tbuckley/cabot-search huggingface dataset:
AB1162 A SELECTIVE AND ORALLY BIOAVAILABLE CXCR7 MODULATOR’S IMPACT ON BLEOMYCIN-INDUCED SKIN FIBROSIS IN A MOUSE MODEL
Authors: Y. Kim, Y. Lee, E. Chae
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by inflammation, vasculopathy, and fibrosis affecting the skin and internal organs. Despite advancements in understanding the pathogenesis and treatment of SSc, there is still a lack of established effective therapies for SSc-induced fibrosis. CXCR7, a typical chemokine receptor (ACKR3), is known to play a role in various diseases, including fibrosis, cancer, coronary artery disease, and inflammatory diseases. This study aims to investigate the relationship between CXCR7 and SSc. Given the insufficient exploration of CXCR7's role in systemic sclerosis, additional research is warranted. <h3>Objectives:</h3> Various animal models replicate specific aspects of systemic sclerosis (SSc). Our choice for this study is the experimental mouse model of bleomycin-induced skin fibrosis, commonly employed to investigate SSc-related pathogenesis. We identified a selective CXCR7 modulator and assessed its anti-fibrotic effects in other fibrotic diseases. This research aims to determine the therapeutic impact of our novel compound, a CXCR7 modulator, on bleomycin-induced skin fibrosis in a mouse model. <h3>Methods:</h3> Female C57BL/6 mice received subcutaneous injections of Bleomycin hydrochloride at a dose of 50 µg/mouse, in a volume of 50 µL every other day (Day 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26). The injection sites were situated at the corners of a 1.5 x 1.5 cm square shaved area. IL1512 was administered orally at doses of 30 and 60 mg/kg, po, while Imatinib was administered intraperitoneally at a dose of 50 mg/kg for 28 days. Following the conclusion of the dosing period, all animals were sacrificed, and pre-shaved skin samples were collected. Skin fibrosis was assessed through measurements of skin collagen content and staining with Hematoxylin/Eosin (HE) and Masson's trichrome. <h3>Results:</h3> In the disease control group, dermal thickness and the area stained with Masson's trichrome were significantly increased compared to the normal control group. However, treatment with IL1512 (30 and 60 mg/kg, po) and Imatinib (50 mg/kg, ip) mitigated the increase in skin thickness. Similarly, the area stained with Masson's trichrome in the IL1512 and Imatinib groups was reduced compared to the bleomycin-treated disease group. Moreover, the administration of IL1512 resulted in a notable, dose-dependent decrease in skin fibrosis compared to the disease control group. <h3>Conclusion:</h3> IL1512 demonstrated a potent efficacy equal to or greater than Imatinib in bleomycin-induced skin fibrosis mouse model. We propose that IL1512 as the first CXCR7 modulator may have therapeutic potential in Systemic sclerosis disease. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1490-HPR THE IMPACT OF DEPRESSION ON PATIENT-REPORTED SYMPTOMS AND PHYSICAL FUNCTIONING IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME
Authors: Ö. Öztürk, D. Şahin, Ö. Feyzioğlu, N. N. Uzun, F. Saritas, M. E. Tezcan
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sjögren's syndrome is associated with numerous extra-glandular symptoms such as fatigue, pain, and sleepiness, which can impact quality of life and are linked to depression. Additionally, Sjögren's syndrome patients with psychological symptoms may experience decreased physical activity levels, reduced therapy compliance, and loss of work productivity. Impaired function is associated symptoms such as pain, fatigue, and depression in patients with primary Sjögren's syndrome [1,2]. <h3>Objectives:</h3> To investigate the effects of depression on disease symptoms and physical functionality in patients with Sjögren's syndrome and determine the relationship between the depression, anxiety, patient-reported symptoms, and physical function. <h3>Methods:</h3> This cross-sectional multicentral study included patients with Sjögren's syndrome aged 20 to 70 years. The presence of psychological symptoms was determined using the Hospital Anxiety and Depression Scale (HADS). The EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) was utilized to assess severity of pain, fatigue, and dryness. The Health Assessment Questionnaire (HAQ) was employed to assess self-reported physical function. Patients were compared based on the presence of depression regarding disease symptoms and physical functionality. The possible correlations between HADS-depression, HADS-anxiety, ESSPRI scores, and HAQ score were investigated. <h3>Results:</h3> A total of 100 patients (96 female) with a mean age of 54.62±9.70 years and a mean disease duration of 5.70±4.49 years were included. According to HADS-depression and HADS-anxiety cut-off values (≥8), 42% and 36% of the patients had depression and anxiety, respectively. Comparison of patients with and without depression showed that more depressive symptoms resulted in poorer physical function, higher pain levels, and total symptom scores (p&lt;0.05). Fatigue and dryness symptoms did not differ regarding the presence of depression symptoms (p&gt;0.05) (Table 1). Additionally, there were significant correlations among ESSPRI-pain, ESSPRI fatigue, ESSPRI total score, HAQ, HADS-anxiety, and HADS-depression (p&lt;0.05) (Table 2). <h3>Conclusion:</h3> Nearly half of patients displayed increased depression levels associated with patient-reported symptoms and physical impairment. Therefore, addressing depression in patients with Sjögren's syndrome may positively impact their physical function and perceived symptoms. Understanding the relationship between depressive symptoms and physical impairment is crucial to enhancing the functional status of patients with Sjögren's syndrome. <h3>REFERENCES:</h3> [1] Hackett et al. Arthritis care &amp; research. 2012: 1760-1764. [2] Cui et al. BMC psychiatry. 2018: 1-8. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1140 DISEASE AND TREATMENT RELATED RISK FACTORS FOR INFECTION-RELATED HOSPITAL ADMISSIONS IN SLE PATIENTS: RETROSPECTIVE DATA FROM PADUA LUPUS COHORT
Authors: G. Hulej, C. Cruciani, F. Arru, F. Vesentini, Z. Rahme, I. A. Gennaio, M. Zen, A. Doria
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease requiring long-lasting immunosuppressive therapy. Both disease itself and therapy expose patients to infections, which represent a major cause of morbidity and mortality, as well as hospital admissions [1]. <h3>Objectives:</h3> The aim of this study was to evaluate the rate of infection-related hospital admissions (irHA) in a monocentric SLE cohort. Disease-related and treatment-related factors associated to irHA were analysed. <h3>Methods:</h3> We retrospectively analyzed data of patients with SLE perspectively collected who attended our outpatient clinic from 1990 to 2023. Follow-up data, comprising demographics, autoantibody profile, cumulative dose of glucocorticoids (GCs), GCs discontinuation (ever), immunosuppressive therapy, disease manifestations according to SLEDAI-2k items (ever), autoantibody profile, remission attainment (ever) were collected. Distribution of each data in the hospitalized and non-hospitalized subgroup were noted and their association to hospitalization was explored by univariate analyses. <h3>Results:</h3> 533 Caucasian patients with SLE were considered (mean±SD age 46±12.9 years, mean±SD disease duration 20±10 years). 142 irHA were recorded with an average of 0.27 (±0.629) admissions per patient per year. Among patients experiencing an irHA, cumulative dose of GCs was on average 25.68 g against 19.99 g in the non-hospitalized subgroup (p&lt;0.05). Hospitalized patients were significantly less likely to have stopped GCs at any point during the observation period (15% vs 85% respectively, p&lt;0.001). Remission attainment for at least 2 years did not significantly correlate with hospitalizations (p=0.1). Serositis and vasculitis were the only disease manifestations statistically associated to irHA (p=0.08 and p=0.015 respectively). Among immunosuppressive drugs, Rituximab was the only one significantly associated to an increased risk of irHA (p = 0.01). <h3>Conclusion:</h3> In our cohort of patients the rate of irHA was lower compared to that reported in literature. Reasons for this finding may relay on the less severe form of SLE that usually affect the Caucasian population and easy accessibility to Italian healthcare with respect to most other countries. GCs cumulative dose and Rituximab were associated to increase irHA, while GCs discontinuation was protective. The retrospective nature of our study represents a limitation to our findings. <h3>REFERENCES:</h3> [1] Zen M, Salmaso L, Barbiellini Amidei C, et al. Mortality and causes of death in systemic lupus erythematosus over the last decade: Data from a large population-based study. <i>Eur J Intern Med</i>. Epub February 2023. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
OP0333-PARE ONLINE PATIENT EDUCATION FOR AXIAL SPONDYLOARTHRITIS SELF-MANAGEMENT
Authors: Z. Clark
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The National Axial Spondyloarthritis Society (NASS) created Your SpAce as part of the Supported Self-management Programme for people living with axial spondyloarthritis (axial SpA). <h3>Objectives:</h3> Your SpAce aims to: educate people living with axial SpA about the condition; share self-management techniques to enable people to manage their symptoms; and reduce isolation felt by connecting them with other people with the condition. <h3>Methods:</h3> NASS ran consultations with people living with axial SpA and healthcare professionals (HCPs) involved in their care to develop a programme for people recently diagnosed, and those diagnosed longer who were currently struggling to manage or had previously not engaged with their condition. The consultation groups agreed that short, engaging videos covering pain, fatigue and flares, alongside lived experience videos and downloadable resources would be most effective. Content was co-produced with a steering group comprising 33% people with lived experience. Monthly online peer support meetings are held alongside the online content to build a community. <h3>Results:</h3> Launched in March 2023, Your SpAce comprises 14 videos and 5 downloadable resources. The videos are hosted on YouTube and have dedicated topic webpages on the NASS website, where the resources sit. The programme was advertised across NASS e-newsletter, member magazine, and social media channels. 124 HCPs ordered promotional packs to signpost their patients and partner organisations disseminated information. The webpages have been visited 22,331 times since launch. Your SpAce webpages ask visitors how confident they feel in managing their pain, flares, and fatigue out of 100 (0=not at all, 100=extremely). The results (862 respondents) indicate the programme is reaching people with low confidence, with 62% of pain poll respondents, 72% of fatigue poll respondents, and 73% of flare poll respondents ranking their confidence 0-40/100. Full results are shown in Table 1. <h3>Conclusion:</h3> Short videos with downloadable resources are an effective way to educate people living with axial SpA about the condition and share self-management techniques. The programme reaches people who are struggling to manage their symptoms and enables them to manage their symptoms and reduce feelings of isolation. NASS are currently developing two new Your SpAce modules. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1206 PROS AND CLINICAL ACTIVITY IN PATIENTS WITH SYSTEMIC SCLEROSIS IN REAL CLINICAL PRACTICE
Authors: J. E. Oller Rodríguez, E. Grau García, C. Riesco Barcena, M. De la Rubia Navarro, L. Mas Sanchez, D. Ramos Castro, S. Leal Rodriguez, A. M. Torrat Noves, P. Muñoz Martínez, A. V. Huaylla Quispe, I. Alcántara Álvarez, B. Villanueva Mañes, I. Martínez Cordellat, I. Cánovas Olmos, H. Charia, L. Gonzalez Puig, J. Ivorra Cortés, C. Nájera Herranz, R. Negueroles Albuixech, E. Tovar-Sugrañes, E. Vicens Bernabeu, J. A. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Although the utility of PROs (Patient-Reported Outcomes) has been demonstrated in various systemic autoimmune diseases, including Systemic Sclerosis, there appears to be a lack of data on some PROs in clinical practice for this disease. <h3>Objectives:</h3> Description of data derived from Patient-Reported Outcomes (PROs) in patients with Systemic Sclerosis (SSc) in real clinical practice. <h3>Methods:</h3> We conducted a single-center cross-sectional and descriptive study of patients diagnosed with SSc (ACR-EULAR 2013 criteria). Clinical evaluation of patients was conducted, and they systematically completed the Spanish version of the SF36 quality of life questionnaire, as well as the HAQ (Health Assessment Questionnaire) and CHFS (Cochin Hand Function Scale) questionnaires, which assess functional disability. In addition, Rodnan index, EUSTAR activity index, and Medsger severity scale were calculated. <h3>Results:</h3> A total of 42 patients with SSc were included, with a mean EUSTAR index score of 4.93 (1.45) points, a mean value of 4.8 on the Rodnan scale, and an average value of 4.05 on the Medsger scale. Regarding PROs, in the SF36 quality of life questionnaire, an average score of 51 (29.5) was obtained, and in the HAQ questionnaire, a mean score of 0.78 points, with 64% of patients scoring below 1. The average CHFS score was 14.29 out of a maximum of 90 points, with 71% of cases scoring below 18 points. We observed a statistically significant association between disease severity according to the Medsger scale and hand functional disability assessed through CHFS (P=0.03). A statistically significant association was also found between increased skin thickening according to the Rodnan index and a higher perception of quality of life by SF36 (P=0.03) and a higher perception of disability in both the CHFS scale (P=0.02) and the HAQ (P=0.03). <h3>Conclusion:</h3> An association was observed between the results obtained with PROs and the assessment of disease activity and severity in patients with Systemic Sclerosis. The role of PROs in the disease can assist us in the management of our patients. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1157 PTGDS REGULATES PRO-INFLAMMATORY FIBROBLASTS AND CHEMOTAXIS OF MACROPHAGES TO PROMOTE SKIN FIBROSIS IN SYSTEMIC SCLEROSIS
Authors: R. Mu, D. Fang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Immune dysregulation plays a crucial role in the pathogenesis of systemic sclerosis (SSc)[1]. Lipocalin-type prostaglandin D synthase (PTGDS), which participates in immune regulation through the synthesis of prostaglandin D2 (PGD2), is associated with autoimmunity and fibrosis[2]. However, the expression, mechanism of action, and pathogenic role of PTGDS in SSc remain unclear. <h3>Objectives:</h3> This study aims to explore the role and potential mechanisms of PTGDS in SSc. <h3>Methods:</h3> The expression of PTGDS in the skin tissues and dermal fibroblasts of SSc patients was analyzed based on GEO data and confirmed through immunohistochemistry, qPCR, and western blotting. The role of PTGDS in inflammation and fibrosis was investigated using a PTGDS-overexpression vector and inhibitor (AT56) in dermal fibroblasts. The pathogenic role of PTGDS in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse model of skin inflammation and fibrosis. <h3>Results:</h3> PTGDS levels were significantly elevated in the skin tissues and dermal fibroblasts of SSc patients, correlating with the severity of skin fibrosis. In vitro studies, overexpression of PTGDS upregulated CCL2, IL-6, IL32, CCL8, CCL13, and CCL19 in dermal fibroblasts. Mechanistically, PTGDS induced senescence of dermal fibroblasts in a P53-P21 pathway-dependent manner, leading to increased secretion of cytokines, chemotaxis of macrophage infiltration and differentiation, activation of surrounding fibroblasts, and enhanced ECM deposition. Oral administration of the inhibitor AT56 significantly reduced BLM-induced skin inflammation and fibrosis in vivo. <h3>Conclusion:</h3> PTGDS could be a promising therapeutic target for improving treatment strategies for skin inflammation and fibrosis in SSc. [1] Fang, D., et al., <i>Immune cell dysregulation as a mediator of fibrosis in systemic sclerosis.</i> Nat Rev Rheumatol, 2022. <b>18</b>(12): p. 683-693. [2] Ito, H., et al., <i>PGD2-CRTH2 pathway promotes tubulointerstitial fibrosis.</i> J Am Soc Nephrol, 2012. <b>23</b>(11): p. 1797-809. <h3>REFERENCES: Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
<i>odd-paired</i> is involved in morphological divergence of snail-feeding beetles
Authors: Junji Konuma, Tomochika Fujisawa, Tomoaki Nishiyama, Masahiro Kasahara, Tomoko F Shibata, Masafumi Nozawa, Shuji Shigenobu, Atsushi Toyoda, Mitsuyasu Hasebe, Teiji Sota
Journal: Molecular Biology and Evolution (2024)

Abstract Body shape and size diversity and their evolutionary rates correlate with species richness at the macroevolutionary scale. However, the molecular genetic mechanisms underlying the morphological diversification across related species are poorly understood. In beetles, which account for one-fourth of the known species, adaptation to different trophic niches through morphological diversification appears to have contributed to species radiation. Here, we explored the key genes for the morphological divergence of the slender to stout body shape related to divergent feeding methods on large to small snails within the genus Carabus. We show that the zinc-finger transcription factor encoded by odd-paired (opa) controls morphological variation in the snail-feeding ground beetle Carabus blaptoides. Specifically, opa was identified as the gene underlying the slender to stout morphological difference between subspecies through genetic mapping and functional analysis via gene knockdown. Further analyses revealed that changes in opa cis-regulatory sequences likely contributed to the differences in body shape and size between C. blaptoides subspecies. Among opa cis-regulatory sequences, single nucleotide polymorphisms on the transcription factor binding sites may be associated with the morphological differences between C. blaptoides subspecies. opa was highly conserved in a wide range of taxa, especially in beetles. Therefore, opa may play an important role in adaptive morphological divergence in beetles.
AB0580 THE USE OF CONTRACEPTIVE METHODS IN WOMEN WITH RHEUMATOID ARTHRITIS- RESULTS FROM RevNatus
Authors: H. Koksvik, B. Jakobsen, I. R. Nilssen, M. Wallenius
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Contraception is an important area of reproductive health for patients with rheumatic diseases given the potential pregnancy risk associated with active disease, teratogenic medications and disease related damage. <h3>Objectives:</h3> To describe the use of contraceptive methods at 12 months post- partum in women with rheumatoid arthritis (RA). <h3>Methods:</h3> We prospectively collected self- reported data on contraceptive methods in women with RA one year post-partum, through the nationwide Norwegian registry on pregnancy and rheumatic diseases (RevNatus) from 2016-2023. All women were diagnosed by a rheumatologist with ICD-10 codes M05.8, M05.9 or M06.0. The use of contraception in 296 women with RA was recorded. Contraceptive methods were classified by relative efficacy based on World Health Organization categories. Highly effective methods: intrauterine devices (IUDs), implants and surgical sterilization. Moderately effective methods: hormonal methods (i.e. oral contraceptive pill, patches, vaginal rings and injections). Ineffective methods: condoms, withdrawal and emergency pill. Medications used at 12 months after delivery were classified by FDA medication pregnancy risk category with A/B/C low risk and D/X high risk. The only drug used in category D/X was methotrexate. <h3>Results:</h3> Mean age was 34 years, (SD= 5). Mean disease duration was 7 years (SD= 4), and mean disease activity measured by DAS28(3)CRP was 2.3 (SD= 0.8). Of the 45 patients who used methotrexate, 28 % used none- or ineffective contraceptive methods. 30 % of the women did not use any contraceptive methods at all, with only 5 % reporting a pregnancy wish. 12.5 % of the women were lactating 12 months postpartum. <b>Table 1.</b> Drug use and effectiveness of contraceptive methods <h3>Conclusion:</h3> Many patients using methotrexate did not use reliable contraceptive method. This suggest that contraceptive use and counseling can be implemented more frequently in women with RA. The study emphasizes the need for increased discussion of contraception for women with RA not desiring pregnancy. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0575 RELATIONSHIP BETWEEN EGO STATE, DISEASE ACTIVITY, AND ACTIVITY OF DAILY LIVING IN RHEUMATOID ARTHRITIS PATIENTS: USING THE UNIVERSITY OF TOKYO EGOGRAM VERSION II (TEG-II)
Authors: Y. Miwa, Y. Miwa, M. Hosaka
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Although there have been several previous reports on the personality patterns of rheumatoid arthritis (RA) patients and their habits and tendencies in thinking, feeling, and behaving when interacting with others (ego state), there have been no new research reports in the last ten years. During this period, the treatment outcome of RA has improved, and changes in ego states are expected. <h3>Objectives:</h3> This study investigated the relationship between ego state, disease activity, and activity of daily living (ADL) in RA patients. <h3>Methods:</h3> 151 RA patients attending outpatient clinics at Showa University Hospital and Showa University Northern Yokohama Hospital who agreed to participate in this study were included. The patient background had age, gender, type of DMARDs, and prednisolone use; the simplified disease activity index (SDAI) was used to assess RA disease activity, and the health assessment questionnaire (HAQ) was used to determine ADL. The University of Tokyo Egogram (TEG-II) was to evaluate ego status; the TEG-II consists of pattern categories and types from critical parental ego (CP), nurturing parental ego (NP), adult ego (A), free child ego (FC), and submissive child ego (AC). The scores for each item were evaluated, and associations with SDAI, HAQ, and gender were examined. <h3>Results:</h3> The AC was the highest (11.10 points), followed by FC (9.83 points), A (9.76 points), CP (9.31 points), and NP (8.32 points) on the TEG-II for all the subject patients. The pattern classification showed that the AC-dominant type was the most common (72 patients, 44.7%), with no significant difference in HAQ remission (&lt;0.5) and non-remission, low disease activity (SDAI≤11) and SDAI&gt;11, nor in gender. Binomial logistic analysis with AC dominance as the objective variable showed only lower CP (odds ratio: 0.687; 95%CI: 0.590-0.800) and lower NP (odds ratio: 0.890; 95%CI: 0.812-0.975). <h3>Conclusion:</h3> In previous reports, TEG-II in RA patients was predominantly NP, but in the present study, AC was predominant. The behavioral pattern was inferred to be cooperative, honest, able to listen to other's opinions and patient, but loose, lax, lacking discipline, inconsistent thought and action, and poor planning. The results may be influenced by improving rheumatoid arthritis performance and decreased disease activity. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>