Medicine and Health Sciences Commons^™

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 …

Tfeb Is A Master Regulator Of Tumor-Associated Macrophages In Breast Cancer, Yong Li, Johnie Hodge, Qing Liu, Junfeng Wang, Yuzhen Wang, Trent D Evans, Diego Altomare, Yongzhong Yao, E. Angela Murphy, Babak Razani, Daping Fan

2020-Current year OA Pubs

BACKGROUND: Tumor-associated macrophages (TAMs) play key roles in the development of many malignant solid tumors including breast cancer. They are educated in the tumor microenvironment (TME) to promote tumor growth, metastasis, and therapy resistance. However, the phenotype of TAMs is elusive and how to regulate them for therapeutic purpose remains unclear; therefore, TAM-targeting therapies have not yet achieved clinical success. The purposes of this study were to examine the role of transcription factor EB (TFEB) in regulating TAM gene expression and function and to determine if TFEB activation can halt breast tumor development.

METHODS: Microarrays were used to analyze the …

Epigenomic Programming In Early Fetal Brain Development, Luolan Li, Ting Wang, Et Al

2020-Current year OA Pubs

No abstract provided.

Maternal Viral Load Monitoring: Coverage And Clinical Action At 4 Kenyan Hospitals., Matthew Sandbulte, Melinda Brown, Catherine Wexler, May Maloba, Brad Gautney, Kathy Goggin, Elizabeth Muchoki, Shadrack Babu, Nicodemus Maosa, Sarah Finocchario-Kessler

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Kenya's guidelines for prevention of mother-to-child transmission of HIV (PMTCT) recommend routine viral load (VL) monitoring for pregnant and breastfeeding women.

METHOD: We assessed PMTCT VL monitoring and clinical action occurring between last menstrual period (LMP) and 6 months postpartum at 4 Kenyan government hospitals. Pregnant women enrolled in the HIV Infant Tracking System from May 2016-March 2018 were included. We computed proportions who received VL testing within recommended timeframes and who received clinical action after unsuppressed VL result.

RESULTS: Of 424 participants, any VL testing was documented for 305 (72%) women and repeat VL testing was documented for …

Multi-Dose Oral Ondansetron For Pediatric Gastroenteritis: Study Protocol For The Multi-Dose Oral Ondansetron For Pediatric Acute Gastroenteritis (Dose-Age) Pragmatic Randomized Controlled Trial, Stephen B Freedman, Sarah Williamson-Urquhart, Anna Heath, Petros Pechlivanoglou, Gareth Hopkin, Serge Gouin, Amy C Plint, Andrew Dixon, Darcy Beer, Gary Joubert, Christopher Mccabe, Yaron Finkelstein, Terry P Klassen

Paediatrics Publications

BACKGROUND: There are limited treatment options that clinicians can provide to children presenting to emergency departments with vomiting secondary to acute gastroenteritis. Based on evidence of effectiveness and safety, clinicians now routinely administer ondansetron in the emergency department to promote oral rehydration therapy success. However, clinicians are also increasingly providing multiple doses of ondansetron for home use, creating unquantified cost and health system resource use implications without any evidence to support this expanding practice.

METHODS/DESIGN: DOSE-AGE is a randomized, placebo-controlled, double-blinded, six-center, pragmatic clinical trial being conducted in six Canadian pediatric emergency departments (EDs). In September 2019 the study began …

Decomposing Loss Aversion From Gaze Allocation And Pupil Dilation, Feng Sheng, Arjun Ramakrishnan, Darsol Seok, Wenjia Joyce Zhao, Samuel Thelaus, Puti Cen, Michael Louis Platt

Faculty, Staff and Student Publications

Loss-averse decisions, in which one avoids losses at the expense of gains, are highly prevalent. However, the underlying mechanisms remain controversial. The prevailing account highlights a valuation bias that overweighs losses relative to gains, but an alternative view stresses a response bias to avoid choices involving potential losses. Here we couple a computational process model with eye-tracking and pupillometry to develop a physiologically grounded framework for the decision process leading to accepting or rejecting gambles with equal odds of winning and losing money. Overall, loss-averse decisions were accompanied by preferential gaze toward losses and increased pupil dilation for accepting gambles. …

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

Adiponectin Inhibits Cardiac Arrest/Cardiopulmonary Resuscitation‑Induced Apoptosis In Brain By Increasing Autophagy Involved In Adipor1‑Ampk Signaling., Yarong He, Bofu Liu, Peng Yao, Yuming Shao, Yanwei Cheng, Jie Zhao, Jiang Wu, Zhi Wei Zhao, Wen Huang, Theodore A. Christopher, Bernard Lopez, Xin-Liang Ma, Yu Cao

Department of Emergency Medicine Faculty Papers

Emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia-reperfusion (GCIR)-induced neuronal death, which results from cardiac arrest (CA). However, the mechanism of how GCIR may affect the balance between apoptosis and autophagy resulting from CA remains to be elucidated. Additionally, the role of adiponectin (APN) in reversing the apoptosis and autophagy induced by GCIR following cardiac arrest-cardiopulmonary resuscitation (CA-C PR) is unclear. Thus, the aim of the present study was to investigate how GCIR affect the apoptosis and autophagy in response to CA and to clarify whether APN may alter the apoptosis and autophagy of neuronal …

Vascular Risk Reduction In Obesity Through Reduced Granulocyte Burden And Improved Angiogenic Monocyte Content Following Bariatric Surgery., David A Hess, Justin Z Trac, Stephen A Glazer, Daniella C Terenzi, Adrian Quan, Hwee Teoh, Mohammed Al-Omran, Deepak L Bhatt, C David Mazer, Ori D Rotstein, Subodh Verma

Physiology and Pharmacology Publications

Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair. We also describe that, at 3 months following bariatric surgery, systemic inflammatory burden was reduced and pro-angiogenic macrophage precursor content was improved in subjects …

Can Unconventional Immunomodulatory Agents Help Alleviate Covid-19 Symptoms And Severity?, Stephen W. Mamber, Steven Krakowka, Jeffrey L. Osborn, Lloyd Saberski, Ryan G. Rhodes, Albert E. Dahlberg, Sunthorn Pond-Tor, Kara Fitzgerald, Neal Wright, Sarah Beseme, John Mcmichael

Biology Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but …

Hypogeusia As The Initial Presenting Symptom Of Covid-19, Lauren E Melley, Eli Bress, Erik Polan

PCOM Scholarly Works

COVID-19 is the disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first arose in Wuhan, China, in December 2019 and has since been declared a pandemic. The clinical sequelae vary from mild, self-limiting upper respiratory infection symptoms to severe respiratory distress, acute cardiopulmonary arrest and death. Otolaryngologists around the globe have reported a significant number of mild or otherwise asymptomatic patients with COVID-19 presenting with olfactory dysfunction. We present a case of COVID-19 resulting in intensive care unit (ICU) admission, presenting with the initial symptom of disrupted taste and flavour perception prior to respiratory …

Selective Autophagy Maintains The Aryl Hydrocarbon Receptor Levels In Hela Cells: A Mechanism That Is Dependent On The P23 Co-Chaperone, Yujie Yang, William K. Chan

School of Pharmacy Faculty Articles

The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after ligand activation. Recently, we discovered that HeLa cells can modulate the AHR levels via protein degradation without exogenous treatment of a ligand, and this degradation is particularly apparent when the p23 content is down-regulated. Inhibition of autophagy by a chemical agent (such as chloroquine, bafilomycin A1, or 3-methyladenine) increases the AHR protein levels in HeLa cells whereas activation …

Proteolysis-Targeting Chimera (Protac) For Targeted Protein Degradation And Cancer Therapy, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently linked ligand of an E3 ubiquitin ligase (E3). Upon binding to the POI, the PROTAC can recruit E3 for POI ubiquitination, which is subjected to proteasome-mediated degradation. PROTAC complements nucleic acid-based gene knockdown/out technologies for targeted protein reduction and could mimic pharmacological protein inhibition. To date, PROTACs targeting ~ 50 proteins, many of which are clinically validated drug targets, have been successfully developed with several …

Demographic And Socioeconomic Characteristics Of Canadian Medical Students: A Cross-Sectional Study., Rishad Khan, Tavis Apramian, Joel Hosung Kang, Jeffrey Gustafson, Shannon Sibbald

Health Studies Publications

BACKGROUND: While the importance of medical students' demographic characteristics in influencing the scope and location of their future practice is recognized, these data are not systematically collected in Canada. This study aimed to characterize and compare the demographics of Canadian medical students with the Canadian population.

METHODS: Through an online survey, delivered in 2018, medical students at 14 English-speaking Canadian medical schools provided their age, sex, gender identity, ethnicity, educational background, and rurality of the area they grew up in. Respondents also provided information on parental income, occupation, and education as markers of socioeconomic status. Data were compared to the …

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 …

Synaptic Dysfunction Induced By Glycine-Alanine Dipeptides In C9orf72-Als/Ftd Is Rescued By Sv2 Replenishment., Brigid K Jensen, Martin H Schuldi, Kevin Mcavoy, Katelyn A Russell, Ashley Boehringer, Bridget M Curran, Karthik Krishnamurthy, Xinmei Wen, Thomas Westergard, Le Ma, Aaron R. Haeusler, Dieter Edbauer, Piera Pasinelli, Davide Trotti

Department of Neuroscience Faculty Papers

The most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an intronic hexanucleotide repeat expansion in the C9orf72 gene. In disease, RNA transcripts containing this expanded region undergo repeat-associated non-AUG translation to produce dipeptide repeat proteins (DPRs), which are detected in brain and spinal cord of patients and are neurotoxic both in vitro and in vivo paradigms. We reveal here a novel pathogenic mechanism for the most abundantly detected DPR in ALS/FTD autopsy tissues, poly-glycine-alanine (GA). Previously, we showed motor dysfunction in a GA mouse model without loss of motor neurons. Here, we demonstrate that mobile …

Association Of Multisetting Community Programs And Policies With Child Body Mass Index: The Healthy Communities Study, Vicki L. Collie-Akers, Stephen B. Fawcett, Jerry A. Schultz, Kandace K. Fleming, Rebecca E. Swinburne Romine, Lorrene D. Ritchie, Edward A. Frongillo Jr., S Sonia Arteaga

Faculty Publications

INTRODUCTION:

Expert opinion suggests that efforts to address childhood obesity should seek to transform the environments in which children operate. The objective of this study was to describe the extent to which multisetting programs and policies interact with community and child predictors and are associated with child body mass index (BMI) in the 130 US communities participating in the Healthy Communities Study.

METHODS:

For 2 years beginning in fall 2013, we collected data through key informant interviews on community programs and policies related to healthy weight among children that occurred in the 10 years before the interview. We characterized community …

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 …

Why Do Graduates Choose To Work In A Less Attractive Specialty? A Cross-Sectional Study On The Role Of Personal Values And Expectations, Van Anh Nguyen, Karen D. Könings, E Pamela Wright Phd, Ms, Med, Rn, Cen, Giang Bao Kim, Hoat Ngoc Luu, Albert J. Scherpbier, Jeroen J. Van Merriënboer

Publications

BACKGROUND: Primary health care (PHC), of which preventive medicine (PM) is a subspecialty, will have to cope with a deficiency of staff in the future, which makes the retention of graduates urgent. This study was conducted in Vietnam, where PM is an undergraduate degree in parallel to medical training. It aims to identify facilitating and hindering factors that impact recruitment and retention of PM graduates in the specialty. METHODS: A cross-sectional study enrolled 167 graduates who qualified as PM doctors from a Vietnamese medical school, between 2012 and 2018. Data were collected via an online questionnaire that asked participants about …

The Positivism Paradigm Of Research., Yoon Soo Park, Lars Konge, Anthony R. Artino

Health, Human Function, and Rehabilitation Sciences Faculty Publications

Research paradigms guide scientific discoveries through their assumptions and principles. Understanding paradigm-specific assumptions helps illuminate the quality of findings that support scientific studies and identify gaps in generating sound evidence. This article focuses on the research paradigm of positivism, examining its definition, history, and assumptions (ontology, epistemology, axiology, methodology, and rigor). Positivism is aligned with the hypothetico-deductive model of science that builds on verifying a priori hypotheses and experimentation by operationalizing variables and measures; results from hypothesis testing are used to inform and advance science. Studies aligned with positivism generally focus on identifying explanatory associations or causal relationships through quantitative …

Late Referrals Of Pediatric Patients With Elevated Blood Pressure, Guido Filler, Laura Torres-Canchala

Paediatrics Publications

Editorial Commentary

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 …

Age At Migration And The Risk Of Psychotic Disorders: A Systematic Review And Meta-Analysis., Kelly K. Anderson, Jordan Edwards

Epidemiology and Biostatistics Publications

OBJECTIVE: To conduct a systematic review and meta-analysis of the existing evidence on the association between age at migration and the risk of psychotic disorders.

METHODS: Observational studies were eligible for inclusion if they presented data on the association between age at migration and the risk of psychotic disorders among first-generation migrant groups. We used two random effects meta-analyses to pool effect estimates for each stratum of age at migration relative to (i) a native-born reference category and (ii) the youngest age stratum (0 to 2 years).

RESULTS: Ten studies met inclusion criteria, and five were included in the meta-analysis. …

Effect Of Pembrolizumab Plus Neoadjuvant Chemotherapy On Pathologic Complete Response In Women With Early-Stage Breast Cancer: An Analysis Of The Ongoing Phase 2 Adaptively Randomized I-Spy2 Trial., Rita Nanda, Minetta C Liu, Christina Yau, Rebecca Shatsky, Lajos Pusztai, Anne Wallace, A Jo Chien, Andres Forero-Torres, Erin D Ellis, Heather Han, Amy Clark, Kathy Albain, Judy C Boughey, Nora T Jaskowiak, Anthony Elias, Claudine Isaacs, Kathleen Kemmer, Teresa Helsten, Melanie Majure, Erica Stringer-Reasor, Catherine Parker, Marie C Lee, Tufia Haddad, Ronald N Cohen, Smita Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Katherine Steeg, Adam Asare, Jeffrey B Matthews, Scott Berry, Ashish Sanil, Richard Schwab, W Fraser Symmans, Laura Van 'T Veer, Douglas Yee, Angela Demichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, Donald A Berry, Laura J Esserman

Articles, Abstracts, and Reports

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed.

Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial.

Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with …

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) …

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: …

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 …

Hypoglycaemia Is Reduced With Use Of Inhaled Technosphere ® Insulin Relative To Insulin Aspart In Type 1 Diabetes Mellitus, E R Seaquist, L Blonde, J B Mcgill, S R Heller, D M Kendall, J B Bumpass, F M Pompilio, M L Grant

2020-Current year OA Pubs

AIM: To evaluate the effect of final HbA

METHODS: In the randomized, phase 3, multicentre AFFINITY-1 study, adults (N = 375) who had type 1 diabetes for ≥ 12 months and an HbA

RESULTS: Participants treated with Technosphere Insulin experienced statistically significantly fewer level 1 and 2 hypoglycaemic events and a lower incidence of level 3 hypoglycaemia than participants treated with insulin aspart. The lower rate of hypoglycaemia with Technosphere Insulin was observed across the range of end-of-treatment HbA

CONCLUSIONS: Participants using Technosphere Insulin experienced clinically non-inferior glycaemic control and lower hypoglycaemia rates across a range of HbA

Three-Dimensional Facial Morphology In Cantú Syndrome, Helen I Roessler, Kathleen Shields, Dorothy K Grange, Nine V A M Knoers, Gijs Van Haaften, Peter Hammond, Mieke M Van Haelst

2020-Current year OA Pubs

Cantú syndrome (CS) was first described in 1982, and is caused by pathogenic variants in ABCC9 and KCNJ8 encoding regulatory and pore forming subunits of ATP-sensitive potassium (K

No Difference In Strength And Clinical Outcome Between Early And Late Repair After Achilles Tendon Rupture, Michael R Carmont, Jennifer A Zellers, Annelie Brorsson, Karin Grävare Silbernagel, Jón Karlsson, Katarina Nilsson-Helander

2020-Current year OA Pubs

PURPOSE: This retrospective study aimed to determine the patient-reported and functional outcome of patients with delayed presentation, who had received no treatment until 14 days following injury of Achilles tendon rupture repaired with minimally invasive surgery and were compared with a group of sex- and age-matched patients presenting acutely. Based on the outcomes following delayed presentation reported in the literature, it was hypothesized that outcomes would be inferior for self-reported outcome, tendon elongation, heel-rise performance, ability to return to play, and complication rates than for acutely managed patients.

METHODS: Repair was performed through an incision large enough to permit mobilisation …