tbuckley/cabot-search huggingface dataset:
THU0621 Comparison of the effect of ANTI-TNF therapy on work disability between patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis over one year– real life data from the czech biologics registry attra
Authors: J Zavada, L Szczukova, J Vencovsky, P Horák, K Pavelka
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To compare the effect of anti-TNF therapy (a-TNF-th) on Work Disability (WD) between RA, PSA and AS. In the Czech Republic (CZ), a-TNF-th is reimbursed for RA if DAS28&gt;5.1 despite therapy with csDMARDs, for PSA if disease is not “adequately controlled” with csDMARDs, and for AS if BASDAI&gt;4 and CRP/ESR elevated above normal. More than 95% of anti-TNF treated patients in CZ are followed up in the ATTRA registry. <h3>Methods</h3> Bionäive patients with RA (n=1085), AS (n=1126) and PSA (n=351) starting a-TNF-th with available baseline data on demography, disease duration and physical function, and on working status at baseline and at 12 months were included in the analysis. Patients older than 60 years, on maternity leave or students were excluded. Work status was self-reported by patients as (A) able to work = [(i) employed, or (ii) unemployed and actively seeking employment], or (B) unable to work = [(iii) on sick leave, or (iv) on disability pension]. Regression analyses were performed to examine the predictors of improvement in WD (change B→A coded as 1, B→A as -1, no change as 0) over 1 year. <h3>Results</h3> Baseline characteristic were significantly different between diagnoses (Table 1). In patients with RA, 60% were able to work at baseline and 61% at 12 month, with PSA 71% and 74% resp., and with AS 72% and 77% resp. The main driver of improvement of WD was a change in the sick leave (RA 6%→2%, PSA 7%→1%, AS 9%→2%). In univariate analyses, diagnosis of AS and younger age at start of a-TNF-th were predictive of improvement in WD. In multivariate analysis, only diagnosis of AS was significantly associated with improvement in WD. <h3>Conclusions</h3> These real life data from CZ show that for improvement of WD, a-TNF-th was most effective in patients with AS. This may be a sequel of disease specific factors or reimbursement policy. <h3>Disclosure of Interest</h3> None declared
Real-time <i>In vivo </i>Diagnosis of Nasopharyngeal Carcinoma Using Rapid Fiber-Optic Raman Spectroscopy
Authors: Kan Lin, Wei Zheng, Chwee Ming Lim, Zhiwei Huang
Journal: Theranostics (2017)

We report the utility of a simultaneous fingerprint (FP) (i.e., 800-1800 cm -1 ) and high-wavenumber (HW) (i.e., 2800-3600 cm -1 ) fiber-optic Raman spectroscopy developed for real-time in vivo diagnosis of nasopharyngeal carcinoma (NPC) at endoscopy.A total of 3731 high-quality in vivo FP/HW Raman spectra (normal=1765; cancer=1966) were acquired in real-time from 204 tissue sites (normal=95; cancer=109) of 95 subjects (normal=57; cancer=38) undergoing endoscopic examination.FP/HW Raman spectra differ significantly between normal and cancerous nasopharyngeal tissues that could be attributed to changes of proteins, lipids, nucleic acids, and the bound water content in NPC.Principal components analysis (PCA) and linear discriminant analysis (LDA) together with leave-one subject-out, cross-validation (LOO-CV) were implemented to develop robust Raman diagnostic models.The simultaneous FP/HW Raman spectroscopy technique together with PCA-LDA and LOO-CV modeling provides a diagnostic accuracy of 93.1% (sensitivity of 93.6%; specificity of 92.6%) for nasopharyngeal cancer identification, which is superior to using either FP (accuracy of 89.2%; sensitivity of 89.9%; specificity of 88.4%) or HW (accuracy of 89.7%; sensitivity of 89.0%; specificity of 90.5%) Raman technique alone.Further receiver operating characteristic (ROC) analysis reconfirms the best performance of the simultaneous FP/HW Raman technique for in vivo diagnosis of NPC.This work demonstrates for the first time that simultaneous FP/HW fiber-optic Raman spectroscopy technique has great promise for enhancing real-time in vivo cancer diagnosis in the nasopharynx during endoscopic examination.
Modern Imaging Techniques in Cardiomyopathies
Authors: M. Fuad Jan, A. Jamil Tajik
Journal: Circulation Research (2017)

Modern advanced imaging techniques have allowed increasingly more rigorous assessment of the cardiac structure and function of several types of cardiomyopathies. In contemporary cardiology practice, echocardiography and cardiac magnetic resonance imaging are widely used to provide a basic framework in the evaluation and management of cardiomyopathies. Echocardiography is the quintessential imaging technique owing to its unique ability to provide real-time images of the beating heart with good temporal resolution, combined with its noninvasive nature, cost-effectiveness, availability, and portability. Cardiac magnetic resonance imaging provides data that are both complementary and uniquely distinct, thus allowing for insights into the disease process that until recently were not possible. The new catchphrase in the evaluation of cardiomyopathies is multimodality imaging, which is purported to be the efficient integration of various methods of cardiovascular imaging to improve the ability to diagnose, guide therapy, or predict outcomes. It usually involves an integrated approach to the use of echocardiography and cardiac magnetic resonance imaging for the assessment of cardiomyopathies, and, on occasion, single-photon emission computed tomography and such specialized techniques as pyrophosphate scanning.
O008 Altered lymph node stromal cells during the earliest phases of rheumatoid arthritis
Authors: C Ospelt, E Karouzakis, J Hähnlein, H Semmelink, R Gay, P-P Tak, D Gerlag, S Gay, L Van Baarsen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiopathogenesis where systemic autoimmunity precedes clinical disease onset. Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSC) play a crucial role in shaping the immune response and maintaining peripheral tolerance. <h3>Objectives</h3> We developed an experimental model for studying the functional capacities of human LNSC during the earliest phases of RA and compared their cellular and molecular characteristics to LNSC from healthy volunteers. <h3>Methods</h3> ACPA +RA patients (n=24), ACPA +RA risk individuals (n=23) and seronegative healthy controls (n=14;HC) underwent ultrasound-guided inguinal lymph node biopsy. Human LNSCs were isolated and expanded <i>in vitro</i> for cellular (flow cytometry), molecular (methylome, transcriptome and microRNA) and functional analyses. <h3>Results</h3> Key LN chemokines CCL19, CCL21 and CXCL13 were induced in LNSCs upon stimulation with TNFα and lymphotoxin α1β2, but to a lesser extent in LNSCs from RA patients. RNA sequencing was performed on LNSC of HC (n=5), ACPA +RA risk individuals (n=6) and ACPA +RA patients (n=4). Of interest, LNSC from ACPA +RA risk individuals and ACPA +RA patients revealed a common significantly differential expressed gene signature compared with HC LNSC. Pathway analysis of this common signature showed, among others, significant enrichment of pathways affecting actin cytoskeleton, focal adhesion and cell junction. Accordingly, in a gel contraction assay LNSC from ACPA +RA risk individuals and RA patients showed impaired collagen contraction compared to healthy LNSC. In RA LNSC a significant enrichment was observed for genes involved in TGFb signalling while in RA-risk LNSC cell cycle genes were differentially expressed compared with HC. DNA methylation analyses revealed common differentially methylated CpG sites (DMS) in LNSC from ACPA +RA patients (n=5) and ACPA +RA risk individuals (n=3) compared with HC (n=4). These DMS were significantly hypomethylated and associated with antigen processing and presentation (HLA-DRB1). <h3>Conclusions</h3> This data point towards alterations in the cytoskeleton and antigen-processing and presentation in LNSC from ACPA+RA risk individuals and RA patients. Further studies are required to investigate the influence of this LNSC abnormality on immune responses. <h3>Disclosure of interest</h3> C. Ospelt: None declared, E. Karouzakis: None declared, J. Hähnlein: None declared, H. Semmelink: None declared, R. Gay: None declared, P.-P. Tak Employee of: Currently: Senior Vice President R and D Pipeline, Global Development Leader and Chief Immunology Officer, GSK, D. Gerlag Employee of: Currently: Head Clinical Unit Cambridge at GSK, S. Gay: None declared, L. Van Baarsen: None declared
FRI0677 Role of nailfold videocapillaroscopy and 22-MHZ doppler ultrasound in the assessment of systemic sclerosis-related digital vasculopathy
Authors: T Schioppo, A Orenti, P Boracchi, O De Lucia, A Murgo, PL Meroni, F Ingegnoli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Microvascular damage plays a critical role in the initiation and perpetuation of systemic sclerosis (SSc). A comprehensive approach should investigate both superficial and deep layers of peripheral microcirculation. In addition to nailfold videocapillaroscopy (NVC), a well-established technique to evaluate outer skin layer vessels, power Doppler ultrasound (PDUS) has been recently used to study microcirculation in the inner levels [1]. <h3>Objectives</h3> To study the severity of microvascular involvement in patients with SSc by using both NVC to measure capillary density (outer layer at the nailfold area) and PDUS to detect perfusion (deeper layers at the nailfold and pulp area). <h3>Methods</h3> 100 SSc consecutive patients fulfilling the 2013 EULAR classification criteria were enrolled. PDUS was performed at the 3rd and 4th finger of the dominant hand after exclusion of ulnar artery occlusion (UAO). In case of UAO non-dominant hand was examined. Ultrasound investigation was performed with Esaote MyLab 70 XVG by means of linear array transducer (10–22 MHz). Power Doppler settings were standardized (Doppler frequency 14.3 MHz, Gain 55%, PRF 750 Hz). PDUS measurements included sagittal scan of nailbed and fingertip qualitatively graded from 1 (no signal) to 4 (marked hyperemia) [2], and resistivity index (RI) of ulnar and radial proper digital arteries. Capillary density (number/mm) was calculated by NVC with magnification 200X performed on two images of the same digits examined by PDUS. <h3>Results</h3> 100 SSc patients, 87 (87%) women, 86 (86%) limited cutaneous SSc, median age 62.2 years old, median disease duration 8 years were evaluated. 7 (7%) patients had UAO. Concordance between fingertip and nailbed perfusion as assessed by PDUS is reported in Table 1. Concordance between fingertip and nailbed perfusion as assessed by PDUS is equal to 0.7398. The lower 97.5% confidence interval limit is 0.6433. Association between capillary density, and fingertip and nailbed perfusion as assessed by PDUS is shown in Table 2. <h3>Conclusions</h3> To our knowledge, this is the first study to correlate NVC and PDUS finding in SSc patients. Fingertip and nailbed PDUS grade concordance was found to be satisfactory. The mean capillary density tends to be greater with respect to grade 1. This is particularly evident comparing grade 4 and grade 1. As such, these two imaging techniques provide different and potentially complementary information on SSc-related peripheral microvascular involvement. There is potential clinical utility in these observations that has yet to be unlocked fully. <h3>References</h3> Lescoat A et al. Arthritis Care Res. 2016;Epub ahead of print. Newman JS et al. Radiology. 1996,198:582–584. <h3>Disclosure of Interest</h3> None declared
THU0184 Adherence profiles to methotrexate of patients with rheumatoid arthritis (RA) eligible for biologics: typologies from forget, a cross-sectional survey of 244 patients
Authors: C Beauvais, V Hautin-Monteil, M-C Ducrot, R-M Flipo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Adherence to Methotrexate (MTX) is not optimal in RA patients [1]. Conflicting determinants of adherence have been identified in literature. Our hypothesis was that the discordant results were related to different typologies of patients. <h3>Objectives</h3> Determine the Methotrexate adherence profiles of patients with RA eligible for biologics. <h3>Methods</h3> The FORGET survey carried out in 2016 was aimed to assess the MTX adherence rate of RA patients, insufficient responders to MTX, biologic-naive, when an initiation of biologics was being considered. Non-adherence was defined as a compliance rate &lt;80% according to the CQR19 (Compliance Questionnaire for Rheumatology) [2]. The factors tested were socio-demographic characteristics, DAS 28, RAID, CQR responses, beliefs, voluntary or involuntary dose skipping, social and medical support. <h3>Results</h3> Of the 244 patients analyzed, the non-adherence rate was 34%. The rather weak correlation between adherence (CQR) and the disease impact (RAID) tended to confirm the hypothesis of different profiles. Four typologies of patients were determined. Groups G1 and G2 were non-adherent patients with high (G1) or lower (G2) impact. Groups G3 and G4 were patients with good adherence with high (G3) or lower impact (G4. Significant adherence factors were found for these 4 groups (p&lt;0.01) (table). <h3>Conclusions</h3> Four adherence profiles to Methotrexate have been identified. Among the non-adherent patients, 2 topologies are opposed: 1- patients in state of suffering, with low support from relatives, negative beliefs and significant professional impact. 2-patients with less disease impact, who perceived their treatment with constraints although well tolerated. Detection of patients9 profiles may allow targeted strategies to improve or maintain adherence. <h3>References</h3> DiBenedetti D Rheumatol Ther 2015. de Klerk E et al, J Rheumatol 1999. <h3>Acknowledgements</h3> This study was funded by Chugai Pharma France. <h3>Disclosure of Interest</h3> C. Beauvais: None declared, V. Hautin-Monteil Employee of: Roche France, M.-C. Ducrot: None declared, R.-M. Flipo: None declared
Antagonism of EG-VEGF Receptors as Targeted Therapy for Choriocarcinoma Progression <i>In Vitro</i> and <i>In Vivo</i>
Authors: Wael Traboulsi, Frédéric Sergent, Houssine Boufettal, Sophie Brouillet, Rima Slim, Pascale Hoffmann, Mohammed Benlahfid, Qun Y. Zhou, Gianfranco Balboni, Valentina Onnis, Pierre A. Bolze, Aude Salomon, Philippe Sauthier, François Mallet, Touria Aboussaouira, Jean J. Feige, Mohamed Benharouga, Nadia Alfaidy
Journal: Clinical Cancer Research (2017)

Purpose: Choriocarcinoma (CC) is the most malignant gestational trophoblastic disease that often develops from complete hydatidiform moles (CHM). Neither the mechanism of CC development nor its progression is yet characterized. We recently identified endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as a novel key placental growth factor that controls trophoblast proliferation and invasion. EG-VEGF acts via two receptors, PROKR1 and PROKR2. Here, we demonstrate that EG-VEGF receptors can be targeted for CC therapy.Experimental Design: Three approaches were used: (i) a clinical investigation comparing circulating EG-VEGF in control (n = 20) and in distinctive CHM (n = 38) and CC (n = 9) cohorts, (ii) an in vitro study investigating EG-VEGF effects on the CC cell line JEG3, and (iii) an in vivo study including the development of a novel CC mouse model, through a direct injection of JEG3-luciferase into the placenta of gravid SCID-mice.Results: Both placental and circulating EG-VEGF levels were increased in CHM and CC (×5) patients. EG-VEGF increased JEG3 proliferation, migration, and invasion in two-dimensional (2D) and three-dimensional (3D) culture systems. JEG3 injection in the placenta caused CC development with large metastases compared with their injection into the uterine horn. Treatment of the animal model with EG-VEGF receptor's antagonists significantly reduced tumor development and progression and preserved pregnancy. Antibody-array and immunohistological analyses further deciphered the mechanism of the antagonist's actions.Conclusions: Our work describes a novel preclinical animal model of CC and presents evidence that EG-VEGF receptors can be targeted for CC therapy. This may provide safe and less toxic therapeutic options compared with the currently used multi-agent chemotherapies. Clin Cancer Res; 23(22); 7130-40. ©2017 AACR.
FRI0607 Long-term and optimization of infliximab in refractory uveitis associated to behÇet disease. multicentre study of 100 patients
Authors: LC Domínguez Casas, V Calvo-Río, E Beltrán, J S-Bursόn, M Mesquida, A Adán, M Hernandez, F L-Longo, M H-Grafella, E Valls, L M-Costa, A Sellas, J G-Serrano, J Callejas, N Ortego, J Herreras, A Follonosa, O Maíz, A Blanco, I Torre, C F-Espartero, V Jovani, D Peitado, D Díaz-Valle, E Pato, C F-Cid, E Aurrecoechea, M García, M Caracuel, A Atanes, F Francisco, S Insua, S González-Suárez, A S-Andrade, L Linares, F Romero, A García, R Almodovar, E Minguez, C Carrasco, E Raya, M Alcalde, C F-Carballido, F Pagés, M González-Vela, C Fernández-Díaz, N Vegas-Revenga, R Demetrio-Pablo, M González-Gay, R Blanco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To assess the long term efficacy and optimization of Infliximab (IFX) in refractory Uveitis of Behçet Disease (BD) <h3>Methods</h3> Multicentre study of Uveitis associated-BD refractory to conventional immunosupressive drug. Ocular inflammation was evaluated with "SUN criteria" (Am J Ophthalmol 2005;140:509–516) and the macular thickening with OCT. Results are expressed as mean±SD or median [IQR] (comparison, Wilcoxon test) <h3>Results</h3> We studied 100 patients/180 affected eyes (54M/46W), mean age 40.7±10.1. The ocular pattern was panuveitis (n=62), posterior (27) and anterior uveítis (11). Before IFX they received iv MP (28), cyclosporine (75), azathioprine (56), metotrexate (43) and others (33). IFX dose ranged between 3–5mg/kg/4 or 8 weeks. In patients in remission IFX was optimized (n=28) or stopped (n=20). <h3>Conclusions</h3> IFX is an effective long term-treatment in refractory Uveitis of BD. Optimization and even discontinuation of IFX after remission is possible. <h3>Disclosure of Interest</h3> None declared
The chromatin accessibility signature of human immune aging stems from CD8+ T cells
Authors: Duygu Ucar, Eladio J. Márquez, Cheng-Han Chung, Radu Marches, Robert J. Rossi, Asli Uyar, Te-Chia Wu, Joshy George, Michael L. Stitzel, A. Karolina Palucka, George A. Kuchel, Jacques Banchereau
Journal: The Journal of Experimental Medicine (2017)

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency.
Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension
Authors: Edda Spiekerkoetter, Yon K. Sung, Deepti Sudheendra, Valerie Scott, Patricia Del Rosario, Matthew Bill, Francois Haddad, Janel Long-Boyle, Haley Hedlin, Roham T. Zamanian
Journal: European Respiratory Journal (2017)

Pulmonary arterial hypertension (PAH) is a devastating disease characterised by occlusive pulmonary vasculopathy. Activation of bone morphogenetic protein receptor 2 (BMPR2) signalling by FK506 (tacrolimus) reverses occlusive vasculopathy in rodent PAH models. Here, we determined the safety and tolerability of low-level FK506 therapy in stable PAH patients. We performed a randomised, double-blind, placebo-controlled, 16-week, single-centre, phase IIa trial in PAH patients with New York Heart Association functional class II/III symptoms using three FK506 target levels (&lt;2, 2–3 and 3–5 ng·mL −1 ). 23 patients were randomised and 20 patients completed the trial. FK506 was generally well tolerated, with nausea/diarrhoea being the most commonly reported adverse event and no observation of line infections in patients on intravenous prostacyclin therapy. PAH patients had significantly lower BMPR2 expression in peripheral blood mononuclear cells versus healthy controls (n=13; p=0.005), which improved after FK506 treatment. While we observed that some patients responded with a pronounced increase in BMPR2 expression as well as improvement in 6-min walk distance, and serological and echocardiographic parameters of heart failure, these changes were not significant. Low-level FK506 is well tolerated and increases BMPR2 in subsets of PAH patients. These results support the study of FK506 in a phase IIb efficacy trial.