tbuckley/cabot-search huggingface dataset:
Immunohistochemical expression of human tissue kallikreins in neoplasms of various organs
Authors: Constantina Petraki, Panagiotis A. Papanastasiou, Vassiliki N. Karavana, Eleftherios P. Diamandis
Journal: Cancer Research (2006)

4358   Human tissue kallikreins are members of a large multigene family of fifteen serine proteases (the genes designated as KLK1–KLK15 and their encoded proteins as hK1–hK15). In addition to the established role of hK3 (PSA) in prostate cancer, many members of the KLK gene family have been proposed as new biomarkers for other cancers, including breast, ovarian and testicular cancer. Most studies are based on quantitative methods and especially, RT-PCR and ELISA measurements. Recently, we have immunohistochemically evaluated most of the above hKs in normal and malignant tissues. In general, most hKs were immunohistochemically revealed in a variety of tissues, indicating that these proteins are not tissue-specific (except for hK2 and hK3 which have prostate-restricted expression). It is worth mentioning that tumors arising from tissues expressing hKs, also showed an immunohistochemical expression (IE). As glandular epithelia constitute the main IE sites, all hKs were expressed in adenocarcinomas of the stomach, colon, pancreas, breast, ovary and prostate. This finding implicates kallikreins in the progression of cancer. Furthermore, urothelial carcinomas, papillary and follicular thyroid carcinomas, gliomas, prolactinomas and hormone-producing pancreatic tumors showed variable kallikrein immunoexpression. In series of prostate, renal cell, colon and urothelial carcinomas, we have studied the correlation of hK IE with the histological type and clinical behavior of these tumors. Our main findings were that the IE of several hKs had a positive correlation with the histological grade and pathological stage of colon, renal cell and prostate cancer. Furthermore, some hKs were independent unfavorable predictors of overall survival for these carcinomas. The hK IE in urothelial carcinomas was variable, without any statistically significant correlation with histological grade or pathological stage. We conclude that it is now possible to immunohistochemically localize many kallikreins in diverse malignancies for the purpose of evaluating these molecules as prognostic and predictive biomarkers.
FRI0691 Association between periodontitis and the risk of palindromic rheumatism: a nationwide, population-based, case-control study
Authors: H-H Chen, W-C Chao, Y-M Chen, D-Y Chen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Some patients with palindromic rheumatism (PR) may develop a chronic connective tissue disease, mainly rheumatoid arthritis (RA). About one to two-thirds of PR patients developed RA during a period of follow-up. Periodontitis (PD) has been found to be associated with RA risk. However, the association between PD and PR risk is unknown. <h3>Objectives</h3> To estimate the association between a history of PD and the risk of incident PR. <h3>Methods</h3> This study used a nationwide, administrative database to identify PR cases and non-PR controls. After exclusion of individuals with rheumatoid arthritis, systemic lupus erythematosus, Sjögren9s syndrome, systemic sclerosis, dermatomyositis or polymyositis before the first PR diagnosis date (index date), we identified 4,421 newly-diagnosed PR cases from 2007 to 2012 and randomly selected 44,210 non-PR controls matched (1:10) for sex, age, and the year of the index date. After adjusting for comorbid diabetes mellitus, we estimated odds ratios (ORs) with 95% confidence intervals (CIs) by conditional logistic regression analysis to quantify the association between a history of PD and the risk of PR. The influences of the lag time and severity of PD were examined by calculating ORs for subgroups of patients based on time interval between the last PD-related visit and the index date and PD-related cumulative cost and visit number. <h3>Results</h3> This study showed an association between a history of PD and newly diagnosed PR (OR, 1.51; 95% CI, 1.41–1.61). The association remained significant after variation of PD definitions. The magnitude of the association was greater in those who had shorter lag time between the last date of PD diagnosis and PR index date and those who had a higher number of visits for PD or greater cumulative cost of PD-related visits. <h3>Conclusions</h3> This study demonstrated a time- and dose-dependent association between PD exposure and PR risk. <h3>References</h3> Sanmarti R, Canete JD, Salvador G. Palindromic rheumatism and other relapsing arthritis. Best practice &amp; research. Clin Rheumatol 2004;18(5):647–612. Chen HH, Huang N, Chen YM, et al. Association between a history of periodontitis and the risk of rheumatoid arthritis: a nationwide, population-based, case-control study. Annals Rheumatic Diseases 2013;72(7):1206–11. <h3>Acknowledgements</h3> The authors would like to thank the Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan, ROC for statistical support. <h3>Disclosure of Interest</h3> None declared
AB1151 Month of birth affects the risk of rheumatic diseases: a nationwide case-control study
Authors: N Koo, J Lee, BW Lee, S-K Kwok, SH Park, JH Ju
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> There have been several studies which demonstrated the impact of birth on the risk of certain diseases such as asthma or cardiovascular diseases. However, rheumatic diseases have not yet been thoroughly investigated in terms of association with birth month. <h3>Objectives</h3> In this study, we sought to determine whether birth month or season could affect the risk of rheumatologic diseases. <h3>Methods</h3> The birth month patterns of patients with rheumatic diseases were compared with to those of general population. We utilized the claims data of Health Insurance Review and Assessment Service (HIRA) which covers nearly 90% of total population in Korea. The associations between birth month/season and 32 diseases were investigated using logistic regression. <h3>Results</h3> Our dataset included 17,247,458 (male 8,224,670; female 9,022,788) individuals from HIRA database from January, 1997 to August, 2015. Among 27 rheumatic diseases, 8 diseases including Crohn9s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), systemic lupus erythematosus, polymyalgia rheumatica (PMR), ankylosing spondylitis (AS), multiple sclerosis, gout, fibromyalgia (FMS) were significantly associated with birth month (P&lt;0.05). In terms of seasonality, CD, UC, RA, Sjogren9s syndrome, PMR, AS, Gout, and FMS demonstrated significant difference. CD, UC and AS showed higher prevalence in individuals born in winter and lower prevalence in summer. On the other hand, people who were born in summer showed higher possibility to have gout and FMS compared to those born in winter. In consistent with previous reports, type 1 diabetes is more prevalent in those born in winter. Angina and myocardial infarction showed higher prevalence in patients born in spring and lower in fall. This consistency reflects the relevance of our dataset and methodology. <h3>Conclusions</h3> We found significant impacts of birth month/season on various rheumatic diseases. Seasonal variation of infective agents, sun exposure or food ingestion during gestation or early infancy may explain the association between birth month/season and certain disease development. <h3>Disclosure of Interest</h3> None declared
Low incidence of vertebral fractures in early spondyloarthritis: 5-year prospective data of the DESIR cohort
Authors: Julie Sahuguet, Jacques Fechtenbaum, Anna Molto, Adrien Etcheto, Clementina López-Medina, Pascal Richette, Maxime Dougados, Christian Roux, Karine Briot
Journal: Annals of the Rheumatic Diseases (2018)

An increased risk of vertebral fractures (VFs) has been reported in spondyloarthritis (SpA). Our hypothesis is that the prevalence of VFs is lower than reported in previous studies, especially in early SpA. This study aimed at assessing the incidence of radiographical VFs over 5 years in early axial SpA.The DESIR (DEvenir des Spondylarthropathies Indifférenciées Récentes) cohort, which included patients with inflammatory back pain highly suggestive of axial SpA, is the basis of this study. All radiographs of the DESIR cohort had been assessed at a central facility, by one investigator specialised in the field of the diagnosis of VFs according to Genant's method. We assessed the prevalence and incidence of VFs and vertebral deformities at baseline and over 5 years.Five-year X-rays were available for 432 patients (mean age 34.3±8.7 years, 53% women). Diagnosis of VF was doubtful and needed adjudication for 19 patients (4.4%). 13 patients had prevalent VFs (3.0%) which were located at the thoracic spine (12 were grade 1). At 5 years, five patients had an incident VF (1.15%); seven vertebrae were fractured, mostly located at the thoracic spine (n=6/7), and of grade 1 (n=6/7).In the DESIR cohort, a population of early SpA, we found a low prevalence and incidence of VFs (3.0% and 1.15 %), respectively. This confirms our hypothesis that the actual prevalence and incidence of VFvertebral fracture in SpA is lower than that reported in the previous studies.
FRI0018 Targeted inhibition of janus kinases abates IFN-GAMMA-INDUCED invasive behavior of fibroblast-like synoviocytes
Authors: T Karonitsch, D Beckmann, K Dalwigk, R Byrne, B Niederreiter, J Holinka, F Sevelda, A Korb-Pap, G Steiner, J Smolen, T Pap, H Kiener
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Emerging evidence suggests that fibroblast-like synoviocytes (FLS) are key effector cells in rheumatoid arthritis (RA) and research into the mechanisms defining FLS activity in RA indicate that cytokines secreted by leukocytes play a crucial role. Nevertheless, the contribution of IFNγ, which is increased in rheumatoid synovitis, to the inflammatory synovial tissue reaction is not known. <h3>Objectives</h3> To explore the function of the T-cell cytokine IFNγ for mesenchymal tissue remodeling in RA, and to determine whether IFNγ-signaling controls the invasive potential of FLS. <h3>Methods</h3> To assess architectural responses, FLS were cultured in three-dimensional micromasses. FLS motility was analyzed in migration-, spreading- and invasion assays. Signaling events relevant to cellular motility were defined by western blots. Baricitinb and siRNA pools were used to suppress Janus Kinase (JAK) functions. <h3>Results</h3> Histological analyses of micromasses revealed unique effects of IFNγ on FLS shape and tissue organization. This was consistent with accelerated migration, pronounced actin and focal adhesion (FA) re-organization upon IFNγ stimulation. Since actin and FA dynamics and, thus, cell motility are integrated by the focal adhesion kinase (FAK), we next analyzed its activity. Indeed, IFNγ stimulation induced the phosphorylation of FAK-Y925, a phosphosite implicated in FAK-mediated cell migration. siRNA knockdown of JAK2, but not JAK1, abrogated FAK activation by IFNγ. Correspondingly, IFNγ-inudced FAK activation and invasion of FLS was abrogated by the JAK-inhibitor baricitinib. <h3>Conclusions</h3> Our study contributes insight into the synovial response to IFNγ and reveals JAK2 as a potential therapeutic target for FLS-mediated joint destruction in arthritis, especially in RA. <h3>Disclosure of Interest</h3> None declared
THU0473 Polysymptomatic distress scale, wide spread pain index, and symptom severity scales, and their correlates in 169 patients with fibromyalgia syndrome
Authors: K Yaseen, S Kaouk, D Bork, WS Wilke, C Gota
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The polysymptomatic distress scale (PSD) is considered a measure of FM severity and ranges from 0 to 31. It is calculated by adding the two components of the American College of Rheumatology (ACR) 2010 fibromyalgia (FM) criteria, widespread pain index (WPI) and symptoms severity scale (SS). <h3>Objectives</h3> Determine the relationship between depression, anxiety, function disability and pain related disability, with fibromyalgia severity as measured by PSD and its subsets, WPI and SS. <h3>Methods</h3> All consecutive FM patients who met the ACR 2010 criteria completed the following questionnaires: PSD, patient health related questionnaire (PHQ-9), a measure of depressive symptoms, general anxiety disorder questionnaire (GAD-7), health assessment questionnaire disability index (HAQ-DI), and pain disability index (PDI). <h3>Results</h3> Of 169 patients, 85.7% were women, mean age 42.3 (13.3), BMI 29.3 (7.1), PHQ-9 13.7 (5.2), GAD-7 10.2 (9.1), HAQ-DI 1.6 (2.9), PDI 6 (2.1), WPI 14.3 (2.7), SS 10 (1.6). In univariate analysis PSD correlated significantly (p&lt;0.01) with PHQ-9 (0.576), PDI (0.422), and GAD-7 (0.356). Widespread pain index correlated significantly with PHQ-9 (0.313), GAD-7 (0.239), HAQ-DI (0.259), and PDI (0.296). Symptom severity scale correlated significantly with PHQ-9 (0.496), GAD-7 (0.337), HAQ-DI (0.275), PDI (0.340). A linear regression analysis model, which included PHQ-9, GAD-7, PDI and HAQ-DI predicted 0.269 of PSD variance, p=0.001, and only PDI remained significantly correlated with PSD. A similar model predicted 0.348 of SS variance, (P&lt;0.0001), and only PHQ-9 remained significantly correlated with SS. This model did not significantly predict WPI variability. <h3>Conclusions</h3> Depression, anxiety, pain disability and functional disability predict a small variance of fibromyalgia severity measured by PSD. In regression analysis, pain disability measured by PDI is the only variable that remains independently correlated with PSD. None of these variables predicted WPI, while depression measured by PHQ-9 remains independently correlated with SS, indicating that PSD subsets measure different dimensions of FM. <h3>Disclosure of Interest</h3> None declared
AB0874 Characteristics of gout in cameroon, central africa: a hospital-based study
Authors: MS Doualla, F Kamdem, F Kemta Lekpa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Few data are available on the characteristics of gout in sub-Saharan Africa (1). <h3>Objectives</h3> We performed this study with the aim to present the clinical, laboratory and imaging characteristics of gout at the time of diagnosis in Cameroon. The results obtained will be compared with data from the Western literature. <h3>Methods</h3> We performed a cross-sectional study among the 10,186 out patients seen at the Rheumatology unit of Douala General Hospital, Douala, Cameroon, between 2004 and 2014. We included patients with gout diagnosis (ACR criteria 1977). The main socio-demographic and clinical data on gout at the time of diagnosis were collected. A p&lt;0.05 was significant. <h3>Results</h3> We included 511 patients (5.02%) including 415 men and 96 women. The mean age was 55.9±10.8 years. Joint pain (n=508, 99.4%), joint effusion (n=198, 38.7%) and fever (n=20, 3.9%) were the main reasons for consultation at diagnosis. Knees (n=300, 62.6), ankles (n=187, 39.0%) and MTP1 joints (n=128, 26.7%) were the most affected joints. Tophi were mainly located at the elbows (n=72, 66.0%), MTP1 (n=20, 18.3%), and ears (n=18, 16.5%) [Table 1]. Gout was as acute (n=255, 49.9%) as it was chronic (n=256, 50.1%). The clinical presentation was oligoarticular in 195 patients (38.7%), monoarticular in 172 patients (34.1%), and polyarticular in 137 patients (27.2%). The mean uric acid level was 82.4±22.3 mg/L, with hyperuricemia found in 401 patients (78.4%). Elevated acute phase reactants was present in 81.9% of patients. Structural involvements related to gout were present in 181 (74.8%) of the 241 patients who had performed an X-ray. Comorbidities were present in 344 patients (67.3%), hypertension (n=208, 40.7%), obesity (n=151, 29.5%), osteoarthritis (n=111, 21.7%), oesogastroduodenal complaints (n=74, 14.5%), diabetes (n=52, 10.2%), and chronic kidney diseases (n=42.8.2%). Associated factors (p&lt;0.05) in the occurrence of gout were obesity, alcohol intake, diuretics intake, and menopause (in women). <h3>Conclusions</h3> Gout has the same clinical, laboratory and imaging characteristics in Cameroon than in Western countries. The main difference comes from the place of the knee as the main joint involved by gouty arthritis at the time of diagnosis in our study. <h3>References</h3> Usenbo A, et al. PLoS One. 2015 Aug 4;10(8):e0133858. <h3>Disclosure of Interest</h3> None declared
THU0270 Homocysteine, antiphospholipid antibodies and risk of vascular events in patients with systemic lupus erythematosus
Authors: G Stojan, W Fu, M Petri
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> SLE patients have higher plasma total homocysteine concentrations compared to healthy controls. Hyperhomocysteinemia in SLE is a potentially modifiable, independent risk factor for stroke and thrombotic events, hypertension, and coronary artery calcification. <h3>Objectives</h3> We investigated the association of homocysteine levels with the presence of antiphospholipid antibodies as well as the potentially additive thrombotic risk in patients with antiphospholipid antibodies who have hyperhomocysteinemia. <h3>Methods</h3> To analyze the association between hyperhomocysteinemia and the presence of antiphospholipid antibodies in SLE, 844 patients with homocysteine measurements were included in the analysis. 237 patients had at least one measurement over 15 umol/L. Patients were followed quarterly after cohort entry. The association of hyperhomocysteinemia with antiphospholipid antibodies is detailed in Table 1. To analyze the prevalence of vascular events among SLE patients with antiphospholipid antibodies based on homocysteine levels, 571 patients with positive antiphospholipid antibodies and at least one homocysteine measurement were included in the analysis. There were 166 patients with at least one homocysteine measurement over 15 umol/L. The lupus anticoagulant was assessed by dRVVT with mixing studies and confirmatory tests. Anticardiolipin and anti-beta2 glycoprotein 1 were measured by ELISA (INOVA). Vascular events were defined as stroke, myocardial infarction, digital gangrene, and deep vein thrombosis. <h3>Results</h3> <h3>Conclusions</h3> SLE patients with elevated homocysteine were less likely (p&lt;0.05) to have any of the antiphospholipid antibodies. Among patients with SLE who have antiphospholipid antibodies, elevated homocysteine is associated with a significantly higher prevalence of myocardial infarction and deep vein thrombosis (p&lt;0.05). <h3>Disclosure of Interest</h3> None declared
A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome
Authors: Ana Huerta, Emilia Arjona, Jose Portoles, Paula Lopez-Sanchez, Cristina Rabasco, Mario Espinosa, Teresa Cavero, Miquel Blasco, Mercedes Cao, Joaquin Manrique, Virginia Cabello-Chavez, Marta Suñer, Manuel Heras, Xavier Fulladosa, Lara Belmar, Amparo Sempere, Carmen Peralta, Lorena Castillo, Alvaro Arnau, Manuel Praga, Santiago Rodriguez de Cordoba
Journal: Kidney International (2017)
SP0009 What is new (win) in psoriatic arthritis
Authors: R Lories
Journal: Annals of the Rheumatic Diseases (2017)

Novel therapies and targets have transformed the management of psoriatic arthritis and related skin disease psoriasis. The successful introduction and widespread use of anti-IL17, anti-IL12/23 and anti-PDE4 strategies have joined the ranks of TNF inhibitors. Novel biological insights into specific disease mechanisms are co-emerging with this new wave of treatment options. The different available treatments allow the community to further focus on optimal patient management aiming at remission or minimal disease activity. Yet, the assessment of the patient and his/her satisfaction with current health status remains challenging. Treat to target initiatives are trying to define optimal care and cure adapted to the specific characteristics of the disease. Molecular knowledge of the disease processes remains scattered and insufficient to build a comprehensive view on the disease for the individual patient that would allow the personalized definition of effective strategies. <h3>Disclosure of Interest</h3> R. Lories Grant/research support from: Celgene, Boehringer-Ingelheim, UCB, Consultant for: Janssen, Celgene, Novartis, Pfizer, UCB, Abbvie, Speakers bureau: Janssen, Celgene, Novartis, Pfizer, Merck, UCB, Abbvie
SAT0648 Ultrasound findings in symptomatic and asymptomatic joints in patients with gout
Authors: MM Basaric, G Radunovic, N Damjanov, M Radak Perovic
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To determine sensitivity and specificity of ultrasound (US) findings for gout: "double contours" (DC) and hyperechogenic aggregates (HAGs) of symptomatic and asymptomatic joints in patients with gout. <h3>Methods</h3> This prospective study included 69 persons (34 patients with primary gout and 35 healthy subjects). Including criteria for patients with gout were: age ≥18 years; diagnosis of primary gout; absence of acute gout attacks during the study tests; the absence of any other inflammatory and infectious joint disease, and secondary gout. The research included: demography and medical history. Physical and US examination covered following structures: 138 radiocarpal joint, 276 patellar and triceps tendon and 414 articular cartilages (first metatarsal, talar and femoral condyle). <h3>Results</h3> Both groups were compatible for age and gender. In the gout group 124 (30%) symptomatic and 284 (70%) asymptomatic joints were found and in healty group all joints was asymptomatic. The sensitivity of the DC for symptomatic joint was 56 to 84% and specificity also was very high 91 to 94% as well as positive and negative predictive value (69 - 86% and 38 - 71%). Sensitivity of DC finding for the asymptomatic joints was 42 to 73% and specificity was 91 to 94%, with also high positive and negative predictive value (69 - 89% and 44 - 62%). The specificity of the HAGs for both symptomatic and asymptomatic joints was very high 99% but sensitivity of HAGs symptomatic structures was moderate (41 do 56%), while its sensitivity for asymptomatic structures was low (18 to 34%), table 1. <h3>Conclusions</h3> Ultrasound examination of symptomatic and asymptomatic joints in patients with gout equally observed structural changes characteristic of gout. The finding of "double contours" in the symptomatic and asymptomatic joints has a very high sensitivity and specificity. Consequently, future research should be focused on the ultrasound examination of asymptomatic joints in patients with gout. <h3>Disclosure of Interest</h3> None declared