tbuckley/cabot-search huggingface dataset:
SP0068 Clinical insights into jia heterogeneity
Authors: A Consolaro
Journal: Annals of the Rheumatic Diseases (2017)

Several epidemiologic surveys have documented a remarkable, yet unexplained, disparity in the prevalence of juvenile idiopathic arthritis (JIA) subtypes among different geographic areas or ethnic groups. Moreover, the therapeutic approach to JIA is not standardized and the availability of the novel and costly biologic medications is not uniform throughout the world. This disparity may have significant impact on disease outcome. The multinational study of the EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA study) is aimed to obtain information on the variability of JIA phenotypes in different geographic areas, the therapeutic approaches of pediatric rheumatologists practicing in diverse countries, and the disease status and outcome of children with JIA currently followed worldwide. Participation in the study was proposed to all pediatric rheumatology centers that are part of the Pediatric Rheumatology International Trials Organization (PRINTO), and to several centers in the US and Canada. Each center was asked to enroll 100 consecutive JIA patients or all consecutive patients seen within 6 months. Each patient received a retrospective and cross-sectional assessment. Parent- and child-reported outcomes were recorded through the administration of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). Participating countries were grouped into 6 geographic areas. Patients were then grouped according to their country9s gross domestic product per capita (GDP) and the total expenditure on health per capita (HE) (source www.who.org).Currently, 8,325 patients from 44 countries have been entered in the web database. Comparison of main epidemiology, treatment, and outcome features across the different geographic areas was performed. Patients living in countries with GDP or HE below the median had lower frequency of remission, higher median cJADAS, higher frequency of damage, and were less frequently prescribed biologic DMARDs. These results were confirmed when analyses were conducted only in oligoarthritis or polyarthritis patients. These results provide further evidence of the wide difference of JIA characteristics across geographic areas in terms of age at disease onset, subtype prevalence, and frequency of anterior uveitis. Overall, patients living in non-Western countries had higher levels of disease activity and cumulative damage than patients followed in North America and Western Europe. This disparity in disease outcomes may be partially due to differences in the availability or affordability of biologics, as confirmed by the evidence of worst outcomes in countries with lower GDP or HE. <h3>Disclosure of Interest</h3> None declared
炎症性腸疾患の標的治療のためのスーパーオキシドジスムターゼ/カタラーゼ模倣ナノメディシン【Powered by NICT】
Authors: Zhang Qixiong, Tao Hui, Lin Yongyao, Hu Ying, An Huijie, Zhang Dinglin, Feng Shibin, Hu Houyuan, Wang Ruibing, Li Xiaohui, Zhang Jianxiang
Journal: Biomaterials (2016)
THU0374 Long-term effects of TNF-ALPHA inhibitors on bone mineral density and the incidence of vertebral fractures in patients with ankylosing spondylitis
Authors: K Beek, M van der Weijden, W Lems, C van Denderen, M Nurmohamed, I der Horst-Bruinsma van
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Ankylosing Spondylitis (AS) is not only characterized by pathological bone formation leading to ankylosis, but also by bone loss which may lead to vertebral fractures (VFx). TNF-alpha inhibitors (TNFi) have proven to be effective in blocking the inflammation process. A few studies also showed an increase of Bone Mineral Density (BMD) in AS patients treated with TNFi <sup>1–3</sup> but the incidence of VFx after two years of treatment was increased.<sup>3–4</sup> <h3>Objectives</h3> To evaluate the long-term effect of TNFi on BMD and the incidence of VFx in patients with AS. <h3>Methods</h3> Consecutive TNFi naive patients diagnosed with AS according to the Modified New York criteria were included. Patients were recruited from the VUmc and the Amsterdam Outpatient clinic Reade and were treated with TNFi for 4 years. BMD at hip and lumbar spine (LS) were measured at baseline, after 2 and 4 years. T-scores were categorized as "normal BMD", "osteopenia" and "osteoporosis", based on the WHO osteoporosis criteria.<sup>5</sup> The incidence of VFx was determined by two observers using the Genant method.<sup>6</sup> <h3>Results</h3> In total, 70 AS patients with complete datasets (67.1% male) were included. The mean age was 41.6 years and the disease duration (time since diagnosis) was 9.8 years. At baseline 42% of the patients had a decreased BMD of the hip and 34% of the spine, of whom 19 patients (27%) had both a decreased hip BMD as well as a decreased lumbar BMD. The BMD of spine and hip improved after 2 and 4 years of TNFi treatment (Table 1). In 7 patients (10%), 8 VFx were observed both at baseline and after 2 years. After 4 years of TNFi-treatment 11 VFx were observed in 9 patients. After 4 years, 2 out of 9 patients with ≥1 VFx had a decreased BMD at hip and lumbar spine whereas the other 7 patients had a normal BMD. The majority of VFx was localized in the mid or lower thoracic spine. <h3>Conclusions</h3> The percentage of relatively young AS patients with a decreased BMD at baseline of the hip and lumbar spine was high (34–41%). After 4 years of TNFi-treatment the BMD of the lumbar spine improved in 8.6% of the patients and of the hip in 7.2% of the patients. At baseline, several vertebral fractures were found and a few additional vertebral fractures were observed after 4 years of treatment. <h3>References</h3> Visvanathan S et al. Ann Rheum Dis 2009. Arends S et al. Arthritis Res Ther 2012. van der Weijden et al. J Reumatol 2016. Maas F et al. ClinExpRheumatol 2016. Kanis JA et al. J Bone MinerRes 1994. Genant HK et al. J Bone MinerRes 1993. <h3>Disclosure of Interest</h3> None declared
FRI0170 Cardiovascular risk factors and disease characteristics are consistently associated with arterial stiffness in rheumatoid arthritis
Authors: S Gunter, C Robinson, G Norton, A Woodiwiss, L Tsang, A Millen, P Dessein
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In the non-rheumatoid arthritis (RA) population, arterial stiffness contributes to cardiovascular disease risk beyond brachial blood pressure and other established cardiovascular risk factors. The increased cardiovascular disease risk in RA is now well documented. In this regard, how RA impacts on arterial stiffness remains uncertain. <h3>Objectives</h3> The aim of the present study was to identify potential determinants of comprehensively assessed arterial stiffness in a relatively large group of ethnically diverse patients with RA. <h3>Methods</h3> Relationships of traditional cardiovascular risk factors and RA characteristics with 9 arterial stiffness markers including central systolic and pulse pressure, pulse wave velocity, augmentation index, forward and reflected wave pressure, reflection magnitude, brachial-to-aortic pulse pressure amplification (a marker of reduced wave reflection) and peripheral pulse pressure were identified in multivariable backward regression models among 177 (118 white, 32 Asian, 22 black, 5 mixed ancestry) patients without established cardiovascular disease. <h3>Results</h3> Recorded characteristics explained 37% (pulse wave velocity) to 71% (reflected wave pressure) of the variability in arterial stiffness. RA duration (partial r=0.17, p=0.04), rheumatoid factor status (partial r=-0.19 to 0.20, p=0.01 to 0.03), leukocyte counts (partial r=0.16 to 0.19, p=0.02 to 0.05) and total cholesterol (-0.18 to 0.26, p=0.00 to 0.03) were associated with enhanced central systolic blood pressure or/and wave reflection markers. C-reactive protein (partial r=-0.24, -0.17 and -0.20, respectively, p≤0.05) was paradoxically related to reduced central pulse pressure, pulse wave velocity and forward wave pressure, and body mass index (partial r=-0.39 to 0.42, p=0.00 to 0.02) and insulin resistance (partial r=-0.21 to -0.20, p=0.00 to 0.01) to reduced wave reflection and peripheral pulse pressure. Exercise (partial r=0.19, p=0.02) and alcohol (partial r=-0.27, p=0.00) consumption were associated with increased pulse pressure amplification and decreased peripheral pulse pressure, respectively. Tumour necrosis factor-α inhibition (partial r=-0.25, p=0.00) was related to reduced pulse wave velocity and tetracycline use (partial r=-0.20, p=0.02) to reduced peripheral pulse pressure. <h3>Conclusions</h3> Traditional cardiovascular risk factors and disease characteristics are consistently associated with vascular hemodynamic alterations in RA. The role of arterial stiffness in cardiovascular disease risk in RA needs further study. <h3>Disclosure of Interest</h3> None declared
Abstract 11672: Incidence of Implantation of Implantable Cardioverter Defibrillators Within 90 Days in Patients Surviving Non-Myocardial Infarction Out-of-hospital Cardiac Arrest in Denmark Between 2001-2012
Authors: Matilde Winther-Jensen, Jesper Kjaergaard, Jens Flensted Lassen, Lars Kober, Christian Torp-Pedersen, Steen Moller Hansen, Freddy K Lippert, Erika Frischknecht Christensen, Christian Hassager
Journal: Circulation (2016)

Introduction: For patients surviving out-of-hospital cardiac arrest (OHCA) with a shockable rhythm, implantable cardioverter defibrillator (ICD) is recommended unless the arrest was caused by a reversible condition (acute myocardial infarction (AMI)). Yet, other factors may also influence decision to implant ICD. Aim: To determine factors associated with implantation of ICD in patients surviving non-AMI OHCA in a nationwide registry covering all OHCAs in Denmark. Methods: We identified 36,950 OHCAs between 2001-2012, 1,933 of whom were without prior ICD, ≥ 18 years, not diagnosed with AMI and surviving until discharge. 1,732 had no ischemic heart disease (IHD) diagnosis, 201 had chronic IHD diagnosis ≤ two days post OHCA. Multiple logistic regression was used to identify factors associated with ICD implantation ≤ 90 days post OHCA. Results: In patients with no IHD, the incidence of ICD implantation increased over time (OR: 1.07 per year, CI: 1.03-1.1, p=0.001, fig 1). Witnessed arrest, bystander defibrillation and cardiac etiology were associated with higher odds of ICD (OR witnessed : 2.2, CI: 1.6-3.0, p&lt;0.001, OR defibrillation : 2.9, CI: 1.6-5.2, p&lt;0.001, OR etiology : 16, CI: 5.7-45, p&lt;0.001), and non-shockable rhythm was associated with lower odds of ICD (OR: 0.2, CI: 0.1-0.3 p&lt;0.001). Age ≥ 80 years was associated with lower odds of ICD in patients without IHD (OR: 0.2, CI: 0.1-0.3, p&lt;0.001) as well as patients with IHD (OR: 0.1, CI: 0.01-0.5, p&lt;0.01). In patients with IHD, top income tertile, Charlson comorbidity index (CCI) 1 and witnessed arrest were associated with higher odds of ICD (OR top income : 9.7, CI: 1.6-58.6, p=0.01, OR CCI1 : 5.3, CI: 1.7-17, p&lt;0.01, OR witnessed : 3.4, CI: 1.1-10, p=0.04). Conclusion: ICD implantation rates increased over the study period in non-IHD patients, but not in patients with IHD. ICD implantation was less likely in patients ≥ 80 years. High income and low comorbidity burden was associated with higher odds in patients with IHD.
Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor
Authors: Penelope M. Tsimbouri, Peter G. Childs, Gabriel D. Pemberton, Jingli Yang, Vineetha Jayawarna, Wich Orapiriyakul, Karl Burgess, Cristina González-García, Gavin Blackburn, Dilip Thomas, Catalina Vallejo-Giraldo, Manus J. P Biggs, Adam S. G. Curtis, Manuel Salmerón-Sánchez, Stuart Reid, Matthew J. Dalby
Journal: Nature Biomedical Engineering (2017)
FRI0462 The pistol-grip deformity is more frequent in patients with axial spondyloarthritis
Authors: O Tosun, D Solmaz, O Gercik, G Karaca, A Tosun, M Ozmen, FE Topal, S Akar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Femoroacetabular impingement (FAI) is characterized by early pathologic contact of the proximal femur with the acetabulum. Pincer impingement is the acetabular cause of FAI.Whereas cam deformity seen as a flattening of the anterior contour of the head/neck junction or an osseous hump leading a decreased femoral head/neck offset. Patient with FAI presents with a hip or a trochanteric painusually in the sitting position or during or after activity. It might also be an important cause of hip osteoarthritis (OA). <h3>Objectives</h3> Therefore in this study we evaluated the frequency of pistol-grip deformity (PGD), described as the most characteristic feature of cam-type FAI, in axial spondyloarthritis (axSpA) patients as a potential alternative cause of hip or trochanteric pain. <h3>Methods</h3> A total 180 patients (107 [59%] male, mean age 41.9±12.8 years) with axSpA according to ASAS criteria and 198 patients (120 [61%] male, mean age 40.5±14.8 years) admitted to the emergency department (mostly due to trauma) and who had pelvic X-ray were included in the study.Patients with hip OA, hip prosthesis, acetabular protrusion or who have radiographs taken improper technique were excluded. An experienced radiologist assessed all anteroposterior pelvic radiographs. PGD was determined by demonstration of spherical or non spherical shape of femur head on AP pelvic radiography. <h3>Results</h3> The axSpA group consists 135 ankylosing spondylitis and 45 non-radiographic axSpA patients. The mean duration of symptoms was 13.8±11.3 years in axSpA patients. Radiographic findings of cam abnormality (figure) were significantly more frequent in axSpA patients in comparison with control subjects (30/150 [20%] vs 17/193 [9%] and <i>P</i>=0.004). Cam-type radiographic abnormality was only present 2 female control subjects and none of female axSpA patients. FAI was significantly correlated with the presence of HLA-B27 (r=0.213 and <i>P</i>=0.048), smoking (r=0.194 and <i>P</i>=0.018), height (r=0.283 and <i>P</i>=0.001) and gender (r=0.443 and <i>P</i>&lt;0.001). <h3>Conclusions</h3> Our results showed that radiographic findings compatible with PGD were frequent in axSpA patients. In addition to repetitive injury tothe proximal femoral physis, new bone formation may be responsible for increased FAI in axSpA.In axSpA patients with hip or trochanteric pain, FAI may be kept in mind as an alternative explanation of the symptoms. <h3>Disclosure of Interest</h3> None declared
Migration of mesenchymal stem cells to tumor cells under hypoxia
Authors: Yanique Rattigan, Sonia Picinich, John Glod, Debabrata Banerjee
Journal: Cancer Research (2008)

2056   Mesenchymal stem cells (MSCs) are multipotent stromal precursor cells that have the ability to differentiate into cell lineages of bone, cartilage, fat and fibrous connective tissues. It has been previously reported that MSCs have the ability to migrate in vivo to the extremely hypoxic tumor microenvironment (TMEN). However, factors involved in the stimulation and migration of MSCs towards the hypoxic TMEN remain poorly defined. Hypoxia is a constant feature of most tumors and has been shown to play a central role in tumor progression. Recent evidence suggests that the recruitment of MSCs to these tumor sites is one of the main mechanisms of tumor angiogenesis. It is therefore important to delineate pathways that contribute to MSC migration as this knowledge will allow us to improve tumor targeting of MSCs. There is emerging evidence, which indicates that MSCs serve as a more efficient delivery vehicle for targeted chemotherapy. Here we provide evidence that chemotactic factors secreted from the hypoxic tumor microenvironment serve as chemoattractants for activation and migration of MSCs towards these sites. Our studies suggest that MSC migration towards MDAMB231 tumor cells cultured in hypoxia (1.5% O 2 ) was enhanced over 1.5 fold compared to tumor cells cultured under normal (21% O 2 ) conditions. Further analysis indicated that hypoxia induced the transcriptional activity of Egr-1 while HIF-1α remained constitutively activated in MSCs. Both these gene products have been suggested to be key regulators of cellular response to hypoxia. Moreover, in response to hypoxia, secreted chemotactic factors such as IL-6, IL-8 and MCP-1 were found to be up-regulated in tumor cells. Collectively, our data suggests that the hypoxic TMEN activates signaling and survival pathways that may be mediated by HIF1-α and Egr-1 which contribute to migration of MSCs to tumors in vivo.
New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures
Authors: Alison H. Harrill, Kimberly A. McAllister
Journal: Environmental Health Perspectives (2017)

This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene-environment interactions in human disease and to inform human health risk assessment.This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models.This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm.These unique resources have the potential to be powerful tools for generating hypotheses related to gene-environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states.These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274.
Expression of PD-L1 in Hormone-naïve and Treated Prostate Cancer Patients Receiving Neoadjuvant Abiraterone Acetate plus Prednisone and Leuprolide
Authors: Carla Calagua, Joshua Russo, Yue Sun, Rachel Schaefer, Rosina Lis, Zhenwei Zhang, Kathleen Mahoney, Glenn J. Bubley, Massimo Loda, Mary-Ellen Taplin, Steven P. Balk, Huihui Ye
Journal: Clinical Cancer Research (2017)

Purpose: Programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) blockade has been unsuccessful in prostate cancer, with poor immunogenicity and subsequent low PD-L1 expression in prostate cancer being proposed as an explanation. However, recent studies indicate that a subset of prostate cancer may express significant levels of PD-L1. Furthermore, the androgen antagonist enzalutamide has been shown to upregulate PD-L1 expression in prostate cancer preclinical models. In this study, we evaluated the effect of neoadjuvant androgen deprivation therapy with abiraterone acetate plus prednisone and leuprolide (Neo-AAPL) on PD-L1 expression in prostate cancer.Experimental Design: Radical prostatectomy (RP) tissues were collected from 44 patients with intermediate- to high-risk prostate cancer who underwent RP after Neo-AAPL treatment. Untreated prostate cancer tissues were collected from 130 patients, including 44 matched controls for the Neo-AAPL cases. Tumor PD-L1 expression was detected by IHC using validated anti-PD-L1 antibodies. Tumor-infiltrating CD8+ cells were analyzed in trial cases and matched controls. Expression of DNA mismatch repair genes was examined in PD-L1-positive tumors.Results: Neo-AAPL-treated tumors showed a trend toward decreased PD-L1 positivity compared with matched controls (7% vs. 21% having ≥1% positive tumor cells; P = 0.062). Treated tumors also harbored significantly fewer tumor-infiltrating CD8+ cells (P = 0.029). In 130 untreated prostate cancers, African American ethnicity, elevated serum PSA, and small prostate independently predicted tumor PD-L1 positivity. Loss of MSH2 expression was observed in 1 of 21 PD-L1-positive tumors.Conclusions: A subset of prostate cancer expresses PD-L1, which is not increased by Neo-AAPL treatment, indicating that combining Neo-AAPL treatment with PD-L1/PD-1 blockade may not be synergistic. Clin Cancer Res; 23(22); 6812-22. ©2017 AACR.
AB0279 High rate of disability pension in chilean rheumatoid arthritis patients without access to biologics. hospital padre hurtado experience
Authors: SE Ibáñez Vodnizza, O Valenzuela, F Silva, MJ Villar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Until the year 2016, most of the Chilean rheumatoid arthritis patients in the public health system did not have acces to biologic treatment. Now the access is limited to those with high disease activity (DAS 28 &gt;5.1). <h3>Objectives</h3> Our main objective was to evaluate the rate of patients benefited by disability pension within the group of rheumatoid arthritis patients seen in our center, before the introduction of biologic treatment for those with high disease activity. Our secondary objective was to estimate the association between having a disability pension and the characteristics of the patients. <h3>Methods</h3> Consecutive rheumatoid arthritis patients (according to the ACR 2010 criteria), 18 years old or older, that attended to our rheumatology consult between September and December of 2015, were included. Patients with other types of pensions (retirement) were excluded. Information about work status, gender, age, years since diagnosis, medications used, DAS 28 ESR and its variables was collected. <h3>Results</h3> 104 patients were included. 38.5% had a disability pension. We found significant differences between the patients with and without disability pensions for age, years since diagnosis, tramadol use, the number of tender joints, the number of swollen joints and DAS 28 ESR (Table 1). After multivariate logistic regression, age (OR 1, 95% CI 1.02–1.15), tramadol use (OR 0.3, 95% CI 0.08–0.92) and the number of swollen joints (OR 1.4, 95% CI 1–1.96) continued to be significantly associated. <h3>Conclusions</h3> Near forty percent of our rheumatoid arthritis patients, that did not have access to biologic treatment, were being paid a disability pension, and this condition was significatly associated with more years of age, tramadol use, and the number of swollen joints. The mean DAS 28 ESR in the patients with disability pension was 5. The limit of a DAS 28 &gt;5.1 to authorize the use of biologic treatment possibly will not help to reduce the rate of patients with disability pension in our group. <h3>Disclosure of Interest</h3> None declared