tbuckley/cabot-search huggingface dataset:
OP0087 Platelet-specific fli1-knockout mice show accelerated wound closure associated with increased myofibroblast formation in the inflammatory phase
Authors: M Hirabayashi, Y Asano, T Yamashita, R Saigusa, S Miura, K Nakamura, T Miyagawa, Y Ichimura, T Taniguchi, A Yoshizaki, S Sato
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is a systemic connective tissue disease characterised by autoimmunity, vascular disorder and fibrosis of skin and other organs (1). Although substantial reports have been hitherto provided upon its pathogenesis in relation to microvasculature, among which are on endothelial and fibroblastic Fli1 deficiencies (1, 2), adequate investigation into hemocytic involvement is yet to be attained. Platelets are well known for its function in hematostasis whereas they also play a part in inflammation, immunity and cellular proliferation (3), thus prompting us to speculate their cardinal role in the development of the disease. <h3>Objectives</h3> Here we aim to unravel the role of platelets in the pathogenesis of SSc, with generation of platelet-specific conditional <i>Fli1</i> knockout (<i>Fli1</i> PcKO) mice to scrutinise its dermal wound healing process. <h3>Methods</h3> We generated <i>Fli1</i> PcKO mice using the Cre-Lox system along with <i>PfCre</i> +/- mice as an appropriate control. We made two excisional wounds on the dorsal skin of each mouse (three months old) using an eight-millimeter-diameter punch and traced the wound surfaces every other day to measure their areas using Image J until all the wounds were epithelised. On a separate experiment, perilesional skin was harvested on the day two, from which we extracted mRNA for the measurement of proinflammatory and profibrotic cytokines. An immunostaining for α-SMA was performed on the skin samples. <h3>Results</h3> The areas of the wounds were calculated and shown in ratio to their initial areas (day 0). <i>Fli1</i> PcKO mice showed a significant decrease in the areas compared to the control on day 2. mRNA measurement revealed a significant increase in <i>Mmp13</i> and significant decreases in <i>Tgfb1</i>, <i>Ifng</i> and <i>Il13</i> for <i>Fli1</i> PcKO. In histopathology, α-SMA positive fusiform-shaped cells were abundant in the granulation tissue of <i>Fli1</i> PcKO mice (Figure; left, <i>PfCre</i> +/-; right, <i>Fli1</i> PcKO; original magnification, ×400). <h3>Conclusions</h3> In dermal injuries on <i>Fli1</i> PcKO mice, inflammatory disturbances precipitate myofibroblast formation in the granulation tissue, thus anticipating wound closure by mechanical contraction. <h3>References</h3> Asano Y et al., Curr Rheumatol Rep. 2013; 15(12):382. Asano Y et al. Am J Pathol. 2010; 176(4):1983–98. Ramirez GA et al., Front Immunol. 2012; 3:160. <h3>Disclosure of Interest</h3> None declared
OP0181 Deletion of the prostaglandin D2 receptor DP1 exacerbates aging-associated and instability-induced osteoarthritis
Authors: Y Ouhaddi, L Habouri, J-P Pelletier, J Martel-Pelletier, M Benderdour, H Fahmi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> <i>The D prostanoid receptor 1</i> (D<i>P1</i>), a <i>receptor</i> for prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) plays important roles in inflammation and cartilage metabolism. However, its role in the pathogenesis of osteoarthritis (OA) remains unknown. <h3>Objectives</h3> We undertook this study to explore the roles of DP1 in the development of OA and to evaluate the efficacy of a DP1 selective agonist in the treatment of OA. <h3>Methods</h3> We compared the development of aging-associated OA and destabilization of the medial meniscus (DMM)-induced OA in DP1-deficient (DP1-/-) and wild-type (WT) mice. The progression of OA was assessed by histology, immunohistochemistry, and microcomputed tomography (micro-CT). Cartilage explants from DP1-/- and WT mice were treated with interleukin-1α (IL-1α) ex vivo, to evaluate proteoglycan degradation. The effect of intra-peritoneal administration of the DP1 selective agonist BW245C on OA progression was evaluated in WT mice. <h3>Results</h3> Compared to WT mice, DP1-/- mice had exacerbated cartilage degradation in both models of OA and this was associated with increased expression of MMP-13, and ADAMTS-5. In addition, DP1-/- mice demonstrated enhanced subchondral bone changes. Cartilage explants from DP1-/- mice showed enhanced proteoglycan degradation following treatment with IL-1α. Intraperitoneal injection of BW245C attenuated the severity of DMM-induced cartilage degradation and bony changes in WT mice. <h3>Conclusions</h3> These findings indicate a critical role for DP1 signaling in OA pathogenesis. Modulation of DP1 functions may constitute a potential therapeutic target for the development of novel OA treatments. <h3>Acknowledgements</h3> This work was supported by the Canadian Institutes of Health Research (CIHR) Grant MOP-130293, the Arthritis Society, and the Fonds de la Recherche du Centre de Recherche du Centre Hospitalier de l9Université de Montréal (CRCHUM). <h3>Disclosure of Interest</h3> None declared
THU0564 IGG4-related disease in the maltese population
Authors: S Chetcuti Zammit, M Rogers, P Ellul
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is an increasingly recognised immune-mediated fibro-inflammatory condition, most commonly affecting the pancreas. <h3>Objectives</h3> The aim of our study was to determine the incidence, organ involvement and outcome of IgG4-RD in the Maltese population. <h3>Methods</h3> The case notes of all patients who had their IgG4 level checked between 2008 and 2015 at Mater Dei Hospital were reviewed. Patients who had their IgG4 level checked inappropriately were excluded. Patients were then stratified according to the "Comprehensive diagnostic criteria for IgG4-related disease" [1]. <h3>Results</h3> 25 patients were included in this retrospective, observational study. 60% (n=15) of patients were males and mean age was 70 years (SD±64.8). The mean IgG4 level was 0.7159 g/L (SD±0.851) (normal range 0.052–1.250g/L). Organs involved included: pancreas (n=15), biliary tree (n=3), salivary glands (n=1), lymph nodes (n=8), lungs (n=4), thyroid gland (n=2), bone (n=1), heart (n=1), sinuses (n=2). 36% (9 patients) had involvement of more than one organ. Blood tests at time of diagnosis demonstrated a raised mean ESR (65.7mm1st Hr; SD±36.1) and a raised mean CRP (143 mg/L SD± 112). White cell count was mostly normal (mean 11.7x10<sup>9</sup>/L SD±4.91). 92% of patients (n=23) had organ swelling on radiological testing. 32% (n=8) of patients had raised IgG4 levels. A histological diagnosis was obtained in 8% (n=2) of patients presenting with cervical lymphadenopathy and sinusitis respectively. According to the "Comprehensive diagnostic criteria for IgG4-RD"<sup>1</sup>, the diagnosis was definite in 4% (n=1), possible in 28% (n=7) and probable in 4% (n=1) of patients. 64% (n=16) only had organ swelling on imaging studies, satisfying 1 criterion. One patient was diagnosed with malignancy during the course of disease. Patients with hepatobiliary and pancreatic involvement underwent ERCP and stenting. Patients who developed pancreatic pseudocyst as a complication of pancreatitis underwent drainage. One patient (4%) developed pancreatic insufficiency and 32% (n=8) experienced recurrent pancreatitis requiring hospital admission. Four patients (16%) passed away. <h3>Conclusions</h3> In concordance with current literature, our study has shown that IgG4-RD in the Maltese population is a rare disorder affecting mainly elderly males. The commonest organs involved were the pancreas and lymph nodes. The inflammatory markers ESR and CRP were always raised, thus acting as possible biomarkers for monitoring of disease activity. <h3>References</h3> Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21–30. <h3>Disclosure of Interest</h3> None declared
SAT0575 Association of human leukocyte a, b and dr antigens in patients with chikungunya virus infection
Authors: JC Rueda, J-I Angarita, AM Santos, E-L Saldarriaga, I Pelaez-Ballestas, B Zaldivar-Castaño, J Londono
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Host factors like innate and adaptive immune response play an important part in disease susceptibility. Also, the role of host genetics factors in the pathogenesis of viral diseases have been reported. Human leukocyte antigen (HLA) is responsible for initiating innate and adaptive immune responses. Studies have demonstrated HLA class II alleles association to susceptibility or resistance to chikungunya virus infection (CHIKV), however there is no evidence of association studies of HLA class I and II in the Latin-American CHIKV epidemic. <h3>Objectives</h3> To evaluate the association of human leukocyte A, B and DR antigens in a group of Colombian patients with CHIKV. <h3>Methods</h3> Characterization of HLA allele A, B, and DR of 62 patients with confirmed CHIKV was compared with 100 unrelated healthy subjects as a control group. The comparison between the different allele frequencies in the patient group and the control population was performed using chi<sup>2</sup>, with Bonferroni correction. A <i>p</i> value &lt;0.05 was considered to be significant. The magnitude of associations was assessed using odds ratio (OR) and confidence intervals (CI) of 95%. To establish the homogeneity of the studied groups, the Hardy-Weinberg disequilibrium was used. <h3>Results</h3> Of the 62 patients studied 46 were female (74,2%). The mean age was 45,0 (SD±16,8) years. Most of the patients were from Barranquilla (64,5%; n: 40). Mean CHIKV immunoglobulin G (IgG) was 38,6 SU (SD±21,7), while IgM was 13,3 SU (SD±7,6). Also C reactive protein levels were high (mean: 14,7 mg/L; SD±8,4). Association alleles of HLA-A, and DR are depicted in table 1. No association was found with HLA-B alleles. <h3>Conclusions</h3> Our study demonstrated the alleles <i>A*28</i> and <i>A*29</i> to be associated with resistance to CHIKV, and alleles <i>A*68</i>, <i>DRB1*01</i>, <i>DRB1*04</i> and <i>DRB1*13</i> to be associated with susceptibility to CHIKV. No association was found in any HLA-B alleles. <h3>Disclosure of Interest</h3> None declared
FRI0581 Hepatitis b increase mortality in pateints with osteoporotic vertebral fractures
Authors: Y-C Chen, C-H Ko
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Hepatitis B virus (HBV) is a major cause of chronic liver diseases worldwide, particularly cirrhosis and hepatocellular carcinoma, and the most important liver disease in Taiwan. However, little is known the impact of hepatitis b on osteoporotic patients. <h3>Objectives</h3> This study aimed to determine if hepatitis b can increase the risk of mortality in patients with osteoporotic vertebral fracture. <h3>Methods</h3> This retrospective study reviewed of cases of osteoporosis patients with acute vertebral fractures between 2001 and 2008. All associated co-morbidities were recorded. Kaplan-Meier and cox regression analysis were performed. <h3>Results</h3> There were 432 patients with acute vertebral fractures. The mean age of 72.85±9.28. 31 (7.2%) patients had chronic hepatitis b. Using the Kaplan-Meier curve, hepatitis b had a significant effect on mortality (p&lt;0.001, by log rank text). After adjusting for potential confounders, patients with hepatitis b still had a high mortality rate (<i>p</i>=0.019; HR: 2.436∼5.136) 2.137, 95% CI: 1.156∼5.136). The mortality rate also increased among smokers (<i>p</i>=0.026; HR: 3.6043.891; 95% CI: 1.056∼12.301). <h3>Conclusions</h3> In this study, hepatitis b increase mortality in osteoporotic vertebral fracture patients. So we should pay attention to this group in osteoporotic management. <h3>References</h3> Chong-Shan Wang et al. Am. J. Trop. Med. Hyg., 66(4), 2002, pp. 389–393. <h3>Acknowledgements</h3> We thank Kaohsiung Chang Gang Memorial Hospital for data support. <h3>Disclosure of Interest</h3> None declared
Mucosa-associated microbiota dysbiosis in colitis associated cancer
Authors: Mathias L. Richard, Giuseppina Liguori, Bruno Lamas, Giovanni Brandi, Gregory da Costa, Thomas W. Hoffmann, Massimo Pierluigi Di Simone, Carlo Calabrese, Gilberto Poggioli, Philippe Langella, Massimo Campieri, Harry Sokol
Journal: Gut Microbes (2017)

Gut microbiota dysbiosis has been associated with inflammatory bowel diseases (IBD). In colorectal cancer, the gut microbiota has also been recognized as potentially involved in aggravating or favoring the tumor development. However, very little is known on the structure and role of the microbiota in colitis associated cancer (CAC), an important complication of IBD in human. Here we analyzed the bacterial and fungal composition of the mucosa associated microbiota of patients suffering CAC, sporadic cancer (SC) and of healthy subjects (HS) by barcode sequences analysis on the following cohort: 7 CAC patients, 10 SC patients and 10 HS using 16S (MiSeq) and ITS2 (pyrosequencing) sequencing, for bacteria and fungi respectively. Mucosa-associated bacterial microbiota in CAC was significantly different from the ones in SC or in HS, while the fungal showed no differences. Comparison between mucosa-associated microbiota on the tumor site or in normal mucosa near the tumor showed very similar patterns. The global mucosa-associated bacterial microbiota in cancer patients was characterized by a restriction in biodiversity but no change for the fungal community. Compared to SC, CAC was characterized by an increase of Enterobacteriacae family and Sphingomonas genus and a decrease of Fusobacterium and Ruminococcus genus. Our study confirms the alteration of the mucosa-associated bacterial microbiota in IBD and SC. Although the cohort is limited in number, this is the first evidence of the existence of an altered bacterial microbiota in CAC clearly different from the one in SC patients.
The Role of Sphingomyelin (SM) in Tissue Factor (TF) Encryption: ATP-Induced Activation of Acid Sphingomyelinase in Macrophages Decrypts Tissue Factor By Hydrolysis of SM in the Outer Leaflet
Authors: Jue Wang, Usha R Pendurthi, L. Vijaya Mohan Rao
Journal: Blood (2016)
SP0069 Registries in musculoskeletal diseases and their regulatory use
Authors: R Vesely
Journal: Annals of the Rheumatic Diseases (2017)

Patient registries collect information about individuals sharing health-related characteristics, for example, a particular disorder, a treatment or a procedure. While randomised controlled trials typically provide the primary evidence supporting marketing authorisations for new medicines, the patients studied may not be fully representative of everyone ultimately receiving the medicine and the trials may provide limited information about the natural history of the disorder. Information collected in patient registries is potentially of value for filling these evidence gaps in certain situations and for providing post-marketing safety and effectiveness information. Multiple stakeholders stand to benefit from using registry information in this way including patients, healthcare providers, policy makers, manufacturers and healthcare regulators. In 2014, the EMA commenced a Registry Initiative aiming to optimise the use of registries in supporting medicines authorisations. Establishing a strategy of early engagement between marketing authorisation applicants and registry holders and a task force to support activities, a pilot phase was undertaken aiming to understand the barriers and enablers in using registries to support marketing authorisation applications and to inform the development of recommendations to optimise their use. On 28 October 2016 the Agency organised Patient Registries Workshop to collect and discuss the information about experience from different patient registries in various therapeutic areas. The topics included: Benefits of registries for regulators Benefits of registries for HTA and payers Benefits for industry Benefits for clinicians and researchers Benefits for patients Challenges in collaboration between registries Technical challenges Governance Sustainability Conclusions of the pilot and the workshop have been utilised in the following activities including workshops to support registries in individual diseases. There are multiple advanced registries in RA and JIA. Utilisation of outcomes of these and other existing or newly planned registries in other musculoskeletal diseases for regulatory purposes current environment offers new opportunities that require further analyses and collaboration. <h3>Disclosure of Interest</h3> None declared
Retrospective Evaluation of Correlations Between Genetic Backgrounds and Stem Cell Transplantation for De Novo Pediatric Acute Myeloid Leukemia: A Study from the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 Clinical Trial
Authors: Taeko Ueno, Genki Yamato, Norio Shiba, Yusuke Hara, Kentaro Ohki, Hitoshi Ichikawa, Myoung-Ja Park, Akira Shimada, Manabu Sotomatsu, Hirokazu Arakawa, Keizo Horibe, Souichi Adachi, Takashi Taga, Akio Tawa, Yasuhide Hayashi
Journal: Blood (2016)
THU0411 Tophus burden. clinical evaluation during 3 years follow-up in gresgo cohort
Authors: A Maya Gutierrez, CO Lopez Lopez, E Alvarez Hernandez, C Gomez Ruiz, I Peláez Ballestas, R Burgos-Vargas, J Vazquez Mellado
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tophus burden (TB) was proposed by OMERACT as mandatory domain for chronic gout studies. Image methods although useful, frequently are not available in daily clinical practice. <h3>Objectives</h3> To evaluate TB clinically in a cohort of gout patients during 3 years follow-up. <h3>Methods</h3> We analyzed baseline and follow-up data (6, 12, 18, 20, 24, 30 and 36 months) of patients with gout (ARA/CGD/ACR-EULAR) from the GRESGO cohort; this analysis includes the patients with ≥1 clinical nodule(s) considered as tophi in the baseline visit. Index tophi size (ITS) was considered as the longer axis of the bigger tophi. TB evaluations: 1) Tophi number (T); 2) ITSt (cm) measured with tape; 3) ITSca (cm), measured with caliper; 4) ITSco, measured with compass. 5) Index tophi hardness (ITh) or consistency, by VAS (0: very soft-10 hard as a rock). This protocol was approved by the local IRB and patients signed and informed consent for their participation. All the patients received treatment for gout and associated diseases according to published guides and available drugs. The evaluations were done by the same group of physicians (Rheumatologists and Residents). Variables: TB measures, demographic, clinical and biochemical variables. HAQ and EUROQoL and VAS for pain and general health. Inter/intraobserver variability were evaluated. Statistical analysis: t test, X2, r, kappa, Friedman and multiple correlation. <h3>Results</h3> 298 patients; 97%males, 203 (68%) tophaceous gout, age, age at onset and duration of the disease were: 46.4±12.7 32.4±12.4 and 14.7±9.3 years respectively. Available ULT: Allopurinol and probenecid, colchicine as prophylaxis. Mean allopurinol dose prescribed at baseline visit was 346.9±154 mg/d and 550±205 mg/d 3 years later.TB values (see table). Index tophi size had r&gt;0.93 among the 3 evaluations (ITSt, ITSca, ITSco) and r&lt;0.3 with ITh. Inter and intraobserver variability was 0.8 and 0.9 respectively; there was significant improvement *(p&lt;0.001) in ITS, sUA, painful, swollen, limited to motion joints, HAQ, EuROQoL, VAS pain, VAS health (patient and physician) also improved significantly. <h3>Conclusions</h3> In our cohort, ITSt was the best measure for TB evaluation, the 3 ITS measures had a good correlation between them and less with ITh or consistency. Patients with tophaceous gout, improved significantly with allopurinol and probenecid during 3 years follow-up in TB (ITSt) as well according to the other OMERACT proposed domains for chronic gout. <h3>Disclosure of Interest</h3> None declared
ヒトノロウイルスとの相互作用のためのコンカナバリンAの金属配位領域の探査【Powered by NICT】
Authors: Kim Duwoon, Lee Hee-Min, Oh Kyung-Seo, Ki Ah Young, A Protzman Rachael, Kim Dongkyun, Choi Jong-Soon, Kim Min Ji, Kim Sung Hyun, Vaidya Bipin, Lee Seung Jae, Kwon Joseph
Journal: Biomaterials (2017)
FRI0156 Do changes in adipocytokines correlate with changes to disease activity in rheumatoid arthritis? findings from the tomorrow study
Authors: M Tada, K Inui, Y Sugioka, T Okano, K Mamoto, T Koike, H Nakamura
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Cytokines released from mast cells evoke inflammation and correlate with arteriosclerotic lesions and autoimmune disease<sup>1</sup>. The relationship between disease activity and lipid metabolism is a notable in research surrounding rheumatoid arthritis (RA). RA patients without disease control reportedly show high titers of leptin or adiponectin as adipocytokines<sup>2</sup>. <h3>Objectives</h3> We analyzed the interaction between changes in disease activity and adipocytokines using data from the TOMORROW (TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality clinical trial) study, a 10-year prospective study (registration number, UMIN000003876). <h3>Methods</h3> We analyzed data collected from the cohort of the TOMORROW study including 193 patients with RA and age- and sex-matched 194 healthy individuals (controls). We compared changes in leptin and adiponectin (Δleptin and Δadiponectin) in both groups between baseline and after 3 years. Correlations with the change in disease activity (ΔDAS28ESR) during 3 years and changes in Δleptin and Δadiponectin in RA were investigated by univariate analysis. <h3>Results</h3> Leptin levels increased in both groups. No significant differences in Δleptin were seen between RA (0.21 ng/ml) and controls (0.18 ng/ml; p=0.37). On the other hand, adiponectin was significantly decreased in controls (-3.3 μg/ml) compared to RA (-1.8 μg/ml; p=0.01). Negative correlations between Δleptin and Δadiponectin were detected in the RA group (r=-0.29, p&lt;0.01). The correlation between adiponectin and DAS28ESR was positive both at baseline (r=0.22, p=0.01) and after 3 years (r=0.18, p=0.01). However, no such tendencies were seen for leptin. Table 1 shows details of the correlations with changes in adipocytokine. In terms of the relationship with ΔDAS28ESR, no correlation was seen with Δleptin (r=0.07, p=0.31) or Δadiponectin (r=-0.01, p=0.91). Changes in lipid metabolic markers and fat percentages were detected as predictive factors for Δadipocytokines. <h3>Conclusions</h3> Leptin increased and adiponectin decreased over the course of 3 years. Correlations between Δadipocytokines and ΔDAS28ESR were not detected. RA patients with high disease activity show higher adiponectin titers. <h3>References</h3> Benoist C., Mathis D. Mast cell in autoimmune disease. Nature. 2002; 420: 875–8. Cho H., Lin J., Chen W., et al. Baseline adiponectin and leptin levels in predicting an increased risk of disease activity in rheumatoid arthritis: a meta-analysis and systematic review. Autoimmunity. 2016; 49: 547–53. <h3>Disclosure of Interest</h3> None declared