tbuckley/cabot-search huggingface dataset:
SAT0136 The influence of hdl-cholesterol and crp on increased insulin resistance and impaired beta-cell function in patients with rheumatoid arthritis
Authors: G. G. Ristić, V. Subota, D. Stanisavljević, B. Glišić, M. Petronijević, D. Stefanović
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Increased CRP in RA pts is associated with lower levels HDL cholesterol. HDL cholesterol may enhance insulin secretion and stimulate glucose uptake into skeletal muscle, adipose tissue, and liver. <h3>Objectives:</h3> To investigate whether low HDL, alone or in combination with CRP, could explain increased insulin resistance (IR) and impaired β-cell function in RA pts in comparison to healthy controls. <h3>Methods:</h3> The study population included 127 nondiabetic subjects (90 RA pts and 37 matched controls). We determined body mass index, waist circumference (WC), and presence of metabolic syndrome (MetS). All pts were on disease modifying antirheumatic drugs, 65.6% on steroids (none on steroids &gt;10 mg/day), and 27.8% on biologic therapy. Laboratory analyses included hsCRP, glucose, insulin, and C-peptide (as a marker of insulin secretion). Insulin resistance (IR) was calculated using the updated Homeostasis Model Assessment (HOMA2-IR), based on fasting plasma glucose and specific insulin concentrations. The output of the HOMA2 model was calibrated to give IR of 1 as normal. HOMA2-B indicates the potential of β-cells to compensate increased IR. Lack of compensatory rise of HOMA2-B implied impaired β-cell function. <h3>Results:</h3> IR was detected in 74.4% of RA pts and in 54.2% controls, p=0.025. RA pts had significantly higher concentration of specific insulin, C peptide, and HOMA2-IR than controls, while HOMA2-B was not statistically different. Both groups were comparable regarding all other factors known to affect glucose metabolism (age, WC, presence of MetS). We found significant differences in inflammation markers between RA pts and controls: ESR 29.5 (14–44) vs. 16.0 (10.0–20.0); hsCRP 5.5 (2.8–15) vs. 3.0 (1.8–3.9); p&lt;0.000 for both, as well as in lipids, especially HDL concentration 1.5±0.4 vs 1.60±0.3, p=0.027 and a number of the pts with low HDL (37.8 vs 13.5%, p=0.007). Univariant regression analysis revealed significant positive effect of HDL on logHOMA2-B (β 0.099, 95%CI 0.029–0.169, p=0.006) and negative, but not significant effect on HOMA2-IR. In the logistic regression, after adjustment for HDL concentration, significant differences for HOMA2-IR and insulin became less important but still persisted (Table), while significance for C peptide became more prominent. When we added the influence of inflammation, this favourable effect of HDL-cholesterol on C-peptide disappeared. <h3>Conclusions:</h3> RA pts had higher IR and impaired β-cell function in comparison to healthy controls. The augmentation of statistical significance for C peptide, as a marker of insulin secretion, after adjustment for low HDL-cholesterol and significant effect of HDL on logHOMA2-B implicate its important role in disturbances of glucose metabolism in RA. <h3>Disclosure of Interest:</h3> None declared
Validation of the WHO-defined 20% circulating blasts threshold for diagnosis of leukemic transformation in primary myelofibrosis
Authors: Mythri Mudireddy, Naseema Gangat, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Ayalew Tefferi
Journal: Blood Cancer Journal (2018)

Leukemic transformation is the most dreaded complication in patients with myeloproliferative neoplasms (MPN); overall risk is estimated at 14% for primary myelofibrosis (PMF), 7% for polycythemia vera (PV) and 4% for essential thrombocythemia (ET) 1 .The dismal prognosis of blast phase MPN (MPN-BP) was recently underlined in a large Mayo Clinic study of 248 informative patients and further validated in a separate cohort of 162 cases recruited from multiple Italian institutions 2 .Current treatment approaches for MPN-BP, including allogeneic hematopoietic stem cell transplant (HCT), are largely ineffective in securing long-term survival 2 .On the other hand, HCT has been shown to produce long-term remissions in ~50% of patients with myelofibrosis, if undertaken before blast transformation 3 .At present, diagnosis of MPN-BP employs the World Health Organization (WHO)-defined criteria for acute myeloid leukemia (AML): presence of ≥20% blasts either in the bone marrow (BM) or in the peripheral blood (PB) 4 .In other words, neither scenario requires compartmental concordance.However, it is currently not clear if this 20% WHO threshold for circulating blasts is valid in the context of primary myelofibrosis (PMF), especially in terms of its prognostic equivalency to that of BM blast percentage-defined blast phase PMF (PMF-BP) and its distinction from accelerated phase disease (PMF-AP),
AB0508 Fixed, low-dose hydroxichloroquine versus weight-adjusted dose in systemic lupus erythematosus patients with low activity
Authors: J.L. Callejas-Rubio, D. Sanchez-Cano, R. Ríos-Fernández, M. Moreno-Higueras, G. Fatoul del Pino, S. Velasco-Fuentes, M. Trigo-Rodríguez, N. Faro-Mínguez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Optimal hydroxichloroquine (HCQ) dose to reduce ocular toxicity risk is 5 mg/kg or actual weight daily, according to new recommendations. In systemic lupus erythematosus patients (SLE) with low or no disease activity, fixed low-dose HCQ might be equally effective in relapse prevention weight-adjusted doses, thus resulting in lower cumulative dose. <h3>Objectives</h3> Our aim was to compare a fixed dose of HCQ 200 mg daily with a weight-adjusted dose (5 mg/kg of actual weight daily) in SLE patients with low activity. <h3>Methods</h3> SLE activity was assessed using the SLE Disease Activity Index (SLEDAI-2K), the Safety of Oestrogen in Lupus Erythematosus National Assessment (SELENA)-SLEDAI and the Physician Global Assessment (PGA, 0–3 scale) in each visit. Low-activity SLE (LLDAS) was defined according to Franklyn et al: 1) a SLEDAI-2K score ≤4, 2) no new SLE-related activity events compared with the previous visit, 3) a PGA score ≤1, 4) prednisone dose ≤7.5 mg daily and 5) stable doses of maintenance immunosuppressant therapy. LLDAS was evaluated at baseline and months 3 and 6. In order to adjust doses to weight, and given the impossibility of fractionating HCQ tablets, the adjusted dose was calculated for every week. For example, for 62 kg patient, the calculated dose would be 5 mgx52 kg=260 mg daily, which would mean 1820 mg weekly. Therefore, the patient would receive 400 mg daily for 2 days and 200 mg daily for 5 days every week. A relapse was defined as an increase of SLEDAI scores≥3, according to current recommendations <h3>Results</h3> A total of 50 LLDAS patients were compared, 25 with a fixed dose and 25 with a weight-adjusted dose. No significant differences regarding body weight between groups were observed: 52 kg (41–58.5 kg) vs. 51 kg (44–55 kg). Baseline activity scale scores were not significantly different. No patient relapsed on follow-up in either of both groups. Finally, the mean HCQ cumulative dose at 6 months was reduced by approximately 9.6 grams. <h3>Conclusions</h3> In LLADS patients, a fixed HCQ dose of 200 mg daily may be as effective as the weight-adjusted dose in preventing disease relapses, thus resulting in a decrease in the HCQ cumulative dose and, therefore, a reduction of the risk of ocular toxicity. <h3>Reference</h3> [1] Franklyn K, Lau CS, Navarra SV, et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016;75:1615–21. <h3>Disclosure of Interest</h3> None declared
Abstract 14480: Effects of High Mechanical Index Impulses From a Diagnostic Ultrasound Transducer During an Intravenous Ultrasound Contrast Infusion in Preventing Adverse Left Ventricular Remodeling in Acute ST Segment Myocardial Infarction
Authors: Wilson Mathias, Jeane M Tsutsui, Bruno G Tavares, Miguel O Aguiar, Mucio T Oliveira, Alexandre Soeiro, Pedro A Lemos, Jose Ramires, Roberto Kalil, Thomas R Porter
Journal: Circulation (2016)

Introduction: In patients with acute ST segment elevation myocardial infarction (STEMI), preliminary clinical trials have demonstrated that high mechanical index (MI) impulses from a diagnostic ult...
AB0239 Development of a novel „molecular disease activity“ tool composed of 8 serum biomarkers for monitoring rheumatoid arthritis
Authors: J. Hurnakova, M. Komarc, R. Horvath, H. Hulejova, J. Zavada, L. Palova Jelinkova, K. Danova, P. Hanova, H. Mann, J. Vencovsky, K. Pavelka, R. Spisek, L. Senolt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Accurate disease activity measurement is a key component of rheumatoid arthritis (RA) management. In 2012, multi-biomarker disease activity (MBDA) test using 12 serum proteins was presented<sup>1</sup>. <h3>Objectives</h3> To develop a novel test for measuring inflammatory activity in RA. <h3>Methods</h3> Serum samples were obtained from 82 patients with RA (60 females, median disease duration 4.2 years, median age 55.2 years, RF positivity 60.3%, ACPA positivity 69.7%). A detailed stepwise analysis of 20 candidate biomarkers selected from the literature search (IL1β, IL-6, IL-7, IL-8, IL-12p70, IL-17A, IL-22, IL-33, IL-34, IFNγ, VEGF, YKL-40, CXCL-13, MMP-3, resistin, visfatin, leptin, adiponectin, calprotectin and CRP) was performed. Methods of factor analysis (a statistical method used to describe variability among observed, correlated variables in terms of a potentially lower number of unobserved variables called factors) were used in order to develop a tool composed of different serum markers that would optimally reflect disease activity in RA. Spearman correlation index was used to explore associations between newly designed tool and clinical as well ultrasound parameters (German US7 score) of disease activity. <h3>Results</h3> We have developed a <i>"Molecular Disease Activity"</i> test covering underlying pathophysiological processes composed of 8 serum markers: calprotectin, CRP, IL-6, MMP-3, VEGF, resistin, IL-22 and IL-7 that optimally reflected inflammatory activity in RA. This model was significantly associated with clinical (DAS28-ESR, DAS29-CRP, CDAI, SDAI) and ultrasound variables (PD syn score, GS syn score) of disease activity in RA, as shown in table 1. <h3>Conclusions</h3> We believe that this newly designed test based on 8 serum markers may contribute to more accurate measurement of inflammatory activity in RA and improvement of patients' outcomes. Further evaluation of this tool in a larger cohort is needed. <h3>Reference</h3> [1] Centola M, Cavet G, Shen Y, et al. Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis. Plos One2013Apr 9;8(4). <h3>Acknowledgements</h3> Supported by the project of Ministry of Health, Czech Rep. No. 0 23 728 and SVV No. 260 373. <h3>Disclosure of Interest</h3> None declared
The Importance of User-Centered Design and Evaluation
Authors: Leora I. Horwitz
Journal: JAMA Internal Medicine (2018)

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FRI0664 Biomarkers for relapse in patients with adult onset still’s disease treated with il-6 inhibitor.
Authors: H. Yamada, Y. Kaneko, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Symptoms and laboratory data in patients with adult onset Still's disease patients (AOSD) at relapse are often non-specific. Especially in AOSD patients treated with tocilizumab, IL-6 receptor inhibitor, inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are almost normal despite flared disease activity. <h3>Objectives:</h3> To identify useful biomarkers for assessing disease activity and relapse in AOSD patients treated with tocilizumab. <h3>Methods:</h3> Consecutive AOSD patients diagnosed by Yamaguchi's criteria in our institution from January 2007 until January 2018 were reviewed. Clinical information was collected from their medical charts. Relapse was defined as a case who required immunosuppressive treatment intensification for AOSD according to their attending physicians. Biomarkers were compared between before relapse and at relapse. <h3>Results:</h3> Forty eight patients with AOSD were enrolled. Thirty relapses during the observation period of 3.5 years were identified. At relapse, white blood cell count (WBC), CRP, ESR, serum ferritin levels, and serum lactate dehydrogenase (LDH) levels significantly increased compared to before relapse (WBC, 12123±1238 /µL vs 7184±607 /µL, P=0.002; CRP, 4.37±1.08 mg/dL vs 0.32±0.18 mg/dL, P=0.003; ESR 39.1±7.78 mm/hr vs 6.67±1.46 mm/hr, P=0.001; ferritin, 78.9±30.9 ng/mL vs 24.9±3.8 ng/mL, P=0.036; LDH, 374.8±48.1 IU/mL vs 214.7±16.8 IU/mL, P=0.005). Six patients were identified to experience relapse with fever, active synovitis, rush or lymphadenopathy while treated with tocilizumab. In patients treated with tocilizumab, while neither CRP nor ESR increased in all patients at relapse (CRP&lt;0.30 mg/dL in all; ESR, 4.50±1.04 mm/hr vs 3.75±1.18 mm/hr, P=0.893), LDH was significantly elevated at relapse compared to before relapse (451.2±92.1 IU/mL vs 211.2±24.6 IU/mL, P=0.04). WBC and serum ferritin levels tended to increase but with no significant difference (WBC: 14620±1547 /µL vs 9500±2285 /µL, P=0.21; ferritin, 236.4±91.2 ng/mL vs 49.2±24.2 ng/mL, P=0.091). <h3>Conclusions:</h3> Instead of CRP and ESR, LDH level was a useful clinical biomarker for relapse of AOSD, especially in those treated with tocilizumab. <h3>Disclosure of Interest:</h3> None declared
Learning from the Canadian experience of capping GP consultation rates
Authors: Eugene Y H Yeung, Roxanna S D Mohammed
Journal: BMJ (2018)

Both sides of the Head to Head debate on whether GPs’ daily number of consultations should be capped focus on urgent situations.1 Consultation caps have been widely implemented in the Canadian primary care system for a long time.2 However, many walk-in clinics are available for patients who are unable …
Abstract 16562: Effects of the G174C Polymorphism in Interleukin-6 Gene Promoter on Inflammatory and Thrombotic Processes and in severity of Coronary Artery Disease in Patients With Advanced Atherosclerosis
Authors: Dimitris Tousoulis, George Hatzis, Nikolaos Papageorgiou, Emmanouel Androulakis, Gerasimos Siasos, Charalambos Antoniades, Andreas Synetos, Stavroula Papaoikonomou, Georgios Bouras, Spyridon Deftereos, Christodoulos Stefanadis
Journal: Circulation (2013)

Background:  Interleukin-6 (IL-6) represents an early marker of inflammatory activation, strongly related to the pathophysiology of coronary artery disease (CAD). However, it remains unclear, whether common polymorphisms within the IL-6 gene affect the mechanisms of CAD. In the present study we examined the impact of the G174C polymorphism on IL-6 gene promoter on inflammatory and thrombotic processes and on the severity of CAD.   Methods:  The study population consisted of 360 patients with angiographically documented CAD and 282 healthy controls. The G174C polymorphism was determined by PCR and digestion with SFA NI restriction enzyme. High sensitivity C-Reactive Protein (hsCRP) (mg/dl) and D-dimers (pg/l) were determined with immunonephelometry, while fibrinogen (mg/dl) with the von Clauss method. IL-6 (pg/ml) and sCD40L (pg/ml) were assessed by ELISA.   Results:  The genotype distribution was: GG: 42.1 %, GC: 41.5%, CC: 16.4% in CAD and GG: 44.3%, GC: 42.1%, CC: 13.6% in controls. Although CC genotype presented a borderline positive trend compared to G carriers regarding the incidence (p=0.07) and severity of CAD (1 vessel vs 2+3 vessels R.R.: 1.091, 95% C. I.: 0.9962-1.194, p=0.07), the difference was not significant. Similarly, CC genotype was not related with levels of fibrinogen (450.26±131.23 vs 446.88±135.33, p=NS), sCD40L (2.146±1.388 vs 2.3±2.29, p=NS) and D-dimers (451.45±286.05 vs 458.83± 296.04, p=NS) not only in CAD, but also in controls (fibrinogen: 368.78±93.579 vs 379.62±100.68, sCD40L: 0.825±0.802 vs 1.121±1.026, D-dimers: 383.85±325.26 vs 366.54±295.8, p=NS for all). Importantly, CC homozygotes were related with significantly higher serum levels of IL-6 and hsCRP compared to GG homozygotes in CAD (4.654±0.918 vs 2.633±1.187 and 2.867±0.87 vs 2.130±0.662, respectively, p   Conclusions:  We have found that the G174C polymorphism on Interleukin-6 gene promoter does not alter the coagulation status. On the contrary, CC homozygosity increases significantly the inflammatory process of both subjects with and without advanced atherosclerosis.
Focus on the Perimeter and Skip the Balloon
Authors: Jan Henzel, Marek Konka, Anna Wójcik, Piotr N. Rudziński, Radosław Pracoń, Witold Śmigielski, Ewa Sitkowska-Rysiak, Andrzej Kurowski, Zofia Dzielińska, Piotr Hoffman, Marcin Demkow
Journal: JACC. Cardiovascular imaging (2018)
AB0482 Similar efficacy of tofacitinib on disease activity in rheumatoid arthritis patients with and without previous biologicals; results from the turkbio registry
Authors: B. Zengin, N. Inanç, S. Akar, G. Can, E. Dalkilic, A. Tufan, S. Senel, S. Serdar Koca, S. Capar, H. Yarkan Tugsal, M. Birlik, N. Akkoc, F. Onen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The aim of this study was to investigate the drug survival, its efficacy and safety in patients withRA based on the database from the Turkish TURKBIO registry <h3>Methods</h3> A total of 180 patients were treated with TOFA forRA. Drug survival was assessed. In 118 patients with available data, treatment response was evaluated using thenumber of sensitive and swollen joints, VAS values, DAS28, HAQ and CRPat weeks 12,24,48 and 60 <h3>Results</h3> At baseline, RA patients had a median(Q1-Q3)disease duration of 14 years.75 patients had used ≥1 biologics previously. The other demographic and clinical features of the patients were shown in table 1. Median(Q1-Q3)followup period was137 weeks. After48 and137 weeks,75% and 48%of the patients respectively, maintained TOFA (figure 1). The most common reason for drug discontinuation was ineffectiveness of treatment(63%), followed by adverse events (23%). After 12 weeks, all disease activity parameters were reduced significantly compared to the baseline and most of them continued to be reduced until week60. No difference was observed in disease activity parameters between the groups with and without previous ≥1biologics at weeks 0,12 and 24 (table 2) Remission rate was(43%)at week 60(observed data) (table 2) A total of 9 adverse events(3infection,3allergic rx,2 rash)were observed during the followup period <h3>Conclusions</h3> Treatment with TOFA may provide good response rates in RA patients refractory previous biologicals <h3>Disclosure of Interest</h3> None declared
SAT0706 Incidence of psoriatic arthritis in germany: analysis of claims data from 65 million people from 2009 to 2012
Authors: P. Sewerin, I. Haase, M. Schneider, B. Ostendorf, R. Brinks
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Epidemiological studies are important for understanding the etiology and burden of psoriatic arthritis (PsA). Currently, there are no data available about the incidence of PsA in Germany. <h3>Objectives</h3> This study aims to estimate the age-standardised incidence of diagnosed PsA for German men and women during 2009 to 2012. <h3>Methods</h3> Estimation of the incidence of a chronic disease from prevalence data is possible if information about the general mortality and excess mortality of diseased compared to non-diseased people are available in terms of the hazard ratio (HR).<sup>1</sup> Prevalence was extracted from the complete diagnosis data (in- and outpatient) from about 80% of the overall German population during 2009 to 2012. Diagnoses are based on claims data from all insurances of the German statutory health insurance (SHI) system. After determining the age-standardised sex-specific prevalence of PsA for each of the four years, the age-standardised incidence for men and women has been estimated. General mortality was obtained from the Federal Statistical Office of Germany. Since the HR is unknown in Germany, we use different scenarios motivated from a systematic review<sup>2</sup> in the range from 1.3 to 1.6. <h3>Results</h3> For each of the years from 2009 to 2012, a total of 127, 138, 146 and 156 thousand patients with diagnosed PsA were identified in about 65 million people from the SHI, respectively. The age-standardised prevalence increases from 1.8 to 2.1 per mil in men, and from 2.1 to 2.5 per mil in women. The estimated age-standardised incidence over the study period is shown in the figure 1. Over the study period, the incidence rate of PsA decreases for both sexes and the rate of men is lower than the rate of women. The average incidence rates are 11.5 and 14.5 per 100'000 person-years for men and women, respectively. This means that about 4700 men and 5900 women contract PsA each year. The impact of the different scenarios in HR is small. <h3>Conclusions</h3> These data from about 65 million people insured in the German SHI for the first time allow an estimation of the incidence of PsA in Germany. A selection bias is likely to be present, because the roughly 20% of the overall German population who could not included in the analysis (mainly privately insured people) are known to have other health risks. However, the results refer to the vast majority of the German population. The analysis cannot be adjusted for potential confounders other than age and sex (e.g., socio-economic position or presence of co-morbidities). <h3>References</h3> [1] Brinks R, Landwehr S, DOI: 10.1093/imammb/dqu024 [2] Gladman DD. Mortality in psoriatic arthritis, Clin Experim Rheuma26(5):S62. <h3>Disclosure of Interest</h3> None declared