tbuckley/cabot-search huggingface dataset:
THU0227 Genome-wide association meta-analysis identifies five new loci for systemic lupus erythematosus
Authors: A Julià, P Carreira, R Blanco, FJ Lόpez-Longo, JJ Pérez-Venegas, A Olivé, JL Andreu, MA Aguirre-Zamorano, P Vela, JM Nolla, JL Marenco de la Fuente, A Zea, JM Pego, M Freire, E Díez, M Lόpez-Lasanta, M Lόpez-Corbeto, N Palau, R Tortosa, E Trallero, A Aterido, D Absher, RM Myers, A Fernandez-Nebro, S Marsal
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Recent genome-wide association studies (GWAS) have identified more than 50 loci associated with systemic lupus erythematosus but they explain less than 30% of the heritability of the disease. Meta-analysis including new populations can contribute to identify additional genetic risk factors. <h3>Objectives</h3> The aim of the presents study was to identify additional genetic risk loci for SLE. <h3>Methods</h3> We performed a meta-analysis using data from a recent large scale GWAS from 4,036 cases and 6,959 controls from Caucasian European ancestry [1] and a newly genotyped cohort of 907 SLE patients and 1,524healthy controls from Spain. Genetic association was tested at the single-marker level using linear regression and at the pathway-level using Fisher9s modified method. <h3>Results</h3> Combining the two cohorts we identified genome-wide significant association (P&lt;5E-8) at five new loci: three SNPs at intragenic regions and two intergenic loci at chromosomes <i>7q11.23</i> (Manhattan plot for chromosome 7 is shown in Figure; new SLE risk region SNPs highlighted in green) and <i>17q21.31</i>. Several of the new associated genes are functionally associated with B cell regulation. After multiple test correction, <i>B Cell Receptor signaling</i>, <i>Biopeptides</i> and <i>Cell surface interactions at the vascular wall</i> pathways were also significantly associated with SLE risk. <h3>Conclusions</h3> In conclusion, we have identified five new risk loci for SLE through a meta-analysis including a new GWAS. <h3>References</h3> Bentham J, Morris DL et al. Nature Genetics 2015. <h3>Acknowledgements</h3> We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaboration. We would also like to thank the international SLE consortium for access to the data. <h3>Disclosure of Interest</h3> None declared
FRI0167 Comparative cardiovascular safety of abatacept and tumor necrosis factor inhibitors in rheumatoid arthritis patients with and without cardiovascular disease: a population-based cohort study
Authors: Y Jin, EH Kang, G Brill, RJ Desai, SC Kim
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD). Recent studies suggested that treatment of RA with tumor necrosis inhibitors (TNFi) can reduce the risk of cardiovascular events. However, it is unclear how abatacept, a selective costimulation modulator, affects cardiovascular risk among RA patients compared with TNFi. <h3>Objectives</h3> To evaluate the comparative cardiovascular safety of abatacept versus TNFi in RA patients with and without underlying CVD. <h3>Methods</h3> We identified RA patients aged ≥18 with ≥2 RA ICD-9 codes (714.xx) separated by ≥7 days but &lt;365 days, from two large insurance claims data across the U.S.: Medicare (2008–2013) and Truven MarketScan (2006–2015). Only new users of abatacept or TNFi (adalimumab, etanercept, certolizumab, golimumab, and infliximab) were included. The primary outcome of interest was a composite endpoint of CVD including myocardial infarction (MI), stroke/transient ischemic stroke, or coronary revascularization. Secondary outcomes were each component of the primary outcome, incident heart failure (HF), and venous thromboembolism (VTE). 1:1 propensity score (PS) matching was performed separately in each database and each subgroups (with or without baseline CVD). Then the PS-matched subgroups were aggregated to form the overall matched cohort. Cox regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of risk of each outcome. Estimates from two different databases were combined through an inverse variance-weighted fixed-effects model. <h3>Results</h3> After 1:1 PS matching, there were 6,102 patient pairs from Medicare and 6,934 pairs from MarketScan. Among them, patients with baseline CVD were 35.3% in Medicare and 14.0% in MarketScan. Baseline characteristics were well balanced between two treatment groups after matching (standardized mean difference &lt;0.1). In Medicare cohort, abatacept consistently showed a decreased risk of composite CVD compared with TNFi in overall and each subgroup (Figure). However, in MarketScan cohort, where the population was younger than Medicare cohort, there was no association between abatacept and CVD compared to TNFi. After combining the two databases, abatacept was significantly associated with reduced risk of composite CVD outcome vs. TNFi in overall cohort (HR =0.79, 95% CI=0.67–0.92) and baseline CVD subgroup (HR =0.79, 95% CI=0.64–0.98). We also observed similar trend for secondary outcomes, where abatacept had decreased risk than TNFi. <h3>Conclusions</h3> In this large multi-database population-based study of RA patients, abatacept treatment was associated with reduced risk of CVD compared to TNFi, especially among older population and patients with prior CVD conditions. <h3>Disclosure of Interest</h3> None declared
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Robert L Coleman, Amit M Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Johanne I Weberpals, Andrew Clamp, Giovanni Scambia, Alexandra Leary, Robert W Holloway, Margarita Amenedo Gancedo, Peter C Fong, Jeffrey C Goh, David M O'Malley, Deborah K Armstrong, Jesus Garcia-Donas, Elizabeth M Swisher, Anne Floquet, Gottfried E Konecny, Iain A McNeish, Clare L Scott, Terri Cameron, Lara Maloney, Jeff Isaacson, Sandra Goble, Caroline Grace, Thomas C Harding, Mitch Raponi, James Sun, Kevin K Lin, Heidi Giordano, Jonathan A Ledermann, M Buck, A Dean, M L Friedlander, J C Goh, P Harnett, G Kichenadasse, C L Scott, H Denys, L Dirix, I Vergote, L Elit, P Ghatage, A M Oza, M Plante, D Provencher, J I Weberpals, S Welch, A Floquet, L Gladieff, F Joly, A Leary, A Lortholary, J Lotz, J Medioni, O Tredan, B You, A El-Balat, C Hänle, P Krabisch, T Neunhöffer, M Pölcher, P Wimberger, A Amit, S Kovel, M Leviov, T Safra, R Shapira-Frommer, S Stemmer, A Bologna, N Colombo, D Lorusso, S Pignata, R F Sabbatini, G Scambia, S Tamberi, C Zamagni, P C Fong, A O'Donnell, M Amenedo Gancedo, A Casado Herraez, J Garcia-Donas, E M Guerra, A Oaknin, I Palacio, I Romero, A Sanchez, S N Banerjee, A Clamp, Y Drew, H G Gabra, D Jackson, J A Ledermann, I A McNeish, C Parkinson, M Powell, C Aghajanian, D K Armstrong, M J Birrer, M K Buss, S K Chambers, L-m Chen, R L Coleman, R W Holloway, G E Konecny, L Ma, M A Morgan, R T Morris, D G Mutch, D M O'Malley, B M Slomovitz, E M Swisher, T Vanderkwaak, M Vulfovich
Journal: The Lancet (2017)
Reply from Authors re: Girish S. Kulkarni, Zachary Klaassen. Trimodal Therapy is Inferior to Radical Cystectomy for Muscle-invasive Bladder Cancer using Population-level Data: Is There Evidence in the (Lack of) Details? Eur Urol 2017;72:488–9
Authors: Thomas Seisen, Alexander P. Cole, Quoc-Dien Trinh
Journal: European Urology (2017)
Accelerated Wound Healing on Skin by Electrical Stimulation with a Bioelectric Plaster
Authors: Hiroyuki Kai, Takeshi Yamauchi, Yudai Ogawa, Ayaka Tsubota, Takahiro Magome, Takeo Miyake, Kenshi Yamasaki, Matsuhiko Nishizawa
Journal: Advanced Healthcare Materials (2017)

Wound healing on skin involves cell migration and proliferation in response to endogenous electric current. External electrical stimulation by electrical equipment is used to promote these biological processes for the treatment of chronic wounds and ulcers. Miniaturization of the electrical stimulation device for wound healing on skin will make this technology more widely available. Using flexible enzymatic electrodes and stretchable hydrogel, a stretchable bioelectric plaster is fabricated with a built-in enzymatic biofuel cell (EBFC) that fits to skin and generates ionic current along the surface of the skin by enzymatic electrochemical reactions for more than 12 h. To investigate the efficacy of the fabricated bioelectric plaster, an artificial wound is made on the back skin of a live mouse and the wound healing is observed for 7 d in the presence and absence of the ionic current of the bioelectric plaster. The time course of the wound size as well as the hematoxylin and eosin staining of the skin section reveals that the ionic current of the plaster leads to faster and smoother wound healing. The present work demonstrates a proof of concept for the electrical manipulation of biological functions by EBFCs.
FRI0159 Infection and malignancy are now the major causes of death in aggressively treated rheumatoid arthritis patients
Authors: N Chaplin, J McNally, J Kitchen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have an increased mortality compared to the general population. Previous studies have shown that this is attributable to cardiovascular and respiratory disease. Over recent years earlier and more aggressive treatment with higher dosage of methotrexate and the earlier use of biologic drugs has improved disease outcomes. The effect on cause of death is unknown. In this retrospective cohort study we found the major cause of death was infection followed by malignancy and found no correlation with seropositivity or gender. <h3>Objectives</h3> To analyse the causes of death in RA patients treated with aggressive disease modifying anti rheumatic drugs (DMARD) and Biologic therapies in Berkshire, UK. <h3>Methods</h3> Patients with RA who died between 2010 and 2016 were identified using the DAWN software DMARD monitoring database. A cohort of 3106 patients with RA are monitored using DAWN software in Berkshire, UK. The causes of death were identified from medical records, general practice records or the local coroners office. <h3>Results</h3> 198 patients on DAWN monitoring died during the 6 year study period. Treatment details and cause of death was identified for 131 RA patients. 71% were seropositive for rheumatoid factor and 61% were female. 91 patients (69%) were treated with methotrexate, 28 hydroxychloroquine (21%), 14 sulphasalazine (21%) and 7 with leflunomide (5%). The majority of patients (81) were on monotherapy (61%), 32 were on 2 DMARDS (24%) and only one was on triple therapy. 4 patients with RA who died were on biologic monotherapy, 10 were treated with biologic and combination DMARD. The most commonly prescribed biologics were etanercept (35%) and rituximab (35%). The leading causes of death in this cohort were pneumonia (39 patients 29%), cerebrovascular disease (16 patients 12%), septicaemia (11 patients 8%) and lung cancer (6 patients 4%). Infection accounted for 57 patients9 deaths (43%) followed by malignancy in 24 patients (18%). Cerebrovascular disease (20 patients, 15%) and cardiovascular disease (13 patients, 9%) were less frequent causes of death in our cohort. Comorbidity data for the cohort was recorded premortem. 49 patients (37%) had cardiovascular disease of any kind. 25% had respiratory disease and 23% had an endocrine comorbidity (predominantly diabetes). <h3>Conclusions</h3> In our large cohort of aggressively treated RA patients, infection followed by malignancy and not cardiovascular disease, was the leading cause of death. Larger prospective studies will be required to see if cumulative drug toxicity of more aggressive early treatment improves outcome from RA but changes mortality from comorbidities over time. <h3>Disclosure of Interest</h3> None declared
Acute Coronary Syndromes
Authors: Filippo Crea, Peter Libby
Journal: Circulation (2017)

Well into the 21st century, we still triage acute myocardial infarction on the basis of the presence or absence of ST-segment elevation, a century-old technology. Meanwhile, we have learned a great deal about the pathophysiology and mechanisms of acute coronary syndromes (ACS) at the clinical, pathological, cellular, and molecular levels. Contemporary imaging studies have shed new light on the mechanisms of ACS. This review discusses these advances and their implications for clinical management of the ACS for the future. Plaque rupture has dominated our thinking about ACS pathophysiology for decades. However, current evidence suggests that a sole focus on plaque rupture vastly oversimplifies this complex collection of diseases and obscures other mechanisms that may mandate different management strategies. We propose segmenting coronary artery thrombosis caused by plaque rupture into cases with or without signs of concomitant inflammation. This distinction may have substantial therapeutic implications as direct anti-inflammatory interventions for atherosclerosis emerge. Coronary artery thrombosis caused by plaque erosion may be on the rise in an era of intense lipid lowering. Identification of patients with of ACS resulting from erosion may permit a less invasive approach to management than the current standard of care. We also now recognize ACS that occur without apparent epicardial coronary artery thrombus or stenosis. Such events may arise from spasm, microvascular disease, or other pathways. Emerging management strategies may likewise apply selectively to this category of ACS. We advocate this more mechanistic approach to the categorization of ACS to provide a framework for future tailoring, triage, and therapy for patients in a more personalized and precise manner.
AB0595 Novel approachs based in current evidence in anca-associated vasculitis with renal involvement treatment
Authors: V Vazquez, G Gonzalez, J Robaina Sindin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> ANCA-associated vasculits (AAV) are a group of multi-system autoinmune diseases characterized by inflamation and necrosis in small and medium vessels.AAV could respond to diferent therapeutics protocols depends on diverse levels of clinical severity and early treatment could improve the outcome of the disease.In spite of recognized efficay of regimens consisting of cyclophosphamide and high-dose corticosteroids to control the AAV,efforts to minimize drugs-related toxicity led to consider targeted therapies. <h3>Objectives</h3> Considering the currently quality evidence in therapies novely proposed to AAV and the severity of renal disease presentation,we suggest new rational approaches emphasizing targeting B-cells therapy and preventing disease relapse <h3>Methods</h3> We identified the latest quality evidence using methodological search filters,assessed the evidence quality with Cochrane Renal Goup check list and determinated the strenght of recommendations by Levels of Evidence (Oxford Centre for Evidence-based Medicine) <h3>Results</h3> Rituximab (RTX), a monoclonal anti-CD 20antibody, has emerged as the biologic agent more using in AAV patients in current publications and unlike latest Guides and Recommendations published,RTX would be recommended in induction and maintenance AAV with renal involvement treatment (Table 1). <h3>Conclusions</h3> Current therapeutical protocols for AVV with renal involvement show that emerging therapies like RTX could improve rates of relapses and treatment-related toxicity. Further studies would provide target-therapeutical options <h3>References</h3> Vazquez V et al. Clinical practice guideline for ANCA-associated vasculitis with renal involvement. Medicina (Buenos Aires). 2015;75 Suppl 1:1–38 Mukhtyar C et al. EULAR recommendations for the management of primary small and medium vesselvasculitis. Ann Rheum Dis 2009;68:310–317. Guillevin L et al. Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis. N Engl J Med 2014;371:1771–80. <h3>Disclosure of Interest</h3> None declared
AB0691 Metformin therapy can restore the balance of TH17 and treg cells in patients with spondyloarthrit
Authors: J He, J Xie, H Niu, R Jia, J Cao, Y Liu, J Li, J Luo, X Sun, X Li, C Lu, C Gao
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Spondyloarthrit (SpA) is a chronic autoimmune disease and is associated with immunological function disorder. Previous studies have observed that increased number of T17 cells and decreased number of Regulatory T (Treg) cell in patients with S [1,2]. However, the current therapy for SpA, focusedon NSAID, biological agents and glucocorticoid, can9t correct the imbalance of Th17 and Treg cells. Metformin has been demonstrated a reducing effect on Th17 cells but an increasing effect on Treg cells, regulating the Thl7/Treg ratio [3]. <h3>Objectives</h3> The study is to explore the effect of metformin therapy on the balance of Th17 and Treg cells in patients with SpA. <h3>Methods</h3> SpA patients (n=27) (from August 1st to November 30th in 2016, both outpatients and inpatients in our department, according to American-European Consensus Group criteria for SpA), who were given metformin (750mg/day for 6 weeks). Laboratory indicators were compared before and after metformin treatment. <h3>Results</h3> The number of Treg cells [25.37 (18.31,45.78) vs.34.43 (25.91,50.31), P=0.015] significantly increased after the treatment. At the same time, there was a significantly decrease in the ratio of Th17/Treg cells [0.26 (0.15,0.48) vs. 0.22 (0.1,0.33), P+0.037]. Besides, Th17 cells were also decreased [7.85 (4.95,10.65) vs. 6.42 (3.7,10.63)]. <h3>Conclusions</h3> Metformin can restore and maintain the balance of Th17 and Treg cells in the patients with SpA. And it may be a potential therapy for SpA. <h3>References</h3> Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides.Arthritis Rheum. 2008;58:2307–17. Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis.Arthritis Rheum. 2009;60:1647–56. Son HJ, Lee J. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediators Inflamm.2014,2014:973986. <h3>Disclosure of Interest</h3> None declared
FRI0242 Association between clinical and radiographic responses, and physical function in a phase 3 study of sarilumab plus methotrexate in patients with active, moderate-to-severe rheumatoid arthritis
Authors: MC Genovese, H van Hoogstraten, W Kampman, S Jayawardena, TW Huizinga
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In MOBILITY (NCT01061736), SC sarilumab (150 or 200 mg q2w) + MTX demonstrated efficacy in adults with RA and inadequate response to MTX. The most common TEAEs were infections, neutropenia, injection site reactions, and increased transaminases. <h3>Objectives</h3> To examine association between clinical response and radiographic progression and functional response (HAQ-DI) in MOBILITY. <h3>Methods</h3> In this post hoc analysis, associations between HAQ-DI and clinical efficacy categories (CDAI, DAS28-CRP, SDAI, and Boolean-based ACR/EULAR remission) were tested at wk 16. Trend for change from baseline (BL) in HAQ-DI across response categories was assessed using the Jonckheere-Terpstra test. <h3>Results</h3> Regardless of definition, percentage achieving remission (CDAI ≤2.8, DAS28-CRP &lt;2.6, SDAI ≤3.3) or no x-ray progression was higher with sarilumab vs Pbo (<i>P</i>&lt;0.05). Overall, there was a significant trend between magnitude of clinical response at wk 16 and improvement in physical function (Table). This trend was also observed for radiographic progression (mTSS change from BL), regardless of cutoff (≤0.5 and ≤0). In patients achieving remission, there was a numerically greater improvement in HAQ-DI with sarilumab vs placebo (Pbo). Even if patients did not achieve remission or LDA, the sarilumab group had generally greater numerical improvements in HAQ-DI vs Pbo. <h3>Conclusions</h3> Achieving LDA or remission, or absence of radiographic progression, was associated with overall greater improvement in physical function. Irrespective of whether patients achieved remission or LDA, sarilumab + MTX showed greater improvements in HAQ-DI than Pbo + MTX. <h3>Acknowledgements</h3> This study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Editorial support was provided by MedThink SciCom and funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. <h3>Disclosure of Interest</h3> M. Genovese Grant/research support from: Roche, Sanofi, GlaxoSmithKline, R-Pharma, RuiYi, and Bristol-Myers Squibb, Consultant for: Roche, Sanofi, GlaxoSmithKline, R-Pharma, RuiYi, and Bristol-Myers Squibb, H. van Hoogstraten Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, W. Kampman Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, S. Jayawardena Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, T. Huizinga Consultant for: Sanofi, Roche, and Abblynx.
AB0552 Antiphospholipid antibodies in giant cell arteritis
Authors: A Hocevar, R Jese, Z Rotar, P Zigon, S Cucnik, M Tomsic
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> The aim of our prospective study was to evaluate the role of antiphospholipid antibodies (aPL) on the clinical presentation of giant cell arteritis (GCA). <h3>Methods</h3> GCA patients diagnosed for the first time between 1. September 2011 and 31. December 2016 at our secondary/tertiary rheumatology center and in whom aPL-Abs were determined at presentation were included. We studied four types of aPL-Abs in patient9s sera: lupus anticoagulants (LA), IgG and IgM isotype of anticardiolipin antibodies (aCL), of antibodies to β2-glycoprotein 1 (aβ2GP1) and of antibodies to phosphatidylserine-prothrombin complex (aPS/PT). LA activity was determined only in patients not receiving anticoagulant therapy. A dilute Russell viper venom time test was used and a ratio above 1.2 was considered positive. aCL, aβ2GPI and aPS/PT were measured using an in-house ELISA. A value above the 99th percentile of healthy control population was taken as positive. <h3>Results</h3> During the 64-month observation period we performed all aPL-Abs tests in 121 GCA patients (81 females (66.9%); median (IQR) age 73.8 (66.4; 78.7) years). We found LA, aCL, aβ2GP1 and aPS/PT in 59 (48.8%), 55 (45.5%), 15 (12.4%) and 18 (14.9%) cases, respectively. Fifty-four patients (44.6%) were single, 25 (20.7%) double, 13 (10.7%) triple and 1 (0.8%) quadruple aPL-Abs positive. 28 patients (23.1%) were aPL-Abs negative. Clinical characteristics of individual aPL-Ab type groups are presented in Table 1. There was one case of concurrent venous thrombotic event in our group (in a patient without aPL-Abs). The presence of aCL was associated with extracranial large vessel vasculitis (RR 1.8 (95% CI 1.1–2.9)). Double- or triple-positivity for any combination of "classic" aPL (LA and/or aCL and/or abeta2GP1) emerged as a marker of severe visual manifestations (RR of 2.1 (95% CI 1.1–4.3) for permanent or transient visual loss in case of double or triple aPL positivity vs. LA, aCL and aβ2GP1 negative cases). At least 1 year follow-up data (median (IQR) of 103 (54; 105) weeks) were available for 73 patients. 32 patients (43.8%) relapsed, most frequently those with positive aβ2GP1 (62.5%). <h3>Conclusions</h3> Our results indicate that aCL could identify GCA patients with extracranial large vessel disease. The double- or triple-positivity for any combination of LA and/or aCL and/or aβ2GP1 seems to be a marker of severe visual manifestations. <h3>Disclosure of Interest</h3> None declared