tbuckley/cabot-search huggingface dataset:
Randomized phase III study of gemcitabine plus S-1 combination therapy versus gemcitabine plus cisplatin combination therapy in advanced biliary tract cancer: A Japan Clinical Oncology Group study (JCOG1113, FUGA-BT).
Authors: Chigusa Morizane, Takuji Okusaka, Junki Mizusawa, Hiroshi Katayama, Makoto Ueno, Masafumi Ikeda, Masato Ozaka, Kazuya Sugimori, Akira Fukutomi, Hiroki Hara, Nobumasa Mizuno, Hiroaki Yanagimoto, Keiji Sano, Kazutoshi Tobimatsu, Kei Yane, Shoji Nakamori, Naohiro Sata, Seigo Yukisawa, Hiroshi Ishii, Junji Furuse
Journal: Journal of Clinical Oncology (2018)

205 Background: Gemcitabine (GEM) plus cisplatin (GC) is the standard of care for advanced biliary tract cancer (BTC). However, GC is considered to be toxic because of nausea, vomiting, and appetite loss, and inconvenient due to requiring hydration before and after administration. GEM plus S-1 (GS) was reported to be promising with preferable efficacy and acceptable toxicity profile (UMIN000001685). This phase III study aimed to confirm the non-inferiority of GS to GC in terms of overall survival (OS). Methods: Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable biliary tract adenocarcinoma (gallbladder, intrahepatic biliary tract, extrahepatic biliary tract, or ampulla of Vater), an ECOG-PS of 0–1, and adequate organ function. In the GC arm, 1 g/m 2 of GEM and 25 mg/m 2 of cisplatin was infused on days 1 and 8 of a 21-day cycle. In the GS arm, 1 g/m 2 of GEM was infused on days 1 and 8, and S-1 60, 80, or 100 mg/day according to body-surface area was administered from days 1 to 14 of a 21-day cycle. The primary endpoint was OS and the secondary endpoints included progression-free survival (PFS), response rate (RR), adverse events (AEs), clinically relevant AEs defined as any of grade 2 or more fatigue, appetite loss, nausea, vomiting, oral mucositis, and diarrhea. The sample size was calculated to be 350 with a one-sided alpha of 5%, a power of 80%, non-inferiority margin of 1.155 in terms of hazard ratio (HR). Results: From May 2013 to March 2016, 354 patients were enrolled. The non-inferiority of GS to GC was demonstrated (median OS: 13.4 months (m) in GC and 15.1 m in GS, HR 0.95; 90% confidence interval (CI), 0.78 to 1.15; P = 0.046 for non-inferiority). Median PFS was 5.8 m in GC and 6.8 m in GS (HR 0.86, 95% CI, 0.70-1.07). RR was 32.4% in GC and 29.8% in GS. Preliminary AEs data demonstrated that both treatments were generally well tolerated, although clinically relevant AEs were observed 34.7% in GC and 31.2 % in GS. Conclusions: GS demonstrated non-inferiority to GC in OS with good tolerability and was considered as new convenient option of standard of care without hydration for advanced BTC. Clinical trial information: UMIN000010667.
THU0239 Serum HMGB1 and TLR4 levels as novel biological markers for the activities of neuropsychiatric systemic lupus erythematosus
Authors: Q Huang, C Yuan, H Ren, M Yang
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a severe complication of SLE, including a variety of neurological and psychiatric features. Previous studies have demonstrated the close relationship between NPSLE and inflammation. HMGB1-TLR4 signaling pathway is the up-stream pathway of NF-κB, which could upregulate the expression of various cytokines and other inflammatory mediators. <h3>Objectives</h3> The objective of the study was to explore the potential mechanism of HMGB1-TLR4 axis in SLE. <h3>Methods</h3> The study population consisted of 107 SLE patients and 43 age- and sex-matched healthy controls. 73 SLE patients had active disease. 36 of these had NPSLE. The serum anti-NR2A antibodies levels were measured by ELISA. Clinical and serological parameters were assessed according to routine procedures. HMGB1 and TLR4 levels were measured by ELISA.Statistical analyses were performed by using the chi-square test and the t-test. <h3>Results</h3> CNS manifestations accounted for 94% (34/36 patients), while involvement of the PNS was 6% (2/36patients). The majority of the manifestations were Seizure disorders (n=17; 47.2%),Headache (n=12; 33.3%), Cognitive dysfunction (n=10; 27.8%), Psychoses (n=8; 22.2%).Within the group of active patients those with NP manifestations had higher HMGB1 levels (0.451 (0.292 to 0.583)) compared to active patients with non-NP manifestations (0.356 (0.098 to 0.436)). In patients with NP (0.429 (0.313 to 0.526)) and non-NP (0.375 (0.196 to 0.478)) manifestations during active periods of the disease, TLR4 levels significant increased in comparison to the controls. TLR4 levels were significantly higher in active patients (0.401 (0.196 to 0.526)) compared to quiescent patients. There was a significant positive correlation between levels of HMGB1 and TLR4 in the total patients group (P&lt;0.0001, r=0.939).We observed a correlation between HMGB1 levels and SLEDAI (P&lt;0.0001, r=0.804). Also, TLR4 levels showed a significant correlation with SLEDAI (P&lt;0.0001, r=0.809). HMGB1 levels correlated with anti-dsDNA levels (P&lt;0.0001, r=0.558). Similarly, TLR4 showed a correlation with anti-dsDNA levels (P&lt;0.0001, r=0.522).We observed a negative correlation in the total SLE group between C3, C4 and HMGB1 levels (P&lt;0.0001, r=-0.545 and P&lt;0.0001, r=-0.270 respective. Also, TLR4 showed a significant negative correlation with C3 and C4 (P&lt;0.0001, r=-0.559 and P&lt;0.0001, r=-0.285 respectively). <h3>Conclusions</h3> Our data suggest that HMGB1-TLR4 axis plays an important role in the pathogenesis of SLE as well as NPSLE. <h3>Acknowledgements</h3> This work was supported by The President Foundation of Nanfang Hospital, Southern Medical University (NO. 2014C009, NO.2015C021). <h3>Disclosure of Interest</h3> None declared
SAT0363 Interstitial lung disease in idiopathic inflammatory myopathies: a report from the remicam registry
Authors: T Cobo-Ibáñez, FJ Lόpez-Longo, B Joven, V Maldonado, I Llorente, C Barbadillo, A Gόmez Gόmez, L Barrio Nogal, R Almodόvar, L Lojo, L Ruiz, MJ de Yébenes García, L Nuño
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Interstitial lung disease (ILD) in idiopathic inflammatory myopathies (IIM) may appear at any time in evolution and is associated with a worse prognosis. <h3>Objectives</h3> To investigate sociodemographics data and clinical characteristics of patients with IIM and ILD from the REMICAM registry. <h3>Methods</h3> A multicenter retrospective study (1980–2014) was performed. Patients were classified as polymiosytis (PM), dermatomyositis (DM), IIM with anti-synthetase antibodies (AB) and overlap syndrome. In addition, ILD was classified according to HRCT pattern: usual interstitial pneumonia (IP), non specific IP, organizing pneumonia, and acute IP. We compared sociodemographic data, clinical characteristics, AB and treatments of patients with and without ILD, patients with ILD according to subgroup of myositis or ILD. <h3>Results</h3> 478 patients were included, of whom 129 (27%) had ILD. Patients with ILD had a higher age at diagnosis, ESR and CRP and worse initial respiratory function. They were characterized by increased frequency of arthritis, systemic and cardiac manifestations, Raynaud, cardiovascular disease, pulmonary hypertension, ischemic ulcers, sclerodactyly and anti-synthetase AB (p&lt;0.001). The differences among patients with ILD were: less arthritis in PM, greater frequency of Raynaud and sclerodactyly in overlap and antisynthetase syndrome, more anti-RNP AB in the overlap syndrome, more anti-synthetase and anti-Ro AB in the antisynthetase syndrome, and a higher prevalence of cutaneous signs and mechanical hands in DM (p&lt;0.001). There were no differences according to the type of ILD or treatments. <h3>Conclusions</h3> We found some clinical manifestations and AB that may help for detection of patients with IIM associated to ILD, as well as clinical manifestations to better differentiate myositis subtypes in patients with ILD. <h3>Disclosure of Interest</h3> None declared
“Beginning with the Smallest Intake”: Children’s Brain Development and the Role of Neuroscience in Global Environmental Health
Authors: Kam Sripada
Journal: Neuron (2017)

Early exposure to environmental toxins like lead, air pollution, and arsenic can have long-lasting and irreversible consequences for children's neurodevelopment, especially in the developing world. Though the number of pollutants increases each year, some neuroscientists are forging partnerships to improve measurement, raise awareness, and promote global health. Early exposure to environmental toxins like lead, air pollution, and arsenic can have long-lasting and irreversible consequences for children's neurodevelopment, especially in the developing world. Though the number of pollutants increases each year, some neuroscientists are forging partnerships to improve measurement, raise awareness, and promote global health.
AB0110 Evaluation of the effect of chuantengtongbi decoction on DBA / 1 MICE cia model
Authors: X-Q Wang, X-D Shen, X-Y Zhang, X Du
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> DBA/1 mouse (H2<sup>q</sup> type) CIA model as a mature model of rheumatoid arthritis is widely used in pharmacology and pharmacodynamics research<sup>[1]</sup>. Chinese medicine treatment of rheumatoid arthritis has accumulated rich experience. The study of Tripterygium glycosides is quite representative, and it has been widely used in the past 30 years. Some Clinical studies showed that tripterygium glycosides treatment of rheumatoid arthritis had good effect<sup>[2]</sup>. ChuanTengTongBi decoction is also the effective prescription commonly used for the treatment of rheumatoid arthritis. <h3>Objectives</h3> To investigate the pathological damage degree of DBA/1 mouse CIA model and the effects of different doses of ChuanTengTongBi decoction on the CIA model mice. <h3>Methods</h3> The mice were divided into normal group, model group, leflunomide group (3.11mg/kg/d), low-dose of ChuanTengTongBi group (0.44g/ml/d), medium-dose group (0.88g/ml/d) and high-dose group (1.76g/ml/d). <h3>Results</h3> The arthritis index (AI) was evaluated every week to determine whether the model was successful. We defined AI score ≥4 as successful model (AI score standard:0, No swelling;1, Slight redness and swelling;2, Moderate redness and swelling of ankle; 3, Severe redness and swelling of the entire paw;4, Maximally inflamed limb with involvement of multiple joints <sup>[3]</sup>). Day 28–42, hind foot redness and swelling of the mouse continued to develop and extended to the forefoot. Compared with the normal group, incidence of CIA model group reached 100%. Day 49, compared with the model group by joint scores, medium-dose group, high-dose group and leflunomide group have Significant differences on CIA model (p&lt;0.01). Compared with the Leflunomide group, low-dose group, medium-dose group and high-dose group have no obvious difference (p&gt;0.05). Compared with the low-dose group, medium-dose group and high-dose group have no difference (p&gt;0.05). <h3>Conclusions</h3> CIA model has a high morbidity, long duration, macroscopic pathological manifestation and irreversible ankle joint deformation, which is consistent with the progress of human RA disease and pathological damage. Medium-dose of ChuanTengTongBi decoction, high-dose and leflunomide group had inhibitory effect on the progress of arthritis, and the effect of high-dose was better than that of leflunomide group. <h3>References</h3> Brand, D.D. Rodent models of rheumatoid arthritis. Comp. Med. 55, 114–122(2005). Shen S, Yang Z, Yiyang H U, et al. The Effect of Tripterygium Wilfordii glycoside on the Expression of CD_4+CD_(25)∼(high) Regulatory T cells,Th1 and Th2 with IgA Nephropathy[J]. Chinese Journal of Integrated Traditional &amp; Western Nephrology, 2013. David D Brand, Kary A Latham, &amp; Edward F Rosloniec. Collagen-induced arthritis. Nature Protocol.5.1270–1274(2007). <h3>Disclosure of Interest</h3> None declared
SAT0294 Comparison of clinical care between chinese and american patients with systemic lupus erythematosus
Authors: J Dong, H Ma, WN Roberts, L Wang, F Khan, KA Lyn Shue, L Zhao, L Pan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In addition to gender and ethnicity, modifiable variables like geography, socioeconomic status, health system structure, education, and physician expertise may influence outcomes in systemic lupus erythematosus (SLE). <h3>Objectives</h3> To compare characteristics of and treatment options for subsets of Chinese and American patients with SLE to elucidate factors that contribute to disease activity and damage. <h3>Methods</h3> Chart review of 77 Chinese (Qingdao) and 48 Midwestern American (Louisville, Kentucky) patients meeting American College of Rheumatology (ACR) criteria for a diagnosis of SLE followed up for four years were analyzed retrospectively. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index (SDI), and disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Statistics were parametric exploratory tests of significance and multiple regression analyses in this hypothesis-generating effort. <h3>Results</h3> The interval between the time of onset and diagnosis was 44 months shorter in the Chinese arm (p=0.001), and Chinese patients followed up at six times greater frequency than American patients (p&lt;0.001). Despite the lack of formal matching, the two cohorts featured similar disease activity according to the SLEDAI. Based on the SDI, rates of organ damage were higher in the American group. Chinese patients received more steroids, cyclophosphamide, hydroxychloroquine, intravenous immune globulin, and cyclosporine than the Louisville group, while the Louisville patients received more mycophenolate mofetil and azathioprine (p=0.001). <h3>Conclusions</h3> The establishment of follow-up and treatment of SLE differs in specific, identifiable ways between these subsets of Chinese and midwestern American patients. Greater access to and increased frequency of follow-up appears associated with a lesser degree of organ damage, supporting the treat-to-target concept as applied to SLE. Complete, controlled trials in both settings are necessary, and further detailed comparison of larger cohorts may inform conclusions about the likelihood of generalizability of trial results from one setting to another. <h3>Disclosure of Interest</h3> None declared
THU0377 Low dose il-2 therapy can recovery th17/treg cell balance in patients with spondyloarthropathy through increasing regulatory t cells numbers
Authors: F Jinnan, X Dan, C Qianqian, Q Kaili, G Chong, L Xiaofeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The imbalance in the number of Th17 and Treg cells is suggested to be associated with the pathogenesis of SpA. Recent studies have shown that interleukin-23 (IL-23) and Th17 play a crucial role in the pathogenesis of SpA. However the status of CD4+CD25+Foxp3+Treg cells which exert immunoregulatory functions are remains to investigate. <h3>Objectives</h3> To explore the status of the immunologic balance between Th17 cells and Treg cells in patients with SPA, and to assess the effect of low dose IL-2 on the peripheral CD4+ T cells. <h3>Methods</h3> Two hundred and two patients, who met the Assessment of Spondyloarthritis International Society (ASAS) criteria were enrolled and given conventional therapy, including Nonsteroidal Anti-inflammatory Drugs (NSAIDs), biological agents, Sulfasalazine, glucocorticoid. Eighty seven patients were not only given conventional therapy, but also injected subcutaneously low-dose IL-2 (50 WIU/day for 5 days). Clinical and laboratory indicators were compared before and after IL-2 treatment. The CD4<sup>+</sup> T cells in peripheral blood were measured by multicolor flow cytometry. The side effects were observed in the course of therapy. <h3>Results</h3> The absolute number and ratio of CD4 + CD25 + FOXp3 + regulatory T cells in peripheral blood of patients with SPA was significantly decreased compared with the healthy control group, (25.13 (18.76,37.37) vs. 33.06 (22.87,42.33), P&lt;0.001); Th17/Treg (0.29 (0.18, 0.49) vs. 0.20 (0.15, 0.34), P=0.001). The absolute number of Treg cells increased more than 3-times (22.70 (14.47, 30.10) vs.67.87 (48.21, 105.82), p&lt;0.001) after 5 days of low-dose IL-2 treatment. Th17/Treg was significantly higher (0.32 (0.18, 0.57) vs. 0.20 (0.15, 0.34), P&lt;0.001) before treatment compared with healthy controls. <h3>Conclusions</h3> The decrease of CD4 + CD25 + FOXp3 + Treg cells might play a key role in the pathogenesis of SpA. Low dose IL-2 therapy can restore and maintain the balance of Th17 and Treg cells by increasing Treg cells numbers selectivity. The therapy is safe. More attention should be paid on the long term benefits of low-dose IL-2 therapy in the further research. <h3>References</h3> Wu Y, Ren M, Yang R, Liang X, Ma Y, Tang Y, et al. Reduced immunomodulation potential of bone marrow-derived mesenchymal stem cells induced CCR4 + CCR6 + Th/Treg cell subset imbalance in ankylosing spondylitis. Arthritis Res Ther. 2011;13:R29. Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008;58:2307–17. Wendling D, Guillot X, Prati C. The IL-23/Th 17 pathway in spondyloarthritis: the royal road. Joint Bone Spine 82(1), 1–4 (2015). <h3>Disclosure of Interest</h3> None declared
THU0523 Mortality and causes of death among juvenile idiopathic arthritis patients in finland
Authors: M Kyllonen, H Kautiainen, K Puolakka, P Vahasalo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Juvenile idiopathic arhritis (JIA) is an inflammatory arthritis that begins before 16 years of age and persists more than 6 weeks. The prevalence of JIA is approximately 1 to 2 per 1,000 children. Only 40–60% of JIA patients had inactive disease at follow-up (1). An increase rate of mortality has been observed in JIA. A follow-up study (1960–1993) in the United States reported early deaths especially in systemic JIA (2). The same was found in an follow-up study in Scotland (3). However two follow -up studies in United States and one study in Germany showed no increased mortality (4,5,6). <h3>Objectives</h3> To explore mortality rates and causes of death in JIA patients in Finland compared with the general population. <h3>Methods</h3> All incidents patients with JIA during 2000–2014 were collected from the nationwide register of special reimbursements for disease-modifying antirheumatics drugs, maintained by the Social Insurance Institution of Finland. The National Population Registry identified three age, sex and residence matched controls for each case. Death certificate data up to 2015 were obtained from the Statistics of Finland. <h3>Results</h3> Altogether 4,180 JIA patients (62% girls) were identified. Mean age at diagnosis was 8.3 years. The average follow-up was 6.6 years (IQR 3.1–10.5). These patients were compared with 12,511 controls. During 28.941 follow-up years, 11 JIA patients (6 girls, 5 boys) and 23 controls (12 girls, 11 boys) died. Mean age at death was 20.3 years (range 11–30) in the JIA patients and 23.1 years (range 9–29) years in the control group. (p=0.17). Cumulative mortality in the patients with JIA was 0.4% (95% Cl 0.2–0.8%) compared to 0.3% (95% Cl 0.2–0.5%) in the controls, hazard ratio was 1.44 (95% Cl 0.70–2.95). Accidents were the most common (54%) cause of death in the patients with JIA, but suicide (39%) in the controls. Alcohol, drug abuse and depression contributed more to deaths in the control (39%) than in JIA group (1%), p=0.053. <h3>Conclusions</h3> Juvenile idiopathic arthritis is not associated with a higher mortality rate in children and young adults. <h3>References</h3> Ravelli et al. Juvenile idiopathic arthritis. Lancet 2007;369: 767–78. French et al. Increased mortality in adults with a history of juvenile rheumatoid arthritis. ArthrRheum 2001;44: 523–527. Thomas et al. National study of cause-spesific mortality in rheumatoid arhtritis, juvenile chronic arthritis and other rheumatic conditions: a 20 year follow up. JRheumatology, 2003;30:958–965. Hashkes P et al. Mortality outcomes in pediatric rheumatology in the US. ArthrRheum 2010;62:599–608. Krause et al. Juvenile idiopathic arthritis in Olmsted County, Minnesota 1960–2013. ArthrRheum 2016; 68: 247–254. Minden et al. Long- term outcome in patients with juvenile idiopathic arthritis. ArthrRheum 2002; 46: 2392–2401. <h3>Disclosure of Interest</h3> None declared
Review: In menopause (intact uterus), estrogen + progestogen, isoflavones, and black cohosh reduce hot flashes
Authors: Dennis G. Maki
Journal: Annals of Internal Medicine (2017)

Source Citation Sarri G, Pedder H, Dias S, Guo Y, Lumsden MA. Vasomotor symptoms resulting from natural menopause: a systematic review and network meta-analysis of treatment effects from the National Institute of Health and Care Excellence guideline on menopause. BJOG. 2017 Mar 9. [Epub ahead of print]. 28276200
AB0203 Expression levels of selected genes can predict the individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment
Authors: D Paran, Y Smith, S Pundak, U Arad, D Levartovsky, I Kaufman, J Wollman, V Furer, A Broyde, O Elalouf, D Caspi, S Pel, O Elkayam
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) patients have many therapeutic options. However, there are limited tools to predict the individual patient9s response to therapy. The Genefron personal diagnostic kit (IFR 300) has been developed based on analysis of large databases to select interferon stimulated gene (ISG) expressions which could predict response to a biologic agent <h3>Objectives</h3> This study aims to evaluate the ability of the Genefron diagnostic kit to predict the individual RA patient response to TNFα blockers. <h3>Methods</h3> Two separate analyses were performed, one retrospective and one prospective analysis. The response of 61 RA patients reported in 2 published data sets was analyzed retrospectively utilizing the Genefron kit. In addition, 18 patients with RA were assessed prospectively, before and 3 months after starting treatment with a TNFα blocker. Clinical assessment included swollen and tender joint counts, patient and physician assessments of disease activity. Patients9 blood samples were obtained before administration of the TNFα blocker and were analyzed utilizing the Genefron diagnostic kit which measures expression levels of selected genes by quantitative real time PCR. <h3>Results</h3> Genefron kit analysis of retrospective data correctly predicted the response to a TNFα blocker in 53 of 61 RA patients (accuracy - 86.8%). In the prospective analysis 6 patients achieved a moderate EULAR response, 6 achieved a good EULAR response and 6 did not respond. According to the EULAR moderate response, the Genefron diagnostic kit predicted the response correctly in 16 of 18 patients (accuracy-89%, sensitivity -100%, specificity - 67%). According to the EULAR good response, the kit predicted the response correctly in 15 of 18 patients (accuracy - 83.3%, sensitivity - 100%, specificity - 75%). <h3>Conclusions</h3> The Genefron diagnostic kit predicted the response to TNFα blockers in a high percentage of RA patients assessed either retrospectively or prospectively in a real life setting. This personal diagnostic kit has the ability to guide selection of a suitable biological drug for the individual RA patient <h3>Disclosure of Interest</h3> None declared