tbuckley/cabot-search huggingface dataset:
POS0349 SINGLE OSTEOCLAST RESORPTION ANALYSIS REVEALS AN INCREASED INTRINSIC OSTEOCLAST ACTIVITY IN RA PATIENTS
Authors: A. Maccataio, G. Schett, U. Steffen (Née Harre)
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Inflamed joints and resulting bone erosions are typical features of rheumatoid arthritis (RA). To prevent long-term bone loss in joints as well as systemically, osteoclasts (OCs) have become a main therapeutic target in RA. Despite utilizing new and improved therapeutic approaches, ongoing bone deterioration cannot always be stopped. It is still controversially debated, whether this bone loss is caused by increased OC precursor numbers in circulation, enhanced OC differentiation, or by OCs being more active. It proved difficult to investigate OC activity, since all common <i>in vitro</i> assays depend on OC numbers, hence the efficiency of OC differentiation. Therefore, new techniques are needed that allow the quantification of OC activity on a single cell basis. <h3>Objectives:</h3> To investigate the OC activity of RA patients and healthy controls independent from the common limitations of standard osteoclast resorption assays, by utilizing a novel single cell approach. <h3>Methods:</h3> Blood monocytes from RA patients were differentiated to OCs and seeded onto calcein-incorporated calcium phosphate-coated (calcein-CaP) plates. After 24h, OC movement and resorption were recorded for up to 24h using a time-lapse fluorescent microscope. At last, the OC nuclei were stained with Hoechst and quantified. Resorption pits of individual OCs were than tracked by utilizing the fluorescence signal of the calcein-CaP coating. From here, the resorption speed of the OCs was calculated. Together with the number of nuclei, determined from the Hoechst signal, the resorptive capacity (resorption speed/nuclei) of each individual OC was calculated. The mean resorptive capacities of the RA patients' OCs were then compared to OCs from controls. <h3>Results:</h3> The resorptive capacity of the OCs was significantly increased by 55% in one half of the RA patients in comparison to NHDs. The other half of the RA cohort displayed resorptive capacities comparable to NHDs. This effect was independent from DAS28, CRP, ACPA status, sex, age and medication strategy, but correlated with joint pain. Furthermore, we observed a significantly elevated erythrocyte sedimentation rate (ESR) in RA patients with increased resorptive capacity. <h3>Conclusion:</h3> Our results suggest, that osteoclasts from RA patients with ongoing joint inflammation reflected by joint pain display an intrinsically increased resorption capacity compared with osteoclasts from healthy donors with the same number of nuclei. This phenomenon likely contributes to the accelerated bone loss in RA patients. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1256 INVESTIGATING CORNEAL AND PERIPAPILLARY CHANGES IN PRIMARY SJÖGREN SYNDROME PATIENTS
Authors: S. Efim, G. Tadsen, I. Oluwatoba-Popoola, H. Bettina, C. Mardin, A. Bajor, C. Framme, T. Witte, K. Hufendiek, D. Ernst
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients with primary Sjögren Syndrome (pSS) can have different manifestations of the disease e.g. the inflammatory occultations of the eye, which can lead to to a change in corneal tropism (e.g. of the subbasal corneal nerve plexus (SNP)) and damage to the trigeminal nerve. This can correlate with the loss of retinal nerve fibers. <h3>Objectives:</h3> The aim of our study was to investigate the corneal and optic nerve metrics as well as the peripapillary microvasculature and to identify potential ocular biomarkers for neuro/microvascular changes in patients with pSS. <h3>Methods:</h3> Central cornea images were prospectively captured from 48 eyes with clinically diagnosed pSS and 38 eyes of age-matched healthy controls using in-vivo corneal confocal microscopy (IVCCM) (Heidelberg Retina Tomograph Rostock Cornea Module - HRT III RCM). Corneal nerve fiber length (CNFL), fiber density (CNFD), branching density (CNBD), total fiber branching density (CTBD), fiber area (CNFA), fiber width (CNFW) and fractal dimension (CNFrac) were measured with ACC Metrics software. OCTA and SD-OCT scans were obtained using SPECTRALIS® II (Heidelberg Engineering, Germany). RNFL and BMO were analyzed with the built-in software. Peripapillary OCTA images (2.9x2.9mm) were analyzed using Erlangen-Angio-Tool. Peripapillary Vessel Area Density (pVAD) was measured at the level of nerve fibre layer plexus (NFLVP) in the innermost circle c1. <h3>Results:</h3> Patients with pSS had significantly lower values of CNFD and a higher value of CNFW compared to controls (CNFD: (22.4±8.3 vs. 26.2±7.6 fibres/mm<sup>2</sup>, Cohen`s D 0.47; CNFW: 0.022±0.001 vs. 0.021±0.001 mm/mm<sup>2</sup>, Cohen`s D 0.52; always p&lt;0.05). There were no statistically significant differences between groups for RNFL, BMO and pVAD measurements. No correlation was found between pVAD and RNFL/ SNP. Correlation analysis for RNFL showed a significant correlation with CNFL (ρ =.246), CTBD (ρ =.245), and CNFrac (ρ =.311) (always p&lt; 0.05). Correlation analysis for BMO showed a significant correlation with CNFD (ρ =.291), CNFL (ρ =.289) and CNFrac (ρ =.252) (always p&lt; 0.05). <h3>Conclusion:</h3> Patients with pSS have a lower CNFD and thicker corneal nerves compared to healthy eyes. Nerve fibre loss and swelling indicate an ongoing corneal inflammatory process. A low to moderate positive correlation between the SNP and optic nerve metrics suggest a link between peripheral and central nerve changes. Peripapillary microvasculature does not seem to be altered in patients with pSS. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1652-PARE EDUCATION OF PATIENTS WITH SJOGREN’S SYNDROME IN BULGARIA - THE ROLE OF RHEUMATOLOGISTS AND THE PATIENT ORGANIZATION
Authors: M. Panchovska, B. Boteva
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients with primary and secondary Sjogren's syndrome have their own specific educational and informational needs, which determine complex care for them [1,2]. The Bulgarian organization for people with heumatic diseases and specialists in rheumatology regularly and annually hold webinars that examine the diagnostic and therapeutic problems of patients. The initiative started 4 years ago. <h3>Objectives:</h3> The purpose of the webinars is to familiarize patients with Sjogren's syndrome and its symptoms as a systemic disease, as well as to emphasize specific problems, such as dental ones and also to give opportunity to patients to ask questions. <h3>Methods:</h3> In 4 consecutive years, webinars were organized with an educational purpose on the essence of the disease, the involvement of the salivary glands, multiple caries, oral candidosis. Of particular interest were dental implantology issues. A special place was devoted to immunosuppressive therapy and possible side effects. The webinars are published in the You tube profile of the Bulgrian organization for people with rheumatic diseases as to have the chance to be watched later <h3>Results:</h3> With the webinars, three goals were achieved: 1. Analysis of the relationship between Sjogren's syndrome and oral health 2. the necessary care for oral health 3. Diagnostic and treatment aspects in terms of awareness. SS is a rare diseases and more than 20 people participated each webinar and more than 300 views in the You tube channel. <h3>Conclusion:</h3> Sjogren's syndrome is a multifaceted disease that raises diagnostic and therapeutic questions. Dental aspects of the disease play a role in diagnosis, course and treatment. Educational webinars aim to achieve a better quality of life for patients with Sjogren's syndrome. Patients are more informed and manage their diseases better. <h3>REFERENCES:</h3> [1] de Souza, S., Bansal, R. &amp; Galloway, J. Managing patients with rheumatoid arthritis. BDJ Team 4, 17064 (2017). https://doi.org/10.1038/bdjteam.2017.64. [2] Singh AG, Singh S, Matteson EL. Rate, risk factors and causes of mortality in patients with Sjögren's syndrome: a systematic review and meta-analysis of cohort studies. <i>Rheumatology (Oxford</i>) 2016;55(3):450–60. [3] Sjögren's Syndrome: Oral Manifestations and Treatment, a Dental Perspective. [4] Cartee DL, Maker S, Dalonges D, Manski MC.J Dent Hyg. 2015 Dec;89(6):365-71. <h3>Acknowledgements:</h3> prof.Georgi Tomov, Faculty of Dental Medicine, Medical University, Plovdiv, Bulgaria · Periodontology DMD, MSc, PhD; Ms Miglena Ivanova, Bulgarian organization for patients with rheumatic diseases. <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1044 IMPACT OF SARCOPENIA ON FATIGUE IN RHEUMATOID ARTHRITIS
Authors: K. Zouaoui, S. Mhamdi, R. Ben Othmane, S. Rahmouni, M. Abbes, S. Boussaid, S. Rekik, H. Sahli, M. Elleuch
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sarcopenia is the loss of muscle mass and/or strength. It was initially associated with the aging process. Recent studies revealed its occurrence in various chronic inflammatory conditions, which could affect the quality of life of patients. <h3>Objectives:</h3> Evaluate the impact of fatigue in patients with rheumatoid arthritis (RA). <h3>Methods:</h3> A monocentric cross-sectional study was conducted on female patients with RA meeting the ACR/EULAR 2010 criteria. Demographic, clinical, paraclinical and therapeutic data of participants were collected. Muscle mass and strength were evaluated to identify sarcopenia. Muscle mass was assessed by measuring the appendicular skeletal muscle mass index (ASMI) using Bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA). Muscle strength was determined by the hand grip test using a dynamometer. Sarcopenia was defined as an ASMI ≤ 5.5 kg/m<sup>2</sup> AND a hand grip test &lt; 16 kg. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F). We used the threshold score of 34 to define fatigue. <h3>Results:</h3> Fifty-five female patients were included. The average age was 58.22±7.9 years [40-76]. Nineteen were of rural origin, 10 were professionally active. Smoking was present in 3.6% (n=2) of our patients. Twenty-nine per cent (n=16) had hypertension and 34.5% (n=19) were diabetic. The average duration of RA progression was 9.2±6.4 years [1-30]. The mean DAS28-CRP was 4±1.8 [1.2-6.5]. Active disease was noted in 89.1% (n=49). The mean Health Assessment Questionnaire (HAQ) was 1.08±0.6 [0.1-2.5]. All our patients had at least one conventional synthetic disease-modifying antirheumatic drug. Biologics were used in 23 patients (41.8%). Fifty-four were treated with corticosteroids, with an average dose of 6±1.9 mg of prednisone. Sarcopenia was detected in 85.5% (n=49) of patients with a hand grip test of 9.48±5.7 kg [1.8-25.6]. The mean appendicular skeletal muscle mass index (IMSA) was 7.42±1.2 kg/m<sup>2</sup> [5.41-11.01] by BIA and 6.47±1.1 kg/m<sup>2</sup> [4.19-8.84] by DEXA. It indicated the presence of sarcopenia in 7.3% (n=4) of the patients using BIA versus 21.8% (n=12) with DEXA. The mean FACIT-F was 32.36 [15-49]. Forty per cent of patients had fatigue. Sarcopenia was associated with greater functional limitations assessed by HAQ (p= 0.046) However, our study did not find a significant correlation between sarcopenia and FACIT-F score (p=0.532). <h3>Conclusion:</h3> Sarcopenia did not seem to be associated with fatigue during rheumatoid arthritis. However, it was associated with poor functional outcomes. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0047-PARE LIRE CONGRESS 2023: CELEBRATING 50 YEARS OF DEDICATION TO RHEUMATIC AND MUSCULOSKELETAL DISEASES (RMDs)
Authors: M. S. Garcia Rodriguez
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Liga Reumatológica Española (LIRE) was founded 50 years ago with the mission to assist individuals affected by rheumatic and musculoskeletal diseases (RMDs) and collaborate with healthcare professionals in researching new treatments to alleviate the daily suffering of over 12 million patients facing more than 250 different pathologies in Spain. To commemorate this milestone, LIRE, in conjunction with its affiliated entities nationwide, proposed a significant event that examines the present and future of RMDs research and addresses the critical issues currently faced by patients and their families in Spain. <h3>Objectives:</h3> The objectives were to celebrate LIRE's 50-year history and bring together the PARE community in Spain. Additionally, the event aimed to facilitate discussions among researchers, patient representatives, and healthcare professionals to address RMDs challenges in Spain. <h3>Methods:</h3> Participant data, including age, gender, and affiliation, were collected. An evaluation questionnaire was administered at the end of the sessions. <h3>Results:</h3> The LIRE Congress 2023 drew a total of 342 participants, representing a diverse range of backgrounds. Among the attendees, 109 were patients affiliated with patient associations, while 72 were healthcare professionals. Additionally, 55 individual patients, 34 staff members from patient associations, and 31 caregivers actively participated. Furthermore, the event welcomed 14 participants from the pharmaceutical or healthcare technology industry, 10 individuals engaged in research and/or education, 7 individuals from public administration and 10 others with diverse backgrounds. This diverse assembly created a vibrant and inclusive atmosphere for discussions on RMDs and PARE in Spain. The event featured innovative studies, including research on pain and mental health, provided practical insights and hosted specialized "Workshops" that encouraged innovation and lively discussion among healthcare professionals and PARE in Spain. <h3>Conclusion:</h3> The LIRE Congress 2023 celebrated the 50th anniversary, marking a significant milestone in RMDs research and treatment. It brought together experts, patient advocates, and healthcare professionals to address the challenges faced by PARE in Spain and present innovative studies. The event served as a valuable knowledge-sharing platform, promoting collaboration and insights to improve the quality of life for people with RMDs and fostering innovation among healthcare professionals. <h3>REFERENCES:</h3> [1] Website of Liga Reumatologica Española (LIRE) https://lire.es/. [2] Programme of the LIRE Congress 2023 – 50 years, 2023. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1420 RISK OF DIABETES MELLITUS IN PATIENTS WITH GIANT CELL ARTHRITIS OR POLYMYALGIA RHEUMATICA: PRELIMINARY RESULTS FROM THE GIANT CELL ARTHRITIS AND DIABETES MELLITUS (GIADIM) TRIAL
Authors: T. E. Eriksen, W. K. H. Dinesen, M. E. R. Sørensen, L. Dreyer, K. S. Duch, E. Gaarn Lindgreen, M. K. Stilling-Vinther, S. Kristensen
Journal: Annals of the Rheumatic Diseases (2024)
POS0699 RNA SEQUENCING REVEALS CRUCIAL NEW PLAYERS IN OSTEOARTHRITIS CARTILAGE CALCIFICATION
Authors: S. Nasi, I. Bernabei, E. Faure, J. Wegrzyn, T. Hügle, N. Busso
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Osteoarthritis (OA) is a degenerative joint disease characterized by pathologic calcification of cartilage, where chondrocytes deposit calcium-containing crystals. Understanding the precise mechanisms behind calcification is challenging but crucial for developing effective therapeutic strategies. <h3>Objectives:</h3> This study aims to identify key players in knee OA cartilage calcification, providing insights for targeted interventions. <h3>Methods:</h3> Primary murine chondrocytes were stimulated with secondary calciprotein particles (CPP2) or left untreated (NT) in DMEM high glucose for 6 hours. Lysates were prepared according to MERCURIUS™ Extraction-free DRUG-seq kit and submitted to Alithea Genomics SA (Lausanne, Switzerland) for Bulk RNA sequencing on an Illumina Novaseq 6000. STARsolo v2.7.9a aligned and quantified reads against the mouse (GRCm38.102) genome. Differentially expressed (DE) genes were identified with DESeq2 (abs(LogFC)&gt;1, FDR &lt; 0.05), and the top 50 DE genes were cross-referenced with human OA datasets from previous studies (<i>i.e.</i> OA <i>vs</i> healthy cartilage, or damaged <i>vs</i> undamaged cartilage). Finally, human primary chondrocytes from 5 osteoarthritis patients were stimulated with CPP2 to validate gene modulation by qRT-PCR. <h3>Results:</h3> We first confirmed that CPP2 induce calcification in primary murine chondrocytes (Figure panel A). Bulk RNA sequencing revealed 1466 differentially expressed genes (668 up- and 798 downregulated) between CPP and NT murine chondrocytes. Out of the top 50 DE genes (Figure panel B), 18 were significantly upregulated and 4 downregulated in at least 1/7 OA cartilage datasets. Interesintgly, previously studied genes in osteoarthritis (ERRFI1, NGF, INHBA, RCAN1, and GREM1) were found and new candidates (S100A10, EIF5A, and TNFRSF12A) emerged. In primary human chondrocytes, we confirmed upregulation of NGF, INHBA, RCAN1 and TNFSFR12A by CPP2, and downregulation of COL9A1 (Figure panel C). <h3>Conclusion:</h3> Our study unveils NGF, INHBA, RCAN1 and TNFSFR12A as key players in cartilage calcification, presenting promising avenues for therapeutic interventions in an area where effective treatments are currently limited. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
OP0030 PREDNISONE THERAPEUTIC EFFECT IN MYOSITIS DEPENDS ON Β-ADRENERGIC PATHWAY ACTIVATION INDUCED BY MYOFIBRES
Authors: M. Giannini, D. Rovito, L. Debrut, C. Keime, A. L. Charles, B. Lannes, B. Geny, D. Metzger, G. Laverny, A. Meyer
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Glucocorticoids (GC) treatment in myositis is empirical and side effects are frequent. Both therapeutic and iatrogenic effects of GC are mediated by glucocorticoid receptor (GR) which is ubiquitously expressed. We have recently shown in experimental myositis (EM) induced in GR(i)skm-/- mice that prednisone (PDN) induces a myofibre-mediated anti-inflammatory phenotype in immune cells. Muscle transcriptomic analysis indicated that PDN induces myofibres release of epinephrine that could mediate therapeutic response. Epinephrine effect depends on its binding to the β-adrenergic receptors (β-AR). β2-AR are the most expressed in immune cells. <h3>Objectives:</h3> The aim of this study was to investigate the importance of β-adrenergic pathway activation in the therapeutic response to PDN in preclinical models of myositis. <h3>Methods:</h3> Human myotubes were treated with proinflammatory cytokines for 2 days. Then, PDN (or vehicle) was added with or without a GR inhibitor for 5 days. EM was induced at day 0 (D0) in 10-week-old mice through the immunisation against a polypeptide from skeletal muscle fast-type C protein. From D14 to D20, mice were treated with oral PDN at the dose of 1 mg/kg/day for 7 days (or vehicle), with or without a β-blocker at the same dose, or with an oral β2-agonist (6 mg/kg/day for 7 days). Muscle strength was assessed at D0, D14 and D20 before the sacrifice (D21). Serum creatine-kinase (CK) levels were assessed at D21. <h3>Results:</h3> PDN increased by 2-fold the epinephrine level in the supernatant of human myotubes treated with proinflammatory cytokines. This effect of PDN was suppressed when a GR inhibitor was added. In vehicle-treated EM mice, a 20% decrease in muscle strength was found at D14 (p=0.0001) up to D20 (p=0.0001) compared to D0. PDN-treated EM mice recovered muscle strength at D20 (p=0.008 vs D14). This effect of PDN was abolished when a β-blocker was co-administered (p=0.0001 vs D0). At sacrifice, CK serum levels were 2 times higher in vehicle-treated EM mice compared to unimmunized mice (p=0.004). PDN normalized CK serum levels in EM mice. This effect of PDN was suppressed when a β-blocker was co-administered (p=0.008 vs unimmunized mice). Conversely, a treatment with a β2-agonist reproduced PDN therapeutic effect on muscle weakness as well as on CK level. These results show that PDN improves myositis in EM through myofibre production of epinephrine and β-adrenergic pathway activation. <h3>Conclusion:</h3> Coadministration of β-blockers might decrease PDN therapeutic effect in myositis. Stimulation of β2-adrenergic pathway might represent a new therapeutic strategy for myositis. <h3>REFERENCES:</h3> [1] Giannini M et al. DOI: 10.1136/annrheumdis-2023-eular.5217. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1261 CLINICAL VALUE OF SALIVARY GLAND ULTRASONOGRAPHY IN EVALUATING SECRETORY FUNCTION, DISEASE ACTIVITY AND LYMPHOMA RISK FACTORS IN PRIMARY SJÖGREN’S SYNDROME
Authors: S. K. Kwok, J. Yang, Y. Park, J. Lee, W. U. Kim, S. H. Park
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Salivary gland ultrasonography (SGUS) is widely used in primary Sjögren's syndrome (pSS). Many studies have investigated its diagnostic usefulness concerning replacing invasive minor salivary gland biopsy (MSGB), however, the broader clinical value remains unclear. <h3>Objectives:</h3> In this study, we aimed to assess the clinical significance of SGUS in evaluating secretory function, disease activity, and lymphoma risk factors in pSS. <h3>Methods:</h3> 150 pSS patients who visited Seoul St. Mary's Hospital between January 2019 and July 2023 were included. All subjects were evaluated with SGUS, MGSB, and secretory function tests. Salivary gland function-related parameters, systemic disease activity-related parameters, and laboratory data related to lymphoma risk factors were retrospectively obtained. The association between SGUS grades and parameters related to secretory function or systemic disease activity was determined. Subgroup analyses based on SGUS grade or the presence of lymphadenopathy (LAP) in SGUS were also performed. <h3>Results:</h3> SGUS grades were significantly correlated with all other parameters related to salivary gland secretory function. Specifically, they were significantly associated with overall ESSDAI scores, scores of ESSDAI glandular domain, scores of ESSPRI dryness domain, and VAS, respectively. Notably, patients with highest SGUS grade (overall score = 6) showed higher prevalence of laboratory risk factors or extraglandular manifestations potentially related to lymphoma development, compared to the others. Patients having LAP detected by SGUS exhibited lower salivary flow rates, and higher scores in ESSDAI, ESSPRI, and VAS. <h3>Conclusion:</h3> Our results suggest that SGUS grades and the presence of LAP in SGUS findings are associated with clinical parameters representing secretory function and disease activity in pSS. High SGUS grades are associated with risk factors for lymphoma development. <h3>REFERENCES:</h3> [1] Esther Mossel et al., Histopathology, salivary flow and ultrasonography of the parotid gland: three complementary measurements in primary Sjögren's syndrome, Rheumatology 2022;61:2472–2482 [2] K. Delli et al., Can salivary gland ultrasonography replace salivary gland biopsy in the diagnosis of Sjögren's syndrome?, Clin Exp Rheumatol 2022; 40: 2443-2449 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>