tbuckley/cabot-search huggingface dataset:
THU0086 Interleukin 17 receptor d (IL-17RD) reduces incidence of collagen induced arthritis
Authors: M. Molendijk, A.M. Mus, P.S. Asmawidjaja, D. Baeten, E. Lubberts
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> IL-17RD is a member of the IL-17 receptor family. In contrast to the other IL-17 receptors, IL-17RA, -RB, -RC and -RE, little is known about the ligand and function of IL-17RD. Recently, IL-17RD has been described to negatively regulate a selection of IL-17A responsive genes. IL-17RD is therefore proposed to limit IL-17A signalling. <h3>Objectives</h3> In this study we examined IL-17RD expression in multiple cells types and its role in the development of collagen induced arthritis. <h3>Methods</h3> Human synovial fibroblasts from Rheumatoid Arthritis (RA) patients were stimulated with tumour necrosis factor α (TNFα), interleukin 1 β (IL-1β) or IL-17A for multiple time points. IL-17RD expression levels were measured via qPCR. Collagen induced arthritis (CIA) was induced in IL-17RD knockout mice and wildtype littermates. At days 1 and 21, mice were immunised intradermally with chicken collagen type II in complete Freund's adjuvant (CFA). Mice were scored 3 times a week for clinical disease defined as swollen joints with a maximum score of 8. Due to ethical reasons, mice were removed from the experiments when they reached a score of 6. CD4<sup>+</sup> memory T cells, CD8<sup>+</sup> memory T cells, CD19<sup>+</sup> B cells and monocytes were isolated from WT spleens and analysed for IL-17RD expression. Blood neutrophil migration assays were performed <i>in vitro</i> using WT and IL-17RD deficient (IL-17RD KO) mouse synovial fibroblasts. <h3>Results</h3> Human synovial fibroblasts from RA patients have baseline expression of IL-17RD. Upon stimulation with TNFα a significant downregulation of IL-17RD expression was measured from 24 hours onwards. IL1β stimulation had a similar effect as TNFα on IL-17RD expression. Lack of IL-17RD did not result in differences in CIA severity, but the incidence of CIA was reduced. IL-17RD is mainly expressed in synovial fibroblasts. IL-17RD KO synovial fibroblasts attract less neutrophils likely by lower production of neutrophil attractants. <h3>Conclusions</h3> An inflammatory environment causes synovial fibroblasts to downregulate IL-17RD expression. Lack of IL-17RD reduces the incidence CIA, which is an IL-17-driven model. The decrease in CIA incidence is likely explained via the reduced attraction of neutrophils to the site of inflammation. <h3>Disclosure of Interest</h3> None declared
Lymphocyte Antigen 6 Complex, Locus C+ Monocytes and Kupffer Cells Orchestrate Liver Immune Responses Against Hepatitis B Virus in Mice
Authors: Li‐Ling Wu, Wei‐Hao Peng, Hui‐Lin Wu, Shi‐Chuen Miaw, Shiou‐Hwei Yeh, Hung‐Chih Yang, Pei‐Hsuan Liao, Jing‐Shan Lin, Yan‐Rong Chen, Yen‐Tien Hong, Hurng‐Yi Wang, Pei‐Jer Chen, Ding‐Shinn Chen
Journal: Hepatology (2019)

To understand the mechanism(s) of age‐dependent outcomes of hepatitis B virus (HBV) infection in humans, we previously established an age‐related HBV mouse model in which 6‐week‐old (N6W) C3H/HeN mice exhibited virus tolerance whereas 12‐week‐old (N12W) counterparts presented virus clearance. By investigating the hepatic myeloid cell dynamics in mice of these two ages, we aim to identify factors associated with HBV clearance. C3H/HeN mice were transfected with an HBV plasmid by hydrodynamic injection. Serum HBV markers were monitored weekly. Hepatic leucocyte populations and their cytokine/chemokine productions were examined at baseline, day 3 (D3), day 7 (D7), and day 14 after injection. C‐C chemokine receptor type 2 (CCR2) antagonist and clodronate (CLD) were respectively administered to N12W and N6W mice to study the roles of lymphocyte antigen 6 complex, locus C (Ly6C) + monocytes and Kupffer cells (KCs) in viral clearance. N12W mice had a significantly higher number of TNF‐α–secreting Ly6C + monocytes and fewer IL‐10–secreting KCs at D3 in the liver than their younger N6W counterparts after HBV transfection. In addition, the elevated number of interferon‐γ + TNF‐α + CD8 + T cells at D7 was only seen in the older cohort. The enhanced Ly6C + monocyte induction in N12W mice resulted from elevated C‐C motif chemokine ligand 2 (CCL2) secretion by hepatocytes. CCR2 antagonist administration hampered Ly6C + monocyte recruitment and degree of KC reduction and delayed HBV clearance in N12W animals. Depletion of KCs by CLD liposomes enhanced Ly6C + monocyte recruitment and accelerated HBV clearance in N6W mice. Conclusions: Ly6C + monocytes and KCs may, respectively, represent the resistance and tolerance arms of host defenses. These two cell types play an essential role in determining HBV clearance/tolerance. Manipulation of these cells is a promising avenue for immunotherapy of HBV‐related liver diseases.
Letter by Sandoval et al Regarding Article, “Designing a Better Mousetrap: Reflections on the November 28, 2017, US Food and Drug Administration Meeting on Next-Generation “High-Sensitivity” Cardiac Troponin Assays to Diagnose Myocardial Infarction”
Authors: Yader Sandoval, Allan S. Jaffe, Fred S. Apple
Journal: Circulation (2019)
A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology
Authors: Paul S. de Vries, Maria Sabater-Lleal, Jennifer E. Huffman, Jonathan Marten, Ci Song, Nathan Pankratz, Traci M. Bartz, Hugoline G. de Haan, Graciela E. Delgado, John D. Eicher, Angel Martinez-Perez, Cavin K. Ward-Caviness, Jennifer A. Brody, Ming-Huei Chen, Moniek P. M. de Maat, Mattias Frånberg, Dipender Gill, Marcus E. Kleber, Fernando Rivadeneira, José Manuel Soria, Weihong Tang, Geoffrey H. Tofler, André G. Uitterlinden, Astrid van Hylckama Vlieg, Sudha Seshadri, Eric Boerwinkle, Neil M. Davies, Anne-Katrin Giese, M. Kamran Ikram, Steven J. Kittner, Barbara McKnight, Bruce M. Psaty, Alex P. Reiner, Muralidharan Sargurupremraj, Kent D. Taylor, Myriam Fornage, Anders Hamsten, Winfried März, Frits R. Rosendaal, Juan Carlos Souto, Abbas Dehghan, Andrew D. Johnson, Alanna C. Morrison, Christopher J. O'Donnell, Nicholas L. Smith
Journal: Blood (2019)
AB1126 No radiographic wrist damage after targeted treatment in juvenile idiopathic arthritis
Authors: W.G. van Braak, D. Schreurs, P. Hissink Muller, C. Nusman, R. Hemke, D. Schonenberg, J. van den Berg, T. Kuijpers, Y. Koopman, M. van Rossum, L. van Suijlekom-Smit, D. Brinkman, C. Allaart, R. ten Cate, M. Maas
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is characterised by chronic inflammation of the joints which can lead to structural bone damage. <h3>Objectives</h3> The objective of this study was to evaluate the response of new onset JIA patients to an early targeted treatment by conventional radiography. <h3>Methods</h3> JIA patients participating in the BeSt for Kids study (NTR 1574) were eligible in case of wrist involvement at inclusion and if conventional radiographs were available at baseline or within 6 months before or after study inclusion. Follow-up radiographs of hands and wrists after 12–36 months were available for comparison. Radiographic bone damage as reflected by carpal length was assessed using the Poznanski score<sup>1</sup>, providing 'Z' as indication of the deviation from a healthy population as measured by radiometacarpal length relative to the second metacarpal length (RM/M2). BoneXpert method<sup>2</sup> was used to automatically determine bone age and bone mineral density (BMD) of the wrist. <h3>Results</h3> Forty JIA (27 female) patients were evaluated for Poznanski score and BMD (mean age 7.2±3.4 years), 26 patients (15 female) were evaluated for bone age (mean age 9.3±2.2 years). Assessed by the mean Z-score of RM/M2, we did not detect wrist damage at baseline nor at follow-up. Assessed by the mean Z-score of the bone age, we did not detect deviating bone age at baseline nor at follow-up. At baseline BMD was significantly diminished compared to healthy controls (Z-score −0.71, 95% CI=−1.12 to −0.30). BMD at follow-up improved significantly (Z-score −0.44, 95% CI=−0.75 to −0.12, p=0.032). Results are summarised in table 1. <h3>Conclusions</h3> In this cohort of JIA patients treated early and targeted at inactive disease, we have detected no radiographic wrist damage at baseline or follow-up as detected by Poznanski score. BMD was significantly diminished at baseline but improved significantly after follow-up. <h3>References</h3> [1] Poznanski AK, Hernandez RJ, Guire KE, Bereza UL, Garn SM. Carpal length in children – a useful measurement in the diagnosis of rheumatoid arthritis and some congenital malformation syndromes. Radiology1978;129:661–8. [2] Anink J, Nusman CM, van Suijlekom-Smit LW, van Rijn RR, Maas M, van Rossum MA. Automated determination of bone age and bone mineral density in patients with juvenile idiopathic arthritis: a feasibility study. Arthritis Res Ther 2014;16:424. <h3>Disclosure of Interest</h3> None declared
Reply to Amirav and Newhouse: PC<sub>20</sub> versus PD<sub>20</sub>: Why Change a Scientifically Well-Established and Clinically Relevant Test?
Authors: David Kaminsky, Allan Coates, Bruce Culver, Donald Cockcroft, Teal Hallstrand, Jeffrey Haynes, Neil MacIntyre, Jack Wanger
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Efficacy of heavy eccentric calf training for treating mid-portion Achilles tendinopathy: a systematic review and meta-analysis
Authors: Myles Calder Murphy, Mervyn J Travers, Paola Chivers, James Robert Debenham, Sean Iain Docking, Ebonie Kendra Rio, William Gibson
Journal: British Journal of Sports Medicine (2019)

Objective To assess the effectiveness of heavy eccentric calf training (HECT) in comparison with natural history, traditional physiotherapy, sham interventions or other exercise interventions for improvements in pain and function in mid-portion Achilles tendinopathy. Design A systematic review and meta-analysis were conducted as per the PRISMA guidelines. Data sources PUBMED, CINAHL (Ovid) and CINAHL (EBSCO) were searched from inception until 24 September 2018. Eligibility criteria Randomised controlled trials comparing HECT to natural history, sham exercise, traditional physiotherapy and other exercise interventions were included. Primary outcome assessing pain and function was the Victorian Institute of Sports Assessment-Achilles. Results Seven studies met the inclusion criteria. This review suggests HECT may be superior to both natural history, mean difference (MD) (95% CI) of 20.6 (11.7 to 29.5, one study) and traditional physiotherapy, MD (95% CI) of 17.70 (3.75 to 31.66, two studies). Following removal of one study, at high risk of bias, due to pre-planned sensitivity analysis, this review suggests HECT may be inferior to other exercise interventions, MD (95% CI) of −5.65 (-10.51 to −0.79, three studies). However, this difference is unlikely to be clinically significant. Conclusion Current evidence suggests that HECT may be superior to natural history and traditional physiotherapy while HECT may be inferior to other exercise interventions. However, due to methodological limitations, small sample size and a lack of data we are unable to be confident in the results of the estimate of the effect, as the true effect is likely to be substantially different. Systematic review registry PROSPERO registration number: CRD4201804493 Protocol reference This protocol has been published open access: Murphy M, Travers MJ, Gibson, W. Is heavy eccentric calf training superior to natural history, sham rehabilitation, traditional physiotherapy and other exercise interventions for pain and function in mid-portion Achilles tendinopathy? Systematic Reviews 2018; 7: 58
Dual Effects of BCOR-PRC1.1 Dependent Gene Regulation Mediate Cooperation of BCOR and TET2 Mutations in Myeloid Transformation
Authors: Eva Johanna Schaefer, Iman Fares, Clifford Meyer, Paloma Cejas, Annie Apffel, Monica Schenone, Henry W Long, R. Coleman Lindsley
Journal: Blood (2018)
SAT0193 Early discontinuation of first line biological treatment with etanercept in patients with rheumatoid arthritis: results from the italian gisea registry
Authors: M. Sebastiani, A. Manfredi, F. Iannone, E. Gremese, A. Bortoluzzi, E. G. Favalli, R. Gorla, F. Salaffi, E. Fusaro, R. Foti, L. Cantarini, R. Caporali, A. Cauli, S. Alivernini, F. P. Cantatore, A. Carletto, F. Conti, S. D'Angelo, O. Epis, G. Cassone, R. Ramonda, V. Grosso, P. Sarzi-Puttini, G. Ferraccioli, G. Lapadula
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Tumor necrosis factor-α inhibitors (TNFi) are usually the first biologic drugs employed in rheumatoid arthritis (RA) after failure of conventional disease-modifying antirheumatic drugs (DMARDs). Retention rate is a useful surrogate marker of effectiveness and safety in real life, but few studies investigated the causes of early discontinuation of these drugs. <h3>Objectives:</h3> Aim of the study was to investigate the possible predictors of early discontinuation (within 1 year of treatment) of etanercept (ETA) in RA patients enrolled into the GISEA (Italian Group for the Study of Early Arthritis) registry. <h3>Methods:</h3> RA patients who began etanercept as first biologic DMARD were included in the study. For all patients age, sex, disease duration, smoking status, the intake of glucocorticoids and DMARD, clinical and serological data, comorbidities and extra-articular manifestations were collected. <h3>Results:</h3> We analyzed 477 RA patients (females/males 382/95, mean age 51.3±14.1 years; mean DAS28 5.4±1.5); rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) were positive in 66% and 62.3%, respectively. Comorbidities were observed in 16.6% of patients, mainly cardiovascular diseases, while extra-articular RA manifestations were recorded in 6.3%. Concurrent DMARDs therapies were reported in 54.3% of patients, mainly methotrexate (40.5%), while 52.4% of subjects taken low doses of steroids. Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 43 patients, adverse events in 22, and other reasons in 5). The presence of comorbidities and a combination therapy with DMARDs different by MTX were independent predictors of early discontinuation of ETA at multivariate analysis (see table 1). The association with MTX didn’t increase the 1-year retention rate of ETA. No significant associations were observed with steroids, presence of RF or ACPA or the disease activity at baseline. <h3>Conclusions:</h3> ETA demonstrated a high persistence in RA patients and after 12 months more than 85% of patients continued the treatment. The presence of comorbidities and a combination therapy with DMARDs different by MTX were associated to an early withdrawal of the drug. <h3>Disclosure of Interest:</h3> None declared
AB0766 Initial characterisation of women with breast implants in a group of patients with systemic sclerosis referred for autologous HSCT
Authors: H. Khoury, R. Burt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The causal relationship between breast implants (BI) and systemic sclerosis (SSc) is still strongly contested. <h3>Objectives</h3> To add further input to this medical controversy, we studied the initial clinical characteristics of patients with breast implants and systemic sclerosis that are referred to our centre for autologous hematopoietic stem cell transplant. <h3>Methods</h3> From 163 patients, with the diagnosis of systemic sclerosis (SSc), limited SSc, CREST, Morphea or scleroderma sine scleroderma, referred to our centre for autologous hematopoietic stem cell transplantation, 132 were found to be females. To identify those with breast implants (BI) or have a history of breast implants, we performed a systemic chart review for all patients. Once the patients with actual breast implant devices or have history of breast implants were identified, alive patients were contacted to check the type of their breast implants (silicone <i>vs</i> saline), the year of insertion, the local complications, whether they were removed or replaced and the year of removal and replacement, and the type of replacement if applicable. Clinical and biological data were collected for all patients and were compared between those who have breast implants or history if breast implants and those who do not have. <h3>Results</h3> From 132 patients with SSc or SSc variants, thirteen had history of BI (9.8%). In 12, the breast augmentation therapy preceded the development of SSc, with median time between BI insertion and the emergence of initial symptoms of SSc of 12 years (range 7–29). The remaining patient showed acceleration of her disease after BI surgery. Surprisingly, in all 12 patients for whom we could know the type of initial implants, the prostheses were saline. When we compared the clinical characteristics of those with BI and those without. Patients with BI appeared to have higher age (mean 49.95 vs 44.42 years, p=0.012, shorter time from initial symptoms to diagnosis (mean 4.76 vs 12.24 months, p=0.0001), more frequently positive ANA (13/13 vs 89/114, p=0.06) and more frequently positive anti RNA polymerase III (7/10 vs 20/78, p=0.004). <h3>Conclusions</h3> Our data may support the hypothesis of a possible association between BI and SSc. Furthermore, these results raise questions regarding the safety of saline breast prosthesis. Finally, our finding may indicate a possible difference in the initial characteristics of SSc patients with BI and those without. <h3>Disclosure of Interest</h3> None declared
A First in Non-Hodgkin Lymphoma Treatment
Authors: Rebecca Voelker
Journal: JAMA (2019)

The first biosimilar to rituximab for patients with non-Hodgkin lymphoma has received FDA approval. Rituximab-abbs is indicated for adults with CD20-positive, B-cell non-Hodgkin lymphoma. It can be used as a single agent or in combination with chemotherapy.
Redox/pH dual-stimuli responsive camptothecin prodrug nanogels for “on-demand” drug delivery
Authors: Ying Qu, Bingyang Chu, Xiawei Wei, Minyi Lei, Danrong Hu, Ruoyu Zha, Lin Zhong, Mengyao Wang, Fangfang Wang, Zhiyong Qian
Journal: Journal of Controlled Release (2019)
HIV-1 Balances the Fitness Costs and Benefits of Disrupting the Host Cell Actin Cytoskeleton Early after Mucosal Transmission
Authors: Shariq M. Usmani, Thomas T. Murooka, Maud Deruaz, Wan Hon Koh, Radwa R. Sharaf, Mauro Di Pilato, Karen A. Power, Paul Lopez, Ryan Hnatiuk, Vladimir D. Vrbanac, Andrew M. Tager, Todd M. Allen, Andrew D. Luster, Thorsten R. Mempel
Journal: Cell Host & Microbe (2019)
AB1005 Relationship between autoimmunity and osteoporosis in Rheumatoid arthritis
Authors: M.C. Carrasco Cubero, S.M. Rojas Herrera, J. Malave Calzada, P. Pérez David, I. Braña Abascal, E. Chamizo Carmona
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoporosis (OP) is more prevalent in patients with rheumatoid arthritis (RA) than in the general population. Positive anti citrullinated peptide antibody (ACPA) has been related with juxta-articular OP, but their relationship with systemic OP in RA is controversial. <h3>Objectives</h3> To determine if RA autoantibodies (FR and ACPA) are associated with bone mineral density (BMD) in a cohort of patients with established RA diagnosed following the <sup>ACR 1987</sup> criteria. <h3>Methods</h3> Observational study. We analysed the relationship between RF and/or ACPA with the DXA BMD values of the femoral neck (CF) and lumbar spine (LS) (GE LUNAR Prodigy). We perform the analysis using logistic regression, bi and multivariate models, and correlation models. The control variables were sex, body mass, age, duration of RA, prednisone and vitamin D. <h3>Results</h3> We included 294 patients with RA who had all the tests, with a mean age of 63.4 (±10.9) years and duration of RA of 9.8 (±7.9) years. There were 229 (77.9%) women, 229 (77.9%) positive-RF, 196 (66.7%) positive-ACPA, 109 (37.1%) deficient in 25-OH cholecalciferol (&lt;20 ng/ml) and 59 (20.1) smoker patients. They received corticosteroids at low doses 207 (70.4%) and suffered some bone fracture 42 (14.3%) patients. In the BMD, 226 (76.9%) patients had a T-<i>score</i> &lt;-1, of who 86 (27.6%) reached a T-<i>score</i> &lt;−2.5 in LS and/or in FN. Lumbar OP was associated with the female sex (OR=3.6). The FN T-<i>score</i> (and, to a lesser extent, lumbar T-<i>score</i>), showed a correlation with age (r=−0.515, p&lt;0.01). No differences were found in the mean values of BMD, T-<i>score</i> y Z-<i>score</i> of FN and LS between positive or negative patients for FR or ACPA (t-student), neither between their possible combinations (one-way ANOVA). Association between positivity of RF, ACPA or their combinations and T-<i>score</i> &lt;-1 (osteopenia) or T-<i>score</i> &lt;−2.5 (OP) in LS or FN were not found. A negative weak correlation was found between the RF and lumbar BMD values (−0.121, p=0.04) and a positive weak correlation between ACPA and FN (0.136 with BMD, 0.131 with T-<i>score</i> and 0138 with Z-<i>score</i>; p&lt;0.05 for all). <h3>Conclusions</h3> OP was very common in our RA population, especially in women and elderly. Any association was demonstrated between OP and the presence/titer of autoantibodies (RF and ACPA) and low dose of corticosteroids treatment. <h3>Disclosure of Interest</h3> None declared
Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis
Authors: Seth A. Sharp, Stephen S. Rich, Andrew R. Wood, Samuel E. Jones, Robin N. Beaumont, James W. Harrison, Darius A. Schneider, Jonathan M. Locke, Jess Tyrrell, Michael N. Weedon, William A. Hagopian, Richard A. Oram
Journal: Diabetes Care (2019)

Previously generated genetic risk scores (GRSs) for type 1 diabetes (T1D) have not captured all known information at non-HLA loci or, particularly, at HLA risk loci. We aimed to more completely incorporate HLA alleles, their interactions, and recently discovered non-HLA loci into an improved T1D GRS (termed the "T1D GRS2") to better discriminate diabetes subtypes and to predict T1D in newborn screening studies.