tbuckley/cabot-search huggingface dataset:
AB0351 Correlation between serum anti-citrullinated protein antibodies and subclinical cardic affection in rheumatoid arthritis patients
Authors: A Helal, G Younis, N Hussein, E Elsharkawy, N Abdelhady Abdelsadek
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA) patients. It has been postulated that chronic inflammatory activity is important for the development of CVD in RA even after adjustment for traditional cardiovascular risk factors.<sup>(1)</sup> One of the changes occurring in the context of inflammation is citrullination. Development of anti-citrullinated protein antibodies (ACPA) is implicated in higher frequency of extra-articular manifestations including cardiovascular complications.<sup>(2)</sup> <h3>Objectives</h3> To assess the relation of ACPA to subclinical cardiac affection in RA patients. <h3>Methods</h3> Thirty RA patients fulfilling the 2010 ACR-EULAR classification criteria for RA with no clinically evident CVD were subjected to full history taking and clinical examination. Disease activity was assessed by 28-joint disease activity score based on C-reactive protein (DAS28-CRP) (4 variables). The levels of ACPA, CRP, total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein cholesterol were measured. The patients were subjected to M-mode and colour Doppler echocardiographic examination. Patients were subdivided into two subgroups according to ACPA positivity (ACPA positive patients represented "group A" and ACPA negative patients represented "group B"). <h3>Results</h3> The frequency of subclinical cardiac affection by echocardiographic examination was significantly higher among group A patients (4 patients had valvular lesion and 9 patients had diastolic dysfunction) than in group B patients (3 patients had diastolic dysfunction), (<i>p</i>=0.011). ACPA level showed significant positive correlation with isovolumic relaxation time (IVRT) in group A patients (prolongation of IVRT is a sign of diastolic dysfunction), (<i>p</i>=&lt;0.001). <h3>Conclusions</h3> The presence of ACPA is related to development of subclinical cardiac involvement in RA patients and all RA patients with high level of ACPA should be routinely evaluated with echocardiography to assess their cardiovascular status. <h3>References</h3> Arnab B, Biswadip G, Arindam P, Shyamash M, Anirban G, Rajan P. Anti-CCP antibody in patients with established rheumatoid arthritis: Does it predict adverse cardiovascular profile? J Cardiovasc Dis 2013; 4(2):102–6. Crowson C, Liao K, Davis J, Solomon D, Matteson E, Knutson K, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J 2013; 166(4):622–28. <h3>Disclosure of Interest</h3> None declared
FRI0500 Avoidance of physical activity leads to reduced inflammatory enthesitis on ultrasound
Authors: K Wervers, I Herrings, JJ Luime, M Moed, I Tchetverikov, AH Gerards, JMW Hazes, M Vis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Enthesitis is one of the manifestations of psoriatic arthritis (PsA), but no clear definition for the diagnosis exists. To further evaluate the added value of sonographic evaluation of entheses in diagnosing enthesitis, more knowledge on factors associated with sonographic enthesitis is needed. <h3>Objectives</h3> We aim to evaluate which clinical characteristics are associated with sonographic enthesitis changes in a cross-sectional PsA population. <h3>Methods</h3> established PsA patients were asked to participate, irrespective of enthesitis complaints. Patients were interviewed on history of musculoskeletal complaints (MSC), more specifically if they had complaints during activities and whether they avoided physical activities (during exercise, work, household tasks, hobbies, chores). Tenderness was determined in the MASEI entheses and those in the Leeds Enthesitis Index (LEI) and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). Previously we showed that a modified Madrid Sonographic Enthesitis Index (MASEI, i.e. excluding knee enthesis thickness and scoring PD-signal semi-quantitatively) distinguishes entheses of PsA patients from those of healthy volunteers (1). A sonographist unaware of clinical findings scored the modified MASEI. Multivariable linear regressions of structural (erosions, calcifications, structure) and inflammatory (thickness, bursitis and PD) modified MASEI scores were performed (transformed for a better distribution). Variables included age, gender, PsA duration, medication use (non/nsaids vs. sDMARDs vs. bDMARDs), LEI + MASES and avoidance (no vs. yes). <h3>Results</h3> 84 PsA patients participated (45 males, mean age 55, median disease duration 8 years). Median modified MASEI was 12 (IQR 7.25–17), with a structural component score of 7 (3–10) and inflammatory component score of 6 (3.5–8.5). 8 patients used no medication or NSAIDs only, 36 used sDMARDs and 40 used bDMARDs. 45 patients reported avoiding activities. In a multivariable analysis, inflammatory modified MASEI was negatively associated with avoidance (i.e. fewer inflammatory changes in patients reporting avoidance) and positively associated with age, BMI and use of biologics. Structural MASEI was positively associated with age only. <h3>Conclusions</h3> Avoiding physical activities is associated with fewer inflammatory changes of the entheses. More inflammatory changes are seen in older or overweight patients and patients on biologicals, in the latter possibly due to more active disease. <h3>References</h3> Wervers K, Rasappu N, Vis M, Tchetverikov I, Kok MR, Gerards AH, et al. AB0733 Masei Shows Substantial Changes in The Entheses of Young Healthy Volunteers – Amending Its PD Score and Excluding Knee Entheses Thickness Provides Better Discrimination of Enthesitis in Psoriatic Arthritis Patients. Ann Rheum Dis 2016;75:1155. <h3>Disclosure of Interest</h3> None declared
AB0089 Electrokinetic characteristics of synoviocytes (SC) and the level of antioxidant protection in rheumatoid arthritis (RA)
Authors: G Kudriavtseva, VI Shishkin, VV Shishkin, YA Malenkov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Known role of SC in the pathogenesis of RA. It is impossible, however, at this level of knowledge to ascertain all the mechanisms for their involvement in the pathological process. Reduced tissue antioxidant protection can affect cellular metabolism, and as might be expected, through the mechanism of autophagy inducing mitochondrial and lysosomal degradation, facilitating cell membrane depolarization. <h3>Objectives</h3> The aim of this work was to study the electrophoretic mobility (EM) of SC of RA patients and its relationship with the activity of antioxidant enzymes: Cu-Zn superoxidismutase (Cu-Zn SOD), Se-glutathione peroxidase (Se-GPO) and catalase (the CAT) in synovial fluid (SF). <h3>Methods</h3> SF has been obtained from the knee of 7 patients with RA and 5 donors. SC isolated by standard methods. EM of SC determined by the automatic microscope. Se level in SF recorded by atomic absorption spectrometry. The activity of the antioxidant enzymes was determined by classical methods of enzymology. <h3>Results</h3> A significant depolarization of the RA SC, resulting in a reduction of their EM as compared to the normal level of the average in 4 times. Activity of antioxidant enzymes is dramatically reduced by a significant decrease of Se concentrations in SF (150 μg/l normally up to 80 μ g/l in RA), which is particularly reflected in the activity of Se GPO (note that SF can be up to 100 Se-containing proteins). <h3>Conclusions</h3> We can assume that aggravated by RA catabolic processes that caused the dysfunction of the lysosomal and mitochondrial structures (autophagy), consistently shoot antioxidant protection of SC and cause depolarization and the decrease in electrophoretic mobility of these cells. <h3>Disclosure of Interest</h3> None declared
AB1145 Gender, age and pulmonary function in dominican patients with rheumatic diseases
Authors: MA Santos, E Tavera, C Tineo, E Loyo, J Reyes
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Interstitial lung disease (ILD) is a frequent entity in patients with rheumatic diseases, worsening the prognosis of those who suffer it (1). Previous studies have used the GAP (Gender, Age, Pulmonary function) model stage system to determine mortality at 1, 2 and 3 years (2). For stage I is 5.6% the first year, 10.9% second and 16.3% the third. GAP II has a mortality of 16.2%, 29.9% y 42.1% for the first, second and third year. For stage III, 39.2%, 62.1% and 76.8% respectively (3) <h3>Objectives</h3> To perform GAP model stage system in Dominican patients with Interstitial Lung Disease (ILD) related to Rheumatic Diseases (RD). <h3>Methods</h3> This is an observational, cross sectional study, with 42 patients who presented ILD related to RD. The GAP model stage system was determined by using demographic variables and pulmonary function tests such as spirometry and lung diffusion capacity (DLCO). <h3>Results</h3> 36 patients were female; the median age was 45±12 years. The mean value for Forced Vital Capacity (FVC) was 72%, Forced expiratory volume in 1 second (FEV1) 73%, and the ratio FEV1/FVC 99%. The DLCO mean value was 66±23 ml/min/mmHg. 35 patients (83.3%) were in stage I, 7 patients (16.6%) in stage II and none in stage III. The statistical significant variables were the time of diagnosis of the RD (<i>p</i>=0.013); with 4.9 years for those in stage I and 10.8 years for stage II; the time of the diagnosis of the ILD (<i>p</i>=0.003) with 2.1 years for patients in stage I and 4.8 years for stage II and smoking (<i>p</i>=0.063). <h3>Conclusions</h3> These findings suggest that the GAP model system is an useful tool to stage patients with interstitial lung disease related to rheumatic diseases. It can also help us make changes in treatment based on the stage. Special attention must be paid to those with a longer time of diagnosis of the RD, time of diagnosis of the ILD and/or smoking. <h3>References</h3> Vij R. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. CHEST 2013;143(3). Hoon S. Comparisons of prognosis between surgically and clinically diagnosed idiopathic pulmonary fibrosis using GAP model. Medicine Journal 2016; vol 95 (11). Ley B. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012, 156:684–691. <h3>Disclosure of Interest</h3> None declared
OP0095 Prediction of connective tissue disease in an at-risk cohort using a novel interferon stimulated gene expression score
Authors: MY Md Yusof, Y El-Sherbiny, A Psarras, E Hensor, A Alase, A Mohamed, M Wittmann, P Emery, EM Vital
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> A period of ANA positivity and other immune dysregulation precedes connective tissue disease, providing a potential opportunity for disease prevention. Type I interferons (IFN-I) play a role in pathogenesis but their role in disease initiation is unclear. <h3>Objectives</h3> To develop biomarkers of progression to systemic autoimmunity, with a view to enabling early intervention for disease prevention. <h3>Methods</h3> A prospective observational study was conducted in 125 patients At Risk of CTD defined by (i) ANA; (ii) ≤1 clinical SLE criteria; (iii) symptom duration &lt;12 months and (iv) treatment-naïve. Progression was defined by meeting 2012 ACR/SLICC SLE, 2016 ACR/EULAR Primary Sjogren9s, or other diagnostic criteria. Expression of 30 selected="selected" ISGs was measured using Taqman. Factor analysis was used to reduce the gene expression data to a limited set of factors, which were compared between patient groups using Mann Whitney U Test. Two factor scores explained 80% of the data variance; "Score A" (composed of IFN-α responsive genes) and "Score B" (genes responsive to IFN-α and γ). 95 healthy controls and 107 SLE patients were used as negative and positive controls. <h3>Results</h3> 82 patients with 1-year follow-up data were studied. 71 were female with mean age 48±15 years. 16 (20%) patients progressed to CTD (SLE=12, Sjogren9s=4) in the following 12 months. At baseline, only IFN Score A was increased in both At Risk-CTD and SLE vs healthy controls; p&lt;0.001. IFN Score B was only increased in true established SLE. In At-Risk patients, IFN Score B was low in patients who did not progress and increased in those who did progress; p=0.004. However, there was no difference in IFN Score A between these two groups; p=0.252 (Figure 1). Although complement levels and lymphocyte counts were lower in SLE, these were not different between the At-Risk progression and non-progression groups. Anti-dsDNA titres were higher in SLE but not different between the progression groups; all p&gt;0.10. <h3>Conclusions</h3> A novel ISG score predicts progression from ANA+ to clinical autoimmune disease. This may allow early intervention to prevent CTD. Analysis of other clinical, immunological and imaging biomarkers are in progress as well as a validation cohort. <h3>Disclosure of Interest</h3> M. Y. Md Yusof: None declared, Y. El-Sherbiny Grant/research support from: AstraZeneca, A. Psarras: None declared, E. Hensor: None declared, A. Alase: None declared, A. Mohamed: None declared, M. Wittmann: None declared, P. Emery Grant/research support from: AstraZeneca, E. Vital Grant/research support from: AstraZeneca
AB0052 Increased peripheral CD8+ T cell responses in sle by low-dose IL-2 treatment
Authors: R Zhang, J He, X Sun, Y Zou, Y Gan, Z Li
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> CD8+ T cell responses to viral pathogens is crucial for the prompt resolution of acute infections. SLE patients are more likely to have infections due to suppression of immune system by long-term glucocorticoid and immunosuppressive agent intake. Our previous study showed that low-dose IL-2 is effective in SLE. <h3>Objectives</h3> The present study is to evaluate the potential anti-infection effect of low-dose IL-2 in refractory SLE patients. <h3>Methods</h3> Nine refractory SLE patients and 9 health controls (HCs) were recruited three cycles of 1 million IU recombinant human IL-2 (rhIL-2), administered subcutaneously every other day for 2 weeks, followed by a 2-week break. The disease activitise were evaluated by rheumatologist. The frequencies of T cell subsets were assayed by flow cytometry. Virus-specific CD8 T cells responses were determined based on TNF-a, IFN-g and Grazmy B producing CD8 T cells upon CMV-EBV-Flu (CEF) viral peptide pool stimulation and subsequent intracellular staining. <h3>Results</h3> Most patients showed good clinical responses after three cycles of low-dose IL-2 treatment. Clinical improvement was observed in SIR-4 response, improved complement 3 and 4 serum level and decreased anti-ds-DNA serum level. Functional profiling of CD8 T cells in low-dose IL-2 treated patients revealed an increased in the frequencies of CEF viral peptide specific TNF-a<sup>+</sup> and Grazmy-B<sup>+</sup> CD8 T cells. Moreover, low-dose IL-2 treated patients showed stronger antigen-specific response demonstrated by an increased stimulated/non-stimulate TNF-a-producing CD 8 T cells proliferation fold. Compared with HCs, SLE patients showed significantly lower frequencies of CEF specific Grazmy-B producing CD8 T cell, and treatment with low-dose IL-2 significantly increased the frequency of these Grazmy-B<sup>+</sup> CD8 T cells in SLE patients. <h3>Conclusions</h3> Low-dose IL-2 treatment was effective and safe in refractory SLE patients. Virus-specific antigen-specific CD8 T cell response could be enhanced upon this treatment which might be potentially valuable in anti-infection in SLE. <h3>References</h3> Bilate AM, Lafaille JJ. Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu Rev Immunol. 2012;30:733–58. Blattman JN, Grayson JM, Wherry EJ, Kaech SM, Smith KA, Ahmed R. Therapeutic use of IL-2 to enhance antiviral T-cell responses in vivo. Nat Med. 2003;9(5):540–7. Palucka K, Banchereau J. Diversity and collaboration for effective immunotherapy. Nat Med. 2016;22(12):1390–1. <h3>Acknowledgements</h3> We thank Pro. Xin Lin for valuable suggestions to this manuscript. The research in the laboratory was funded by grants from the NSFC (21010000237, NSFC by Pro. Jing He and Zhanguo Li. <h3>Disclosure of Interest</h3> None declared
THU0712 Dutch norm scores for four dutch-flemish promis item banks important for patients with rheumatoid arthritis
Authors: MH Crins, LD Roorda, HC de Vet, R Westhovens, M Boers, J Dekker, CB Terwee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In the assessment of patients with rheumatoid arthritis (RA) it is important to measure physical function, fatigue, pain behavior and pain interference. The Patient-Reported Outcomes Measurement Information System (PROMIS) initiative developed item banks for measuring these concepts. These item banks were translated into Dutch-Flemish language. <h3>Objectives</h3> To facilitate interpretation and implementation of PROMIS in the Netherlands, we aimed to calibrate and validate the Dutch-Flemish PROMIS Physical Function (DF-PROMIS-PF), Fatigue (DF-PROMIS-FA), Pain Behavior (DF-PROMISPB) and Pain Interference (DF-PROMIS-PI) Item Banks in the general Dutch population, to obtain Dutch norm scores for these item banks. <h3>Methods</h3> 3365 persons of the general Dutch population completed a web-based survey, of which 1309 persons completed the full DF-PROMIS-PF (121 items), 1007 persons completed the full DF-PROMIS-FA (95 items), and 1049 persons completed the full DF-PROMIS-PB (39 items) and the full DF-PROMIS-PI (40 items). The sample was stratified for gender, age, education, and ethnicity according to the distribution of the 2015 census of the general Dutch population. A one-factor confirmatory factor analysis (CFA) was performed per item bank to assess unidimensionality. A graded item response model (GRM) was fitted per item bank to evaluate the item characteristics of the item banks and to facilitate future development of computer adaptive tests (CATs). Ordinal regression models were used to evaluate Differential Item Functioning (DIF) for language (Dutch vs. English) as a measure of cross-cultural validity. <h3>Results</h3> All four item banks showed good fit to the GRM: they showed good fit indices for CFA and high percentages of explained variance by first factor. The item banks showed only little local dependency and the scalability coefficients suggested strong scalability for all four item banks. The item characteristics showed good coverage across the range of the four concepts. DIF analyses are in progress. <h3>Conclusions</h3> The item banks exhibited good psychometric properties in the general Dutch population. The four Dutch-Flemish PROMIS item banks can be used to develop CATs for measuring physical function, fatigue, pain behavior and pain interference in the Netherlands. Dutch norm scores are presented. <h3>Disclosure of Interest</h3> None declared
A risk score for prediction of contrast induced nephropathy after percutaneous coronary intervention
Authors: Roxana Mehran, Eve D. Aymong, George Dangas, Andrea S. Abizaid, Alexandre A. Abizaid, Gary S. Mintz, Milena G. Adamian, Issam Moussa, Alexandra J. Lansky, Gregg W. Stone, Jeffrey W. Moses, Martin B. Leon
Journal: Journal of the American College of Cardiology (2003)
Association between bevacizumab-related hypertension and response to treatment in metastatic colorectal cancer patients.
Authors: Isabel Jose Dionisio de Sousa, João Casalta-Lopes, Joana Rodrigues, Ana Pais, Nuno Bonito, Paula Sousa Jacinto, Mariela Marques, Joao Ribeiro, Maria Helena Gervasio
Journal: Journal of Clinical Oncology (2015)

e14636 Background: Almost 20-25% of colorectal cancer (CRC) patients present metastases at the time of diagnosis. Multiple signaling pathways have been implied on the stimulation of tumoral angiogenesis, being the VEGF (vascular endothelial growth factor) pathway among the most important ones. Bevacizumab has become standard of care as first line treatment of metastatic CRC (mCRC), after proving increased response rates and improvement in survival outcomes. Hypertension (HTN) is a common complication of the treatment with bevacizumab and due to its close relation with anti-angiogenic mechanism, may represent a clinical biomarker to predict the efficacy of the treatment. The aim of this study was to retrospectively evaluate if HTN grades 2 to 4 were correlated with response to treatment with bevacizumab in first line, as well as with improved progression free survival (PFS) and overall survival (OS), in a series of mCRC patients. Methods: Retrospective evaluation of clinical records of patients with histologically proven mCRC, treated with bevacizumab as first line treatment, between January 2008 and December 2014. Results: Seventy-nine patients were evaluated. 51.9% of patients developed HTN G2-G4 during chemotherapy-bevacizumab treatment. In the group of patients who developed bevacizumab-related HTN 73,2% presented response to treatment (CR+PR) and 97,6% achieved disease control (CR,PR or stable disease) compared to 18,4% of patients with response and 65,8% with disease control in the group who did not (p < 0,001 responders vs non responders; p < 0,001 controlled vs non controlled disease). Median PFS was not reached and median OS was 28 months (22.7-33.3). Significant statistical difference was obtained in PFS between the 2 groups (p < 0.001). In the group that developed bevacizumab-related HTN median OS was 33 months (25.7–40.3) and in the one who did not median OS was 21 months (16.5-25.5) with no significant statistical difference between the 2 groups (OS p 0,118). Conclusions: In this subset of patients, HTN G2-4 demonstrated to be predictive of response to treatment with bevacizumab and of PFS.