tbuckley/cabot-search huggingface dataset:
SAT0112 Prevalence and incidence over 3 years of different comorbidities in rheumatoid arthritis (RA): a 3 year longitudinal study in 769 established ra patients
Authors: L Gossec, M Soubrier, F Foissac, F Fayet, N Balandraud, T Bardin, C Beauvais, G Chales, I Chary-Valckenaere, E Dernis, L Euller-Ziegler, R-M Flipo, M Gilson, T Marhadour, X Mariette, G Mouterde, S Pouplin, P Richette, A Ruyssen-Witrand, T Schaeverbeke, C Sordet, M Dougados
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Comorbidities including cardiovascular (CV) risk, cancer and osteoporosis are frequent in RA.[1] <h3>Objectives</h3> To quantify at baseline and 3 years later, the prevalence (at baseline) and incidence (over 3 years) of some selected comorbidities. <h3>Methods</h3> This was an open long term (3 years) extension of the COMEDRA 6-month randomized controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling.[2] Comorbidity status was assessed through face-to-face interviews and nurses provided advice on screening and management, at baseline and 3 years later. The frequency of comorbidities was assessed at both timepoints and incidence of new cases was assessed as overall % of patients and as relative increase in the given comorbidity. <h3>Results</h3> Of the 970 recruited patients, 776 (80%) were followed up at 2–4 years (15, 1.5%, had died) and 769 (79%) had available data for comorbidities at both timepoints: at baseline, mean (±SD) age 58 (±11) years, mean disease duration 14 (±10) years; 614 (80%) were women and 538 (70%) were receiving a biologic with a mean DAS28 of 3.1±1.3. At baseline, the most frequent comorbidities were history of fracture (31.9%) and high blood pressure (30.9%) and at 3 years the comorbidity which had most increased (i.e., incidence) in this population aged around 60 years, was high blood pressure (4%) whereas smoking had decreased (Table). <h3>Conclusions</h3> Comorbidities are frequent in RA though screening does not always address the most frequent or severe comorbidities. Efforts must be pursued to improve comorbidity screening and prevention. <h3>References</h3> Ref 1. Baillet A, Gossec L et al. Ann Rheum Dis. 2016;75(6):965–73. Ref 2. Dougados M, Soubrier M, et al. Ann Rheum Dis. 2015;74(9):1725–33. <h3>Acknowledgements</h3> grant from Roche France and from the French National Research Program (PHRC AOM 12072). <h3>Disclosure of Interest</h3> None declared
Early Immune-Related Adverse Events and Association with Outcome in Advanced Non–Small Cell Lung Cancer Patients Treated with Nivolumab: A Prospective Cohort Study
Authors: Shunsuke Teraoka, Daichi Fujimoto, Takeshi Morimoto, Hayato Kawachi, Munehiro Ito, Yuki Sato, Kazuma Nagata, Atsushi Nakagawa, Kojiro Otsuka, Keiichiro Uehara, Yukihiro Imai, Kaori Ishida, Junya Fukuoka, Keisuke Tomii
Journal: Journal of Thoracic Oncology (2017)
THU0105 Prediction of response to CERTOLIZUMAB-PEGOL in rheumatoid arthritis (PRECEPRA) by functional MRI of the brain – an interim analysis of an ongoing investigator initiated phase III trial
Authors: H Schenker, A Hess, L Konerth, M Sergeeva, J Prade, A Kleyer, M Reiser, A Hueber, M Englbrecht, E Feist, RE Voll, B Bannert, C Baerwald, J Rösch, A Doerfler, G Schett, J Rech
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as one third of patients do not respond adequately to TNFi. <h3>Objectives</h3> We investigated whether brain activity associated to arthritis measured by functional magnetic resonance imaging (fMRI) can function as a predictor of response to TNFiin RA patients. <h3>Methods</h3> This is an interim analysis of the first 50 patients of the PreCePRA trial, a multi-center, double-blind, placebo-controlled fMRI trial on patients with RA. [1] [2] Active RA patients failing csDMARDs with a DAS28-ESR &gt;3.2 and at least three tender and/or swollen joints received a baseline brain BOLD fMRI scan upon joint compression at screening. Patients werethen randomized into a 12-week double-blinded treatment phase with placebo (arm 1) or 200mg certolizumab-pegol eow (arm 2; fMRI Bold signal&gt;2000 voxel i.e. 2cm<sup>3</sup>, arm 3; fMRI Bold signal &lt;2000 voxel). LDA 3mo. Primary end point was DAS28-ESR low disease activity at 12 weeks. A 12 weeks follow-up phase in which patients were switched from the placebo to the treatment arm folowed the blinded phase. fMRIwas carried out at baseline as well as after 12 and 24 weeks of or placebo. <h3>Results</h3> In 31 patients (responders) baseline signal volume i.e. sum of significantly coupled voxels after the FDR thresholding was significatly higher compared to 19 patients (non-responders) (p&lt;0.001) allowing discrimination between the two groups prior to treatment. In responders we detected an persitent decrease of the BOLD volume from baseline to week 12 and week 24 (r<sup>2</sup>=0.561) whereas the BOLD volume in non-responders persitently increased (r<sup>2</sup>=0.589). <h3>Conclusions</h3> Based on this interim analysis we conclude that high BOLD volumes in fMRI, indicating high-level brain representation of pain in arthritis. These data represent the first encouring signal of the PreCePRA brain fMRI study supporting the concept that increased RA-related brain activity is related to response to TNFi. <h3>References</h3> Rech, J., et al., Association of brain functional magnetic resonance activity with response to tumor necrosis factor inhibition in rheumatoid arthritis. Arthritis Rheum, 2013.65(2): p. 325–33. Hess, A., et al., Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A, 2011.108(9): p. 3731–6. <h3>Disclosure of Interest</h3> None declared
Recurrent seasonal outbreak of an emerging serotype of Shiga toxin-producing Escherichia coli (STEC O55:H7 Stx2a) in the south west of England, July 2014 to September 2015
Authors: Noëleen McFarland, Nick Bundle, Claire Jenkins, Gauri Godbole, Amy Mikhail, Tim Dallman, Catherine O'Connor, Noel McCarthy, Emer O'Connell, Juli Treacy, Girija Dabke, James Mapstone, Yvette Landy, Janet Moore, Rachel Partridge, Frieda Jorgensen, Caroline Willis, Piers Mook, Chas Rawlings, Richard Acornley, Charlotte Featherstone, Sharleen Gayle, Joanne Edge, Eleanor McNamara, Jeremy Hawker, Sooria Balasegaram
Journal: Eurosurveillance (2017)

The first documented British outbreak of Shiga toxin-producing Escherichia coli (STEC) O55:H7 began in the county of Dorset, England, in July 2014. Since then, there have been a total of 31 cases of which 13 presented with haemolytic uraemic syndrome (HUS). The outbreak strain had Shiga toxin (Stx) subtype 2a associated with an elevated risk of HUS. This strain had not previously been isolated from humans or animals in England. The only epidemiological link was living in or having close links to two areas in Dorset. Extensive investigations included testing of animals and household pets. Control measures included extended screening, iterative interviewing and exclusion of cases and high risk contacts. Whole genome sequencing (WGS) confirmed that all the cases were infected with similar strains. A specific source could not be identified. The combination of epidemiological investigation and WGS indicated, however, that this outbreak was possibly caused by recurrent introductions from a local endemic zoonotic source, that a highly similar endemic reservoir appears to exist in the Republic of Ireland but has not been identified elsewhere, and that a subset of cases was associated with human-to-human transmission in a nursery.
AB0244 Microwave radiometry-derived thermal changes of small joints as potential additional biomarker in rheumatoid arthritis: a prospective study
Authors: K Laskari, G Pentazos, K Prekas, I Raftakis, E Siores, PP Sfikakis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Microwave Radiometry (MR) is a rapid, non-invasive method that detects in-depth tissue temperatures. Using joint ultrasound as reference method, in a proof-of-concept study, we have found that an increased temperature at the knee joint detected by MR in the absence of relevant clinical signs reflects the presence of subclinical synovial inflammation in rheumatoid arthritis (RA) (1). <h3>Objectives</h3> To test the hypothesis that temperature of small joints assessed by MR correlates to global disease activity levels in RA, a disease in which small joints are primarily affected. <h3>Methods</h3> Ten patients with active, untreated RA underwent clinical and laboratory assessments, joint ultrasound and MR of hand and foot small joints (RTM 01 RES microwave computer based system, Bolton, UK) at baseline, as well as 15, 30 and 90 days after treatment onset. Twenty aged-matched healthy individuals served as controls. <h3>Results</h3> Using 1248 separate MR-derived recordings from RA patients we created several thermo-scores involving different small joint combinations and compared them with clinical and ultrasound data. The best performing thermo-score involved the sum of temperatures of 16 small joints (2nd-5th metacarpal and proximal inter-phalangeal joints, bilaterally). This thermo-score correlated positively to DAS28 disease activity score (p=0.001), tender joint count (p=0.002), swollen joint count (p=0.001), patient9s visual analogue scale (p&lt;0.001), CRP (p=0.040), but not ESR levels, as well as to the standard Ultrasound Score of 7 joints (p≤0.025) (2). The MR-derived thermo-score could also discriminate patients in high [mean (SD) 9.2 (5.6)], moderate [mean (SD) 7.1 (3.5)] and low disease activity/remission [mean (SD) 4.2 (1.8)] (p=0.015), or aged-matched healthy subjects [mean (SD) 5.0 (1.7)] (p=0.002). Moreover, individual changes from baseline to follow-up end mirrored the corresponding DAS28 changes in 7/10 patients. <h3>Conclusions</h3> Increased in-depth temperatures of small joints detected by MR, which are indicative of local inflammation, may serve as an additional biomarker in RA. Optimization of MR equipment and technique may result in an objective measurement of RA disease activity in clinical practice. <h3>References</h3> E. Zampeli, et al. Detection of subclinical synovial inflammation by microwave radiometry. PLoS ONE. 2013;(8)5:e64606. Backhaus M, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009;61(9):1194–201. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> None declared
FRI0043 Peptides highly specific to the variable region of TNF-ALFA-specific references licensed (RL) monoclonal antibodies (MAB), as potential tool to effectively assess similarity between biosimilars and the correspondig RL MAB
Authors: E Favoino, C Ionescu, F Perosa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Monoclonal antibodies (mAb) have greatly facilitated the development of highly specific immunotherapy, with a significant improvement of clinical outcome in certain rheumatologic diseases. However, the approaching of many references licensed mAb (RLM) to the end of their licensing period, have stimulated a tremendous interest in the synthesis of a new generation of low-cost mAb referred to as biosimilars (BS) mAb (BSM), because of their similarity to the RLM. An essential requirement imposed by Regulatory Agencies for a mAb to be considered BS is that its variable region (VR) primary sequence must be highly similar to that of RLM. However, epitope recognition and affinity of a mAb very much depends on its VR conformational structure, which may differ even between two mAb bearing highly similar (but not identical) VR. The availability of reagents highly specific to the RLM VR may offer an unique opportunity to define whether a mAb can or cannot be considered BS to a given RLM. <h3>Objectives</h3> To isolate and characterize phage clone-expressing peptide (pc) which are highly specific for the VR of two anti-TNF-α RLP namely mAb Infliximab (Inf) and Golimumab (Gol). <h3>Methods</h3> Cross-inhibition ELISA on recombinant TNF-α (rTNF-α) was performed to define the spatial relationship among the epitopes detected by mAb. mAb-specific phage clones expressing peptide (pc) were obtained by the panning of a phage peptide display library with TNF-a specific mAb. Characterization of pc-specificity and of the spatial relationship between pc- and the TNF-a-binding site on the variable region of mAb was assessed by binding and inhibition assay. <h3>Results</h3> mAb Inf and Gol specifically and dose-dependently cross-inhibited each to the other in the binding to rTNF-a, indicating the recognition by these 2 mAb of the same or two distinct spatially related epitopes on TNF-a. The panning of mAb Inf and Gol with a phage peptide display library resulted in the isolation of one Inf-specific pc (pcInf) and three Gol-specific pc (pcGol1 to 3). Binding assay showed that pcInf and the three pcGol specifically reacted with the corresponding mAb. Furthermore, pcInf and pcGol3 specifically and dose-dependently inhibited the binding of the corresponding mAb to rTNF-α, suggesting the recognition by the pc of the corresponding mAb antigen-combining site. Finally, pcInf and all three pcGol did not react with two additional TNF-a antagonists, suggesting that they are highly specific for mAb Inf and Gol respectively. <h3>Conclusions</h3> The highly specificity of the pc described indicates that they can be eventually employed to predict similarity between a newly synthesized BSM and the claimed RLM, based on the BSM reactivity (or the lack of reactivity) with RLM-specific pc. <h3>Disclosure of Interest</h3> None declared
AB0179 Degradation of type VII collagen (C7M) is associated with systemic sclerosis – development of a novel neo-epitope specific assay
Authors: J Sand, P Juhl, L Iversen, T Karlsmark, M Karsdal, A-C Bay-Jensen, M Mogensen, AS Siebuhr, D Leeming
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Type VII collagen (col7) is the main component of the anchoring fibrils that connects the basement membrane to the underlying interstitial matrix and has mainly been investigated for its role in blistering skin diseases. It has been investigated for its role in dystrophic epidermolysis bullosa, a severe skin disease. Furthermore, increased levels of type VII collagen in skin has been reported for patients with systemic sclerosis (SSc). <h3>Objectives</h3> The objective was to develop and characterize a blood-based marker assessing col7 degradation in patients with SSc. <h3>Methods</h3> We identified a specific fragment of col7 in serum from COPD patients, which was not found in controls, using mass spectrometry. A monoclonal antibody was raised against the first ten amino acids of the neo-epitope (KLH-CGG-GPPGPPGRLV) and employed in a competitive ELISA (C7M). The C7M assay was validated technically and was subsequently evaluated in 2 cohorts including SSc patients. The first cohort (SSc#1; n=35) consisted of early (&lt;2 years of SSc symptoms; n=16) and late (&gt;10 years of disease with stable skin for at least 6 months, n=19) diffuse SSc patients, while the second cohort (SSc#2; n=119) consisted of limited (n=78) and diffuse (n=41) SSc patients. Serum C7M levels were likewise measured in healthy subjects and compared to the levels of SSc patients using the Kruskal-Wallis test with Dunn9s multiple comparisons test comparing healthy individuals with the two SSc cohorts. <h3>Results</h3> A technically robust competitive ELISA (C7M), which was highly specific for a col7 fragment was developed. The assay showed acceptable inter- (13%) and intra-assay (9%) variation, linearity (102% dilution recovery), analyte stability (102% recovery after 4 freeze/thaw cycles), and interference. The C7M marker was evaluated by comparing serum levels in healthy donors with patients with SSc (Figure). Serum C7M levels were not associated with age, gender, BMI, or disease duration. The geometric mean serum C7M level in healthy donors was 4.6 ng/mL (95% CI 3.7–5.6 ng/mL). The geometric mean serum C7M levels were significantly elevated in both cohorts of patients with SSc (SSc#1, 13.6 ng/mL [95% CI 11.1–16.5], p&lt;0.0001; SSc#2, 9.2 ng/mL [95% CI 8.3–10.2], p&lt;0.0001). Furthermore, a significant difference were observed between the two cohorts (P=0.05). <h3>Conclusions</h3> The C7M ELISA enabled quantification of type VII collagen degradation in serum. Elevated serum C7M levels indicated that the remodeling of type VII collagen was significantly increased in patients with SSc, suggesting a pathological role. <h3>Acknowledgements</h3> We thank Biogen Idec9s SSc department for their contribution. <h3>Disclosure of Interest</h3> None declared
THU0540 Efficacy and safety of adalimumab in behÇet's disease related uveitis: a multicenter retrospective observational study
Authors: C Fabiani, A Vitale, G Emmi, L Vannozzi, G Lopalco, S Guerriero, I Orlando, R Franceschini, D Bacherini, L Cimino, A Soriano, B Frediani, M Galeazzi, F Iannone, C Salvarani, L Cantarini
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Current information on the use of adalimumab (ADA) in the treatment of ocular Behçet9s disease (BD) is still based mainly on small series or case reports; nonetheless preliminary evidence is promising. <h3>Objectives</h3> The study aim was to evaluate the efficacy of ADA in a large series of BD-related uveitis. <h3>Methods</h3> We performed a multicenter retrospective observational study including 40 selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end-point was: reduction of ocular inflammatory flares. Secondary end-points were: improvement of Best Corrected Visual Acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. <h3>Results</h3> During the first 12 months of ADA therapy the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (<i>p</i>&lt;0.0001). Similarly BCVA improved if compared to baseline (7.4±2.9 versus 8.5±2.1, <i>p</i>=0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27±42.8 microns at the end of follow up (<i>p</i>&lt;0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3 and 12-month follow-up if compared to baseline (<i>p</i>&lt;0.0001 and <i>p</i>=0.006, respectively). <h3>Conclusions</h3> ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation. <h3>Disclosure of Interest</h3> None declared
AB1211-HPR The use of subcutaneous methotrexate in polish patients with rheumatoid arthritis
Authors: M Przygodzka, K Sikorska-Siudek, R Radomski, S Bojanowski
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Methotrexate (Mtx) should be the drug of the first choice in rheumatoid arthritis (RA) if there are no contraindications to use it. The efficacy of Mtx is measured by remission or low disease activity and depends on the dose taken. Higher doses (25–30 mg/week) are more effective, but intolerance is the main cause of discontinuation of oral treatment. Subcutaneous Mtx is efficient alternative in those cases. <h3>Objectives</h3> The aim of this study was to evaluate subcutaneous Mtx use frequency in Polish patients and change oral form for subcutaneous as well. <h3>Methods</h3> The disease activity was assessed by Disease Activity Score 28 (DAS 28) during the first visit (V1) and after 3 months therapy (V2) and compliance with therapy as well. <h3>Results</h3> There were 194 RA patients diagnosed by the ACR and 1997 and/or ACR/EULAR 2010 criteria. 144 patients were treated by oral Mtx (group A) and 50 patients (group B) by subcutaneous Mtx at the time of study enrolment (V1).37 patients of group A (26%) required changes in therapy during V2, 24 (17%) were switched to subcutaneous Mtx (group A1). 6 patients of group B (12%) required change of treatment during V2, including 2 patients (4%) with subcutaneous Mtx, who were switched to oral Mtx.The main cause of changing therapy from oral to subcutaneous was gastrointestinal intolerance of high dose of Mtx. 69 patients (12%) of group A required additional steroid therapy compared to 18 (36%) of group B. Average DAS 28 decreased by 0.58 in group A1 in oral treatment and during the subcutaneous treatment time decreased by next 0.23. In group A1 during oral treatment 14 (58%) patients used 25 mg/week and 20 patients (83%) used 25 mg/week during subcutaneous treatment time. <h3>Conclusions</h3> Patients treatment by oral Mtx often require modification of therapy in comparison to patients treated by subcutaneous Mtx, including more frequent use of steroids The main cause of oral intolerance are ailments of the digestive system. Change of oral to subcutaneous therapy allows administration of higher doses of Mtx and results in decrease of DAS28 in comparison to the patients continuing their oral treatment. <h3>Disclosure of Interest</h3> None declared
Erratum: The availability of jobs in the biopharmaceutical industry is 45-fold greater for hematology oncology than medical specialties
Authors: V Kaestner, V Prasad
Journal: Blood Cancer Journal (2017)

Correction to: Blood Cancer Journal (2017) 7, e609; doi:10.1038/bcj.2017.91. Published online 15 September 2017 In our paper, the title refers to job advertisements (as articulated clearly in the text) and not jobs per se. The title should read ‘Job postings for biopharmaceutical industry in medicaljournals is 45-fold greater for hematology oncology than medical specialties.
Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells
Authors: Alejandro V. Villarino, Giuseppe Sciumè, Fred P. Davis, Shigeru Iwata, Beatrice Zitti, Gertraud W. Robinson, Lothar Hennighausen, Yuka Kanno, John J. O’Shea
Journal: The Journal of Experimental Medicine (2017)

Innate lymphoid cells (ILCs) patrol environmental interfaces to defend against infection and protect barrier integrity. Using a genetic tuning model, we demonstrate that the signal-dependent transcription factor (TF) STAT5 is critical for accumulation of all known ILC subsets in mice and reveal a hierarchy of STAT5 dependency for populating lymphoid and nonlymphoid tissues. We apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in natural killer (NK) cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15. We also uncover surprising features of STAT5 behavior, most notably the wholesale redistribution that occurs when NK cells shift from tonic signaling to acute cytokine-driven signaling, and genome-wide coordination with T-bet, another key TF in ILC biology. Collectively, our data position STAT5 as a central node in the TF network that instructs ILC development, homeostasis, and function and provide mechanistic insights on how it works at cellular and molecular levels.