tbuckley/cabot-search huggingface dataset:
SP0173 The challenges of a small organization
Authors: M Kosanovic
Journal: Annals of the Rheumatic Diseases (2017)

When a group of citizens establishes a non-profit and a non-government organisation in our country, those volunteers are carried by great enthusiasm. At the beginning when founding an NGO the main problems are lack of experience and financial resources. Those deficiencies can be overcome by some other qualities such as the personal competencies of volunteers. As NGOs are seen by the public rather critically in our country, our organization had to face several additional challenges. In my presentation I will illustrate the following aspects: the non-attractiveness of NGOs for volunteers, the lack of awareness how volunteering is important for a society, the lack of knowledge how to attract volunteers and how to manage them, the lack of knowledge how to define the volunteers9 positions and how to monitor their work, the lack of their systemic, continuing education and the lack of rewards, recognition and appreciation to acknowledge the most dedicated volunteers. <h3>Disclosure of Interest</h3> None declared
THU0050 Microrna-365 inhibits il-1β-induced catabolic factor expression by targeting hif-2α in human primary chondrocytes
Authors: MH Lee, J-I Hong, HS Hwang, KM Son, Ha Kim
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> MicroRNAs, small noncoding RNA molecules, are involved in the pathogenesis of various diseases such as cancer and arthritis. Endothelial PAS domain protein-1/hypoxia-inducible factor-2α (EPAS-1/ HIF-2α) is a catabolic transcription factor that regulates osteoarthritis (OA) cartilage destruction. <h3>Objectives</h3> In this study, we examined whether microRNA-365 (miR-365) affects interleukin (IL)-1β-induced expression of catabolic factors in chondrocytes via regulation of HIF-2α. <h3>Methods</h3> Total RNA was isolated from normal and OA cartilage tissues and human chondrocytes. miR-365 expression was quantified by TaqMan assay. The effects of miR-365 on HIF-2α and HIF-2α-modulated genes were assessed by quantitative real-time reverse polymerase chain reaction (qRT-PCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Direct interaction of miR-365 with the 39 untranslated region (UTR) of HIF-2α mRNA was examined using a luciferase reporter assay. Nitrite concentration was measured in culture medium using a Griess assay. <h3>Results</h3> miR-365 levels were significantly decreased in human OA cartilage relative to normal cartilage. Overexpression of miR-365 significantly suppressed IL-1β-induced expression of HIF-2α in human articular chondrocytes. Pharmacological inhibition of various IL-1β-associated signaling pathways revealed mitogen-activated protein kinase and nuclear factor-κB as the primary pathways driving IL-1β-mediated decreases in miR-365 and subsequent increase in HIF-2α expression. Using a luciferase reporter assay encoding the 39UTR of human HIF-2α mRNA, we showed that overexpression of miR-365 significantly suppressed IL-1β-induced up-regulation of HIF-2α. Furthermore, miR-365 overexpression significantly suppressed IL-1β-induced expression of catabolic factors, including cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-1, -3 and -13, and nitric oxide (NO) production in chondrocytes. <h3>Conclusions</h3> MiR-365 regulates IL-1β-stimulated catabolic effects in human chondrocytes by modulating HIF-2α expression. <h3>References</h3> Yang et al. Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction, Nat. Med. 16 (2010) 687–693. Akhtar et al. Haqqi, MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes, Arthritis Rheum. 62 (2010) 1361–1371. Park et al. MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1beta-induced catabolic effects in human articular chondrocytes, Osteoarthritis Cartilage 21 (2013) 981–989. <h3>Acknowledgements</h3> This study was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2014R1A1A2059823 and 2016R1D1A1B03932259). <h3>Disclosure of Interest</h3> None declared
THU0284 Predicting survival in 6240 patients with primary sjÖgren' syndrome (big data sjÖgren project)
Authors: P Brito-Zerόn, N Acar-Denizli, M Zeher, A Rasmussen, X Li, C Baldini, J-E Gottenberg, D Danda, L Quartuccio, G Hernandez-Molina, AA Kruize, S-H Park, M Kvarnström, S Praprotnik, D Sene, E Bartoloni, R Solans, T Mandl, Y Suzuki, M Rischmueller, G Nordmark, G Fraile, A Sebastian, H Bootsma, T Nakamura, V Valim, R Giacomelli, R Seror, V Devauchelle-Pensec, B Hofauer, M Bombardieri, V Trevisani, D Hammenfors, R Priori, SG Pasoto, J Morel, S Retamozo, TA Gheita, F Atzeni, C Vollenveider, X Mariette, M Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To correlate the main features at diagnosis with survival in a multicenter international cohort of patients with primary Sjögren syndrome (SS). <h3>Methods</h3> The Big Data Sjögren Project was formed in 2014 to take a “high-definition” picture of the main features of primary SS by merging international SS databases (9302 consecutive patients recruited from 21 countries of the 5 continents) <h3>Results</h3> Data about survival at the last visit was available in 6240 patients (5831 women, mean age at diagnosis of 53yrs, 82% White). After a mean follow-up of 7.1yrs, 407 (6%) patients died. Patients who died were more frequently men (10% vs 6%, p=0.004) and White (96% vs 81%, p&lt;0.001), had a higher mean age at diagnosis (64 vs 52yrs. p&lt;0.001) and a higher frequency of abnormal ocular (95% vs 87%, p&lt;0.001) and oral (90% vs 79%, p&lt;0.001) tests in comparison with survivors; sicca symptoms and salivary gland biopsy were unrelated to survival. Immunologically, patients who died showed a higher frequency of RF (52% vs 46%, p=0.039) and cryoglobulins (18% vs 7%, p&lt;0.001). Logistic regression identified as independent variables the age at diagnosis (OR 1.07), male gender (OR 1.77), abnormal ocular (OR 5.79) and oral (OR 2.10) tests, and cryoglobulins (OR 3.10). Time-adjusted multivariate Cox proportional-hazards regression analysis confirmed age at diagnosis (OR 1.12, CI95% 1.10–1.14), male gender (OR 2.12, CI95% 1.36–3.29) and cryoglobulins (OR 2.43, CI95% 1.72–3.42) as independent variables related to death. <h3>Conclusions</h3> An older age at diagnosis, male gender and serum cryoglobulins were the principal risk factors associated with death in this large multiethnic cohort of patients with primary SS. <h3>Disclosure of Interest</h3> None declared
FRI0456 Age at spondyloarthritis diagnosis and risk of cardiovascular comorbidity: results from the comospa study
Authors: MH Derakhshan, NJ Goodson, J Packham, R Sengupta, H Marzo-Ortega, A Molto, S Siebert
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Spondyloarthritis (SpA) and chronic inflammatory diseases are associated with a number of cardiovascular comorbidities. It is unknown whether age at SpA diagnosis is associated with cardiovascular outcomes in later life. <h3>Objectives</h3> To examine the relationship between “younger age at SpA diagnosis” and risk of various cardiovascular comorbidities. <h3>Methods</h3> COMOSPA is a large worldwide cross-sectional study comprising 3984 patients from 23 countries evaluating comorbidities in patients with SpA (1). We evaluated the association between “younger age at SpA diagnosis” (defined in 5-year blocks) and cardiovascular comorbidities using uni-variable and multi-variable binary logistic regression. Each model comprised one cardiovascular co-morbidity as dependent and “age at SpA diagnosis” as predictor adjusted for age, sex, BMI, history of smoking, alcohol, NSAIDs, DMARDs, biologics, steroids and other relevant factors <h3>Results</h3> The data of 3923 patients (64% male) were available for analysis. Current age ranged from 18 to 100 with median (IQR) of 42 (32–53) years. The median (IQR) age at SpA diagnosis was 33 (25–43) years. Main reported cardiovascular-related comorbidities were hypertension (22.4%), ischemic heart disease (IHD) (2.6%), stroke (1.3%) and diabetes mellitus (5.5%). The risk of hypertension, after adjustment for potential confounding factors was associated with younger age at SpA diagnosis (OR=1.10, 95% CI: 1.05 -1.16), indicating 10% higher risk of hypertension for each 5 year younger age at time of SpA diagnosis (Table). Confounding variables showing significant association with hypertension were current age (OR=1.12, 95% CI: 1.10–1.13, <i>p</i>&lt;0.001), male gender (OR=1.47, 95% CI: 1.20–1.80, <i>p</i>&lt;0.001), current BMI (OR=1.09, 95% CI: 1.07–1.11, <i>p</i>&lt;0.001), ever use of steroids (OR=1.24, 95% CI: 1.03–1.50, <i>p</i>=0.027) and ever use of synthetic DMARDs (OR=1.28, 95% CI: 1.05–1.57, <i>p</i>=0.017), but not ever use of NSAIDs or biologic DMARDs. The other cardiovascular comorbidities were not associated with “younger age at SpA diagnosis” after adjustments for relevant confounding factors in multivariable analyses (Table) <h3>Conclusions</h3> Younger age of SpA diagnosis is associated with increased risk of developing hypertension but not other cardiovascular comorbidities in this study. The explanation for this association is not clear and does not appear to be due to increased NSAID exposure. <h3>References</h3> Molto A, et al. Ann Rheum Dis 2016;75:1016–23. <h3>Disclosure of Interest</h3> None declared
AB1085 Measuring patient satisfaction of biological treatments in a regional hospital
Authors: D Grados, A Retamero, A Riveros, C Baliu, E Nogues, D Ferrandez, F Bové, AM Colquechambi, M Cucurell
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To determine/measure the satisfaction degree of patients with rheumatologic (rheumatoid arthritis, spondyloarthropathies and other arthritis) and dermatological (psoriasis, psoriatic arthritis and suppurative hidrosadenitis) disease treated with a biological drug. <h3>Methods</h3> Descriptive prospective study conducted in a Regional Hospital with a reference area of 109,530 inhabitants. A survey was conducted to all patients, thepatientswhocollectedtheir medication at the Pharmacy Service (self-administration treatment) and the patients who came for consultation (treatment administered by the nursing staff). The satisfaction degree before and after the biological treatmentwas evaluated.From 0 to 10, where 0 was the maximum dissatisfaction and 10 the maximum satisfaction; and improvement of pain, where 0 implied no improvement and 10 maximum improvement. Clinical records were reviewed and a database was generated for exploitation with SPSS-vs 22. All patients received an information sheet from the study and signed an informed consent form. <h3>Results</h3> A total of 100 patients were analyzed: 45 men and 55 women. The mean age was 53 years (SD 14.9). 42% of patients were actively employed. Distribution of patients by pathologies: 46 (46%) rheumatoid arthritis, 25 (25%) psoriasis, 16 (16%) psoriatic arthritis, 8 (8%) spondyloarthropathies, 2 (2%) suppurative hydrosadenitis and 1 (1%) juvenile idiopathic arthritis. Distribution of biological drugs: 49 (49%) adalimumab, 20 (20%) ustekinumab, 18 (18%) etanercept, 6 (6%) golimumab, 3 (3%) tocilizumab, 2 (2%) secukinumab,1 (1%) certolizumab. The treatment was self-administered in 61 patients. Only 30 (30%) patients had undergone previous biological treatment. At present, 43 patients had some additional treatment, 38 with methotrexate and 5 with leflunomide. <h3>Conclusions</h3> The satisfaction degree of patients with their biological treatment is very high regardless of the route of administration. Most of them are in monotherapy or with low doses of FAME. 61% of patients self-administer the drug at home. 93% of patients consider that there has been a change in their quality of life and that they can lead a normal life. <h3>Disclosure of Interest</h3> None declared
Medication Reconciliation vs Medication Review—Reply
Authors: Adam J. Rose, Shira H. Fischer, Michael K. Paasche-Orlow
Journal: JAMA (2017)

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OP0019 Dmard withdrawal in ra patients achieving therapeutic response with certolizumab pegol combined with dmards: interim results from a canadian observational randomized study
Authors: J Pope, E Rampakakis, E Grant, L Bessette, J Lazovskis, B Haraoui, JS Sampalis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The efficacy and safety of certolizumab pegol in the treatment of adult patients with moderate to severe rheumatoid arthritis (RA), when administered either in combination with methotrexate (MTX) or as monotherapy, has been previously shown in several controlled clinical trials. However, a detailed assessment of certolizumab pegol in combination with a wide range of non-biologic disease-modifying drugs (nbDMARDs) used in real-life routine clinical practice is lacking compared to switching to monotherapy after achieving a response when added to nbDMARD(s). <h3>Objectives</h3> The objective is to compare the effectiveness and tolerability of certolizumab pegol given as add-on to nbDMARDs, including MTX and others, or as monotherapy after achieving a DAS28(ESR) improvement of ≥1.2 In this descriptive interim analysis, preliminary data on the effectiveness of certolizumab pegol given in combination nbDMARDs or monotherapy, are presented. <h3>Methods</h3> RA patients who had certolizumab pegol added to their existing DMARD regimen due to inadequate response to their nbDMARD(s) were eligible. At 3 or 6 months, those patients who achieved a change in DAS28 of ≥1.2 were randomized to continue combination therapy (Combination group) or withdraw nbDMARD therapy (Monotherapy group) and be followed for 18 months. A sample size of 125 randomized patients per group was calculated to have 100 randomized (50 per group) to find a difference of 15% in response. <h3>Results</h3> A total of 121 patients were enrolled, of whom 79 were randomized to continue combination therapy (n=35) or withdraw nbDMARDs (n=44). No significant differences were observed between-groups in baseline age, gender (83% vs. 71% female), race (89% vs. 91% Caucasian), rheumatoid factor status (56% vs. 60% positive), or prior biologic experience (17% vs. 11%). At 18 months, upon adjusting for baseline scores, similar improvements were observed between groups in DAS28 ESR (-2.1 vs. -2.0). Furthermore, the odds of achieving DAS28 LDA (OR [95% CI]: 0.96 [0.28–3.31]), ΔDAS28&gt;1.2 (0.97 [0.29–3.26]), or both (1.00 [0.29–1.49]), were not different between the Combination and Monotherapy groups. Similarly, no differences were observed between groups at 12 months of treatment with respect to these outcomes. <h3>Conclusions</h3> The results of this interim analysis suggest that, among RA patients achieving a therapeutic response when on combination therapy with certolizumab pegol and nbDMARDs, nbDMARDs could be withdrawn without impact on treatment effectiveness over the next year. Additional analyses with the full number of patients will be conducted to confirm this finding. <h3>Disclosure of Interest</h3> None declared
FRI0346 Renal involvement in granulomatosis with polyangiitis
Authors: N Bulanov, E Makarov, E Kuznetsova, M Bulanova, P Novikov, S Moiseev
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> We assessed the frequency, clinical features and prognosis of renal involvement in granulomatosis with polyangiitis (GPA) and current treatment approaches. <h3>Methods</h3> We performed a retrospective analysis of 234 patients with GPA, diagnosed according to Chapel-Hill Consensus Conference 2012 classification, 81 male and 153 female, aged 53 (41; 62) years. 54 patients (23.1%) had localized GPA. 174 (74.4%) were ANCA positive. Median follow up was 61.5 (32; 105) months. 103 patients (44%) had a history of renal involvement. Frequencies of proteinuria, hematuria, hypertension, rapidly progressive glomerulonephritis (RPGN), acute kidney injury (AKI) and chronic kidney disease (CKD) grades were analyzed. <h3>Results</h3> In 25 patients (24.3% of 103) renal involvement developed at disease onset, the other 78 patients (75.7%) developed glomerulonephritis after a median of 3 (1; 12) months. Hematuria was present in 94 (91.3%), proteinuria in 85 patients (82.5%), nephrotic syndrome in 11 patients (10.7%), hypertension in 31 patients (30.1%). Rapidly progressive glomerulonephritis (RPGN) defined by the doubling of serum creatinine within ≤3 months developed in 29 patients (28.2% of 103). Myeloperoxidase-ANCA-positive patients (n=12) developed RPGN significantly more often than proteinase-3-ANCA-positive patients (n=78): 7 (58.3%) vs 22 (28.2%) (p=0.0499). 11 (10.7%) patients developed AKI, stage 3 being the most common (in 8 patients). 40 (38.8%) patients exhibited indolent renal disease course, i.e. without worsening of renal function. By the end of the follow-up, 33 (32.0%) patients were diagnosed with CKD grade 3b-5, among them 11 patients (10.7%) developed end-stage renal disease (ESRD). 6 patients (5.8%) died. As the first line induction therapy all patients received corticosteroids in combination with cyclophosphamide in 93 patients (90.3%), rituximab (RTX) in 3 patients (2.9%), mycophenolate mofetil in 7 patients (6.8%). RTX was used for remission induction in 27 (26.2%) patients due to refractory or recurrent disease. During follow-up, 74 patients (71.8%) developed one or more severe relapses with a relapse rate of 0.27 per patient-year. 50 (48.5%) patients had renal relapses (0.096 per patient-year). <h3>Conclusions</h3> Prevalence of renal involvement in the studied group was lower than expected, most likely because of a large proportion of patients with localized GPA. Our study showed that RPGN was not the most common feature of renal involvement. Almost 40% of patients developed indolent course of kidney disease. Nevertheless one third of patients developed CKD G3B or worse by the end of the follow up. Despite effective induction therapy with high-dose corticosteroids, cytotoxic agents and/or RTX relapses, both renal and extrarenal, are frequent. <h3>Disclosure of Interest</h3> None declared
Neonatal <scp>BCG</scp> vaccination and atopic dermatitis before 13 months of age: A randomized clinical trial
Authors: L. M. Thøstesen, J. Kjærgaard, G. T. Pihl, N. M. Birk, T. N. Nissen, P. Aaby, A. K. G. Jensen, A. W. Olesen, L. G. Stensballe, D. L. Jeppesen, C. S. Benn, P.‐E. Kofoed
Journal: Allergy (2017)

Abstract Background Studies have suggested that Bacillus Calmette‐Guérin ( BCG ) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. Methods The Danish Calmette Study was conducted 2012‐2015. Within 7 days of birth new‐borns were randomised 1:1 to BCG or no BCG . Exclusion criteria were gestational age &lt;32 weeks, birth weight &lt;1000 g, known immunodeficiency or no Danish‐speaking parent. Data were collected through telephone interviews and clinical examinations until 13 months. Results Clinical atopic dermatitis was diagnosed in 466/2,052 (22.7%) children in the BCG group and 495/1,952 (25.4%) children in the control group ( RR = 0.90 [95% confidence intervals 0.80‐1.00]). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition ( RR 0.84 (0.74‐0.95)) and children without atopic predisposition ( RR 1.09 [0.88‐1.37]) (test of no interaction, P = .04). Conclusion Among children with atopic predisposition, the number‐needed‐to‐treat with BCG to prevent one case of atopic dermatitis was 21 (12‐76).
Increased CD73 and reduced IFNG signature expression in relation to response rates to anti-PD-1(L1) therapies in EGFR-mutant NSCLC.
Authors: Katie Streicher, Brandon W. Higgs, Song Wu, Karen Coffman, Gautam Damera, Nick Durham, Lydia Greenlees, Yelena Lazdun, Li Cheng, Zachary Cooper, Koustubh Ranade
Journal: Journal of Clinical Oncology (2017)

11505 Background: Anti-PD-1(L1) therapies appear to be less efficacious in NSCLC patients whose tumors have EGFR activating mutations, but the underlying mechanism is poorly understood. We investigated the relationship between Methods: Flow cytometry and/or quantitative PCR were used to evaluate genes and proteins in five NSCLC EGFR mt cell lines and 6 wt lines. Anti-EGFR TKIs gefitinib and osimertinib were used at concentrations ranging from 0.001-100uM; EGF was used at 50 ng/mL. CP1108/NCT01693562 was a nonrandomized phase 1/2 trial evaluating durvalumab (10 mg/kg Q2W) in advanced NSCLC. As of 24OCT16, 304 previously treated patients in CP1108 were enrolled. RNA sequencing was conducted on available tumor specimens from 97 patients in CP1108. CP1108 and TCGA were separated by EGFR status for genomic comparisons. Results: Median CD73 expression was increased 10-fold in EGFR mt NSCLC cell lines (n = 5) compared to wt cell lines (n = 6). EGF induced CD73 protein levels 5-40-fold in 3/6 EGFR wt lines. There was dose-dependent inhibition of CD73 expression (45-70 fold maximum) following treatment with gefitinib or osimertinib in 3/5 mt cell lines and 4/6 wt lines, suggesting a causal relationship between the EGFR pathway and CD73 expression. Consistent with these observations, EGFR mutant tumors had ≥2 fold increased expression of CD73 compared to wt (p &lt; 0.05) in TCGA and CP1108 NSCLC adenocarcinoma patients. These EGFR mutants had significantly lower levels of IFNg signature, previously reported to be associated with enhanced benefit from durvalumab. Conclusions: Our findings identify a novel relationship in NSCLC between EGFR pathway activation, expression of the immunosuppressive molecule CD73 and reduced expression of IFNg mRNA signature. These results prompt the hypothesis that over-expression of CD73 in EGFR-mt NSCLC may explain, at least in part, the reduced benefit from anti-PD-1(L1) in this subset of NSCLC, and suggest evaluating anti-CD73 in combination with EGFR TKIs or anti-PD-L1 in EGFR-mt NSCLC.