tbuckley/cabot-search huggingface dataset:
AB0489 The sle-key® rule-out test performs well as an aid in clinical practice
Authors: D Massenburg, J Oldenberg, A Sell, T Krause, AF Wells
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The SLE-key® test was developed by ImmunArray and was validated to rule out SLE with 94% sensitivity, 75% specificity and a negative predictive value (NPV) of 93%<sup>1</sup>. We reported earlier that the SLE-key® RuleOut test could aid in the diagnosis and disposition of a cohort of 55 patients in our clinical practice<sup>2</sup>. <h3>Objectives</h3> We have now expanded this cohort and report here the usefulness of the SLE-key® test in aiding the management of a cohort of challenging and suspected SLE patients in a large clinical practice. <h3>Methods</h3> In patients referred to the Rheumatology and Immunotherapy Center, in Franklin, WI, results from the SLE-key® RuleOut test were included as part of the clinical evaluation. Serum samples were collected from individual subjects with informed consent and tested at VERACIS (Richmond, VA), using the SLE-Key® iCHIP®<sup>1</sup>. <h3>Results</h3> We reviewed the diagnoses and clinical disposition of patients both before and after SLE-key® testing. In particular, we looked at the ability of the SLE-key® test to enhance our ability to reach a definitive diagnosis across the full cohort of patients, at the disposition of patients who were referred with a suspicion of SLE as part of the differential diagnosis, at the impact of SLE-key® testing on the diagnosis of the subset of patients who presented with minimal symptoms, and at the group of patients who had been referred following an ANA test. Results are summarized in Table 1. In the cases where SLE was ruled out, patients were treated for a variety of disorders including fibromyalgia, joint pain, MCTD, Sjogren9s disease and others. <h3>Conclusions</h3> The diagnosis of patients referred in the clinical rheumatology setting remains an ongoing challenge. The SLE-key® RuleOut test provides a laboratory aid to improve the diagnostic and dispositive efficiency saving undue concern, time and resources both to the patient and to the healthcare system. A retrospective analysis of our practices prior to the introduction of SLE-key® is warranted. <h3>References</h3> Putterman et al., Journal of Immunological Methods, 2016. Massenburg et al., Arthritis Rheumatol. 2016; 68 (suppl 10). <h3>Disclosure of Interest</h3> None declared
Response to Comment on Bloomgarden et al. Is HbA1c &amp;lt;7% a Marker of Poor Performance in Individuals &amp;gt;65 Years Old? Diabetes Care 2017;40:526–528
Authors: Zachary T. Bloomgarden, Daniel Einhorn, Yehuda Handelsman
Journal: Diabetes Care (2017)

We appreciate that Pogach and Aron (1) disagree with our commentary (2). It is logical to assume, as these authors appear to have done, that lower HbA1c is associated with greater likelihood of hypoglycemia. We reiterate that a great deal of evidence, some discussed in our commentary (2), supports the notion that HbA1c levels in the “good” range are associated with better outcome rather than with more hypoglycemia. Indeed, agents reducing cardiovascular end points, not causing hypoglycemia, and allowing good control (at any age) are available.

Are older adults specifically ill-suited to “good” control? An Action to …
AB0634 Rituximab in systemic sclerosis-interstitial lung disease, a case series of 18 patients
Authors: G Guzelant, M Melikoglu, B Musellim, DD Yilmaz, I Fresko, E Seyahi, G Hatemi, S Ugurlu, V Hamuryudan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Interstitial lung disease (ILD) is a severe complication of systemic sclerosis (SSc). Immunosuppressives such as cyclophosphamide (CYC) and mycophenolate mophetil (MMF) are used in its treatment with no proven efficacy (1). Rituximab (RTX) appears to be an emerging agent according to case series. <h3>Objectives</h3> This retrospective study aims to evaluate the efficacy of RTX on SSc-ILD in a group of patients followed in our center. <h3>Methods</h3> A chart review revealed 18 patients (16 women, 2 men; mean age 50.3±12.1 SD years (range 30–72), mean disease duration 8.3±9.3 SD years) with SSc who have been diagnosed as having ILD (confirmed by high-resolution thorax computed tomography and pulmonary function tests) and have been treated with one or more cycles of RTX. Efficacy was evaluated according to the criteria of the American Thoracic Society: improvement= an increase in FVC≥10% or DLCO≥15%; worsening= a decrease in FVC≥10% or DLCO≥15%; stabilization= changes in FVC less than 10% or DLCO less then 15% (2). <h3>Results</h3> Four patients were treatment naive for ILD when they received RTX (Group 1). The mean duration between the diagnosis of ILD and RTX treatment in Group 1 was 3.5 months (range 0–14 months). The average RTX cycle in this group was 2 with 1 patient also receiving mycophenolate mophetil in combination with RTX. The mean follow-up time after the initiation of RTX in this group was 12.2±6.8 SD months (range 7–22 months). FVC/DLCO was stable or improved in 2/4 compared to baseline and worsened in 2/4 at the end of follow-up at group 1. Fourteen patients had a 10.2 years-history of SSc and have been treated with immunosuppressives (cyclophosphamide, azathioprine, methotrexate, MMF) for ILD before RTX (Group 2). The mean duration between the diagnosis of ILD and RTX treatment in Group 2 was 71.2 months (range 5–246 months). These patients received a mean of 3 cycles of RTX with 5 receiving MMF (n=3) or AZA (n=2) in addition to RTX. One patient died after 3 months following the first RTX cycle (unknown reason) and 1 was unsuitable for spirometry because of microstomia. Of the remaining 12 patients in Group 2, improvement or stabilisation was seen in 7 and worsening was seen in the remaining 5 patients. <h3>Conclusions</h3> RTX appears to be modestly effective for ILD of SSc. The duration of ILD as well as the presence or absence of previous immunosuppressive therapy do not appear as playing a role in response. <h3>References</h3> Avouac J et al. EULAR Scleroderma Trials and Research group (EUSTAR) recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2009. An Official ATS/ERS/JRS/ALAT Statement: IPF: Evidence-based Guidelines for Diagnosis and Management. <h3>Disclosure of Interest</h3> None declared
SP0064 To be and to become: reflections on my transition
Authors: W Olsder
Journal: Annals of the Rheumatic Diseases (2017)

The importance of successfully transitioning pediatric patients to adult care is increasingly recognized across a wide range of health care providers. However, there are still many challenges occurring during the transition phase. This presentation will contribute to these challenges by sharing the journey of a young person with arthritis on the transition to adult care. As a young patient with arthritis, I made the journey from pediatric care to adult care a couple of years ago. I am diagnosed with arthritis since I was 14 years old. In this presentation, I will show the experiences of my own transition. Furthermore, as the chair of Youth-R-Well.com, an organization for young people with RMDs in the Netherlands, I will share some of the main points around transition I learned from other young patients. For every person, the transition to adult care is experienced different. Therefore, I will try to give some main answers from personal journeys on the questions: How is the transition experienced by a young patient? What are the current challenges faced by a young patient during the transition? What should be the role of the parents during the transition? What are best practices for the transition to adult care? <h3>Disclosure of Interest</h3> None declared
FRI0166 Radiographic structural damage is worse in the dominant than the non-dominant upper extremity in patients with rheumatoid arthritis
Authors: S Nakazaki, T Murayama, S Kato
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The relationship between mechanical stress and radiographic damage in rheumatoid arthritis (RA) has been detected in patients with hemiplegia<sup>1)</sup> or poliomyelitis<sup>2)</sup>. In patients without neurological disorder, Koh reported that radiographic damage was worse and progressed faster in the dominant hand in individuals with early RA<sup>3)</sup>. However, few studies have detected the radiographic damage in the whole upper extremity on the mechanical stress. <h3>Objectives</h3> To examine the relationship between mechanical stress and radiographic damage in RA, we evaluated the joint destruction of the dominant and non-dominant upper extremity. <h3>Methods</h3> The joint destruction of the upper extremity (shoulder, elbow, wrist, metacarpo-phalangeal, interphalangeal, proximal interphalangeal) in 295 patients with RA, who were from 25 years to 91 years (mean age 64 years, mean disease duration 183 months, 86% females and 97% right-handed), was assessed according to the eroded joint, which was defined as ≥2 by Larsen scores for radiographic damage. These were divided into the dominant and non-dominant upper extremity. The Wilcoxon signed-rank test was used to examine the difference between the eroded joint count (EJC) in the dominant and the non-dominant upper extremity. <h3>Results</h3> The mean EJC in the dominant and the non-dominant upper extremity was 2.4 and 2.05 respectively. The EJC was significantly more in the dominant than the non-dominant upper extremity. And, in regards to every joint of upper extremity, the eroded joint rate was higher in the dominant than the non-dominant <h3>Conclusions</h3> The eroded joint count of the upper extremity was significantly more in the dominant than the non-dominant one, therefore it was suggested that the mechanical stress influenced the radiographic damage in patients with RA <h3>References</h3> John H Bland, et al.: Hemiplegia and rheumatoid hemiarthritis. Arthritis Rheum (11) 1: 72–80, 1968. E N Glick, et al.: Asymmetrical rheumatoid arthritis after poliomyelitis. Br Med J 3: 26–28, 1967. Jung Hee Koh, et al.: Radiographic structural damage is worse in the dominant than the non-dominant hand in individuals with early rheumatoid arthritis. PLOS ONE, doi: 10. 1371/journal. Phone.0135409 August 6, 2015. <h3>Disclosure of Interest</h3> None declared
FRI0180 Multiple sclerosis risk-alleles study in patients with demyelinating side effects on anti tnf alpha therapy
Authors: S Bitoun, C Verstuyft, C Miceli-Richard, J-M Berthelot, C Richez, C Cauquil, C Sordet, S Melac-Ducamp, L Gossec, B Beatrice, E Dernis, E Houvenagel, M-A Boutry-Bacle, X Mariette, R Seror
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tumor Necrosis Factor alpha (TNFα) is a key cytokine in inflammatory rheumatic diseases. TNF inhibitors (TNFi) has revolutionized treatment of rheumatic diseases, but may cause flares of multiple sclerosis (MS). Two Single Nucleotide Polymorphisms, (SNPs) <i>rs1800693</i> and <i>rs4149584</i>, located within <i>TNF receptor superfamilly 1</i> (<i>TNFRSF1A</i>) locus have been shown to increase the risk of developing MS [1]. The rs1800693*G allele leads to a dysfunctional TNFα soluble receptor that inhibits TNFα signaling while <i>rs4149584</i> is involved in TNF receptor associated periodic syndrome. <h3>Objectives</h3> The aim of this study was to look for a possible the association between <i>TNFRSF1A</i> polymorphisms and demyelinating complications occurring during TNFi therapy. <h3>Methods</h3> Patients who presented with a demyelinating disorder (central or peripheral involvement) while treated with TNFi (cases), were recruited between March 2013 and December 2015, through the physicians involved in the CRI ("Club Rhumatismes et Inflammation") a nationwide network of the French Society of Rheumatology. Rheumatoid arthritis patients treated with TNFi, from the French ReAct cohort, and who did not develop demyelinating complication constituted the control population (n=294). The frequency of <i>rs1800693</i> and <i>rs4149584</i> TNFRSF1A SNPs were compared between cases and controls. <h3>Results</h3> Twenty-four cases with demyelinating disorders, recruited from 11 centers with a median age of 39.7 years (range 30.4–75.8); of which 16 (67%) were females were included in the study. Neurological symptoms occurred after a median of 18.3 (1–66) months of anti TNFi; 15 (62.5%) had central neurologic involvement and 9 (37.5%) had peripheral involvement. The median follow-up was 26 (4–54) Months. No significant difference in the frequency of the <i>rs1800693</i> MS risk-alleles (39,5% for cases vs 38,6% for controls) was observed. Similarly no difference was observed between cases (2%) and controls (4%) for <i>rs4149584.</i> <h3>Conclusions</h3> This study was unable to show an association between MS-associated SNPs within <i>TNFRSF1A</i> locus and the occurrence of demyelination while taking TNFi, suggesting that demyelination might be linked to other genetic factors or other pathways. <h3>References</h3> De Jager PL, Jia X, Wang J, et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 2009;41:776–82. doi:10.1038/ng.401. <h3>Disclosure of Interest</h3> None declared
THU0067 NLRP3 inflammasome activity in monocytes is regulated by 12/15-lipoxygenase
Authors: Y Kusche, K Barczyk-Kahlert, J Roth
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Activation of the NLRP3 inflammasome is a major inflammatory pathway in monocytes in response to various exogenous and endogenous stimuli. However, negative regulation of inflammasome activity is not well understood. Glucocorticoids (GC) are drugs of choice for the treatment of many inflammatory diseases. Recently, we could show that treatment of monocytes with GC leads to re-programming towards a specific population involved in resolution of inflammation. Gene analysis has shown up-regulated expression of 12/15-lipoxygenase (12/15-LOX) in GC-and LPS/GC-treated monocytes. 12/15-LOX reacts with polyunsaturated-fatty-acids to generate anti-inflammatory lipid-mediators, which contribute to resolution of inflammation. <h3>Objectives</h3> The aim of our study was to determine the contribution of 12/15-LOX on the inflammatory response on murine monocytes. <h3>Methods</h3> Bone marrow-derived monocytes were isolated from wild-type (wt) C57BL/6 and 12/15-LOX<sup>-/-</sup> mice and stimulated with GC and/or LPS as well as various inhibitors or stimulants. Gene expression was analyzed using qRT-PCR. Protein expression was examined by Western-Blot, Flow-Cytometry and ELISA. T-cell response was analyzed by co-culture of stimulated monocytes with allogenic T-cells. <h3>Results</h3> 12/15-LOX<sup>-/-</sup> monocytes showed slightly higher secretion of IL-1β as compared to wt cells after LPS stimulation. The differences between wt and 12/15-LOX<sup>-/-</sup> were much more pronounced when monocytes were additionally exposed to ATP. LPS treatment markedly enhanced expression of pro-IL-1β in 12/15-LOX<sup>-/-</sup> monocytes. No differences could be observed between wt and 12/15-LOX<sup>-/-</sup> monocytes in secretion of other proinflammatory mediators as well as the expression of inflammasome components. However, expression of cleaved caspase-11 was up-regulated in 12/15-LOX<sup>-/-</sup> monocytes exposed to LPS. Additionally, inhibition of caspase-11, caspase-1 and 5-LOX significantly reduced the high secretion of IL-1β in 12/15 LOX<sup>-/-</sup> monocytes. Interestingly, 12/15-LOX<sup>-/-</sup> rather than wt monocytes stimulated with LPS led to enhanced T-cell proliferation. <h3>Conclusions</h3> Our results demonstrate that 12/15-LOX plays a regulatory role during inflammatory immune response by counteracting the NLRP3 inflammasome activity through down-regulation of caspase-11 and 5-LOX activity. Thus, we identified a novel negative regulatory pathway of inflammasome activity. <h3>References</h3> Barczyk, K. et al. Glucocorticoids promote survival of anti-inflammatory macrophages via stimulation of adenosine receptor A3. Cancer 116, 1–3 (2010). Conrad, D.J. The arachidonate 12/15 lipoxygenases. A review of tissue expression and biologic function. Clinical reviews in allergy&amp;immunology17, 71–89 (1999). <h3>Disclosure of Interest</h3> None declared
Differentially androgen regulated genes in androgen dependent (LNCaP) and independent (C4-2) prostate cancer cells
Authors: Satoko Kojima, David J. Mulholland, Susan E. Ettinger, Colleen C. Nelson, Martin E. Gleave
Journal: Cancer Research (2005)

4373  Prostate cancer (CaP) ultimately progresses to androgen independence (AI). Development of a lethal phenotype involves enhanced pro-survival cell signaling and altered androgen receptor (AR) function. The diversity of genes implicated in CaP progression is due, in part, to the heterogeneity and multifocal nature of CaP. Gene microarrays evaluated two critical variables involved in acquisition of AI CaP: (1) androgen responsive genes in AR and PSA secreting CaP cells and (2) differential gene expression in LNCaP androgen dependent (AD) and the closely related C4-2 (AI) CaP cells. LNCaP and C4-2 cells were cultured in androgen depleted medium for 2 days followed by treatment with or without 1 nM R1881. Total RNA was compared to control samples on the same chip each containing 14,000 70-mer oligos. Microarray experiments were repeated three times and confirmed by Northern blot and real time-PCR. GeneSpring 6.1 (Silicon Genetics) software was used to profile for significant changes in gene expression. Genes altered by addition (A+) or removal (A-) of androgens were measured as A+/A- and classified as up-regulated (> 1.5 fold) or down-regulated (
AB0752 Consensus statement on the use of methotrexate in psoriatic arthritis patients
Authors: J Tornero, E Loza, JDD Cañete
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Methotrexate (MTX) is the cornerstone in rheumatic diseases, including psoriatic arthritis (PsA), but the complexity of PsA and the paucity of randomised controlled studies and strategic trials need a clear analysis. <h3>Objectives</h3> To develop recommendations for the management of MTX in PsA (musculoskeletal manifestations) based on best evidence and experience <h3>Methods</h3> The coordinators formulated 14 questions about MTX use (indications, efficacy, safety) in patients with PsA. A systematic literature review was performed to answer these questions. Using this information, inclusion and exclusion criteria were stablished as well as the search strategies (Medline, Embase and the Cochrane Library), that were designed by an expert librarian. Two different reviewers selected the articles, first by title and abstract, then by detailed review, and collected data independently. Evidence tables were produced. With this evidence the coordinators proposed 12 preliminary recommendations that will be discussed and voted in a nominal group of expert meeting. The level of evidence and grade of recommendation will be defined using the Oxford Center for Evidence Based Medicine. Agreement will be stablished if at least 80% of the experts voted yes (yes/no). <h3>Results</h3> A total of 12 preliminary recommendations on the use of MTX in PsA were proposed (see table). <h3>Conclusions</h3> This document aims to help to answer usual clinical questions and facilitate decision making when treating PsA patients with MTX. <h3>Disclosure of Interest</h3> J. Tornero: None declared, E. Loza Grant/research support from: Abbie, Pfizer, Roche, Gebro, BMS, UCB, J. Cañete: None declared
AB0212 Clinical and sociodemographic characteristics associated with response to methotrexate (MTX) in a cohort of patients with rheumatoid arthritis (RA) naÏve to dmard
Authors: E Chamizo-Carmona, C Carrasco Cubero, PJ Cossio Jimenez, SM Rojas Herrera, TL Rodriguez Araya, R Veroz Gonzalez, JJ Aznar Sanchez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> RA treatment involves starting early with a DMARD. MTX achieves good sustained response in 30–40% of patients (pts). When MTX response is insufficient add other DMARD by achieve RA remission. Different factors may affect the response to MTX <h3>Objectives</h3> To analyze the clinical and demographic characteristics related to response to MTX in RA pts DMARD-naïve <h3>Methods</h3> We enrolled between 2011 and 2015, pts&gt;18years RA diagnosed (ACR 1987 criteria), treated firs with MTX monotherapy (MTXm). A case-control study (MTXm persistence with CRP-DAS28&lt;3.2 and suspension of MTXm by ineffectiveness or toxicity, respectively) was performed. We collected information that can influence the response to MTXm by medical records review and patient survey. A descriptive and analitical study with SPSS statistics 21 was performed <h3>Results</h3> We included 222 pts (70 men and 152 women). The characteristics of cases (123) and controls (99) are shown in the table. The causes of MTXm suspension were remission (7), intolerance/toxicity (19) and inefficiency (79). MTX was discontinued in 40 (18.2%) pts, 28 (12.7%) of them by intolerance/toxicity. Of 123 (55.4%) responders, 71 (32.0%) were CRP-DAS28&lt;2.6. MTXm response was associated with age at onset ≥60 years (χ2 18.47, p&lt;0.01, OR 3.67), rheumatoid factor (RF) &lt;100 IU (χ2 10.92, p&lt;0.01, OR 3.16) and current smoking (χ2 12.71, p&lt;0.01, OR 2.95). Tobacco was associated with RF+ (χ2 8.9 p&lt;0.01 OR 2.59 (1.37; 4.89) and ACPA+ (χ2 4.49 p&lt;0.05 OR 1.88 (1.04, 3.38). We found no association with gender, education, job, coffee, tea or alcoho drinks, comorbidities, cardiovascular risk, possitivity ACPA or FR, RA presentation, treatment delay, or corticosteroid use. We found no correlation between age of RA-onset and RF or ACPA levels and MTXm duration. MTXm persistence at 5 years was 59% pts and their median survival was 93 months (77.14 to 108.8). We only found significant differences in favor of non-smokers and RF&lt;100 <h3>Conclusions</h3> The initial treatment of RA with MTX is an effective and safe option, with a high drug survival. MTX response was not associated with antibody positivity (RF or ACPA), but it was significantly better in non-smokers patients and RF &lt;100. Smoking cessation could significantly improve the response to MTX of RA patients <h3>References</h3> Saevarsdottir S, et al. Arthritis Rheum 2011;63:26–36. V. K. Ranganath et al. Rheumatology 2013;52:1809–1817. <h3>Disclosure of Interest</h3> None declared