tbuckley/cabot-search huggingface dataset:
SP0140 Imaging the arthritic joint
Authors: J. Brewer
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Advanced imaging approaches such as multiphoton laser scanning microscopy (MPLSM) enable the real-time visualisation of cellular behaviour throughout the development of immune responses <i>in vivo</i>. These techniques have brought new insights into the spatial and temporal organisation of the immune system, for example the T cell/Dendritic cell interactions in the lymph node during the decision to induce immunological priming versus immunological tolerance. We believe that understanding cellular interactions in the joint will similarly transform our understanding of the importance of time and tissue specific regulation of the immune system in homeostasis and in diseases such as Rheumatoid Arthritis. Furthermore, using cell fate mapping, we have integrated imaging data in different cellular locations with transcriptional analysis to reveal the underlying molecular basis of these interactions. We propose that the key T cell/DC interactions controlling the development of immune responses and their molecular basis are influenced by the distinct anatomical and temporal context in which they take place, providing targets for therapeutic intervention as well as indicating biomarkers to report immune function. <h3>Disclosure of Interest</h3> None declared
Phospho flow cytometry of PBMCs in psoriasis
Authors: A.K. Aarebrot, S.M. Solberg, R. Davies, L.I. Bader, T.D. Holmes, S. Gavasso, Y.T. Bryceson, R. Jonsson, L.F. Sandvik, S. Appel
Journal: British Journal of Dermatology (2018)
AB1024 Risk of drug induced liver injury from nsaids in patients with gout
Authors: E. Mikhnevich, T. Pavlovich, T. Rayeuneva, E. Mytnik, E. Leonchik, V. Tettegah
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Drug Induced Liver Injury (DILI) in patients under nonsteroidal anti-inflammatory drugs (NSAIDs) is more frequently presented by hepatocellular damage when serum alanine aminotransferase (ALT) level exceeds 2 times (or more) the upper limits of norms.<sup>1</sup> The value of minimal hypertransaminasemia (MHTE) (when serum ALT exceeds the upper limit of normal up to twice) is still not clear today. <h3>Objectives</h3> To define the terms of DILI development and the value of MHTE in patients with gouty arthritis (GA) under NSAIDs. <h3>Methods</h3> 189 patients (25,6%) of 738 with GA<sup>ACR, 1977</sup> were included in our retrospective study. At the onset of gout attack, all patients had normal basal serum ALT, which elevated after starting NSAIDs therapy. Pre-existing liver impairment was not registered. Patients were divided into 2 groups according to the changes in serum ALT after NSAIDs treatment: patients with MHTE (n=101) and those with DILI (n=88). The mean age of 55<sup>49–60</sup> years and 54<sup>44–59,5</sup> years as well as the sex distribution (men 90,1% and 93,3%, respectively) were compatible in both the groups (p&lt;0,05). In DILI group, elevated serum ALT exceeded 2–3 times the upper norms in 81,8% (n=72) of patients; 3–5 times in 14,8% (n=5); more than 5 times in 3,4% (n=3) with the mean serum ALT being of 89<sup>75–108,5</sup> U/L. In MHTE group, serum ALT exceeded the upper norms by more than 50% in 50,5% (n=51) of cases. After NSAIDs therapy, the mean serum ALT of 51(<sup>47–57</sup>U/L was revealed. <h3>Results</h3> The mean duration of NSAIDs therapy in the groups made 8<sup>5–10</sup> days in MHTE group and 10<sup>6–14</sup> days in DILI group. Statistically significant difference (U=3236, p&lt;0,001) was revealed between the groups when comparing the duration of NSAIDs treatment. In addition, in DILI group, 97,7% of patients received NSAIDs in high doses (χ<sup>2</sup>=19,4; p&lt;0,001) during all period of treatment. ROC analysis showed that the probability of DILI development decreased in patients with GA taking NSAIDs in high doses during less than 11 days (AUC=0,64±0,04, p=0,010, S=47,7%, Sp-82,2%, OR-4,21, 95% Cl – 3,38–5,24). <h3>Conclusions</h3> 25,6% of patients with GA have demonstrated elevated serum ALT after NSAIDs therapy: MHTE developed in 13,7% of cases, DILI in 11,9%. Our study showed that MHTE developed in the period less than 11 days of high dose NSAIDs treatment with DILI being likely to occur during more prolonged treatment. MHTE group may be considered as a risk group for DILI development. <h3>Reference</h3> [1] Aithal G. P. Hepatotoxicity related to antirheumatic drugs. Nat. Rev. Rheumatol. 2011; 7: 139–150. <h3>Disclosure of Interest</h3> None declared
A Pilot Prospective Single-Arm Clinical Study on Decitabine Plus CAG or IA Followed with HLA-Mismatched Nonmyeloablative Transplantation (micro transplantation) on De Novo Elderly Acute Myeloid Leukemia and Int-2/High Risk Myelodysplastic Syndrome Patients
Authors: Jie Sun, Yan Huang, Weijia Huang, Lizhen Liu, Jimei Ge, Yunfei Qiu, Zhang En Fan, Xiaorong Hu, Zhen Cai, He Huang
Journal: Blood (2018)
THU0676 A systematic review and meta-analysis of viral exposures as a risk factor for rheumatoid arthritis
Authors: F. Kudaeva, M.R. Speechley, J.E. Pope
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune disease with a complex and poorly understood etiology. Development of autoimmune disease stems from a combination of immune, genetic, hormonal and environmental factors. Infections are viewed as triggers of some autoimmune disorders, including RA. <h3>Objectives</h3> Different viral exposures have been implicated in the etiology of RA via several mechanisms of immune activation, such as molecular mimicry. The purpose of this systematic review was to summarise the evidence relating to the association between putative viral exposures and the development of RA <h3>Methods</h3> A systematic literature search was conducted using MEDLINE-OVID, EMBASE-OVID, PUBMED and Cochrane library databases. Articles were included if they were case-controls, cross-sectional or cohort studies and were published in English. Case-series were included if there was a lack of other study designs. <h3>Results</h3> Of 6724 citations, 78 studies were selected for review, and 48 were included in meta-analysis. Studies had poor quality. Based on the IgG antibodies (n=12 studies) and viral DNA detection (n=3 studies), the odds of parvovirus B19 (PBV19) infection were increased in RA patients than in controls (odds ratio (OR) (95% CI)=1.77 (1.11; 2.80), p=0.02, OR (95% CI)=3.53 (1.00; 12.53), p=0.05 for PVB19 IgG and DNA, respectively). For Epstein-Barr virus (EBV), patients with RA had not significant OR of anti-Epstein-Barr nuclear antigen (EBNA) (n=17 studies, OR (95% CI)=1.05 (0.79; 1.39), p=0.75), but significant OR of anti-viral capsid antigen (VCA) (n=18 studies, OR (95% CI)=1.5 (1.07; 2.10), p=0.02) and anti-early antigen (EA) (n=11 studies, OR (95% CI)=2.74 (1.27; 5.94), p=0.01). Cytomegalovirus (CMV) was not associated with RA (n=13 studies, OR (95% CI)=1.24 (0.78; 1.95), p=0.36). Chronic hepatitis B (HBV) was not associated with RA in 5 case-control (OR (95% CI)=1.37 (0.83; 2.25, p=0.22) and 1 cohort studies (HR 1.09 (0.74, 1.63), p&gt;0.05). Chronic hepatitis C (HCV) was associated with increased risk of RA in 7 case-control (OR (95% CI=2.82 (1.35; 5.90, p=0.006) and 1 cohort studies (HR 2.03 (1.27, 3.22), p&lt;0.01). There seem to be a risk of persistent arthritis after Chikungunya fever (CHIKV) (n=2 studies, OR (95% CI)=90 (15.2; 134.3). <h3>Conclusions</h3> Studies about the risk of RA after viral exposures suffer from inconsistent methodological quality. There is a risk of RA after Parvo B19 infection and possibly HCV but not EBV or HBV. There seems not to be a risk of RA after EBV infection. CHIKV is associated with the persistent inflammatory arthritis. There is not enough evidence to support an association between some viruses and RA development, but they probably lead to RA in genetically susceptible individuals. <h3>Disclosure of Interest</h3> None declared
SAT0542 Interleukin-12 and interleukin-23 are key pathogenic players in giant cell arteritis
Authors: R. Conway, L. O’Neill, P. Gallagher, G. McCarthy, C. Murphy, D. Veale, U. Fearon, E. Molloy
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Giant cell arteritis (GCA) is the most common form of systemic vasculitis; the pathogenesis is unclear. Current evidence suggests both the T<sub>H</sub>1 and T<sub>H</sub>17 pathways are important but the proximal initiators and effector cytokines are unknown. IL-12 and IL-23 secreted by dendritic cells are hypothesised as stimulators of these pathways. We have previously reported the efficacy of IL-12/23 blockade with ustekinumab in refractory GCA in a prospective clinical trial. <h3>Objectives</h3> To assess the role of IL-12 and IL-23 in GCA pathogenesis. <h3>Methods</h3> IL-12 and IL-23 were quantified by immunohistochemistry in temporal artery (TA) biopsies. TA explant, peripheral blood mononuclear cell (PBMC), and myofibroblast outgrowth culture models were established from patients with GCA and disease controls. PBMCs and TA explants were cultured for 24 hours in the presence or absence of IL-23 (10 ng/ml) or IL-12 (50 ng/ml). Gene expression was quantified by Real-time PCR and cytokine secretion by ELISA. Myofibroblast outgrowths were assessed following 28 days culture and quantified by counting the number of outgrowths/high-power field (hpf). <h3>Results</h3> Immunohistochemistry demonstrated IL-12p35 and IL-23p19 in inflammatory cells in TA biopsies (n=33). IL-12p35 and IL-23p19 were only detected in positive TA biopsies. IL-12p35 was increased in those with cranial ischaemic complications (p=0.026) and those with large vessel vasculitis (p=0.006). IL-23p19 was increased in those with two or more relapses (p=0.007). In cultured PBMCs, IL-12 stimulation increased IL-6 (n=17, p=0.009), IL-22 (n=16, p=0.003), and IFN-γ (n=14, p=0.0001) secretion and decreased IL-8 (n=15, p=0.0006) secretion, while IL-23 stimulation increased IL-6 (n=40, p=0.029), IL-22 (n=16, p=0.001), IL-17A (n=16, p=0.0003) and IL-17F (n=9, p=0.012) secretion. In the TA explant culture model, IL-23 stimulation increased gene expression of IL-8 (n=13, p=0.0001) and CCL-20 (n=9, 0.027) and protein expression of IL-6 (n=61, p=0.002) and IL-8 (n=60, p=0.004), IL-12 stimulation (n=14) had no effect; however, IFN-γ and IL-17A were not detectable in this model. IL-12 (n=20, p=0.0005) and IL-23 (n=33, p&lt;0.0001) stimulation increased the quantity of myofibroblast outgrowths from TA biopsies. In all experiments there were no significant differences between biopsy positive GCA, biopsy negative GCA, and disease controls. <h3>Conclusions</h3> IL-12 and IL-23 play central and distinct roles in stimulating inflammatory and proliferative pathways in GCA. Our results were consistent in patients with biopsy positive and negative GCA, and in disease controls, suggesting that IL-12 and IL-23 play proximal roles in inducing these pathways. <h3>Disclosure of Interest</h3> None declared
SAT0359 Evolution of renal function in gout after normalisation of serum uric acidlevel
Authors: E. Gazaix-Fontaine, A. Ostertag, H.-K. Ea, F. Lioté
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Chronic kidney disease (CKD) is one of the main causes of mortality in gout. In addition, hyperuricemia can contribute to the decrease of renal function. <h3>Objectives</h3> The aim of this study was to evaluate the evolution of renal function after reducing serum uric acid (sUA) level to therapeutic target in gout, and to identify the factors that might influence this evolution. <h3>Methods</h3> Patients with gout were followed at a single university-based hospital. They were free of urate lowering therapy (ULT) and had an estimated glomerular filtration rate (eGFR) higher than 15 ml/min. Renal function was measured at start of ULT and when sUA was reduced below 360 µmol/L (or 6.0 mg/dL). ULT was allopurinol or febuxostat at the choice of clinician. <h3>Results</h3> In this retrospective study, 63 patients (pts) were included with an initial mean sUA level of 541 µmol/l (±86). Overall 42 pts were treated with allopurinol and 21 with febuxostat for an average length of 278 days (±185). After ULT, mean eGFR differed significantly:+2.6 [IC95%: −0.279; 5.484; p=0.08],+3 [IC95%: 0.167; 5.794; p=0.04] and +2,7 [IC95%: 0.490; 4.960; p=0.02] ml/min/1,73 m<sup>2</sup> depending on the calculation method, Cockcroft-Gault (C-G), MDRD and CKD-EPI, respectively. eGFR improvement was statistically significant, p=0.04, 0.02 et 0.01, respectively. Initial eGFR &gt;45 ml/min/1,73 m<sup>2</sup> was associated with a better outcome of eGFR expressed in percentage:+4.7% vs −7.3% (p=0.02),+6.3% vs −4.9% (p=NS),+6.2% vs −5.3% (p=0.03) according to the calculation method, C-G, MDRD and CKD-EPI, respectively. We also found a better evolution of renal function when patients were treated with allopurinol compared to febuxostat, but confounding bias might have occurred since their mean eGFR was also better. In contrast, neither sex, BMI, presence of hypertension nor diabetes showed any significant effect on eGFR improvement. <h3>Conclusions</h3> Renal function was significant different after normalisation of sUA in gout patients. We observed an improvement of eGFR which is consistent with recent studies. Interestingly, when initial renal function was at CKD IIIa level or higher (eGFR &gt;45 ml/min/1,73 m<sup>2</sup>), renal outcome was even better. It strengthens the rationale to treat high sUA as soon as possible. <h3>Acknowledgements</h3> Thanks to Frédéric Lioté<sup>1,2,3</sup>, Hang-Korng Ea<sup>1,2,3</sup> and Agnès Ostertag<sup>2</sup> <sup>1</sup> Rheumatology Department and <sup>2</sup> INSERM UMR 1132 Bioscar, Centre Viggo Petersen, (AP-HP) hospital Lariboisière; <sup>3</sup> Univ. Paris Diderot, USPC, Paris, France <h3>Disclosure of Interest</h3> None declared
THU0482 Relationship between mild vertebral body deformity and kellgren-lawrence’s osteoarthritis level with the prevalence of non-traumatic dorsal and lumbar back pain in female patients with risk of osteoporotic vertebral collapse
Authors: C.A. Guillen-Astete, C. Ijoán, J.R. Quiñones-Torres, M. Vázquez Díaz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> There is a lack of information about the meaning of mild vertebral body deformities and its relationship with back pain. Many patients with this kind of wedges are sent to rheumatology clinics to assess the possibility to start treatment for secondary prevention of osteoporosis fractures. <h3>Objectives</h3> The present study aims to determine the relationship of the number of medical consultations due to dorsal or lumbar pain and two categorical variables: Presence or absence of mild vertebral wedge (Genant's first level of classification) and Kellgren-Lawrence's osteoarthritis classification levels I-II and III-IV. <h3>Methods</h3> We conducted a retrospective follow-up of 1131 patients with and without mild vertebral body deformities along three years to compare the frequency of axial pain episodes assessed in emergency units and their chance to evolve to moderate or severe wedges. <h3>Results</h3> : In the group without deformities, the cumulative incidence of dorsal or lumbar pain episodes was 7.2% per year, and the incidence density was 7805 cases per 100 patients-year. In the group with mild deformities, the cumulative incidence of dorsal or lumbar pain episodes was 7.0% per year, and the incidence density was 7318 cases per 100 patient-year (p=0.77 and 0.58, respectively). We grouped patients according to their osteoarthritis severity. The cumulative incidence of dorsal and lumbar pain episodes along the period of observation, in patients with a spinal Kellgren-Lawrence's osteoarthritis degree I-II and III-IV were 19.8% (CI95% 12.10%&gt;27.49%) and 31.5% (CI95% 18.27%&gt;44.72%), respectively (p&lt;0.0001). The density of incidence for both groups was 6.18 cases per 100 patients-year and 11.3 cases per 100 patients-year, respectively (p&lt;0.0001). The difference in proportions of patients who developed a moderate or severe Genant's vertebral deformities was not statistically significant among patients with or without mild vertebral wedges. <h3>Conclusions</h3> Our results point that back pain incidence is not related to the presence of mild vertebral wedges but the severity of axial osteoarthritis. Also, the behaviour of starting a secondary osteoporosis prevention treatment after the detection of a mild vertebral wedge is not supported by our results. <h3>Disclosure of Interest</h3> None declared
AB0215 Association of rheumatoid factor immunoglobulin a seropositivity with risk of erosive arthritis in patients with rheumatoid arthritis: an observational study
Authors: A.I. Pereira, C. Vaz, J.M.R. Gama, L. Inês
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In patients with rheumatoid arthritis (RA), erosive arthritis is a major determinant of long-term prognosis. Seropositivity for immunoglobulin (Ig) M rheumatoid factor (RF) or cyclic citrullinated peptide antibodies (anti-CCP) are risk factors for erosive arthritis. However, RA patients can also present IgA RF. The risk for erosive arthritis associated with RF IgA seropositivity is not established. <h3>Objectives</h3> To evaluate the risk for erosive arthritis associated with IgA RF seropositivity in RA patients. <h3>Methods</h3> Cross-sectional observational study, including RA patients (fulfilling the 2010 ACR/EULAR classification criteria) and consecutively observed in a hospital-based rheumatology outpatient clinic, from April to August 2017. At time of inclusion, patient characteristics were evaluated, including: gender, age, RA duration since time of diagnosis, smoking habits, seropositivity for IgA RF, IgM RF and anti-CCP, erosive arthritis in hand and feet X-rays. Risk association for erosive arthritis was analysed with univariate and multivariable logistic regression models for the putative risk factors and confounders. Odds ratios (OR) and 95% confidence intervals (CI) of IgM RF, IgA RF, and anti-CCP seropositivity for erosive arthritis were estimated. Statistical significance was set at 0.05. <h3>Results</h3> 86 patients were included. The univariate logistic regression showed significant positive associations of IgA RF, IgM RF and anti-CCP with erosive arthritis. In the multivariate analyses, adjusting for confounders (gender, age, disease duration and smoking), the OR for erosive arthritis associated with IgA RF, IgM RF and anti-CCP were respectively: OR=2.42 (95% CI 0.72–8.07; p=0.152); OR=3.54 (95% CI 1.16–10.83; p&lt;0.05); OR=4.13 (95% CI 1.33–12.82; p&lt;0.05). The seropositivity for IgM RF, IgA RF and anti-CCP were strongly associated among each other (Chi-square test with p&lt;0.001 for all associations). <h3>Conclusions</h3> In this RA cohort, the IgA RF was associated with erosive arthritis in univariate analysis, but did not prove to be an independent risk factor in multivariate regression, due to its strong association with IgM RF and anti-CCP. Determination of IgA RF does not seem to add predictive value for erosive arthritis in RA patients. <h3>Disclosure of Interest</h3> None declared
THU0128 Do biological dmards prevent long term articular damage by rheumatoid arthritis in routine clinical care?
Authors: S. Baghban, L. Krens, M. Henstra, M. Vermeer, K. van der Elst, H. Bernelot Moens
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Treatment of rheumatoid arthritis is primarily aimed to achieve remission and thereby reduce the risk of permanent joint damage. Preventing disabling joint damage is an important long term goal for patients. Effectiveness of bDMARDs on disease activity has been proven in randomised controlled studies; however studies on long term joint damage are scarce and show conflicting results.<sup>1,2</sup> <h3>Objectives</h3> To compare joint damage more than 5 years after RA diagnosis in patients who have never used bDMARDs and in patients treated with bDMARDs. Joint damage is measured with the Rheumatoid Arthritis Articular Damage (RAAD) score, a clinical method comprising all joints that may be affected by RA.<sup>3</sup> <h3>Methods</h3> Retrospective cohort study in RA patients in a Dutch teaching hospital diagnosed between 2006 and 2011. Inclusion criteria were receiving a DMARD for at least 12 months and availability of a RAAD-score after a disease duration of 5 years or more. Exclusion criteria was receiving a DMARD for an other indication than RA. The exposure of interest was the type of treatment (sDMARD or bDMARD). <h3>Results</h3> Among 305 patients included, 101 used a bDMARD (table 1). Baseline characteristics were not significantly different in terms of prognostic factors for joint damage progression, with the exception of patients in the bDMARD group being younger. During follow up, the highest DAS28 was higher in the bDMARD group 5.0 vs 4.3, p&lt;0.001. After 8.5 years, more than half of the patients in bDMARD (55.4%) and sDMARD (57.4%) groups had no joint damage (RAAD-score 0). No significant differences in long term joint damage were observed, even after adjusting for potential confounders (b=−0.26, 95% CI −1.9–1.4, p=0.76). <h3>Conclusions</h3> In this cohort joint damage is not significantly different between patients treated with sDMARD(s) alone and those also using a bDMARD. Given the higher disease activity in the bDMARD group it is possible that this treatment prevented long-term joint damage by RA. Since there was limited joint damage in these groups this analysis should be repeated after longer disease duration and preferably in randomised cohorts. <h3>References</h3> [1] Ciubotariu, et al. Joint damage progression in patients with rheumatoid arthritis in clinical remission. Do biologics perform better than synthetic antirheumatic drugs?J Rheumatol2014:1576–82. [2] Klarenbeek, et al. The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis2011:1039–46. [3] Zijlstra, et al. The rheumatoid arthritis articular damage score: first steps in developing a clinical index of long term damage in RA. Ann Rheum Dis2002:20–3. <h3>Disclosure of Interest</h3> None declared
Abstract 17830: Relationship of Left Ventricular Mass to Lean Body Mass in the Obese Pediatric Population
Authors: Susan M Dusenbery, Jason S Kerstein, Sarah D de Ferranti, Michael M Mendelson, Steven D Colan, Kimberlee Gauvreau, Puneeta Arya
Journal: Circulation (2016)

Introduction: Left ventricular hypertrophy (LVH) and obesity are established independent risk factors of cardiovascular mortality. Identifying increased left ventricular mass (LVM) in pediatric obe...