tbuckley/cabot-search huggingface dataset:
Decreased chance of a live born child in women with rheumatoid arthritis after assisted reproduction treatment: a nationwide cohort study
Authors: Bente Mertz Nørgård, Michael Due Larsen, Sonia Friedman, Torben Knudsen, Jens Fedder
Journal: Annals of the Rheumatic Diseases (2019)

No studies have examined the efficacy of assisted reproductive technology (ART) treatment in women with rheumatoid arthritis. Therefore, we examined the chance of live birth after ART treatment in women with rheumatoid arthritis compared with women without rheumatoid arthritis.Our cohort study is based on nationwide Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 30 June 2017. The cohorts comprised 1149 embryo transfers in women with rheumatoid arthritis, and 198 941 embryo transfers in women without rheumatoid arthritis. Our outcome was live birth per embryo transfer, and we controlled for multiple covariates in the analyses. In subanalyses, we examined a chance of biochemical/clinical pregnancy after ART and a possible impact of corticosteroid use prior to embryo transfer.The adjusted OR (aOR) for a live birth per embryo transfer in women with rheumatoid arthritis, relative to women without rheumatoid arthritis, was 0.78 (95% CI 0.65 to 0.92). The aORs for biochemical and clinical pregnancies were 0.81 (95% CI 0.68 to 0.95) and 0.82 (95% CI 0.59 to 1.15), respectively. Corticosteroid prescription prior to embryo transfer increased the OR for live birth (aOR=1.32 (95% CI 0.85 to 2.05)).The chance of a live birth was significantly reduced in women with rheumatoid arthritis receiving ART treatment, relative to women without rheumatoid arthritis, and our result suggested that the problem was related to an impaired chance of embryo implantation. The role of corticosteroid use prior to embryo transfer must be a subject for further research.
FRI0554 Which axial magnetic resonance imaging combination is optimal for assessing activity in spondyloarthritis?
Authors: M. Plier, F. Lecouvet, N. Michoux, M.S. Stoenoiu, B.R. Lauwerys, A. Nzeusseu Toukap
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> None <h3>Objectives</h3> To determine the optimal axial Magnetic Resonance Imaging (MRI) combination for assessing disease activity in spondyloarthritis <h3>Methods</h3> In this single centre cross-sectional study, patients with a known diagnosis of axial spondyloarthritis were selected. Clinical activity was defined by an Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) ≥1.3. Bone marrow oedema was quantified by the Berlin spine score and the global score for sacroiliac joints (SIJ). The ASDAS-CRP and MRI activity evaluation of the full spine and SIJ were available in the entire cohort. Receiver operating characteristic curves were done to test the performance of different MRI combinations in identifying patients with ASDAS-CRP ³ 1.3. Performance was interpreted as follows: 0.61–0.70=fair, 0.71–0.80=moderate. A pairwise comparison of the area under the curves (AUC) was made to rank these MRI scores according to their diagnostic performance. <h3>Results</h3> 44 patients were assessed (30 were men; mean age was 37 years; mean disease duration was 5.0 years; median serum CRP level was 4.0 mg/L; mean ASDAS-CRP was 2.6; n=36 with ASDAS≥1.3, and n=8 for ASDAS&lt;1.3). MRI activity score (MRIAS) performance was moderate for thoracic spine alone and SIJ in combination with thoracic spine or thoraco-lumbar spine or cervico-thoracic spine or total spine. Performance was fair for SIJ alone and total spine alone. MRIAS yielded the highest specificity for SIJ alone (Se=44%, Sp=100%), and the highest sensitivity for thoracic spine alone (Se=89%, Sp=50%). MRIAS for SIJ in combination with the thoracic spine yielded the highest AUC (0.78, p=0,0002). However, no significant difference was observed between MRIAS with a moderate performance (p<i>&gt;</i>0.05, whatever AUCs comparisons). <h3>Conclusions</h3> For assessing disease activity in axial spondyloarthritis MRI of the SIJ in combination with the thoracic spine performed as good as MRI based on a more extended imaging of the spine. <h3>Disclosure of Interest</h3> None declared
AB1122 Dialysis treatment of systemic vasculitis in paediatric patients
Authors: P. Miteva, D. Roussinov, R. Shumnalieva, S. Monov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Childhood-onset systemic vasculitis is a rare but serious condition with high mortality rate even with proper treatment. Renal involvement at presentation is a high risk for end stage renal disease (ESRD). <h3>Objectives</h3> The aim of our study was to review the results of the dialysis treatment in paediatric patients with systemic vasculitis in a single dialysis centre for children in Bulgaria. <h3>Methods</h3> For a period of 20 years we observed 9 clinical cases of systemic vasculitis – 5 cases of Goodpasture syndrome (GPS) – 4 girls and 1 boy from 6 to 17 years old; one 6 year old girl and one 12 year old boy with Granulomatosis with polyangitis (GPA); an 8 month old boy with microscopic polyangiitis (mPAN), and one 8 year old girl with Takayasu arteritis. Seven of the children were treated by hemodialysis because of progressive kidney failure leading to ESRD, one of them was treated by continuous ambulatory peritoneal dialysis (CAPD) and one conservatively. <h3>Results</h3> In the GPS group one of the girls still continues on hemodialysis with no pulmonary symptoms for more than 14 years follow-up. The second girl was treated with immunoadsorption after which reminded antibody negative. On the follow-up she is managed conservatively for chronic kidney disease. Two of the girls died because of severe pulmonary bleeding caused by exposure to fragrant smoke during incense. The boy was treated conservatively because of mild pulmonary and kidney involvement and died from pulmonary bleeding caused by smoke. In the GPA group the girl underwent kidney transplantation and died one month later, and the boy died because of severe pulmonary bleeding. The 8 month old boy with mPAN was treated by dialysis with some clinical improvement but after six months died because of thrombus in the right atrium. The girl with Takayasu arteritis was treated with CAPD but died because of cardiopulmonary complications. <h3>Conclusions</h3> End stage renal disease is poor prognostic factor for survival in paediatric patients with systemic vasculitis. 75% of the children died in a period of 5 months after initiation of dialysis treatment. <h3>Disclosure of Interest</h3> None declared
Wandering out of the GWAS wilderness: a new pathway paradigm for complex disease genetics
Authors: Jeffrey Sturek, Imre Noth
Journal: Thorax (2019)

A genetic contribution to asthma susceptibility has long been recognised.1 Despite multiple approaches, from candidate genes to genome-wide association studies (GWAS), a large proportion of this heritability remains unexplained.2 The reasons for this are myriad and are largely generalisable to similar approaches in other complex diseases and phenotypes. Candidate gene studies are well based in known pathophysiology and can be powered to identify small effect sizes, but often provide limited insight into new biology or therapeutic opportunities. GWAS are largely unbiased (tagging single-nucleotide polymorphism (SNP) selection not withstanding) and provide opportunities for discovery, but identifying the biologically functional variant can prove daunting, and other important variants likely do not survive genome-wide significance corrections where sample sizes, and hence statistical power, are limited. Both of these approaches in isolation are also likely to miss the influence of genetics on the complex phenotypic response to environmental exposures. In this issue of Thorax , Dizier et al report an interesting pathway-based approach to a gene by environment (G×E) analysis of a well-established epidemiological association between environmental tobacco smoke (ETS) exposure and bronchial hyper-responsiveness (BHR).3 This hybrid method has some of the benefits of multiple modalities and may provide a new avenue for further clarifying the genetic underpinnings of other complex diseases.

The basis for the current study …
SAT0527 Rituximab prescription patterns and efficacy in the induction treatment of anca-associated vasculitis in a belgian multicentric cohort
Authors: F. Vandergheynst, P. Chasseur, J.-B. Nicolas, C. von Frenckell, D. Blockmans
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The RAVE trial has revolutionised the induction treatment of ANCA-Associated Vasculitis (AAV, including GPA, granulomatosis with polyangiitis and MPA, microscopic polyangiitis), by demonstrating non-inferiority of rituximab compared with cyclophosphamide<sup>1</sup>. <h3>Objectives</h3> To study AAV patients’ characteristics, rituximab prescription practices and efficacy in AAV induction treatment in 4 Belgian university hospitals. The patient population, selected according to the Belgian reimbursement criteria, is relatively homogeneous and comparable to the one of RAVE trial. <h3>Methods</h3> 57 patients, receiving rituximab as AAV induction therapy since May 2014, were enrolled in an observational retrospective multicenter trial involving 4 Belgian university hospitals. We have focused on the type of AAV (GPA/MPA), ANCA specificity (anti-PR3/MPO), prescriber’s speciality, used reimbursement criteria, organ involvements, severity of the flares (according to BVAS-WG definition) and finally rituximab efficacy in AAV induction treatment by considering the RAVE primary (complete remission without prednisone) and secondary (complete remission with prednisone &lt;10 mg, rates of relapses) outcomes at 6, 12, 18 and 24 months. <h3>Results</h3> The most frequent subtype of AAV was GPA (84%). The main indication was relapsing disease (54.4%), followed by contra-indication to cyclophosphamide (38.6%). 66.7% of the patients reached complete remission with prednisone &lt;10 mg at 6 months, and 55.3% at 12 months, 40% at 18 months, 25% at 24 months respectively. In the “severe disease” subgroup, 73% reached complete remission with prednisone &lt;10 mg at 6 months, 58.8% at 12 months, 50% at 18 months and 32% at 24 months. The rates of complete remission without steroids were very low at 6, 12, 18 and 24 months (between 0%–6%) but our patients were not asked to follow a glucocorticoid tapering scheduled for complete withdrawal of prednisone after 6 months and were usually maintained under low-dose prednisone. Relapse rates were high between 18 and 24 months both in the total group and in the severe disease subgroup (due to the fact that rituximab is not reimbursed for maintenance treatment in Belgium). The subtype of ANCA was not predictive of the risk of relapse. <h3>Conclusions</h3> Our results confirm – in a “real-life” cohort of patients selected according data of RAVE trial – those of RAVE regarding complete remission rates at 6 months with prednisone 10 mg/j. The high prevalence of relapses – in particular after 18 months – underlines the need to optimise maintenance treatment after an induction treatment with rituximab. <h3>Reference</h3> [1] Specks U, Merkel PA, Seo P, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med2013:369(5):417–27. <h3>Disclosure of Interest</h3> None declared
Phase 1 Study of Adct-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Classical Hodgkin Lymphoma
Authors: Mehdi Hamadani, Graham P. Collins, Felipe Samaniego, Alexander I Spira, Andrew Davies, John Radford, Paolo Caimi, Tobias Menne, Joseph Boni, Hans Cruz, Jay Feingold, Shui He, Jens Wuerthner, Steven M. Horwitz
Journal: Blood (2018)
Abstract 13980: Variation in the Management of Patients With Obstructive Coronary Disease: Insights From the VA CART Program
Authors: Steven M Bradley, Maggie A Stanislawski, P. Michael Ho, Thomas M Maddox, John S Rumsfeld
Journal: Circulation (2013)

Background: Prior studies have shown variation in the use of percutaneous coronary intervention (PCI) relative to coronary artery bypass graft (CABG) surgery. However, these studies have not addres...
Layer‐by‐Layer Cerium Oxide Nanoparticle Coating for Antioxidant Protection of Encapsulated Beta Cells
Authors: Nicholas J. Abuid, Kerim M. Gattás‐Asfura, Emily A. Schofield, Cherie L. Stabler
Journal: Advanced Healthcare Materials (2019)

In type 1 diabetes, the replacement of the destroyed beta cells could restore physiological glucose regulation and eliminate the need for exogenous insulin. Immunoisolation of these foreign cellular transplants via biomaterial encapsulation is widely used to prevent graft rejection. While highly effective in blocking direct cell-to-cell contact, nonspecific inflammatory reactions to the implant lead to the overproduction of reactive oxygen species, which contribute to foreign body reaction and encapsulated cell loss. For antioxidant protection, cerium oxide nanoparticles (CONPs) are a self-renewable, ubiquitous, free radical scavenger currently explored in several biomedical applications. Herein, 2-12 alternating layers of CONP/alginate are assembled onto alginate microbeads containing beta cells using a layer-by-layer (LbL) technique. The resulting nanocomposite coatings demonstrate robust antioxidant activity. The degree of cytoprotection correlates with layer number, indicating tunable antioxidant protection. Coating of alginate beads with 12 layers of CONP/alginate provides complete protection to the entrapped beta cells from exposure to 100 × 10
SAT0235 Subcutaneous methotrexate is safer and more effective than oral methotrexate alone and in combination
Authors: K. H. C. Li, T. Jones, M. Grove, A. Roberts, F. Birrell
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Methotrexate (MTX) is established as both first line therapy and combination therapy anchor drug for Rheumatoid Arthritis (RA) and other peripheral inflammatory arthritis such as Psoriatic Arthritis (PsA). There is evidence subcutaneous (sc) MTX is more effective than oral MTX, with fewer treatment failures<sup>1–3</sup>, but it is not known if this holds true in routine practice and in combination. <h3>Objectives:</h3> To show the safety &amp; efficacy of sc MTX therapy in routine practice, compared to oral MTX, alternate monotherapy and combination therapies. <h3>Methods:</h3> The Therapy Audit Monitoring System (TAMS, www.therapyaudit.com/tamonitor) was installed Jan 2014. Since then all new patients starting disease modifying therapy and existing patients are entered. The database was queried for diagnosis, dose and response, together with adverse events (defined as ALT&gt;80U/l or neutrophils&lt;2.0x10<sup>9</sup>/l). Statistical comparisons used the two proportion Z test, T-test or exact rate ratio test, as appropriate: significance threshold p&lt;0.05. <h3>Results</h3> <h3>Conclusions:</h3> sc MTX is safe and effective in routine practice at doses up to 40 mg. It has lower toxicity than oral MTX in monotherapy and combination, despite a higher mean dose with highly significant reduction in neutropenia rate and the same rate of liver problems compared to oral. This is the largest study of sc MTX yet reported and supports use of higher doses in selected patients and aggregation or replication of data like this may support license extension for sc MTX beyond 30 mg. If patients are usually switched to sc MTX when oral MTX is ineffective or not tolerated, many do not progress to biologic therapy: delivering good care at lower cost. <h3>References</h3> [1]Schiff MH, Jaffe JS, Freundlich B. Ann Rheum Dis2014;73(8):1549–51. [2]Braun J, et al. A&amp;R2008;58(1):73–81. [3] Hazlewood GS,eta l. T. Ann Rheum Dis2016;75(6):1003–08. <h3>Disclosure of Interest:</h3> None declared
FRI0640 Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis in three large independent cohorts
Authors: L. De Winter, P. Vandormael, V. Stouten, H. W. van Steenbergen, P. Geusens, J. Lenaerts, A. H. M. van der Helm-van Mil, P. Verschueren, V. Somers
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Despite recent progress in biomarker discovery for RA diagnostics, still over one third of RA patients are seronegative for RF and ACPA, a number which is even higher in early disease. In both the University of Hasselt (UH) cohort (n=292) and Leiden Early Arthritis Clinic (EAC) cohort (n=600), 38% of RA patients were seronegative for RF and ACPA. Testing for novel autoantibodies to UH peptides UH-RA.1 and UH-RA.21, reduced the serological gap from 38% to 29% in the UH cohort (P=0.03) and from 38% to 32% in the EAC cohort (P=0.01), with associated specificities in rheumatic controls ranging from 88–96% <sup>1</sup>. <h3>Objectives:</h3> Our aim is to validate the reactivities of autoantibodies against UH-RA.1 and UH-RA.21 peptides in early and seronegative RA patients from the CareRA cohort. <h3>Methods:</h3> Peptide enzyme-linked immunosorbent assays have been developed to screen for the presence of antibodies to UH-RA peptides. Cut-off for seropositivity was defined by 2 x SD above the mean antibody level of the healthy control group <sup>1</sup>. Antibody reactivity to UH-RA.1 and UH-RA.21 was evaluated in baseline samples, collected before the start of treatment, of 223 early RA patients from the CareRA cohort. <h3>Results:</h3> Antibodies to UH-RA.1 and UH-RA.21 were found in respectively 5% and 21% of the baseline samples from the CareRA cohort. These antibodies were found in similar levels in both RF/ACPA seropositive and seronegative patients. In the CareRA cohort, 24% of patients were seronegative for RF and ACPA and combining the presence of autoantibodies to UH-RA.1 and UH-RA.21 with RF/ACPA serology, reduced the seronegative population from 24 % to 18% (P=0.13). <h3>Conclusions:</h3> Screening for antibodies against novel UH peptides UH-RA.1 and UH-RA.21 has now been performed in three large independent cohorts. This study validates the presence of antibody reactivity to these UH-RA peptides in seronegative and early RA. This might reinforce current diagnostics and improve early diagnosis and intervention in RA. <h3>Reference</h3> 1. De Winter, et al. Rheumatology (Oxford)2016;55(8):1431–6. <h3>Disclosure of Interest:</h3> None declared
Anxiety-Linked Attentional Bias: Is It Reliable?
Authors: Colin MacLeod, Ben Grafton, Lies Notebaert
Journal: Annual Review of Clinical Psychology (2019)

There is substantial evidence that heightened anxiety vulnerability is characterized by increased selective attention to threatening information. The reliability of this anxiety-linked attentional bias has become the focus of considerable recent interest. We distinguish between the potential inconsistency of anxiety-linked attentional bias and inconsistency potentially reflecting the psychometric properties of the assessment approaches used to measure it. Though groups with heightened anxiety vulnerability often exhibit, on average, elevated attention to threat, the evidence suggests that individuals are unlikely to each display a stable, invariant attentional bias to threat. Moreover, although existing assessment approaches can differentiate between groups, they do not exhibit the internal consistency or test-retest reliability necessary to classify individuals in terms of their characteristic pattern of attentional responding to threat. We discuss the appropriate uses of existing attentional bias assessment tasks and propose strategies for enhancing classification of individuals in terms of their tendency to display an attentional bias to threat.
AB0392 Rheumatoid arthritis and risk of incident chronic kidney disease: a systematic review and meta-analysis of cohort studies
Authors: P. Ungprasert, S. Raksasuk
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) may have a higher risk of developing chronic kidney disease (CKD) compared with general population. However, the data on this risk are limited and not well-characterised. <h3>Objectives</h3> This systematic review and meta-analysis aimed to comprehensively investigate the risk of incident CKD among patients with RA by reviewing all available studies. <h3>Methods</h3> A systematic review was performed using MEDLINE and EMBASE database from inception to December 2017 to identify all cohort studies (either retrospective or prospective) that compared the risk of incident CKD in patients with RA versus individuals without RA. Adjusted point estimates were extracted from individual studies and the pooled risk ratio and 95% confidence interval (CI) were calculated using random-effect, generic inverse-variance method of DerSimonian and Laird. Visualisation of funnel plot was used for evaluation for publication bias. <h3>Results</h3> A total of 4 retrospective cohort studies with 1,627,981 participants were included. The risk of incident CKD was significantly increased among patients with RA with the pooled risk ratio of 1.52 (95% CI, 1.28–1.80). The statistical heterogeneity of this study was high with an I<sup>2</sup> of 82%. The forest plot of this systematic review and meta-analysis is shown as figure 1. The funnel plot was relatively symmetric and, thus, did not suggest the presence of publication bias in favour of positive studies. Abbreviation: SE, standard error; IV, inverse variance; CI, confidence interval, RA, rheumatoid arthritis; CKD, chronic kidney disease <h3>Disclosure of Interest</h3> None declared
Thymic regulatory T cells arise via two distinct developmental programs
Authors: David L. Owen, Shawn A. Mahmud, Louisa E. Sjaastad, Jason B. Williams, Justin A. Spanier, Dimitre R. Simeonov, Roland Ruscher, Weishan Huang, Irina Proekt, Corey N. Miller, Can Hekim, Jonathan C. Jeschke, Praful Aggarwal, Ulrich Broeckel, Rebecca S. LaRue, Christine M. Henzler, Maria-Luisa Alegre, Mark S. Anderson, Avery August, Alexander Marson, Ye Zheng, Calvin B. Williams, Michael A. Farrar
Journal: Nature Immunology (2019)