tbuckley/cabot-search huggingface dataset:
POS0101 MORTALITY TRENDS IN POLYMYOSITIS AND DERMATOMYOSITIS IN MEXICO: A GENERAL POPULATION-BASED STUDY FROM 2000 TO 2019
Authors: P. Munguía-Realpozo, C. Mendoza Pinto, I. Etchegaray-Morales, S. Méndez-Martínez, J. Orbe-Sosa, L. G. Vázquez De Lara-Cisneros, M. García-Carrasco
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Inflammatory myopathies refer to a group of autoimmune diseases that affect the skin and different organs, leading to disability and a significant economic burden. In recent years, health information has become available in open access, which allows us to assess the mortality rates of various diseases. <h3>Objectives:</h3> To assess mortality trends in polymyositis/dermatomyositis (PM/DM) in Mexico between 2000 and 2019, overall and by sex, age group, and geographic regions. <h3>Methods:</h3> Data were acquired from Health Information Open Access databases, and we identified deaths for PM/DM (ICD-10) recorded from 2000 to 2019. Age-standardized mortality rates (ASMR) per 100,000 persons were calculated for PM/DM and non-PM/DM overall, by sexes, and by geographic region. Annual percentage change (APC) in ASMR was calculated using Joinpoint regression software. <h3>Results:</h3> We found 1,456 deaths from PM/DM in Mexico from 2000 to 2019. The gender distribution of PM/DM deaths was 69.8% in women and 30.2% in men. Compared to non-PM/DM, PM/DM individuals had a higher proportion in the younger population (younger than 45 years) (40.2% vs. 22.3%). Overall, a significant downtrend in the ASMR was identified from 2007 to 2017 in subjects with PM/DM (APC -3.2%; 95% CI, -5.3 to -1.0; <i>p</i> = 0.008), while mortality trends were stable for non-PM/DM individuals. Similar trends were identified by sex in PM/DM patients. The Joinpoint analysis did not identify variation in temporal trends in mortality rates by geographic region; however, an increment in the proportion of deaths in the ratio of PM/DM to non-PM/DM ASMR was detected in the Northern and Southern regions (+17.6% and +84.9%, respectively). <h3>Conclusion:</h3> Over 20 years, we observed that deaths due to PM/DM occurred predominantly in females. A notable decrease in overall mortality rates was identified between 2007 and 2017. Differences by sex, age, and geographic region were also detected. <h3>REFERENCES:</h3> [1] Svensson J, Arkema E V, Lundberg IE, Holmqvist M. Incidence and prevalence of idiopathic inflammatory myopathies in Sweden: a nationwide population-based study. Rheumatology (Oxford). 2017 May;56(5):802–10. [2] Mendoza-Pinto C, Etchegaray-Morales I, Garcia-Carrasco M, Munguía-Realpozo P, Méndez-Martínez S, Osorio-Peña AD, et al. Twenty-year trends in all-cause mortality of patients with systemic lupus erythematosus in Mexico: Results from a nationwide health registry. Lupus. 2022;31(3):382–91. [3] Datos abiertos. Secretaría de Salud/Dirección General de Información en Salud [Internet]. Available from: http://www.dgis.salud.gob.mx/contenidos/basesdedatos/Datos_Abiertos_gobmx.html <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1404 THE CLINICAL SPECTRUM OF ANTI-U1RNP(+) PATIENTS: LONG TERM FOLLOW-UP FROM A SINGLE CENTER COHORT
Authors: A. Koutsogianni, M. Patsouras, A. V. Goules, P. G. Vlachoyiannopoulos
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Anti-U1-RNP autoantibody is known to define patients with mixed connective tissue disease (MCTD). These patients may present with overlapping clinical manifestations resembling systemic lupus erythematosus or scleroderma. However, the full clinical spectrum and long-term outcome of anti-U1RNP (+) patients has not been adequately investigated. <h3>Objectives:</h3> The aim of the current study was to describe the clinical spectrum and associations of anti-U1-RNP (+) patients. <h3>Methods:</h3> From the 25-year database of the immunology laboratory of the Department of Pathophysiology, those patients with ANA&gt;1:320 and anti-U1RNP (+) were identified and their medical records were carefully reviewed. Demographic features, cumulative clinical, laboratory and immunological data, as well as given treatment were recorded and retrospectively analyzed. Anti-U1RNP (+) only patients were compared to those with at least another autoantibody while clinical associations were explored among serious complications including renal, CNS and hematologic manifestations. <h3>Results:</h3> Eighty five patients were identified and included in the study. The mean±SD age at disease onset was 35.3±17.3 years and the mean±SD disease duration from disease onset to last follow up was 15.2±10.3 years while 72 (84.7%) of patients were females. The most common presenting clinical manifestations were Raynaud's phenomenon (46.4%), rash (17.9%) and small hand arthritis (14.3%). During follow up, 40 (47%) patients eventually fulfilled the classification criteria for MCTD, 29 (34%) for SLE, 8 (9%) for Ssl, 4 (4.5%) SjD, 1 (1%) primary relapsing polychondritis and 1 (1%) retroperitoneal fibrosis. Anti-Ro antibodies were eventually detected in 22(25.%) patients, anti-Sm in 27 (31.8%), anti-La in 4 (4.5%), anti-phospholipid antibodies (aPLs) in 17 (20%) and anti-dsDNA in 24 (28%) patients. The presence of anti-Ro autoantibodies was statistically associated with renal involvement (p=0.045) while anti-Sm autoantibodies with the development of both serositis (p=0.008) and central nervous system involvement (p=0.007). Malar rash (p&lt;0.001) and fever (p=0.039) were strongly associated with renal involvement. At the end of follow up, 3 patients had seizures (of whom 2 had aPLs) and 2 developed stroke (of whom 1 had aPLs). No patient developed end-stage renal disease while severe hematologic manifestations were very rare. <h3>Conclusion:</h3> Anti-URNP (+) patients display a mild clinical phenotype with a good long term outcome. The presence of additional autoantibodies may be associated with a less favorable prognosis. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0751 CHRONOEFFICACY AND CHRONOTOXICITY OF IGURATIMOD AGAINST RHEUMATOID ARTHRITIS IN EXPERIMENTAL RATS
Authors: Y. Jia, Q. Dong, H. Dong, Z. Wang, Z. LI
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The circadian rhythm is a universal biological process regulated by the Earth's rotation and solar cycles. It affects various bodily functions and symptom of disease, such as Rheumatoid arthritis (RA). The clinical symptoms of RA show an earlier circadian rhythm. Not coincidentally, several classical DMARDs such as triptolide, brucine and methotrexate have shown different efficacy or toxicity in the treatment of RA varies with different administration times. It is not clear whether the effect of iguratimod, a highly effective and safe novel DMARDs used in China and Japan, in treating RA also has similar characteristics. <h3>Objectives:</h3> Here we aimed to investigate the chronoefficacy and chronotoxicity of iguratimod against collagen-induced arthritis (CIA) in rats. <h3>Methods:</h3> CIA model was induced in Wistar rats and then treated with iguratimod (6 mg/kg/day, gavage.) at different circadian time points ZT8 or ZT20. Arhtirits index, paw thickness, weight were measured. Serum inflammatory factors were assessed using enzyme-linked immunosorbent assay. Related pathological tests were evaluated by hematoxylin-eosin staining. Sreum factors associated with liver damage were assessed using colorimetry assay. Expression of clock genes in joints were detected by immunohistochemical method. <h3>Results:</h3> CIA rats oral administration with iguratimode at ZT20 had lower levels of foot swelling, Cartilage and bone destruction, inflammatory cell infiltration, key inflammatory factors (IL-6, TNF-α and IL-17A) than at ZT8. On the other hand, iguratimode significantly decreaed the weight of rat increased the level of Histamine, AST and ALT compared with control rats, but without different between ZT20-treatment and ZT8-treatment. Furthermore, the levels of Bmal1 and CLOCK were markedly decreased by iguratimodedosing at ZT20 only. <h3>Conclusion:</h3> These results indicated that iguratimode dosed at ZT20 was more effective in protecting against CIA than drug dosed at ZT8. While the hepatotoxicity of iguratimode didn't seem to have a time pattern. The chronoefficacy of iguratimode might be related to the regulation of clock genes. Our work is of great importance. The therapeutic effects of existing drugs cannot meet the treatment needs of patients. Therefore, new drugs or treatment options have always been under development. It would be very encouraging if a reasonable drug regimen which is developed based on our results can improve the therapeutic effect. And, this improvement is very cost-effective and fast. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> This study was supported by National Natural Science Foundation of China Youth Fund (81873301, 81903883). <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0560 DYSFUNCTION OF ALVEOLAR EPITHELIAL CELL REPAIR IN HUMANIZED PULMONARY FIBROSIS MOUSE MODEL
Authors: Z. H. LI, R. Mu
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Progressive fibrosing interstitial lung diseases (PF-ILDs) are one of the leading causes of death in patients with rheumatic and musculoskeletal diseases. However, due to the limitations of in vitro organoid models and the self-limitation of <i>in vivo</i> fibrosis models, the link between alveolar repair and fibroblast activation in PF-ILDs remains unclear. The humanized pulmonary fibrosis mouse model reported in recent years is beneficial to understand stromal-epithelial axis. <h3>Objectives:</h3> The humanized model was used to simulate the direct effect of PF-ILDs lung fibroblasts on alveolar epithelial cells <i>in vivo</i>, and to observe the abnormal regeneration features of alveolar epithelial stem/progenitor cells, type II alveolar epithelial cells (AT2) cells. <h3>Methods:</h3> Human PF-ILDs lung fibroblasts transfected with fluorescent reporter gene were injected into the mice with severe combined immunodeficiency via tail vein to establish a humanized pulmonary fibrosis model. Mice were sacrificed on the 14th and 35th days after injection, respectively, and the degree of fibrosis in the model was evaluated from the imaging and histological aspects. The abnormal differentiation state of AT2 cells in the humanized model was detected by immunohistochemistry, including indicators related to the intermediate state of differentiation, cell senescence, and Epithelial-Mesenchymal transition (EMT). <h3>Results:</h3> The humanized mouse model based on PF-ILDs lung fibroblasts (LL29A) was successfully established. After LL29A cells were injected into mice, they mainly colonized the lungs and continued to expand. Pulmonary fibrosis appeared on the 14th day after injection, and the fibrosis was mainly derived from mice. Fibrosis persisted after 35 days and was gradually maintained by collagen secretion from human fibroblasts. PF-ILDs lung fibroblasts can directly induce alveolar epithelial cell damage, and then induce alveolar epithelial cell senescence and EMT, and differentiate into KRT5<sup>+</sup> basal-like cells, which hinders lung regeneration and promotes lung fibrosis. <h3>Conclusion:</h3> In this study, we established a mouse model of humanized pulmonary fibrosis and revealed that human PF-ILDs lung fibroblasts lead to aberrant alveolar epithelial cell regeneration in vivo, mainly by generating KRT5<sup>+</sup> basal-like cells and inducing senescence of AT2 cells, EMT phenotypic differentiation, and inhibition of lung regeneration. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0839 TREATMENT OF NON-SYSTEMIC SJÖGREN SYNDROME: POTENTIAL PREVENTION OF VISCERAL INVOLVEMENT USING EARLY IMMUNOSUPPRESSANT AGENT/BIOTHERAPY, EXPERIENCE OF A SINGLE CENTER
Authors: A. Belbezier, T. T. T. Nguyen, M. Arnaud, B. Ducotterd, M. Vangout, A. Bocquet, C. Guerin, A. Deroux, C. Mansard, F. Sarrot-Reynauld, L. Bouillet
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sjögren's disease (SS) is a systemic autoimmune pathology manifested mainly by a dry syndrome, intense asthenia and arthromyalgia. Systemic manifestations may also occur. Since 2019, immunosuppressant agents (IS) or biotherapies are recommended only for patients with systemic involvement. However, before 2019, in some cases, paucisymptomatic patients had been treated with IS/biotherapies, often off-label. <h3>Objectives:</h3> We propose to evaluate the benefit and safety of using IS/biotherapy in patients with SS without systemic involvement. <h3>Methods:</h3> We retrospectively collected the clinical records of all patients with SS diagnosed according to ACR/EULAR diagnostic criteria followed up between January 1980 and October 2023 at Grenoble University Hospital (France). <h3>Results:</h3> Eighty-three patients were included: 64 with an initially non-systemic form. Of these patients with an initially non-systemic form, 24 were treated with IS/biotherapy. None of them developed secondary systematization, whereas 11 out of 40 patients in the untreated group did (p&lt;0.05). On the other hand, IS/biotherapy did not appear to improve dry syndrome. There were no serious adverse events. <h3>Conclusion:</h3> Early introduction of an IS/biotherapy treatment appears to provide a benefit for the patient without side effects. <h3>REFERENCES:</h3> [1] Shiboski CH, Shiboski SC, Seror R, <i>et al.</i> 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts. <i>Ann Rheum Dis</i>. 2017;76:9–16. [2] Ramos-Casals M, Brito-Zerón P, Bombardieri S, <i>et al.</i> EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies. <i>Ann Rheum Dis</i>. 2020;79:3–18. [3] Brito-Zerón P, Retamozo S, Kostov B, <i>et al.</i> Efficacy and safety of topical and systemic medications: a systematic literature review informing the EULAR recommendations for the management of Sjögren's syndrome. <i>RMD Open</i>. 2019;5:e001064. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0905 IMMUNE CELL-SPECIFIC CHARACTERIZATION OF HIGH-RESOLUTION COMPUTED TOMOGRAPHY (HRCT) PATTERNS IN INFLAMMATORY RHEUMATIC DISEASES WITH LUNG INVOLVEMENT: A STUDY IN NEWLY DIAGNOSED PATIENTS
Authors: T. Hoffmann, M. Förster, P. Oelzner, C. Kroegel, U. Teichgräber, D. Renz, J. Böttcher, P. C. Schulze, G. Wolf, M. Franz, A. Pfeil
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Lung involvement is the most common organ involvement in inflammatory rheumatic disease (IRD). The current state of the art is to perform a high-resolution computed tomography (HRCT) for evaluation and diagnosis. The main pattern in HRCT in IRD included pure ground glass opacity (GGO) as primary inflammatory pattern and non-specific interstitial pneumonia (NSIP) as well as usual interstitial pneumonia (UIP) representing fibrotic pattern. <h3>Objectives:</h3> The aim of this study was to characterise HRCT pattern by different immune cells at the time of IRD diagnosis with lung involvement. <h3>Methods:</h3> 74 patients with newly diagnosed IRD (connective tissue disease n = 46, myositis n =12, vasculitis n = 10 and rheumatoid arthritis n = 6) as well as newly diagnosed lung involvement in the context of interstitial lung disease (ILD) in HRCT were included in the study. In HRCT, the patients presented pure GGO, NSIP or UIP pattern. The study cohort was divided in a GGO (n = 29) and NSIP/UIP group (n = 45). For the quantification of immune cells an immunological bronchoalveolar lavage was performed, with subsequent implementation of a differential cell image and flow cytometry. Additionally, all patients were naïve for immunosuppressive therapy, received no glucocorticoids and were non-smokers. <h3>Results:</h3> In the GGO group, macrophages (relatively +15.3 %) and B-lymphocytes (relatively +95.2 %) were significant higher compared to NSIP/UIP group. Neutrophils were significant lower (relatively -56.6%) in GGO group. No significant difference was observed between the groups for lymphocytes and T-cells (CD3+). Further, intraephithelial lymphocytes (CD4+CD103+) were significant increased (relatively +35.1%) and T-regular cells (CD4+CD25+CD103+) were significant reduced (relatively -26.3 %) in the GGO group. Regarding, T helper cells (CD3+CD4+) and cytotoxic T cells (CD3+CD8+) no significant difference between the GGO versus NSIP/UIP group was detected. <h3>Conclusion:</h3> The study present that at the onset of IRD with lLD is associat with an increase of B-lymphocytes and decrease of T-regular cells in GGO HRCT pattern. The reduction of T- regular cells in the immunological BAL is possibly associat with the IRD-ILD. Further studies should be initiated to verify these initial results. <h3>Funding:</h3> This study is a part of the Investigator Initiated study "Diagnostic procedures for detection of pulmonary manifestations at the onset of inflammatory rheumatic diseases (IRD)" which is supported by Boehringer Ingelheim Pharma GmbH &amp; Co. KG, Binger Str. 173, 55216 Ingelheim, Germany. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0814 SARCOPENIA AND SARCOPENIC OBESITY IN PRIMARY SJÖGREN’S SYNDROME
Authors: A. Alunno, E. Di Ruscio, S. Cappannari, M. E. Carugno, E. Matone, I. Olivieri, L. Serio, F. M. Mariani, P. Altieri, C. Ferri, F. Carubbi
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sarcopenia is defined as loss of skeletal muscle mass and function that generally occurs with ageing. It is commonly paralleled by relative or absolute body fat gain, identifying sarcopenic obesity (SO). SO is a strong and independent risk factor for frailty, comorbidities and mortality in the general and especially the older population (1-2). The SARC-F questionnaire is a validated screening tool to identify probable sarcopenic patients. The questionnaire screens patients for self-reported signs suggestive of sarcopenia, which include deficiencies in strength, walking, rising from a chair, climbing stairs, and experiencing falls. Each of the self-reported parameters receives a minimum and maximum score of 0 and 2, respectively, with the greatest maximum SARC-F score being 10 (validated cut-off value≥4). <h3>Objectives:</h3> To explore the burden of sarcopenia and SO in primary Sjögren's syndrome (pSS). <h3>Methods:</h3> Consecutive patients with pSS according to the 2016 ACR/EULAR classification criteria compiled the SARC-F questionnaire as well as other patient reported outcomes (e.g., VAS dryness). Demographic, clinical and serological data were also collected at enrollment. <h3>Results:</h3> 144 patients with pSS were recruited. Of these, 39 (27%) displayed a SARC-F score ≥4. SARC-F scores were directly correlated with BMI and among these 39 patients, 12 (31%) were also obese. Patients with higher SARC-F scores had a similar age and disease duration compared to those with SARC-F&lt;4 but they displayed higher values of VAS pain, VAS fatigue and VAS dryness (total and of individual domains) and as a consequence higher ESSPRI scores (Table 1). On the contrary disease activity (measured by ESSDAI) was comparable in the 2 groups. Individual ESSDAI domains were equally affected in the 2 groups except haematological manifestations that were more frequent in patients with SARC-F score ≥4 (odds ratio 5.7; 96% confidence interval 1.5-21.7). Previous use of glucocorticoids was not associated to higher SARC-F scores. According to the 2022 European Society for Clinical Nutrition and Metabolism (ESPEN) and European Association for the Study of Obesity (EASO) consensus (2) patients with SARC-F score≥4 are currently being assessed with additional tests such as strength tests as well as body composition assessment via bioelectrical impedance analysis to better characterize sarcopenia/SO. <h3>Conclusion:</h3> Sarcopenia/SO can affect a relevant proportion of patients with pSS and SO identifies a specific subset of pSS patients characterized by higher values of VAS pain, VAS fatigue and VAS dryness and, consequently, higher ESSPRI scores. <h3>REFERENCES:</h3> [1] Br J Nutr. 2021 Dec;126((11)):1749–57 [2] Obes Facts. 2022 May; 15(3): 321–335 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0726 CAN DEPLETION OF FAPα SYNOVIAL FIBROBLASTS LEAD TO AMELIORATION OF INFLAMMATORY ARTHRITIS?
Authors: C. I. Hsieh, H. Y. Chen, W. Y. Tseng, Y. J. Jan, Y. J. Huang, C. F. Kuo, K. H. Yu, P. H. Tsai, S. F. Luo
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Fibroblast activation protein α (FAPα) is a cell surface serine protease expressed by activated fibroblasts, and it was found that FAP-deficiency mice have less cartilage degradation, inflammation, and bone erosion. Moreover, the fibroblast-like synoviocytes from rheumatoid arthritis patients have higher expression of FAPα in synovium tissue. <h3>Objectives:</h3> We evaluated the ability of the <sup>68</sup>Ga-labelled FAPI as a diagnostic method for RA diagnosis. We also investigated that <sup>177</sup>Lu-labelled FAPI could lead to amelioration of RA by depletion of FAP<sup>+</sup> FLS and subsequent inhibition of lymphocyte function. <h3>Methods:</h3> The collagen-induced arthritis (CIA) DBA1/J mice were used as the inflammatory arthritis model. The images from <sup>68</sup>Ga-FAPI-04 PET/CT examinations of CIA mice were analyzed, and the tracer uptakes would be quantified by the standardized uptake value (SUV) and compared with the disease score and incidence rate. Then <sup>177</sup>Lu-labeled FAPI-04 was used to target FAPα-expressed cells in CIA mice as radiation therapy. <h3>Results:</h3> The paws in CIA mice with higher SUV since 1 week after booster immunization had a higher incidence rate of arthritis. The SUV also correlated with arthritis scores because the expression of FAPα increased in CIA mice. Moreover, the <sup>177</sup>Lu-labeled FAPI-04 treated group has a lower arthritis score compared with untreated CIA mice. <h3>Conclusion:</h3> We provide the basic features of FAPα- expressed FLSs in RA pathophysiology and advances in targeted therapies. We present that Ga<sup>68</sup>-FAPI-04 can be a useful tracer for predicting arthritis, and targeting to FAPα- expressed FLSs may be a potential way for arthritis treatment. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> This work was supported by grants from the Keelung Chang Gung Memorial Hospital, Taiwan, R.O.C. (CMRPG2K0172 and CMRPG2K0173) and NSTC-Granted Research Projects (NSTC 112-2314-B-182 -015 -MY3). <h3>Disclosure of Interests:</h3> <b>None declared.</b>