tbuckley/cabot-search huggingface dataset:
THU0564 Efficiency and safety evaluation of biosimilar infliximab for treatment of paediatric non-infectious uveitis in single centre
Authors: B. Sozeri, E. Kardes, L.G. Bolac, B.I. Sezgin Akçay
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Biosimilar infliximab (Remsima) has been introduced in our country, together with other European countries in 2014. Information regarding the use in child age group is limited but it is reported that its therapeutic efficiency and safety is similar to the reference molecule regarding the paediatric Chron disease <h3>Objectives</h3> In this study, our aim was to reporte the efficiency and safety of BI used for children with non-infectious uveitis <h3>Methods</h3> In this study, there were 13 subjects (9 boys, and 4 girls) diagnosed with non-infectious uveitis. BI (Remsima9 treatment had been given in 5 mg/kg in 0.,2.,4 th week and then every 8th week. Ophthalmic assessment of disease activity and ocular complications were measured throughout the trial with the use of slit-lamp biomicroscopy for uveitis activity, according to the SUN criteria. The Drug exposure has been evaluated by calculated of patient year (HY), adverse event (AE) was assessed using the CTCAE criteria. The median values due to the small number of patients are considered <h3>Results</h3> The patients who were include the study, 5 had diagnosed extended oligo JIA, 2 with enthesitis-related arthritis (ERA), 2 with persistent oligo JIA, 2 with pars planitis and one of them Behcet's disease. At the time of evaluation, the median age was 10 years,<sup>3–13</sup> age at diagnosis of their disease 8 years,<sup>1–13</sup> respectively. The median age of uveitis diagnosis was 8 years. The median disease duration before BI was 10 months. All of the patients had methotrexate therapy with BI and BI before. Only one patient used a different biological agent prior to BI, and revealed they were determined that considered unresponsive. Other patients (n=12) had biosimilar infliximab as first biologic drug due to the activation of disease after using the drug methotrexate. After therapy of BI, in all of the patients, joint and eye symptoms were improvement. The systemic steroid therapy was cut down in the first month in all patients, 2 of them continue prophylactic topical steroids. The median duration of BI therapy was 10 months. There was one case of anaphylaxis in all the patients, whereas five of them frequent upper respiratory tract infection have been observed as side effect <h3>Conclusions</h3> In this preliminary report, This biosimilar infliximab treatment appears to be safe and effective in paediatric age group on the paediatric patients with non-infectious uveitis. These results must be supported by multicenter studies and registries. <h3>Disclosure of Interest</h3> None declared
How many lymph nodes should be removed to define an optimal D2 lymphadenectomy for gastric cancer in the modern era? An analysis of 2,947 patients from a two-institution database in China.
Authors: Changming Huang, Jun Lu, Chaohui Zheng, Ping Li
Journal: Journal of Clinical Oncology (2016)

4051 Background: Although current guidelines suggest that 16 or more lymph nodes (LNs) are required for the appropriate staging of gastric cancer, the effect on survival of the minimum number of examined LNs (eLNs) in the different types of gastrectomy remains unclear. Methods: We retrospectively analyzed 2662 patients who underwent curative gastrectomy with D2 lymphadenectomy for gastric cancer at Fujian Medical University Union Hospital from Jan 2000 to Dec 2010 and randomly divided them into development (70%, n＝1863) and validation (30%, n＝799) datasets. An additional external validation was performed using the data set (n＝285) that was collected during the same period from the Sun Yat-sen University Cancer Center in Guangzhou, China. A hypothetical TNM classification (hTNM) was proposed based on eLNs and prognosis. Results: The mean numbers of nodes removed during radical distal and total gastrectomy were 26±9.6 and 29±10.7, respectively (p＜0.01). The optimal LNs count thresholds were determined to be 16 and 21 for patients who underwent curative distal and total gastrectomy, respectively. The hTNM staging system had higher linear trend and likelihood ratioΧ2 scores and lower AIC values than the seventh AJCC TNM classification; thus, the hTNM staging system exhibited superior prognostic stratification. Similar results were found in the two validation datasets. Conclusions: To maximize the survival benefit after radical total gastrectomy (RTG) for gastric cancer, a minimum of 21 LNs should be removed. For patients undergoing RTG, the hTNM staging system may predict survival more accurately and discriminatively, and this proposed system could have good clinical utility.
AB0640 Implausible anti-smith antibody is not implausible to autoimmune disease in chinese population using the euroimmun line immunoassays
Authors: Y. Wu, Y. Meng
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anti-Sm antibody is important test for lupus. In China, many labs detected anti-Sm using Euroimmun line immunoassays (LIA) kit, which mixture with purified Sm and RNP antigens as target antigens in Sm/RNP band and purified Sm antigens in Sm band. On the instruction, anti-Sm results should be determined according to the 2 bands. That is divided as true anti-Sm positive cases (having positive Sm and Sm/RNP bands) and implausible cases (having Sm band without Sm/RNP band), the value of implausible anti-Sm is not very clear now. <h3>Objectives</h3> We aimed at investigating the clinical value of the implausible anti-Sm in Chinese population. <h3>Methods</h3> Total of 39 766 patients were analysed for anti-Sm antibody using the EURO lineimmuno assay skit, of which 1208 cases are positive for anti-Sm. All cases with positive anti-Sm were divided into true anti-Sm group and implausible group according to the result of Sm/RNP band. The proportion of clinical diagnosis including autoimmune diseases (AIDs) and non-immune diseases (NAIDs) and the level of some clinical serum indexeswere retrospectively analysed for the implausible anti-Sm cases. <h3>Results</h3> Implausible anti-Sm were evidenced in 271/1208 (22.42) of all positive anti-Sm cases. Among patients with positive anti-Sm, 177 cases have definitive diagnoses (65.31%, 177/271), with autoimmune diseases accounting for 68.36% (121/177), of whom 96 had systemic lupus erythematosus (SLE) (79.34%). In addition, there are 5 implausible cases with rheumatoid arthritis (RA), 3 with Sjogren syndrome (SS) and 10 with mixed connective tissue diseases (MCTDs). The titer of antinuclear antibodies (ANA) in patients with implausible anti-Sm is lower than ones with true anti-Sm. Impausible group have the same gender ratio, mean onset age and frequency of autoantibodies with true group. The prevalence of one of NAIDs, kidney disease, was significantly lower in implausible group than in true group (X2=3.841, p=0.05). <h3>Conclusions</h3> Implausible anti-Sm have great diagnostic value in AIDs just as true anti-Sm. Patients with implausible anti-Sm have less incidence of evolving to autoimmune injury and kidney injury. Patients with implausible anti-Sm but without autoimmune diseases may be potential autoimmune disease victims. <h3>Acknowledgements</h3> This work was supported by fund of Department of Science and Technology of Sichuan Province, Grant No. 2016 JY0035 and the fund of Health and Family Planning Commission of Sichuan Province, Great. No.16pg326. <h3>Disclosure of Interest</h3> None declared
Immunotherapy Resistance by Inflammation-Induced Dedifferentiation
Authors: Arnav Mehta, Yeon Joo Kim, Lidia Robert, Jennifer Tsoi, Begoña Comin-Anduix, Beata Berent-Maoz, Alistair J. Cochran, James S. Economou, Paul C. Tumeh, Cristina Puig-Saus, Antoni Ribas
Journal: Cancer Discovery (2018)

Abstract A promising arsenal of targeted and immunotherapy treatments for metastatic melanoma has emerged over the last decade. With these therapies, we now face new mechanisms of tumor-acquired resistance. We report here a patient whose metastatic melanoma underwent dedifferentiation as a resistance mechanism to adoptive T-cell transfer therapy (ACT) to the MART1 antigen, a phenomenon that had been observed only in mouse studies to date. After an initial period of tumor regression, the patient presented in relapse with tumors lacking melanocytic antigens (MART1, gp100) and expressing an inflammation-induced neural crest marker (NGFR). We demonstrate using human melanoma cell lines that this resistance phenotype can be induced in vitro by treatment with MART1 T cell receptor–expressing T cells or with TNFα, and that the phenotype is reversible with withdrawal of inflammatory stimuli. This supports the hypothesis that acquired resistance to cancer immunotherapy can be mediated by inflammation-induced cancer dedifferentiation. Significance: We report a patient whose metastatic melanoma underwent inflammation-induced dedifferentiation as a resistance mechanism to ACT to the MART1 antigen. Our results suggest that future melanoma ACT protocols may benefit from the simultaneous targeting of multiple tumor antigens, modulating the inflammatory response, and inhibition of inflammatory dedifferentiation-inducing signals. Cancer Discov; 8(8); 935–43. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 899
Increased risk of dementia in 50 year olds with raised blood pressure below treatment threshold, study finds
Authors: Susan Mayor
Journal: BMJ (2018)

Fifty year olds with blood pressure that is higher than normal but below the conventional treatment threshold have increased risk of developing dementia in later life, latest findings from the long running UK Whitehall II study of civil servants1 have shown.

“Our work confirms the detrimental effects of midlife hypertension for risk of dementia,” said lead author Archana Singh-Manoux, from the National Institute of Health and Medical Research in Paris (INSERM), France, and University College London, UK.

She added, “It also suggests that at age 50, the risk of dementia may be increased in people who have raised levels of systolic blood …
Screening of SirT1 activating compounds and their cytotoxicity in prostate cancer cell lines.
Authors: Maofu Fu, Nagarajan Pattabiraman, Chenguang Wang, Xiaoming Ju, Anthony Sauve, Richard G. Pestell
Journal: Journal of Clinical Oncology (2012)

e13545 Background: Our previous studies demonstrated that the human androgen receptor (AR) is an acetylated protein, and acetylation of the AR in the hinge region is essential for its ligand-dependent transactivation. The AR acetylation mimic mutant, ARK630Q, and a somatic mutation from the prostate cancer patient at the AR acetylating motif, ARK630T, showed enhanced receptor/coactivator binding and led to accelerated prostate cancer cell growth. SirT1, an NAD+-dependent class III HDAC, suppresses AR and inhibits prostate cell proliferation via deacetylation of AR. Deletion of the SirT1 gene in mice resulted in prostatic intraepithelial neoplasia (PIN) lesion formation associated with reduced autophagy. Our hypothesis is that small molecules with SirT1 activating properties could be potential novel agents for treatment of AR-expressing prostate cancer. Methods: We performed in-silico screening for small molecule antagonists of SirT1 based on computational model prediction of a known SirT1 activator, resveratrol, and identified potential activators for SirT1. The cytotoxicity of these compounds to the prostate cancer cell lines was tested by MTT assay. Results: Among the twelve compounds tested, three compounds, C5, C6 and C10, were found to inhibit AR expression in LNCaP cells and have cytotoxicity in several prostate cell lines including LNCaP, C4W2 and NeuT-transformed prostate epithelial cell line at concentration of 50 µM. Conclusions: Currently, we are testing the effects of these small molecules on the NAD+-dependent deacetylation activity of SirT1 and their effects on AR acetylation as its molecular mechanism of cell growth inhibition. The ultimate goal of this study is to develop early phase clinical trials in prostate cancer patients by blocking AR acetylation using these SirT1 activators.
Island Pedicle Flap—Its Place in History
Authors: Pooja Reddy, Quynh-Giao Nguyen, Ikue Shimizu
Journal: JAMA Dermatology (2018)

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AB0844 Efectiveness and retention rate of certolizumab pegol in spondyloarthritis. real life data
Authors: R. Expósito-Molinero, R. Garcia-Portales, J.R. Lamua-Riazuelo, A. Urruticoechea-Arana, P. Navarro-Alonso, J.S. Rey-Rey, M. Fernandez-Prada, C.M. Gonzalez Fernandez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Certolizumab pegol (CZP) is available for patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). The efficacy and the safety of CZP are well established from clinical trials. However, evidence of its effectiveness in regular clinical practice is limited. <h3>Objectives</h3> To evaluate the effectiveness and safety of CZP in a real word setting in axSpA patients. <h3>Methods</h3> Multicentric cohort of SpA patients treated with CZP according to routine clinical practice. The study was approved by the local Ethics Committee. Maximum follow-up was 12 months. Clinical response was evaluated through BASDAI, ASDAS, BASFI and MASES scores. Safety variables: discontinuation rate. <h3>Results</h3> 336 patients with axSpA were included: 56.5% male, mean age 45.8 (±12.1) years, median disease time 4.3 (0, 49.5) years, 68.5% of patients were HLAB27 positive, and never smokers 64.7%. Prior bDMARD received (27.2% none; 37.9% 1, 35%≥2). At baseline 36.8% had concomitant DMARDs and 82.8% NSAIDs. 31.8% of patients had peripheral arthritis and 42.7% entesitis at baseline. CZP retention time 10.3 months. Statistically significant differences in BASDAI, BASFI, ASDAS y MASES were observed at the last visit comparing to baseline (table 1). In the last observation, 41.0% of the patients achieved BASDAI50, 34% were in ASDAS remission (ASDAS &lt;1.3) and 49% presented a minimal clinical improvement (ASDAS at least 1.1). 46.3% of patients had resolution of the enthesitis (MASES=0). According to Kaplan-Meier analysis, the drug survival of CZP was 83.3%, and no differences were observed in retention rates when CZP were used as first option (83.3%) or after failure to other biologicals (79.1%) (figure 1). 56/336 (16.7%) withdrawn CZP treatment: 34/336 (10.1%) due to lack of effectiveness, 16/336 (4.8%) due to adverse event and 6/336 (1.8%) for other reason. Serious adverse event was found in 23/336 (6.8%) patients. <h3>Conclusions</h3> Real life experience from this nationwide rheumatology study, demonstrated the effectiveness and safety of CZP in patients with axSpA, with a significant reduction of BASDAI, BASFI, ASDAS and MASES scores. No differences were observed in the retention rate regardless previous biological treatment. <h3>Disclosure of Interest</h3> R. Expósito-Molinero: None declared, R. Garcia-Portales Consultant for: Celgene, Speakers bureau: UCB, Pfizer, Roche, J. R. Lamua-Riazuelo: None declared, A. Urruticoechea-Arana: None declared, P. Navarro-Alonso: None declared, J. S. Rey-Rey Speakers bureau: UCB, Abbvie, Pfizer, BMS, Roche, Celgene, M. Fernandez-Prada: None declared, C. Gonzalez Fernandez Consultant for: MSD, Janssen, Novartis, Celgene, Speakers bureau: Abbie, Janssen, MSD, Novartis, Roche, UCB, BMS
建立失禁相关性皮炎(IAD)相关国际通用术语:在30个国家/地区进行根特全球(IAD)分类工具(GLOBIAD)心理测量特性的设计和评估
Authors: D. Beeckman, K. Van den Bussche, P. Alves, M.C. Arnold Long, H. Beelev, G. Ciprandi, F. Coyer, T. de Groot, D. De Meyer, E. Deschepper, A.M. Dunk, A. Fourie, P. García-Molina, M. Gray, A. Iblasi, R. Jelnes, E. Johansen, A. Karadag, K. Leblanc, Z. Kis Dadara, S. Meaume, A. Pokorna, M. Romanelli, S. Ruppert, L. Schoonhoven, S. Smet, C. Smith, A. Steininger, M. Stockmayr, N. Van Damme, D. Voegeli, A. Van Hecke, S. Verhaeghe, K. Woo, J. Kottner
Journal: British Journal of Dermatology (2018)

几十年来,婴儿尿布皮炎(尿布疹)的最佳预防和治疗方法一直都是研究热点。然而,这种皮肤问题也会出现在成人身上,这时被称作失禁相关性皮炎(IAD)。它是刺激性接触性皮炎(一种由接触刺激物而非致敏物导致的湿疹)的一种特殊类型,由皮肤与尿液或粪便长时间接触导致。很难确切知道IAD患者究竟有多少,因为目前尚无一套国际公认的诊断标准(例如,一份可用于鉴别疾病的特定症状和标准清单)将其与其他有类似症状的皮肤病(如压力性溃疡)区分开来。目前存在十种不同的量表/工具(即疾病诊断和严重程度排序方法),但有些十分复杂,因而需要有一种量表/工具来确保研究结果具有可比性。因此,来自13个国家/地区的34位专家携手合作,共同开发出了一款工具,取名为GLOBIAD,于2015年启用。该工具随后被翻译成14种不同的语言。30个国家/地区的823位专家使用GLOBIAD对34张IAD照片进行了分类,并检验结果是否匹配,从而测试了该工具的准确性。该研究发现,GLOBIAD的开发是一项重大进展,有助于在全球临床实践和研究中,对IAD进行更好的系统评估。但是,这种工具还有待进一步验证。
SAT0161 Influence of disease activity in rheumatoid arthritis on radiographic progression of concomitant interphalangeal joint osteoarthritis
Authors: C. Lechtenboehmer, V. Jaeger, D. Kyburz, U. A. Walker, T. Hügle
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> The role of inflammation in in distal interphalangeal (DIP) osteoarthritis (OA) is not clear. Unlike the situation in psoriatic arthritis, DIP joints are considered not to be affected in rheumatoid arthritis (RA). Despite synovitis and bone marrow edema are also associated with radiographic progression of hand OA, the radiological course of DIP-OA and joints affected from RA differ substantially. <h3>Objectives:</h3> To clarify the influence of RA disease activity and bone erosions on radiologic progression of DIP joint OA. <h3>Methods:</h3> In sequential radiographs of 1988 RA patients available within the Swiss rheumatic disease registry (SCQM), we scored 15904 DIP joints for the presence of erosions as well as the severity of osteophytes, subchondral sclerosis and joint space narrowing according to the modified Kellgren Lawrence Grade (KLG). Progression was defined as an increase of KLG. <h3>Results:</h3> The mean patient age was 56.1 years (SD 11.1). The median follow-up time was 4.5 years (IQR 3.1 – 7.0). DIP-OA was present in 60% of patients at baseline. Age, female sex and higher body mass index but not anti-citrullinated protein antibodies or rheumatoid factors were associated with the presence of DIP-OA. Preexisting DIP-OA (odds ratio [OR] 4.7, p&lt;0.001) and female sex (OR 1.4, p=0.009) were predictors for radiologic progression, whilst metacarpophalangeal joint erosions or DAS28-ESR had no influence on the radiological course of DIP-OA. <h3>Conclusions:</h3> Known risk factors for DIP-OA are replicated in patients with RA. RA disease activity, autoantibody status or metacarpophalangeal joint erosions where not associated with DIP-OA presence or progression, indicating distinct roles of inflammation in the pathogenesis of RA and OA. <h3>Disclosure of Interest:</h3> None declared
ZNF341 controls STAT3 expression and thereby immunocompetence
Authors: Stefanie Frey-Jakobs, Julia M. Hartberger, Manfred Fliegauf, Claudia Bossen, Magdalena L. Wehmeyer, Johanna C. Neubauer, Alla Bulashevska, Michele Proietti, Philipp Fröbel, Christina Nöltner, Linlin Yang, Jessica Rojas-Restrepo, Niko Langer, Sandra Winzer, Karin R. Engelhardt, Cristina Glocker, Dietmar Pfeifer, Adi Klein, Alejandro A. Schäffer, Irina Lagovsky, Idit Lachover-Roth, Vivien Béziat, Anne Puel, Jean-Laurent Casanova, Bernhard Fleckenstein, Stephan Weidinger, Sara S. Kilic, Ben-Zion Garty, Amos Etzioni, Bodo Grimbacher
Journal: Science Immunology (2018)

Homozygous nonsense mutations in ZNF341 impair its ability to activate STAT3 transcription and thereby cause immunodeficiency.
Prevalence of Dietary Supplement Use in US Children and Adolescents, 2003-2014
Authors: Dima M. Qato, G. Caleb Alexander, Jenny S. Guadamuz, Stacy Tessler Lindau
Journal: JAMA Pediatrics (2018)

This study uses NHANES data to estimate the prevalence of dietary supplement use, including both nutritional products and alternative medicines, among US children and adolescents between 2003 and 2014.
Biologic refractory disease in rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis
Authors: Lianne Kearsley-Fleet, Rebecca Davies, Diederik De Cock, Kath D Watson, Mark Lunt, Maya H Buch, John D Isaacs, Kimme L Hyrich
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Biologic disease-modifying antirheumatic drugs (bDMARDs) have revolutionised treatment and outcomes for rheumatoid arthritis (RA). The expanding repertoire allows the option of switching bDMARD if current treatment is not effective. For some patients, even after switching, disease control remains elusive. This analysis aims to quantify the frequency of, and identify factors associated with, bDMARD refractory disease. Methods Patients with RA starting first-line tumour necrosis factor inhibitor in the British Society for Rheumatology Biologics Register for RA from 2001 to 2014 were included. We defined patients as bDMARD refractory on the date they started their third class of bDMARD. Follow-up was censored at last follow-up date, 30 November 2016, or death, whichever came first. Switching patterns and stop reasons of bDMARDs were investigated. Cox regression identified baseline clinical factors associated with refractory disease. Multiple imputation of missing baseline data was used. Results 867 of 13 502 (6%) patients were bDMARD refractory; median time to third bDMARD class of 8 years. In the multivariable analysis, baseline factors associated with bDMARD refractory disease included patients registered more recently, women, younger age, shorter disease duration, higher patient global assessment, higher Health Assessment Questionnaire score, current smokers, obesity and greater social deprivation. Conclusions This first national study has identified the frequency of bDMARD refractory disease to be at least 6% of patients who have ever received bDMARDs. As the choice of bDMARDs increases, patients are cycling through bDMARDs quicker. The aetiopathogenesis of bDMARD refractory disease requires further investigation. Focusing resources, such as nursing support, on these patients may help them achieve more stable, controlled disease.