tbuckley/cabot-search huggingface dataset:
AB1032 Comparison of different techniques for detecting ANTI-DFS70 antibodies
Authors: JM Lόpez-Ortega, Ά Sánchez-Herrero, N Estañ-Capell, D García Ybáñez-, E Valls-Pascual, C Vergara-Dangond, M Aguilar-Zamora, L Montolio-Chiva, À Martínez-Ferrer, JJ Alegre-Sancho
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Antinuclear antibodies (ANA) positivity with a dense fine speckled (DFS) pattern by indirect immunofluorescence (IIF), as per the definition of the International Consensus on ANA Patterns (ICAP), is not uncommon and is linked to the presence of anti-DFS70 antibodies. These antibodies, in the absence of others, are very valuable as biomarkers of exclusion of a systemic autoimmune disease (SAD). <h3>Objectives</h3> To evaluate anti-DFS70 antibody detection by two different laboratory techniques and its relation with different IIF patterns, including DFS pattern. <h3>Methods</h3> During three months, the serum of patients with positive ANA was consecutively collected. Three groups of patients were established according to their IIF pattern: a first group (D) with a DFS pattern as per ICAP; a second group (M) with other speckled with positive mitosis patterns; and a third group (C), as a control, with well defined homgeneous and speckled patterns. In order to perform a preliminary analysis, 10 serum samples were randomly selected from each group. In each serum sample, an ANA screening by IIF on Hep-2000 cells (Fluorescent IgG ANA-Ro Test System – Immunoconcepts) using an AP-16 Elite/Zenit-Up/GSight system from Menarini, and an anti-DFS70 antibodies detection by two different laboratory techniques (IIF on Hep-2 cells [Hep-2/DFS70 Knock-out - Immco Diagnostics] and inmunoblot [ANA+DFS70 Dot Blot – Alphadia]) were performed. Simultaneously, antibodies against extractable nuclear antigens (ENA), nucleosomes (NUS) and histones (HIS) were tested. <h3>Results</h3> In group D, positivity for anti-DFS70 antibodies was confirmed in 7/10 cases, all of them being negative for other ANA. In group M, 2/10 serum samples were positive for anti-DFS70 and 2/10 were positive for anti- NUS antibodies, none of them being positive for anti-ENA. In group C, no sample was positive for anti-DFS70 antibodies, while all of them showed positivity for antibodies against ENA, NUS and HIS. The detection of anti-DFS70 was found to be equal by the two methods in 8 of the 9 positive cases, being both negative in the others. In no case the presence of anti-DFS70 was associated with a diagnosis of SAD. <h3>Conclusions</h3> Both IIF and immunoblot are suitable methods for detecting anti-DFS70 antibodies. We propose to determine anti-DFS70 and to perform an ENA screening in case of finding a DFS pattern of ANA by IIF, and to investigate anti-DFS70 in other speckled patterns with positive mitosis if no other specificities have been previously found. <h3>Disclosure of Interest</h3> None declared
SAT0735-HPR Patients' assessment of the applicability of the ultrasound image method
Authors: JA Mendonça, WH Rodrigues Ferreira, IMM Laurindo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The applicability of ultrasonography in diagnosis and monitoring of rheumatic diseases has been steadily growing but little is known about the patient9s perspective. <h3>Objectives</h3> To assess the patient9s knowledge of the ultrasound (US) method and its clinical applicability as well as to evaluate how much was learned after a lecture. <h3>Methods</h3> Patients with rheumatic diseases were invited to an educational meeting that included an US lecture. They were asked to fill out a questionnaire before and after the 35-minute lecture about US and its clinical uses. The questionnaire included questions about their disease and treatment, their educational background (years of study) and ten questions about US and its clinical uses (table).These ten questions had to be answered with <i>"yes", "no"</i>, or <i>"I am not sure"</i>. <h3>Results</h3> A total of 70 patients attended the lecture and answered the questionnaires. Their demographic characteristics were as follows: Mean ± SD: age 63±12 years, disease duration: 9.6±0.8 years, the most frequent self- reported diagnosis was rheumatoid arthritis (57,2%), while osteoarthritis accounted for another 20%. Most patients had only eight years of study (64.3%) and a university degree was reported by 14%. The questionnaire responses of 66 patients with rheumatic diseases were analysed. There was a noticeable increase in the positive responses to these questions: 1, 2, 3 and 7, after the lecture, 44% (p=0.001); 29% (p=0.001); 10% (p=0.06); 27% (p=0.009), respectively. Although only 26% of the patients have had an articular US, in 65% it led to a change in treatment. Positive answers to some questions, which were perhaps too complex, showed a discrete increase, less than 10%, conceivably due to the surprisingly high background of positive answers. <h3>Conclusions</h3> As expected, the US image method was familiar to most but not its applicability in articular diseases. After the lecture there was an increase in understanding of the positive impact of US in rheumatic diseases, implying that short and focused lectures are a useful tool in educational programs for patients. <h3>Disclosure of Interest</h3> None declared
SP0018 Controling the balance between cancer and autoimmunity
Authors: A Marabelle
Journal: Annals of the Rheumatic Diseases (2017)

Immunotherapy is revolutionizing cancer therapy with a paradigm shift: antibodies are now designed to target immune cells rather than cancer cells with the aim of stimulating the anti-tumor immune response. Monoclonal antibodies targeted against CTLA-4, PD-1 or PD-L1 and anti-CTLA-4 + anti-PD-1 combinations have shown potent activity with significant improvements in the overall survival of patients. Multiple other immunomodulatory drugs are currently in development. These novel therapies generate immune related adverse events that mimick auto-immune diseases. These side effects represent a major challenge for the implementation of immunotherapy in oncology. The aim of this talk will be to provide an update on the clinical results of combination therapies and discuss the current challenges and perspectives for the future of immuno-oncology. <h3>Disclosure of Interest</h3> A. Marabelle Grant/research support from: BMS, MERUS, Consultant for: ROCHE, GENMAB, PIERRE FABRE, LYTIX, PFIZER, Speakers bureau: ROCHE, MSD, BMS, ASTRA ZENECA
FRI0692 Allopurinol and the risk of ventricular arrhythmias in the elderly: a study using u.s. medicare data
Authors: J Singh, J Cleveland
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Recent studies have shown that hyperuricemia and gout, a condition with hyperuricemia associated with joint inflammation and/or renal manifestations, are associated with a higher risk of coronary artery disease (CAD), acute cardiovascular events including myocardial infarction (MI) and stroke, and cardiovascular mortality. Emerging data suggest that gout and hyperuricemia may also be associated with cardiac arrhythmias such as atrial fibrillation <h3>Objectives</h3> To assess whether allopurinol use is associated with a reduction in the risk of ventricular arrhythmias (VA). <h3>Methods</h3> We used the 5% random sample of Medicare beneficiaries from 2006–2012 to examine new allopurinol use and the risk of incident VA. Multivariable Cox regression analyses were adjusted for demographics (age, race, gender), comorbidity, cardiac medications and conditions associated with VA. We calculated hazard ratios (HR) and 95% confidence intervals (CI). <h3>Results</h3> Of the 28,755 episodes of new allopurinol use, 2,538 were associated with incident VA (8.8%). Among patients with incident VA, 54% were male, 78% were White, and the mean Charlson-Romano comorbidity score was 4.8. The crude incidence of VA per 1,000,000 person-days declined as the duration of allopurinol use increased: 1–180 days, 151; 181 days-2 years, 105; and &gt;2 years, 85. In multivariable-adjusted analyses, compared to non-use, allopurinol use was associated with lower HR of VA of 0.82 (95% CI, 0.76 to 0.90). Compared to allopurinol non-use, longer allopurinol use durations were significantly associated with lower multivariable-adjusted HR for VA: 1–180 days, 0.96 (95% CI, 0.85 to 1.08); 181 days to 2 years, 0.76 (95% CI, 0.68 to 0.85); and &gt;2 years, 0.72 (95% CI, 0.60 to 0.87). Multiple sensitivity analyses adjusting for cardiac conditions, anti-arrhythmic drugs and alternate definitions confirmed our findings with minimal/no attenuation of estimates. <h3>Conclusions</h3> Allopurinol use and use duration &gt;6 months were independently associated with a lower risk of VA. Future studies need to assess the pathophysiology of this potential benefit. <h3>Disclosure of Interest</h3> J. Singh Grant/research support from: Takeda, Savient, Consultant for: from Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology, J. Cleveland: None declared
AB0960 Growth and sexual maturation in girls with juvenile idiopathic arthritis
Authors: LM Gonçalves, SH Machado, RM Xavier, PJC Marόstica, P Lora, L Trindade
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases with onset before the age of 16 years and joint inflammation as a main feature. Longitudinal growth is one of the main physical changes in childhood and adolescence. The etiology of delayed growth in children with JIA is multifactorial and strongly associated with prolonged inflammatory activity. <h3>Objectives</h3> To evaluate growth, sexual maturation, and the difference between final and expected height in girls with JIA and no glucocorticoid treatment for at least six months, as compared to a group of healthy girls. <h3>Methods</h3> This cross-sectional study involved 44 girls with JIA, diagnosed according to International League of Associations for Rheumatology (ILAR) criteria, and 59 healthy controls, aged between eight and 18 (incomplete) years with no comorbid chronic diseases. Demographic data were collected from all participants, and disease and treatment variables were compiled for the patient group. Anthropometric measurements were converted into z-scores based on WHO standards. Sexual maturation was classified according to Tanner stages. <h3>Results</h3> BMI and height z-scores were lower in girls with JIA as compared to control participants. These values differed significantly in Tanner stage II. Three (6.8%) girls with JIA had height-for-age z-scores &lt;-2 (short stature). Girls with polyarticular JIA and higher cumulative glucocorticoid doses were significantly more likely to present with short stature. The percentage of prepubertal girls in the JIA group was significantly higher than that observed in the control group, (<i>p</i>=0.012). Age of menarche, adult height, and the difference between actual and expected height did not differ between groups. <h3>Conclusions</h3> These findings suggest that even six months after the suspension of glucocorticoid treatment, children with more severe forms of JIA and exposure to higher doses of glucocorticoids are still susceptible to growth impairment and delayed puberty. <h3>References</h3> PETTY RE, SOUTHWOOD TR, MANNERS P, et al.: International League of Associations for Rheumatology classificayion of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004, 31:390–2. BECHTOLD S, SIMON D: Growth abnormalities in children and adolescents with juvenile idiopathic arthritis. Rheumatol int 2014; 34:1483–8. GIANNINI C, MOHN A, CHIARELLI F:Growth abnormalities in children with type 1 diabetes, juvenile chronic arthritis, and asthma. Int J Endocrinol 2014; 2014: 265954. <h3>Disclosure of Interest</h3> None declared
SAT0003 Single-nucleotide polymorphisms associated with P2X7R function regulate the onset of gouty arthritis
Authors: J Tao, M Cheng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout is an inflammatory disease, considered to be caused by the increased production of IL-1β stimulated by monosodium urate (MSU) crystals. However, some hyperuricemia patients, even gouty patients with tophi in the joints, never have gout attack, indicating some other pathogenic pathways participating in the secretion of IL-1β rather than MSU in the pathogenesis of acute gouty arthritis. ATP-P2X7R-IL-1β axis may be one of them. <h3>Objectives</h3> The purpose of this study is to explore the role of ATP in the pathogenesis of gout, and the association between ATP receptor (P2X7R) function associated single nucleotide polymorphisms and gout arthritis. <h3>Methods</h3> The non-synonymous SNPs loci of P2X7R in Chinese people were screened, to compare the frequencies of different alleles and genotype distribution of selective SNPs in 117 gouty patients and 95 hyperuricemia patients. Then peripheral white blood cells were purified from the peripheral blood of randomly selected 43 gout patients and 36 hyperuricemia patients from the total. After culturing the cells with MSU or MSU+ATP, supernatants were collected and the concentrations of IL-1β were detected by enzyme linked immunosorbent assay (ELISA). <h3>Results</h3> 1. Eight SNPs loci including rs1653624, rs10160951, rs1718119, rs7958316, rs1621388, rs16950860, rs208294, rs17525809 and rs2230912 were screened and detected, and rs1653624, rs7958316 and rs17525809 were demonstrated associated with gout arthritis. 2. After the stimulation with MSU+ATP, the concentrations of IL-1β in supernatants of gouty patients were significantly higher than that in hyperuricemia groups [(131.08±176.11)pg/ml vs (50.84±86.10)pg/ml]. Furthermore, gouty patients carrying susceptibility genotype AA or AT of rs1653624 had significant higher concentration than that carrying non-susceptibility genotype TT [(104.20±164.25)pg/ml vs (21.90±12.14)pg/ml]. However, no differences were found while stimulated with MSU alone. <h3>Conclusions</h3> ATP promotes the pathogenesis of gouty arthritis by increasing the secretion of IL-1 β, and its receptor (2X7R) function associated single nucleotide polymorphisms may be related to gouty arthritis, which indicates that ATP-P2X7R signaling pathway plays a significant regulatory role in the pathogenesis of gout. <h3>Acknowledgements</h3> This study was sponsored and funded by the Anhui Provincial Natural Science Foundation (1708085MH191) and grants from the National Natural Science Foundation of China (81671601). <h3>Disclosure of Interest</h3> None declared
AB0508 Effect of alcohol consumption and smoking on disease damage in systemic lupus erythematosus: data from korean lupus network (KORNET) registry
Authors: JN Kim, S-K Kim, J-Y Choe, CU Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> We assessed correlations of smoking habits and alcohol consumption with disease activity or damage in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> A total of 505 patients with SLE were enrolled in the KORean lupus Network (KORNET) SLE registry from January 2014 to January 2016. Disease activity and organ damage were measured by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index, respectively. Multivariate logistic regression analysis was used to analyze associations with cutaneous lesions. <h3>Results</h3> There are no differences in SLEDAI-2K and SLICC/ACR damage indexes according to either smoking status or alcohol consumption. More frequent cutaneous damage was observed in current alcohol drinkers compared to non-current alcohol drinkers (p=0.020). Cutaneous damage was significantly associated with alcohol consumption [Odds ratio (OR) 4.048, 95% confidence interval (CI) 1.251 – 12.102, p=0.020]. Both low (1–5 glasses/week) and high (≥6 glasses/week) amounts of alcohol consumption had a significant impact on cutaneous damage compared to the absence of current alcohol consumption (p=0.033 and p=0.027, respectively). Pairwise comparison of alcohol consumption and smoking status with cutaneous damage showed that only alcohol consumption was significantly associated with the presence of cutaneous damage, compared to non-current alcohol consumption and non-current smoking (OR 3.513, 95% CI 1.130 – 10.920, p=0.030). <h3>Conclusions</h3> Current alcohol consumption, but not smoking, might influence the development of cutaneous damage in patients with SLE. <h3>Disclosure of Interest</h3> None declared
Studies on PAMAM dendrimers as an efficient gene delivery vector
Authors: Zhong Hui, He Zhiguo, Li Guiyuan, Shen Shourong, Li Xiaoling
Journal: Cancer Research (2007)

3308    Abstract:  PAMAM dendrimers is a new class of highly branched spherical polymers and has a unique surface of positively charged primary amine groups. They can form complex with DNA by electrostatic interaction, and delivery gene into cells. In this work, the ability of G5 PAMAM dendrimers binding and transferring DNA to cells has been investigated, the effect of PAMAM dendrimers/DNA complex to cell viability was evaluated, and the tissue distribution and biocompatibility of PAMAM dendrimers/DNA complex was analyzed. It was found that G5 PAMAM dendrimers could bind DNA and transfer it to cultured cells efficiently with low cycotoxicity. The complex of PAMAM dendrimer/DNA could remain intact in a broad pH range, and also could prevent DNA from being degraded by restriction enzyme. Taken as marker genes, the EGFP-C2 gene could be delivered by PAMAM dendrimers to many organs after intravenous injection and had high expression in liver, kidney, lung and spleen. It also could be found that PAMAM dendrimers/DNA complex could selectively bind with some kinds of plasma proteins, which may be correlated with its transportation  in vivo . The leukemia’s gene therapy with PAMAM dendrimers/p16 and LRRC4 genes is being carried on currently. In conclusion, PAMAM dendrimers, a high-efficiency, low-cytotoxicity gene vector, appears to have potential for fundamental research and genetic therapy  in vitro  and  in vivo .
FRI0103 Contribution of subjective disease activity score 28 (DAS28) components to the response to treatment of rheumatoid arthritis
Authors: KM Son, SY Lee, YI Seo, J-E Choi, HA Kim
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Some patients with rheumatoid arthritis (RA) do not respond adequately to treatment. <h3>Objectives</h3> We investigated the contributions made by the subjective components of the disease activity score 28 (DAS28) to the treatment response of RA. In addition, factors associated with poor response to treatment at 6 months, despite normalization of objective measures, were examined. <h3>Methods</h3> A total of 426 newly diagnosed RA patients treated from August 2011 to December 2014 were included. The DAS28-P score (the subjective components of the DAS28 relative to the total components) was calculated as DAS28-P = 0.56*sqrt(TJC28) + 0.014*(VAS-GH) / 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.78In(ESR) + 0.014*(VAS-GH). The EULAR response was assessed after 6 months of treatment. Of those who failed to attain good EULAR responses, those for whom the objective measures (the ESR, the CRP level, and swollen joints) were normalized were defined as having failed treatment because of subjective measures. <h3>Results</h3> The mean age of all patients was 54 years and 79% were female. The median (IQR) DAS28 score at baseline was 4.8 (4.04–5.49) and that after 6 months of treatment 3.21 (2.41–3.95). Good responders (according to the EULAR criteria) numbered 180 (38.9%), moderate responders 150 (32.4%), and non-responders 96 (20.7%). The DAS28-P score fell significantly from baseline to 6 months in good (0.43 versus 0.28, <i>p</i>&lt;0.001) and moderate responders (0.44 versus 0.4, <i>p</i>=0.003), but not in non-responders (0.43 versus 0.45, <i>p</i>=0.727). Younger age, a lower DAS28 score, and a lower DAS28-P score at baseline were related to a good EULAR response. Subjects who failed to respond because of subjective measures tended to have higher DAS28-P scores at baseline. <h3>Conclusions</h3> We found that RA patients with high DAS28-P scores, reflecting subjective measures, were less likely to achieve good EULAR responses 6 months after treatment initiation and tended not to be classified as good responders despite normalization of objective measures. <h3>Disclosure of Interest</h3> None declared
SAT0693 Serum uric acid levels and hormone replacement therapy type: a retrospective case-control study of postmenopausal women
Authors: JH Jung, J-H Kim, YH Lee, GG Song, SJ Choi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Serum uric acid levels increase in postmenopausal women but decrease when hormone replacement therapy (HRT) is administered. However, no study has evaluated the effects of different types of HRT on serum uric acid levels. <h3>Objectives</h3> We examined whether estrogen monotherapy, estrogen-progestogen combination therapy, and tibolone use affected serum uric acid levels in this population. <h3>Methods</h3> We performed a retrospective case-control study of postmenopausal women. From 2005 to 2015, postmenopausal women measured serum uric acid levels more than twice were included. Patients were grouped according to HRT regimen: estrogen monotherapy, estrogen-progestogen combination therapy, or tibolone. The control group did not receive HRT. Differences in serum uric acid levels were examined in each group. Our analysis was adjusted to accommodate different follow-up intervals for individual patients. Multiple variables were adjusted using the Tukey-Kramer method. Age, body mass index, hypertension, diabetes mellitus, dyslipidemia, alcohol consumption, smoking status, and co-medications were also adjusted. <h3>Results</h3> In the control group, the serum uric acid level increased to 0.86±0.27 mg/dL (least squares mean ± standard error). In comparison, after adjusting for multiple variables, the serum uric levels in the estrogen-progestogen combination therapy group were found to be significantly lower (-0.41±0.29 mg/dL, P&lt;0.001). However, the serum uric acid levels in the estrogen monotherapy and tibolone groups did not differ significantly from the control group level. <h3>Conclusions</h3> Serum uric acid levels decreased in response to estrogen-progestogen combination therapy in postmenopausal women. We attribute our findings to the effects of progesterone, rather than estrogen. <h3>References</h3> Roddy E, Doherty M. Epidemiology of gout. Arthritis Res Ther. 2010;12:223. Hak AE, Curhan GC, Grodstein F, Choi HK. Menopause, postmenopausal hormone use and risk of incident gout. Ann Rheum Dis. 2010;69:1305–9. Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women–the Third National Health and Nutrition Examination Survey. Arthritis Res Ther. 2008;10:R116. Bruderer SG, Bodmer M, Jick SS, Meier CR. Association of hormone therapy and incident gout: population-based case-control study. Menopause. 2015;22:1335–42. <h3>Acknowledgements</h3> No grants or other support were received for this study. <h3>Disclosure of Interest</h3> None declared
Biomarker Analyses and Overall Survival (OS) from the Randomized, Placebo-Controlled, Phase 3, Fastact-2 Study of Intercalated Erlotinib with First-Line Chemotherapy in Advanced Non-Small-Cell Lung Cancer (NSCLC)
Authors: T.S.K. Mok, J.S. Lee, L. Zhang, C. Yu, S. Thongprasert, G.E.I. Ladrera, V. Srimuninnimit, M.I. Truman, B. Klughammer, Y. Wu
Journal: Annals of Oncology (2012)