tbuckley/cabot-search huggingface dataset:
SAT0117 Retention rates of adalimumab, etanercept, and infliximab as 1st- or 2nd-line biotherapy for rheumatoid arthritis patients in daily practice in auvergne
Authors: M Soubrier, B Pereira, T Frayssac, A Fan, M Couderc, S Malochet-Guinamand, S Mathieu, Z Tatar, A Tournadre, J-J Dubost
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The use of anti-tumor necrosis factor-alpha agents, or anti-TNFs, has greatly improved the treatment of rheumatoid arthritis (RA). The first three anti-TNFs available to us (infliximab, adalimumab, and etanercept) are the most widely used in treating RA. Their efficacy and safety, demonstrated in extensive randomized and controlled trials (RCTs), were not shown to vary significantly when compared indirectly based on randomized studies. Nevertheless, the randomized studies were of short duration and included a selected population that differed from patients treated in daily practice. <h3>Objectives</h3> To compare, in real-life conditions, the retention rates of the initial anti-TNF treatment (etanercept [ETN], adalimumab [ADA], and infliximab [IFX]) initiated as first-line biotherapy for rheumatoid arthritis (RA) and to evaluate, in case of failure, the switch to another anti-TNF or a non-anti-TNF biological. <h3>Methods</h3> Monocentric retrospective cohort including all patients with RA starting a first anti-TNF between 2001 and 2015. <h3>Results</h3> Among the 346 patients analyzed, 201 received ETN, 82 ADA, and 63 IFX. The first anti-TNF was interrupted in 151 cases. The retention rates were 82.8%, 67.6%, 46.5%, 28.1%, and 22.5% at 1, 2, 5, 10, and 15 years, respectively, with a median retention duration of 52.8 [18.9 -136.2] months (ETN: 59.3 [19.1-NA), ADA: 79.9 [19.3–136.2], and IFX: 37.2 [17.5–134.5], p=0.49). The predictive factors of discontinuation were active RA (DAS28-CRP HR: 1.22 [1.03–1.45]), inflammatory syndrome (ESR HR: 1.01 [1.0–1.02]; CRP HR: 1.00 [1.00–1.01]), absence of MTX treatment (HR: 0.60 [0.43–0.83]), and corticosteroid use (HR: 1.91 [1.31–2.78]). The patients who switched to another anti-TNF treatment had an inferior retention than those who switched to a non-anti-TNF treatment (HR: 0.39 [0.17 - 0.87], p: 0.02). p=0.02). <h3>Conclusions</h3> In real life, there was no difference in retention among the three anti-TNF agents, and 25% of patients continued them at 15 years. After failure of an anti-TNF, the switch to a non-anti-TNF biotherapy showed better retention. <h3>Disclosure of Interest</h3> None declared
Association of Thyroid Function With Life Expectancy With and Without Cardiovascular Disease
Authors: Arjola Bano, Klodian Dhana, Layal Chaker, Maryam Kavousi, M. Arfan Ikram, Francesco U. S. Mattace-Raso, Robin P. Peeters, Oscar H. Franco
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> Variations in thyroid function within reference ranges are associated with an increased risk of cardiovascular disease (CVD) and mortality. However, the impact of thyroid function on life expectancy (LE) and the number of years lived with and without CVD remains unknown. <h3>Objective</h3> To investigate the association of thyroid function with total LE and LE with and without CVD among euthyroid individuals. <h3>Design, Setting, and Participants</h3> The Rotterdam Study, a population-based, prospective cohort study. We included participants without known thyroid disease and with thyrotropin and free thyroxine (FT<sub>4</sub>) levels within the reference ranges. <h3>Main Outcomes and Measures</h3> Multistate life tables were used to calculate total LE and LE with and without CVD among thyrotropin and FT<sub>4</sub>tertiles. Life expectancy estimates in men and women aged 50 years and older were obtained using prevalence, incidence rates, and hazard ratios for 3 transitions (healthy to CVD, healthy to death, and CVD to death), adjusting for sociodemographic and cardiovascular risk factors. <h3>Results</h3> The mean (SD) age of the 7785 participants was 64.7 (9.8) years, and 52.5% were women. Over a median follow-up of 8.1 (interquartile range, 2.7-9.9) years, we observed 789 incident CVD events and 1357 deaths. Compared with those in the lowest tertile, men and women in the highest thyrotropin tertile lived 2.0 (95% CI, 1.0 to 2.8) and 1.4 (95% CI, 0.2 to 2.4) years longer, respectively, of which, 1.5 (95% CI, 0.2 to 2.6) and 0.9 (95% CI, −0.2 to 2.0) years longer without CVD. Compared with those in the lowest tertile, the difference in life expectancy for men and women in the highest FT<sub>4</sub>tertile was −3.2 (95% CI, −5.0 to −1.4) and −3.5 (95% CI, −5.6 to −1.5) years, respectively, of which, −3.1 (95% CI, −4.9 to −1.4) and −2.5 (95% CI, −4.4 to −0.7) years without CVD. <h3>Conclusions and Relevance</h3> At the age of 50 years, participants with low-normal thyroid function live up to 3.5 years longer overall and up to 3.1 years longer without CVD than participants with high-normal thyroid function. These findings provide supporting evidence for a reevaluation of the current reference ranges of thyroid function and can help inform preventive and clinical care.
AB1140 Who disability assessment schedule 2.0 is related to upper and lower extremity specific quality of life
Authors: KS Park, Y-H Cheon
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Musculoskeletal complaints influence disability, but the relative contribution of concurrent upper and lower extremity health-related quality of life (HRQOL) on patient perceptions of disability is unclear. <h3>Objectives</h3> We evaluated whether two disease specific quality of life instruments (DASH and WOMAC) reflect a patient9s perception of general disability using the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) and determined whether disability components are explained by upper and lower extremity HRQOL. <h3>Methods</h3> We recruited 421 randomly chosen participants 50 years or older without stroke, cancer, or history of surgery for musculoskeletal disease who participated in the Namgang Cohort. Upper extremity HRQOL was determined with the DASH score and lower extremity HRQOL with the WOMAC; as a measure of disability, we obtained WHODAS 2.0 component. Multiple regression modeling was used to assess the relative contributions made by upper and lower extremity HRQOL to disability. <h3>Results</h3> Most patients reported knee pain (61.0%), shoulder (17.1%), elbow (28.5%) and hand (56.1%). Mean WHODAS 2.0 total score was 28.06 (SD=14.2), corresponding to mild to moderate disability and WOMAC and DASH scores were 23.2 (SD=22.1) and 22.4 (SD=19.3). When adjusted for age, sex, level of education, spouse, self rated health, hypertention, DM and depression, the DASH total score was correlated with the getting around (β=0.137, p=0.032) and social participation (β=0.226, p&lt;0.001) and the WOMAC total score was correlated with the getting around (β=0.362, p&lt;0.001) and social participation (β=0.289, p&lt;0.001) <h3>Conclusions</h3> We found that in a community-based population, perceived actibity limitation and social participation were associated with upper and lower extremity HQRQOL. Since the WHODAS 2.0 does not target a specific disease (as oppose to the DASH, WOMAC), it can be used to compare disabilities caused by different diseases. <h3>References</h3> Pösl M, Cieza A, Stucki G. Psychometric properties of the WHODASII in rehabilitation patients. Qual Life Res. 2007;16(9):1521–31. Silva C, Coleta I, Silva AG, Amaro A, Alvarelhão J, Queirόs A, Rocha N. Adaptation and validation of WHODAS 2.0 in patients with musculoskeletal pain. Rev Saude Publica. 2013 Aug;47(4):752–8. Tazaki M, Yamaguchi T, Yatsunami M, Nakane Y. Measuring functional health among the elderly: development of the Japanese version of the World Health Organization Disability Assessment Schedule II. Int J Rehabil Res. 2014 Mar;37(1):48–53. <h3>Acknowledgements</h3> This work was supported from the Ministry of Agriculture Food and Rural Affairs in Korea. <h3>Disclosure of Interest</h3> None declared
AB0264 The perforin A91V gene and clinical features analysis in chinese SO-JIA cases with macrophage activation syndrome
Authors: P Wei, H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of rheumatoid disease, especially in the systemic onset juvenile idiopathic arthritis (SoJIA). we aimed to investigate the clinical characteristics of 31 SOJIA cases with MAS and the perforin A91V gene were detected in part cases <h3>Methods</h3> gene-specific polymerase chain reaction (PCR) primers were used to analyze the perforin A91Vgene polymorphism. <h3>Results</h3> 31 soJIA cases were associated with MAS.25 out of 31 cases (83%) had infections prior to MAS. Serum ferritin was significantly increased in 27 cases (87.10%). High concentrations of triglycerides (23cases, 74.19%) and lactic dehydrogenase (27cases, 87.10%) are observed. What is more, Creatine Kinase (CK) increased in all cases that had been checked. Well-differentiated macrophages phagocytosing hematopoietic elements were found in all cases (100%).6 cases (19.35%) merged with multiple organ dysfunctions (MODS). The perforin A91V (NCBI: SNP rs35947132) variant gene was detected in twenty cases, but no mutation was found. Corticosteroids, immunosuppressant, cell cycle inhibitors, immunoglobulin, Tumor necrosis factor (TNF) antagonist and plasmapheresis were effective. After treatment, 28cases (90.32%) children were in remission, while 3 out of 31 cases died with mortality of 9.68%. <h3>Conclusions</h3> MAS is a life-threatening complication of systemic onset juvenile idiopathic arthritis. Most cases were preceded by infection. Unremitted fever, progressive hepatosplenomegaly, lymphadenopathy, cytopenias, elevated serum liver enzymes significantly increased serum ferritin are the main feature. Early diagnosis and treatment is the key to improve prognosis. The perforin gene mutations in our patients have not found yet. <h3>Disclosure of Interest</h3> None declared
SAT0229 The use of antimalarial drugs during pregnancy can prevent the development of preeclampsia in women with systemic lupus erythematosus
Authors: MA Saavedra, D Miranda-Hernández, A Lara-Mejía, A Sánchez, CV Cruz-Reyes, U Angeles, LJ Jara
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The antimalarial drugs decrease the risk of lupus activity during gestation, but the beneficial effect on other maternal-fetal complications is controversial. <h3>Objectives</h3> To analyze the beneficial effect of antimalarial drugs on maternal-fetal complications in pregnant women with systemic lupus erythematosus (SLE). <h3>Methods</h3> A prospective cohort of pregnant women with SLE (ACR 1997) from January 2009 to June 2015 was studied. The patients were assessed every 4 to 6 weeks and postpartum both, by a rheumatologist and a gynecologist. Clinical, biochemical, and immunological characteristics, along with maternal and fetal complications were registered. For analysis, the patients were allocated to one of two groups: pregnancies exposed to antimalarial drugs in comparison to those not exposed. A logistic regression analysis including variables such as smoking, obesity, infections, first pregnancy, age, SLE flare, drugs (prednisone, antimalarials, aspirin, and azathioprine), anti-DNA antibodies, anticardiolipin antibodies, and antiphospholipid syndrome was performed. <h3>Results</h3> We studied 197 lupus pregnancies, 154 expose to antimalarial drugs and 47 unexposed. We found no differences between groups in age, years of evolution of SLE, first pregnancy, childhood-onset SLE, lupus nephritis, and use of prednisone, aspirin and azathioprine. The rate of most maternal and fetal complications was also similar in both groups (Table). A lower incidence of preeclampsia was observed in patients exposed to antimalarial drugs compared to those not exposed (9% vs 23%, p=0.01). Additionally, 2 maternal deaths in patients not exposed to antimalarial drugs. The logistic regression analysis showed that the use of antimalarial drugs during pregnancy is a protective factor for the development of preeclampsia (RR 0.1, 95% CI 0.05–0.58, p=0.004); on the other hand, active SLE before pregnancy (RR 4.8, 95% CI 1.3–17.8, p=0.01) and lupus nephritis (RR 2.9, 95% CI 0.9–8.8, p=0.05) were associated factors with the development of preeclampsia. <h3>Conclusions</h3> Our study suggests that the use of antimalarial drugs during pregnancy can prevent the development of preeclampsia in women with SLE. <h3>Disclosure of Interest</h3> None declared
AB0569 Change in serum level of soluble E-selectin and MMP-9 in children with kawasaki disease
Authors: H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Kawasaki disease (KD)is a kind of febrile disorder without definite etiology. Coronary artery aneurysms are the major complication of Kawasaki disease (KD). r11le pathogenesis of the vascular damage remains unknown.This study Wfl8 conducted to explore the pathophysiological role of E-selectin (ES), CMatrix metalloproteinase 9 (MMP-9) in KD.and to look for the evidenee of direct relationship between the plasma levels of ES,MMP-9 and the incidence of the coronary artery lesion (CAL). <h3>Methods</h3> Soluble ES and MMP-9,were measured in 68 patients with KD,20 patients with febrile disease and 20 healthy children by using double antibody sandwich enzyme linked immunosorbent assay (ELISA).Patients with KD were separated into acute phase group, subacute phase group, recovery phase group. coronary artery lesion group (CAL), non-coronary artery lesion group (NCAL). <h3>Results</h3> KS and MMP-9 levels in the acute phase group,subacute phase group were significantly higher than those in the healthy group. Plasma ES and MMP-9 levels of CAL group were significanfly higher than those of NCAL group in acute phase. ne peak level of ES and MMP-9 appeared in the acute phase.There Was a significant correlation between KS and MMP-9 levels in KD patients (r=0.643, P&lt;0.01). <h3>Conclusions</h3> the increase of plasma PS and ES levels in KD acute phase and subacute phase might play an important role in the pathophysiology of the VasCUlax damage.KS and MMP-9 may potentially be a predictor of CAL in patients. <h3>Disclosure of Interest</h3> None declared
AB0966 The clinical observation of immunoadsorption in treatment of children with refractory autoimmune diseases
Authors: P Zeng, H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Explore the clinical efficacy and safety of the immunoadsorption assisted treatment of children with refractory autoimmune diseases. <h3>Methods</h3> Use HA280 type resin perfusion machine for four times of whole blood immunoadsorption treatment for one case of a 4-year-old child combined with severe dermatomyositis and pulmonary infection, one case of 9-year-old child with severe allergic purpura combined with gastrointestinal bleeding, intestinal perforation, after intestinal tract partial hepatectomy, one case of 11-year-old child with systemic juvenile idiopathic arthritis combined with head and facial cellulites and macrophage activation syndrome. Observe the improvement of its clinical manifestations, serum immunoglobulin, complement, liver and kidney function, myocardial enzymes, autoantibodies. <h3>Results</h3> The children9s signs and symptoms improved significantly after treatment of whole blood immunoadsorption, the sensitivity of the adrenal cortex hormones increased, liver and kidney function, myocardial enzymes improved, the levels of serum IGG descended, complement (C3, C4) rose, anti-cyclic citrullinated peptide (CCP) was negative. <h3>Conclusions</h3> The whole blood perfusion immunity adsorption treatment is able to to reduce blood plasma IGG, improvement complement C3 and C4 level, eliminates anti-CCP immune body in vivo, reduce the cardiac muscle zymogram and the liver enzyme in a short time, increase sensitivity to the adrenal cortex hormone, alleviate immunological disease9s symptom in active stage, have the affirmative function to make the baby pass the dangerous period safely. The child whole blood fills the class immunity adsorption not to present the untoward effect. No untoward effect happened. <h3>Disclosure of Interest</h3> None declared
Serum Immune Profiling for Early Detection of Cervical Disease
Authors: Radwa Ewaisha, Gitika Panicker, Paul Maranian, Elizabeth R. Unger, Karen S. Anderson
Journal: Theranostics (2017)

Background: The most recent (2012) worldwide estimates from International Agency for Research on Cancer indicate that approximately 528,000 new cases and 270,000 deaths per year are attributed to cervical cancer worldwide.The disease is preventable with HPV vaccination and with early detection and treatment of pre-invasive cervical intraepithelial neoplasia, CIN.Antibodies (Abs) to HPV proteins are under investigation as potential biomarkers for early detection.Methods: To detect circulating HPV-specific IgG Abs, we developed programmable protein arrays (NAPPA) that display the proteomes of two low-risk HPV types (HPV6 and 11) and ten oncogenic high-risk HPV types (HPV16,18,31,33,35,39,45,51, 52 and 58).Arrays were probed with sera from women with CIN 0/I (n=78), CIN II/III (n=84), or invasive cervical cancer (ICC, n=83).Results: Abs to any early (E) HPV protein were detected less frequently in women with CIN 0/I (23.7%) than women with CIN II/III (39.0%) and ICC (46.1%, p<0.04).Of the E Abs, anti-E7 Abs were the most frequently detected (6.6%, 19.5%, and 30.3%, respectively).The least frequently detected Abs were E1 and E2-Abs in CIN 0/I (1.3%) and E1-Abs in CIN II/III (1.2%) and ICC (7.9%).HPV16-specific Abs correlated with HPV16 DNA detected in the cervix in 0% of CIN 0/I, 21.2% of CIN II/III, and 45.5% of ICC.A significant number (29 -73%) of E4, E7, L1, and L2 Abs had cross-reactivity between HPV types.Conclusion: HPV protein arrays provide a valuable high-throughput tool for measuring the breadth, specificity, and heterogeneity of the serologic response to HPV in cervical disease.
Isoprostanes, neuroprostanes and phytoprostanes: An overview of 25 years of research in chemistry and biology
Authors: Jean-Marie Galano, Yiu Yiu Lee, Camille Oger, Claire Vigor, Joseph Vercauteren, Thierry Durand, Martin Giera, Jetty Chung-Yung Lee
Journal: Progress in Lipid Research (2017)
Modular organization of the brainstem noradrenaline system coordinates opposing learning states
Authors: Akira Uematsu, Bao Zhen Tan, Edgar A Ycu, Jessica Sulkes Cuevas, Jenny Koivumaa, Felix Junyent, Eric J Kremer, Ilana B Witten, Karl Deisseroth, Joshua P Johansen
Journal: Nature Neuroscience (2017)
Abstract 15890: Reduced Na/K Pump Current, Enhanced Contractility and Negative Force-frequency Relationship in Cardiomyocytes and Hearts Isolated from Mice Expressing Unphosphorylatable Phospholemman
Authors: Karen L Aughton, Andrew R Hall, William Fuller, Michael J Shattock
Journal: Circulation (2010)

Phospholemman (PLM) is a member of the FXYD family of Na/K ATPase accessory proteins expressed in cardiac tissue. It has been suggested that PLM phosphorylation provides the primary mechanism linking kinase activation to Na/K pump stimulation. PLM has previously been shown to be basally phosphorylated (by around 40%) and this can be further increased by PKC and/or PKA activation and by rapid pacing. Na/K pump current in myocytes isolated from PLM knock-out mice (PLMKO) is increased and, in isolated hearts, deletion of PLM causes a reduction in left ventricular pressure (LVDP) and a switch to a positive force-frequency gradient (FFRG) (cf a negative FFRG in WT hearts). To investigate the role of PLM phosphorylation a novel knock-in mouse (PLM-KI) was generated in which the endogenous allele was globally replaced with one expressing unphosphorylatable PLM (serines 63, 68 and 69 substituted with alanines). Na/K pump current was recorded using the perforated-patch technique in voltage-clamped myocytes isolate...
AB0429 Short-term effects of low dose glucocorticoids on bone metabolism in early rheumatoid arthritis
Authors: M Vitiello, O Viapiana, N Malavolta, G Saviola, R Bortolotti, L Idolazzi, F Bertoldo, G Orsolini, M Risoli, D Gatti, M Rossini
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Glucocorticoids (GCs) are frequently used in the treatment of Rheumatoid Arthritis (RA). Studies in humans about the effects on bone turnover markers and modulators are poor, and results are discordant and controverse, probably because conducted with different doses and underlying diseases. <h3>Objectives</h3> To evaluate changes in serum bone turnover markers and Wnt inhibitors at 7- and 30-days after initiation of low dose GCs treatment of early RA. <h3>Methods</h3> 27 adult patients suffering from early RA were prospectively enrolled. Blood tests including C-Reactive Protein (CRP), amino-terminal propeptide of type 1 procollagen (P1NP, marker of bone formation), carboxy-terminal telopeptide of type 1 collagen (CTX, marker of bone resorption), Sclerostin, and Dickkopf-related protein 1 (DKK1) were detected at baseline and 7 and 30 days after starting low dose of GC (methylprednisolone 4 mg/day). <h3>Results</h3> At baseline we observed a significant positive correlation between CRP and DKK1 serum levels (r=0,63; p&lt;0,05) and between DKK1 and CTX serum levels (r =0,38; p&lt;0,05). A significant decrease in serum levels of CRP, P1NP, and Sclerostin was observed after 7 and 30 days of GC treatment (p&lt;0,05). About DKK1, it has been detected a not significant tendency to decrease after starting GC. CTX serum levels showed no significant changes. <h3>Conclusions</h3> This study has shown that a low dose GC treatment might have complex and conflicting short-term effects on bone metabolism in early RA (a reduction of bone formation, without increase of bone resorption), different from those observed with higher dose, in other diseases or in healthy subjects. The observed decrease in P1NP and Sclerostin serum levels might mean that also low dose of GC could acutely suppress bone formation and induce loss of function and/or number of osteocytes. <h3>Disclosure of Interest</h3> None declared
Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA
Authors: Walter K. Mowel, Sam J. McCright, Jonathan J. Kotzin, Magalie A. Collet, Asli Uyar, Xin Chen, Alexandra DeLaney, Sean P. Spencer, Anthony T. Virtue, EnJun Yang, Alejandro Villarino, Makoto Kurachi, Margaret C. Dunagin, Gretchen Harms Pritchard, Judith Stein, Cynthia Hughes, Diogo Fonseca-Pereira, Henrique Veiga-Fernandes, Arjun Raj, Taku Kambayashi, Igor E. Brodsky, John J. O’Shea, E. John Wherry, Loyal A. Goff, John L. Rinn, Adam Williams, Richard A. Flavell, Jorge Henao-Mejia
Journal: Immunity (2017)
Biallelic <i>Dicer1</i> Loss Mediated by <i>aP2-Cre</i> Drives Angiosarcoma
Authors: Jason A. Hanna, Catherine J. Drummond, Matthew R. Garcia, Jonathan C. Go, David Finkelstein, Jerold E. Rehg, Mark E. Hatley
Journal: Cancer Research (2017)

Angiosarcoma is an aggressive vascular sarcoma with an extremely poor prognosis. Because of the relative rarity of this disease, its molecular drivers and optimal treatment strategies are obscure. DICER1 is an RNase III endoribonuclease central to miRNA biogenesis, and germline DICER1 mutations result in a cancer predisposition syndrome, associated with an increased risk of many tumor types. Here, we show that biallelic Dicer1 deletion with aP2-Cre drives aggressive and metastatic angiosarcoma independent of other genetically engineered oncogenes or tumor suppressor loss. Angiosarcomas in aP2-Cre;Dicer1Flox/- mice histologically and genetically resemble human angiosarcoma. miR-23 target genes, including the oncogenes Ccnd1 as well as Adam19, Plau, and Wsb1 that promote invasiveness and metastasis, were enriched in mouse and human angiosarcoma. These studies illustrate that Dicer1 can function as a traditional loss-of-function tumor suppressor gene, and they provide a fully penetrant animal model for the study of angiosarcoma development and metastasis. Cancer Res; 77(22); 6109-18. ©2017 AACR.