tbuckley/cabot-search huggingface dataset:
POS1046 METHOTREXATE REDUCES THE RISK OF SEVERE FORMS OF DENGUE IN PATIENTS WITH RHEUMATOID ARTHRITIS. PROSPECTIVE OBSERVATIONAL STUDY IN A PERUVIAN TERTIARY HOSPITAL
Authors: F. Liñán Ponce, J. Leiva Goicochea, P. Jauregui Rojas, D. Sevilla Rodriguez, C. Leiva Rodriguez, E. Hidalgo Bravo, G. Obregon Atanacio, I. Loyola Macalapú
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> It is known that methotrexate is effective in joint involvement caused by the Zika and chikungunya viruses, but its effect on patients with rheumatoid arthritis infected with dengue is unknown. <h3>Objectives:</h3> To analyze the existing relationship between dengue severity according to the disease-modifying antirheumatic drug used in patients with rheumatoid arthritis. <h3>Methods:</h3> Prospective observational study. The sample was made up of 120 patients with rheumatoid arthritis infected by the dengue virus: 60 users of methotrexate and 60 users of others (leflunomide: 40, sulfasalazine: 14, hydroxychloroquine: 6), then the cases of classic and severe dengue were counted. in both groups. The Chi square test was used to relate the study variables. <h3>Results:</h3> Patients using methotrexate presented a lower percentage of severe dengue with a shorter duration of illness compared to the group of other drugs. No differences were found in terms of AR activity during dengue infection in both groups. <h3>Conclusion:</h3> Methotrexate reduces the risk of severe forms of dengue in patients with rheumatoid arthritis. <h3>REFERENCES:</h3> [1] Romão VC, Fonseca JE. Etiology and risk factors for rheumatoid arthritis: A state-of-the-art review. Front Med (Lausanne) [Internet]. 2021 [cited June 22, 2023];8. Available at: https://pubmed.ncbi.nlm.nih.gov/34901047/ [2] Lin Y-J, Anzaghe M, Schülke S. Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis. Cells [Internet]. 2020 [cited 2023 June 22];9(4):880. Available at: http://dx.doi.org/10.3390/cells9040880 [3] Qian X, Qi Z. Mosquito-borne flaviviruses and current therapeutic advances. Viruses [Internet]. 2022 [cited 2023 June 22];14(6):1226. Available at: https://pubmed.ncbi.nlm.nih.gov/35746697/ <h3>Acknowledgements:</h3> To doctors Ovidio Villena and Fernando Gross, who provided all the facilities to carry out this work. <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1523 TUBERCULOSIS UNDER BIOTHERAPY IN CHRONIC INFLAMMATORY RHEUMATISMS: A COHORT STUDY
Authors: S. Zaher, K. Nassar, A. Ajerouassi, S. Janani
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Biological agents have revolutionized the management of chronic inflammatory rheumatisms (CIR), significantly improving patients' quality of life. However, this advancement is not without risks, and the emergence of tuberculosis as an adverse effect is a growing concern, particularly in endemic regions. <h3>Objectives:</h3> Our study aims to assess the frequency of tuberculosis in the context of chronic inflammatory rheumatisms, along with the clinical and paraclinical profile of affected patients. <h3>Methods:</h3> Cohort Study with Retrospective Data Collection on Patients with CIR over a 5-Year Period from January 2018 to January 2023. The cohort includes patients monitored for rheumatoid arthritis and spondylarthritis based on ACR 2010 and ASAS criteria, respectively, who have been administered biological agents. All patients underwent epidemiological, clinical, and paraclinical assessments (QuantiFERON test and chest X-ray) before starting biologic therapy. Patients with a positive QuantiFERON test received chemoprophylaxis according to the national protocol. Patient data were collected and analyzed. <h3>Results:</h3> We included 134 patients monitored for Chronic Inflammatory Rheumatisms (81 RA/52 SA). The female-to-male ratio was 1.3. The mean age was 44 years (±15.5). The average disease duration was 15 years (±7.96). No recent tuberculosis exposure (&lt;6 months) was observed. Six cases of tuberculosis were identified under biologic therapy, with a frequency of 4%. We noted 2 cases of miliary pulmonary tuberculosis, 2 cases of gastrointestinal tuberculosis, one case of neuro-meningeal tuberculosis, and one case of lymph node tuberculosis. The average diagnostic delay for tuberculosis is 28 weeks. All tuberculosis cases occurred under Anti-TNF therapy: 5 cases with Infliximab and one case with Adalimumab. The clinical presentation of tuberculosis in our series was marked by general malaise in all patients, cough in 2 cases, digestive symptoms in 2 cases, and cauda equina syndrome in one case. The diagnosis was confirmed by bacteriological testing in 3 cases, histopathological examination in 2 cases, and clinical-radiological findings in one patient. All patients received anti-tubercular drugs according to the national protocol, with favorable outcomes in 4 cases and fatal outcomes in 2 patients. <h3>Conclusion:</h3> The frequency of tuberculosis under biologic therapy, although relatively low at 4% in our study, nevertheless underscores the need for close monitoring and thorough pre-treatment assessment before initiating this type of therapy. The results demonstrate that, despite precautions taken, cases of tuberculosis can occur, highlighting the complexity of managing this population of immunocompromised patients. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1003 SPATIAL ANALYSIS OF HUMAN SUBMANDIBULAR GLANDS REVEAL NEUTROPHILS ORGANIZED IN TERTIARY LYMPHOID STRUCTURES OF SIALADENITIS
Authors: L. Munoz, C. Reichardt, M. Munoz-Becerra, A. Rigau, X. Shan, G. Schett, M. Eckstein
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Inflammatory infiltrates of submandibular glands are commonly found during acute and chronic sialadenitis. The type of infiltrates dictates the pathological diagnosis. <h3>Objectives:</h3> We sought to investigate the architecture of leukocyte infiltrates of human submandibular glands (SMG) with obstructive sialadenitis (OS), IgG4 sialadenitis (IgG4) and Sjögren sialadenitis by high-dimensional image mass cytometry (IMC) with especial focus on the spatial organization of single cell types. <h3>Methods:</h3> Formalin fixed paraffin embedded human SMG specimens were arranged in 6mm tissue microarrays and stained with a panel of 15 metal labelled antibodies for IMC analyses. Briefly, Hyperion imaging system was used to retrieve signals from each mass channel including iridium 191 for DNA (Figure 1). Multiplexed images were saved as Mathcad files and exported as individual ome.tiff images using the MCD viewer software. Tiff stacks were done with the Image-J software. Single cell masks were generated with the Steinbock Docker Container employing a deep-learning based image segmentation with the option Mesmer of DeepCell. The information of segmented cells was stored in a SpatialExperiment object, which was then used for graph construction, spatial visualization, and spatial analysis. In order to visualize the location and interactions among cells, an expansion interaction graph based on the centroids of the cells was constructed with a threshold = 15 using the buildSpatialGraph function. The cytomapper R package provides the cytomapperShiny function that allows gating of cells based on their marker expression and visualization of selected cells directly on the images. <h3>Results:</h3> Standard histopathological examinations reveal distinctive features of sialadenitis cases, including periductal inflammation, acinar atrophy, and various degrees of chronic inflammation and fibrosis. The multiplexed immunostaining allowed a deep characterization of immune cell infiltrates, highlighting the involvement of various immune components. We have identified 10 cell types based on the pattern of expression of immune markers. The most striking finding was the quantification and visualization of various cell-cell interactions with regard of each cell type. Importantly, we found a significant amount of neutrophils organized in tertiary lymphoid infiltrates of both IgG4 and Sjögren sialadenitis (Figure 2). <h3>Conclusion:</h3> A thorough understanding of the pathological intricacies of sialadenitis in human submandibular glands is vital for a better understanding of supportive role of innate immune cells at tertiary lymphoid structures of autoimmune diseases. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1241 RELIABILITY OF HISTOPATHOLOGICAL SALIVARY GLAND BIOPSY ASSESSMENT IN SJÖGREN’S DISEASE
Authors: C. Xavier, D. Calderaro, S. Araújo, L. A. Tanure, G. Resende, D. Wanderley, G. A. Ferreira
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Diagnosis of Sjogren's disease relies on a combination of clinical and laboratory findings. Minor Salivary Gland biopsy (MSGB) abnormalities hold significant relevance within the diagnostic framework. However, previous research has noted limited concordance with MSGB assessments, attributed to variations in histological criteria and underestimation of characteristics such as focus score (FS) and germinal centers. <h3>Objectives:</h3> This study aimed to assess the interobserver and intraobserver reliability of MSGB analysis, using the recommendations published by the EULAR group in 2017. <h3>Methods:</h3> The intra and interobserver reproducibility of MSGB of 196 adult patients, aged ≥18, with suspicion of Sjogren's disease was analyzed by two pathologists. Examiner A (ExA) reviewed the slides twice, with a two-month gap, using a standardized blind procedure. Examiner B (ExB) assessed 115 slides randomly. ExA's first-round assessments were compared with the routine examiners (ExR) and ExB (interobserver analysis), and with the second-round assessments (intraobserver analysis). All pathologists, including ExR, underwent prior training for MSGB analysis following the EULAR 2017 recommendations. Agreement of the pathologists on qualitative variables was analyzed using the Kappa coefficient. For quantitative FS agreement, the Intraclass Correlation Coefficient (ICC) was calculated. <h3>Results:</h3> Overall, interobserver and intraobserver analyses showed good agreement (k ≥ 0.6) for area, dichotomized FS (presence or absence of FS ≥ 1), and histological diagnosis of focal lymphocytic sialadenitis. Conversely, assessment of structural damage indicated only modest to fair agreement (k ≤ 0.4) for interobserver reliability. A comparable pattern, although with higher values, was seen in the intraobserver analysis. Table 1 depicts the results for each parameter. The ICC for FS was 0.71 (95% CI 0.63-0.77) when comparing the ExR and ExA evaluations, 0.86 (95% CI 0.77-0.91) when comparing the ExA and ExB evaluations, and 0.93 (95% CI 0.91-0.95) for the intraobserver evaluation (ExA-ExA). <h3>Conclusion:</h3> In this single-center cross-sectional study, inter and intraobserver reliability exhibited favorable levels for histological diagnosis of focal lymphocytic sialadenitis, while reliability for estimating structural damage was comparatively lower. This discrepancy may be the result of less preparation of pathologists for assessing damage, compared to the assessment of inflammatory alterations. Imperatively improving the reliability of MSBG requires the establishment of robust standardization of histopathological assessment and comprehensive training of pathologists. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
OP0079 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-AND-TOCILIZUMAB CONTROLLED PHASE II TRIAL OF VDJ-001, A HIGH-AFFINITY IL-6R ANTAGONIST ANTIBODY, FOR THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: H. Ye
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Objectives:</h3> VDJ-001 is a novel humanized IgG1 monoclonal antibody designed to enhance the therapeutic index of Tocilizumab. Based on a random B-cell hyper-mutation and display technology, which mimics the native mechanism of antibody affinity maturation <i>in vivo,</i> VDJ-001 has been selected for its higher-affinity and more potent biological activities in comparison with Tocilizumab. The present study is to assess the comparative efficacy and safety of VDJ-001 in patients with rheumatoid arthritis following its pre-clinical and early clinical evaluation. <h3>Methods:</h3> In this double-blind, placebo and positive drug-controlled phase II study, 180 adult patients with moderate-to-severe active rheumatoid arthritis who had inadequate response to methotrexate (MTX) were randomly assigned to 4-treatment arms in 1:1:1:1 ratio, i.e., 4 mg/kg and 6 mg/kg of VDJ-001, 8 mg/kg of Tocilizumab, or placebo, i.v. q4w. All patients also received standard dose of methotrexate treatment. The primary endpoint was to compare the proportion of patients achieving ACR20 response at week 12; while secondary endpoint included the comparative analysis of patients achieving ACR50 and ACR70 responses at week 12 (NCT05957107, CTR20220613). <h3>Results:</h3> Both doses of VDJ-001 are safe and well-tolerated in 90 patients, most of them with low grade I-II of adverse reaction. Their safety profile is similar to Tocilizumab arm, which could be managed very well even during Covid-19 restriction period. In comparison with placebo arm (&lt;60% responders), patients treated with both doses of VDJ-001 and Tocilizumab all reached a similar significant efficacy (p&lt;0.05) on ACR20 response (&gt;80% responders). Moreover, a clear trend on the potency ranking has been observed on ACR50/70 responders, i.e. VDJ-001 6mg/kg (64.3%) &gt; Tocilizumab 8mg/kg (55.8%) &gt; VDJ-001 4mg/kg (42.9%) &gt; placebo (8.1%) for ACR50 responders; while VDJ-001 6mg/kg (33.3%) &gt; Tocilizumab 8mg/kg (25.6%) &gt; VDJ-001 4mg/kg (16.7%) &gt; placebo (0%) for ACR70 response rates. There is a good correlation between pharmacokinetics and pharmacodynamics (sIL-6R) of VDJ-001 and Tocilizumab in a dose-dependent manner; while the disease biomarker change (ESR) is highly correlated with their corresponding efficacy. <h3>Conclusion:</h3> VDJ-001 is safe and effective in patients with rheumatoid arthritis. Its higher affinity and higher biological activity seem to be associated with the tendency of higher efficacy. The highly competitive rate (33.3%) on ACR70 response makes VDJ-001 6 mg/kg one of the best treatment options for RA patients. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Beijing VDJBio Co., Ltd. <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0129-HPR ASSOCIATION BETWEEN DEPRESSION AND OUTCOME REGARDING PAIN AFTER PARTICIPATION IN A FIRST-LINE INTERVENTION PROGRAM FOR KNEE AND HIP OSTEOARTHRITIS. A STUDY FROM THE SWEDISH OSTEOARTHRITIS REGISTER
Authors: K. Gustafsson, J. Kvist, T. Jönsson, M. Eriksson, O. Rolfson
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Depression has been shown to contribute to poorer patient-reported outcomes after joint replacement surgery in patients with knee and hip osteoarthritis (OA). However, it is not known how depression before participation in a first-line intervention OA program affects the outcome of the intervention. <h3>Objectives:</h3> To evaluate if medically treated depression, identified before participation in first-line intervention, is associated with poorer outcome regarding pain after the intervention among patients with knee and/or hip OA. <h3>Methods:</h3> In this longitudinal observational register-based cohort study, we included 44,311 patients who had participated in a first-line OA intervention program including patient education and exercise. All data was extracted from the Swedish Osteoarthritis Register between 2008 and 2016. Patients were stratified by most affected joint into a knee OA- and a hip OA cohort. Multiple logistic regression was used to assess the association between medically treated depression during the 3 years before baseline and patient-reported deterioration in pain (≥2 on a numeric rating scale) from baseline to the 3-month follow-up after participation in the first-line OA intervention program. We adjusted for baseline variables; age, sex, educational level, pain intensity, BMI, Charnley score, supervised exercises and desire for surgery. <h3>Results:</h3> Sixteen percent (n=2,224/13,787) of patients with knee OA and 16% (n=4,968/30,524) of patients with hip OA had medically treated depression before participation in the first-line OA intervention program. The adjusted analyses showed an association between depression and deterioration in pain after participating in first-line OA intervention for patients with knee OA (OR; 1.25 [95% CI, 1.11-1.40], but no statistically significant association was found in patients with hip OA (OR; 1.10 [95% CI, 0.94-1.29]). <h3>Conclusion:</h3> Poorer outcome regarding pain after 3-months participation in a first-line OA intervention program was influenced by having medically treated depression before inclusion in the program, in patients with knee OA but not in patients with hip OA. To optimize the use of health care resources, future research should focus on identifying what support patients with knee OA and depression need to improve the results from a first-line OA intervention. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Kristin Gustafsson: None declared, Joanna Kvist: None declared, Therese Jönsson: None declared, Marit Eriksson: None declared, Ola Rolfson Novartis (advisor board), AstraZenica (reaearch advisor), Pfizer (institutional research support as PI).
OP0191 DOMINATING PREVALENCE OF CALCIUMPYROPHOSPHAT (CPP) CRYSTALS AMONG INFLAMMATORY SYNOVIAL FLUID SAMPLES IN AN UNBIASED ANALYSIS AT THE LARGEST SWISS TERTIARY CENTER
Authors: T. Manigold, A. B. Leichtle
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Crystal arthritides mainly comprise of gout and calciumpyrophosphat (CPP) Deposition Disease, known as CPPD or pseudogout. The prevalence, medical and socioeconomic impact of gouty arthritis is well recognized and estimated to affect 5% of the population in developed countries. However, while chondrocalcinosis, a non-pathogenic deposition of CPP crystals in cartilage, shows a high and increasing prevalence in persons over 60 years, the prevalence of CPP arthritis in daily practice remains unclear. <h3>Objectives:</h3> We herein sought to assess the unbiased prevalences of crystal and crystal arthritides in synovial fluid (SF) samples at the largest hospital in Switzerland. <h3>Methods:</h3> We included SF samples, obtained between 2015-2023 at the University hospital Bern (Inselspital), the largest hospital in Switzerland. Samples from all Departments were considered and analyzed, irrespectively of the indication for arthrocentesis and final diagnosis. Crystal analysis was performed by rheumatologists and specifically trained lab personnel. Crystals were assessed based according to negative (MSU) or positive (CPP) birefringence under polarized light as well as positive staining with alizarin red (BCP) under ordinary light microscopy. All results were documented in a semiquantitative manner (little, moderate, massive). In parallel, leucocyte counts including fractions of mononuclear and polynuclear were assessed in most SF samples. <h3>Results:</h3> We analyzed 4777 samples from 3239 patients. Crystals were found in 39.2% of all samples, with CPP being detected in 59.3%, while 40.7% were positive for MSU. As for BCP 9.3% of samples stained positive for alizarin red. Cell numbers in SF were available in 2899 samples, among which 1703 (58.7%) were classified as inflammatory (&gt;2000 cells/ul), and 1196 (41.3%) as non-inflammatory (&lt;2000 cells/ul). Among inflammatory samples 38.5% were crystal positive, with CPP predominating with 58.4% versus 41.6% MSU, whereas 7.3% of samples stained positive for BCP crystals. Neither the mean of total leucocyte numbers nor the yields of polynuclear cells were significantly different between MSU and CPP positive samples. <h3>Conclusion:</h3> Contrary to the general belief that gout is the most common form of crystal arthritis, our data indicate that CPP arthritis may in fact be the most common cause among multimorbid patients at a tertiary center. To our knowledge this is the largest study assessing the unbiased prevalence of crystals in in SF. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Tobias Manigold Hoffmann LaRoche, Janssen, Novartis, Hoffman-LaRoche, Novartis, Hoffmann-LaRoche, Hoffmann LaRoche, Janssen, Novartis, EliLilly, Hoffmann LaRoche, Sandoz, Alexander Benedikt Leichtle: None declared.
POS1178 ASSOCIATIONS BETWEEN ALTERED GUT MICROBIOME, METABOLITES, AND HLA-B27 POSITIVITY IN PATIENT WITH ANKYLOSING SPONDYLITIS
Authors: T. Huang, Y. Chen, X. Wang, H. Yang, L. Zhang, K. Hashimoto, Y. Luo, Y. Pu, Y. Liu
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Ankylosing spondylitis (AS) is an autoimmune disorder linked to the human leukocyte antigen B27 (HLA-B27) gene. While the abnormal composition of the gut microbiome and its related disturbed metabolites may co-contribute to AS, the relationship between HLA-B27, the gut microbiota, and their metabolites in AS patients is still largely uncharted. <h3>Objectives:</h3> We sought to further investigate the relationship between HLA-B27, the gut microbiota, and their metabolites in AS patients. <h3>Methods:</h3> We conducted an integrated analysis of the gut microbiome and metabolome, examining 88 fecal samples across three groups: HLA-B27-positive AS patients (n = 28), HLA-B27-positive healthy controls (n = 30), and HLA-B27-negative healthy controls (n = 30) (Table 1). <h3>Results:</h3> Our analysis uncovered disturbances in the gut microbiome and fecal metabolites in HLA-B27-positive participants, particularly in those diagnosed with AS. We identified 40 species displaying gradual changes in relative abundance across the three groups. Metabolome profiling, when coupled with microbial functional analysis, revealed three compromised pathways of amino acid metabolism within AS, including tryptophan metabolism, cysteine metabolism, and biosynthesis of branched-chain amino acids, ornithine, and lysine. By employing correlation networks between differential bacterial species, fecal metabolites, and clinical parameters in AS, we identified several novel AS-associated species and metabolites, including <i>Negativibacillus massiliensis, Bacteroidetes bacterium 41-46, Lachnospiraceae bacterium oral taxon 082, N</i>-acetylornithine, and tridecanedioic acid (Figure 1). These AS-associated features showed a high degree of accuracy in differentiating AS from HLA-B27-positive and negative healthy controls. <h3>Conclusion:</h3> Our results imply that HLA-B27 may contribute to the onset of AS through its impact on the abnormal gut microbiome, and the disturbance of microbiota-driven metabolites in the presence of HLA-B27 may influence the development of AS in this population. Ultimately, this study opens promising paths for creating innovative therapeutic strategies to address AS. <h3></h3> <b>Table 1.</b> Demographic and clinical characteristics of the participants <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>