tbuckley/cabot-search huggingface dataset:
Abstract 18044: Predictors of Bicuspid Aortic Valve Associated Aortopathy in Pediatric Patients
Authors: Michael Grattan, Andrea Prince, Anders Franco-Cereceda, Michele Petrovic, Salah A Mohamed, Bart Loeys, Harry Dietz, Seema Mital, Cedric Manlhiot, Gregor Andelfinger, Luc Mertens
Journal: Circulation (2015)

Bicuspid aortic valve (BAV) is the most common congenital heart disease and is commonly associated with significant ascending aorta dilation. Valve morphology and function have been proposed as potential risk factors; however evaluating their role is difficult, as BAV morphology and valve function are inherently related. Our objective was to determine whether BAV morphology and function are independently associated with ascending aorta dilation in pediatric patients. We performed a multicenter, retrospective, cross-sectional study of pediatric patients with BAV that were followed after 2003. The last patient echocardiogram prior to valve intervention was analyzed for BAV morphology, presence and severity of aortic stenosis (AS) and insufficiency (AI), and aortic root and ascending aorta dimensions. The relationship of potential risk factors to ascending aorta dimensions at different ages was determined using linear regression. Data was obtained from 1725 patients (68% male). The most common BAV morphology was right-left (R-L) coronary cusp fusion (65%) followed by right-non (R-N) fusion (34%) and left-non fusion (1%). Fourteen percent of patients had at least moderate AS and 7% had at least moderate AI. R-L fusion was associated with coarctation (55%), while R-N fusion was less associated with coarctation (19%) and more associated with valve dysfunction (24% and 12% with at least moderate AS and AI). Twenty-seven percent of patients had significant ascending aorta dilation (Z score &gt;3). AS and AI were associated with more significant ascending aorta dilation and a faster Z-score progression over time. R-N fusion was associated with ascending aorta dilation; however, when valves with AS and AI were excluded, there were no differences related to morphology. In patients with no AS or AI, 15% had significant ascending aorta dilation. In this large pediatric cohort of patients with BAV, we show that valve morphology is not independently associated with ascending aorta dilation. Valve dysfunction (both AS and AI) is associated with more significant dilation; however, even in valves with normal function, there is significant ascending aorta dilation. We suggest that there is an inherent arterial abnormality, possibly modified by aortic flow patterns.
Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial
Authors: Mark C Genovese, Roy Fleischmann, Bernard Combe, Stephen Hall, Andrea Rubbert-Roth, Ying Zhang, Yijie Zhou, Mohamed-Eslam F Mohamed, Sebastian Meerwein, Aileen L Pangan
Journal: The Lancet (2018)
Association of <i>ERBB</i> Mutations With Clinical Outcomes of Afatinib- or Erlotinib-Treated Patients With Lung Squamous Cell Carcinoma
Authors: Glenwood D. Goss, Enriqueta Felip, Manuel Cobo, Shun Lu, Konstantinos Syrigos, Ki Hyeong Lee, Erdem Göker, Vassilis Georgoulias, Wei Li, Salih Guclu, Dolores Isla, Young Joo Min, Alessandro Morabito, Andrea Ardizzoni, Shirish M. Gadgeel, Andrea Fülöp, Claudia Bühnemann, Neil Gibson, Nicole Krämer, Flavio Solca, Agnieszka Cseh, Eva Ehrnrooth, Jean-Charles Soria
Journal: JAMA Oncology (2018)

Treatment choice for lung squamous cell carcinoma could be aided by identifying predictive biomarkers.To assess whether patient outcomes in the LUX-Lung 8 trial were associated with ERBB gene family member aberrations in tumor specimens.Ad hoc secondary analysis of the LUX-Lung 8 trial conducted at 183 centers in 23 countries from March 30, 2012, to January 30, 2014. Eligible patients had stage IIIB or IV lung squamous cell carcinoma with progressive disease after 4 or more cycles of platinum-based chemotherapy. Tumor genetic analysis (TGA) was performed using next-generation sequencing in a cohort enriched for patients with progression-free survival (PFS) of more than 2 months. Epidermal growth factor receptor (EGFR) expression levels were assessed by immunohistochemistry in a separate cohort of patients from the LUX-Lung 8 population. Associations of PFS and overall survival (OS) with ERBB gene alterations and EGFR expression levels were assessed. This analysis was conducted from February 26, 2015, to June 12, 2017.Patients were randomized 1:1 to treatment with afatinib dimaleate (40 mg/d; n = 398) or erlotinib hydrochloride (150 mg/d; n = 397).Overall survival, PFS, pooled and individual ERBB gene mutations, ERBB copy number alterations, and EGFR expression.Tumor specimens from 245 patients were eligible for next-generation sequencing (TGA subset: 132 patients treated with afatinib; 113 patients treated with erlotinib). In this population, outcomes were improved with afatinib vs erlotinib treatment (PFS: median, 3.5 vs 2.5 months; hazard ratio [HR], 0.69; 95% CI, 0.51-0.92; P = .01; OS: median, 8.4 vs 6.6 months; HR, 0.81; 95% CI, 0.62-1.05; P = .12). Of 245 patients in the TGA subset, 53 (21.6%) had tumors with 1 or more ERBB mutations. Among afatinib-treated patients, PFS (median, 4.9 vs 3.0 months; HR, 0.62; 95% CI, 0.37-1.02; P = .06) and OS (median, 10.6 vs 8.1 months; HR, 0.75; 95% CI, 0.47-1.17; P = .21) were longer among those with ERBB mutation-positive disease than among those without. The presence of HER2 mutations was associated with favorable PFS and OS following afatinib vs erlotinib treatment. There was no apparent association between copy number alteration or EGFR expression level and outcome.Next-generation sequencing may help identify patients with lung squamous cell carcinoma who would derive additional benefit from treatment with afatinib. The role of ERBB mutations, particularly HER2 mutations, as predictive biomarkers for afatinib treatment in this setting warrants further evaluation.ClinicalTrials.gov Identifier: NCT01523587.
Obesity Paradox in the Clinical Significance of Effective Prosthetic Orifice Area After Aortic Valve Replacement
Authors: Augustin Coisne, Sandro Ninni, Jean-Louis Edmé, Thomas Modine, Stéphanie Mouton, Rosario Pilato, Hélène Ridon, Marjorie Richardson, Cedric Klein, Staniel Ortmans, Claire Seunes, Anne-Laure Madika, Guillaume Ledieu, Mathilde Jacquelinet, Bertrand Boutie, Alexandre Altes, Flavien Vincent, Mohamad Koussa, Bruno Jegou, André Vincentelli, Francis Juthier, Emmanuel Robin, Bart Staels, Patrizio Lancellotti, David Montaigne
Journal: JACC. Cardiovascular imaging (2018)
Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1–infected individuals
Authors: Mathieu Uzzan, Minami Tokuyama, Adam K. Rosenstein, Costin Tomescu, Ivo N. SahBandar, Huaibin M. Ko, Louise Leyre, Anupa Chokola, Emma Kaplan-Lewis, Gabriela Rodriguez, Akihiro Seki, Michael J. Corley, Judith Aberg, Annalena La Porte, Eun-young Park, Hideki Ueno, Ioannis Oikonomou, Itai Doron, Iliyan D. Iliev, Benjamin K. Chen, Jennifer Lui, Timothy W. Schacker, Glaucia C. Furtado, Sergio A. Lira, Jean-Frederic Colombel, Amir Horowitz, Jean K. Lim, Nicolas Chomont, Adeeb H. Rahman, Luis J. Montaner, Lishomwa C. Ndhlovu, Saurabh Mehandru
Journal: Science Translational Medicine (2018)

Gut homing CD4+ T cells expressing the integrin α4β7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-α4β7 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-α4β7 treatment. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4β7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for maintaining viral reservoirs, their attrition by anti-α4β7 therapy has important implications for HIV-1 therapeutics and eradication efforts and defines a rational basis for the use of anti-α4β7 therapy in HIV-1 infection.
SAT0430 Assessment of acr and slicc classification criteria in the asia pacific lupus collaboration cohort
Authors: R. Kandane-Rathnayake, V. Golder, W. Louthrenoo, S.-F. Luo, Y.-J. Wu, A. Lateef, S. Sockalingam, S. Navarra, L. Zamora, L. Hamijoyo, Y. Katsumata, M. Harigai, M. Chan, S. O’Neill, F. Goldblatt, C.S. Lau, A. Hoi, M. Nikpour, E. Morand
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with systemic lupus erythematosus (SLE) are commonly assessed using the classification criteria developed by the American College of Rheumatology (ACR), or more recently by the Systemic Lupus International Collaborating Clinics (SLICC). Although SLE is highly prevalent and severe in Asians, no comparison of patients meeting these criteria in predominantly Asian SLE patients has been performed. <h3>Objectives</h3> To compare patients meeting the ACR and SLICC classification criteria in the Asia Pacific Lupus Collaboration (APLC) cohort. <h3>Methods</h3> All patients fulfilled either the <sup>ACR (1997)</sup> criteria (≥4 of 11 items) or SLICC criteria (≥4 of 17 items, including ≥1 clinical and ≥1 immunologic criteria, or biopsy-proven lupus nephritis (LN) +≥1 immunological criterion), evaluated at enrolment. Demographic and clinical data were compared using Kruskal Wallis (for medians) chi-squared (proportions) tests. <h3>Results</h3> 1735 patients were studied with a median ([IQR] (range)) follow up of 795 [532, 1087] (0, 1443) days. 1716 (98.9%) and 1668 (96.1%) patients met SLICC and ACR criteria respectively. 1649 (95%) patients met both criteria, 67 (3.9%) patients met SLICC criteria only and 19 (1.1%) patients met ACR criteria only. Patients in ACR-only and SLICC-only groups were significantly older than those who met both criteria (ACR-SLICC group); ACR-only patients had longer observation period (table 1). 15/67 SLICC-only patients had non-scarring alopecia, which is not an ACR item, and 14 had LN with ≥1 immunologic criterion. Discrepancies between the 19 ACR-only patients and the ACR-SLICC group were predominantly observed in the immunological criteria. Both ACR-only and SLICC-only patients had lower SLEDAI-2k score at recruitment when compared to ACR-SLICC group, and a fewer SLICC-only patients were in flare (table 1). During the observation period, SLICC-only patients had the lowest time-adjusted mean (TAM) SLEDAI-2k and prednisolone dose; lowest proportions of flares and damage accrual, and highest proportion of patients achieving Lupus Low Disease Activity State (LLDAS) at least once. In contrast, ACR-only patients had the highest proportion of patients experiencing flares and least proportion of achieving LLDAS (table 1). <h3>Conclusions</h3> We observed a high overlap between the two classification criteria, but the use of both criteria captured a larger cohort overall. In this cohort, patients meeting SLICC but not ACR criteria had less active disease. <h3>Disclosure of Interest</h3> None declared
AB1479-HPR Multifaceted intervention to improve medication understanding and compliance among patients with autoimmune inflammatory rheumatic diseases
Authors: R Thakran, S.S. Baghel, C. Messi, S. Garg, S. Kapoor, V. Kashyap, Q. Zaheer, A. Malaviya
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Non-compliance with treatment in patients with autoimmune inflammatory rheumatic diseases are directly associated with relapse, deformities and higher treatment cost. Many of times it can be related to poor understanding of complex drug regimen. Consistent reports of suboptimal treatment adherence among patients with autoimmune inflammatory rheumatic disease underscore the importance of understanding how adherence can be promoted and supported. <h3>Objectives</h3> To evaluate the efficacy of various methods of drug explanation to AIRD patients in rheumatology OPD. <h3>Methods</h3> It is a retrospective study of 100 DMARD naive first visit patients in rheumatology OPD. Demographic and clinical information were noted in pre-designed performa. After prescription of DMARDs regimen by rheumatologists, various methods are used to explain the advised prescription such as using permanent markers on medication strips, making envelops, using different medication performa in their local language, as well as counselling regarding importance of medication; done by rheumatology nurse. Adherence rate and reasons of non adherence was measured by different methods like interview, pill counts, review of prescription on their routine follow up visits. <h3>Results</h3> 1. 79.8% of patients fully understood and had adherence with their prescribed medication. 2. 20.2% were non-adherent with the prescribed treatment, varying from occasional to complete failure. The factors for non-adherence were identified. a) 25% patients stopped when no symptoms. b) 22.5% got influenced by alternative therapy. c) 20% family pressure and financial constrains. d) 12% of myths about side effects of medication. e) 15% lost follow up. f) 5% had doubts could not understood properly. On statical analysis of all methods of drug explanation, use of permanent marker on medicine strips were found to be most effective. <h3>Conclusions</h3> As per results non –adherence to treatment due to poor understanding of drug regimen is very low. But another factors were identified which have influence over adherence rate. In a busy OPD a single sitting counselling is not adequate. To summarise patients need more intensified and focused counselling to improve adherence. <h3>Reference</h3> [1] Improving treatment adherence in patients with rheumatoid arthritis: what are the options? Marengo MF,et al.Int J Clin Rheumtol.2015 <h3>Acknowledgements</h3> Special thanks Dr. Parth Sharma and Mr. Himanshu Negi <h3>Disclosure of Interest</h3> R. Thakran: None declared, S. Baghel: None declared, C. Messi: None declared, S. Garg Consultant for: Advisory board of ipca,pfizer,roche, S. Kapoor Consultant for: Advisory board of intas,zydus, V. Kashyap: None declared, Q. Zaheer: None declared, A. Malaviya Consultant for: Advisory board of ipca,pfizer,roche
Abstract 9733: Atrial Fibrosis is Associated With Higher DC Cardioversion Failure Rates in Persistent Atrial Fibrillation
Authors: Mohamed R Labedi, Abdulmohsin Ahmadjee, Mathias Koopman, Nassir Marrouche, Brent Wilson, Nazem Akoum
Journal: Circulation (2015)

Introduction: DC cardioversion (DCCV) is commonly performed in atrial fibrillation (AF). We examined the association between atrial fibrosis quantified using late gadolinium enhancement MRI (LGE-MRI) and acute success and recurrence of AF following DCCV. Methods: Persistent AF patients without previous catheter ablation who underwent LGE-MRI and DCCV were included in the study. Acute DCCV success was defined by achievement of sinus rhythm. Demographic patient data as well as comorbidities and medications were collected from chart revisions. Results: 241 patients were included (63% male). 186 patients (77.48%) were on oral anti-coagulation, 31 (12.9%) were on class I anti-arrhythmic drugs (AAD) and 46 (19.1%) were on class III AAD at the time of cardioversion. DCCV was acutely successful in 183 patients (75.9%). AF recurred after DCCV in 194 patients (80.5%) after an average follow up of 81 days. In univariate analysis, atrial fibrosis (HR 1.04; p=0.049) and body mass index (BMI) (HR 1.04; p=0.03) were associated with DCCV failure, while left atrial area, beta blocker, calcium channel blocker, class I and class III anti-arrhythmic drug use were not. In multivariate analysis, only atrial fibrosis was a significant predictor of DCCV failure (HR 1.03; p=0.03). During follow up, anti-arrhythmic drug use (class I drugs HR 0.21; p=0.045; class III drugs HR 0.27; p=0.042) was associated with maintenance of sinus rhythm. Conclusions: LGE-MRI quantified atrial fibrosis predicts failure of DCCV in persistent AF patients while AAD use was associated with maintenance of sinus rhythm.
SP0122 Tapering in axial spondyloarthritis – to do or not to do?
Authors: D. Poddubnyy
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> According to the current version of the ASAS-EULAR management recommendations for axial spondyloarthritis, tapering of a biological disease modifying anti-rheumatic drug (bDMARD) can be considered once a remission is achieved. Tapering is opposed to a complete discontinuation that is associated with a very high disease flare risk (70%–100%) in axial spondyloarthritis. The question of tapering in axial spondyloarthritis has been addressed in a number of small clinical trials: in the majority of the them, tapering (either dose reduction or increase of the injection/infusion interval) could be done without a disease flare. It is, however, not clear, whether the tapering has any beneficial effect for a patient (i.e., in terms of safety) in addition to a cost-saving effect. Further, a number of questions related to tapering still requires an evidence-based answer: a) what is the optimal time-point of the initiation of tapering (e.g, 3, 6 or 12 months after remission achievement)? b) what is the optimal tapering regimen? c) are there reliable predictors of sustained remission/disease flare during tapering? The question of a bDMARD tapering after remission achievement will be at least partially answered in ongoing phase 4 trials with TNF blockers in non-radiographic axial spondyloarthritis. An appropriately designed and powered long-term trial is needed to investigate possible long-term benefits and risks of treatment tapering in axial spondyloarthritis. <h3>Disclosure of Interest</h3> None declared
SAT0482 Undifferentiated connective tissue disease at risk for systemic sclerosis: predictive role of anti-topoisomerase and avascular areas
Authors: A. Riccardi, V. Messiniti, S. Fasano, G. Valentini
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc) is a condition characterised by Raynaud's phenomenon and either SSc marker autoantibodies or typical capillaroscopic findings or both, unsatisfying classification criteria for SSc<sup>1</sup> and reported to evolve into definite SSc in about 50% of 60 cases over a 12–102 months follow-up time.<sup>2</sup> We found marker autoantibody positivity to predict the evolution into <sup>SSc satisfying 2013</sup> ACR criteria for the disease.<sup>3</sup> <h3>Objectives</h3> To investigate in patients followed-up for a longer time if distinct marker autoantibody specificities have a different predictive value. <h3>Methods</h3> Sixty-five patients consecutively admitted to a tertiary Rheumatology Unit from November 1 st 2000 to December 31 st 2016 and diagnosed as UCTD-risk-SSc were enrolled in the study. Patients were monitored for a median of 27 months (range 6–144) and were evaluated twice yearly to assess disease progression. Kaplan-Meier curves and the log-rank test were used to analyse differences in fulfilling the criteria for SSc between subsets. Risk prediction was assessed by univariate Cox regression analysis. <h3>Results</h3> During follow-up 40/53 marker autoantibody-positive patients (75.5%) versus 3/12 (25%) marker autoantibody negative ones satisfied SSc criteria (p=0.006). Out of them, 11/12 (91.7%) anti-topoisomerase (Scl70) positive versus 29/40 (72.5%) anti-centromere (ACA) positive patients evolved into definite SSc (p=0.04). In univariate analysis, anti-Scl70 positivity increased by 2-fold the risk of a definite SSc outcome (HR 2.1 95% CI 0.9–4.4) with respect to ACA positivity (HR 0.5 95% CI 0.2–1.0) (p=0.05). In addition 3/3 (100%) patients with avascular areas at baseline versus 40/62 (64.5%) with megacapillaries only or no capillaroscopic abnormalities satisfied SSc criteria over a 12–38 months follow-up time (p=0.06). <h3>Conclusions</h3> We confirm that autoantibody positivity patients presents a faster evolution. Moreover we first detected an increased HR of Scl-70 versus ACA positivity and a potential role of baseline detected avascular areas. <h3>References</h3> [1] Valentini G. Undifferentiated Connective Tissue Disease at risk for systemic sclerosis (SSc) (so far referred to as very early/early SSc or pre-SSc). Autoimmun Rev2015. [2] Valentini G, et al. Early Systemic Sclerosis: Analysis of the Disease Course in Patients With Marker Autoantibody and/or Capillaroscopic Positivity. Arthritis Care Res2014. [3] van den Hoogen F, et al. 2013classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis2013. <h3>Disclosure of Interest</h3> None declared
The acute-to-chronic workload ratio: an inaccurate scaling index for an unnecessary normalisation process?
Authors: Lorenzo Lolli, Alan M Batterham, Richard Hawkins, David M Kelly, Anthony J Strudwick, Robin T Thorpe, Warren Gregson, Greg Atkinson
Journal: British Journal of Sports Medicine (2018)

An important question for researchers and practitioners is whether an individual’s risk of injury increases if they make prior changes to their training load.1 In this field of research, ‘load’ typically refers to in-training distances covered, speed and accelerations.1 Attention has generally focused on whether a person’s acute (eg, 7 day) increase in load, normalised to that person’s prior ‘baseline’ of chronic (eg, 28 day) load, predicts injury.1 To obtain this normalised predictor, acute load is typically divided by chronic load to provide the acute-to-chronic workload ratio (ACWR).1 

Fundamentally, simple ratios (Y/X) are formulated to ‘ control for ’ a denominator variable (eg, preceding chronic load) that is perceived to have an important biological influence on the numerator variable (eg, acute load).2 Within this notion of ‘ control for ’,3 it is generally posited that the denominator is a ‘nuisance’ variable that is associated with the numerator of interest.2 Logically, a simple ratio index provides meaningful relative measures for clinical and prognostic purposes only if (1) there is a ‘true’ and ‘proportional’ association between numerator and denominator in the first place, and (2) the ratio normalises for the denominator in a consistent manner for all individuals in the measurement range.2 

We have demonstrated recently that the typical practice in the current literature1 of including, …