Maxim Pimkin, Vikram R Paralkar

Faculty, Staff and Students Publications

Ribosomal RNAs (rRNAs) are the most abundant cellular RNAs, and their synthesis from rDNA repeats by RNA polymerase I accounts for the bulk of all transcription. Despite substantial variation in rRNA transcription rates across cell types, little is known about cell-type-specific factors that bind rDNA and regulate rRNA transcription to meet tissue-specific needs. Using hematopoiesis as a model system, we mapped about 2,200 ChIP-seq datasets for 250 transcription factors (TFs) and chromatin proteins to human and mouse rDNA and identified robust binding of multiple TF families to canonical TF motifs on rDNA. Using a 47S-FISH-Flow assay developed for nascent rRNA …

The Modifying Effect Of The Serum-To-Dialysate Potassium Gradient On The Cardiovascular Safety Of Ssris In The Hemodialysis Population: A Pharmacoepidemiologic Study, Magdalene M Assimon, Patrick H Pun, Sana M Al-Khatib, Maurice Alan Brookhart, Bradley N Gaynes, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

Background: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs).

Methods: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus < 4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study.

Results: …

Loss Of Activity-Induced Mitochondrial Atp Production Underlies The Synaptic Defects In A Drosophila Model Of Als, Nicholas E Karagas, Richa Gupta, Elham Rastegari, Kai Li Tan, Ho Hang Leung, Hugo J Bellen, Kartik Venkatachalam, Ching-On Wong

Faculty, Staff and Students Publications

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapb^P58S) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapb^P58S-induced changes in NMJ morphology by either a loss of endoplasmic …

Elevated Nras Expression During Dcis Is A Potential Driver For Progression To Basal-Like Properties And Local Invasiveness, Ze-Yi Zheng, Hanan Elsarraj, Jonathan T Lei, Yan Hong, Meenakshi Anurag, Long Feng, Hilda Kennedy, Yichao Shen, Flora Lo, Zifan Zhao, Bing Zhang, Xiang H-F Zhang, Ossama W Tawfik, Fariba Behbod, Eric C Chang

Faculty, Staff and Students Publications

BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression. In this study, we investigated whether NRAS expression at the DCIS stage can control transition from luminal DCIS to basal-like invasive breast cancers.

METHODS: Wilcoxon rank-sum test was performed to assess expression of NRAS in DCIS compared to invasive breast tumors in patients. NRAS …

Intensive Blood Pressure Lowering In Patients With Malignant Left Ventricular Hypertrophy, Simon B Ascher, James A De Lemos, Minjae Lee, Elaine Wu, Elsayed Z Soliman, Ian J Neeland, Dalane W Kitzman, Christie M Ballantyne, Vijay Nambi, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry

Faculty, Staff and Students Publications

Background: Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death.

Objectives: The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences.

Methods: A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type …

Cronkhite-Canada Syndrome: First Case Report From Egypt And North Africa, Ahmed Elsayed Alzamzamy, Ashraf Aboubakr, Hussein H Okasha, Abeer Abdellatef, Shaimaa Elkholy, Mahmoudd Wahba, Mohamed Alboraie, Hussein Elsayed, Mohamed O Othman

Faculty, Staff and Students Publications

Background: Gastrointestinal (GI) polyposis is a rare condition in GI diseases. To date about 500 cases of Cronkhite-Canada syndrome (CCS) have been reported worldwide.

Case summary: We report a 60-year-old female patient who presented with dyspepsia, abdominal pain, and weight loss of 1-year duration. Her physical examination showed alopecia and onychodystrophy. Upper endoscopy revealed diffuse markedly thickened gastric mucosa involving the whole stomach with thickened gastric rugae and numerous polypoidal lesions. Histopathological examination showed marked hyperplasia of the foveolar glands with inflammatory cell infiltration. Endoscopic ultrasound showed a significantly hypertrophic mucosa and muscularis mucosa, while the submucosa and the muscularis …

How Can We Optimise Health Technology Assessment And Reimbursement Decisions To Accelerate Access To New Cardiovascular Medicines?, Martin R Cowie, Biykem Bozkurt, Javed Butler, Andrew Briggs, Maria Kubin, Adrian Jonas, Amanda I Adler, Bray Patrick-Lake, Faiez Zannad

Faculty, Staff and Students Publications

Regulatory approvals of, and subsequent access to, innovative cardiovascular medications have declined. How much of this decline relates to the final step of gaining reimbursement for new treatments is unknown. Payers and health technology assessment (HTA) bodies look beyond efficacy and safety to assess whether a new drug improves patient outcomes, quality of life, or satisfaction at a cost that is affordable compared to existing treatments. HTA bodies work within a limited healthcare budget, and this is one of the reasons why only half of newly approved drugs are accepted for reimbursement, or receive restricted or "optimised" recommendations from HTA …

Comparison Of Longitudinal Skeletal Thigh Muscle Findings With Magnetic Resonance Imaging In Patients With Peripheral Artery Disease With-Versus-Without Diabetes Mellitus, Olga A Gimnich, Carlos B Ortiz, Eric Y Yang, Changyi Chen, Salim S Virani, Panos Kougias, Alan B Lumsden, Joel D Morrisett, Christie M Ballantyne, Vijay Nambi, Gerd Brunner

Faculty, Staff and Students Publications

The aim of this secondary analysis of The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT) was to determine longitudinal changes over 24-months in skeletal thigh muscle volumes and individual muscle compartments in peripheral artery disease (PAD) patients with and without diabetes. A total of 48 patients with available magnetic resonance imaging (MRI) of the distal superficial femoral artery (SFA) at baseline and 2-years were included in this analysis. Muscle volumes and SFA wall, lumen, and total vessel volumes were quantified. Intra-reader reproducibility of muscle tracings was assessed with the intraclass correlation coefficient (ICC) using …

Smart And Multi-Functional Magnetic Nanoparticles For Cancer Treatment Applications: Clinical Challenges And Future Prospects, Elham Aram, Masome Moeni, Roya Abedizadeh, Davood Sabour, Hamid Sadeghi-Abandansari, Jabbar Gardy, Ali Hassanpour

Faculty, Staff and Students Publications

Iron oxide nanoparticle (IONPs) have become a subject of interest in various biomedical fields due to their magnetism and biocompatibility. They can be utilized as heat mediators in magnetic hyperthermia (MHT) or as contrast media in magnetic resonance imaging (MRI), and ultrasound (US). In addition, their high drug-loading capacity enabled them to be therapeutic agent transporters for malignancy treatment. Hence, smartening them allows for an intelligent controlled drug release (CDR) and targeted drug delivery (TDD). Smart magnetic nanoparticles (SMNPs) can overcome the impediments faced by classical chemo-treatment strategies, since they can be navigated and release drug via external or internal …

Expert Clinical Management Of Severe Immune-Related Adverse Events: Results From A Multicenter Survey On Hot Topics For Management, Mar Riveiro-Barciela, Maria Jose Soler, Ana Barreira-Diaz, Sheila Bermejo, Sebastian Bruera, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

There are differences in recommendations for the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). To assess the real-world management of irAEs, three surveys regarding ICI-induced hepatitis (IIH), renal irAEs, and myositis were developed and sent to experts in each area. Fifty-six surveys were completed (17 IIH, 20 renal irAEs, and 19 myositis). All experts agreed on performing imaging in every suspected case of severe IIH. Sixty-five percent agreed on performing a liver biopsy in patients not responding to corticosteroids. The most common indication for corticosteroid use (59%) was for severe IIH not improving after discontinuation …