tbuckley/cabot-search huggingface dataset:
OP0213 THE IMPACT OF TNFΑ INHIBITORS ON GLUCOCORTICOIDS USE AMONG PATIENTS WITH ARTHRITIS
Authors: R. Hafthorsdottir, A. Gunnarsdottir, T. Love, G. Gröndal, B. Gudbjornsson
Journal: Annals of the Rheumatic Diseases (2020)

Background: Glucocorticoid steroid (GC) use among patients with arthritis is common. The introduction of TNFα inhibitors (TNFi) has been a breakthrough in the treatment of arthritis leading to remission for many patients. However, there is scarce information on the impact of TNFi on the use of GC among patients with inflammatory joint diseases. Objectives: To explore oral GC use in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) before and after the initiation of TNFi therapy. Furthermore, to evaluate if patients on long term GC treatment were receiving active preventive osteoporosis treatment and how treatment with TNFi affected the use of topical steroids in patients with PsA. Methods: Clinical data on patients with RA, PsA and axSpA who initiated TNFi therapy with etanercept, infliximab, adalimumab or golimumab for the first time between 2005-2015 was collected from the ICEBIO registry. ICEBIO is a nationwide registry on all patients treated with biologics for rheumatologic disorders in Iceland. The use of oral GC, topical steroids and bisphosphonates was collected from the Icelandic Prescription Medicines Registry (IPMR) for a period of four years, two years before and after the initiation of TNFi. Medication use was then evaluated by counting the number of individuals receiving a medication in a given year, the total number of prescriptions, and the defined daily dose (DDD). Five controls were randomly selected from IPMR and matched on age, sex and time frame. Results: 621 patients with RA, PsA or axSpA received 2630 prescriptions (4.2 prescription per patient; 3105 controls received 1337 prescriptions or 0.4 prescription per individual) for GC during the study period. GC use varied between patient groups (Figure 1). The total GC use (DDD) doubled over the two-year period leading up to TNFi treatment but decreased sharply after the initiation of TNFi. The number of individuals on GC decreased by one third after initiating TNFi therapy and the majority of those who continued GC treatment were patients with RA (Figure 1). Of those patients on long term GC treatment (&gt;7.5 mg/day for three months) 38% were receiving bone protective therapy against corticosteroid induced osteoporosis. The use of topical steroids decreased by half among PsA patients and one third discontinued the treatment after initiating TNFi (Figure 2). Conclusion: TNFi therapy does impact GC use among patients with arthritides, however a large portion of RA patients are still on GC two years after initiating TNFi therapy. Better osteoporosis prophylaxis and treatment is warranted for those patients on long term GC Disclosure of Interests: Rebekka Hafthorsdottir: None declared, Anna Gunnarsdottir: None declared, Thorvardur Love: None declared, Gerdur Gröndal: None declared, Björn Gudbjornsson Speakers bureau: Novartis and Amgen
Alarming Antimicrobial Resistance Trends Emerge Globally
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Intensive immunosuppression reduces deaths in covid-19-associated cytokine storm syndrome, study finds
Authors: Susan Mayor
Journal: BMJ (2020)

Intensive immunosuppressive treatment with high dose glucocorticoids, followed by an interleukin-6 (IL-6) receptor antagonist where needed, accelerates respiratory recovery and reduces deaths in patients with covid-19-associated cytokine storm syndrome (CSS), an observational study 1 has shown.Researchers from the Netherlands conducted a historically controlled comparison of a strategy with intensive immunosuppression and close monitoring versus supportive care."This comparison suggests that clinically relevant improvement of respiratory status was 79% more likely and can be accelerated by a median of seven days.Hospital mortality can be reduced by 65% and the need for mechanical ventilation by 71%," the team, led by Sofia Ramiro, from Zuyderland Medical Center in Heerlen, reported.
Anosmia and loss of smell in the era of covid-19
Authors: Abigail Walker, Gillian Pottinger, Andrew Scott, Claire Hopkins
Journal: BMJ (2020)

### What you need to know

A 46 year old ophthalmologist presents with a two week history of loss of sense of smell and taste. He believes he may have been exposed to covid-19 but, at the time, did not meet the criteria for testing. 

With the discovery of covid-19 and as the clinical syndromes associated with this virus have been defined, many areas of practice require updating. This article is a guide to assessment and management of patients with loss of smell based on review of the current literature and guidelines from the British Rhinology Society and ENT UK, the professional membership body representing ear, nose, and throat surgery in the UK.1

Olfactory dysfunction is common: estimates of point prevalence in the general population before the covid-19 pandemic suggest that 19.1% of adults (80% in people over 75) suffer from complete or partial loss of smell.2

Causes can be broadly subdivided into conductive (physical barriers to odorants reaching the olfactory system) and sensorineural (failure of the olfactory system to detect odorants). Causes are outlined in table 1, with the more common causes in the top half of the table and less common causes in the bottom half. A comprehensive history is invaluable, especially if consultations are performed remotely.

View this table:

Table 1 
Causes of loss of smell



Points to …
Abstract 14932: Early Canadian Experience Using Selexipag as Part of an Oral Triple Therapy Regimen in Pediatric Patients With Severe Pulmonary Arterial Hypertension
Authors: Konstantin Averin, Susan Richards, Erika Vorhies, Angela Bates
Journal: Circulation (2019)

Introduction: Use of prostacyclins in the treatment of severe pediatric pulmonary arterial hypertension (PAH) has increased significantly over the past three decades. Chronic IV or SC administratio...
Noncanonical STAT3 activity sustains pathogenic Th17 proliferation and cytokine response to antigen
Authors: Catherine H. Poholek, Itay Raphael, Dongwen Wu, Shankar Revu, Natalie Rittenhouse, Uzodinma U. Uche, Saikat Majumder, Lawrence P. Kane, Amanda C. Poholek, Mandy J. McGeachy
Journal: The Journal of Experimental Medicine (2020)

The STAT3 signaling pathway is required for early Th17 cell development, and therapies targeting this pathway are used for autoimmune disease. However, the role of STAT3 in maintaining inflammatory effector Th17 cell function has been unexplored. Th17ΔSTAT3 mice, which delete STAT3 in effector Th17 cells, were resistant to experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Th17 cell numbers declined after STAT3 deletion, corresponding to reduced cell cycle. Th17ΔSTAT3 cells had increased IL-6–mediated phosphorylation of STAT1, known to have antiproliferative functions. Th17ΔSTAT3 cells also had reduced mitochondrial membrane potential, which can regulate intracellular Ca2+. Accordingly, Th17ΔSTAT3 cells had reduced production of proinflammatory cytokines when stimulated with myelin antigen but normal production of cytokines when TCR-induced Ca2+ flux was bypassed with ionomycin. Thus, early transcriptional roles of STAT3 in developing Th17 cells are later complimented by noncanonical STAT3 functions that sustain pathogenic Th17 cell proliferation and cytokine production.
Temporal trends of the association between ambient temperature and hospitalisations for cardiovascular diseases in Queensland, Australia from 1995 to 2016: A time-stratified case-crossover study
Authors: Peng Lu, Guoxin Xia, Qi Zhao, Rongbin Xu, Shanshan Li, Yuming Guo
Journal: PLoS Medicine (2020)

Background In the context of global warming, studies have turned to assess the temporal trend of the association between temperature and health outcomes, which can be used to reflect whether human beings have adapted to the local temperature. However, most studies have only focused on hot temperature and mortality. We aim to investigate the temporal variations in the association between ambient temperature and hospitalisations for cardiovascular diseases in Queensland, Australia from 1995 to 2016. Methods and findings We obtained data on 1,855,717 cardiovascular hospitalisations (mean age: 65.9 years, 42.7% female) from all 443 postal areas in Queensland, Australia between January 1, 1995 and December 31, 2016. Grid-level meteorological data were downloaded from scientific information for landowners. We used a time-stratified case-crossover design fitted with a conditional quasi-Poisson regression model and time-varying distributed lag nonlinear model (DLNM) to evaluate the association between temperature and cardiovascular hospitalisations and the temporal trends of the associations. Stratified analyses were performed in different age, sex, and climate zones. In all groups, relative risks (RRs) of cardiovascular hospitalisations associated with high temperatures (heat effects) increased, but cold effects showed a decreasing trend from 1995 to 2016. The increasing magnitude of heat effects was larger (p = 0.002) in men than in women and larger (p < 0.001) in people aged ≤69 years than in those aged ≥70 years. There was no apparent difference amongst different climate zones. The study was limited by the switch from ICD-9 to ICD-10 coding systems, by being unable to separate first-time hospitalisation from repeated hospitalisations, and possibly by confounding by air pollution or by influenza infections. Conclusion The impacts of cold temperatures on cardiovascular hospitalisations have decreased, but the impacts of high temperatures have increased in Queensland, Australia. The findings highlight that Queensland people have adapted to the impacts of cold temperatures, but not high temperatures. The burden of cardiovascular hospitalisations due to high temperatures is likely to increase in the context of global warming.
Heritable risk for severe anaphylaxis associated with increased α-tryptase–encoding germline copy number at TPSAB1
Authors: Jonathan J. Lyons, Jack Chovanec, Michael P. O’Connell, Yihui Liu, Julij Šelb, Roberta Zanotti, Yun Bai, Jiwon Kim, Quang T. Le, Tom DiMaggio, Lawrence B. Schwartz, Hirsh D. Komarow, Matija Rijavec, Melody C. Carter, Joshua D. Milner, Patrizia Bonadonna, Dean D. Metcalfe, Peter Korošec
Journal: Journal of Allergy and Clinical Immunology (2020)
Rhinitis 2020: A practice parameter update
Authors: Mark S. Dykewicz, Dana V. Wallace, David J. Amrol, Fuad M. Baroody, Jonathan A. Bernstein, Timothy J. Craig, Chitra Dinakar, Anne K. Ellis, Ira Finegold, David B.K. Golden, Matthew J. Greenhawt, John B. Hagan, Caroline C. Horner, David A. Khan, David M. Lang, Desiree E.S. Larenas-Linnemann, Jay A. Lieberman, Eli O. Meltzer, John J. Oppenheimer, Matthew A. Rank, Marcus S. Shaker, Jeffrey L. Shaw, Gary C. Steven, David R. Stukus, Julie Wang, Mark S. Dykewicz, Dana V. Wallace, Chitra Dinakar, Anne K. Ellis, David B.K. Golden, Matthew J. Greenhawt, Caroline C. Horner, David A. Khan, David M. Lang, Jay A. Lieberman, John J. Oppenheimer, Matthew A. Rank, Marcus S. Shaker, David R. Stukus, Julie Wang, Mark S. Dykewicz, Dana V. Wallace, David J. Amrol, Fuad M. Baroody, Jonathan A. Bernstein, Timothy J. Craig, Ira Finegold, John B. Hagan, Desiree E.S. Larenas-Linnemann, Eli O. Meltzer, Jeffrey L. Shaw, Gary C. Steven
Journal: Journal of Allergy and Clinical Immunology (2020)
Abstract 9685: Positive Modulation of Exogenous L-carnosine on Left Ventricular Systolic and Diastolic Performance in Conscious, Chronically-Instrumented Dogs With Pacing-Induced Heart Failure: Assessment by Left Ventricular Pressure-Volume Analysis
Authors: Tiankai Li, Hideo Tachibana, Tomohiko Ukai, Zhi Zhang, Xiaowei Zhang, Nobuyuki Ohte, Heng-Jie Cheng, David Herrington, David Zhao, Che Ping Cheng
Journal: Circulation (2019)

Background: L-Carnosine (L-C), an endogenous dipeptide with high concentrations in the heart, has been shown to play multifactorial roles in supporting the body’s metabolic activities, [Ca2+]i regu...
Clinical Parameters, Fuel Oxidation, and Glucose Kinetics in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin
Authors: Yuejuan Qin, John Adams, Carolina Solis-Herrera, Curtis Triplitt, Ralph DeFronzo, Eugenio Cersosimo
Journal: Diabetes Care (2020)

OBJECTIVE To examine the mechanisms responsible for improved glycemia with combined sodium–glucose cotransporter 2 inhibitor (SGLT2i) plus dipeptidyl peptidase 4 inhibitor therapy in type 2 diabetes. RESEARCH DESIGN AND METHODS Fifty-six patients (HbA1c 8.9 ± 0.2% [74 ± 2 mmol/mol]) were randomized to dapagliflozin (DAPA) 10 mg, DAPA/saxagliptin (SAXA) 10/5 mg, or placebo (PCB) for 16 weeks. Basal endogenous glucose production (EGP) (3-3H-glucose), urinary glucose excretion, glucose/lipid oxidation, HbA1c, and substrate/hormone levels were determined before treatment (Pre-Tx) and after treatment (Post-Tx). RESULTS At week 16, HbA1c decrease was greater (P &amp;lt; 0.05) in DAPA/SAXA (−2.0 ± 0.3%) vs. DAPA (−1.4 ± 0.2%) and greater than PCB (0.2 ± 0.2%). Day 1 of drug administration, EGP (∼2.40 mg/kg/min) decreased by −0.44 ± 0.09 mg/kg/min in PCB (P &amp;lt; 0.05) but only by −0.21 ± 0.02 mg/kg/min in DAPA and DAPA/SAXA (P &amp;lt; 0.05 vs. PCB). At week 16, EGP increased to 2.67 ± 0.09 mg/kg/min (DAPA) and 2.61 ± 0.08 mg/kg/min (DAPA/SAXA), despite reductions in fasting plasma glucose by 47 and 77 mg/dL, respectively, and no changes in PCB. Baseline plasma free fatty acids rose by 40 µmol/L with DAPA but declined by −110 with PCB and −90 µmol/L with DAPA/SAXA (P &amp;lt; 0.05, Pre-Tx vs. Post-Tx). In DAPA, carbohydrate oxidation rates decreased from 1.1 ± 0.1 to 0.7 ± 0.1 mg/kg/min, whereas lipid oxidation rates increased from 0.6 ± 0.1 to 0.8 ± 0.1 mg/kg/min (P &amp;lt; 0.01). In DAPA/SAXA, the shift in carbohydrate (1.1 ± 0.1 to 0.9 ± 0.1 mg/kg/min) and lipid (0.6 ± 0.1 to 0.7 ± 0.1 mg/kg/min) oxidation was attenuated (P &amp;lt; 0.05). CONCLUSIONS The addition of SAXA to DAPA resulted in superior glycemic control compared with DAPA monotherapy partly because of increased glucose utilization and oxidation. Although the decrease in insulin/glucagon ratio was prevented by SAXA, EGP paradoxical elevation persisted, indicating that other factors mediate EGP changes in response to SGLT2i-induced glucosuria.
A pH‐Sensitive Self‐Assembled and Carrier‐Free Nanoparticle Based on Charge Reversal for Enhanced Synergetic Chemo‐Phototherapy
Authors: Chen Liu, Qiuhong Liu, Luping Chen, Mao Li, Jieli Yin, Xuan Zhu, Dengyue Chen
Journal: Advanced Healthcare Materials (2020)

To overcome biological barriers for nanoparticles (NPs) efficaciously accumulated at tumor sites, as well as enhancing the performance of drug delivery systems, a carrier-free nanoparticle based on charge reversal is designed for improved synergetic chemo-phototherapy for cancer treatment. In this system, doxorubicin (Dox) and zinc phthalocyanine (ZnPc) are self-assembled through noncovalent interactions (π-π stacking, hydrophobic forces) to avoid the possible toxicity of excipient, complex chemical conjugations and batch-to-batch variation. A trace amount of poly(2-(di-methylamino) ethylmethacrylate)- poly[(R)-3-hydroxybutyrate]- poly(2-(dimethylamino) ethylmethacrylate (PDMAEMA-PHB-PDMAEMA) is modified on the surface of Dox-ZnPc to construct the novel nanoparticles, namely DZP, with long-term stability, and with a dual-drug load content of up to ≈90％. The drug delivery system (DDS) can effectively decrease its toxicity among physical circulation and increase the accumulation at the tumor site. Moreover, the developed DZP nanoparticles show excellent photo-chemotherapy, photoacoustic (PA) and fluorescence (FL) imaging characteristics for multimodal imaging-guided synergetic therapy.
From Ventilators to Vaccines: Reframing the Ethics of Resource Allocation
Authors: R. Thomas Day, Bradley S. Guidry, Brian C. Drolet, Ellen W. Clayton
Journal: The American Journal of Bioethics (2020)

The United States has never experienced the grim realities of a resource-limited healthcare environment like that brought by COVID-19. Dire projections of overwhelmed ICUs introduced the public to ...
Flattening the Rationing Curve: The Need for Explicit Guidelines for Implicit Rationing during the COVID-19 Pandemic
Authors: Kayte Spector-Bagdady, Naomi Laventhal, Megan Applewhite, Janice I. Firn, Norman D. Hogikyan, Reshma Jagsi, Adam Marks, Renee McLeod-Sordjan, Lisa S. Parker, Lauren B. Smith, Christian J. Vercler, Andrew G. Shuman
Journal: The American Journal of Bioethics (2020)

This article refers to:Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force
Diabetic Foot Problems During the COVID-19 Pandemic in a Tertiary Care Center: The Emergency Among the Emergencies
Authors: Paola Caruso, Miriam Longo, Simona Signoriello, Maurizio Gicchino, Maria Ida Maiorino, Giuseppe Bellastella, Paolo Chiodini, Dario Giugliano, Katherine Esposito
Journal: Diabetes Care (2020)

As a consequence of the coronavirus disease 2019 (COVID-19) pandemic, profound changes in daily lives have occurred. In Italy, the exponential spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection required extraordinary measures to limit viral transmission, leading to an almost complete lockdown of the country (1).

The mandatory lockdown significantly affected patients with chronic diseases, including people with diabetes and diabetic foot ulceration (DFU), which represents a heavy burden for health care systems in terms of mortality and reduced quality of life (1,2). The interruption of preventive education, early treatment, and diagnosis may have led to increased hospitalization of patients with severe DFU at high amputation risk (3). The aim of this study was to evaluate clinical features and amputation risk of individuals with diabetes and DFU admitted to a tertiary care center during the COVID-19 lockdown compared with a population admitted in the first 5 months of 2019.

Patients with diabetes and DFU admitted to the Division of Endocrinology and Metabolic Diseases at the Teaching Hospital of University of Campania “Luigi Vanvitelli” (Naples, Italy) from 9 March 2020 to 18 May 2020 were included in this study. This cohort was compared with a population of patients admitted …
Loss of SIRT4 promotes the self-renewal of Breast Cancer Stem Cells
Authors: Lutao Du, Xiaoyan Liu, Yidan Ren, Juan Li, Peilong Li, Qinlian Jiao, Peng Meng, Fang Wang, Yuli Wang, Yun-Shan Wang, Chuanxin Wang
Journal: Theranostics (2020)

Rationale: It has been proposed that cancer stem/progenitor cells (or tumor-initiating cells, TICs) account for breast cancer initiation and progression. Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent class-III histone deacetylases and mediate various basic biological processes, including metabolic homeostasis. However, interplay and cross-regulation among the sirtuin family are not fully understood. As one of the least studied sirtuin family members, the mitochondrial sirtuin SIRT4 is a tumor suppressor gene in various cancers. However, its role in cancer stemness, as well as initiation and progression of breast cancer, remains unknown. Methods: The expression of SIRT4 in breast cancer was analyzed using the TCGA breast cancer database and 3 GSEA data. Normal breast epithelial cells MCF10A and breast cancer cell lines MCF-7, MDA-MB-231, BT549, MDA-MB-468 were used to establish SIRT4 gene knockdown and corresponding overexpression cells. Identified MTT cytotoxicity assays, cell invasion and motility assay, sorting of SP, confocal immunofluorescence microscopy, mouse mammary stem cell analysis, glutamine and glucose production, clonogenic and sphere-formation assay, mass spectrometric metabolomics analysis and ChIP-seq to further explore SIRT4 biological role in breast cancer. Results: We elucidated a novel role for SIRT4 in the negative regulation of mammary gland development and stemness, which is related to the mammary tumorigenesis. We also uncovered an inverse correlation between SIRT4 and SIRT1. Most importantly, SIRT4 negatively regulates SIRT1 expression via repressing glutamine metabolism. Besides, we identified H4K16ac and BRCA1 as new prime targets of SIRT4 in breast cancer. Conclusions: These results demonstrate that SIRT4 exerts its tumor-suppressive activity via modulating SIRT1 expression in breast cancer and provide a novel cross-talk between mitochondrial and nuclear sirtuins.