tbuckley/cabot-search huggingface dataset:
SAT0032 Mesenchymal stem cells alleviate experimental autoimmune cholangitis through immunosuppression mediated by galectin-9
Authors: J. Fan, X. Tang, H. Chen, L. Sun, Q. Wang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Mesenchymal stem cells (MSCs) play anti-inflammatory role by secreting some kinds of bioactive molecules. However, the effect of MSCs on chronic autoimmune liver disease, such as primary biliary cholangitis (PBC) and its underlying mechanism remains elusive. <h3>Objectives</h3> The aim of this study was to assess the efficacy of UC-MSCs treatment (UC-MSCT) in 2OA-BSA-induced murine autoimmune cholangitis and explore its underlying mechanisms. <h3>Methods</h3> UC-MSCs were transplanted into experimental autoimmune cholangitis mice. Biochemical and histological analysis were performed based on the blood and liver tissues. The immunomodulatory effects of UC-MSCs and its cytoprotective function were also investigated. <h3>Results</h3> We found that UC-MSCT significantly ameliorated liver inflammation in 2OA-BSA induced autoimmune cholangitis mice, primarily by diminishing Th1 and Th17 responses, and modifying liver chemokine activity. We also found that UC-MSCs significantly repressed the proliferation of CD4 +T cells and suppressed the differentiation of Th1 and Th17 cells, both of which were dependent on galectin-9 (Gal-9). Furthermore, we determined the signal transducer and activator of transcription (STAT) and c-Jun N-terminal kinase (JNK) signalling pathways were involved in the production of Gal-9 in MSCs. <h3>Conclusions</h3> The present study shows that UC-MSCs exert profound inhibitory effects on inflammatory responses and that they ultimately alleviate the liver injury in experimental autoimmune cholangitis mice. Further, we demonstrate that UC-MSCs inhibit Th1 and Th17 cell responses as well as aberrant chemokine activity through Gal-9 mediated immunosuppression. Additionally, our research reveals that the induction of Gal-9 in MSCs is mediated by the involvement of the STAT and JNK signalling pathways. These findings may help in the development of stem cell therapies for the treatment of PBC. <h3>Disclosure of Interest</h3> None declared
Alastair James Watt
Authors: Ruth Taylor
Journal: BMJ (2018)

Alastair James Watt was born in Chingola, Zambia. He excelled at sport and played rugby for Norwich, Barts, University of London, and Saracens. He was a fine athlete, competing for the Hackney Harriers. He still holds the U16’s 400 m record at his school (58.7 seconds).

Alastair became a keen cyclist after one too many rugby injuries. He was known as the “beast” by his fellow riders …
Evaluation of self-collected vaginal specimens for the detection of high-risk human papillomavirus infection and the prediction of high-grade cervical intraepithelial lesions in a high-burden, low-resource setting
Authors: P.J. Toliman, J.M. Kaldor, S.G. Badman, S. Phillips, G. Tan, J.M.L. Brotherton, M. Saville, A.J. Vallely, S.N. Tabrizi
Journal: Clinical Microbiology and Infection (2018)
SAT0352 Prevalence and characteristics of coronary disease and cardiovascular risk factors in a cohort of patients with psoriatic arthritis
Authors: S.A. Rodríguez Montero, N. Plaza Aulestia, M.J. Pérez Quintana, M.L. Velloso Feijoo, J. L
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> We performed a descriptive study of our patients with psoriatic arthritis (PsA) over 40 years old, attending to the presence of coronary disease and cardiovascular risk factors in each group of treatment (DMARDS vs biologic therapy). <h3>Methods</h3> Patients older than 40 years, diagnosed with psoriatic arthritis attending clinics at the Department of Rheumatology were analysed to determine how many of them presented coronary disease. The following information was recorded: age, sex, disease duration and age at the coronary event, HLA-B27 positivity, hypertension, type II diabetes and hyperlipidemia, on medical records and discharge reports for each patient. <h3>Results</h3> All 137 patients were identified from an electronic database. We found a male predominance: 57% versus 43% of women. Mean age 57.05±10.6 years. Of the 137 patients, 82% had only peripheral arthritis, while 18% also showed axial involvement. With regard to the latter subgroup, 16% patients had a positive HLA-B27 test, 56% were HLA-B27 negative and 28% showed lack of HLA-B27 test. Almost all patients (87%) were in DMARDs therapy, while 31% received biologic therapy: etanercept 42%, secukinumab 16%, adalimumab 12%, ustekinumab 12%, infliximab 9,5%, golimumab 4,7% and certolizumab 2%. About 7% of patients didn't receive DMARDS neither biologic therapy, because of intolerance. Results regarding to cardiovascular risk factors, and coronary disease are as follows: <h3>Conclusions</h3> There is solid epidemiologic evidence linking PsA to cardiovascular risk factors and an increased risk of developing cardiovascular disease<sup>1</sup>. Furthermore, over the past two decades it has become increasingly clear that chronic inflammation is an independent risk factor for cardiovascular events. In our study the ratio of ischaemic heart disease for patients with PsA in DMARD therapy is four times higher than that of biologic treatment group. This may be due to the greater percentage of cardiovascular risk factors in the first group, although, the cardioprotective effect of biologic therapies, must be taken into account, as there are some studies that show association between antiTNF and significant reduction in carotid IMT<sup>2</sup>. Proper management of cardiovascular risk requires aggressive control of disease activity. <h3>References</h3> [1] Int. J. Mol. Sci2018;19(1):58. doi:10.3390/ijms19010058 [2] Int J Rheumatol2012;2012:714321. <h3>Disclosure of Interest</h3> None declared
Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy
Authors: Saranya Sridhar, Alexander Luedtke, Edith Langevin, Ming Zhu, Matthew Bonaparte, Tifany Machabert, Stephen Savarino, Betzana Zambrano, Annick Moureau, Alena Khromava, Zoe Moodie, Ted Westling, Cesar Mascareñas, Carina Frago, Margarita Cortés, Danaya Chansinghakul, Fernando Noriega, Alain Bouckenooghe, Josh Chen, Su-Peing Ng, Peter B. Gilbert, Sanjay Gurunathan, Carlos A. DiazGranados
Journal: New England Journal of Medicine (2018)

In efficacy trials of a tetravalent dengue vaccine (CYD-TDV), excess hospitalizations for dengue were observed among vaccine recipients 2 to 5 years of age. Precise risk estimates according to observed dengue serostatus could not be ascertained because of the limited numbers of samples collected at baseline. We developed a dengue anti–nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay and used samples from month 13 to infer serostatus for a post hoc analysis of safety and efficacy.
FLIM reveals alternative EV-mediated cellular up-take pathways of paclitaxel
Authors: H. Saari, E. Lisitsyna, K. Rautaniemi, T. Rojalin, L. Niemi, O. Nivaro, T. Laaksonen, M. Yliperttula, E. Vuorimaa-Laukkanen
Journal: Journal of Controlled Release (2018)

In response to physiological and artificial stimuli, cells generate nano-scale extracellular vesicles (EVs) by encapsulating biomolecules in plasma membrane-derived phospholipid envelopes. These vesicles are released to bodily fluids, hence acting as powerful endogenous mediators in intercellular signaling. EVs provide a compelling alternative for biomarker discovery and targeted drug delivery, but their kinetics and dynamics while interacting with living cells are poorly understood. Here we introduce a novel method, fluorescence lifetime imaging microscopy (FLIM) to investigate these interaction attributes. By FLIM, we show distinct cellular uptake mechanisms of different EV subtypes, exosomes and microvesicles, loaded with anti-cancer agent, paclitaxel. We demonstrate differences in intracellular behavior and drug release profiles of paclitaxel-containing EVs. Exosomes seem to deliver the drug mostly by endocytosis while microvesicles enter the cells by both endocytosis and fusion with cell membrane. This research offers a new real-time method to investigate EV kinetics with living cells, and it is a potential advancement to complement the existing techniques. The findings of this study improve the current knowledge in exploiting EVs as next-generation targeted drug delivery systems.
THU0390 Patients with systemic sclerosis develop focal fibrosis over time, and increased ecv diffuse fibrosis seen in poor prognostic group – a first longitudinal cardiac mri study
Authors: R.B. Dumitru, L.-A. Bissell, B. Erhayiem, G. Fent, E.M. Hensor, A. Giollo, A. Kidambi, J. Greenwood, F. Del Galdo, S. Plein, M.H. Buch
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Subclinical SSc-cardiomyopathy is described in up to 2/3 of the patients when sensitive methods such as cardiac MRI(CMR) are used. The prognostic implications and the natural history of these findings is unknown. <h3>Objectives</h3> To evaluate in SSc patients, free of cardiovascular (CV) risk factors and CV disease (CVD) the prevalence, clinical association and natural history of CMR abnormalities over 3 years. <h3>Methods</h3> 35 SSc patients, fulfilling the ACR/EULAR criteria, with no CVD, diabetes and ≤1 CV risk factor had 2 CMRs, 3 years apart. A 3T CMR with late gadolinium enhancement (LGE), T1 mapping for extracellular volume (ECV) quantification and stress perfusion(data available later)was undertaken. Initial CMR was compared with CMR results of 30 healthy controls(HC). <h3>Results</h3> 35 pts had an initial CMR:26(74%) female, mean(SD) age 55(,<sup><sup>13</sup></sup>15 (43%) dcSSc, 11 (31%) ACA+, 12 (34%) Scl70+,15 with(43%) interstitial lung disease(ILD) and 13 (37%) with history of digital ulcers(DU). 21 (60%) received any DMARD over the 3 year period and 10 (29%) prior treatment with cyclophosphamide. The first CMR(CMR1) of SSc pts vs HC showed higher ECV% values and comparable left ventricle(LV) volumes(table 1). LGE was present in 9/22 pts vs 1/30 HC. 22/35 pts had a second CMR (CMR2) at year 3(Y3). A further 5 pts had evidence of LGE, total of 14 (40%): 7/14 had dcSSc, 6/14 males, 2 ACA positive, 6 Scl70 positive. LGE distributed in the basal and mid segments, mainly in a linear or patchy pattern. Of those with LGE at CMR1 (5/9 pts with LGE on CMR1 had CMR2) no change in the LGE pattern at CMR2 was observed. None of the initial CMR measures associated with LGE development at Y3 (p&gt;0.05). Whilst ECV had an overall decrease, ECV incresed in patients with ILD [mean diff.(CI) 3 (-1,6),p=0.14]and in those with higher mRSS at baseline(r=0.455,p=0.04). A significant decrease over the 3 years was observed in LV end-diastolic volume (LVEDV/BSA), LV end-systolic volume(LVESV/BSA) and left ventricular stroke volume (LVSV/BSA) (table 1). A decrease in LVEDV/BSA was noticed for those with a history of DU[mean diff.(CI) −5(−12,2), p=0.1], ILD[mean diff.(CI) −6(−12,0.5),p=0.07)]and shorter disease duration(r=-0.504, p=0.02). <h3>Conclusions</h3> This longitudinal CMR study in SSc demonstrates that CMR is sensitive to change over time. More individuals developed LGE (of focal fibrosis) despite immunosuppressive treatment, and ECV% (diffuse fibrosis) appeared to worsen in a poor prognostic group. Functional changes were also observed. These data justify larger studies to inform stratification strategy for CMR in SSc, and also provide new insights for further investigation. <h3>Disclosure of Interest</h3> None declared
The European Thoracic Oncology Platform Lungscape project: Clinical outcome data as a basis for molecular correlations in resected non-small cell lung cancer.
Authors: Solange Peters, Walter Weder, Peter Meldgaard, Kenneth John O'Byrne, Ania Wrona, Christophe Dooms, Javier Hernandez-Losa, Antonio Marchetti, Marianne Nicolson, Qiang Tan, Egbert F. Smit, Anne-Marie C. Dingemans, Spasenija Savic, Fiona Helen Blackhall, Paul Baas, Eloisa Jantus-Lewintre, Keith M Kerr, Urania Dafni, Rafael Rosell, Rolf A. Stahel
Journal: Journal of Clinical Oncology (2013)

7514 Background: Lungscape allowed building the largest virtual biobank of radically resected NSCLC with comprehensive annotated clinical data, with the aims of expediting knowledge on biomarkers and facilitating translation of research to the clinic. Methods: 2,403 stage I-III radically resected NSCLC cases from 15 sites with mandatory comprehensive clinical annotations including at least 2 years of follow-up have been collected retrospectively. A systematic data review of every single case was performed. Relapse-free survival (RFS), time to relapse (TTR) and overall survival (OS) have been analyzed overall and by subgroups. Results: Median age of the cohort is 66 years, with 35% women, and respectively 14%, 32% and 49% never, current and former smokers. Histological types included 52% adenocarcinoma, 40% squamous cell carcinoma, and 4.5% large cell carcinoma and some rarer/mixed subtypes. As shown in the Table, median RFS, TTR and OS differ significantly by stage (p&lt;0.001). Stage remained a significant predictor for outcome in the multivariate Cox models in the presence of other potential prognostic factors. Conclusions: This is the first report on the full Lungscape series based on 7th TNM classification on OS, RFS and TTR across clinical and pathological subgroups. This complete clinical dataset, in particular the information on TTR will be invaluable to investigate the impact of molecular characteristics on outcome, allowing refining TNM staging using biomarkers. Ultimately Lungscape will provide a platform for marker-driven trials of novel therapeutics. [Table: see text]
THU0007 Genetic variants in sle susceptibility loci, xkr6 and glt1d1, are associated with childhood-onset sle in a korean cohort
Authors: Y.B. Joo, J. Lim, B.P. Tsao, S.K. Nath, K. Kim, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a polygenic autoimmune disease that occurs in all ages. It has been well documented that younger age of SLE onset is associated with more severe clinical manifestations and worse outcomes. However, impact of genetic variants on age of SLE onset was not fully understood. <h3>Objectives</h3> We investigated a cumulative effect of reported SLE-risk variants on childhood-onset SLE and searched for new risk loci of childhood-onset SLE using a genome-wide SNP analysis. <h3>Methods</h3> We analysed 96 Korean childhood-onset (&lt;16 years old) and 685 adult-onset SLE (≥16 years old) who were previously genotyped by both Immunochip and genome-wide SNP arrays. Individual genetic risk scores (GRS) from well-validated SLE susceptibility loci (45 Asian confirmed non-HLA loci and an HLA-DRB1 amino acid haplotype model) were calculated and tested for their association with childhood-onset SLE. Association of each genetic variant with childhood-onset SLE was analysed using a multivariable logistic regression adjusting for population substructure. <h3>Results</h3> Mean age of SLE onset was 12.5±2.5 years in childhood-onset SLE and 29.0±9.4 in adult-onset SLE. GRS from SLE susceptibility loci was significantly higher in childhood-onset SLE than adult-onset SLE (p=0.001). Two SNPs, rs7460469 in <i>XKR6</i> and rs7300146 in <i>GLT1D1</i>, showed the most significant associations with childhood-onset SLE (p=1.26x10–8, OR=0.18, and p=1.49x10–8, OR=0.35, respectively). Especially, rs7300146 in <i>GLT1D1</i> was the cis expression quantitative trait locus (eQTL) for<i> SLC15A4</i>, which has been known an SLE susceptibility gene in a Chinese population. The model consisting of SLE GRS and the two newly identified loci to predict childhood-onset SLE attained an area under curve (AUC) of 0.71 in a receiver operating characteristics (ROC) curve. <h3>Conclusions</h3> Childhood-onset SLE is associated with a high cumulative SLE-risk effect and two novel SNPs rs7460469 and rs7300146, providing the first predictive model for childhood-onset SLE in Koreans. <h3>References</h3> [1] Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients. Ann Rheum Dis. 2011;70(1):151–156. [2] Risk Alleles for Systemic Lupus Erythematosus in a Large Case-Control Collection and Associations with Clinical Subphenotypes. PLoS Genet. 2011Feb;7(2):e1001311. [3] High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry. Nat Genet. 2016;48:323–330. [4] The HLA-DRβ1 amino acid positions 11–13–26 explain the majority of SLE-MHC associations. Nat Commun, 2014:5:5902. <h3>Disclosure of Interest</h3> None declared
OP0329-HPR Outcomes that matter to people living with inflammatory arthritis; a global standard set, developed by the international consortium for health outcome measurement (ICHOM) working group for inflammatory arthritis
Authors: M. Oude Voshaar, Z. Das Gupta, M.A. Van de Laar, H.E. Vonkeman
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Value-based health care (VBHC) is a framework for improving efficiency of healthcare in which competition on value for patients is the central concept. Public reporting of patient outcomes by healthcare providers is proposed as a mechanism that will accelerate identification and adoption of innovations that increase value, through shared learning and sparking competition on outcomes that matter to patients. A key barrier to the implementation of VBHC in inflammatory arthritis (IA) is the absence of a universally accepted set of patient outcomes and risk adjustment variables that are appropriate and feasible to implement in different healthcare systems worldwide. <h3>Methods</h3> The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary international working group (WG), consisting of 24 experts, including six patient representatives, to develop a standard set of patient-centred outcomes for IA. The process followed a structured approach using a modified Delphi process to reach consensus on 1) medical conditions to be covered by the set, 2) outcome domains, 3) outcome measures, 4) case mix variables and – definitions. Each step was supported by systematic literature reviews and consultation of (external) experts on the topic under consideration. <h3>Results</h3> The WG decided to include rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis in the IA Standard Set. Twenty-four outcome domains were initially identified in the 130 randomised trial reports and 28 qualitative studies that were found in the systematic literature reviews. Ultimately, pain, fatigue, activity limitations, overall physical and mental wellbeing, work/school/housework ability and productivity, inflammatory disease activity including therapeutic response (i.e. has the patient achieved the treatment target?), and serious adverse events were included. The measurement properties of 21 patient-reported outcome measures were assessed for all of the included domains. 20 of these were linked to an item response theory-based common reporting metric. This allows users of the ICHOM IA set to choose their preferred instrument while allowing comparison of outcomes. A number of risk adjustment variables and time points for collection were recommended to allow global benchmarking. <h3>Conclusions</h3> We present the ICHOM standard set of outcomes for Inflammatory Arthritis, that we encourage providers of care to implement to facilitate global comparison of outcome data and stimulate shared learning. <h3>Disclosure of Interest</h3> None declared
Social Network Characteristics Are Associated With Type 2 Diabetes Complications: The Maastricht Study
Authors: Stephanie Brinkhues, Nicole H.T.M. Dukers-Muijrers, Christian J.P.A. Hoebe, Carla J.H. van der Kallen, Annemarie Koster, Ronald M.A. Henry, Coen D.A. Stehouwer, Paul H.M. Savelkoul, Nicolaas C. Schaper, Miranda T. Schram
Journal: Diabetes Care (2018)

OBJECTIVE The relation between clinical complications and social network characteristics in type 2 diabetes mellitus (T2DM) has hardly been studied. Therefore, we examined the associations of social network characteristics with macro- and microvascular complications in T2DM and investigated whether these associations were independent of glycemic control, quality of life, and well-known cardiovascular risk factors. RESEARCH DESIGN AND METHODS Participants with T2DM originated from the Maastricht Study, a population-based cohort study (n = 797, mean age 62.7 ± 7.6 years, 31% female). Social network characteristics were assessed through a name generator questionnaire. Diabetes status was determined by an oral glucose tolerance test. Macro- and microvascular complications were defined as a history of cardiovascular disease and the presence of impaired vibratory sense and/or retinopathy and/or albuminuria, respectively. We assessed cross-sectional associations of social network characteristics with macro- and microvascular complications by use of logistic regression adjusted for age, HbA1c, quality of life, and cardiovascular risk factors, stratified for sex. RESULTS A smaller network size, higher percentages of family members, and lower percentages of friends were independently associated with macrovascular complications in both men and women. A smaller network size and less informational support were independently associated with microvascular complications in women, but not in men. CONCLUSIONS This study shows that social network characteristics were associated with macro- and microvascular complications. Health care professionals should be aware of the association of the social network with T2DM outcomes. In the development of strategies to reduce the burden of disease, social network characteristics should be taken into account.
DIAGNOSIS OF SUPERFICIAL NON-AMPULLARY DUODENAL EPITHELIAL TUMORS USING MAGNIFIED ENDOSCOPY WITH NARROW-BAND IMAGING
Authors: N Kakushima, M Yoshida, K Takizawa, M Tanaka, N Kawata, S Ito, K Imai, K Hotta, H Ishiwatari, H Matsubayashi, Y Yamaguchi, H Ono
Journal: Endoscopy (2018)

Endoscopic diagnosis to differentiate between low grade adenoma (Vienna category 3, C3) and high grade adenoma/intramucosal carcinoma (C4/5) among superficial non-ampullary duodenal epithelial tumors (SNADET) is important to judge the appropriate treatment. Using magnified endoscopy with narrow-band imaging (MNBI), we have previously extracted 8 MNBI combinations of mucosal and vascular patterns and reported that the presence of multiple combinations within a lesion is suggestive of C4/5 (sensitivity 91%, specificity 100%) (APDW 2017). However, inter-observer agreement of 8 combinations was not satisfactory. The aim of this study was to establish an easier MNBI diagnostic approach for SNADET.