Abstract Background Ankylosing Spondylitis (AS) patients face several challenges due to the nature of the disease and its physical and psychological complications. Sleep disorders are among the most important concerns. Sleep disorders can aggravate the signs and symptoms of the disease and ultimately reduce the quality of patients’ lives. This study uses a systematic review and meta-analysis to pool the reported prevalence of sleep disorders among AS patients. Methods To find related studies, the WoS, PubMed, ScienceDirect, Scopus, Embase, and Google Scholar databases were systematically searched without a lower time limit. Heterogeneity among the identified studies was checked using the I2 index, and the Begg and Mazumdar correlation test examined the existence of published bias. Comprehensive Meta-Analysis (v.2) software was adopted to analyze the data. Results In the review of 18 studies with a sample size of 5,840, the overall pooled prevalence of sleep disorders among AS patients based on the random effects method was found to be 53% (95% CI: 44.9–61). The highest and lowest prevalence was in Egypt at 90% and Australia at 19.2%, respectively. Our meta-regression results show that with the increase in ‘sample size’ and ‘year of publication’, the overall prevalence of sleep disorders in patients with AS decreases (p < 0.05). Conclusion The results of the present study indicate a high and significant prevalence of sleep disorders among AS patients. Thus, health policymakers and healthcare providers must focus on timely diagnosis and effective educational and therapeutic interventions for the prevention and proper treatment of sleep disorders in this population of patients.

Abstract Background Gout is a common inflammatory arthritis caused by increased serum uric acid levels. Untreated or insufficiently treated gout can lead to deposition of monosodium urate crystals in joints, cartilage, and kidneys. Although Tongfengding capsules, a Chinese patent medicine, have long been used to treat gout, their effects and safety have not been reviewed systematically. This study evaluated its efficacy and safety for gout in adults. Methods Randomized controlled trials involving Tongfengding capsule for gout in adults were searched from PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CBM, CNKI, and VIP databases, and analyzed using the Cochrane Handbook criteria. The primary outcome measures were the total effective rate. The secondary outcome measures including the blood uric acid (BUA), 24-h urinary total protein (24-h UTP), blood urea nitrogen (BUN), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and adverse effects. The risk of bias was evaluated in all included studies. RevMan ver. 5.3.5 and GRADE profiler was used for data analysis and assessing the quality of evidence, respectively. Results Six studies (n = 607 Chinese participants) were included. Tongfengding capsules plus conventional treatment significantly increased the total effective rate (RR 1.21, 95% CI 1.11–1.33), while reducing the BUA (MD − 66.05 μmol/L, 95% CI − 81.26 to − 50.84), 24-h UTP (MD − 0.83 g/24 h, 95% CI − 0.96 to − 0.70), BUN (MD − 0.90 mmol/L, 95% CI − 1.60 to − 0.20), IL-6 (MD − 6.99 ng/L, 95% CI − 13.22 to − 0.75), IL-8 (MD − 12.17 ng/L, 95% CI − 18.07 to − 6.27), TNF-α (MD − 8.50 ng/L, 95% CI − 15.50 to − 1.51), and adverse effects (RR 0.21, 95% CI 0.04–0.95). Conclusion Tongfengding capsules plus conventional treatment is safe and beneficial for adults with gout compared with conventional treatment.

Abstract Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22–2.31; HR: 2.28, 95% CI 1.50–3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20–4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06–0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Abstract Background The importance of proinflammatory T-cells and their cytokine production in patients with autoimmune arthritis has been widely described. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have come into focus as a potential therapeutic concept. The aim of this study was to investigate the influence of MSCs on the phenotype, cytokine profile, and functionality of naive and non-naive CD4+ T-cells from healthy donors (HD) and patients with autoimmune arthritis under Th17-cytokine polarizing conditions in an explorative way using a transwell system prohibiting any cell–cell-contact. Methods Magnetically isolated naive and non-naive CD4+ T-cells were stimulated under Th17-polarizing proinflammatory cytokine conditions in presence and absence of bone marrow derived mesenchymal stromal cells (MSCs). After an incubation period of 6 days, the proportions of the T-cell subpopulations TEMRA (CD45RA+CD27−), memory (CD45RA−CD27+), effector (CD45RA−CD27−) and naive cells (CD45RA+CD27+) were determined. Quantitative immunofluorescence intensity was used as a measure for IL-9, IL-17 and IFN-γ production in each subpopulation. Results In isolated naive CD4+ T-cells from HD and patients, MSCs suppressed the differentiation of naive towards an effector phenotype while memory and naive cells showed higher percentages in culture with MSCs. In patients, MSCs significantly decreased the proportion of IL-9 and IL-17 producing effector T-cells. MSCs also reduced IFN-γ production in the naive and memory phenotype from HD. Conclusions The results of the study indicate significant immunomodulatory properties of MSCs, as under Th17-polarizing conditions MSCs are still able to control T-cell differentiation and proinflammatory cytokine production in both HD and patients with autoimmune arthritis.

Abstract Background The extra-musculoskeletal manifestations (EMMs) such as recurrent acute anterior uveitis (rAAU), psoriasis (Ps), and inflammatory bowel disease (IBD), are related to the Spondyloarthritis (SpA), as well as they are associated with disease activity and poor prognosis. However, there are no data addressing its relevance regarding therapeutic decision-making in clinical practice. Objective To evaluate the impact of EMMs to drive the treatment decision-making in patients with SpA in a 12-month follow-up. Patients and methods SpA patients, according to the axial and peripheral ASAS classification criteria, as well as CASPAR criteria, with any active EMM, defined as main entry criteria, were included in this longitudinal cohort study. Individuals with a history of any disease or condition that could be associated with some of the studied endpoints, including neoplasms and infectious diseases, were excluded. Specific tools related to each EMM, including Psoriasis Area Severity Index (PASI), ophthalmologic evaluation, according to the Standardization of Uveitis Nomenclature (SUN) criteria, and gut complaints were used at baseline and during the 3-, 6- and 12-month of follow-up as outcomes measures over time. Descriptive and inferential analyses were used appropriately, including Pearson’s correlation test, chi-squared test, and ANOVA. P value less than 0.05 was considered as significant. Results A total of 560 patients were enrolled, of whom 472 meet the eligibility criteria. The majority (N = 274; 59.6%) had one or more EMM related to SpA umbrella concept. Among the EMM, the one that most influenced therapeutic decision-making was psoriasis (28.5%), followed by uveitis (17.5%) and IBD (5.5%), regardless of musculoskeletal manifestations. Clinical improvement of EMMs outcomes was observed in most patients over 12-month follow-up, especially in those with rAAU and IBD (P < 0.001). Conclusion Our results showed that EMMs guided the therapeutic decision-making in half of SpA patients, regardless of musculoskeletal condition, suggesting the inter-disciplinarity among the rheumatologist, ophthalmologist, dermatologist, and gastroenterologist plays a crucial role to manage them.

Abstract Behçet's disease (BD) is a systemic vasculitis that can affect multiple systems, including the skin, mucous membranes, joints, eyes, gastrointestinal and nervous. However, the pathogenesis of BD remains unclear, and it is believed that immune-inflammatory reactions play a crucial role in its development. Immune cells are a critical component of this process and contribute to the onset and progression of BD. By regulating the function of these immune cells, effective control over the occurrence and development of BD can be achieved, particularly with regards to monocyte activation and aggregation, macrophage differentiation and polarization, as well as T cell subset differentiation. This review provides a brief overview of immune cells and their role in regulating BD progression, which may serve as a theoretical foundation for preventing and treating this disease. Behçets Behçet s (BD systems skin membranes joints eyes nervous However unclear immuneinflammatory inflammatory achieved aggregation polarization

Abstract Background Juvenile Dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children. Imaging exams are useful for muscle assessment, with ultrasonography (US) being a promising tool in detecting disease activity and tissue damage. There are few studies about muscle elastography. Objectives Our aim was to associate clinical, laboratory, and nailfold capillaroscopy (NC) assessments with US in JDM patients; and to compare the findings of US and Strain Elastography (SE) from patients and healthy controls. Methods An analytic cross-sectional study was performed with JDM patients and healthy controls. Patients underwent clinical exam to access muscle strength and completed questionnaires about global assessment of the disease and functional capacity. Patients were submitted to NC and measurement of muscle enzymes. All subjects underwent US assessment, using gray scale, Power Doppler (PD), and SE. Results Twenty-two JDM patients and fourteen controls, aged between 5 and 21 years, matched for age and sex were assessed. In qualitative and semi-quantitative gray scale, we observed a higher frequency of alterations in patients (p < 0.001), while in PD, there was a higher frequency of positivity in patients’ deltoids and anterior tibialis (p < 0.001). Active disease was associated with an important change in the semi-quantitative gray scale in deltoids (p = 0.007), biceps brachii (p = 0.001) and quadriceps femoris (p = 0.005). The SE demonstrated a high negative predictive value of 87.2. Conclusion US was able, through gray scale, to differentiate JDM patients from controls, while PD achieved such differentiation only for deltoids and anterior tibialis. The semi-quantitative gray scale showed disease activity in proximal muscles. SE was not able to differentiate patients from controls.

Abstract Objectives Cardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients. Methods A total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis. Results Higher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962–31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p < 0.001). Besides, we found that high serum levels of hs-cTnI were significantly correlated with disease activity. Moreover, patients with higher serum levels of hs-cTnI tended to suffer from poor prognosis. Conclusions Serum hs-cTnI testing may play a role in screening for cardiac involvement in IIM patients. Abnormal levels of serum hs-cTnI were associated with increased disease activity and poor prognosis. Key Points Among all the cardiac biomarkers, the serum levels of hs-cTnI were independently associated with cardiac involvement in IIM patients. The serum levels of hs-cTnI were significantly correlated with disease activity in IIM patients. The abnormal hs-cTnI levels were correlated with poor prognosis in IIM patients.

Abstract Background The defect of B cell self-tolerance and the continuous antigen presentation by T cells (TCs) mediated by autoreactive B cells (BCs) play a key role in the occurrence and development of systemic lupus erythematosus (SLE). PD-1/PD-L1 signaling axis negatively regulates the immune response of TCs after activation and maintains immune tolerance. However, the effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B/CD4+TCs in the peripheral blood of patients with SLE has not been studied in detail. Methods PD-1/PD-L1 and Ki-67 levels in peripheral blood (PB) of 50 SLE patients and 41 healthy controls (HCs) were detected through flow cytometry, and then the expression of PD-1+/−cells and PD-L1+/−cells Ki-67 was further analyzed. CD19+B/CD4+TCs were separated for cell culture and the supernatant was collected to determine proliferation and differentiation of TCs. IL-10 and IFN-γ secretion in the supernatant was also determined using ELISA. Results The PD-1, PD-L1, and Ki-67 levels on CD19+B/CD4+TCs in patients with SLE were higher than HCs. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ cells was higher than that of PD-L1− cells, and the proliferative activity of PD-1+ cells was higher than that of PD-1− cells. In the system co-culturing CD19+B/CD4+TCs from HCs/SLE patients, activated BCs promoted TCs proliferation and PD-L1 expression among TCs. Addition of anti-PD-L1 to co-culture system restored the proliferation of TCs, and inhibited IL-10/IFN-γ level. The addition of anti-PD-L1 to co-culture system also restored Tfh and downregulated Treg in HCs. Conclusions Axis of PD-1/PD-L1 on CD19+B/CD4+TCs in PB of SLE patients is abnormal, and cell proliferation is abnormal. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ and PD-1+ cells compared with PD-L1− and PD-1− cells in SLE patients, respectively. CD19+B/CD4+TCs in SLE patients can interact through PD-1/PD-L1.

Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2–4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0–56.0) years old and disease duration of 12.0 (6.0–12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.

Abstract Objective The study explored improvements in pulmonary inflammation and fibrosis in a bovine type II collagen-induced rheumatoid arthritis-associated interstitial lung disease mouse model after treatment with baricitinib and the possible mechanism of action. Methods A rheumatoid arthritis-associated interstitial lung disease mouse model was established, siRNA Jak2 and lentiviral vectors were transfected with human embryonic lung fibroblast cells. And the levels of relevant proteins in mouse lung tissue and human embryonic lung fibroblasts were detected by Western blotting. Results The levels of JAK2, p-JAK2, p-STAT3, p-SMAD3, SMA, TGFβR2, FN and COL4 were increased in the lung tissues of model mice (P < 0.5) and decreased after baricitinib intervention (P < 0.05). The expression levels of p-STAT3, p-SMAD3, SMA, TGFβR2, FN and COL4 were reduced after siRNA downregulation of the JAK2 gene (P < 0.01) and increased after lentiviral overexpression of the JAK2 gene (P < 0.01). Conclusion Baricitinib alleviated fibrosis in the lung tissue of rheumatoid arthritis-associated interstitial lung disease mice, and the mechanism of action may involve the downregulation of Smad3 expression via inhibition of the Jak2/Stat3 signaling pathway, with consequent inhibition of the profibrotic effect of transforming growth factor-β1.

Abstract Introduction/Objectives Psoriatic arthritis (PsA) is a chronic multisystem osteoarticular disease that requires specialized care. Most Brazilians depend on the public healthcare provided by the Unified Health System (Sistema Único de Saúde, SUS). This study aimed to describe the epidemiological characteristics of patients with PsA in follow-up in SUS, focusing on the incidence and prevalence of the disease, comorbidities, and hospitalizations. Methods We collected data from the Outpatient Data System of SUS (Sistema de Informações Ambulatoriais do SUS, SIA/SUS) regarding outpatient visits and hospitalizations in the Brazilian public healthcare system from January 2008 to March 2021 using the Techtrials Disease Explorer® platform and the medical code related to PsA were selected. Results We evaluated 40,009 patients and found a prevalence of 24.4 cases of visits due to PsA per 100,000 patients in follow-up in SUS. Female patients were predominant (54.38%). The incidence of visits due to PsA has been increasing in recent years and we observed an incidence of 8,982 new visits in 2020. The main comorbidities of these patients were osteoarthritis, lower back pain, shoulder injuries, oncological diseases, crystal arthropathies, and osteoporosis. Hospitalizations were mainly due to treating clinical or cardiovascular conditions and performing orthopedic procedures. Conclusion The number of visits due to PsA in SUS has increased in recent years, mainly on account of new diagnoses of the disease, although the prevalence found in this study's population was lower than that observed in the general population.

Abstract Objectives The deposition of monosodium urate (MSU) crystals within synovial joints and tissues is the initiating factor for gout arthritis. Thus, MSU crystals are a vital tool for studying gout's molecular mechanism in animal and cellular models. This study mainly compared the excellence and worseness of MSU crystals prepared by different processes and the degree of inflammation induced by MSU crystals. Methods MSU crystals were prepared using neutralization, alkali titration, and acid titration methods. The crystals' shape, length, quality, and uniformity were observed by polarized light microscopy and calculated by the software Image J. The foot pad and air pouch models were used to assess the different degrees of inflammation induced by the MSU crystals prepared by the three different methods at different time points. Paw swelling was evaluated by caliper. In air pouch lavage fluid, inflammatory cell recruitment was measured by hemocytometer, and the level of IL-1β TNF- α, and IL-18 by ELISA. Inflammatory cell infiltration was assayed by immunohistochemistry of air pouch synovial slices. Results For the preparation of MSU crystals with the same uric acid, the quantity acquired by the alkalization method was highest, followed by neutralization, with the acid titration method being the lowest. The crystals prepared by neutralization were the longest. The swelling index of the foot pad induced by MSU crystals prepared by acid titration was significantly lower than that of the other methods at 24 h. The inflammatory cell recruitment and level of 1-1β, TNF-α, and IL-18 in air pouch lavage fluid were lowest in animals with crystals prepared by acid titration. IL-1β secretion induced by MSU crystals prepared by acid titration was significantly lower than that of the other two groups, but there was no significant difference in IL-18 secretion between the three groups in THP-1 macrophages and BMDMs. Conclusions All three methods can successfully prepare MSU crystals, but the levels of inflammation induced by the crystals prepared by the three methods were not identical. The degree of inflammation induced by MSU crystals prepared by neutralization and alkalization is greater than by acid titration, but the quantity of MSU crystals obtained by the alkalization method is higher and less time-consuming. Apparently, the window of inflammation triggered by acid titration preparation is shorter compared to other forms of crystal preparation. Overall, MSU crystals prepared by the alkaline method should be recommended for studying the molecular mechanisms of gout in animal and cellular models.

Abstract Background Takayasu's arteritis (TA) is a vasculitis that affects the aorta and its branches and causes stenosis, occlusion, and aneurysms. Up to 60% of TA patients are associated with cardiac involvement which confers a poor prognosis. Global longitudinal strain (GLS) analysis is an echocardiographic technique that can detect the presence of subclinical systolic dysfunction. Hence, this study aimed to describe the prevalence of subclinical systolic dysfunction in patients with TA using the GLS method and to correlate this finding with disease activity using the ITAS-2010 (Indian Takayasu Activity Score). Methods Thirty patients over 18 years of age who met the American College of Rheumatology (ACR) 1990 criteria for TA were included. The sample was submitted for medical record review, clinical and echocardiographic evaluation, and application of ITAS-2010. The cutoff for systolic dysfunction was GLS > - 20%. Results Of the 30 patients analyzed, 25 (83.3%) were female, and the mean age was 42.6 years (± 13.2). The median time since diagnosis was 7.5 years [range, 3-16.6 years], and the type V angiographic classification was the most prevalent (56.7%). Regarding echocardiographic findings, the median ejection fraction (EF) was 66% [61-71%] and the GLS was - 19.5% [-21.3 to -15.8%]. Although half of the participants had reduced GLS, only two had reduced EF. Eleven patients (33.%) met the criteria for activity. An association was found between disease activity and reduced GLS in eight patients (P = 0.02) using the chi-square test. Conclusion GLS seems to be an instrument capable of the early detection of systolic dysfunction in TA. The association between GLS and disease activity in this study should be confirmed in a study with a larger sample size.