tbuckley/cabot-search huggingface dataset:
SP0028 Effects of inflammation on bone in inflammatory arthritis
Authors: E.M. Gravallese
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Research in my laboratory is devoted to the study of the pathogenesis of rheumatoid arthritis (RA), with a particular interest in the fundamental mechanisms of bone and cartilage destruction. Key research findings include the identification of osteoclasts as the cell type responsible for bone destruction in RA, and receptor activator of NF-kB ligand (RANKL) as the critical cytokine produced by cells within RA synovial tissues that promotes osteoclastogenesis. More recently, we have identified the inhibitory effects of synovial inflammation on bone formation in RA, and focused on the effects of inflammation in inhibiting the Wnt signalling pathway, resulting in the impairment of osteoblast function. We have also studied the mechanisms that prevent healing of bone erosions in RA, and will discuss a completed clinical trial that addresses the question of erosion healing. Mechanisms of bone loss in RA will be contrasted to mechanisms of bone formation in spondyloarthritis. Finally, we have identified specific pathways in the innate immune system that regulate bone remodelling in the setting of inflammation, and these appear to be directly relevant to inflammatory arthritis. This lecture will thus cover what we have learned about basic mechanisms, and will discuss the clinical implications of this work for the practicing physician. <h3>Disclosure of Interest</h3> E. Gravallese Grant/research support from: Abbvie, Lilly, Pfizer (all completed), Consultant for: Sanofi/Genzyme, Employee of: New England Journal of Medicine
SP0110 Autoantibody standardisation in rheumatic diseases. the role of the european consensus finding study group on autoantibodies in rheumatic diseases (ECFSG)
Authors: J. Rönnelid
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> The aim of the European Consensus Finding Study Group on autoantibodies in rheumatic diseases (ECFSG), a.k.a the EULAR autoantibody study group, is to achieve a common consensus in autoantibody diagnostics: a laboratory result should be the same, independent of the country or laboratory where the result is obtained.Since 1988, the ECFSG has yearly distributed unknown sera to European laboratories (presently 43) for evaluation in a clinical context. These sera are chosen to reveal differences between different laboratories. The results are discussed in conjunction to the European Workshop for Rheumatology Research (EWRR) every year. Use of reference materials helps to align test results by adopting internationally used measurement units, but reference materials are missing for many autoantibody specificities. Since 2014 an ECFSG focus has been on evaluating samples that might constitute new reference materials for companies producing autoantibody measurement assays, as well as for clinical laboratories. Hitherto investigated autoantibody specificities are provided in the table 1.In my talk I will present the work of ECFSG, including the characterisation of the samples that have constituted raw material for currently available reference materials. I will also tell about our first characterisation of a tentative new reagent sample, that thereafter was produced as reference material by the National Institute of Biological Standards and Control (NIBCS) in the UK. In November 2017 that reagent was endorsed by the World Health Organisation (WHO) to become the new international reference reagent for anti-double stranded DNA (anti-dsDNA) antibodies. <h3>Disclosure of Interest</h3> None declared
Disruption of a −35 kb Enhancer Impairs CTCF Binding and <i>MLH1</i> Expression in Colorectal Cells
Authors: Qing Liu, Julie A.I. Thoms, Andrea C. Nunez, Yizhou Huang, Kathy Knezevic, Deborah Packham, Rebecca C. Poulos, Rachel Williams, Dominik Beck, Nicholas J. Hawkins, Robyn L. Ward, Jason W.H. Wong, Luke B. Hesson, Mathew A. Sloane, John E. Pimanda
Journal: Clinical Cancer Research (2018)

Purpose:MLH1 is a major tumor suppressor gene involved in the pathogenesis of Lynch syndrome and various sporadic cancers. Despite their potential pathogenic importance, genomic regions capable of regulating MLH1 expression over long distances have yet to be identified.Experimental Design: Here, we use chromosome conformation capture (3C) to screen a 650-kb region flanking the MLH1 locus to identify interactions between the MLH1 promoter and distal regions in MLH1-expressing and nonexpressing cells. Putative enhancers were functionally validated using luciferase reporter assays, chromatin immunoprecipitation, and CRISPR-Cas9-mediated deletion of endogenous regions. To evaluate whether germline variants in the enhancer might contribute to impaired MLH1 expression in patients with suspected Lynch syndrome, we also screened germline DNA from a cohort of 74 patients with no known coding mutations or epimutations at the MLH1 promoter.Results: A 1.8-kb DNA fragment, 35 kb upstream of the MLH1 transcription start site enhances MLH1 gene expression in colorectal cells. The enhancer was bound by CTCF and CRISPR-Cas9-mediated deletion of a core binding region impairs endogenous MLH1 expression. A total of 5.4% of suspected Lynch syndrome patients have a rare single-nucleotide variant (G > A; rs143969848; 2.5% in gnomAD European, non-Finnish) within a highly conserved CTCF-binding motif, which disrupts enhancer activity in SW620 colorectal carcinoma cells.Conclusions: A CTCF-bound region within the MLH1-35 enhancer regulates MLH1 expression in colorectal cells and is worthy of scrutiny in future genetic screening strategies for suspected Lynch syndrome associated with loss of MLH1 expression. Clin Cancer Res; 24(18); 4602-11. ©2018 AACR.
Atorvastatin Inhibits the HIF1α-PPAR Axis, Which Is Essential for Maintaining the Function of Human Induced Pluripotent Stem Cells
Authors: Yoshiki Nakashima, Chika Miyagi-Shiohira, Hirofumi Noguchi, Takeshi Omasa
Journal: Molecular Therapy (2018)

We herein report a novel mechanism of action of statin preparations using a new drug discovery method. Milk fat globule-EGF factor 8 protein (MFG-E8) was identified from the secretory component of mouse embryonic fibroblast (MEF) as a cell adhesion-promoting factor effective for screening active cellular agents of human induced pluripotent stem cells (hiPSCs) in vitro using electrochemical impedance. Our analyses showed that atorvastatin did not cause death in myocardial cells differentiated from hiPSCs but reduced the pluripotent cell survival in vitro when using serum- and albumin-free media, and inhibited the ability to form teratomas in mice. This result could have been already the cytopathic effect of atorvastatin, and complete elimination of hiPSCs was confirmed in the xenotransplantation assay. The administration of atorvastatin to hiPSCs caused the expression of hypoxia inducible factor (HIF)1α mRNA to be unchanged at 6 hr and downregulated at 24 hr. In addition, the inhibition of the survival of hiPSCs was confirmed by HIF1α-peroxisome proliferator-activated receptor (PPAR) axis inhibition. These results suggest that the addition of atorvastatin to hiPSC cultures reduces the survival of pluripotent cells by suppressing the HIF1α-PPAR axis. In summary, the HIF1α-PPAR axis has an important role in maintaining the survival of pluripotent hiPSCs.
Endoscopic ultrasonography-guided fine-needle biopsy from the pancreatic head of a patient with Roux-en-Y reconstruction
Authors: Tesshin Ban, Hiroshi Kawakami, Yoshimasa Kubota, Shinya Ashizuka, Kazusato Oshikawa
Journal: Endoscopy (2018)

Although endoscopic ultrasonography-guided fine needle biopsy (EUS-FNB) has been developed, its implementation is still challenging in patients with surgically altered anatomy [1] [2] [3]. A 68-year-old man who had undergone laparoscopic total gastrectomy with Roux-en-Y reconstruction for gastric cancer 40 months previously was admitted to our department. His serum carcinoembryonic antigen (CEA) level was increased at 43.6 ng/mL. Abdominal computed tomography (CT) scanning revealed an obscure mass beside the pancreatic head ([Fig. 1 a]). An 18F-fluorodeoxyglucose positron emission tomography/CT scan revealed abdominal accumulation of tumor near the surgical staples ([Fig. 1 b]).
Rhabdomyolysis during high dose interleukin-2 treatment of metastatic melanoma after sequential immunotherapies: a case report
Authors: Joseph I. Clark, Shams Bufalino, Shruti Singh, Ewa Borys
Journal: Journal for ImmunoTherapy of Cancer (2018)

The treatment options for metastatic malignant melanoma have drastically changed recently,including the increased use of immunotherapeutic agents that offer significant responses. Accordingly, it hasbecome common for sequential administration of such agents. Despite this, no guidelines exist on propersequencing or potential unique toxicities associated with such sequencing.We describe here the first incidence, to our knowledge, of clinically significant rhabdomyolysis associated with high-dose interleukin-2 after prior treatment with ipilimumab, genetically engineered T-cell therapy and subsequent single agent pembrolizumab in a patient with BRAF wild type metastatic malignant melanoma.Further studies into the biology of sequential immunotherapy in the treatment of cancer are warranted.
Beyond maximum grade: modernising the assessment and reporting of adverse events in haematological malignancies
Authors: Gita Thanarajasingam, Lori M Minasian, Frederic Baron, Franco Cavalli, R Angelo De Claro, Amylou C Dueck, Tarec C El-Galaly, Neil Everest, Jan Geissler, Christian Gisselbrecht, John Gribben, Mary Horowitz, S Percy Ivy, Caron A Jacobson, Armand Keating, Paul G Kluetz, Aviva Krauss, Yok Lam Kwong, Richard F Little, Francois-Xavier Mahon, Matthew J Matasar, María-Victoria Mateos, Kristen McCullough, Robert S Miller, Mohamad Mohty, Philippe Moreau, Lindsay M Morton, Sumimasa Nagai, Simon Rule, Jeff Sloan, Pieter Sonneveld, Carrie A Thompson, Kyriaki Tzogani, Flora E van Leeuwen, Galina Velikova, Diego Villa, John R Wingard, Sophie Wintrich, John F Seymour, Thomas M Habermann
Journal: The Lancet Haematology (2018)
OP0234 Infliximab therapy in patients with takayasu arteritis
Authors: E.H. Park, E.Y. Lee, Y.J. Lee, Y.J. Ha, B.Y. Choi, W.-H. Yoo, J.C. Paeng, H.Y. Suh, J.S. Park, S. Shon, Y.W. Song
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Takayasu arteritis (TAK) is a chronic inflammatory disease that predominantly affects the aorta and its main branches. Glucocorticoids (GCs) are the cornerstones of the initial treatment of TAK. However, most patients relapse with steroid withdrawal. <h3>Objectives</h3> To evaluate the efficacy and safety of infliximab (IFX) in Korean patients with active TAK. <h3>Methods</h3> Patients with active TAK were enrolled in a single-centre prospective open label trial. Active disease was defined according to the National Institutes of Health (NIH) criteria. Concomitant GCs were tapered to prednisone ≤10 mg/day or equivalent at 2 weeks prior to the initiation of IFX. Patients received intravenous infusions of IFX, at a starting dose of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks, up to week 46, and were followed up to week 54. At week 30, patients with partial remission received increased dose of IFX by 1.5 mg/kg, and patients who failed with IFX terminated the study. At week 38 and 46, patients with symptom of active disease or high serum level of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), were instructed to increase the IFX dose by 1.5 mg/kg, up to 9.5 mg/kg, at each point. All the patients underwent Positron Emission Tomography-Computed Tomography (PET-CT) at baseline and week 30. The primary efficacy end point was the achievement of partial or complete remission at week 30. <h3>Results</h3> Twelve patients with TAK were enrolled and treated with IFX; 1 patient with study violation was excluded from analysis. At week 30, 3 patients (27.3%) achieved complete remission and 6 patients (54.5%) achieved partial remission. Statistically significant improvements were seen at week 30 for all of major secondary measures, including change from baseline in Indian Takayasu Clinical Activity Score 2010 ITAS 2010 (median 11.0, interquartile range [IQR] 10.0–11.8; 6.0, IQR 5.0–9.0, p=0.004), ITAS.A (14.0, IQR 12.0–14.0; 7.0, IQR 6.0–10.5, p=0.003) and serum levels of ESR (56.0, IQR 44.0–82.5; 26.0, IQR 20.0–56.5, p=0.031) and CRP (1.3, IQR 0.7–2.6; 0.2, IQR 0.1–2.1, p=0.019). PET parameters were significantly reduced, including maximum standardised uptake value (3.50, IQR 3.10–3.84; 3.10, IQR 2.49–3.27, p=0.023), target-to-vein ratio (1.34, IQR 1.13–1.95; 1.31, IQR 1.05–1.45, p=0.032), and target-to-liver ratio (2.38, IQR 1.47–3.05; 1.92, 1.51–2.18, p=0.014) from baseline to week 30. Serum levels of pentraxin-3, soluble human leukocyte antigen-E (sHLA-E), interleukin-6 tended to decrease, while tumour necrosis factor-α level increased after IFX therapy. There were no serious adverse events (SAEs) or AEs necessitating discontinuation of IFX. <h3>Conclusions</h3> Treatment with IFX may lead to remission or improvement with lower glucocorticoid requirement in TAK (clinicaltrials.gov NCT02457585). <h3>Disclosure of Interest</h3> None declared
Impact of a multifaceted prevention program on ventilator-associated pneumonia including selective oropharyngeal decontamination
Authors: C. Landelle, V. Nocquet Boyer, M. Abbas, E. Genevois, N. Abidi, S. Naimo, R. Raulais, L. Bouchoud, F. Boroli, H. Terrisse, J.-L. Bosson, S. Harbarth, J. Pugin
Journal: Intensive Care Medicine (2018)

We describe the impact of a multifaceted program for decreasing ventilator-associated pneumonia (VAP) after implementing nine preventive measures, including selective oropharyngeal decontamination (SOD).We compared VAP rates during an 8-month pre-intervention period, a 12-month intervention period, and an 11-month post-intervention period in a cohort of patients who received mechanical ventilation (MV) for > 48 h. The primary objective was to assess the effect on first VAP occurrence, using a Cox cause-specific proportional hazards model. Secondary objectives included the impact on emergence of antimicrobial resistance, antibiotic consumption, duration of MV, and ICU mortality.Pre-intervention, intervention and post-intervention VAP rates were 24.0, 11.0 and 3.9 VAP episodes per 1000 ventilation-days, respectively. VAP rates decreased by 56% [hazard ratio (HR) 0.44, 95% CI 0.29-0.65; P < 0.001] in the intervention and by 85% (HR 0.15, 95% CI 0.08-0.27; P < 0.001) in the post-intervention periods. During the intervention period, VAP rates decreased by 42% (HR 0.58, 95% CI 0.38-0.87; P < 0.001) after implementation of eight preventive measures without SOD, and by 70% after adding SOD (HR 0.30, 95% CI 0.13-0.72; P < 0.001) compared to the pre-intervention period. The incidence density of intrinsically resistant bacteria (to colistin or tobramycin) did not increase. We documented a significant reduction of days of therapy per 1000 patient-days of broad-spectrum antibiotic used to treat lower respiratory tract infection (P < 0.028), median duration of MV (from 7.1 to 6.4 days; P < 0.003) and ICU mortality (from 16.2 to 13.5%; P < 0.049) for patients ventilated > 48 h between the pre- and post-intervention periods.Our preventive program produced a sustained decrease in VAP incidence. SOD provides an additive value.
AB1462-HPR Activity limitations and perceived health-related quality of life in people with inclusion body myositis – a cross-sectional study
Authors: M Regardt, B. Eriksson, L. Christopher-Stine
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy with muscle weakness around thighs, knees and finger flexion muscles. Most people are 50 years or older at onset and there are more men than women with ratio of 2–3: 1. The diagnosis leads to activity limitations in daily life. <h3>Objectives</h3> The aim of this study was to describe how individuals with IBM describe their activity limitation and how they estimate their perceived health-related quality of life as well as to describe the correlation between activity limitation and experienced health-related quality of life. <h3>Methods</h3> A quantitative cross-sectional study involving a total of 29 people with IBM participated. Data collection was performed in Stockholm Sweden. The Myositis Activities Profile (MAP) were used to measure activity limitation and the Short Form-36 (SF-36) were used to measure experienced health-related quality of life. <h3>Results</h3> Activity limitations were estimated from no difficulty to impossible to do. The activity with the highest value (very difficult) was movement. There was a significant difference between individuals with IBM and Swedish normative references measured with SF-36 in physical function, physical role function, general health and social function (p≤0.01). There were high correlations between SF-36 physical and social function with MAP's movement, household activities, social activity, work/school and leisure (−0.872 ≥r<sub>s≤</sub>-0.702; p≤0.001). <h3>Conclusions</h3> Participants estimated activity limitations in many areas, of which movement was estimated as very difficult. The study demonstrated correlation between activity limitations and the experience of impaired health-related quality of life. In order to make positive impact on the health-related quality of life, it is important to focus on social areas such as family, friends and leisure activities, as well as optimising everyday living with proper mobility tools. <h3>Acknowledgements</h3> We would like to thank all the participant for taking time to be part of this study. We acknowledge The Myositis Association for making this study possible with a fellowship grant. <h3>Disclosure of Interest</h3> None declared
AB1482-PARE Participation in clinical trials has a positive impact on the psychological and employment well-being of patients with inflammatory arthritis
Authors: H Alkoky, C. Tierney, V. Ramasamy, P. Knight, E. Ingram, S.-E. Aconstaninesei, A. Pakozdi, Y. Abbye-Nayake, H. Tahir
Journal: Annals of the Rheumatic Diseases (2018)
SAT0378 The trend of treg and th17 cells changes in p2x7r-regulated acute gouty arthritis model rats
Authors: X.-J. Dai, J.-H. Tao, X. Fang, Q. Lin, M.-Y. Li, Y. Xia, X.-M. Li, X.-P. Li, Y.-P. Wang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> ATP may be the second causative signal for the onset of gout, which acts on P2 × 7R to regulate the development of acute gouty arthritis.<sup>1</sup>Both regulatory T cells and Th17 cells are important in the development and progression of inflammatory diseases.<sup>2</sup> <h3>Objectives</h3> To investigate the effect of P2 × 7R on Treg and Th17 cells in acute gouty arthritis model of rats and its role in acute gouty arthritis. <h3>Methods</h3> Eighty male SD rats were randomly divided into three groups: After establishment of acute gouty arthritis model, rats were given P2 × 7R agonist ATP, P2 × 7R inhibitor BBG and PBS, respectively. The rats were sacrificed at 6 hour, 12 hour, 24 hour, 48 hour and 72 hour after treatment. The spleens of the rats were grinded and the expression of Treg and Th17 cells were detected by flow cytometry. Comparison the levels and the ratio of Treg and Th17 cells at the different time points. <h3>Results</h3> <b>(1)</b>The expression levels of Treg and Th17 in the spleen: After treatment at 12 hour, The expression levels of Treg and Th17 in the ATP group were significantly higher than that in the BBG and control groups (p=0.001, 0.021; p=0.01, 0.025); The expression levels of Treg and Th17 in control group were higher than that in BBG group (p=0.021, 0.044); There were no significant differences in the three groups at 72 hour after treatment (p=0.052,0.116). <b>(2)</b>.The expression trend of Treg and Th17 in different time points: the level of Treg was increased at 6 hour, but decreased gradually at12 h, 24 hour and then increased at 48 hour again; The level of Th17 was increased at 6 hour,12 h and 24 hour, but decreased gradually at 48 hour, 72 hour. <b>(3)</b>. The ratio of Treg/Th17 gradually decreased in the first three time points, increased at 48 hour and 72 hour in three groups. The ratio of Treg/Th17 in ATP group was lower than that in BBG group and control group at 12 hour, with significant difference (p&lt;0.05). But at other four time poins, the ratios were no significant differences among the three groups. <h3>Conclusions</h3> Activation of P2 × 7R decreased the ratio of Treg/Th17 in acute gouty arthritis rat model that showed an acute change trend along with the time, suggesting that P2 × 7R-regulated the ratio of Treg/Th17 cells affected acute gouty arthritis. <h3>References</h3> [1] Tao JH, Zhang Y, Li XP. P2X7R: a potential key regulator of acute gouty arthritis. Semin Arthritis Rheum2013;43(3):376–380. [2] Noack M. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmunity reviews2014;13(6):668–677. <h3>Acknowledgements</h3> This work was supported by grants from the National Natural Science Foundation of China (81671601). <h3>Disclosure of Interest</h3> None declared
SP0054 The contribution of regulatory b cells in protecting rheumatic diseases
Authors: C. Mauri
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> B cells are considered central to the pathogenesis of patients with rheumatic diseases (RD) including Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In addition to producing autoantibodies, B cells suppressing inflammatory responses, known as regulatory B cells (Bregs) are numerically and functionally defective in rheumatic diseases. The production of interleukin 10 (IL-10) classically defines a Breg, however the stability and/or plasticity of this population is not well understood. In addition to producing autoantibodies, B cells suppressing inflammatory responses, known as regulatory B cells (Bregs) are numerically and functionally defective in RD patients. The production of interleukin 10 (IL-10) classically defines a Breg, however the stability and/or plasticity of this population is not well understood. Additionally, IL-10 +B cells have been shown to co-express pro-inflammatory cytokines such as TNFa and IL-6, further complicating Breg classification. Characterising the signals inducing Breg differentiation and the subsequent stability and/or plasticity of this population may aid in understanding the factors contributing to Breg dysfunction in RD patients. Novel findings unravelling the signals required and the stability of B regs versus B effector cells in RDs will be discussed. <h3>Disclosure of Interest</h3> None declared
Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling
Authors: Debanjan Dhar, Laura Antonucci, Hayato Nakagawa, Ju Youn Kim, Elisabeth Glitzner, Stefano Caruso, Shabnam Shalapour, Ling Yang, Mark A. Valasek, Sooyeon Lee, Kerstin Minnich, Ekihiro Seki, Jan Tuckermann, Maria Sibilia, Jessica Zucman-Rossi, Michael Karin
Journal: Cancer Cell (2018)
Validation of a rapid whole blood test for diagnosing Helicobacter pylori infection. Conflicting results from the Helisal test (multiple letters) [2]
Authors: A Duggan, R Logan, R J Robinson, M A Stone, J F Mayberry, B Delaney, Hobbs Fdr., S Wilson, P Moayyedi, Axon Atr.
Journal: BMJ (1997)