tbuckley/cabot-search huggingface dataset:
OP0151 Docosahexaenoic acid treatment of rheumatoid arthritis: a randomized, double-blind, placebo-controlled, cross-over study
Authors: T Neumann, C Dawczynski, M Dittrich, K Goetze, A Welzel, P Oelzner, S Voelker, AM Schaible, F Troisi, L Thomas, S Pace, A Koeberle, O Werz, P Schlattmann, S Lorkowski, G Jahreis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Epidemiological studies and clinical investigations indicate a beneficial impact of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) on the inflammatory activity of rheumatoid arthritis (RA). However, the knowledge about the physiological effects of the individual compounds eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is limited. <h3>Objectives</h3> In our pilot study presented here, we investigated the clinical benefit of daily intake of foods enriched with microalgae oil as source of DHA in RA patients. In particular, the influence on disease activity and changes in the profile of pro-inflammatory/non-resolving and anti-inflammatory/pro-resolving lipid mediators was examined. <h3>Methods</h3> This is a randomized, double-blind, cross-over study on 38 patients (32 females/ 6 males) with active RA (DAS28≥2.4). They were allocated to consume foods enriched with microalgae oil from <i>Schizochytrium sp.</i> (2.1 g DHA/day) or sunflower oil (placebo) for 10 weeks while maintaining stable immunosuppressive treatment. <h3>Results</h3> Thirty-two patients finished the study but seven patients were excluded from analysis because their DHA increase in erythrocyte lipids (EL) was less than 25% after 10 weeks of intervention indicating insufficient adherence to the intervention. Supplementation of DHA led to a decline in tender joints (TJ68) 8.4±5.6 to 6.0±5.0 (p=0.03), swollen joints (SJ66) 5.6±3.5 to 3.9±3.5 (p=0.07) and DAS28 4.3±1.0 to 3.9±1.2 (p=0.07). Joint counts in the placebo arm remained stable (TJ68) 6.7±4.9 to 8.8±8.0 (p=0.12), swollen joints (SJ66) 3.5±3.0 to 4.2±3.7 (p=0.40) and DAS28 4.0±0.9 to 4.1±1.2 (p=0.45). Ultrasound score (US-7) remained stable (15.1±9.5 to 12.4±7.0; p=0.160) while it increased in the placebo arm (11.4±7.0 to 14.0±8.8; p=0.03). The amount of n-3 PUFA in erythrocyte increased in supplemented patients (7.0±1.2% to 10.6±1.4%; p&lt;0.001) and the ratios of aracidonic acid (AA) /EPA (18.5±6.3 to 12.6±5.5; p&lt;0.001) and AA/DHA (3.8±1.0 to 1.8±0.6; p&lt;0.001) dropped significantly. Fatty acid distribution in erythrocyte lipids (n-3 PUFA, AA/EPA and AA/DHA) remained stable in the control arm. <h3>Conclusions</h3> The study shows that microalgae DHA supplements can ameliorate disease activity in patients with active RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state. <h3>Disclosure of Interest</h3> None declared
SAT0135 Cardiovascular risk in rheumatoid arthritis patients from southern brazil and its association with serum levels and genotypic variation of mannose binding lectin
Authors: B Stadler, TAFG Dos Santos, T Skare, R Nisihara, R Petisco, I Goeldner, S Utiyama, IJT Messias-Reason
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The binding lectin mannose (MBL) is a serum protein of collectin family that appears to be involved in the inflammatory process and in the genesis of atherosclerotic disease. <h3>Objectives</h3> To study the association of serum levels of MBL and its genotypic variation with carotid arteries intimal thickness (IMT) in rheumatoid arthritis (RA) patients from Southern Brazil. <h3>Methods</h3> Serum level, MBL genotyping and IMT were studied in 90 RA patients along with their demographic, clinical and laboratory profile. MBL levels were measured in 90 healthy controls. <h3>Results</h3> There was significant difference between mean serum levels of MBL in patients with RA and controls (528 ng/mL vs 937.5 ng/mL, p=0.05, respectively). The median IMT in RA patients was 0.59 mm (0.51 to 0.85 mm). There was no correlation between levels of MBL with disease activity measured by DAS-28 (disease activity score-28), erythrocyte sedimentation rate (ESR), autoantibodies presence or IMT (p=NS). A negative correlation was found between MBL levels with CRP levels (p=0.02). The mutation vat codon 54 (variant B) and HYPA haplotype were the most frequent (67.5% and 31.7%, respectively) in the RA sample. Dominant genotypes (A/A) are associated with lower IMT when compared with heterozygotes (A/O; p=0.04) and homozygous recessive (O/O; p=0.05). Also dominant genotypes had lower CRP when compared with heterozygous (p=0.04) or with recessive genotypes (p=0.05). <h3>Conclusions</h3> RA patients had lower MBL levels than controls. MBL serum levels are negatively associated with CRP; low producers of MBL had increased thickness of the IMT than high producers. <h3>References</h3> Scarno A, Perrotta FM, Cardini F, Carboni A, Annibali G, Lubrano E, et al. Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis. World J Orthop [Internet]. 2014;5(3):328–35. Available from: http://www.wjgnet.com/2218-5836/full/v5/. Ip WK, Lau YL, Chan SY, Mok CC, Chan D, Tong KK, et al. Mannose-binding lectin and rheumatoid arthritis in southern Chinese. Arthritis Rheum. 2000;43(8):1679–87. J Maury CP, Aittoniemi J, Tiitinen S, Laiho K, Kaarela K, Hurme M, et al. Variant mannose-binding lectin 2 genotype is a risk factor for reactive systemic amyloidosis in rheumatoid arthritis. Jounal Intern Med. 2007;262:466–9. Graudal NA, Homann C, Madsen HO, Svejgaard A, Jurik AG, Graudal HK, et al. Mannan Binding Lectin in Rheumatoid Arthritis. A Longitudinal Study. J Rheumatol. 1998;25(4):629–35. Carvalho EG, Utiyama SRR, Kotze LMS, Reason ITM. Lectina ligante de manose (MBL): características biolόgicas e associação com doenças. Res bras alerg imunopatol. 2007;30(5):187–93. <h3>Disclosure of Interest</h3> None declared
AB0239 Dkk1 is not associated with inflammatory activity indexes in rheumatoid arthritis, but with functional disability related to the long evolution of the disease
Authors: R Giraldo-Bustos, EL Saldarriaga, AM Santos, JI Angarita, JG Ballesteros, JC Rueda-Sanchez, A Vasquez, L Valero, S Arias, J Londono
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by joint destruction, deformity, lower functional status and decrease in life expectancy. Wnt signaling pathway recently it has been implicated in bone homeostasis. Studies suggest that overexpression of inhibitors of the way, like the Dickkopf 1 protein (DKK1) has been implicated in bone destruction <h3>Objectives</h3> To compare circulating levels of DKK1 in patients with RA to their disease activity and functional status <h3>Methods</h3> 379 consecutive patients with early and established RA were evaluated at the Hospital Militar Central in Bogota-Colombia, between March 2015 and November 2016. A complete medical history related to RA was obtained. Disease activity was evaluated by DAS28-CRP, CDAI, SDAI and RAPID3. functional status was measurement using MDHAQ and the Steinbrocker functional classification. DKK1 levels measured by ELISA using an Abcam® kit <h3>Results</h3> The mean age was 60,7±13,1 years, disease duration 13,1±10,9 years, 80,4% were female. Higher levels of DKK1 were not associated with higher disease activity by CDAI (p=0,70), SDAI (p=0,84), DAS28 with CRP (p=0,80) or RAPID3 (p=0,70). Interestingly Higher levels of DKK1 were significantly associated to greater disability and lower functional status according to the Steinbrocker functional grading (p=0.013) and with severe disability by MDHAQ (p=0.004), Table 1. Other variables associated with joint destruction were osteoporosis, elevated rheumatoid factor, smoking, and hospitalization <h3>Conclusions</h3> Higher levels of DKK1 were found in patients with lower functional status. This association was not found in patients with greater disease activity according to CDAI, SDAI, DAS28 and RAPID3. This could be explaining by greater structural damage though more studies would be needed to explore this possibility <h3>References</h3> Huizinga TW, Pincus T. In the Clinic. Rheumatoid arthritis. Ann Intern Med. 2010 Jul 6;153(1):ITC1–1-ITC-15. <h3>Disclosure of Interest</h3> None declared
THU0740-HPR Influence of biofeedback therapy on the micro-circulation in systemic sclerosis
Authors: M Ramkhelawon, RA Grekhoff, G Suleymanova, SA Kharchenko
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Microcirculatory disorders are one of the most important clinical symptoms of systemic sclerosis (SSc), therefore we found it feasible to evaluate the clinical efficacy of biofeedback (BFB) in the complex therapy of patients with SSc based upon analysis of nailfold capillaroscopy. <h3>Objectives</h3> To study the impact of the method of biofeedback therapy on microcirculation disturbances in patients with SSc. <h3>Methods</h3> The study included 40 patients with SSc under observation. Among the patients examined, 95% were women and 5% were men. The average age of the patients - 38±3,3 years, duration of illness - 14±2,6 years. Raynaud9s phenomenon (RP) was observed in all the patients. A severe form of RP was seen in 80% of the patients. The effectiveness of biofeedback therapy was analyzed by studying the dynamics of the measures from the nailfold capillaroscopy and comparing the data obtained of patients from the main and control groups. <h3>Results</h3> It was found that, patients who were under biofeedback therapy, showed significant positive dynamics in the following signs of capillaroscopic picture: dilation of the capillaries (c2 =9,643 p=0,026), morphological changes of the capillaries (c2 =4,90 p=0,027), and hemorrhage (c 2 =4,514 p=0,034). In the control group of patients, in only one indicator of capillaroscopy that a significant change was noted, particularly by the presence of dilated capillaries (c2 =5,833 with p=0,016). These findings suggest that treatment results were significantly better in the main study group of patients with SSc. <h3>Conclusions</h3> The implementation of biofeedback therapy favors a decrease in reflex musculo-tonic syndromes, improvement of microcirculation and peripheral blood flow and significantly allows an amelioration in the results of SSc therapy. <h3>Disclosure of Interest</h3> None declared
OP0232 Sustained safety and efficacy over 10 years with belimumab (BEL) plus standard systemic lupus erythematosus (SLE) therapy (SOC) in patients with SLE
Authors: DJ Wallace, EM Ginzler, JT Merrill, RA Furie, W Stohl, W Chatham, A Weinstein, J McKay, WJ McCune, M Petri, J Fettiplace, D Roth, B Ji, A Heath
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Preliminary safety and efficacy data from the Phase II BEL open-label extension study (LBSL02; NCT00071487) have been reported. <h3>Objectives</h3> Here we present the final 10-year data. <h3>Methods</h3> This was a multicentre, open-label, continuation trial (BEL112626; NCT00583362) of BEL + SoC in patients with a satisfactory response in the parent study. Patients received intravenous BEL 10 mg/kg every 4 weeks. Baseline was prior to the first ever dose of BEL. <h3>Results</h3> Of 298 patients in the continuation trial, 131 (44%) remained at Year 10. Total BEL exposure was 2154 patient-years. Adverse events (AEs) remained stable or decreased (Table). Two deaths (pseudomonal lung infection; cytomegaloviral pneumonia) were possibly related to BEL. SLE Responder Index (SRI) response increased (Figure). A British Isles Lupus Assessment Group (BILAG) flare (1 new A/2 new B scores) occurred in 72.6% of patients and 41.9% had a severe flare (SLE Flare Index). Prednisone dose decreased from baseline to Year 10 (Table). Of patients receiving &gt;7.5 mg/day baseline prednisone, 32.6% (14/43) decreased their dose to ≤7.5 mg/day by Year 10; 9.5% (9/95) of patients receiving baseline prednisone ≤7.5 mg/day had a dose increase to &gt;7.5 mg/day. <h3>Conclusions</h3> Over 10 years BEL + SoC was well tolerated and the rates and nature of AEs were consistent with the known profile of BEL. Efficacy was maintained and prednisone use decreased in those receiving &gt;7.5 mg/day at baseline. <h3>Acknowledgements</h3> Study funded by GSK. Editorial assistance provided by Katie White, PhD, Fishawack Indicia Ltd, UK; funded by GSK. <h3>Disclosure of Interest</h3> D. Wallace Grant/research support from: GSK, Consultant for: GSK, E. Ginzler Grant/research support from: GSK, J. Merrill Grant/research support from: GSK, Bristol-Myers Squibb, Consultant for: Anthera Pharmaceuticals, Inc., GSK, EMD Serono, Inc., Lilly, AstraZeneca, Bristol-Myers Squibb, UCB, Celgene, Biogen, R. Furie Grant/research support from: GSK, Consultant for: GSK, W. Stohl Grant/research support from: GSK, Pfizer, Consultant for: Johnson &amp; Johnson, W. Chatham Grant/research support from: GSK, A. Weinstein Grant/research support from: GSK, HGS, Consultant for: GSK, HGS, J. McKay Grant/research support from: GSK, MedImmune, Anthera Pharmaceuticals, Inc., Johnson &amp; Johnson, Lilly, Xencor, Inc., W. McCune Grant/research support from: GSK, Lilly, M. Petri Grant/research support from: GSK, Consultant for: GSK, J. Fettiplace Shareholder of: GSK, Employee of: GSK, D. Roth Shareholder of: GSK, Employee of: GSK, B. Ji Shareholder of: GSK, Employee of: GSK, A. Heath Shareholder of: GSK, Employee of: GSK
AB0273 Very high, but not lower, radiographic progression leads to an increase in haq-di. results from the swiss scqm ra cohort
Authors: R Mueller, R Thalmann, N Graf, H Schulze-Koops, J von Kempis
Journal: Annals of the Rheumatic Diseases (2017)

Background: Numerous predictors of radiographic progression in RA patients have been identified over the last years.In general, analyses of radiographic progression in RA rather focus on radiographic non-progression or repair.High radiographic progression in spite of therapy has, to our knowledge not been analysed in detail in the last years, neither in RCTs nor in cohort studies.Objectives: To analyse radiographic, demographical and clinical data in RA patients with high radiographic progression before and after the individual peak radiographic progression.Methods: We included all RA patients from the Swiss registry SCQM with at least two subsequently scored radiographs.Radiographic destruction was scored using the Ratingen erosion score.To analyse high radiographic progression we selected for the highest (peak) radiographic progression in every individual patient for the analysis.The individual peak radiographic progression was analysed in groups as change of Ratingen scores/year: 0-≤10, 10-≤20, 20-≤30, >30 (groups 1-4, follow up 1998 -2015).The baseline disease characteristics were compared using standard descriptive statistics (Kruskal-Wallis or Chi-square tests).The change of DAS 28 and HAQ-DI scores before and after peak progression was analysed with the Wilcoxon signed rank tests.Results: 3 patients were included into the analysis.3'049 patients had a peak radiographic progression between 0 and ≤10/year, 773 between 10 and ≤20, 150 between 20 and ≤30, and 61 of >30.All patient groups were within the same age range (mean: 56.5 -60.5 years).Rheumatoid factor and ACPA were more frequent in patient groups with higher peak radiographic progression (RF: 73.6, 80.0, 88.9, 90.0; ACPA: 66.8, 73.4,74.3, 82.1, respectively).When the rate of radiographic progression before and after peak progression was analysed, 69.7%, 74.7%, 76.9%, and 93.3% of the patients had a radiographic progression of 25% or lower as compared to peak progression before and 76.1%, 81.8%, 91.1%, and 93.8% after this peak progression, respectively for patients in groups 1 to 4 (Figure A).The disease activity, as assessed by DAS 28, was significantly higher in all patient groups before peak progression and lower thereafter (Figure B, p<0.001).Average HAQ-DI scores increased after peak radiographic progression in group 4 (Figure C, p=0.005) whereas it is stable or even decreases among the patients of the other patient groups.Conclusions: These data show that higher disease activity precedes radiographic peak progression, which is, if high, overall rare.Radiographic progression before and after the individual peak radiographic progression was far lower as compared to the time of radiographic peak progression.Only the highest individual peak (change of Ratingen score >30/year) radiographic progression was followed by an increase of HAQ-DI scores.
AB1049 Clinical utility of autoantibodies against extractable nuclear antigens in routine care: frequency of repeated test requests and diagnostic value of ANTI-JO-1 (ANTI-HISTIDYL-TRNA SYNTHETASE)
Authors: P Jobanputra, F Malik, E Derrett-Smith, T Plant, A Richter
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> High-throughput high-sensitivity ELISAs for autoantibodies associated with CTD, such as extractable nuclear antigens (ENA), are used widely. Anti-Jo-1 (anti-histidyl-tRNA synthetase), one of this panel, is believed to confer a poor prognosis due to an association with interstitial lung disease (ILD) and myositis. <h3>Objectives</h3> To describe: the pattern of anti-ENA positive tests; frequency of repeated requests; stability and repeatability of anti-Jo-1 tests; clinical characteristics of anti-Jo-1 +ves compared with controls; and diagnostic value of anti-Jo-1 for ILD. <h3>Methods</h3> All anti-ENA test requests, from any hospital department, between Jan 2013 and Dec 2014 were identified. Serum samples are screened for ENA (Quanta Lite® ENA profile, Inova Diagnostics) and positive samples have specific ENA antibodies levels quantified. Data from anti-Jo-1 positive patients and controls was extracted from electronic records allowing a minimum of 12 months after first test. <h3>Results</h3> 4009 samples from 3581 patients were tested. The first sample tested, chronologically, was designated test of interest. 616 (17.2%) patients were anti-ENA screen +ve, and 40 (1.1%) anti-Jo-1 +ve (&gt;20 AU/mL). Anti-ENA tests were done more than once for 350/3581 (9.8%) patients (428/4009 (10.7%) samples) and for 7/40 (17.5%) of anti-Jo-1 +ve patients. The median interval between 1st and 2nd requests: 124 days (IQR 233 days). The Table shows data for anti-Jo-1 patients and randomly selected ENA -ve controls. The frequency of ILD, myositis and Raynaud9s was comparable. Sensitivity and specificity of Jo-1 for ILD, a key feature of "anti-synthetase syndrome", were 50% (CI 19–81%) and 68% (CI 59–77%) respectively. Positive predictive value 12.5% (CI 4 to 27%) and negative predictive value 93.8% (CI 86–98%). Of patients with the highest anti-Jo1 titres (≥40 AU/mL, 10/40 patients, 25%): 3 had ILD, 1 myositis and 2 had a malignancy (disseminated melanoma and CML). Bland-Altman plots show that anti-Jo-1 values remained stable when patients were re-tested at another time but re-testing available stored samples from +ve patients showed important variation (Figure). <h3>Conclusions</h3> Anti-Jo-1 is uncommon in a heterogenous hospital population and is only weakly predictive for ILD. When tested repeatedly levels remain stable over many months. Repeated testing for anti-ENA is common and potentially unnecessary. Controls over repeated requests could yield cost savings. <h3>Disclosure of Interest</h3> None declared
SP0139 Meaningful patient and public involvement in planning research
Authors: A Redmond
Journal: Annals of the Rheumatic Diseases (2017)

Historically, services providing care for people with long term conditions (LTCs), together with any associated research agendas, have been driven entirely by clinicians. In many cases this is well meaning and is done with some consideration of what patients need, but almost always the end result relies on the clinicians9 interpretation of what <i>they</i> think patients need. Recently it has become more usual to involve patents in planning research projects and service changes directly. Initial attempts to give patients genuine input were <i>ad hoc</i> in nature and so patient contributions could be lacking, ignored or misinterpreted. In many cases having poor patient input is worse than no input at all as it lends false credibility to the process. Lately a range of formal requirements, arrangements and methods have become adopted and this presentation will focus on how these can be brought to bear to ensure meaningful patient and public involvement in planning research. From national guidance such as the UK9s INVOLVE initiative, to local standard operating procedures we will share experiences and lessons learned. The session will close with a practical summary of how to make PPI contributions genuine and meaningful, and some insights into possible future developments as this aspect of the research process matures and consolidates. <h3>Disclosure of Interest</h3> None declared
Targeting Bcl-2 Enhances the Anti-Tumor Effects of Lenalidomide and Dexamethasone in in Vitro and In Vivo Models of Multiple Myeloma
Authors: Aneel Paulus, Sharoon Akhtar, Yamima Bashir, Shumail M. Paulus, Richa Menghani, Vivek Roy, Sikander Ailawadhi, Asher A. Chanan-Khan
Journal: Blood (2016)
Mucocutaneous inflammation in the Ikaros Family Zinc Finger 1‐keratin 5–specific transgenic mice
Authors: M. Ueta, J. Hamuro, H. Nishigaki, N. Nakamura, K. Shinomiya, K. Mizushima, Y. Hitomi, R. Tamagawa‐Mineoka, N. Yokoi, Y. Naito, K. Tokunaga, N. Katoh, C. Sotozono, S. Kinoshita
Journal: Allergy (2017)

Our genomewide association study documented an association between cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis (CM-SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). Few studies examined biological and pathological functions of IKZF1 in mucosal immunity. We hypothesized that IKZF1 contributes to the mucocutaneous inflammation.Human skin and conjunctival tissues were obtained for immunohistological studies. Primary human conjunctival epithelial cells (PHCjECs) and adult human epidermal keratinocytes (HEKa) also used for gene expression analysis. We also generated K5-Ikzf1-EGFP transgenic mice (Ikzf1 Tg) by introducing the Ik1 isoform into cells expressing keratin 5, which is expressed in epithelial tissues such as the epidermis and conjunctiva, and then examined them histologically and investigated gene expression of the epidermis. Moreover, Ikzf1 Tg were induced allergic contact dermatitis.We found that human epidermis and conjunctival epithelium expressed IKZF1, and in PHCjECs and HEKa, the expression of IKZF1 mRNA was upregulated by stimulation with polyI:C, a TLR3 ligand. In Ikzf1 Tg, we observed dermatitis and mucosal inflammation including the ocular surface. In contact dermatitis model, inflammatory infiltrates in the skin of Ikzf1 Tg were significantly increased compared with wild type. Microarray analysis showed that Lcn2, Adh7, Epgn, Ifi202b, Cdo1, Gpr37, Duoxa1, Tnfrsf4, and Enpp5 genes were significantly upregulated in the epidermis of Ikzf1 Tg compared with wild type.Our findings support the hypothesis that Ikaros might participate in mucocutaneous inflammation.