tbuckley/cabot-search huggingface dataset:
Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial
Authors: Marc S Sabatine, Lawrence A Leiter, Stephen D Wiviott, Robert P Giugliano, Prakash Deedwania, Gaetano M De Ferrari, Sabina A Murphy, Julia F Kuder, Ioanna Gouni-Berthold, Basil S Lewis, Yehuda Handelsman, Armando Lira Pineda, Narimon Honarpour, Anthony C Keech, Peter S Sever, Terje R Pedersen
Journal: The Lancet Diabetes & Endocrinology (2017)
AB0260 The predictors of fragility fractures in patients on aromatase inhibitors: an observational study
Authors: N Meah, R Sinha, M Bukhari
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The use of aromatase inhibitors (AIs), given after breast cancer, has been associated with a low bone mineral density (BMD) and as a risk factor for fragility fractures. We have reported on the risk factor for low BMD in a previous abstract and it showed that the use of AIs significantly reduced lumbar spine BMD and femoral neck BMD (1). The FRAX ™ tool uses the femoral neck BMD to predict fractures on a population basis but ignores the lumbar spine. Some patients who have undergone bilateral hip replacements would not be able to estimate their FRAX ™ risk accurately. <h3>Objectives</h3> To determine the predictors of fragility fractures in an observational cohort of female patients on aromatase inhibitors. <h3>Methods</h3> Female patients referred for BMD estimation in a scanner in the North West of England between 2004 and 2014 on aromatase inhibitors were identified from a dual X-ray absorptiometry database. Demographics and other risk factors, as well as fragility fractures, were recorded. Initially, those who had sustained a fracture were compared to those who had not sustained a fracture using chi-squared tests for categorical variables and T-tests for continuous variables. Following that, univariate and multivariate logistic regression models were fitted looking at the predictors of fracture. Variables included age at scan, height, weight, alcohol, smoking, family history, rheumatoid arthritis, secondary osteoporosis as defined by FRAX™, body mass index and steroid exposure, in addition to BMD in the lumbar spine and femoral neck. <h3>Results</h3> 2029 female patients were scanned in the referral period. The mean age at scan was 66 (SD 10.46). 356/2029 (17.55%) had sustained a fracture. Results of the univariate analysis are shown in table 1, significant predictors are indicated with an asterisk (*). In the multivariate model, the variables that predicted fractures in this cohort were age at scan (OR 1.03 95% CI 1.02,1.05), femoral neck BMD (OR 0.74 95% CI 0.02,0.29) and lumbar spine BMD (OR 0.34 95% CI 0.14,0.80). Using the femoral neck multivariate model resulted in an area under the curve of 0.6720 and using the lumbar spine was 0.6653. <h3>Conclusions</h3> In the univariate analysis, many risk factors are associated with fractures within this cohort of female patients on aromatase inhibitors but both univariate analysis and multivariate analysis showed that lumbar spine BMD is a good predictor of fractures. This is not included in the FRAX ™ tool and would enable fracture risk to be calculated in patients who have undergone hip replacements. <h3>References</h3> Ann Rheum Dis 2014;73 Suppl3 SAT0472. <h3>Disclosure of Interest</h3> None declared
Abstract 12776: Novel Left Ventricle Contractility Index as a Marker of Left Ventricular Function in Aortic Stenosis
Authors: Elaine Boey, Hui Wen Sim, Benjamin Tan, Wei Qin Lin, Liang Zhong, Ru San Tan, William Kong, Kian Keong Poh
Journal: Circulation (2016)

Introduction: The maximal rate of change of pressure-normalized wall stress dσ*/dt max is a novel, non-invasive, load-independent index of left ventricular (LV) global contractility. We aim to evaluate the relationship between dσ*/dt max and aortic stenosis (AS). Methods: 417 patients with severe AS (aortic valve area [AVA] &lt;1cm 2 ) and no more than moderate concomitant other valvular pathology underwent echocardiography to characterise LV dimension, structure and dσ*/dt max . Univariate and multivariate analyses were performed. Results: Critical and non critical severe AS were defined as AVA≤0.8cm 2 and AVA≤1.0cm 2 respectively. Univariate analysis is presented in Table 1. dσ*/dt max was reduced in subjects with critical severe AS compared to non-critical severe AS (2.17± 0.79s-1 vs 2.46 ± 0.82s-1, p&lt;0.001). Furthermore, dσ*/dt max was found to correlate with other indices of AS severity. Multivariate analysis showed that dσ*/dt max correlated with indexed AVA (B=0.20, p&lt;0.001), LV ejection fraction (B=0.154, p&lt;0.001), cardiac output (B=0.377, p&lt;0.001) and LV mass index (B=-0.664, p&lt;0.001). dσ*/dt max did not co-relate with age, gender, body mass index or body surface area. Conclusions: dσ*/dt max correlates with indices of AS severity and may be a reflection of underlying LV dysfunction in severe AS.
FRI0601 Hyperferritinemic syndrome in a general universitary hospital
Authors: F Pierini, IJ Gandino, JM Martinez Perez, S Ruta, M Scolnik, ER Soriano
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Hyperferritinemia is associated with severe inflammatory conditions, such as rheumatic diseases with systemic inflammatory responses, and multiorgan dysfunction syndromes. <h3>Objectives</h3> To determine which diseases are associated with hyperferritinemia in a tertiary hospital; to compare ferritin levels between these different entities and to evaluate relationship between levels of ferritin and mortality in these patients. <h3>Methods</h3> A retrospective study was carried out in which all patients over 18 years with at least one determination of serum ferritin equal to or greater than 1000 ng/ml were identified in the laboratory database of our hospital between 1/1/2006 and 6/30/2016. Corresponding electronic medical records were reviewed and demographic data and clinical data were collected. Mortality was assessed at the end of follow-up. Descriptive statistical analysis and logistic regression analysis were performed in order to identify variables associated with mortality. <h3>Results</h3> A total of 1979 patients were included, 1235 men (62.4%) with a mean age of 63.2 years (SD 17.2). Only 36 patients (1.8%) presented a rheumatologic diagnosis as the only cause of high levels of ferritin, with Still9s disease (n=8) and systemic Vasculitis (n=9) being the main diagnoses. Table 1 shows patients9 characteristics grouped according to whether the elevation of ferritin was associated with a rheumatic disease or not. Median serum ferritin and transferrin saturation in both groups were similar (see Table 1). Mortality was lower for rheumatologic causes (5.9% vs 37.2%, p&lt;0.001). Variables that were associated with mortality in multivariable logistic regression analysis were: maximum ferritin value (OR 1,0004, 95% CI 1,0003–1,0004, p&lt;0.001) and age (OR 1.03, 95% CI 1.02–1.04, p&lt;0.001), whereas the diagnosis of a rheumatic disease was a protective factor (OR 0.11, 95% CI 0.03–0.47, p=0.003). ROC curve for ferritin and mortality showed an area under the curve of 0.59 (95% CI 0.58–0.62). Ferritin levels greater than 3000 ng/ml showed a specificity of 89.2% and a sensitivity of 19.7% for mortality, regardless of cause of ferritin elevation. <h3>Conclusions</h3> Rheumatic diseases, represents a very small percentage of the causes of elevation of ferritin above 1000 ng/ml, and were associated with lower mortality than the non-rheumatic causes. Serum ferritin levels were significantly associated with increased mortality regardless of the underlying cause. <h3>Disclosure of Interest</h3> None declared
AB0648 Disease-related autoantibody profile in systemic sclerosis in greece
Authors: C Liaskos, E Marou, T Simopoulou, M Barmakoudi, G Efthymiou, T Scheper, W Meyer, DP Bogdanos, L Sakkas
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Autoantibodies (autoAbs) help in diagnosis and predicting clinical phenotypes in systemic sclerosis (SSc). <h3>Objectives</h3> To determine the clinical utility of 13 SSc-related autoAbs in SSc patients in Greece. <h3>Methods</h3> 131 consecutive patients with SSc (111 female, mean age 58.1±14 years; 49 with diffused cutaneous SSc [dcSSc] and 82 with limited cutaneous SSc [lcSSc]) were analyzed by a multiplex line immunoassay (Euroimmun) for autoAbs against 13 SSc-related antigens. Twenty two patients with primary Raynaud phenomenon (RP), and 22 healthy controls were also analyzed <h3>Results</h3> ANA by indirect immunofluorescence was present in 128 (97.7%) patients with SSc. Excluding anti-Ro52, 113 (89.3%) SSc patients were positive for at least one autoAb: anti-Topo I abs in 54 (41.2%), anti-CENPA in 37 (28.2%, all reactive with CENPB), anti-RNA polymerase III (RP11) in 19 (14.5%), anti-RNA polymerase III (RP155) in 13 (9.9%), anti-fibrillarin in 4 (3.1%), anti-Ku in 6 (4.6%), anti-NOR90 in 8 (6.1%), anti-PM/Scl100 in 2 (1.5%), and anti-PM/Scl75 in 4 (3.1%). There was no immunoreactivity for Th/To or PDGFR. Overall, 102 (77.9%) SSc patients had autoAbs against Topo I, CENPA or CENPB, RP11 or RP155. Anti-Topo I abs were strongly associated with dcSSc, interstitial lung disease (ILD) (p&lt;0.001), and pulmonary arterial hypertension (PAH) (p=0.019). Anti-CENB abs were associated with lcSSc, and negatively associated with ILD. Anti-RP11 and anti-NOR90 abs were associated with male gender, and anti-NOR90 associated with ILD. In PR individuals and healthy individuals anti-Ro52 immunoreactivity was found in 9.1% and 13.6%, respectively, but no other immunoreactivity was detected. <h3>Conclusions</h3> Anti-Scl70, anti-CENP and anti-RNA pol III are the most prevalent autoAbs in SSc. Anti-Topo I and anti-NOR90 abs are associated with ILD and/or PAH. <h3>Disclosure of Interest</h3> C. Liaskos: None declared, E. Marou: None declared, T. Simopoulou: None declared, M. Barmakoudi: None declared, G. Efthymiou: None declared, T. Scheper Employee of: Euroimmun AG, W. Meyer Employee of: Euroimmun AG, D. Bogdanos: None declared, L. Sakkas: None declared
AB0596 Interferon-Γ release assay (T-SPOT.TB) in the diagnosis of tuberculosis infection in patients with behcet's disease: a single center experience in china
Authors: W Zheng, X Wu, P Chen, L Zhao, J Liu, L Zhang, X Liu, Y Zhao, X Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In many aspects Behcet9s disease (BD) is correlated with tuberculosis (TB). They may mimic each other on clinical manifestations. For example erythema nodosa, arthritis, gut lesions could be occurred in both disease and it is difficult for differential diagnosis. Some patients with newly-diagnosed BD were found to have active or latent or old TB and anti-TB therapy could relieve some of the symptoms. In etiology, it has been postulated that tubercle bacilli may act as a trigger of BD through the mechanism of molecular mimicking. Vice versa, defective cell-mediated immunity in BD patients may increase individual susceptibility of TB.It is extremely important to clarify TB existence or not in BD patients. Since BD patients commonly need glucocorticoid and immunosuppressant or even biologic agent such as anti-TNFa. And these medications may increase the risk of occurrence or flare of TB. But positive result of PPD shows little value in this special population due to acupuncture reaction in BD patients.In this pilot study, the values of interferon-γ release assay (T-SPOT-TB) in diagnosing active TB in BD patients were explored. <h3>Objectives</h3> To investigate the diagnostic value of the T-SPOT.TB in BD patients complicated with tuberculosis infection. <h3>Methods</h3> The clinical, radiology and laboratory data were collected and analyzed in 175 hospitalized BD patients from the Peking Union Medical College Hospital between January 2010 and March 2015. Statistical analysis was carried out using IBM SPSS version 20. <h3>Results</h3> Of the 175 BD patients, the positive rate of tuberculosis infection in BD patients was 34.3%. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the T-SPOT.TB test for the diagnosis of ATB were 87.5%, 73%, 36.8%, 98.3%, respectively. Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.24 and 0.17. The median number of SFCs in the BD-ATB group was higher than that in the BD-LTB group and BD-OTB (p&lt;0.001 and p=0.012). By ROC method, it was suggested that 70 SFCs act as a cutoff for diagnosing BD-ATB with the sensitivity, specificity, PPV, NPV, PLR and NLR were 87.5%, 85%, 24.6%, 98.5%, 5.79 and 0.15, respectively. The rates of LTB infection had no significant difference between BD patients and healthy controls. Agreement between T-SPOT.TB and TST in BD patients measured by the kappa coefficient was poor (kappa =0.37).Multiple logistic regression analysis revealed that BD patients with positive T-SPOT.TB had the highest likelihood of ATB (OR 11.93, 95% CI 2.108–67.508, p=0.005). <h3>Conclusions</h3> T-SPOT.TB is a promising test in the diagnosis of BD complicated with tuberculosis infection, and higher number of SFCs may has a higher risk of ATB. <h3>Disclosure of Interest</h3> None declared
Pazopanib and taxane combinations for metastatic or recurrent soft tissue sarcoma: A retrospective case series.
Authors: Sarmen Sarkissian, John P. Fruehauf
Journal: Journal of Clinical Oncology (2016)

e22528 Background: Soft tissue sarcomas (STSs) are a rare group of neoplasms without curative potential in the metastatic setting. Pazopanib(P) and taxanes(T) are active agents supported in the NCCN guidelines for treatment of STSs. Methods: In a series of patients screened between August 2012 and December 2015 we combined pazopanib 200-800 mg PO daily with docetaxel 36 mg/m2 IV Q14d or paclitaxel 75mg/m2 IV D1,8,15 per 28d cycles. We describe a retrospective review of our data including PFS, mOS, CBR, ORR, and AEs. Results: Nine patients were evaluable for data collection. Common histological subtypes included: Synovial, myxofibrosarcoma, epithelioid angiosarcoma, chondrosarcoma, epithelioid, high grade sarcoma, angiosarcoma, desmoid tumor, (all n = 1) and leiomyosarcoma (n = 2). At the time of analysis, patients had received 156 cycles of pazopanib, mean 17.3, 53 cycles of docetaxel, mean 7.5, and 28 cycles of paclitaxel, mean 14. The clinical benefit rate (CBR) was 100% (1 CR, 1 near CR, 5 SD, and 2 PR). The overall response rate was 44.4% (4/9 patients). The median length of progression-free survival (mPFS) was 12.0 months (95% CI, 9.72-24.88) and the median overall survival had not been reached at the time of analysis. Seven of the nine patients were still alive and one was still on treatment at the time of analysis. Dose limitations or therapy interruptions secondary to adverse events (AE) were noted in seven of nine patients, including transaminase elevations, fatigue, anemia, and dermatologic issues. All patients resumed therapy after dose adjustments, with no treatment related mortality. Conclusions: The P+T combination demonstrated significant antitumor activity in this group of patients. While this is a small series, these data are superior to single agent pazopanib activity shown in the PALETTE trial, which had a mPFS = 4.6mo and CBR = 44% versus 12.0 mo and 100% respectively for PT. The toxicity profile was also acceptable. These data support a prospective phase II trial to further assess this combination in STS.
AB0715 Differences in the co-morbidities described from spondyloarthritis patients with or without concomitant fibromyalgia
Authors: E Roussou, M Karela, A Georgiou
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To assess the differences in the occurrence of co-morbidities from cardiovascular, respiratory, renal/urological and Central nervous systems (CNS) between patients with spondyloarthritis (SpA) not having headache as presenting symptom and those having headache assuming that those describing headache represent secondary (s) fibromyalgia (FM). (previous submitted abstract provides justification on headache as presenting symptom associated with secondary sFM). <h3>Methods</h3> Data obtained through a questionnaire from 776 patients seen in clinic with SpA was analysed with reference to headache as symptom at presentation. From the total 776 patients 13 patients did not record an answer to the question and were hence excluded. The remaining 763 patients were divided in 2 groups: Those having headache at presentation (n=117) considered having sFM, and those not having headache at presentation (n=656). The data of patients with sFM were compared with the data of patients who did not report headache as a presentation symptom therefore not having FM with regards to age, disease duration, delay in diagnosis, disease activity (BASDAI) functional ability (BASFI), ESR, CRP and associated co morbidities from cardiovascular, respiratory, renal/urinary, and CNS systems. Central nervous system was evaluated by symptoms of dizziness and numbness. Independent sample T test was used to explore differences between the 2 groups and confidence intervals obtained. <h3>Results</h3> Table shows demographics and disease characteristics as well as differences between SpA patients presenting with headache (indicating secondary FM), and those not presenting with headache. A greater proportion of patients with SpA and headache (sFM) report cardiovascular and CNS co-morbidities. There was no significant difference noted in the respiratory or renal/ urological co-morbidities amongst the 2 sub-groups. <h3>Conclusions</h3> A significantly higher proportion of patients described cardiovascular and CNS co-morbidities in the sFM group of SpA. No significant difference was noted in the 2 sub-groups with regards to the respiratory or renal systems. <h3>Disclosure of Interest</h3> None declared
<i>VHL</i> Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma
Authors: Xiaosai Yao, Jing Tan, Kevin Junliang Lim, Joanna Koh, Wen Fong Ooi, Zhimei Li, Dachuan Huang, Manjie Xing, Yang Sun Chan, James Zhengzhong Qu, Su Ting Tay, Giovani Wijaya, Yue Ning Lam, Jing Han Hong, Ai Ping Lee-Lim, Peiyong Guan, Michelle Shu Wen Ng, Cassandra Zhengxuan He, Joyce Suling Lin, Tannistha Nandi, Aditi Qamra, Chang Xu, Swe Swe Myint, James O. J. Davies, Jian Yuan Goh, Gary Loh, Bryan C. Tan, Steven G. Rozen, Qiang Yu, Iain Bee Huat Tan, Christopher Wai Sam Cheng, Shang Li, Kenneth Tou En Chang, Puay Hoon Tan, David Lawrence Silver, Alexander Lezhava, Gertrud Steger, Jim R. Hughes, Bin Tean Teh, Patrick Tan
Journal: Cancer Discovery (2017)

Abstract Protein-coding mutations in clear cell renal cell carcinoma (ccRCC) have been extensively characterized, frequently involving inactivation of the von Hippel–Lindau (VHL) tumor suppressor. Roles for noncoding cis-regulatory aberrations in ccRCC tumorigenesis, however, remain unclear. Analyzing 10 primary tumor/normal pairs and 9 cell lines across 79 chromatin profiles, we observed pervasive enhancer malfunction in ccRCC, with cognate enhancer-target genes associated with tissue-specific aspects of malignancy. Superenhancer profiling identified ZNF395 as a ccRCC-specific and VHL-regulated master regulator whose depletion causes near-complete tumor elimination in vitro and in vivo. VHL loss predominantly drives enhancer/superenhancer deregulation more so than promoters, with acquisition of active enhancer marks (H3K27ac, H3K4me1) near ccRCC hallmark genes. Mechanistically, VHL loss stabilizes HIF2α–HIF1β heterodimer binding at enhancers, subsequently recruiting histone acetyltransferase p300 without overtly affecting preexisting promoter–enhancer interactions. Subtype-specific driver mutations such as VHL may thus propagate unique pathogenic dependencies in ccRCC by modulating epigenomic landscapes and cancer gene expression. Significance: Comprehensive epigenomic profiling of ccRCC establishes a compendium of somatically altered cis-regulatory elements, uncovering new potential targets including ZNF395, a ccRCC master regulator. Loss of VHL, a ccRCC signature event, causes pervasive enhancer malfunction, with binding of enhancer-centric HIF2α and recruitment of histone acetyltransferase p300 at preexisting lineage-specific promoter–enhancer complexes. Cancer Discov; 7(11); 1284–305. ©2017 AACR. See related commentary by Ricketts and Linehan, p. 1221. This article is highlighted in the In This Issue feature, p. 1201
AB1010 Ultrasound morphostructural pattern of the tibiofibular joint. preliminary results
Authors: C Hernández-Díaz, L Ventura-Rios, M Maldonado, G Sanchez-Bringas
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The anatomy of the proximal tibiofibular (TF) joint is directly related to its ability to withstand stress applied in either a longitudinal or axial fashion. It is traditionally evaluated by CT scan, however, in certain conditions, it could be evaluated by ultrasound (US) conveniently; so far US has not been using to evaluate the TF joint. US is an innocuous, accessible and cheap image technique, that has demonstrated its utility for evaluating joints in several pathologic conditions, and might have an important role in the early diagnosis of inflammatory, degenerative or even tumoral lesions at the level of the TF joint; there are no studies that have evaluated the morpho- structural pattern of the TF joint. <h3>Objectives</h3> To describe the morphostructural pattern of the tibiofibular joint in healthy subjects. <h3>Methods</h3> Subjects older than 18 yrs old, with no history of past/present lesion of the knee, without any joint or neurovascular disease were included. A short questionnaire related to physical activity applied, and clinical evaluation to discard instability performed. US of both knees in extension done, using an Esaote ® MyLab 70 ultrasound equipment with a 7.5 - 12 MHz linear transducer. Descriptive statistics done <h3>Results</h3> Thirty-six patients (27 women, 75%) included, mean age 41.2±8.9 years, mean weight 71±12.46 kg, mean height 1.61±0.09 ms and BMI 71.07±12.40. 69% of the subjects practice mild exercise activities. By US mean distance between tibia and fibula were 3.2±1.17 cm; the mean thickness of the ligaments (superior and inferior) was 3.2±0.99 cm and 3.2±0.89 respectively, and in the superior e inferior fibular ligaments were 3.2±0.99 cm and 3.2±0.89 cm respectively. Ligaments were hyperechoic in 61.1%, a well-defined border was seen only in 48.6%. Inside of joints a hypoechoic tissue was observed <h3>Conclusions</h3> These preliminary results suggest that US can be a useful tool for evaluating the tibiofibular joint. <h3>Disclosure of Interest</h3> None declared