tbuckley/cabot-search huggingface dataset:
THU0036 Abatacept increases regulatory b cell effect on t cell proliferation through the production of il-10 and tgf-Βeta in vitro and in rheumatoid arthritis patients
Authors: G. Carvajal Alegria, P. Gazeau, A. Saraux, V. Devauchelle-Pensec, D. Cornec, J.-O. Pers, P. Pochard
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Abatacept is a CD152 agonist known to inhibit T cell proliferation but recent data suggest that it could act directly on B cells.<sup>1–2</sup> <h3>Objectives</h3> To demonstrate the effect of Abatacept (versus IgG control) on regulatory functions of B cells on T cell proliferation in an established <i>in vitro</i> co-culture model. To evaluate its role, <i>in vivo</i>, by measuring the regulatory functions of B cells from rheumatoid arthritis patients before and after the Abatacept treatment. <h3>Methods</h3> Peripheral and tonsilar T cell and B cell from healthy controls were purified. The biotinylation of Abatacept was used to study its binding on T and B cells by flow cytometry and confocal microscopy. A well-established co-culture model between CpG-stimulated B cells and anti-CD3/anti-CD28 stimulated T cells was set up in which Abatacept or an IgG control was added to evaluate any change in B cell regulatory functions. Activation markers (e.g. CD25, CD69, CD40, CD152) and regulation markers (e.g. FoxP3, TGF-β) were assessed by flow cytometry. Similar analysis were also performed on rheumatoid arthritis patients before and three months after Abatacept therapy. All patients gave their informed consent. <h3>Results</h3> Abatacept increases the inhibition of T cell proliferation by B cells compared to IgG control in the co-culture model (p=0.03). Interestingly, alone, Abatacept does not modify T cell proliferation. This can be explained by the increase in IL-10 and TGF-β producing B cells and the CD152 expression. Abatacept is able to bind B cells at day 0 of co-culture and B and T cells at day 4.5 of co-culture. Abatacept has a direct effect on B cells by increasing the CD25 (p=0.03) and CD152 expression (p=0.02) reflecting a higher activation level. Nevertheless, Abatacept had no direct effect on B cell proliferation. In RA patients, the treatment with Abatacept resulted in an increased regulation of T cell proliferation and this effect is related to a higher percentage of IL-10 secreting B cells 3 months after the therapy (p=0.03). <h3>Conclusions</h3> In our <i>in vitro</i> and <i>in vivo</i> models, Abatacept has a direct effect on B cells leading to an increase capability of regulation of T cell proliferation which directly linked to higher production of IL-10 and TGFβ. <h3>References</h3> [1] Gazeau, et al. Rheumatology (Oxford)2016Jun;55(6):1138–40. [2] Carvajal Alegria, et al. Ann Rheum Dis2016Nov;75(11):e73. <h3>Disclosure of Interest</h3> None declared
Circumferential treatment of long-segment Barrett’s esophagus using the next-generation cryoballoon
Authors: Arvind Trindade, Marcia Canto
Journal: Endoscopy (2019)

A 71-year-old man was referred for ablation of a long segment of Barrett’s esophagus, 6 cm in length, with confirmed multifocal low grade dysplasia. He was offered radiofrequency ablation (RFA) but declined this treatment as a family member had experienced extreme pain associated with RFA. Given cryotherapy is efficacious for Barrett’s ablation [1] and is associated with less pain than RFA [2] [3], the patient was offered cryotherapy, which he accepted.
SAT0692 Breastfeeding is not associated with anti-citrullinated antibodies development in individuals at risk for rheumatoid arthritis
Authors: D. Alpizar-Rodriguez, M. Ruediger, B. Möller, J. Dudler, A. Ciurea, P. Zufferey, D. Kyburz, U. Walker, I. von Mühlenen, P. Roux-Lombard, C. Lamacchia, C. Gabay, A. Finckh
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> <b>'</b>Systemic autoimmunity associated with rheumatoid arthritis' (RA), is a pre-clinical stage preceding the onset of clinical RA, characterised by the presence of autoantibodies, such as anti-citrullinated protein antibodies (ACPA) or anti-carbamylated protein antibodies (antiCarP). Breastfeeding has been proposed as a protective factor for RA development,<sup>1</sup> but there are some controversies.<sup>2</sup> To establish the causal role of a putative risk factor, longitudinal studies are needed, in particular in the pre-stages of RA development. <h3>Objectives</h3> To <b>s</b>tudy the association between breastfeeding and the development of systemic autoimmunity associated with RA. <h3>Methods</h3> This ongoing prospective study includes individuals genetically at risk of developing RA, namely first-degree relatives of RA patients (RA-FDR). Individuals without clinical evidence of RA were enrolled, and assessed yearly clinically and biologically. We included all RA-FDR women with available ACPA status (anti-CCP 2, 3.1 or 3.0) and information about breastfeeding. The primary outcome was ACPA positivity. The exposure of interest was breastfeeding and duration of breastfeeding (categorised as 0, 1–7 and ≥7 months). The presence of antiCarP was a secondary outcome. We used logistic regression to analyse univariable and multivariable associations. <h3>Results</h3> A total of 882 women were included, of which 57 (6%) were ACPA positive. The characteristics of ACPA positive and negative participants were balanced, except for an older age in ACPA positives (median 52 versus 45 years; table 1). In the univariable analysis, ACPA positivity was not significantly associated with breastfeeding (OR 1.5, p=0.16) or with breastfeeding duration (OR=1.8, p=0.14). In the multivariable analysis adjusted by age, smoking, number of pregnancies and years of education, there was a weak, but not significant, association between breastfeeding for more than 7 months and ACPA positivity (OR 2.16, p=0.10). Among 728 women with available antiCarP results, 70 (10%) were positive, of which 27 (40%) breastfed. Breastfeeding for more than 7 months was not significantly associated with antiCarP in univariable or multivariable analyses (OR 1.3, p=0.52 and OR 1.9, p=0.16, respectively). <h3>Conclusions</h3> Among women at risk of RA, breastfeeding was not associated with the presence of ACPA or antiCarP. Our results do not support a protective role of breastfeeding in the development of systemic autommunity associated with RA. <h3>References</h3> [1] Orellana C, et al. Ann Rheum Dis2017;76:1845–52. [2] Berglin E, et al. Scand J Rheumatol2010;39:454 -60. <h3>Disclosure of Interest</h3> None declared
THU0277 Which mri lesions in the sacroiliac joint are associated with the diagnosis of axial spondyloarthritis after 2 years follow up in the echography in spondyloarthritis cohort (ECHOSPA)?
Authors: W.P. Maksymowych, D. Loeuille, S. Wichuk, J. Paschke, O. Judet, M. Breban, M.-A. D’Agostino, R.G. Lambert
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> <h3>Objectives</h3> To assess the baseline distribution and prognostic capacity of MRI lesions in the SIJ of patients diagnosed with axSpA after 2 years follow up in the ECHOSPA cohort. <h3>Methods</h3> Consecutive outpatients with age &lt;50 years and symptoms&gt;3 months suggestive of SpA (inflammatory back pain, peripheral arthritis or inflammatory arthralgia, enthesitis or dactylitis, uveitis with B27 positivity, a family history of SpA) were enrolled in the prospective French ECHOSPA cohort study. The diagnosis of SpA was ascertained by an expert committee, blind to MRI evaluation, after at least 2 years of follow-up. MRI scans from 223 cases were available for evaluation by 2 readers and an adjudicator who assessed MRI lesions in the SIJ according to updated consensus definitions from the ASAS-MRI group. These were recorded in an ASAS consensus-derived eCRF that comprises global assessment (active and/or structural lesion typical of axSpA present/absent) and detailed scoring of individual lesions (SPARCC SIJ inflammation, SPARCC SIJ structural). Clinical, lab, and imaging variables associated with the diagnosis of axSpA at 2 years were first identified by univariate regression. A base model of all clinical/lab variables associated with axSpA was included as a group in multivariate logistic regression models that tested the independent association with MRI lesions. <h3>Results</h3> Mean age of the 223 cases was 39.6 (10.5) years, mean symptom duration was 2.5 (4.1) years, 49.5% were HLA-B27 +and 63.7% were female. Primary inclusion criterion was IBP in 53%, IA in 27%, ED in 9%, B27 +U in 8% and Fam in 4%. At 2 years follow up, 165 (74%) were deemed to have axSpA. In group comparisons (table 1) and univariate regression, both active and structural MRI lesions were associated with diagnosis of axSpA at 2 years (p=0.03, p=0.01, respectively). Age, B27, and psoriasis were the clinical variables associated with diagnosis of axSpA at 2 years in univariate analysis (all p&lt;0.0001) and were included together with gender in multivariate analyses. Active and structural lesions typical of axSpA and SPARCC BME score ≥2 were each independently associated with diagnosis of axSpA at 2 years (OR(95% CI)- 6.8 (1.4–34.1) (p=0.02); 17.9 (2.2–146.6) (p=0.007); 4.9 (1.3–18.4) (p=0.02). With all variables simultaneously added to the model, only structural lesions were significantly associated. <h3>Conclusions</h3> Assessment of both active and structural lesions on MRI may help determine which patients have axSpA with higher diagnostic certainty over time. <h3>Disclosure of Interest</h3> None declared
Abstract 20445: Highly-Reactive Isolevuglandins Promote Atrial Arrhythmia Susceptibility in Obesity
Authors: Joseph K Prinsen, Prince J Kannankeril, Liudmila V Yermalitskaya, Scott R Jafarian-Kerman, Tatiana N Sidorova, Joey V Barnett, Olivier Boutaud, Alyssa H Hasty, Katherine T Murray
Journal: Circulation (2016)

Introduction: Obesity is a powerful independent risk factor for atrial fibrillation (AF) with a 5% risk of AF for every unit of BMI increase. Recent evidence reveals structural abnormalities in est...
Performing an Inadvertent Procedure
Authors: Arjun Gupta, Snigdha Jain, Carol Croft
Journal: JAMA (2019)

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SAT0649 Correlation between clinical manifestations and 18f-fdg uptake in patients with polymyalgia rheumatica
Authors: D. Prieto-Peña, J. Loricera, I. Martínez-Rodríguez, J. Banzo, M. Calderón-Goercke, V. Calvo-Río, C. González-Vela, M. González-Gay, J. Hernández, R. Blanco
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Polymyalgia rheumatica (PMR) is an inflammatory disease characterised by pain and stiffness of the neck, shoulder and pelvic girdles. It can also be accompanied by other non-specific symptoms such as inflammatory low back pain, diffuse lower limb pain and constitutional syndrome. The role of <sup>18</sup>F-FDG PET/CT is increasing in the diagnosis of PMR but it remains unknown if there is a correlation between clinical symptoms and <sup>18</sup>F-FDG uptake. <h3>Objectives</h3> Our aim was to asses if the localization of pain of patients with PMR correlates with <sup>18</sup>F-FDG uptake in the corresponding region of interest. <h3>Methods</h3> Retrospective study of 75 patients with PMR and their respective PET/CT scans from a referral centre. PMR diagnosis was based on 2012 EULAR/ACR criteria. <h3>Results</h3> We evaluated 75 patients (27 men and 48 women) with a mean age ±SD of 68.2±10.7 years. A PET/CT was performed in all of them. Pattern of F-FDG uptake in patients with different clinical manifestations were summarised in the <b>TABLE</b>. Twenty-two out of thirty-three patients (66.7%) with <sup>18</sup>F-FDG uptake in sternoclavicular joints had shoulder girdle pain. In all patients with morning stiffness (n=11) an increase of <sup>18</sup>F-FDG uptake in shoulders was observed. Twenty-three patients of thirty-two patients (71.8%) with<sup>18</sup>F-FDG uptake in hips had pelvic girdle pain. The remaining localizations of <sup>18</sup>F-FDG uptake in PET/CT scans did not show significant correlations with clinical symptoms. <h3>Conclusions</h3> In patients with PMR, the presence of shoulder girdle pain seems to correlate with F-<sup>18</sup>FDG uptake in sternoclavicular joints, morning stiffness with <sup>18</sup>F-FDG uptake in shoulders and pelvic girdle pain with <sup>18</sup>FDG uptake in hips. No other significant correlations were found between any other symptom and <sup>18</sup>F-FDG uptake. <h3>Disclosure of Interest</h3> None declared
Global Transcriptome Profiling Identifies a Key Mir-185-PAK6 Axis That Promotes Survival of Leukemic Stem Cells and Drug-Insensitive Blasts in BCR-ABL+ Human Leukemia
Authors: Andrew Wu, Lin Hanyang, Katharina Rothe, Min Chen, Jens Ruschmann, Oleh Petriv, Kieran O'Neill, Tobias Maetzig, David Knapp, Naoto Nakamichi, Ryan Brinkman, Inanc Birol, Donna L Forrest, Carl Hansen, R. Keith Humphries, Connie J. Eaves, Xiaoyan Jiang
Journal: Blood (2018)
Chronic hyperammonemia induces peripheral inflammation that leads to cognitive impairment in rats: Reversed by anti-TNF-α treatment
Authors: Tiziano Balzano, Sherry Dadsetan, Jerónimo Forteza, Andrea Cabrera-Pastor, Lucas Taoro-Gonzalez, Michele Malaguarnera, Sara Gil-Perotin, Laura Cubas-Nuñez, Bonaventura Casanova, Agueda Castro-Quintas, Alejandro Ponce-Mora, Yaiza M. Arenas, Paola Leone, Slaven Erceg, Marta Llansola, Vicente Felipo
Journal: Journal of Hepatology (2019)
High Pesticide Exposure Events and Olfactory Impairment among U.S. Farmers
Authors: Srishti Shrestha, Freya Kamel, David M. Umbach, Laura E. Beane Freeman, Stella Koutros, Michael Alavanja, Aaron Blair, Dale P. Sandler, Honglei Chen
Journal: Environmental Health Perspectives (2019)

Background: Olfactory impairment (OI) is common among older adults and independently predicts all-cause mortality and the risk of several major neurodegenerative diseases. Pesticide exposure may impair olfaction, but empirical evidence is lacking. Objective: We aimed to examine high pesticide exposure events (HPEEs) in relation to self-reported OI in participants in the Agricultural Health Study (AHS). Methods: We conducted multivariable logistic regression to examine the associations between HPEEs reported at enrollment (1993–1997) and self-reported OI at the latest AHS follow-up (2013–2015) among 11,232 farmers, using farmers without HPEEs as the reference or unexposed group. Results: A total of 1,186 (10.6%) farmers reported OI. A history of HPEEs reported at enrollment was associated with a higher likelihood of reporting OI two decades later {odds ratio (OR)=1.49 [95% confidence interval (CI): 1.28, 1.73]}. In the analyses on the HPEE involving the highest exposure, the association appears to be stronger when there was a >4-h delay between HPEE and washing with soap and water [e.g., OR=2.07 (95% CI: 1.48, 2.89) for 4–6 h vs. OR=1.39 (95% CI: 1.11, 1.75) for <30 min]. Further, significant associations were observed both for HPEEs involving the respiratory or digestive tract [OR=1.53 (95% CI: 1.22, 1.92)] and dermal contact [OR=1.47 (95% CI: 1.22, 1.78)]. Finally, we found significant associations with several specific pesticides involved in the highest exposed HPEEs, including two organochlorine insecticides (DDT and lindane) and four herbicides (alachlor, metolachlor, 2,4-D, and pendimethalin). HPEEs that occurred after enrollment were also associated with OI development. Conclusions: HPEEs may cause long-lasting olfactory deficit. Future studies should confirm these findings with objectively assessed OI and also investigate potential mechanisms. https://doi.org/10.1289/EHP3713
SIRT1 Mediates Enhanced Mitochondrial Oxidative Phosphorylation in Chronic Myelogenous Leukemia Stem Cells
Authors: Ajay Abraham, Shaowei Qiu, Balu K Chacko, Hui Li, Andrew J Paterson, Jianbo He, Puneet Agarwal, Mansi Shah, Robert S. Welner, Victor M Darley-Usmar, Ravi Bhatia
Journal: Blood (2018)
Long-Term Outcomes Among Patients Discharged From the Hospital With Moderate Anemia
Authors: Nareg H. Roubinian, Edward L. Murphy, Dustin G. Mark, Darrell J. Triulzi, Jeffrey L. Carson, Catherine Lee, Patricia Kipnis, Steven Kleinman, Vincent X. Liu, Gabriel J. Escobar
Journal: Annals of Internal Medicine (2018)

Randomized clinical trial findings support decreased red blood cell (RBC) transfusion and short-term tolerance of in-hospital anemia. However, long-term outcomes related to changes in transfusion practice have not been described.To describe the prevalence of anemia at and after hospital discharge and associated morbidity and mortality events.Retrospective cohort study.Integrated health care delivery system with 21 hospitals serving 4 million members.445 371 surviving adults who had 801 261 hospitalizations between January 2010 and December 2014.Hemoglobin levels and RBC transfusion, rehospitalization, and mortality events within 6 months of hospital discharge. Generalized estimating equations were used to examine trends over time, accounting for correlated observations and patient-level covariates.From 2010 to 2014, the prevalence of moderate anemia (hemoglobin levels between 7 and 10 g/dL) at hospital discharge increased from 20% to 25% (P < 0.001) and RBC transfusion declined by 28% (39.8 to 28.5 RBC units per 1000 patients; P < 0.001). The proportion of patients whose moderate anemia had resolved within 6 months of hospital discharge decreased from 42% to 34% (P < 0.001), and RBC transfusion and rehospitalization within 6 months of hospital discharge decreased from 19% to 17% and 37% to 33%, respectively (P < 0.001 for both). During this period, the adjusted 6-month mortality rate decreased from 16.1% to 15.6% (P = 0.004) in patients with moderate anemia, in parallel with that of all others.Possible unmeasured confounding.Anemia after hospitalization increased in parallel with decreased RBC transfusion. This increase was not accompanied by a rise in subsequent RBC use, rehospitalization, or mortality within 6 months of hospital discharge. Longitudinal analyses support the safety of practice recommendations to limit RBC transfusion and tolerate anemia during and after hospitalization.National Heart, Lung, and Blood Institute.
Genomic Landscape of Pancreatic Adenocarcinoma in Younger versus Older Patients: Does Age Matter?
Authors: Irit Ben-Aharon, Moshe Elkabets, Raphael Pelossof, Kenneth H. Yu, Christine A. Iacubuzio-Donahue, Steven D. Leach, Maeve A. Lowery, Karyn A. Goodman, Eileen M. O'Reilly
Journal: Clinical Cancer Research (2019)

State-of-the-art genomic analyses of pancreatic adenocarcinoma (PDAC) have yielded insight into signaling pathways underlying carcinogenesis. PDAC is characterized by substantial genomic heterogeneity. We aimed to determine whether early-onset PDAC (EOPC; ≤55 years) displays a distinctive molecular landscape from average-age onset PDAC (AOPC; ≥70 years).Three distinct datasets for PDAC were analyzed. In the first, patients undergoing treatment at Memorial Sloan Kettering (MSK) were consented for MSK-IMPACT next-generation sequencing. The second cohort analyzed was The Cancer Genome Atlas (TCGA) dataset for differences in somatic mutations, gene expression, and protein expression. The third dataset was an Australian cohort of PDAC. Clinical data were correlated with genomic analyses.A total of 293 samples were analyzed, yielding 90 patients aged ≤55 years and 203 patients aged ≥70 years. Among the genes known to be associated with carcinogenesis, SMAD4 displayed higher mutation rates in younger patients. Comprehensive transcriptomic analysis of cellular pathways indicated that the TGFβ pathway has increased activation, and the expression levels of phospho-GSK3 were higher in EOPC. Survival outcomes revealed no differences between age groups.These exploratory analyses suggest that there may be somatic gene alterations within the population of patients with early-onset PDAC that involve unique cellular pathways compared with average-onset PDAC. Former studies imply these cellular pathways may play a role in smoking-related PDAC carcinogenesis. Larger genomic datasets are warranted for future evaluation to extend these observations.
SAT0072 Mirna-146a is a key player in bone metabolism and osteoporosis
Authors: V. Saferding, M. Hofmann, J.S. Brunner, M.F. Militaru, A. Puchner, S. Hayer, M. Timmen, R. Stange, J.S. Smolen, S. Blüml
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Micro RNAs (miRNAs) play a crucial role in the regulation of bone metabolism. MiR-146a, an important anti-inflammatory miRNA, was found to negatively impact osteogenesis and bone regeneration <i>in vitro</i>, by controlling the differentiation of mesenchymal stem cells. But to date the role of miR-146a in bone remodelling, its influence on bone stability and development of osteoporosis is not known. <h3>Objectives</h3> The objective of this project is the analysis of the role of miR-146a in bone metabolism. <h3>Methods</h3> Systemic bone, tibiae and femur, of wt and miR-146a deficient animals was assessed histologically and via µCT analysis, over a period of 3 to 18 months of age. Serum cytokine levels were analysed by Elisa. MRNA expression levels in bone were analysed by qPCR. To induce osteoporosis, ovariectomy (OVX) induced bone loss was performed. <h3>Results</h3> When we analysed bone volume of long bones histologically as well as with µCT analysis we detected significantly increased trabecular bone mass in miR-146a deficient compared to wt animals, starting at an age of 6 months. However, cortical thickness of systemic bones from miR-146a knock out animals was significantly reduced compared to control mice. Analysis of serum in aged miR-146a deficient animals displayed elevated activity of bone resorbing osteoclasts as amounts of CTX I in miR-146a<sup>-/-</sup> mice were significantly increased compared to wt animals. Q-PCR analysis of important osteoclast as well as osteoblast marker genes in bones <i>ex vivo</i> displayed elevated expression of signature molecules of both cell types in aged miR-146a deficient mice, suggesting a regulatory role of miR-146a in both osteoclasts as well as osteoblasts. When we induced osteoporosis using the OVX disease model, histological analysis of long bones showed significant trabecular bone loss in ovariectomized wt mice. In contrast, we detected no trabecular bone loss in ovariectomized miR-146a knock out animals, suggesting that loss of miR-146a deficiency protects bone loss induced by oestrogen deficiency. <h3>Conclusions</h3> MiR-146a seems to control bone turnover and miR-146a deficient mice accrue bone over time. Moreover this miRNA has a negative influence on bone loss occurring during oestrogen loss induced osteoporosis. Therefore miR-146a could be possibly used as a therapeutic target in the treatment of osteoporosis. <h3>Disclosure of Interest</h3> None declared