tbuckley/cabot-search huggingface dataset:
SP0069 Improving adherence in gout therapy
Authors: A. Abhishek
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Gout is the commonest inflammatory arthritis and affects between 2.5% and 3.9% of the adult population in the western world, with even higher prevalence estimates reported elsewhere. It is the only form of arthritis that can be "cured" with simple, inexpensive pharmacologic urate lowering treatment. Such medicines offer the potential for "cure" to most people with gout. However, despite this, gout patients have the lowest adherence to long-term pharmacologic treatment among people with different rheumatic diseases. The reasons for this are multifactorial but include misconceptions about the disease and its treatment among patients, physicians and the wider community. The long-term management of gout is overseen by primary care physicians in most countries. Recent studies have explored alternate models of gout managment and care, such as by community pharmacists and nurses. Such interventions have associated with a high uptake of urate lowering treatment and excellent persistence with treatment for upto five years. This lecture will summarise the key barriers to the uptake of and adherence with urate lowering treatment. Recent randomised controlled trials and pilot studies examining the role of nurses and pharmacists in the management of gout using a treat-to-target approach will be discussed. New data about the mechanism by which such interventions may promote adherence with urate lowering treatment will be presented. <h3>Disclosure of Interest</h3> A. Abhishek Grant/research support from: AstraZeneca, Ironwood, OxfordImmunotech, Speakers bureau: Menarini
Carfilzomib in Relapsed or Refractory Multiple Myeloma Patients with Early or Late Relapse Following Prior Therapy: An Analysis of Overall Survival in Subgroups from the Randomized Phase 3 Aspire and Endeavor Trials
Authors: Maria-Victoria Mateos, Hartmut Goldschmidt, Jesus F San-Miguel, Julie Blaedel, Mihaela Obreja, Zhao Yang, Zsolt Szabo, Xavier Leleu
Journal: Blood (2018)
DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans
Authors: Gergely Karsai, Florian Kraft, Natja Haag, G. Christoph Korenke, Benjamin Hänisch, Alaa Othman, Saranya Suriyanarayanan, Regula Steiner, Cordula Knopp, Michael Mull, Markus Bergmann, J. Michael Schröder, Joachim Weis, Miriam Elbracht, Matthias Begemann, Thorsten Hornemann, Ingo Kurth
Journal: Journal of Clinical Investigation (2019)

BACKGROUND. Sphingolipids are important components of cellular membranes and functionally associated with fundamental processes such as cell differentiation, neuronal signaling, and myelin sheath formation. Defects in the synthesis or degradation of sphingolipids leads to various neurological pathologies; however, the entire spectrum of sphingolipid metabolism disorders remains elusive.
Trends in Clinical Breast Density Assessment From the Breast Cancer Surveillance Consortium
Authors: B L Sprague, K Kerlikowske, E J A Bowles, G H Rauscher, C I Lee, A N A Tosteson, D L Miglioretti
Journal: JNCI Journal of the National Cancer Institute (2018)

Changes to mammography practice, including revised Breast Imaging Reporting and Data System (BI-RADS) density classification guidelines and implementation of digital breast tomosynthesis (DBT), may impact clinical breast density assessment. We investigated temporal trends in clinical breast density assessment among 2 990 291 digital mammography (DM) screens and 221 063 DBT screens interpreted by 722 radiologists from 144 facilities in the Breast Cancer Surveillance Consortium. After age-standardization, 46.3% (95% CI = 44.1% to 48.6%) of DM screens were assessed as dense (heterogeneously/extremely dense) during the BI-RADS 4th edition era (2005-2013), compared to 46.5% (95% CI = 43.8% to 49.1%) during the 5th edition era (2014-2016) (P = .93 from two-sided generalized score test). Among DBT screens in the BI-RADS 5th edition era, 45.8% (95% CI = 42.0% to 49.7%) were assessed as dense (P = .77 from two-sided generalized score test) compared to 46.5% (95% CI = 43.8% to 49.1%) dense on DM in BI-RADS 5th edition era. Results were similar when examining all four density categories and age subgroups. Clinicians, researchers, and policymakers may reasonably expect stable density distributions across screened populations despite changes to the BI-RADS guidelines and implementation of DBT.
AB0397 Prevalence and factors associated with depression among patients affected by chronic inflammatory arthritis: preliminary results of a single-centre experience in italy
Authors: S. Pezzato, S. Tomassi, E. Fracassi, A. Giollo, C. Caimmi, F. Martinis, M.G. Gnatta, D. Cristofalo, C. Bonetto, M.L. Marognolli, S. Tosato, A. Carletto
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Depression and anxiety disorders are more common in chronic inflammatory arthritides (CIA) than in the general population.<sup>1</sup> In rheumatoid arthritis (RA), depressive and anxiety symptoms have been associated with disease activity and pain perception,<sup>1</sup> physical disability,<sup>2</sup> health care costs,<sup>3</sup> and mortality.<sup>4</sup> To our knowledge, data on the prevalence of depression in Italian patients with RA are scarce. <h3>Objectives</h3> To estimate the prevalence and factors associated with depression among patients affected by RA. <h3>Methods</h3> During an one year period, patients affected by RA have been consecutively enrolled. For each patient demographics and disease characteristics were recorded; the Hospital Anxiety and Depression Scale (HADS) was administered. HADS is a validate questionnaire to assess depressive and anxiety symptoms in patients affected by somatic disorders admitted to general hospital. An HADS ≥11 was considered diagnostic for depression. <h3>Results</h3> The table summarises the main results. We recruited 231 patients affected by RA, finding a prevalence of depression of 13.9% (95% CI 9.4%–18.3%). Overall, patients with depression, when compared with patients without, were older, more frequently females, with a lower education, higher physician global assessment and patient global assessment, more comorbidities. In particular, they had any cardiovascular, neurologic or musculoskeletal issue (p=0.018, p=0.032, p=0.014, respectively) and more often used glucocorticoids or NSAIDs. Conversely, no association was found between depressive symptoms and the use of biologic therapies or the presence of inflammatory markers. Interestingly, a positive history of depression was present only in few patients with an HADS ≥11. <h3>Conclusions</h3> These preliminary results suggest that more than one every seven patients with RA could suffer from depression, thus depression might be undiagnosed in a significant number of patients. Comorbidities, anti-inflammatory medications and both physician- and patient- driven evaluation of disease burden were the most striking factors associated with depression in this cohort of patients with RA. <h3>References</h3> [1] Kojima M, et al. Arthritis and rheumatism2009Aug 15;61(8):1018–24. [2] Peck JR, et al. Arthritis and rheumatism1989Sep;32(9):1100–6. [3] Joyce AT, et al. J Rheumatol2009Apr;36(4):743–52. [4] Ang DC, et al. J Rheumatol2005Jun;32(6):1013–9. <h3>Disclosure of Interest</h3> None declared
SAT0655 Myositis and fasciitis by magnetic resonance imaging in recent-onset polymyalgia rheumatica and effect of tocilizumab therapy
Authors: J.P. Laporte, F. Garrigues, A. Huwart, S. Jousse-Joulin, T. Marhadour, D. Guellec, D. Cornec, V. Devauchelle-Pensec, A. Saraux
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In everyday practice, myofascial lesions are not usually evaluated on MRIs obtained for patients with PMR. <h3>Objectives</h3> To assess the prevalence of myofascial inflammatory lesions visible by magnetic resonance imaging (MRI) and their changes after tocilizumab therapy in active polymyalgia rheumatica (PMR). <h3>Methods</h3> We conducted a post hoc analysis of data from the TENOR study of tocilizumab monotherapy in PMR.<sup>1</sup> The 18 patients each received tocilizumab injections at weeks 0, 4, and 8. The shoulder and pelvic girdles were assessed at baseline then at weeks 2 and 12 using T1- and T2-STIR-weighted MRI. Radiologists blinded to patient data assessed each muscle group for myositis and fasciitis on baseline, week-2, and week-12 MRIs. Reproducibility was estimated by having two radiologists assess the week-2 MRIs of 13 patients then computing the kappa coefficient. <h3>Results</h3> For myofascial lesion detection, intraobserver reproducibility was almost perfect (κ=0.890) and interobserver reproducibility was substantial (κ=0.758). At baseline, all patients had at least one inflammatory myofascial lesion (example on right shoulder fig 1); sites involved were the shoulder in 10 (71.4%) patients, hip in 13 (86.7%), ischial tuberosity in 9 (60.0%), and pubic symphysis in 12 (80.0%). Sites involved at week 12 were the shoulder in 8 (53.3%) patients, hip in 5 (33.3%), ischial tuberosity in 1, and pubic symphysis in 3 (20.0%). At week 12, of 103 muscle groups studied in all, 43 (41.7%) had no inflammatory lesions, compared to 33 at baseline (Mac Nemar; p&lt;0.001) but some areas seemed to be more responsive to tocilizumab compared to other areas. Improvements were noted in 66 (64.1%) muscle groups, worsening in 2 (1.9%), no change in 35 (34.0%). <h3>Conclusions</h3> Myositis and fasciitis are common in recent-onset PMR and improve during tocilizumab therapy. They could be used for the diagnosis in routine practice and as criteria of outcome evaluation. <h3>References</h3> [1] Devauchelle-Pensec V, Berthelot JM, Cornec D, Renaudineau Y, Marhadour T, Jousse-Joulin S, et al. Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study. Ann Rheum Dis2016;75:1506–1510. <h3>Disclosure of Interest</h3> J. P. Laporte: None declared, F. Garrigues: None declared, A. Huwart: None declared, S. Jousse-Joulin: None declared, T. Marhadour: None declared, D. Guellec: None declared, D. Cornec: None declared, V. Devauchelle-Pensec: None declared, A. Saraux Grant/research support from: Chugai, Speakers bureau: Chugai
Annals Consult Guys - Low Risk for Postoperative Myocardial Infarction: What Do We Really Know?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2019)

Web Exclusives15 January 2019Annals Consult Guys - Low Risk for Postoperative Myocardial Infarction: What Do We Really Know?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author and Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0028 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Julia FaheyLICommunity Hospital13 February 2020 re post op MI s/p Mastectomy... I need to know which side was the radiation to the op site after mastectomy. Much higher risk if on the left side... Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Bayer. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Proctor & Gamble, Pfizer, and Johnson & Johnson. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 2019Volume 170, Issue 2Page: CG1KeywordsDiagnostic techniquesDisclosureMuscular dystrophiesMyocardial infarctionResearch grantsResearch reporting guidelines ePublished: 15 January 2019 Issue Published: 15 January 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Activation of Anxiogenic Circuits Instigates Resistance to Diet-Induced Obesity via Increased Energy Expenditure
Authors: Xiangyang Xie, Haili Yang, Juan Ji An, Jessica Houtz, Ji-Wei Tan, Haifei Xu, Guey-Ying Liao, Zhi-Xiang Xu, Baoji Xu
Journal: Cell Metabolism (2019)

Anxiety disorders are associated with body weight changes in humans. However, the mechanisms underlying anxiety-induced weight changes remain poorly understood. Using Emx1Cre/+ mice, we deleted the gene for brain-derived neurotrophic factor (BDNF) in the cortex, hippocampus, and some amygdalar subregions. The resulting mutant mice displayed impaired GABAergic transmission and elevated anxiety. They were leaner when fed either a chow diet or a high-fat diet, owing to higher sympathetic activity, basal metabolic rate, brown adipocyte thermogenesis, and beige adipocyte formation, compared to control mice. BDNF re-expression in the amygdala rescued the anxiety and metabolic phenotypes in mutant mice. Conversely, anxiety induced by amygdala-specific Bdnf deletion or administration of an inverse GABAA receptor agonist increased energy expenditure. These results reveal that increased activities in anxiogenic circuits can reduce body weight by promoting adaptive thermogenesis and basal metabolism via the sympathetic nervous system and suggest that amygdalar GABAergic neurons are a link between anxiety and metabolic dysfunction.
Risk Model for Overall Survival for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Validated for Patients on Ibrutinib, Idelalisib, Venetoclax, or Chemoimmunotherapy
Authors: Jacob D. Soumerai, Ai Ni, Mohamed Darif, Anil Londhe, Guan Xing, Yong Mun, Neil E. Kay, Tait D. Shanafelt, Kari G. Chaffee, Richard R. Furman, Peter Hillmen, Jeff Sharman, John F. Seymour, Asher A. Chanan-Khan, John C. Byrd, Jeffrey A. Jones, Lucille A. Ferrante, Lyndah K. Dreiling, Mehrdad Mobasher, Thomas Stark, Vijay Reddy, Angela J. Howes, Danelle James, Pankaj Bhargava, Andrew D. Zelenetz
Journal: Blood (2018)
A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease
Authors: Jo Howard, Claire Jane Hemmaway, Paul Telfer, D. Mark Layton, John Porter, Moji Awogbade, Timothy Mant, Daniel D. Gretler, Kobina Dufu, Athiwat Hutchaleelaha, Mira Patel, Vincent Siu, Sandra Dixon, Noel Landsman, Margaret Tonda, Joshua Lehrer-Graiwer
Journal: Blood (2019)
Serial Biomarker Monitoring Early after HCT Identifies Different Risks for Relapse and Graft-Vs-Host Disease
Authors: Mina D. Aziz, Jay Shah, Urvi Kapoor, Christina N. Dimopoulos, Francis A. Ayuk, William J. Hogan, Elisabeth Schreiner, Hannah K. Choe, Yi-Bin Chen, Elizabeth O. Hexner, Aaron Etra, Pietro Merli, Wolf Roesler, Carrie Kitko, Muna Qayed, Matthias Wölfl, Stephan Mielke, Kitsada Wudhikarn, Ryotaro Nakamura, Rainer Ordemann, Michael A. Pulsipher, Ran Reshef, Sarah Anand, Gregory Yanik, George Morales, Steven Kowalyk, Rachel Young, Nicolaus Kroeger, Tal Schechter-Finkelstein, Matthew Hartwell, Stephanie Gergoudis, Allan Augustine, Umut Ozbek, John E. Levine, James L.M. Ferrara
Journal: Blood (2018)
Abstract 15121: Induction of an Embryonic Cell Program After Myocardial Infarction in Non-Cardiomyocytes - Cardiac Resident Stem Cells or Fibroblasts?
Authors: Stefanie Doppler, Marcus-André Deutsch, Xinghai Li, Thomas Ratschiller, Harald Lahm, Caroline Jerrentrup, Gianluca Santamaria, Martina Dreßen, Sean M. Wu, Rüdiger Lange, Markus Krane
Journal: Circulation (2016)

Introduction: The existence of activated cardiac resident stem cells after myocardial infarction (MI) is still subject of controversial discussion. Hypothesis: We hypothesized that the adult mammal...
OP0229 The association of biologic drug-levels with infection risk: results from the british society for rheumatology biologics register for rheumatoid arthritis
Authors: M. Jani, W.G. Dixon, M. Lunt, D. De Cock, J.D. Isaacs, A.W. Morgan, A.G. Wilson, D. Plant, K. Watson, A. Barton, K. Hyrich
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> High dose tumour necrosis factor inhibitor (TNFi) drugs are associated with an increased serious infection (SI) risk.<sup><sup>1</sup></sup> It is feasible that high biologic levels predict dose-dependent adverse events such as SI. No registries have systematically evaluated the effect of drug levels on infection risk. <h3>Objectives</h3> To assess the effect of biologic drug levels in rheumatoid arthritis (RA) patients on (i) all infections (AI) (ii) SI (infections requiring hospitalisation, IV antibiotics or lead to death) <h3>Methods</h3> Patients recruited to both the British Society for Rheumatology Biologics Register-RA (safety data) and the Biologics in RA Genetics and Genomics Syndicate (serological samples) were included. Both are large national prospective RA cohorts. Biologic drug levels were measured at 3/6/12 months after biologic initiation and stratified as low/normal or high drug levels (HL) as per thresholds defined using concentration-effect curves for each drug. The risk of first and total infections within the first year was analysed. Events occurring on drug or within 90 days of last dose were included. The risk of an event was compared between low/normal vs HL groups using Cox proportional-hazard models. Factors affecting both drug levels and infection risk were adjusted for in the models. <h3>Results</h3> 703 patients (286 etanercept, 179 adalimumab, 120 certolizumab, 104 tocilizumab and 14 infliximab) had clinical data and serological samples. 74% were women, mean (SD) age 58<sup><sup>12</sup></sup> years, on a first biologic (89%). The crude rate/1000 pyrs was 314 and 464 for AI; 54 and 76 for SI in the low/normal and HL groups respectively. The adjusted hazard ratio for AI within the first year differed significantly between the two groups with the HL group having 50 percent higher risk of AI (HR: 1.51; 95% CI: 1.14, 2.01) (table 1). The most common types of AI in the HL group were lower (34%) and upper (16%) respiratory tract infections, urinary tract infections (15%), skin infections including shingles (8%). <h3>Conclusions</h3> RA patients with high biologic drug levels have a higher risk of infection. Monitoring drug levels may be helpful in prediction of infection. In disease remission patients with HL, biologic dose tapering may lower infection risk. <h3>Reference</h3> [1] Singh JA, Cameron C, et al. Lancet2015;368:258–265. <h3>Acknowledgements</h3> Funded by an MRC CiC award and BMA Doris Hillier grant to MJ, AB, WGD, KLH. <h3>Disclosure of Interest</h3> None declared
Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia with Pre-Transplant Conditioning Using Fludarabine, Reduced-Dose Cyclophosphamide, and Low-Dose Thymoglobulin:Â Ksgct Prospective Study
Authors: Shinichi Kako, Yoshinobu Kanda, Makoto Onizuka, Nobuyuki Aotsuka, Kensuke Usuki, Takayoshi Tachibana, Takeshi Kobayashi, Jun Kato, Shingo Yano, Hiroaki Shimizu, Katsuhiro Shono, Masatsugu Tanaka, Shokichi Tsukamoto, Takehiko Mori, Etsuko Yamazaki, Shinichiro Okamoto
Journal: Blood (2018)
AB0016 Chromatin localization of survivin in cd4+ t-cells of patients with rheumatoid arthritis
Authors: S. Andres, K.M. Andersson, A. Damdimopoulos, G. Katona, M.I. Bokarewa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Oncoprotein survivin emerged as an important player in the pathogenesis of rheumatoid arthritis (RA). Results of genome-wide study suggest that survivin may take part in transcription stimulation of the RA-specific genes. <h3>Objectives</h3> To identify and describe survivin-dependent differences in transcription pattern between CD4<sup>+</sup> T-cells of RA patients and healthy subjects focusing in particular on a subset of genes involved in maturation of Th1 and Th17 cells. <h3>Methods</h3> CD4<sup>+</sup> T-cells were isolated from PBMC of 3 RA patients and 5 non-smoking and 2 smoking healthy controls using a positive selection and activated by Pam3cys+Concanavalin A+LPS. Chromatin immunoprecipitation (ChIP) was done using rabbit polyclonal anti-Survivin, purified DNA was prepared into libraries using ThruPLEX (Rubicon) and sequenced using Hiseq 2000 (Illumina). Resulting fastq sequencing files were mapped to the human reference genome (hg38) using the STAR aligner. Peaks were associated with the closest transcription start site. Enriched peak regions (p&lt;10–5) were identified in survivin-ChIP samples above background ("input") using the Homer software. The peaks were analysed using gene ontology (GO) technique as implemented in GOrilla and GSEA software. The genes, scored high in RA and not present/low in any controls or <i>vice versa</i> were identified. The enriched GO groups were searched for presence of Th1/Th17 regulating genes. <h3>Results</h3> We identified 11 145 survivin-bound chromatin sequencies. Out of them, GO technique indicated 770 genes in RA samples (7.3%) and 766 genes in healthy controls (19.5%) which were annotated and enriched (&gt;log-5) in GO terms. In the screening for genes regulating maturation of Th1/Th17 cells, CBLB, IRF1, STAT3, SGK1 and TNFSF14 were identified among the genes enriched in RA samples, while EGR3 and ETS1 were enriched only in healthy controls. Additionally, transcription factors Ezh2, Rad21, Ctbp2 and Suz12 were identified as common for both RA and healthy groups genes, associated with significant GO enrichment. <h3>Conclusions</h3> This study confirms the role of survivin as a transcription mediator in CD4 +T cells and is suggested to influence multiple genes involved in RA pathology. <h3>References</h3> [1] Andersson KME, et al. Pathogenic Trans differentiation of Th17 Cells Contribute to Perpetuation of Rheumatoid Arthritis during Anti-TNF Treatment. Mol. Med. 2015;21:536–43. [2] Hu D, et al. Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis. Nat. Commun. 2017;8:1600. <h3>Disclosure of Interest</h3> None declared