tbuckley/cabot-search huggingface dataset:
THU0302 Survival of disease-modifying drugs (DMARD) in patients with recent diagnosis of psoriatic arthritis in daily clinical practice
Authors: D. Freites Nuñez, L. León, Z. Rosales, J. Font, C. Lajas, E. Pato, L. Rodríguez, B. Fernández, J.-A. Jover, L. Abasolo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Psoriatic arthritis (PsA) is a chronic inflammatory disease that benefits from DMARDs, in this regard knowing more about these therapies is a great step forward in the management of these patients in daily clinical practice. <h3>Objectives</h3> To evaluate the survival of DMARDs used in recent diagnose PsA patients as well as the causes of discontinuation and to analyse the possible associated factors. <h3>Methods</h3> Retrospective longitudinal observational study. Subjects: Inception cohort of patients from January 2010 to , December 2014 and followed up to December 2016, diagnosed with PsA according to ICD-10 code. Main outcome: discontinuation of conventional synthetic DMARDs (csDMARDs) and biological originator DMARDs (boDMARDs) due to: Adverse drug reactions (ADRs); Improvement or remission; Inefficacy; Patient`s decision and Physician's decision. Covariables: sociodemographic and clinical. Statistical analysis: To estimate DMARDs discontinuation rates, survival techniques were used, expressing the incidence rate (IR) per 100 patients*year with their respective CI at 95%. Multivarite Cox regression models were performed to analyse the factors associated with DMARDs discontinuation and the results were expressed in Hazard ratio (HR) and 95% CI. <h3>Results</h3> 191 patients with recent diagnosis of PsA were included, with a 379.70 Patients*year follow-up. 50.3% were male, the mean age at diagnosis was 50±14.6 years old. 46.6% of the patients had a history of cutaneous psoriasis. The HLA-B27 was positive in 20% of patients. 50% of the patients started a DMARDs at the first visit. Throughout the follow-up, all patients received csDMARDs and 23 used boDMARDs. The median DMARD per patient was 2[.<sup><sup>1–3</sup></sup> Methotrexate (MTX) was the most used drug 69.7%. According to the treatment regimen, 30% were on combination therapy, the most frequent was antiTNF +MTX (33%). 103 discontinuations were recorded with a IR 27.13 [22.36–32.90] within these, 44 were related with ADRs (IR 11.59 [8.62–15.57]), 24 (IR 6.32 [3.58–11.13]) were due to inefficiency, 9 (IR 2.37 [1.23–4.55]) were registered after remission, 12 (IR 3.16 [1.79–5.56]) by decision of the patient and 12 (IR 3.16 [1.79–5.56]) by doctor's decision. The DMARDs median survival was 1.8 years [1.4–2.7]. Table 1 shows the discontinuation rates for each type of DMARDs and the multivariate analysis for the factors associeted with DMARDs discontinuation is in table 2. <h3>Table 1</h3> <h3>Conclusions</h3> In our study, the DMARD discontinuation rate was 27.13, mainly related with ADRs. We have also found some psychological, clinical and therapy regimen factors that can modify the DMARDs survival on PsA. We observed that MTX, presented the longest survival independent of the rest of the factors. <h3>Disclosure of Interest</h3> None declared
SAT0113 Clusterin serum levels are elevated in patients with early rheumatoid arthritis and predict disease activity and treatment response
Authors: T. Lennerová, H. Mann, O. Růžičková, O. Šléglová, L. Vernerová, M. Tomčík, K. Pavelka, J. Vencovský, L. Šenolt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Clusterin (also known as apolipoprotein J) is an extracellular chaperone that participates in a number of biological processes, including inflammation and apoptosis. Recent data suggest its possible protective role in the development of bone erosions and autoimmune disorders. <h3>Objectives</h3> The aim of our study was to analyze the serum levels of clusterin in patients with early rheumatoid arthritis (RA) and in healthy individuals, and to examine their potential association with disease activity and treatment response. <h3>Methods</h3> The serum levels of clusterin were determined by ELISA (BioVendor) in 56 patients with early RA before and three months after initiation of treatment, and in 56 age/sex-matched healthy subjects. Disease activity was evaluated by Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and 28-joint Disease Activity Score (DAS28). Response to therapy was assessed based on the SDAI/CDAI definition. Receiver operating characteristic (ROC) curve analysis of clusterin levels was performed to predict disease activity and treatment response after six months of treatment. The area under the curve (AUC) and the 95% confidence interval (CI) were calculated. Data are presented as mean±SD. <h3>Results</h3> Clusterin levels at baseline were significantly higher in patients with early RA than in healthy individuals (75.1±12.4 vs 56.7±9.7, p&lt;0.001). After three months of therapy, the concentrations of clusterin decreased and reached levels comparable to those in healthy subjects (57.7±9.7 vs 56.7±9.7, p &gt;0.05). Although there was no association between clusterin levels and disease activity at baseline, clusterin levels positively correlated with SDAI and CDAI at month 3 (r = 0.269, p=0.047 and r = 0.294, p=0.030, respectively) and at month 6 (r = 0.339, p=0.013 and r = 0.318, p=0.021, respectively) after treatment initiation. Using ROC analysis, clusterin baseline levels predicted remission and low disease activity according to SDAI (AUC = 0.709 (95% CI 0.548; 0.869), p=0.019) and CDAI (AUC = 0.829 (95% CI 0.721; 0.937), p&lt;0.001), and major treatment response after 6 months of therapy (AUC = 0.696 (95% CI 0.549; 0.842), p=0.015 for both). <h3>Conclusions</h3> We demonstrate elevated serum concentrations of clusterin in patients with early rheumatoid arthritis and suggest clusterin as a biomarker for predicting disease activity and treatment response. <h3>Acknowledgements:</h3> Supported by the project of MHCR for conceptual development of research organization 00023728, research project SVV 260 373 and project GAUK No. 534217. <h3>Disclosure of Interest:</h3> None declared
ACC/AHA/ASNC Guidelines for the Clinical Use of Cardiac Radionuclide Imaging—Executive Summary
Authors: Francis J. Klocke, Michael G. Baird, Beverly H. Lorell, Timothy M. Bateman, Joseph V. Messer, Daniel S. Berman, Patrick T. O’Gara, Blase A. Carabello, Richard O. Russell, Manuel D. Cerqueira, Martin G. St. John Sutton, Anthony N. DeMaria, James E. Udelson, J. Ward Kennedy, Mario S. Verani, Kim Allan Williams, Elliott M. Antman, Sidney C. Smith, Joseph S. Alpert, Gabriel Gregoratos, Jeffrey L. Anderson, Loren F. Hiratzka, David P. Faxon, Sharon Ann Hunt, Valentin Fuster, Alice K. Jacobs, Raymond J. Gibbons, Richard O. Russell
Journal: Circulation (2003)
Investigative use of bronchoscopy, lavage and bronchial biopsies in asthma and other airways diseases
Authors: S Hurd, E Bleecker, E Regis Mcfadden, H Cleveland, San Bousbey, E Francisco, Rochester Edell, W Eschenbacher, P Godard, R Goldstein, S Holgate, O Hunninghake, Iowa City, A Laitinen, Sweden Lund, L Lichtenstein, ; Prograis, J Rankin, West Haven, ; Sri, C Reed, H Reynolds, R Wood
Journal: European Respiratory Journal (1992)

While bronchoscopy is performed routinely in the clinical practice of pulmonary medicine, additional research applications have been developed using this procedure to obtain cellular and other components of the airway alveolar lining fluid from patients with a variety of lung diseases [1].The results of these studies have enhanced our understanding of the pathogenesis and management of pulmonary disease.Recently, extensive scientific data (over 200 published reports during the last five years) have accumulated, which document that investigative bronchoscopy can be safely performed to study the tracheobronchial tree of individuals with asthma and individuals with other obstructive pulmonary diseases.In subjects with asthma endoscopic procedures that include bronchoalveolar lavage [2, 3, 4], segmental airway lavage [5), mucosal biopsies, endobronchial brushing, and biopsies [6, 7, 8], placement of measurement devices [9] and direct assessment of airway physiology, can be performed when appropriate precautions are observed [10].The research potential for investigative bronchoscopy and instrumentation of the airways is considerable and it is expected that these approaches will continue to provide information about the pathogenesis of airway diseases.An earlier workshop, convened by the National Institutes of Health in 1984, developed guidelines [11] for ensuring the safety of subjects undergoing bronchoscopy and bronchoalveolar lavage.The purpose of the present workshop was to review the vast experience gained since then from the world-wide practice
THU0471 Risk factors of low bone mineral density in patients with systemic sclerosis
Authors: S.V. Monov, D. Monova, M. Stambolova, R. Shumnalieva
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is a multisystem autoimmune disease, characterised by diffuse fibrosis, degenerative changes, and vascular abnormalities in the skin, joints, and internal organs. The effect of systemic sclerosis on bone density is not well understood. <h3>Objectives</h3> The aim of this study is to evaluate the risk factors of low bone mineral density (BMD) and occurrence of fracture and fracture-related mortality in patients with SSc. <h3>Methods</h3> Demographics, disease manifestations of SSc, biological inflammatory parameters, functional disability, scleroderma health assessment questionnaire, immunological status, BMD (lumbar spine and femoral neck), risk factors for low BMD, fractures, and fracture-related mortality were collected in patients with SSc. BMD was measured by using a dual-energy X-ray absorptiometry in lumbar spine (L1-L4) and femoral neck. Fisher's Exact and Student's t-tests were used to evaluate differences between women with and without low BMD. Logistic regression was used for multivariate analysis. <h3>Results</h3> Forty eight consecutive unselected SSc women were approached. The mean age of women was 48,32±15,56 years, the mean disease duration was 10,12±4,78 years, Twenty-nine women (60,42%) had low BMD, of those 11 (37,93%) had osteoporosis, mean BMD in lumbar spine was −2,86±0,38 and in femoral neck was −2,22±0,26. Twenty three (47,92%) women with SSc were postmenopausal. In correlation analysis and in multiple regression models, there were correlations between BMD and longer duration of SSc (p&lt;0,01), family history of osteoporosis (p&lt;0.05), age (p&lt;0,01), menopause (p&lt;0,01), low body mass index (p&lt;0,02), presence of internal organ involvement (p&lt;0,05), malabsorption syndrome (p&lt;0,05), joint involvement (severe joint pain and erosive arthropathy) (p&lt;0,05), and immunological status (positivity of anti-DNA topoisomerase I antibodies) (p&lt;0,05). 4 women (4/29) with low BMD had a fracture, compared to 2 without low BMD. Fracture-related mortality did not occur in any patients. <h3>Conclusions</h3> Our data suggest that women with SSc are at risk of low BMD and fracture, especially when other risk factors for osteoporosis are present. A number of clinically relevant factors (longer duration of SSc, presence of internal organ involvement, joint involvement, immunological status) are associated with low BMD. <h3>Disclosure of Interest</h3> None declared
SAT0016 Il-12 suppress tr1 cells in the sjÖgren’s syndrome
Authors: G. Yao, J. Qi, L. Sun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Sjögren's syndrome (SS) is a systemic autoimmune disorder characterised by lymphocytic infiltration of salivary and lachrymal gland leading to dry mouth and eye dryness progressively. It is known that pro-inflammatory cytokines and dysfunction of immune cells play an important role in the pathogenesis of SS. The regulatory T cell type 1 (Tr1) cells have strong immunosuppressive properties and alleviate inflammatory diseases. However, the role of Tr1 cells in SS and the underlying mechanism is still not fully understood. <h3>Objectives</h3> This study aims to determine the association of Tr1 cells with the disease pathogenesis using a murine model of SS and patients with SS. <h3>Methods</h3> The frequencies of Tr1 cells in blood, cervical lymph nodes and their association with disease severity were determined in SS mice. Since proinflammatory interleukine 12 (IL-12) have the ability to regulate the generation of Tr1 cells, the serum IL-12 and its association with disease severity and Tr1 cells were also examined. The involvement of IL-12 and a Tr1 response was examined by recombinant IL-12 treatment or anti-IL-12 antibody neutralisation in SS mice and monitored for SS development. The mouse naive CD4 +cells were treated with IL-12 under Tr1 polarising condition. The frequency of Tr1 cells and their association with IL-12 and disease activity were verified in SS patients. <h3>Results</h3> Tr1 cells significantly decreased in SS mice and patients with SS, which correlated negatively with disease activity and proinflammatory IL-12 (<b>figure 1A,B</b>). IL-12 suppressed Tr1 cell polarisation <i>ex vivo</i>. SS mice treated with the recombinant IL-12 displayed significantly lower saliva flow rates and pronounced inflammation and tissue damage in salivary glands, accompanying with reduction of Tr1 cells. However, anti-IL-12 antibody treatment profoundly increased the numbers of Tr1 cells and ameliorated the reduction in salivary secretion and inflammation and tissue damage in salivary glands in SS mice (<b>figure <b>1</b>C</b>). <h3>Conclusions</h3> Our findings indicate that proinflammatory IL-12 with its capacity to inhibit Tr1 cell generation may be a critical pathogenic factor in Sjögren's syndrome. Targeting IL-12 and Tr1 cells may be a novel therapeutic strategy for the treatment of Sjögren's syndrome. <h3>Disclosure of Interest</h3> None declared
Diagnostic accuracy of MRE and ultrasound for Crohn's disease – Authors' reply
Authors: Stuart A Taylor, Steve Halligan, Gauraang Bhatnagar, Arun Gupta, Antony Higginson, Andrew Slater, Damian Tolan, Peter Wylie, Ian Zealley, Susan Mallett
Journal: The Lancet. Gastroenterology & hepatology (2019)
AB0350 Temporo-mandibular joint involvement in rheumatoid arthritis
Authors: S. Zrour, H. Mouanaa, A. Arfa, H. Hachfi, M. Jguirim, I. Bejia, T. Mongi, M. Youness, N. bergaoui
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Temporomandibular joint (TMJ) disorder in rheumatoid arthritis (RA) may be associated with significant osteoarticular destruction and may be responsible of significant functional impairment. <h3>Objectives</h3> We aimed in this study to determine the prevalence of TMJ involvement and its correlations with RA parameters. <h3>Methods</h3> We report a descriptive monocentric cross-sectional study of 90 consecutive RA, followed at the Rheumatology department of Monastir Teaching Hospital in Tunisia, during 06 months (November 2016 to April 2017) and 46 matched volunteers. Clinical assessment and stomatological examination were performed in all cases. <h3>Results</h3> Sixty-three RA patients out of 90 (70%) had TMJ involvement. TMJ painful mobilisation, mastication difficulties, swollen TMJ, dental malocclusion and limitation of mouth opening were noted in 55 (81%), 49 (74%), 20 (30.3%), 19 (29%) and 8 (12%) of cases, respectively. Compared with the control group, painful palpation of TMJ (p&lt;0.000) was significantly associated with RA. In RA, TMJ disorder is more common in adults between 40 and 60 years of age, patients with HAQ&gt;0.5 and a high total Vander Heijde Sharp radiographic score (SS). TMJ painful mobilisation is significantly associated with increased body mass index (BMI). Swollen TMJ is significantly associated with age (more frequent in elderly subjects), increased BMI, high RA disease activity (high DAS 28 ESR and/or DAS 28 CRP) and HAQ&gt;0.5. Limitation of mouth opening is significantly associated with age (more common in elderly subjects), overweight, high methotrexate dose (20 mg/day), leflunomide and biotherapy use. Dental malocclusion was significantly associated with high doses corticosteroids (more than 5 mg/day). Mastication difficulties are significantly associated with more than 10 year RA duration, HAQ&gt;0.5 and radiological impairment. <h3>Conclusions</h3> Temporomandibular disorder is frequent in RA (70%). TMJ disorder is observed especially in active (high DAS 28), serious (radiological impairment, HAQ&gt;0.5) and advanced (more than 10 year duration) RA. Physicians must be careful to assess systematically TMJ in RA patients. <h3>Reference</h3> [1] Aliko A, Ciancaglini R, Alushi A, Tafaj A, Ruci D. Temporomandibular joint involvement in rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. International Journal of Oral and Maxillofacial Surgery2011;40:704–9. <h3>Disclosure of Interest</h3> None declared
The intestine responds to heart failure by enhanced mitochondrial fusion through glucagon-like peptide-1 signalling
Authors: Genki Naruse, Hiromitsu Kanamori, Akihiro Yoshida, Shingo Minatoguchi, Tomonori Kawaguchi, Masamitsu Iwasa, Yoshihisa Yamada, Atsushi Mikami, Masanori Kawasaki, Kazuhiko Nishigaki, Shinya Minatoguchi
Journal: Cardiovascular Research (2019)

Abstract Aims Glucagon-like peptide-1 (GLP-1) is a neuroendocrine hormone secreted by the intestine. Its receptor (GLP-1R) is expressed in various organs, including the heart. However, the dynamics and function of the GLP-1 signal in heart failure remains unclear. We investigated the impact of the cardio-intestinal association on hypertensive heart failure using miglitol, an α-glucosidase inhibitor known to stimulate intestinal GLP-1 production. Methods and results Dahl salt-sensitive (DS) rats fed a high-salt diet were assigned to miglitol, exendin (9-39) (GLP-1R blocker) and untreated control groups and treated for 11 weeks. Control DS rats showed marked hypertension and cardiac dysfunction with left ventricular dilatation accompanied by elevated plasma GLP-1 levels and increased cardiac GLP-1R expression as compared with age-matched Dahl salt-resistant (DR) rats. Miglitol further increased plasma GLP-1 levels, suppressed adverse cardiac remodelling, and mitigated cardiac dysfunction. In cardiomyocytes from miglitol-treated DS hearts, mitochondrial size was significantly larger with denser cristae than in cardiomyocytes from control DS hearts. The change in mitochondrial morphology reflected enhanced mitochondrial fusion mediated by protein kinase A activation leading to phosphorylation of dynamin-related protein 1, expression of mitofusin-1 and OPA-1, and increased myocardial adenosine triphosphate (ATP) content. GLP-1R blockade with exendin (9-39) exacerbated cardiac dysfunction and led to fragmented mitochondria with disarrayed cristae in cardiomyocytes and reduction of myocardial ATP content. In cultured cardiomyocytes, GLP-1 increased expression of mitochondrial fusion-related proteins and ATP content. When GLP-1 and exendin (9-39) were administered together, their effects cancelled out. Conclusions Increased intestinal GLP-1 secretion is an adaptive response to heart failure that is enhanced by miglitol. This could be an effective strategy for treating heart failure through regulation of mitochondrial dynamics.
SP0068 Dect imaging in gout – ready for prime time?
Authors: N. Dalbeth
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Dual energy computed tomography (DECT) allows visualisation of urate crystal deposition in people with hyperuricaemia and gout. This technology is increasingly used in clinical practice for gout diagnosis, and can also guide treatment decisions in gout. The diagnostic properties of DECT will be described and compared with other advanced imaging methods such as ultrasonography. The potential for false positive results due to artefact, and false negative results in the case of small urate crystal deposits will be demonstrated. The role of DECT in monitoring of treatment response, understanding mechanisms of disease, and facilitating patient understanding of the condition will be explored. <h3>Disclosure of Interest</h3> N. Dalbeth Consultant for: Kowa, Horizon
CD38-Driven Mitochondrial Trafficking Promotes Bioenergetic Plasticity in Multiple Myeloma
Authors: Christopher R. Marlein, Rachel E. Piddock, Jayna J. Mistry, Lyubov Zaitseva, Charlotte Hellmich, Rebecca H. Horton, Zhigang Zhou, Martin J. Auger, Kristian M. Bowles, Stuart A. Rushworth
Journal: Cancer Research (2019)

Metabolic adjustments are necessary for the initiation, proliferation, and spread of cancer cells. Although mitochondria have been shown to move to cancer cells from their microenvironment, the metabolic consequences of this phenomenon have yet to be fully elucidated. Here, we report that multiple myeloma cells use mitochondrial-based metabolism as well as glycolysis when located within the bone marrow microenvironment. The reliance of multiple myeloma cells on oxidative phosphorylation was caused by intercellular mitochondrial transfer to multiple myeloma cells from neighboring nonmalignant bone marrow stromal cells. This mitochondrial transfer occurred through tumor-derived tunneling nanotubes (TNT). Moreover, shRNA-mediated knockdown of CD38 inhibits mitochondrial transfer and TNT formation in vitro and blocks mitochondrial transfer and improves animal survival in vivo. This study describes a potential treatment strategy to inhibit mitochondrial transfer for clinical benefit and scientifically expands the understanding of the functional effects of mitochondrial transfer on tumor metabolism. SIGNIFICANCE: Multiple myeloma relies on both oxidative phosphorylation and glycolysis following acquisition of mitochondria from its bone marrow microenvironment.See related commentary by Boise and Shanmugam, p. 2102.
PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia
Authors: Zhaohui Gu, Michelle L. Churchman, Kathryn G. Roberts, Ian Moore, Xin Zhou, Joy Nakitandwe, Kohei Hagiwara, Stephane Pelletier, Sebastien Gingras, Hartmut Berns, Debbie Payne-Turner, Ashley Hill, Ilaria Iacobucci, Lei Shi, Stanley Pounds, Cheng Cheng, Deqing Pei, Chunxu Qu, Scott Newman, Meenakshi Devidas, Yunfeng Dai, Shalini C. Reshmi, Julie Gastier-Foster, Elizabeth A. Raetz, Michael J. Borowitz, Brent L. Wood, William L. Carroll, Patrick A. Zweidler-McKay, Karen R. Rabin, Leonard A. Mattano, Kelly W. Maloney, Alessandro Rambaldi, Orietta Spinelli, Jerald P. Radich, Mark D. Minden, Jacob M. Rowe, Selina Luger, Mark R. Litzow, Martin S. Tallman, Janis Racevskis, Yanming Zhang, Ravi Bhatia, Jessica Kohlschmidt, Krzysztof Mrózek, Clara D. Bloomfield, Wendy Stock, Steven Kornblau, Hagop M. Kantarjian, Marina Konopleva, Williams E. Evans, Sima Jeha, Ching-Hon Pui, Jun Yang, Elisabeth Paietta, James R. Downing, Mary V. Relling, Jinghui Zhang, Mignon L. Loh, Stephen P. Hunger, Charles G. Mullighan
Journal: Nature Genetics (2019)
Develop new roles to retain senior GPs, says partnership review
Authors: Abi Rimmer
Journal: BMJ (2019)

GPs considering early retirement should be able to take on different roles that allow them to work in primary care without the pressure of delivering clinical care, a government commissioned review has said.

The review of the GP partnership model, led by Wessex Local Medical Committee chief executive Nigel Watson, published its final report on Tuesday.1 Among its key recommendations, the report called for the number of GPs working both in practices and in roles that support primary care to be increased.

While the interim report recommended a primary care fellowship …
Interferon-alfa2 Treatment of Patients with Polycythemia Vera and Related Neoplasms Impacts Deregulation of Oxidative Stress Genes and Antioxidative Defence Mechanisms. Potential Implications of IFN-Alfa Induced Changes in TP53, NRF2 and CXCR4 for Genomic Instability and CD34+ Mobilisation
Authors: Vibe Skov, Caroline Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Journal: Blood (2018)