tbuckley/cabot-search huggingface dataset:
OP0215 Role of inhibitory igg fc receptor iib on b cells and monocytes in yaa-related murine lupus
Authors: S Hirose, L Qingshun, M Ohtsuji, H Nishimura, H Amano, SJ Verbeek
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> FcγRIIB-deficient C57BL/6 (B6) mice spontaneously develop severe lupus nephritis in combination with <i>Yaa</i> locus (TLR7-duplication). <h3>Objectives</h3> The aim of this study is to clarify the cell type-specific roles of FcγRIIB for the pathogenesis of <i>Yaa</i>-related lupus. <h3>Methods</h3> We established B cell-specific (CD19<sup>Cre</sup>.<i>Yaa</i>), myeloid-derived cell-specific (C/EBPα<sup>Cre</sup>.<i>Yaa</i>), and dendritic cell (DC)-specific (CD11c<sup>Cre</sup>.<i>Yaa</i>) FcγRIIB-deficient mice on B6.<i>Yaa</i> background, and compared the disease features of these mice with full FcγRIIB-deficient B6.FcγRIIB<sup>-/-</sup>.<i>Yaa</i> mice. <h3>Results</h3> CD19<sup>Cre</sup>.<i>Yaa</i> mice developed milder lupus nephritis compared to B6.FcγRIIb<sup>-/-</sup>.<i>Yaa</i> mice, indicating that FcγRIIB deficiency on only B cells is not sufficient for the development of severe disease. Surprisingly, C/EBPα<sup>Cre</sup>.<i>Yaa</i> mice developed similar mild disease as CD19<sup>Cre</sup>.<i>Yaa</i> mice whereas CD11c<sup>Cre</sup>.<i>Yaa</i> stayed disease free. These observations indicate that, in B6. FcγRIIB<sup>-/-</sup>.<i>Yaa</i> mice, FcγRIIB deficiency on both B cells and myeloid cells, but not on DCs, contribute to the development of severe lupus with high autoantibody titers. Flow cytometric analysis showed that the frequency of peripheral Gr-1<sup>-</sup>, but not Gr-1<sup>+</sup>, monocytes was increased and correlated positively with the frequency of splenic PNA<sup>+</sup> activated B cells in B6.FcγRIIB<sup>-/-</sup>.<i>Yaa</i> and C/EBPa<sup>Cre</sup>.<i>Yaa</i>, but not CD19<sup>Cre</sup>.<i>Yaa</i>, mice. This suggests a link between FcγRIIB deficiency on monocytes, the high frequency of Gr-1<sup>-</sup> monocytes and B cell activation. Transcriptome analysis of Gr-1<sup>+</sup> and Gr-1<sup>-</sup> monocytes revealed that B cell-stimulating factor-3 (BSF-3), IL-10, and IL-1β were all up-regulated in Gr-1<sup>-</sup> monocytes. <h3>Conclusions</h3> FcγRIIB on B cells and monocytes controls B cell activation and autoimmune responses via different but synergistic pathways in <i>Yaa</i>-related lupus nephritis. <h3>References</h3> Boross P, et al. J. Immunol. 187:1304–1313, 2011. <h3>Disclosure of Interest</h3> None declared
FRI0446 Prevalence and characteristics of spondyloarthritis according to asas criteria in patients with inflammatory bowel disease – results from the spice cohort
Authors: J Haschka, S Hirschmann, A Kleyer, M Englbrecht, J Zimmermann, F Faustini, D Simon, CP Figueiredo, A Cavallaro, C Muschitz, R Kocijan, H Resch, R Atreya, J Rech, MF Neurath, G Schett
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Musculoskeletal symptoms are considered as one of the most frequent extra-intestinal manifestation in Inflammatory Bowel Disease (IBD) patients with a prevalence of up to 40% involving axial and/or peripheral joints. Data on the prevalence of musculoskeletal disease, in particular of SpA are limited and vary considerably due to different criteria the studies have used to define musculoskeletal disease in IBD patients. <h3>Objectives</h3> To define the prevalence of axial and peripheral spondyloarthritis (SpA) according to Assessment of Spondyloarthritis International Society (ASAS) in patients with Crohn9s disease (CD) and ulcerative colitis (UC). <h3>Methods</h3> The SPICE cohort (Spondyloarthritis in Inflammatory Bowel Disease Cohort Erlangen) comprises prospectively recruited colonoscopy- proven Crohn9s Disease (CD) or Ulcerative Colitis (UC) patients, who received a pre-defined and standardized musculoskeletal assessment by the rheumatologist. Duration and activity of gastrointestinal and rheumatic disease (axial and peripheral) was documented and fulfillment of ASAS classification criteria for axial and peripheral SpA was tested. <h3>Results</h3> 102 IBD patients (62 with CD and 40 with UC) with a median (IQR) disease of 11.0 (18.0) years were assessed. 38.2% fulfilled ASAS criteria for SpA with no difference between CD and UC. ASAS axial SpA criteria were fulfilled by 12%, ASAS peripheral SpA criteria by 31.4% of the IBD patients. Inflammatory back pain was present in 24.5% with MRI signs of sacroiliitis in 48% of IBD patients with inflammatory back pain. Disease activity according to ASDAS-CRP was moderate to high in 91% of the patients with axial SpA. Peripheral arthralgia was present in 71.6%, while arthritis was found in 18.6% of the IBD patients. <h3>Conclusions</h3> Both major forms of IBD show a similar burden of musculoskeletal disease. More than one third of inflammatory bowel disease patients show axial or peripheral SpA according to ASAS criteria. Peripheral SpA is more commonly found than axial SpA. <h3>References</h3> Harbord M, Annese V, Vavricka SR, et al. The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease. J Crohn Colitis 2016; 239–254. Karreman MC, Luime JJ, Hazes JMW, Weel AEAM. The prevalence and incidence of axial and peripheral spondyloarthritis in inflammatory bowel disease: a systematic literature review and meta-analysis. J Crohn Colitis 2016; 1–12. <h3>Disclosure of Interest</h3> None declared
Immunity to metastatic mammary carcinoma in STAT6-deficient mice involves reduction of immature myeloid cells and production of nitric oxide by M1 macrophages.
Authors: Pratima Sinha, Virginia K. Clements, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2004)

2348   Following surgical removal of primary 4T1 mammary carcinoma, >60% of BALB/c Stat6-deficient mice reject spontaneous metastatic disease and survive indefinitely. In contrast, 100% of post-surgery Stat6-competent BALB/c mice die from metastatic disease. Because the immune response in Stat6-deficient mice is so potent, we are examining the mechanisms underlying enhanced immunity. Several cell populations could be involved: 1) Type 1 CD4+ T cell responses are hypothesized to enhance CD8-mediated anti-tumor immunity. Because Stat6 is a transcription factor required for IL-4 and IL-13-mediated signaling and Stat6 −/−  mice lack this factor, their CD4 responses are polarized towards a Type 1 response. 2) Type 1 macrophages have tumoricidal activity because of their production of nitric oxide (NO). Preferential generation of Type 1 macrophages is thought to facilitate anti-tumor immunity. 3) Excess immature myeloid cells (IMC) which are frequently induced by large tumor burdens cause immune suppression and block anti-tumor immunity. We have determined if any of these cells are involved in the potent anti-tumor immunity of Stat6-deficient mice. Both BALB/c and Stat6 −/−  mice with primary tumors in situ have levels of IMC in excess of 30% of splenocytes. However, following surgical removal of primary tumor, IMC levels in Stat6-deficient mice revert to  −/−  mice were added to cultures of splenocytes from D011.10 transgenic mice (specific for ovalbumin peptide 323-339/I-A d ) pulsed with ova peptide, and proliferation was measured. Suppression resulted from arginase production since treatment of IMC with an arginase inhibitor reversed suppression. To determine if macrophages of BALB/c and Stat6 −/−  mice differ in NO production, IL4 and IL13 pretreated macrophages were stimulated with IFNγ and LPS. Although BALB/c macrophages had significantly reduced NO production, NO levels of Stat6 −/−  macrophages were unaffected, suggesting that Stat6 −/−  macrophages are of the M1 type and are cytotoxic. Taken together these observations suggest that in Stat6 −/−  mice enhanced immunosurveillance is a combined effect of rapid recovery from arginase-mediated IMC-induced T cell suppression and the presence of NO producing M1 type macrophages. Therefore, reduction of IMC and production of M1 macrophages are pre-requisites for protective immunosurveillance and immunotherapy.
Evaluation of severity score-guided approaches to macrolide use in community-acquired pneumonia
Authors: Aran Singanayagam, Stefano Aliberti, Catia Cillóniz, Antoni Torres, Francesco Blasi, James D. Chalmers
Journal: European Respiratory Journal (2017)

International guidelines including those in the UK, Japan, Australia and South Africa recommend the avoidance of macrolides in patients with low-severity community-acquired pneumonia (CAP). We hypothesised that severity scores are poor predictors of atypical pneumonia and response to macrolide therapy, and thus, inadequate tools for guiding antibiotic prescriptions. Secondary analysis of four independent prospective CAP datasets was conducted. The predictive values of the CURB-65 and pneumonia severity index (PSI) for clinically important groups of causative pathogens were evaluated. The effect of macrolide use according to risk class was assessed by multivariable analysis. Patients (3297) were evaluated, and the predictive values of CURB-65 and PSI for atypical pathogens were poor (AUC values of 0.37 and 0.42, respectively). No significant differences were noted among the effects of macrolide use on mortality in patients with mild, moderate and severe CAP, according to either CURB-65 (interaction testing severe versus mild disease OR=0.74 (0.29–1.89)) or PSI (severe versus mild disease OR=3.4 (0.055–2.10)), indicating that severity scores were not significant modifiers of response to macrolide therapy. Severity scores did not accurately predict response to macrolide therapy in CAP, suggesting that current guidance to use these tools for empirical antibiotic choices might not be justified.
Dural MALT Lymphoma Detected by 11C-Methionine PET/CT
Authors: Salvatore Annunziata, Annarosa Cuccaro, Carmelo Caldarella, Stefan Hohaus
Journal: Clinical Nuclear Medicine (2017)

Abstract A 53-year-old man had a diagnosis of mucosa-associated lymphoid tissue lymphomas of the dura in the left tentorium. The patient underwent whole-body 18 F-FDG PET/CT and 11 C-methionine PET/CT in order to complete the staging of dural mucosa-associated lymphoid tissue lymphoma. 11 C-methionine uptake was detected in multiple meningeal sites, including left tentorium, with no significant FDG uptake in the same regions.
AB0090 N-ACETYL-L-CYSTEINE (NAC) controls osteoclastogenesis through regulating TH17 differentiation and RANKL production in rheumatoid arthritis
Authors: H-R Kim, K-A Lee, S-H Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> NAC is a thiolic antioxidant produced by the body and serves as a precursor of glutathione synthesis. In rheumatoid arthritis (RA), oxidative stress is an important mechanism causing destructive proliferative synovitis. <h3>Objectives</h3> This study aimed to determine the regulatory role of N-Acetyl-L-cysteine (NAC), an antioxidant, in IL-17-induced osteoclast differentiation in RA. <h3>Methods</h3> After RA synovial fibroblasts were stimulated by IL-17, the expression and production of RANKL was determined by real-time PCR and ELISA. Human peripheral blood monocytes were cultured with M-CSF, IL-17, RANKL, and/or various concentrations of NAC, followed by counting of the cells for tartrate-resistant acid phosphatase activity to determine osteoclast formation. Osteoclastogenesis was also determined after cocultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4<sup>+</sup> T cells were cultured with NAC under Th17 condition, IL-17, IFN-g, IL-4, Foxp3, RANKL and IL-2 expression and production was determined by flow cytometry or ELISA. <h3>Results</h3> When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mTOR, JNK and IkB. When human peripheral blood CD14<sup>+</sup> monocytes were cultured with M-CSF and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4<sup>+</sup> T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. <h3>Conclusions</h3> NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA. <h3>Acknowledgements</h3> This research was supported by a grant of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea (NRF-2014R1A2A2A01007223) and the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea (HI13C1704). <h3>Disclosure of Interest</h3> None declared
AB1001 Clinical versus ultrasound evaluation of peripheral enthesites in a cohort of spondyloarthritis
Authors: A Haddouche, S Haid, S Bencheikh, S Slimani, A Abdessemed, N Brahimi, A Ladjouze
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Clinical versus ultrasound evaluation of peripheral enthesites in a cohort of spondyloarthritis <h3>Methods</h3> A monocenter prospective study of all SpAs ≥18 years meting the ASAS criteria for SpA followed in a rheumatology center over a period from January 2015 to April 2016. Demographic, clinical, lab and ultrasound characteristics were noted. Fifteen entheseal sites were investigated bilaterally: insertions of supra-spinatus, sub-scapular, medial and lateral epicondylar tendons, triceps brachialis, gluteus medius, quadriceps proximal and distal insertion (patellar ligament, medial and lateral collateral ligament), Achilles tendon, plantar aponeurosis. These sites were assessed clinically and with US during the same visit and then results were compared between the clinical and the US examination. <h3>Results</h3> A total of 208 patients were included, mainly men (63.5%). The mean age was 40.2±11.7 years and the mean duration of the SpA was 11.8±8.7 years. Axial radiographic SpA was the most frequent phenotype (69.2%) and ankylosing spondylarthritis was the most frequent sub-group (57.7%). At examination, 88.9% had an active disease (ASDAS-ESR and/or ASDAS-CRP&gt;1.3) and 64.4% of SpAs were taking NSAID. Clinical examination and US revealed at least one abnormal enthesis in 55.3% and 86.1%, respectively. Overall, 6240 entheses were examined, 44.2% were considered abnormal by clinical examination and 83.2% by US. The US abnormalities were entesophytes (69.5%), erosions (54.8%), hypochogenicity (49%), thickening (46.4%), bursitis (30.5%), calcifications (20.9%) and finally Doppler signal near the cortical bone in 20% of the examined entheses. The evidence of entheseal abnormalities by clinical examination has a poor likehood ratio (LR) for the presence of any US abnormality (LR + =1.4, LR- =0.8), for the acute US abnormalities (LR + =1.25, LR-=0,8), for the chronic US abnormalities (LR + =1.3, LR =0.8) as well as for the presence of the Doppler signal (LR + =1.1, LR- =0.9) at all sites. <h3>Conclusions</h3> US is useful to detect structural and inflammatory abnormalities of the enthesis in the SpA and can complete physical examination in order to better evaluate enthesitis. <h3>Disclosure of Interest</h3> None declared
Working when exhausted is unacceptable
Authors: Paul D McGovern
Journal: BMJ (2017)

Stain’s argument for bringing back 24 hour shifts is underpinned by flawed premises.1 Most worrisome is the suggestion that doctors should work such shifts because they’re eventually going to do it anyway. “Bad practice to gain experience in more bad practice” is not a valid education strategy. This “toughen ’em up” approach is exemplified by Stain …
Annals Story Slam - Out of the Mouths of Babes
Authors: Shelly Dev
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 September 2017Annals Story Slam - Out of the Mouths of BabesFREEShelly Dev, MDShelly Dev, MDFrom University of Toronto, Toronto, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0061 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Out of the Mouths of Babes "Out of the Mouths of Babes," by Dr. Shelly Dev (Duration 06:29)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From University of Toronto, Toronto, Ontario, Canada.Current Author Address: Shelly Dev, MD, University of Toronto, Toronto, Ontario, Canada; e-mail, shelly.[email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 September 2017Volume 167, Issue 6Page: SS1KeywordsMouth ePublished: 19 September 2017 Issue Published: 19 September 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
AB0055 Il-1 beta and CASPASE-1 p45 expression in peripheral blood mononuclear cells of patients with adult-onset still's disease
Authors: S Bindoli, F Fabris, L Punzi, P Galozzi, P Sfriso
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Adult-onset Still9s disease (AOSD) is a systemic inflammatory condition characterized by episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. The inflammatory status of AOSD could result from a deregulation of the NLRP3 inflammasome as Interleukin-1 (IL-1) is pivotal in the pathogenesis of AOSD. <h3>Objectives</h3> To evaluate IL-1 beta and caspase-1 p45 expression in AOSD patients. <h3>Methods</h3> 11 AOSD patients with systemic chronic disease (mean age: 44.5±15.6 years; mean disease duration: 3.0±1.7 years) and 5 healthy donors (mean age: 41.8±7.5) were enrolled. Anakinra (in 6 patients) and DMARDs (in 5 patients) adequately controlled the disease. PBMCs (peripheral blood mononuclear cells) obtained by Ficoll centrifugation were stimulated with lipopolysaccharide (LPS) [10 ng/ml] and ATP [1 mM] for 0.5, 1, 6 and 24 hours. IL-1β level was measured in the supernatant by ELISA and the expression of caspase-1 p45 at protein level was detected by Western Blotting. <h3>Results</h3> In unstimulated PBMCs minimal IL-1β production was found both in AOSD patients and controls. After 6 hours stimulation, IL-1β level was increased whereas we observed a reduced processing of caspase-1 p45 particularly in AOSD patients treated with Anakinra. <h3>Conclusions</h3> Patients with refractory AOSD, who therefore need Anakinra, seem to have an increased production of IL-1β compared to healthy controls and to AOSD patients who respond to standard therapies. Altered processing of caspase-1 p45 in AOSD patients support the involvement of the NLRP3 inflammasome pathway in the pathogenesis of the disease. <h3>Disclosure of Interest</h3> None declared
SAT0511 Thumb base osteoarthritis: associations between synovitis on ultrasound and pain
Authors: S Ermurat, F Kroon, M Kortekaas, M Reijnierse, M Kloppenburg
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Hand osteoarthritis (OA) affects the interphalangeal (IP) joints but also the first carpometacarpal (CMC1) joint in the thumb base. Previous ultrasonography (US) studies of the IP joints have shown that inflammatory and structural features are frequently present and associated with clinical signs and symptoms. Until now, US studies specifically assessing the CMC1 joint have not been performed. <h3>Objectives</h3> To investigate associations between inflammatory features, structural damage and pain in CMC1 OA. <h3>Methods</h3> Cross-sectional data of 87 hand OA patients participating in the EChography in Hand OA (n=63) and the Etanercept in Hand OA (n=24) study at the Leiden University Medical Center were used in this analysis. Both CMC1 joints were assessed with US for synovial thickening, effusion and power Doppler signal (PDS) on a 0–3 scale by experienced ultrasonographers. Presence of pain upon palpation of the thumb base was assessed by trained research nurses on the same day as the US. Hand radiographs were scored blinded for clinical and US features, according to the Osteoarthritis Research Society International atlas for osteophytes (0–3), joint space narrowing (JSN, 0–3), sclerosis (0–1) and malalignment (0–1) in the CMC1 joint. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using generalized estimating equations to investigate associations between US or radiographic features and thumb base pain on joint level. <h3>Results</h3> Of 87 patients (mean age 60.3 years, 82% women, mean BMI 27.2 kg/m<sup>2</sup>) 174 CMC1 joints were assessed, of which 54 (31%) were painful. The US features synovial thickening, effusion and PDS were found in 26%, 33% and 25% of the joints, respectively. Radiographic features were present in 55% (osteophytes), 79% (JSN), 20% (sclerosis) and 12% (malalignment) of the joints. No associations were seen between inflammatory US features and pain upon palpation of the thumb base (Table). However, osteophytes and sclerosis were associated with more pain (RR 2.5 [95% CI 1.4 to 4.6] for osteophytes grade 3 versus no osteophytes, and RR 2.0 [95% CI 1.3 to 3.2] for presence of sclerosis). Other radiographic features (JSN, malalignment) showed a trend for increased risk of pain on palpation, and for osteophytes and JSN a dose-response relation was apparent. <h3>Conclusions</h3> Radiographic features, especially osteophytes and JSN, were prevalent and more frequently present than US inflammatory features in the CMC1 joints of hand OA patients. In contrast to what is known from studies in IP joints, the presence of inflammatory US features was not associated with pain in the thumb base, but structural damage was. These results suggest differences in etiology of pain in thumb base compared to IP OA, with a larger role for structural damage in thumb base OA. <h3>Disclosure of Interest</h3> None declared