tbuckley/cabot-search huggingface dataset:
AB0868 Lumbar muscles stiffness in patients with axial spondyloarthritis is altered in comparison with healthy subjects
Authors: I.C. Aranda-Valera, S. Alcaraz-Clariana, L. Garcia-Luque, J.L. Garrido-Castro, I. Martinez-Sanchez, C. Gonzalez, P. Gardiner, P.M. Machado, E. Collantes
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Axial Spondyloarthritis (axSpA) patients have inflammation and/or structural damage in the lumbar spine that reduces their mobility and quality of life. The biomechanical features of axSpA have not been investigated in detail, but could prove to be a very important factor contributing to pain, stiffness and loss function. Myotonometry is being used to quantify stiffness muscles in a valid and reliable way. <h3>Objectives</h3> To measure and compare the stiffness in the erector spinae muscles of axSpA patients and healthy subjects to analyse if there are any significant differences between them. <h3>Methods</h3> 20 axSpa patients and 20 healthy subjects matched in age, BMI and sex, were recruited. The stiffness of the lumbar erector spinae (ES) muscles was assessed at L4–5 using myotonometry (MyotonPRO©) (figure 1). Measures were obtained twice in the left and right muscles, in a first test and five minutes later. PRO questionnaires, radiographic structural damage and metrology for axSpA were also assessed. Lumbar spinal mobility was also measured using an inertial sensor system (ViMove©). <h3>Results</h3> No statistical differences were found between left and right muscles neither after five minutes, so the mean values were used for analyses. All muscular measures, except Decrement showed statistically significant differences between groups. The table shows results of muscular stiffness parameters analysed, statistical differences in all parameters between groups and correlations of these parameters with conventional metrology, patient reported questionnaires (only patients) and structural damage. For control subjects, the only significant correlation was between stiffness and age. However in the axSpA patients, the myoton readings correlated with mobility measures, especially with BASMI, frontal flexion (not extension), lateral flexion and rotation, measured with the inertial sensors system. Some correlations (p&lt;0.05) were also found for BASFI and BAS-G but not for BASDAI or ASQoL. <h3>Conclusions</h3> axSpA increases lumbar muscle stiffness with respect to healthy individuals. Muscle stiffness, as measured by myotonometry, was related to loss of movement and this could be contributing to a loss of function independently of structural damage and inflammation in axSpA. These new outcome measures could be helpful for understanding the evolution of the disease and for the functional assessment. <h3>Acknowledgements</h3> This study has been funded by Foreum, the XXI University of Cordoba Reearch Program and Junta de Andalucía (CS-S0029/2016). <h3>Disclosure of Interest</h3> None declared
Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater
Authors: Martin Reck, Delvys Rodríguez–Abreu, Andrew G. Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O´Brien, Suman Rao, Katsuyuki Hotta, Kristel Vandormael, Antonio Riccio, Jing Yang, M. Catherine Pietanza, Julie R. Brahmer
Journal: Journal of Clinical Oncology (2019)

Purpose In the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non–small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab. Patients and Methods Patients were randomly assigned to pembrolizumab 200 mg every 3 weeks (for up to 2 years) or investigator’s choice of platinum-based chemotherapy (four to six cycles). Patients assigned to chemotherapy could cross over to pembrolizumab upon meeting eligibility criteria. The primary end point was progression-free survival; OS was an important key secondary end point. Crossover adjustment analysis was done using the following three methods: simplified two-stage method, rank-preserving structural failure time, and inverse probability of censoring weighting. Results Three hundred five patients were randomly assigned (pembrolizumab, n = 154; chemotherapy, n = 151). At data cutoff (July 10, 2017; median follow-up, 25.2 months), 73 patients in the pembrolizumab arm and 96 in the chemotherapy arm had died. Median OS was 30.0 months (95% CI, 18.3 months to not reached) with pembrolizumab and 14.2 months (95% CI, 9.8 to 19.0 months) with chemotherapy (hazard ratio, 0.63; 95% CI, 0.47 to 0.86). Eighty-two patients assigned to chemotherapy crossed over on study to receive pembrolizumab. When adjusted for crossover using the two-stage method, the hazard ratio for OS for pembrolizumab versus chemotherapy was 0.49 (95% CI, 0.34 to 0.69); results using rank-preserving structural failure time and inverse probability of censoring weighting were similar. Treatment-related grade 3 to 5 adverse events were less frequent with pembrolizumab compared with chemotherapy (31.2% v 53.3%, respectively). Conclusion With prolonged follow-up, first-line pembrolizumab monotherapy continues to demonstrate an OS benefit over chemotherapy in patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations, despite crossover from the control arm to pembrolizumab as subsequent therapy.
Intrabone hematopoietic stem cell gene therapy for adult and pediatric patients affected by transfusion-dependent ß-thalassemia
Authors: Sarah Marktel, Samantha Scaramuzza, Maria Pia Cicalese, Fabio Giglio, Stefania Galimberti, Maria Rosa Lidonnici, Valeria Calbi, Andrea Assanelli, Maria Ester Bernardo, Claudia Rossi, Andrea Calabria, Raffaella Milani, Salvatore Gattillo, Fabrizio Benedicenti, Giulio Spinozzi, Annamaria Aprile, Alessandra Bergami, Miriam Casiraghi, Giulia Consiglieri, Nicoletta Masera, Emanuela D’Angelo, Nadia Mirra, Raffaella Origa, Immacolata Tartaglione, Silverio Perrotta, Robert Winter, Milena Coppola, Gianluca Viarengo, Luca Santoleri, Giovanna Graziadei, Michela Gabaldo, Maria Grazia Valsecchi, Eugenio Montini, Luigi Naldini, Maria Domenica Cappellini, Fabio Ciceri, Alessandro Aiuti, Giuliana Ferrari
Journal: Nature Medicine (2019)
Abstract 17811: Changes in Profile, Management and Early Mortality of STEMI Patients According to Gender. Data Over 20 Years From the FAST-MI Program 1995-2015
Authors: Etienne Puymirat, Martine Gilard, Bernard Jouve, Séverine Marchand, Florence Leclercq, Stephane Manzo-Silberman, Khalife Khalife, Christophe Tron, Pascal Motreff, Farzin Beygui, Jean Ferrieres, Francois Schiele, Tabassome Simon, Nicolas Danchin
Journal: Circulation (2017)

Introduction: the impact of gender on clinical presentation, management and outcome in STEMI patients is debated. We assessed 20-year trends in presentation, management and early mortality in relat...
Let’s share, help deliver and sustain the WHO global action plan on physical activity
Authors: Andrew Murray, Charlie Foster, Emmanuel Stamatakis
Journal: British Journal of Sports Medicine (2019)

The first Global Action Plan for Physical Activity1 (GAPPA) has been launched by the World Health Organisation. The cover is shown in figure 1.

Increasing physical activity (PA) will improve health. The science is strong on the benefits for people of all ages. The role PA plays in reducing the risk of non-communicable diseases, such as cardiovascular disease, type 2 diabetes and depression, is well recognised.2 3 Increasing PA is a global health priority and can also contribute towards attaining many of the 17 United Nations Sustainable Development Goals set for 2030.4 

Many countries have produced quality research and good policy frameworks on PA but large gaps remain between what we know/advise and what we do. These gaps were neatly described by Brownson et al as ‘parallel universes’.5 What is needed is a coherent route map to guide policy action and to support partnerships and help implement approaches that increase PA across the globe. GAPPA now provides that common road map.

GAPPA did not happen overnight. Over a decade of …
Abstract 12340: Risk Model of Aortic Valve Replacement After Cardiovascular Surgery based on 2,227 Cases From a National Japanese Database: The Japan Cardiovascular Surgery Database (JACVSD)
Authors: Suguru Ohira, Hiroaki Miyata, Kiyoshi Doi, Noboru Motomura, Shinichi Takamoto, Hitoshi Yaku
Journal: Circulation (2015)

Objective: To create a risk model to assess outcomes of aortic valve replacement after cardiovascular surgery (ReAVR) using a national Japanese database. Methods: The Japan Adult Cardiovascular Surgery Database is a web-based data system involving more than 500 hospitals. Between 2007 and 2012, 2,227 patients who underwent ReAVR for aortic stenosis were retrospectively analyzed. Patients with a previous history of AVR were also included. Results: The background of prior surgery (including overlapping cases) was: CABG, 30.9%; valve, 65.4%; and thoracic aorta, 14.7%. The mean age was 70.4. Types of prosthesis used were: bioprosthesis, 51.3%; and mechanical valve, 48.7%. The rate of isolated ReAVR was 59.5%. Concomitant procedures were: CABG, 14.6%; mitral valve surgery, 30.4%; and aortic surgery, 5.7%. The overall hospital mortality rate was 8.7%. Major complications (reoperation, prolonged ventilation, mediastinitis, stroke, and newly required dialysis) occurred in 26.0%. The incidence of stroke was 3.7%, and that of AV block was 3.5%. ORs for hospital mortality were as follows: age, 1.4 (reference ≦60, 5-year increments); male, 1.4; urgency, 1.7; EF ≦30%, 2.0; NYHA classification IV, 1.7; MR ≧2, 1.5; creatinine &gt;2.0 mg/dL, 2.7; liver dysfunction (cirrhosis, AST or ALT &gt;100 U/L, or bilirubin &gt;1.5 mg/dL), 2.3; peripheral artery disease, 1.6; and recent stroke (&lt;2 weeks), 4.8. The type of previous surgery was not a predictor for mortality. In addition to the above-mentioned risk factors, ORs for the composite outcome (mortality and major complications) were as follows: carotid stenosis, 2.5; respiratory dysfunction (FEV1.0 &lt;75%, or bronchodilator use), 1.8; prior valve surgery, 1.3; preoperative inotropic agents, 2.0; endocarditis, 1.7; concomitant CABG, 1.4; and concomitant valve surgery, 1.5. As a performance metric model, C-indexes of hospital mortality and the composite outcome were 0.77 and 0.71, respectively. Conclusions: Based on a national Japanese database, early outcomes after ReAVR were satisfactory, despite these operations being associated with a higher risk than the primary operations. The type of previous surgery was not a risk for mortality after ReAVR.
AB0651 Frequency of pulmonary hypertension in behÇet’s disease
Authors: B. Armagan, M. Oksul, Y.Z. Sener, A. Sari, A. Erden, G.K. Yardimci, L. Kilic, U. Kalyoncu, O. Karadag, S. Apras Bilgen, S. Kiraz, I. Ertenli, A. Akdogan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Behçet's disease (BD) is a systemic vasculitis that involvement of pulmonary arteries can be seen. <h3>Objectives</h3> The aim of this study was to determine the frequency and the causes of pulmonary hypertension (PH) in patients with BD. <h3>Methods</h3> We studied consecutively 154 BD patients who were fulfilled the International Study Group criteria for diagnosis of BD. All patients were evaluated with transthoracic echocardiography (TTE) for the presence of PH. BD patients were categorised according to the involved organs in 5 groups: group 1 mucocutaneus and articular, group 2 ocular, group 3 vascular, group 4 gastrointestinal and group 5 neurologic involvements. The presence of PH was defined as estimated sPAB ≥40 mmHg, by TTE. Every subject evaluated by a detailed medical history and physical examination was performed. Additional laboratory results were obtained from hospital file records. <h3>Results</h3> The mean age (SD) and the median (min-max) disease duration of the patients were 41.8±12.6 years and 126 (6–540) months respectively. PH was detected in 17 (11%) BD patients. Only 9 (52%) patients were symptomatic (NYHA FC &gt;1). Left sided heart disease (Group II: 9 (52%) patients) was the leading cause of PH. Four (23%) patients had group IV PH and 75% (3/4) were symptomatic. Diastolic dysfunction (DD) was found in 32 (20.8%) patients and only 1 patient had systolic dysfunction. The number of patients with DD was significantly higher in patients with PH as compare to patients without PH (8 (47.1%) vs 24 (17.6%), <b>p=0.005</b>). There were no difference in demographic and clinical features of patients with and without PH. Only acneiform lesion was more frequently in patients without PH as compare to patients with PH, <b>p=0.047</b> (table 1). There were no differences in frequency of PH in BD groups (table 2). <h3>Conclusions</h3> The most frequent cause of PH in BD patients was group II PH. There were also significant number of patients with group IV PH. Pulmonary endarterectomy may be an option of treatment in inactive patients with group IV PH. <h3>Disclosure of Interest</h3> None declared
Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions
Authors: Vitor H. Teixeira, Christodoulos P. Pipinikas, Adam Pennycuick, Henry Lee-Six, Deepak Chandrasekharan, Jennifer Beane, Tiffany J. Morris, Anna Karpathakis, Andrew Feber, Charles E. Breeze, Paschalis Ntolios, Robert E. Hynds, Mary Falzon, Arrigo Capitanio, Bernadette Carroll, Pascal F. Durrenberger, Georgia Hardavella, James M. Brown, Andy G. Lynch, Henry Farmery, Dirk S. Paul, Rachel C. Chambers, Nicholas McGranahan, Neal Navani, Ricky M. Thakrar, Charles Swanton, Stephan Beck, Phillip Jeremy George, Avrum Spira, Peter J. Campbell, Christina Thirlwell, Sam M. Janes
Journal: Nature Medicine (2019)
Idelalisib for Treatment of Follicular Lymphoma and Chronic Lymphocytic Leukemia in Clinical Trials Versus the Real World: Treatment Duration and Survival Are Associated with Pretreatment Modified Charlson Score
Authors: Steven T Bird, Natasha Flowers, Fang Tian, Donna Przepiorka, Tae Hyun Jung, Rongrong Wang, Zebulin Kessler, Corinne Woods, Bo Kim, Barry W. Miller, Michael Wernecke, Stephen McKean, Clara Kim, Kate Gelperin, Jeffrey A Kelman, David J Graham
Journal: Blood (2018)
AB1272 Increasing strengths of evidence for role of nurses in the management of chronic inflammatory arthritis: results of a systematic literature review
Authors: V. Lion, M. Schirmer
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In 2011 EULAR first published European recommendations for the potential role of nurses in the management of patients with rheumatic diseases.<sup>1</sup> Since then, the EULAR recommendations were well disseminated and positively evaluated both across Europe and the United States (US).<sup>2</sup> <h3>Objectives</h3> To assess new evidence for the role of nurses in the management of chronic inflammatory arthritis (CIA) obtained since the 2011 EULAR recommendations. <h3>Methods</h3> A systematic literature search was performed for the time between 1/2010 and 9/2016 based on the PRISMA guidelines, using the search strategies and eligibility criteria and categorising evidence as did the EULAR taskforce. <h3>Results</h3> A total of 44 articles and 10 abstracts were identified fulfilling the eligibility and exclusion criteria. Strong new evidence exists for recommendation 3 with nurse-led telephone services to enhance continuity of care and to provide ongoing support (evidence level 3), and – at least in part – for recommendation 6, that nurses should promote self-efficacy (evidence level 1B) and empowerment (evidence level 2B), but sense of control was not studied. Some new evidence also exists for recommendations 7 and 8 (level 2B). <h3>Conclusions</h3> This literature review reveals new evidence for a role of nurses in managing CIA-patients especially with RA and in stable and low disease activity, and thus further supports the existing 2011 EULAR-recommendations. <h3>References</h3> [1] van Eijk-Hustings Y, van Tubergen A, Boström C, et al. (2012) EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis. Ann Rheum Dis71:13–19 [2] van Eijk-Hustings Y, Ndosi M, Buss B, et al. (2014) Dissemination and evaluation of the European League Against Rheumatism recommendations for the role of the nurse in the management of chronic inflammatory arthritis: results of a multinational survey among nurses, rheumatologists and patients. Rheumatology53:1491–96 <h3>Acknowledgements</h3> - <h3>Disclosure of Interest</h3> None declared
Remarkable Functional Constraints on the Antigen Receptors of CLL Stereotyped Subset #2: High-Throughput Immunogenetic Evidence
Authors: Katerina Gemenetzi, Andreas Agathangelidis, Lesley-Ann Sutton, Elisavet Vlachonikola, Chrysi Galigalidou, Fotis Psomopoulos, Maria Gounari, Achilles Anagnostopoulos, Raphael Sandaltzopoulos, Richard Rosenquist, Kostas Stamatopoulos, Anastasia Hadzidimitriou
Journal: Blood (2018)
AB0289 Paraoxonasa 1 activity is modulated by anti-rheumatic treatment and l55m polymorphism in patients with rheumatoid arthritisfrom southern mexico
Authors: O. Zaragoza-García, M.E. Moreno-Godínez, I. Parra-Rojas, J.E. Navarro-Zarza, N. Castro-Alarcón, I.P. Guzmán-Guzmán
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme with anti-atherogenic properties. Although genetic polymorphisms are known to modulate PON-1 activity,<sup>1</sup> other factors as the consumption of disease-modifying anti-rheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs) can also modulate its function.<sup>2</sup> <h3>Objectives</h3> To analyse the association between PON-1 activity according to L55M polymorphism and anti-rheumatic treatment in patients with rheumatoid arthritis (RA) from southern Mexico. <h3>Methods</h3> Serum PON1 activity, using 4-chlorometyl phenylacetate (4-CMPA) as substrate<sup>3</sup> was quantified in 246 RA patients (181 treated with DMARDs, NSAIDs and/or corticosteroids, and 65 without treatment). The PON1 rs854560 genotype (L55M) was determined by the PCR-RFLP method. <h3>Results</h3> PON-1 activity was decreased in RA patients under treatment anti-rheumatic. In addition, an effect of LM/MM genotype of L55M polymorphism was noted in treated patients who exhibiting the lowest PON-1 activity (10.45 vs 13.91 U/mL, p=0.05). The distribution of L55M genotypes were; 86.8% (LL), 12.8% (LM) and 0.4% (MM). The Leflunamide and diclofenac drugs were associated with the mainly decrease of the PON-1 activity (p&lt;0.05), compared with others DMARDs, NSAIDs and corticosteroids drugs used to RA in pharmacological regimens. <h3>Conclusions</h3> PON-1 activity is impaired in association with the anti-rheumatic treatment and L55M polymorphism, so in patients with RA the susceptible background genetic could contribute to increasing the cardiovascular risk linked to PON-1 activity. <h3>References</h3> [1] Leviev I, Deakin S, James RW. Decreased stability of the M54 isoform of paraoxonase as a contributory factors to variations in human serum paraoxonase concentrations. J Lipid Res. 2001;42:528–535. [2] Dilek E, Polat MF. In vitro inhibition of three different drugs used in rheumatoid arthritis treatment on human serum paraoxanase 1 enzyme activity. Protein Pept Lett. 2016;23(1):3–8. [3] Richter RJ, Jarvik GP, Furlong CE. Determination of paraoxonase 1 status without the use of toxic organophosphate substrates. Cir Cardiovasc Genet. 2008;1:147–152. <h3>Disclosure of Interest</h3> None declared
Distinct Molecular Profiles and Immunotherapy Treatment Outcomes of V600E and V600K <i>BRAF</i>-Mutant Melanoma
Authors: Inês Pires da Silva, Kevin Y.X. Wang, James S. Wilmott, Jeff Holst, Matteo S. Carlino, John J. Park, Camelia Quek, Matthew Wongchenko, Yibing Yan, Graham Mann, Douglas B. Johnson, Jennifer L. McQuade, Rajat Rai, Richard F. Kefford, Helen Rizos, Richard A. Scolyer, Jean Y.H. Yang, Georgina V. Long, Alexander M. Menzies
Journal: Clinical Cancer Research (2019)

BRAF V600E and V600K melanomas have distinct clinicopathologic features, and V600K appear to be less responsive to BRAFi±MEKi. We investigated mechanisms for this and explored whether genotype affects response to immunotherapy.Pretreatment formalin-fixed paraffin-embedded tumors from patients treated with BRAFi±MEKi underwent gene expression profiling and DNA sequencing. Molecular results were validated using The Cancer Genome Atlas (TCGA) data. An independent cohort of V600E/K patients treated with anti-PD-1 immunotherapy was examined.Baseline tissue and clinical outcome with BRAFi±MEKi were studied in 93 patients (78 V600E, 15 V600K). V600K patients had numerically less tumor regression (median, -31% vs. -52%, P = 0.154) and shorter progression-free survival (PFS; median, 5.7 vs. 7.1 months, P = 0.15) compared with V600E. V600K melanomas had lower expression of the ERK pathway feedback regulator dual-specificity phosphatase 6, confirmed with TCGA data (116 V600E, 17 V600K). Pathway analysis showed V600K had lower expression of ERK and higher expression of PI3K-AKT genes than V600E. Higher mutational load was observed in V600K, with a higher proportion of mutations in PIK3R1 and tumor-suppressor genes. In patients treated with anti-PD-1, V600K (n = 19) had superior outcomes than V600E (n = 84), including response rate (53% vs. 29%, P = 0.059), PFS (median, 19 vs. 2.7 months, P = 0.049), and overall survival (20.4 vs. 11.7 months, P = 0.081).BRAF V600K melanomas appear to benefit less from BRAFi±MEKi than V600E, potentially due to less reliance on ERK pathway activation and greater use of alternative pathways. In contrast, these melanomas have higher mutational load and respond better to immunotherapy.