Medical Specialties Commons^™

Prevalence And Clinical Features Of Inflammatory Bowel Diseases Associated With Monogenic Variants, Identified By Whole-Exome Sequencing In 1000 Children At A Single Center, Eileen Crowley, Neil Warner, Jie Pan, Sam Khalouei, Abdul Elkadri, Karoline Fiedler, Justin Foong, Andrei L Turinsky, Dana Bronte-Tinkew, Shiqi Zhang

Paediatrics Publications

BACKGROUND & AIMS: A proportion of infants and young children with inflammatory bowel diseases (IBDs) have subtypes associated with a single gene variant (monogenic IBD). We aimed to determine the prevalence of monogenic disease in a cohort of pediatric patients with IBD.

METHODS: We performed whole-exome sequencing analyses of blood samples from an unselected cohort of 1005 children with IBD, aged 0-18 years (median age at diagnosis, 11.96 years) at a single center in Canada and their family members (2305 samples total). Variants believed to cause IBD were validated using Sanger sequencing. Biopsies from patients were analyzed by immunofluorescence and …

Secukinumab Provides Sustained Low Rates Of Radiographic Progression In Psoriatic Arthritis: 52-Week Results From A Phase 3 Study, Future 5., Désirée Van Der Heijde, Philip Mease, Robert B M Landewé, Proton Rahman, Hasan Tahir, Atul Singhal, Elke Boettcher, Sandra Navarra, Xuan Zhu, Gregory Ligozio, Aimee Readie, Shephard Mpofu, Luminita Pricop

Articles, Abstracts, and Reports

OBJECTIVE: To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.

METHODS: Patients with active PsA, stratified by prior anti-TNF use (naïve or inadequate response), were randomized to s.c. secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load regimens or placebo at baseline, at weeks 1, 2 and 3 and every 4 weeks starting at week 4. Radiographic progression was assessed by change in van der Heijde-modified total Sharp score (vdH-mTSS; mean of two readers). Statistical analysis used a linear mixed-effects model (random …

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Surgical Endoepicardial Linear Ablation For Ventricular Tachycardia With Postinfarction Left Ventricular Aneurysm, Changcheng Liu, Zhaoping Su, Liangshan Wang, Bo Li, Jin Wang, Yang Yu, Chengxiong Gu

The Texas Heart Institute Journal

This retrospective study evaluated the feasibility of surgical endoepicardial linear ablation for ventricular tachycardia in patients with postinfarction left ventricular aneurysm. Sixty-four patients with multivessel coronary artery disease and left ventricular aneurysm but no mural thrombosis of the aneurysm or valve disease were treated at our institution from March 2012 through July 2015. All underwent off-pump coronary artery bypass grafting and left ventricular aneurysm repair by linear plication. Twenty-three patients (35.9%) had ventricular tachycardia and underwent surgical endoepicardial linear ablation on the beating heart guided by epicardial substrate mapping with the Carto 3 system. The remaining 41 patients (64.1%) composed …

Cardiac Involvement By Burkitt Lymphoma In A 49-Year-Old Man, Kainat Khalid, Nadeen Faza, Nasser M Lakkis, Rashed Tabbaa

The Texas Heart Institute Journal

Malignant metastases are among the most common cardiac masses. We report a rare case of cardiac involvement by Burkitt lymphoma in a 49-year-old man who presented with a 2-month history of dyspnea and palpitations. A transthoracic echocardiogram revealed 2 intracardiac masses in the right atrium (one of which partially encased the tricuspid valve), myocardial infiltration, and pericardial disease. Results of pleural fluid cytology and flow cytometry confirmed involvement by Burkitt lymphoma. Subsequent chemotherapy markedly reduced the intracardiac tumor burden and resolved the patient's presenting symptoms. Our case highlights the importance of cardiac imaging in diagnosing systemic illness, initiating early and …

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …

Acute Maltodextrin Supplementation During Resistance Exercise, Dylan T Wilburn, Steven B Machek, Thomas D Cardaci, Paul S Hwang, Darryn S Willoughby

Faculty, Staff and Students Publications

Most of the research investigating the ergogenic enhancing mechanisms of carbohydrate have been conducted using aerobic based exercise. Therefore, the purpose of this study was to investigate the effects of pre-exercise maltodextrin ingestion on resistance exercise performance, serum insulin, epinephrine, glucose, and muscle glycogen concentrations. In a double blind, cross over, repeated measures design, participants completed four sets to failure at 70% of 1-RM with 45s rest on the angled leg press with or without pre-exercise maltodextrin (2g/kg) after a 3hr fast. Serum glucose, epinephrine, and insulin were assessed at baseline, 30 min post-ingestion, immediately after, and 1hr post-exercise with …

Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase Ii, Randomized, Double-Blind, Placebo-Controlled Study (Energize), W Frank Peacock, Zubaid Rafique, Konstantin Vishnevskiy, Edward Michelson, Elena Vishneva, Tatiana Zvereva, Rajaa Nahra, Dao Li, Joseph Miller

Faculty, Staff and Students Publications

OBJECTIVES: Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED).

METHODS:This exploratory, phase II, multicenter, randomized, double‐blind, placebo‐controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10‐hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum …

Characteristics Of Nontuberculous Mycobacterial Infections At A Midwestern Tertiary Hospital: A Retrospective Study Of 365 Patients., Claire E Hannah, Bradley A Ford, Jina Chung, Dilek Ince, Karolyn A Wanat

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease.

Methods: We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, …

Age-Dependent Involvement Of Gut Mast Cells And Histamine In Post-Stroke Inflammation, Maria Pilar Blasco, Anjali Chauhan, Pedram Honarpisheh, Hilda Ahnstedt, John D'Aigle, Arunkumar Ganesan, Sriram Ayyaswamy, Frank Blixt, Susan Venable, Angela Major, David Durgan, Anthony Haag, Julia Kofler, Robert Bryan, Louise D Mccullough, Bhanu Priya Ganesh

Faculty, Staff and Students Publications

BACKGROUND: Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation, and mast cells residing in the gut are a primary source of histamine.

METHODS: Stroke was induced in male C57BL/6 J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice; mice underwent MCAO surgery and were euthanized at 6 h, 24 h, …

Protein-Altering Germline Mutations Implicate Novel Genes Related To Lung Cancer Development., Xuemei Ji, Semanti Mukherjee, Maria Teresa Landi, Yohan Bosse, Philippe Joubert, Dakai Zhu, Ivan Gorlov, Xiangjun Xiao, Younghun Han, Olga Gorlova, Rayjean J Hung, Yonathan Brhane, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, Jinyoung Byun, Konstantin H Dragnev, John K Field, Lambertus Fa Kiemeney, Philip Lazarus, Shan Zienolddiny, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Pier A Bertazzi, Angela C Pesatori, Nancy Diao, Li Su, Lei Song, Ruyang Zhang, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Erich Wichmann, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Lesley M Butler, Kenneth Offit, Preethi Srinivasan, Chaitanya Bandlamudi, Matthew D Hellmann, David B Solit, Mark E Robson, Charles M Rudin, Zsofia K Stadler, Barry S Taylor, Michael F Berger, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, María Soler Artigas, Sanjay Shete, Hermann Brenner, Stephen Chanock, Paul Brennan, James D Mckay, Christopher I Amos

Articles, Abstracts, and Reports

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) and replication (adjusted OR = 2.93, P = 2.22 × 10-3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is …

Nk Cell-Derived Gm-Csf Potentiates Inflammatory Arthritis And Is Negatively Regulated By Cis, Cynthia Louis, Fernando Souza-Fonseca-Guimaraes, Yuyan Yang, Damian D'Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J Davis, Jeffrey J Babon, Bogoljub Ciric, Eric Vivier, Warren S Alexander, Nicholas D Huntington, Ian P Wicks

Department of Neurology Faculty Papers

Despite increasing recognition of the importance of GM-CSF in autoimmune disease, it remains unclear how GM-CSF is regulated at sites of tissue inflammation. Using GM-CSF fate reporter mice, we show that synovial NK cells produce GM-CSF in autoantibody-mediated inflammatory arthritis. Synovial NK cells promote a neutrophilic inflammatory cell infiltrate, and persistent arthritis, via GM-CSF production, as deletion of NK cells, or specific ablation of GM-CSF production in NK cells, abrogated disease. Synovial NK cell production of GM-CSF is IL-18–dependent. Furthermore, we show that cytokine-inducible SH2-containing protein (CIS) is crucial in limiting GM-CSF signaling not only during inflammatory arthritis but also …

Seizure Freedom Improves Health-Related Quality Of Life After Epilepsy Surgery In Children., Puneet Jain, Mary Lou Smith, Kathy Speechley, Mark Ferro, Mary Connolly, Rajesh Ramachandrannair, Salah Almubarak, Andrea Andrade, Elysa Widjaja

Paediatrics Publications

AIM: To determine whether epilepsy surgery improved health-related quality of life (HRQoL) and whether seizure freedom after surgery mediated the improvement in HRQoL.

METHOD: This multicenter cohort study compared HRQoL after epilepsy surgery to pharmacological management in children with drug-resistant epilepsy (DRE). HRQoL was measured using the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire at baseline and 1-year follow-up. The mediator between treatment type and HRQoL was seizure freedom.

RESULTS: Two hundred and thirty-seven patients were recruited (surgery group: n=147 [92 males, 45 females]; pharmacological group: n=90 [53 males, 37 females]). Mean age at seizure onset was 6 years …

Randomized Phase Ii Study Of Stereotactic Body Radiotherapy And Interleukin-2 Versus Interleukin-2 In Patients With Metastatic Melanoma., Brendan Curti, Marka R Crittenden, Steven K Seung, Christopher B Fountain, Roxanne Payne, Shuching Chang, Jessica Fleser, Kimberly Phillips, Ian Malkasian, Lyn B Dobrunick, Walter Urba

Articles, Abstracts, and Reports

BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma.

METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) …

The Β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis In Obese Humans, Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.

METHODS. Before and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and …

Dietary Fat And Sugar Differentially Affect Β-Adrenergic Stimulation Of Cardiac Erk And Akt Pathways In C57bl/6 Male Mice Subjected To High-Calorie Feeding, Sadia Ashraf, Gizem Yilmaz, Xu Chen, Romain Harmancey

Faculty, Staff and Student Publications

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear.

OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways.

METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet …

Results Of The Adhere Upper Airway Stimulation Registry And Predictors Of Therapy Efficacy., Erica Thaler, Richard Schwab, Joachim Maurer, Ryan Soose, Christopher Larsen, Suzanne Stevens, Damien Stevens, Maurits Boon, Colin Huntley, Karl Doghramji, Tina Waters, Alan Kominsky, Armin Steffen, Eric Kezirian, Benedikt Hofauer, Ulrich Sommer, Kirk Withrow, Kingman Strohl, Clemens Heiser

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE/HYPOTHESIS: The ADHERE Registry is a multicenter prospective observational study following outcomes of upper airway stimulation (UAS) therapy in patients who have failed continuous positive airway pressure therapy for obstructive sleep apnea (OSA). The aim of this registry and purpose of this article were to examine the outcomes of patients receiving UAS for treatment of OSA.

STUDY DESIGN: Cohort Study.

METHODS: Demographic and sleep study data collection occurred at baseline, implantation visit, post-titration (6 months), and final visit (12 months). Patient and physician reported outcomes were also collected. Post hoc univariate and multivariate analysis was used to identify predictors of …

Dietary Fat And Sugar Differentially Affect Β-Adrenergic Stimulation Of Cardiac Erk And Akt Pathways In C57bl/6 Male Mice Subjected To High-Calorie Feeding, Sadia Ashraf, Gizem Yilmaz, Xu Chen, Romain Harmancey

Faculty, Staff and Student Publications

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear.

OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways.

METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet …

Network Meta-Analysis To Compare Venaseal With Other Superficial Venous Therapies For Chronic Venous Insufficiency., Raghu Kolluri, Janice Chung, Sue Kim, Nibir Nath, Bhoomika Bajaj Bhalla, Tarun Jain, Joseph Zygmunt, Alun Davies

Heart and Vascular Articles

OBJECTIVE: Several randomized controlled trials (RCTs) have compared different interventions for chronic venous insufficiency (CVI) management, but mixed comparison of these interventions is lacking. The aim of this network meta-analysis was to compare VenaSeal closure system (Medtronic, Minneapolis, Minn) with endovenous laser ablation (EVLA), radiofrequency ablation (RFA), mechanochemical ablation, sclerotherapy, and surgery for management of CVI to achieve anatomic success (complete closure of treated vein within 6 months after intervention) as the primary outcome and health-related quality of life (HRQoL; EuroQol-5 Dimension, Aberdeen Varicose Vein Questionnaire), Venous Clinical Severity Score (VCSS), pain scores, and adverse events as secondary outcomes.

METHODS: …

Association Of Intensive Lifestyle Intervention, Fitness, And Body Mass Index With Risk Of Heart Failure In Overweight Or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From The Look Ahead Trial, Ambarish Pandey, Kershaw V Patel, Judy L Bahnson, Sarah A Gaussoin, Corby K Martin, Ashok Balasubramanyam, Karen C Johnson, Darren K Mcguire, Alain G Bertoni, Dalane Kitzman, Jarett D Berry, Look Ahead Research Group

Faculty, Staff and Students Publications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.

METHODS: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these …

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …

Mechanical Thrombectomy For Acute Ischemic Stroke In The Cardiac Catheterization Laboratory., Steven A Guidera, Sudhir Aggarwal, J Doyle Walton, David Boland, Roy Jackel, Jeffrey D Gould, Brooke Kearins, Joseph Mcgarvey, Yan Qi, Brian Furlong

Department of Radiology & Diagnostic Medical Imaging

OBJECTIVES: The aim of this study was to determine the feasibility of establishing a mechanical thrombectomy (MT) program for acute ischemic stroke in a community hospital using interventional cardiologists working closely with neurologists.

BACKGROUND: American Heart Association/American Stroke Association 2018 guidelines give a Class I (Level of Evidence: A) recommendation for MT in eligible patients with large vessel occlusion stroke. Improvement in neurological outcomes with MT is highly time sensitive. Most hospitals do not have trained neurointerventionalists to perform MT, leading to treatment delays that reduce the benefit of reperfusion therapy.

METHODS: An MT program based in the cardiac catheterization …

De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton

Faculty, Staff and Students Publications

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 …

Modified Danielson Technique For Prosthetic Aortic Valve Endocarditis And Aortoventricular Discontinuity, Gianfranco Filippone, Claudia Calia, Mario Finazzo, Fabio Fazzari, Giovanni Caruana, Vincenzo Argano

The Texas Heart Institute Journal

Endocarditis is a devastating complication of prosthetic aortic valve replacement. The infective process can destroy aortic annulus tissue, making conventional surgical valve replacement difficult or impossible and causing aortoventricular discontinuity. Several treatment techniques have been proposed. One of these, the Danielson technique, involves translocating the aortic valve to the native ascending aorta, débriding the abscess cavity, closing the coronary ostia, and bypassing the coronary arteries with a Y anastomosis between 2 vein grafts. We describe our use of a modified Danielson technique in a 68-year-old man with advanced prosthetic valve endocarditis that was associated with aortic annulus destruction and aortoventricular …

Robotic-Assisted Percutaneous Coronary Intervention Through Transradial Approach: Experience In 4 Patients With Complex Lesions, Amornpol Anuwatworn, Muhammad Ali Kahn, Tomasz Stys, Marian Petrasko, Adam Stys

The Texas Heart Institute Journal

Robotic-assisted percutaneous coronary intervention can reduce the exposure of interventional cardiologists to radiation and minimize the risk of occupational orthopedic injuries from wearing heavy protective aprons. The PRECISE (Percutaneous Robotically-Enhanced Coronary Intervention) study showed the efficacy and safety of robotic-assisted procedures for relatively low-risk lesions in single coronary arteries. Several reports have described robotic-assisted treatment of complex high-risk lesions, mostly through the transfemoral approach. We report 4 cases of patients in whom we used the transradial approach to treat complex lesions in the left anterior descending coronary artery with bifurcation balloon angioplasty reconstruction (2 cases), in the ostium of the …

Histologic Abnormalities Of The Ascending Aorta: Effects On Aortic Remodeling After Intracardiac Repair Of Tetralogy Of Fallot, Ujjwal Kumar Chowdhury, Lakshmi Kumari Sankhyan, Sheil Avneesh, Ruma Ray, Mani Kalaivani, Suruchi Hasija, Abhinavsingh Chauhan

The Texas Heart Institute Journal

We evaluated aortic tissue specimens from patients undergoing tetralogy of Fallot repair, to determine whether histologic abnormalities affect postsurgical aortic remodeling and other patient-related variables.

Using light microscopy, we studied full-thickness aortic wall tissue operatively excised from 118 consecutive patients undergoing intracardiac repair of tetralogy of Fallot. We performed multiple linear regression analysis to identify independent predictors of change in aortic root dimensions, which we measured with echocardiography after repair and every 3 months thereafter.

Thirty histologically normal specimens were used as controls. Elastic fiber fragmentation was found in 74.6% of the abnormal specimens, mucoid extracellular matrix accumulation in 49.2%, …

Nr2f1 Heterozygous Knockout Mice Recapitulate Neurological Phenotypes Of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome And Show Impaired Hippocampal Synaptic Plasticity, Chun-An Chen, Wei Wang, Steen E Pedersen, Ayush Raman, Michelle L Seymour, Fernanda R Ruiz, Anping Xia, Meike E Van Der Heijden, Li Wang, Jiani Yin, Joanna Lopez, Megan E Rech, Richard A Lewis, Samuel M Wu, Zhandong Liu, Fred A Pereira, Robia G Pautler, Huda Y Zoghbi, Christian P Schaaf

Faculty, Staff and Students Publications

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) has been identified as an autosomal-dominant disorder characterized by a complex neurological phenotype, with high prevalence of intellectual disability and optic nerve atrophy/hypoplasia. The syndrome is caused by loss-of-function mutations in NR2F1, which encodes a highly conserved nuclear receptor that serves as a transcriptional regulator. Previous investigations to understand the protein's role in neurodevelopment have mostly used mouse models with constitutive and tissue-specific homozygous knockout of Nr2f1. In order to represent the human disease more accurately, which is caused by heterozygous NR2F1 mutations, we investigated a heterozygous knockout mouse model and found that this model …

Thrombotic, Inflammatory, And Hif-Regulated Genes And Thrombosis Risk In Polycythemia Vera And Essential Thrombocythemia, Radhika Gangaraju, Jihyun Song, Soo Jin Kim, Tsewang Tashi, Brandi N Reeves, Krishna M Sundar, Perumal Thiagarajan, Josef T Prchal

Faculty, Staff and Students Publications

Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). The pathophysiology of thrombosis in these disorders remains unclear, and we hypothesized that upregulation of thrombotic, inflammatory, and hypoxia-inducible factor (HIF)-regulated genes may play a role in it. We performed unbiased RNA sequencing in granulocytes and platelets of PV patients and found differential expression of several thrombotic, inflammatory, and HIF-regulated genes. The expression of many of these genes positively correlated with JAK2 expression and JAK2V617F allelic burden. We then validated these findings by quantitative polymerase chain reaction analyses of selected gene transcripts in …

Pain Squad+ Smartphone App To Support Real-Time Pain Treatment For Adolescents With Cancer: Protocol For A Randomised Controlled Trial., Lindsay Jibb, Paul C Nathan, Vicky Breakey, Conrad Fernandez, Donna Johnston, Victor Lewis, Sarah Mckillop, Serina Patel, Christine Sabapathy, Caron Strahlendorf, J Charles Victor, Myla E Moretti, Cynthia Nguyen, Amos Hundert, Celia Cassiani, Graziella El-Khechen Richandi, Hayley Insull, Rachel Hamilton, Geoffrey Fang, Susan Kuczynski, Jennifer Stinson

Paediatrics Publications

INTRODUCTION: Pain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents with real-time pain self-management support. The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes.

METHODS AND ANALYSIS: This will be a …

Public Social Media Consultations For Dermatologic Conditions: An Online Survey, Elizabeth Schoenberg, Doaa Shalabi, Jordan Wang, Nazanin Saedi, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

The use of social media in medicine has been increasingly studied in recent years, especially concerning its role in patient outreach, education, diagnosis, and management. Dermatology is a unique field in that patients can post photographs of their skin ailments when seeking online medical advice and information. This study examines the role of public social media consultations for dermatologic conditions. A large portion of patients utilize social media for dermatologic consultations and many do not seek care from a dermatologist afterward. Future studies should trend this phenomenon, especially as the use of social media continues to expand.