tbuckley/cabot-search huggingface dataset:
SAT0106 Advances in therapeutic management with first biological therapy in rheumatoid arthritis throughout 15 years
Authors: P. Bogas, C. Plasencia, V. Navarro-Compán, D. Benavent, G. Bonilla, L. Nuño, I. Monjo, G. González, J. Molina, A. Balsa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In the last two decades the treatment in patients with rheumatoid arthritis (RA) has undergone major advances, especially due to the appearance of new therapies, the use of the "treat to target" strategy and a better understanding of the "window of opportunity" concept. However, data from clinical practise confirming the benefits of using these strategies are scarce. <h3>Objectives</h3> To investigate whether the proportion of patients (pts) with RA in maintained remission (R) or low disease activity (LDA) after starting a first biological agent has increased over time and which factors are associated with this change. <h3>Methods</h3> Analysis of a database from a prospective cohort including 365 pts with RA starting a 1st biological agent (BA) (TNF inhibitor, abatacept or tocilizumab) in a tertiary hospital between 2000-2014. Demographic, clinical and analytical data were collected at the beginning of treatment and clinical activity (DAS28) was measured every 6 months. For this study, 3 groups were established according to BA initiation date: interval 1 (i1) (between 2000-2004), (i2) 2005-2009 and (i3) 2010-2014, with a minimum follow-up of 2 years at all pts. For each interval, the percentage of pts achieving maintained (at least 3 consecutive visits) R (DAS28 &lt;2.6) or LDA (DAS28 &lt;3.2) was determined. In addition, all variables collected were compared between groups by ANOVA and chi square test. <h3>Results</h3> Out of the 365 pts initiating a 1st BA, 133 started in i1, 122 in i2 and 110 in i3. Of these, 38% (n=137) achieved maintained R/LDA. This percentage increased significantly in successive intervals (31% in i1 vs, 38% in i2 vs 45% in i3, p=0.02). Baseline characteristics of pts achieving R/LDA are shown in table 1A. For patients in i2 and i3, compared to the previous interval (i1 and i2 respectively), a significant higher frequency of use of BA with different mechanisms of action (0% in i1 vs 2.2% in i2 vs 34% in i3, p&lt;0.001), women (56% in i1 vs 76% in i2 vs 84% in i3, p=0.01) and concomitant methotrexate (56% in i1 vs 74% in i2 vs 81% in i3, p=0.03) was found. On the other hand, the percentage of optimized pts increased significantly over time (13% in i1 vs 32% in i2 vs 56% in i3, p&lt;0.001; table 1B). <h3>Conclusions</h3> The percentage of pts with RA achieving maintained R/LDA after initiating a 1st BA has progressively increased over time. This is probably related to a greater use of BAs with different mechanisms of action and concomitant methotrexate. The sustained control of disease activity may allow using more frequently optimized doses of BA. <h3>Disclosure of Interest:</h3> None declared
FRI0122 Drug survival of adalimumab in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis over 10 years in real-world setting of czech registry attra
Authors: K. Pavelka, J. Zavada, Z. Kristkova, L. Szczukova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Drug survival in real clinical practice is reflecting both efficacy and safety of the drug. It is valuable outcome measure complementary to data from RCT. <h3>Objectives</h3> To evaluate 10 years efficacy and survival of adalimumab (ADA) in Czech registry ATTRA. To analyse reasons for drug discontinuation and analyse baseline demographic and clinical characteristics predictive for drug discontinuation. We also aimed to compare survival of ADA between 3 different diagnosis (RA, AS, SpA). Finally we aimed to compare survival between different anti TNF drugs. <h3>Methods</h3> All patients fulfilled criteria of Czech Rheum. Soc. for indication of anti TNF therapy and were included in registry. They were followed each 3 month first year and than each 6 month. The main outcome measures in RA were DAS 28, HAQ, EuroQuol, SF36, CRP, in AS BASDAI, HAQ and ASDAS. Reasons for drug discontinuation were reported as primary failure, secondary failure, adverse advent, remission and others. Statistics – survival on therapy was estimated by Kaplan-Meier analysis. The search for outcome predictors was performed by log-rank test (continuous predictors were appropriately categorized). <h3>Results</h3> Altogether 3159 patients with RA, 1785 with AS and 723 with PsA were included. 1598 patients with RA were treated with adalimumab and retention was 75,8 % in one year, 43,8 % in 5 years and 27,7 % in 10 years. The reasons for drug discontinuation were: primary failure 24,9 %, secondary failure 30,5 %, and adverse events (19,8 %) Predictive factors for adalimumab retention in rheumatoid arthritis were: younger age &lt; 50 years, failure of ≤ 1 csDMARDs in past, combination therapy with csDMARDs at baseline. Sex, RF and anti CCP were not predictive. Drug retention was longest in AS (median 99,6 m), than PsA (median 62,5 m) and shortest in RA (median 43,9 m) (graph 1). Drug survival in rheumatoid arthritis was longer on etanercept than on infliximab (p &lt; 0,001), longer on adalimumab than infliximab (p &lt; 0,001) and equal between adalimumab and etanercept (p = 0,85). <h3>Conclusions</h3> Adalimumab retention in registry ATTRA was comparable to other European registries. Predictors of drug retention in RA were: younger age (&lt; 50 years), ≤ 1 csDMARDs in past and in combination with csDMARDs. Survival on adalimumab was longer in AS, than PsA and RA and the same was true for all three anti TNF drugs. Survival on drug in rheumatoid arthritis was longer in adalimumab and etanercept compared to infliximab. <h3>References</h3> Key words: biologic therapy, registry ATTRA <h3>Disclosure of Interest</h3> None declared
FRI0149 Inflammation intensity-dependent expression of osteoinductive wnt proteins is critical for ectopic new bone formation in ankylosing spondylitis
Authors: H. Liu, X. Li, J. Wang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To investigate the molecular mechanism underlying the inflammation- related ectopic new bone formation in ankylosing spondylitis (AS). <h3>Methods</h3> Spinal tissues and sera were collected from patients or normal volunteers to detect the expression of Wnt proteins. An <i>in vitro</i> cell culture system mimicking the local inflammatory microenvironment of bone-forming sites was established to study the relationship between inflammation and Wnt expression, the regulatory mechanism of inflammation-induced Wnt expression and the role of Wnt signalling in new bone formation. A modified collagen-induced arthritis (mCIA) and a proteoglycan -induced spondylitis (PGIS) animal model were used to confirm the key findings<i> in vivo</i>. <h3>Results</h3> The levels of osteoindcutive Wnt proteins were obviously increased in the sera and spinal ligament tissues of patients with AS. Only constitutive low-intensity TNF-α stimulation, but not short-term or high-intensity TNF-α stimulation, induced persistent expression of osteoinductive Wnt proteins and subsequent bone formation through NF-κB (p65) and JNK/AP-1 (c-Jun) signalling pathways. Furthermore, inhibition of either Wnt/β-catenin or Wnt/PKCδ pathway significantly suppressed new bone formation. The increased expression of Wnt proteins was confirmed in both mCIA and PGIS models. A kyphotic and ankylosing phenotype of the spine was observed during long-term observation in mCIA model. Inhibition of either Wnt/β-catenin or Wnt/PKCδ signalling pathway significantly reduced the incidence and severity of this phenotype. <h3>Conclusions</h3> Inflammation intensity-dependent expression of osteoinductive Wnt proteins is a key link between inflammation and ectopic new bone formation in AS. Activation of both canonical Wnt/β-catenin and noncanonical Wnt/PKCδ pathways is required for inflammation-induced new bone formation. <h3>Disclosure of Interest</h3> None declared
Colorectal Carcinomas Containing Hypermethylated MLH1 Promoter and Wild-Type BRAF/KRAS Are Enriched for Targetable Kinase Fusions
Authors: Emiliano Cocco, Jamal Benhamida, Sumit Middha, Ahmet Zehir, Kerry Mullaney, Jinru Shia, Rona Yaeger, Liying Zhang, Donna Wong, Liliana Villafania, Khedoudja Nafa, Maurizio Scaltriti, Alexander Drilon, Leonard Saltz, Alison M. Schram, Zsofia K. Stadler, David M. Hyman, Ryma Benayed, Marc Ladanyi, Jaclyn F. Hechtman
Journal: Cancer Research (2019)

Kinase fusions are rare and poorly characterized in colorectal carcinoma, yet they present unique opportunities for targeted therapy. In this study, we characterized kinase fusions from patients with advanced colorectal carcinoma who had MSK-IMPACT testing of their tumors between January 2014 and June 2018. Patients were analyzed for the presence of fusions, microsatellite instability (MSI), and RAS/BRAF mutations. Mismatch repair (MMR), IHC, and promoter hypermethylation status of MLH1 (MLH1ph) in microsatellite instability-high (MSI-H) colorectal carcinoma with fusions were investigated. Fusion transcripts were confirmed using a targeted RNA-seq panel assay. Of 2,314 colorectal carcinomas with MSK-IMPACT testing, 21 harbored kinase fusions. Overall 57% (12/21) of colorectal carcinoma fusions were MSI-H/MMR-D. Loss of MLH1 and MLH1ph was confirmed in all 12 and all 10 cases with available material, respectively. Fusions were present in 5% of MSI-H/MMR-D colorectal carcinoma compared with 0.4% of MSS/MMR-P colorectal carcinoma (P < 0.001) and 15% of MSI-H/MMR-D colorectal carcinoma with wild-type RAS/BRAF. Of 24 total MLH1-deficient colorectal carcinomas with MLH1ph and wild-type RAS/BRAF, 10 (42%) harbored kinase fusions. Kinase fusions in MSI-H colorectal carcinoma were associated with sporadic MLH1ph rather than with Lynch syndrome, and these patients may be eligible for kinase inhibitors, particularly following resistance or toxicity in response to immunotherapy. These findings identify a molecular subset of colorectal carcinoma with kinase fusions that may be responsive to kinase inhibitors.Significance: A high frequency of targetable kinase fusions in BRAF/RAS wild-type, MSI-H colorectal carcinoma offers a rationale for routine screening to identify patients with colorectal carcinoma with kinase fusions that may be responsive to kinase inhibitors.See related commentary by Valeri, p. 1041.
Sex-Related Differences in Low-Gradient, Low–Ejection Fraction Aortic Stenosis
Authors: Philipp Emanuel Bartko, Marie-Annick Clavel, Mohamed-Salah Annabi, Abdellaziz Dahou, Robin Ristl, Georg Goliasch, Helmut Baumgartner, Christian Hengstenberg, João L. Cavalcante, Ian Burwash, Maurice Enriquez-Sarano, Jutta Bergler-Klein, Joseph Rodés-Cabau, Philippe Pibarot, Julia Mascherbauer
Journal: JACC. Cardiovascular imaging (2019)
AB0455 Impact of one-year treatment with biotechnologic drugs on work disability and activity impairment in patients with rheumatoid arthritis
Authors: M. Manara, R. Caporali, R. Gorla, E. Fusaro, R. Pellerito, P.A. Rocchetta, P. Sarzi Puttini, S. Capri, L. Sinigaglia
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Disease activity significantly impacts on work ability of patients with Rheumatoid Arthritis (RA). Biologic agents can control disease activity, but their effects on productivity outcomes were not adequately investigated in Italian population. <h3>Objectives</h3> Aim of the study was to evaluate the impact of biologic therapy on work productivity outcomes in a cohort of biologic-naïve patients with active RA from northern Italy. <h3>Methods</h3> This is a multicentre prospective study on patients with active RA in working age (18–65 years), scheduled to undergo their first biologic treatment. Demographics and clinical data were collected at baseline and at 6 and 12 months, together with productivity outcomes assessed with the RA-specific work productivity survey (WPS-RA)<sup>1</sup> and the Health and Labour Questionnaire (HLQ)<sup>2</sup>. Primary outcome was the productivity loss or gain after 1 year of treatment. <h3>Results</h3> We included 100 patients from 7 rheumatology centres in northern Italy with active RA [mean DAS28: 5,1 (SD 0,9), median SDAI: 25,2 (IQR 18,7–33,2)]. Most of them were females (85%), with a mean age of 49,1 (SD: 10,3) years and a median disease duration of 7 (IQR: 3–14) years. Patients were treated with TNF-inhibitors (68%), Abatacept (24%) or Tocilizumab (8%). At baseline 39 patients were unemployed. After 1 year of treatment, 85 patients were still on follow-up, with an improvement in all indexes of disease activity [mean DAS28: 2,8 (SD 1,3), median SDAI: 5,1 (IQR 1,9–12,9)]. A significant reduction in number of days of work missed (absenteeism) and of reduced productivity (presenteeism) was observed in employed subjects, as well as a significant decrease in number of days missed of household work and social activities in all the study population (table 1). <h3>Conclusions</h3> One year of treatment with biological drugs was associated with a significant improvement in outcomes related to productivity both within and outside home in a cohort of patients with RA. <h3>References</h3> [1] Osterhaus JT. Arthritis Res Ther. 2009;11:R73. [2] Van Roijen L. Int J Technol Assess Health Care1996;12:405–15. <h3>Disclosure of Interest</h3> M. Manara: None declared, R. Caporali: None declared, R. Gorla: None declared, E. Fusaro: None declared, R. Pellerito: None declared, P. A. Rocchetta: None declared, P. Sarzi Puttini: None declared, S. Capri Consultant for: Pfizer, L. Sinigaglia: None declared
Physiotherapist-delivered stress inoculation training integrated with exercise versus physiotherapy exercise alone for acute whiplash-associated disorder (StressModex): a randomised controlled trial of a combined psychological/physical intervention
Authors: Michele Sterling, Rob Smeets, Gerben Keijzers, Jacelle Warren, Justin Kenardy
Journal: British Journal of Sports Medicine (2019)

Objective There are few effective treatments for acute whiplash-associated disorders (WAD). Early symptoms of postinjury stress predict poor recovery. This randomised controlled trial (StressModex) investigated whether physiotherapist-led stress inoculation training integrated with exercise is more effective than exercise alone for people with acute WAD. Methods 108 participants (&lt;4 weeks) at risk of poor recovery (moderate pain-related disability and hyperarousal symptoms) were randomly assigned by concealed allocation to either physiotherapist-led stress inoculation training and guideline-based exercise (n=53) or guideline-based exercise alone (n=55). Both interventions comprised 10 sessions over 6 weeks. Participants were assessed at 6 weeks and at 6 and 12 months postrandomisation. Analysis was by intention to treat using linear mixed models. Results The combined stress inoculation training and exercise intervention was more effective than exercise alone for the primary outcome of pain-related disability at all follow-up points. At 6 weeks, the treatment effect on the 0–100 Neck Disability Index was (mean difference) −10 (95% CI −15.5 to −4.48), at 6 months was −7.8 (95% CI −13.8 to −1.8) and at 12 months was −10.1 (95% CI −16.3 to −4.0). A significant benefit of the stress inoculation and exercise intervention over exercise alone was also found for some secondary outcomes. Conclusion A physiotherapist-led intervention of stress inoculation training and exercise resulted in clinically relevant improvements in disability compared with exercise alone—the most commonly recommended treatment for acute WAD. This contributes to the case for physiotherapists to deliver an early psychological intervention to patients with acute WAD who are otherwise at high risk of a poor outcome. Trial registration number ACTRN12614001036606.
FRI0084 Intense aerobic and resistance exercise reduces the frequency of peripheral blood regulatory cell populations in elderly patients with rheumatoid arthritis
Authors: S. Andersson, E. Lange, D. Kucherski, S. Svedlund, K. Önnheim, J. Lord, I.-L. Mårtensson, K. Mannerkorpi, I. Gjertsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> RA is an autoimmune joint disease driven by complex immune dysregulation. Exercise can improve immune health and is beneficial for physical function in elderly patients with RA, but the immunological mechanisms are largely unknown. <h3>Objectives</h3> We evaluated the effect of a person-centred randomised controlled exercise programme on regulatory immune cell populations in aged persons with RA. <h3>Methods</h3> Aged persons with RA were randomised to either a 20 week of aerobic and resistance exercise intervention of moderate-to high intensity (n=24) or to an active control group performing low-intensity home exercise (n=25). Blood samples were collected at baseline and after 20 weeks. The frequency of the adaptive regulatory populations Foxp3 +CD25+CD127 CD4+T cells and CD24hiCD38hi B cells and the CD33 +CD11b+myeloid derived suppressor cells were assessed using flow cytometry. <h3>Results</h3> After 20 weeks of exercise intervention there was a decrease in the frequency of Foxp3 +CD25+CD127 regulatory T cells and CD24hiCD38hi B cells but no change was observed in the active control group. The reduction in Tregs by exercise was most pronounced in the female participants. Despite lower levels of adaptive immune cell populations the disease activity did not increase. <h3>Conclusions</h3> Aerobic and resistance exercise in elderly patients with rheumatoid arthritis lead to a decreased number of regulatory Foxp3 +CD25+CD127 regulatory T cells and CD24hiCD38hi B cells. This decrease was not associated with an increased disease activity score or increased inflammation. <h3>Disclosure of Interest</h3> None declared
Utilising the Delphi Process to Develop a Proficiency-based Progression Train-the-trainer Course for Robotic Surgery Training
Authors: Justin W. Collins, Jeffrey Levy, Dimitrios Stefanidis, Anthony Gallagher, Mark Coleman, Tom Cecil, Anders Ericsson, Alexandre Mottrie, Peter Wiklund, Kamran Ahmed, Johann Pratschke, Gianluca Casali, Ahmed Ghazi, Marcos Gomez, Andrew Hung, Anne Arnold, Joel Dunning, Martin Martino, Carlos Vaz, Eric Friedman, Jean-Marc Baste, Roberto Bergamaschi, Richard Feins, David Earle, Martin Pusic, Owen Montgomery, Carla Pugh, Richard M. Satava
Journal: European Urology (2019)
Abstract 15234: Cardiovascular Disease Risk Prediction Using Machine Learning: A Prospective Cohort Study of 423,604 Participants
Authors: Ahmed M. Alaa, Thomas Bolton, Emanuele Di Angelantonio, James Harvey Rudd, Mihaela van der Schaar
Journal: Circulation (2018)

Introduction: Identifying people at risk of cardiovascular diseases (CVD) is a cornerstone of preventative cardiology. Risk prediction models currently recommended by clinical guidelines are based ...
Progression of Structural Damage in the Sacroiliac Joints in Patients With Early Axial Spondyloarthritis During Long‐Term Anti–Tumor Necrosis Factor Treatment: Six‐Year Results of Continuous Treatment With Etanercept
Authors: Valeria Rios Rodriguez, Kay‐Geert Hermann, Anja Weiß, Joachim Listing, Hildrun Haibel, Christian Althoff, Fabian Proft, Olaf Behmer, Joachim Sieper, Denis Poddubnyy
Journal: Arthritis & Rheumatology (2019)

Objective To evaluate radiographic progression in the sacroiliac ( SI ) joints and to identify its predictors during long‐term treatment (up to 6 years) with the tumor necrosis factor ( TNF ) inhibitor etanercept in patients with early axial spondyloarthritis (SpA). Methods Patients with early axial SpA who were treated with etanercept for up to 6 years in the Etanercept versus Sulfasalazine in Early Axial Spondyloarthritis ( ESTHER ) trial were selected based on the availability of radiographs of the SI joints. Two readers who were blinded with regard to clinical data scored the radiographs according to the modified New York criteria (range 0–4 per SI joint). A sacroiliitis sum score (total range 0–8) was calculated as the mean of the scores of the 2 readers. Active and chronic inflammatory changes in the SI joints on magnetic resonance imaging ( MRI ) performed at baseline, year 2, and year 4 were assessed according to the Berlin MRI scoring system. Results Of the 76 patients originally included in the study, 42 had radiographs of the SI joints available at baseline and at least 1 follow‐up time point (year 2, 4, or 6). The mean ± SD change in the sacroiliitis sum score was 0.13 ± 0.73, −0.27 ± 0.76, and −0.09 ± 0.68, in the time intervals baseline to year 2, year 2 to year 4, and year 4 to year 6, respectively. In the longitudinal mixed model analysis, elevated C‐reactive protein level (β = 0.58 [95% confidence interval 0.24, 0.91]) and MRI SI joint osteitis score (β = 0.06 [95% confidence interval 0.03, 0.10]) were independently associated with progression of the sacroiliitis sum score. Conclusion Our findings indicate that long‐term anti‐ TNF therapy decelerates the progression of structural damage in the SI joints. Elevated CRP level and presence of osteitis on MRI were independently associated with radiographic sacroiliitis progression.
Abstract O.47: Prediction of IVIG Resistance using Kawasaki Disease Risk Scores and Baseline Coronary Z-Scores at a Single North American Center
Authors: Mary Beth F Son, Susan Kim, Kimberlee Gauvreau, Alexander Tang, Fatma Dedeoglu, David Fulton, Mindy S Lo, Robert P Sundel, Jane W Newburger
Journal: Circulation (2015)

Aim: At a single pediatric tertiary care center, we assessed the performance of established Japanese risk scores (RS) to identify patients (pts) with Kawasaki Disease (KD) at higher risk for re-treatment (re-tx). We also sought to determine if the addition of baseline coronary Z-scores to RS could improve the prediction re-tx. Methods: We reviewed available clinical, lab and echocardiogram (echo) data for KD pts treated from 1/2006 to 5/2014. The maximum z-score (zMax) of the right coronary artery (RCA) or left anterior descending artery (LAD) at baseline was used. Abnormal coronary arteries at baseline echo were defined as zMax ≥2 in the RCA or LAD. Kobayashi, Sano, Egami and Harada scores were calculated, comparing low and high risk scores to re-tx. The zMax was incorporated into each RS with 1 point added (+1) if baseline zMax ≥2. In an alternative approach, zMax was added as a covariate in a logistic regression model. The discrimination of each model was assessed using the c statistic. Results: Of 339 pts, 214 (63%) were male, and median age was 3.2 y (range 0.1-14.1 y). At diagnosis, 29% (97/339) had ≤3 classical criteria for KD, and 25% (85/339) received IVIG re-tx. At baseline, the median zMax was 1.37 (-1.64-14.2) and 26% (88/339) had zMax ≥2. Classification as high risk by all four RS was significantly associated with re-tx (p&lt;0.001-0.02). Baseline zMax &lt;2 vs. ≥2 was also associated with re-tx (50 [21%] vs. 30 [34%], p&lt;0.02). The ORs for re-tx were significant for all RS, but c-statistics were low, with a c statistic &lt;0.7 (range of 0.57-0.61). RS +1 for zMax ≥2 did not improve the prediction for re-tx (c statistic 0.58-0.63). However, the addition of zMax ≥2 as a covariate improved the discrimination of all RS for re-tx (c-statistic 0.6-0.67). Conclusions: Published RS for predicting IVIG resistance are associated with higher rates of re-tx in our patient population, but are not sufficient to discriminate patients at risk for re-tx. With the addition of baseline zMax as a covariate to the RS, prediction for re-tx was improved, although still modest. Further study in larger, multi-center studies are needed to validate these findings and to better understand the risk factors for re-tx in KD in North American children.