tbuckley/cabot-search huggingface dataset:
SAT0390 Diffusion weighted imaging (DWI) is more useful than short TAU inversion recovery (STIR) sequence in diagnosis of non-radiographic axial spondyloarthritis (SPA) and both sequences are particularly useful in early disease stage
Authors: CWS Chan, HY Chung
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Diffusion weighted imaging (DWI) is a new Magnetic Resonance Imaging (MRI) sequence proposed for spondyloarthritis (SpA) diagnosis. Whether it is more useful than the traditional short tau inversion recovery (STIR) sequence in disease diagnosis had not been evaluated. <h3>Objectives</h3> By comparing with traditional STIR sequence in a group of back pain patients newly referred to rheumatology clinics, we evaluated the usefulness of DWI in SpA diagnosis at different stages. <h3>Methods</h3> All new patients referred to the rheumatology clinics with persistant back pain were recruited. DWI and STIR MRI were performed. Conventional radiographs of the pelvis were assessed according to the modified New York criteria for ankylosing spondylitis. Bone marrow edema (BME) and active sacroiliitis according to the ASAS definition were evaluated in STIR and DWI by two independent observers. <h3>Results</h3> One hundred and thirty-three patients were recruited. Ninety patients (67.7%) had a clinical diagnosis of SpA. Average back pain duration was 8.5±8.9 years. The presence of Human Leukocyte Antigen (HLA) B27 was found in 42.9% of the study population. Inter-observer correlations were excellent (STIR 95.4%, p&lt;0.001; DWI 69.5%, p&lt;0001). DWI was found to be comparable to STIR in disease diagnosis (sensitivity DWI 34.1% vs STIR 34.3%; specificity DWI 85% vs STIR 93.8%) and when applied to the Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA (sensitivity DWI 78.9% vs 79.5%; specificity DWI 75.0% vs 78.8%). DWI is better than STIR in non-radiographic axial SpA group (sensitivity DWI 37.8% vs STIR 33.8%; specificity DWI 85.3% vs STIR 95.6%). In the group with disease duration less than 3 years, the two images showed improved sensitivity (sensitivity DWI 34.5% vs STIR 41.4%; specificity DWI 84.6% vs STIR 88.5%). <h3>Conclusions</h3> DWI is useful in SpA diagnosis especially in non-radiographic axial SpA group. Both DWI and STIR are especially useful for early disease diagnosis. <h3>Disclosure of Interest</h3> None declared
Targeted induction of apoptosis by chimeric granzyme B fusion proteins carrying EGFR- and ErbB2/HER2-specific binding domains for tumor cell recognition
Authors: Benjamin Dälken, Ulrike Giesübel, Shirley K. Knauer, Winfried S. Wels
Journal: Cancer Research (2006)

2205   The serine protease granzyme B (GrB) of cytotoxic T-lymphocytes and natural killer cells efficiently induces apoptosis in target cells by direct activation of caspases and cleavage of central caspase substrates. We employed human GrB as a cytotoxic effector function in chimeric fusion proteins that also contain the EGFR ligand TGFalpha or an ErbB2-specific single-chain antibody fragment (scFv) for selective targeting to tumor cells. EGFR and ErbB2 (HER2) are overexpressed on many human tumors of epithelial origin and transmit important growth and survival signals. GrB-TGFalpha (GrB-T) and GrB-scFv(FRP5) (GrB-5) molecules expressed in the yeast Pichia pastoris were bifunctional, cleaving synthetic and natural GrB substrates, and binding specifically to tumor cells expressing EGFR or ErbB2 on their surface. Upon cell binding the chimeric molecules were internalized into intracellular vesicles, but in contrast to unmodified GrB, could be released into the cytosol by the endosomolytic reagent chloroquine. Treatment with picomolar to nanomolar concentrations of GrB-5 and GrB-T resulted in selective and rapid tumor-cell killing, accompanied by clear signs of apoptosis such as chromatin condensation, membrane blebbing, formation of apoptotic bodies and activation of endogenous initiator and effector caspases. These bifunctional, immunotoxin-like proteins might be useful to study GrB-induced apoptosis without the requirement for perforin, but also hold promise for further development as targeted cancer therapeutics of human origin.
Abstract 15618: S-nitrosoglutathione Reductase is Essential for Protecting Female Hearts From Ischemia-Reperfusion Injury
Authors: Kevin Casin, Jonathan Fallica, Mark J Kohr
Journal: Circulation (2016)

Pre-menopausal female hearts exhibit reduced susceptibility to ischemia-reperfusion (I/R) injury compared to males. Our recent study suggests that this protection results in part from enhanced endo...
SAT0373 Evaluation of american college of rheumatology provisional composite response (CRISS) index in the fasscinate trial
Authors: D Khanna, V Berrocal, C Denton, A Jaheris, H Spotwood, C Lin, J Siegel, D Furst
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Treatment with tocilizumab (TCZ) in early systemic sclerosis (SSc; FaSScinate trial) resulted in consistent, but not statistically significant, improvements in skin sclerosis (mRSS) at wks 24 and 48<sup>1</sup>. The CRISS index has been proposed as a composite index for trials in SSc<sup>2</sup>. CRISS is a 2-step process that assigns a probability of improvement for each subject ranging from 0.0 [no improvement] to 1.0 [marked improvement]. Step 1 assesses clinically meaningful decline in cardio-pulmonary-renal involvement and assigns a probability of 0.0. For remaining subjects, 5 variables are used to calculate probability of improvement. These are: FVC%, mRSS, patient (PT GA) and physician globals (MD GA), and HAQ-DI. <h3>Objectives</h3> To assess the performance of CRISS index in the FaSScinate trial. <h3>Methods</h3> In FaSScinate, pts ≥18 y with active SSc were randomized 1:1 to TCZ or placebo (PLA) for 48 wks. Step 1 CRISS was captured using review of serious adverse event data. Non-parametric Wilcoxon test was used to assess significant differences between the CRISS scores in both arms. Analyses were carried out for subject who had complete data at baseline and 24 weeks and at baseline and 48 weeks. <h3>Results</h3> 87 pts (43 TCZ, 44 PBO) were enrolled. Baseline characteristics were similar between arms. 4 subjects in the PBO group and none in TCZ met the pre-defined definition of worsening in Step 1 and were given a score of 0.0. For remaining subjects, we calculated probability score for each subject. Using CRISS as a continuous measure, the median score was statistically significant and favored TCZ compared to PBO at wks 24 and 48 (p=0.04 and 0.01; Table). Table also presents the individual components of Step 2 where only FVC% was statistically significant favoring TCZ at wk 48. <h3>Conclusions</h3> In this post-hoc analysis, CRISS index was able to discriminate TCZ from PBO, supporting its validity in an independent cohort. <h3>References</h3> Khanna D. Lancet. 2016. Khanna D. Arthritis Rheum. 2016. <h3>Disclosure of Interest</h3> D. Khanna Grant/research support from: NIH/NIAMS and NIH/NIAID, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer Ingelheim, Genentech/Roche, Sanofi-aventis, GSK, Corbus, Cytori, EMD Serono, V. Berrocal: None declared, C. Denton Consultant for: Actelion, Bayer, GSK, CSL Behring, Merck-Serono, Genentech-Roche, Inventiva, Sanofi-Aventis, Boehringer Ingelheim, A. Jaheris Shareholder of: Roche stock and options, Employee of: Genentech, H. Spotwood Employee of: Roche, C. Lin Employee of: Genentech, J. Siegel Employee of: Genentech, D. Furst Grant/research support from: Amgen, BMS, NIH, Novartis, Pfizer, Roche/Genentech, Consultant for: AbbVie, Amgen, BMS, Cytori, Novartis, Pfizer, Roche/Genentech, UCB
Abstract 17176: Prognostic Importance of Defibrillator Appropriate Shocks and Anti Tachycardia Pacing in Mild Heart Failure Patients
Authors: Yitschak Biton, Arthur J Moss, Alon Barsheshet, Valentina Kutyifa, Scott Mcnitt, Wojciech Zareba, Ilan Goldenberg
Journal: Circulation (2015)

Background: Previous studies had shown that patients with heart failure (HF) who receive implantable cardioverter-defibrillator (ICD) for primary prevention are at increased risk for mortality if they receive a shock. However, information about the prognostic importance of therapies [both shock and anti-tachycardia pacing (ATP)] delivered for a different ventricular arrhythmia (VA) rate is limited. Methods: We evaluated the risk for death among 1790 ICD implanted patients from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy using a time dependent analysis. Patients were categorized to mutually exclusive groups by either the rate of the treated VA (categorized at 200 bpm) or the type of the therapy and VA rate (ATP or shock both categorized at 200 bpm), the reference group was patients that had no device therapy. Results: During a median follow-up time of 4 years 423 patients had appropriate ICD therapy, with 163 receiving therapy for VA&lt; 200 bpm only, and 260 for VA≥200 bpm. ICD therapy for VA≥200 was associated with significant increased mortality (HR=2.27 CI 1.48-3.48, p&lt;.001), while therapy for VA&lt;200 was not different from the no therapy group (HR=1.45 CI=0.86-2.44, p=0.162). Accordingly, in a second model both shocks and ATPs for VA≥200 were associated with increased mortality (HR=2.96 CI 1.91-4.60 p&lt;.001 and HR=2.22 CI 0.96-5.14, p=0.063 respectively), while shocks and ATPs for VA&lt;200 did not differ from the no therapy group (HR=1.43 CI 0.52-3.92 p=0.489 and HR=1.43 CI 0.80-2.56, p=0.232 respectively). Conclusions: In mild HF patients, who receive ICD for primary prevention, mortality is associated with the rate of the arrhythmia rather than the device rendered therapy.
THU0481 Validation of the proposed 2016 revision to 2010 acr preliminary fibromyalgia diagnostic criteria in a tertiray care setting
Authors: S Ahmed, A Aggarwal, A Lawrence
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The 2010 Fibromyalgia Diagnostic Criteria was designed for primary care<sup>1</sup>. The 2011 modification was a simplified version for self-reporting of fibromyalgia<sup>2</sup>. The 2016 revision combines both, and is supposed to be used also in tertiary setting<sup>3</sup>. This requires validation. <h3>Objectives</h3> To validate the Proposed 2016 revision with respect to (1) expert physician diagnosis and (2) 1990 ACR Classification Criteria. <h3>Methods</h3> Patients referred to a tertiary care centre with suspicion of Fibromyalgia were evaluated using the Proposed 2016 revision. Patients with other rheumatological diseases were excluded. Considering the expert physician opinion and American College of Rheumatology (ACR) 1990 Classification as gold standards, sensitivity, specificity, and likelihood ratios were calculated. Also, validated Hindi language versions of Brief Patient Health Questionnaire (BPHQ), Generalised Anxiety Disorder-7 (GAD7), and Toronto Alexithymia Scale-20 (TAS20) were filled up by the participants. <h3>Results</h3> Out of 101 patients, 77 were diagnosed as Fibromyalgia by the expert. The 2016 criteria and ACR1990 criteria were met by 79 and 67 patients respectively. The 2016 had high sensitivity but much lower specificity as compared with either the expert diagnosis or ACR1990 criteria (Table 1). Visual Analogue Scale (VAS) for pain, BHPQ, GAD7, and TAS20 scores were 7.2±2.3, 14.1±5.1, 11.3±5.5 and 58.0±14.0 (Mean±SD) respectively. Patients with or without fibromyalgia as per each of the three criteria had no significant difference in these scores. <h3>Conclusions</h3> Non-tender point based criteria have been validated in primary care. However, in tertiary care where patients are referred to as fibromyalgia, there are mimics with similar comorbidities as evident by high BPHQ, GAD7 and TAS20 scores. Even after exclusion of other rheumatological conditions, the 2016 Criteria has poor specificity. Thus, it should be used as a screening tool than a diagnostic criterion in tertiary care. <h3>References</h3> Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 May;62(5):600–10. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol. 2011 Jun;38(6):1113–22. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016 Dec;46(3):319–329. <h3>Disclosure of Interest</h3> None declared
SAT0682 Prevalence of sarcopenia in patients with chronic inflammatory rheumatic diseases
Authors: A Tournadre, P Jaffeux, T Frayssac, A Fan, M Couderc, JJ Dubost, S Malochet-Guinamand, S Mathieu, Z Tatar, JC Jourdy, M Soubrier
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Evaluation of sarcopenia is of major relevance because of these clinical repercussions on morbidity and mortality. Although the definition should include both low muscle mass and function, a combination of the 2 criteria was not reported in inflammatory rheumatic diseases (IRDs). <h3>Objectives</h3> To determine in a cohort of IRDs the prevalence of sarcopenia using established combined criteria (EWGSOP) (1). <h3>Methods</h3> Sarcopenia defined as both low muscle mass (skeletal muscle index (SMI) &lt;7.26 kg/m<sup>2</sup> for men; &lt;5.45 kg/m<sup>2</sup> for women) and impaired muscular function (handgrip strength or gait speed) (1) was assessed in active rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsoA) patients before initiating first biologic. Body composition (DXA) and related factors were compared using univariate, multivariate and correlation analysis. <h3>Results</h3> 148 patients were included (Table). Sarcopenia with decrease in muscle mass and function was observed in 5 RA (7.8%), one SpA (1.7%) and one PsoA (9.1%). Sarcopenia in terms of reduced SMI only (1) was not more frequent occuring in 5 RA (7.8%), 3 SpA (5.1%) and one PsoA (9.1%). Grip strength was decreased in RA as well as muscle mass compared to SpA and PsoA but the difference was no longer significant when adjusted on age, sex, disease duration (Table). Only fat distribution differed with a trunk/peripheral fat ratio higher in PsoA. In RA, lean mass was negatively correlated with disease duration and sedentary time. In SpA and PsoA, fat mass was correlated with age, disease activity, HAQ. HAQ and CRP level negatively correlated with lean mass. No association between treatments and body composition was observed. <h3>Conclusions</h3> Sarcopenia with combined criteria (muscle mass and function) occurred in 7.8% of RA corresponding to the values of the general population aged over 70 years-old (2). Reduced muscle mass only was not highly prevalent and lower than that reported in elderly suggesting important cofactors such as functional limitations or muscle quality in sarcopenia associated with rheumatic diseases. <h3>References</h3> Cruz-Jentoft AJ et al. Age Ageing 2010;39:412–23. Spira D, et al. Z Gerontol Geriatr 2016;49:94–9. <h3>Disclosure of Interest</h3> None declared
AB1018 Detection of ANTI-DFS70 antibodies by indirect immunofluorescence (IIF) on novel HEP-2/DFS70-KO substrate for discriminating antinuclear antibodies (ANA) – positive healthy individuals (HI) and patients with systemic lupus erythematosus (SLE)
Authors: E Aleksandrova, Z Verizhnikova, A Novikov, T Panafidina, T Popkova
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Autoantibodies against intracellular antigens are a serological hallmark of ANA-associated systemic autoimmune rheumatic diseases (AARD) such as SLE. IIF on HEp-2 cells for ANA remains the “gold standard” but it has very low positive predictive value. Up to 20% of serum samples from HI have been reported to have a positive ANA IIF test, the majority of them due to the presence of anti-dense fine speckled 70 (anti-DFS70) antibodies. Monospecific anti-DFS70 antibodies represent a biomarker that can be used to discriminate AARD patients (pts) from HI in ANA IIF positive subjects. Recognition of the DFS70 ANA IIF pattern can be challenging. The DFS-KO Hep-2 cells inhibit anti-DFS70 antibodies reactions, providing clear differentiation of the DFS pattern from classical ANA patterns. <h3>Objectives</h3> To evaluate the utility of a novel HEp-2/DFS70-KO IIF substrate for the detection of anti-DFS70 antibodies in HI and SLE pts. <h3>Methods</h3> We studied 45 HI (36 F/9 M; age 50.4 [24.0–72.0] years, median [interquartile range 25–75%]) and 12 pts with SLE (ACR criteria, 1997) (10 F/2M, age 38.9 [17.0–65.0] years; disease duration 100.3 [4.0–432.0] months; SLEDAI 2K score 11.7 [2–30]; SLICC damage index score 1.28 [0–4]). Serum samples were tested for classical ANA and anti-DFS70 antibodies by IIF technique with a mixture of standard HEp-2 cells and DFS70-KO HEp-2 cells (“Trinity Biotech”, Bray, Ireland) as a substrate. Fluorescence titers ≥1: 160 were considered as positive for ANA patterns. <h3>Results</h3> ANA were present in 7/45 (15.6%) of HI and in 12/12 (100%) of SLE pts. All SLE pts and 3/45 (6.7%) of HI showed classic ANA patterns (homogeneous, speckled, and mixed) in the absence of DFS70 pattern. 4/45 (8.9%) of HI had classic ANA negative/anti-DFS70 antibodies positive IIF results. Isolated anti-DFS70 antibodies were found in 57% of ANA IIF positive HI. Among HI classic ANA and anti-DFS70 antibodies were detected in the low- to medium-titer range (1:160–1:320). The frequency of anti-DFS70 antibodies did not correlated with age. <h3>Conclusions</h3> The detection of isolated anti-DFS70 antibodies may be regarded as an exclusion criterion for the diagnosis of SLE. The testing for anti-DFS70 antibodies in a single step by HEp-2/DFS70-KO IIF method should be included into a modified ANA diagnostic algorithm. Additional investigations are required to evaluate the clinical relevance of anti-DFS70 autoantibodies. <h3>Disclosure of Interest</h3> None declared
Factors associated with disease progression in early-diagnosed pulmonary arterial hypertension associated with systemic sclerosis: longitudinal data from the DETECT cohort
Authors: Carina Mihai, Milos Antic, Rucsandra Dobrota, Diana Bonderman, Harbajan Chadha-Boreham, John Gerry Coghlan, Christopher P Denton, Martin Doelberg, Ekkehard Grünig, Dinesh Khanna, Vallerie V McLaughlin, Ulf Müller-Ladner, Janet E Pope, Daniel M Rosenberg, James R Seibold, Madelon C Vonk, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2017)

Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc). In this longitudinal study, we aimed to identify factors associated with an unfavourable outcome in patients with SSc with early PAH (SSc-PAH) from the DETECT cohort.Patients with SSc-PAH enrolled in DETECT were observed for up to 3 years. Associations between cross-sectional variables and disease progression (defined as the occurrence of any of the following events: WHO Functional Class worsening, combination therapy for PAH, hospitalisation or death) were analysed by univariable logistic regression.Of 57 patients with PAH (median observation time 12.6 months), 25 (43.9%) had disease progression. The following factors (OR (95% CI)) were associated with disease progression: male gender (4.1 (1.2 to 14.1)), high forced vital capacity % predicted/carbon monoxide lung diffusion capacity (DLCO)% predicted ratio (3.6 (1.2 to 10.7)), high Borg Dyspnoea Index (1.7 (1.1 to 2.6)) and low DLCO% predicted (non-linear relationship).More than 40% of early-diagnosed patients with SSc-PAH had disease progression during a short follow-up time, with male gender, functional capacity and pulmonary function tests at PAH diagnosis being associated with progression. This suggests that even mild PAH should be considered a high-risk complication of SSc.
SP0113 New trends in biomarkers in inflammatory joint disease
Authors: E. Feist
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> This lecture provides an overview on new developments in biomarker research and standardisation in inflammatory joint diseases. The presentation includes an introduction of established and new biomarkers in serum and synovial fluid as well as methods for their detection. Furthermore, an overview on different modifications of auto-antigens (including citrullinated and carbamylated isoforms) and their role in immune response and pathogenesis of disease will be given. The diagnostic performance of new and established biomarkers will be discussed including antibodies against modified antigens also illustrated by difficult to diagnose cases. In this context, special attention will be attributed to the predictive value of biomarkers for diagnosis of disease and treatment response. <h3>Disclosure of Interest</h3> None declared
AB0188 Effect of MIR-19A and MIR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis
Authors: H Li, H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway are key factors of the pathogenic mechanisms underlying systematic juvenile idiopathic arthritis (SJIA). <h3>Objectives</h3> The present study aimed to investigate the association between microRNA (miR)-19a, miR-21 and the JAK/STAT signaling pathway. <h3>Methods</h3> A total of 20 patients with SJIA were included in the study, and peripheral blood mononuclear cells (PBMCs) from 20 normal controls were also collected.RNAiso was used to extract total RNA, and the RNA was then reverse transcribed into cDNA. Primers were designedto detect the mRNA of miR-19a and miR-21, and U6 was set as the internal parameter. In addition, the mRNA of STAT3, suppressor of cytokine signaling 3 (SOCS3), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected, and β-actin was set as the internal parameter. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of these proteins in patients with SJIA and control subjects, and non-parametric tests were used to analyze the statistical differences in 2-ΔΔCq between the two groups. <h3>Results</h3> The expression levels of miR-19a and miR-21 were significantly lower in the SJIA group compared with the control group (P&lt;0.05). SOCS3, TNF-α and STAT3 were shown to be the target genes of miR-19a and miR-21, as determined by Targetscan. The expression levels of STAT3, SOCS3,TNF-α and IL-6 mRNA were significantly higher compared with those of the control group (P&lt;0.05). <h3>Conclusions</h3> In the PBMCs of the patients with SJIA, miR-19a and miR-21 expression levels were lower compared with those of the control group, and the JAK/STAT signaling pathway was activated, which indicated that miR-19a and miR-21 may participate in the activation ofthe JAK/STAT signaling pathway. <h3>Disclosure of Interest</h3> None declared