Inflammatory Arthritis Research Articles

Association Between Inflammatory Arthritis, Genetic Risk, and the Long-Term Risk of Degenerative Aortic Stenosis: A Prospective Cohort Study.

Inflammatory arthritis is recognized to increase cardiovascular disease risk, but its association with degenerative aortic stenosis is not well understood. This prospective cohort study used participants from the UK Biobank, focusing on 4 major types of inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout. The primary outcome was the incidence of degenerative aortic stenosis. The primary analysis used Cox proportional hazards models to evaluate the association between inflammatory arthritis and the long-term risk of degenerative aortic stenosis, as well as to explore potential effect modifiers. Genetic risk was evaluated using polygenic risk scores and self-reported family history of cardiovascular diseases. The study included 497 567 participants, with 271 129 women (54.5%) and 468 015 White individuals (94.1%). The median age was 58 years. Over a median follow-up of 12.58 years, 4571 cases (0.9%) of degenerative aortic stenosis were identified. Compared with the control group, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout were associated with increased risks of degenerative aortic stenosis by 54% (hazard ratio [HR], 1.54 [95% CI, 1.28-1.85]), 72% (HR, 1.72 [95% CI, 1.19-2.50]), 176% (HR, 2.76 [95% CI, 1.43-5.32]), and 36% (HR, 1.36 [95% CI, 1.20-1.54]), respectively. These associations were independent of genetic risk (P for interaction>0.05). Additionally, we identified significant interactions between sex (P for interaction=0.036), age (P for interaction<0.001), and socioeconomic status (P for interaction=0.014) with rheumatoid arthritis, ankylosing spondylitis, and gout on the incidence of degenerative aortic stenosis, respectively. Inflammatory arthritis is significantly associated with an increased long-term risk of degenerative aortic stenosis, underscoring the need for enhanced risk assessment for degenerative aortic stenosis in these populations.

Acute kidney injury and outcomes in hospitalized children with autoimmune rheumatic disease

BackgroundAutoimmune rheumatic diseases (ARDs) in children can negatively impact renal function, potentially leading to acute kidney injury (AKI). This study compares the prevalence of AKI and other adverse in-hospital outcomes among hospitalized children with ARDs.MethodsA retrospective analysis was conducted using the United States Nationwide Inpatient Sample (NIS) database from 2005 to 2020. The study included children aged 1–17 years with ARDs, categorized into inflammatory arthritis, ANCA-associated vasculitis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and other connective tissue diseases. Logistic regression assessed associations between ARD types and outcomes, including AKI, dialysis, and major adverse events.ResultsAmong 13,891 children with ARDs, 8.2% developed AKI and 1.3% required dialysis. Compared to inflammatory arthritis, ANCA-associated vasculitis significantly increased the risk of AKI (aOR = 11.20, 95% CI: 8.08–15.51) and dialysis (aOR = 40.60, 95% CI: 13.54-121.71). SLE also elevated risks of AKI (aOR = 4.16, 95% CI: 3.20–5.40) and dialysis (aOR = 11.34, 95% CI: 4.15–31.01). Children with SSc had increased risks of infection/pneumonia (aOR = 2.51, 95% CI: 1.84–3.41) and sepsis (aOR = 2.13, 95% CI: 1.26–3.58).ConclusionsChildren with ARDs, especially those with ANCA-associated vasculitis and SLE, face elevated risks of AKI and dialysis. These findings underscore the importance of vigilant monitoring and tailored management in this population.

Rehabilitation and Long Term Outcomes Including Return to Work or Sport Following Reverse Total Shoulder Arthroplasty.

Reverse total shoulder arthroplasty has become an excellent surgical option for patients suffering from various shoulder pathologies including rotator cuff arthropathy, inflammatory arthritis and proximal humerus fractures. The goals of this operation are to reduce pain, restore function, and allow patients to be able to return to both work and sport. This article provides insight into the return to work and sport of patients who have undergone reverse total shoulder arthroplasty. Recent literature has demonstrated that patients who have undergone reverse total shoulder arthroplasty demonstrate high rates of return to work and sport. Variations in patient age, sex, work intensity, type of sport and rehabilitation protocols can also play a factor in being able to return to work and sport. Patients who have undergone reverse total shoulder arthroplasty are able to return to work and sport in a timely manner. A structured rehabilitation protocol, appropriate patient selection and excellent communication between surgeon and patient is crucial to achieve a successful return to work and sport.

CX3CR1+ age-associated CD4+ T cells contribute to synovial inflammation in late-onset rheumatoid arthritis

BackgroundRecent evidence suggests that clonally expanded cytotoxic T cells play a role in various autoimmune diseases. Late-onset rheumatoid arthritis (LORA) exhibits unique characteristics compared to other RA forms, suggesting distinct immunological mechanisms. This study aimed to examine the involvement of cytotoxic T cells in LORA.MethodsFresh peripheral blood samples were collected from 78 treatment-naïve active RA patients, 12 with difficult-to-treat RA, and 16 healthy controls. Flow cytometry was employed to measure the proportions of CX3CR1+cytotoxic CD4+ and CD8+ T cells in these samples. Additionally, immunohistochemical staining was performed on lymphoid node and synovial biopsy samples from patients with RA.ResultsCX3CR1+cytotoxic CD4+ T cells were specifically increased in untreated, active patients with LORA, displaying features of CXCR3mid age-associated T helper cells known as “ThA”. CX3CR1⁺CD4⁺ T cells were identified as a cytotoxic ThA subset, as nearly all of these cells specifically expressed granzyme B. These cells were observed in enlarged lymph nodes and were found to infiltrate synovial tissues from patients with LORA. The proportions of CX3CR1+CD4+ T cells positively correlated with arthritis activity in LORA. The number of cells decreased after treatment with methotrexate, tumor necrosis factor inhibitors, and interleukin-6 inhibitors, whereas T-cell activation modulators did not affect them. Moreover, PD-1+CD38+CX3CR1+CD4+ T cells were identified as a treatment-resistant T cell subset that was characteristically increased in difficult-to-treat RA. CX3CR1+CD8+ T cells showed no significant difference between RA patients and healthy individuals, and no correlation with disease activity was observed. However, a correlation with age was observed in RA patients.ConclusionsOur findings suggest that the immunopathogenesis of RA differs by age of onset, with CX3CR1+ age-associated cytotoxic CD4+ T cells playing a significant role in LORA. Additionally, the presence of a specific CX3CR1+ T cell subset may be linked to treatment resistance.

Can Wearable Device Promote Physical Activity and Reduce Pain in People with Chronic Musculoskeletal Conditions?

Objective: The purpose of this systematic review is to identify and appraise the evidence on the effectiveness of using wearable devices to promote physical activity and reduce pain in people with chronic musculoskeletal pain. Methods: Systematic searches of electronic databases PubMed, CINAHL, and Medline (Ovid) were undertaken for randomised control trials and observational studies of wearable-based interventions in patients with chronic musculoskeletal conditions. Result: Thirteen studies were included in this review. The methodological quality of the included articles was found to vary between moderate and high quality. Studies included patients with osteoarthritis hip/knee (number; n = 5), low back pain (n = 3), rheumatoid arthritis (n = 1), juvenile idiopathic arthritis (n = 1), inflammatory arthritis (n = 1), spondylarthritis (n = 1), and ankylosing spondylitis (n = 1). The intervention group of some of the studies included additional components associated with the use of wearable devices such as step or diet diary, motivational interviewing or counselling, goal setting, and multidimensional and tailored exercise programme interventions delivered in person, remotely, or in a hybrid format. Intervention duration ranged from 1 week to 28 weeks. There were no serious adverse events related to the use of wearables. Overall, evidence from this systematic review shows that wearable technology intervention was effective in increasing physical activity significantly, especially where extra components (counselling, coaching, prescribed physical activity, goal setting, physiotherapist) were used among clinical and non-clinical populations. However, no significant effect was found in pain reduction with the use of wearable devices. Conclusions: It is concluded that the use of wearable technology should be encouraged in patients with chronic musculoskeletal conditions. Additional research is needed, such as increasing the duration of the intervention, which may have an impact on pain.

Towards painless and productive research relationships: reflections on study design by a researcher with chronic pain for participants with chronic pain

Building flexibility into the research design of a study allows for responsiveness to the embodied and fluctuating nature of participants’ chronic illnesses, which may be shaped, for instance, by flare-ups and periods of remission of acute pain. Whilst the methodology literature has, to some extent, considered how to accommodate the pain of research participants when designing a study, consideration of how methodological choices are responsive to the researcher's pain needs has not to date been foregrounded. From the perspective of a researcher with Ankylosing Spondylitis (AS), a form of inflammatory arthritis characterized by chronic pain, and Crohn's disease, a type of inflammatory bowel disease, characterized by stomach and joint pain, this paper provides insight into pain and researcher-participant relationships, from the perspective of a researcher in pain, designing a study to accommodate her own pain needs, as well as anticipating the needs of prospective participants in pain. This paper proposes the use of flexible, remote, and asynchronous research methods as ways to make studies inclusive for researchers living with pain, whilst fostering the most fruitful research relationships with participants who also live with pain, thereby moving towards a position of shared vulnerability. It also highlights the relative absence of the researcher's needs and possible vulnerability in ethics forms and considered by research ethics committees, in comparison to the needs and vulnerability of participants.

Microbiota from young mice counteracts susceptibility to age-related gout through modulating butyric acid levels in aged mice.

Gout is a prevalent form of inflammatory arthritis that occurs due to high levels of uric acid in the blood leading to the formation of urate crystals in and around the joints, particularly affecting the elderly. Recent research has provided evidence of distinct differences in the gut microbiota of patients with gout and hyperuricemia compared to healthy individuals. However, the link between gut microbiota and age-related gout remained underexplored. Our study found that gut microbiota plays a crucial role in determining susceptibility to age-related gout. Specifically, we observed that age-related gut microbiota regulated the activation of the NLRP3 inflammasome pathway and modulated uric acid metabolism. More scrutiny highlighted the positive impact of 'younger' microbiota on the gut microbiota structure of old or aged mice, enhancing butanoate metabolism and butyric acid content. Experimentation with butyrate supplementation indicated that butyric acid exerts a dual effect, inhibiting inflammation in acute gout and reducing serum uric acid levels. These insights emphasize the potential of gut microbiome rejuvenation in mitigating senile gout, unraveling the intricate dynamics between microbiota, aging, and gout. It potentially serves as a therapeutic target for senile gout-related conditions.

Microbiota from young mice counteracts susceptibility to age-related gout through modulating butyric acid levels in aged mice

Gout is a prevalent form of inflammatory arthritis that occurs due to high levels of uric acid in the blood leading to the formation of urate crystals in and around the joints, particularly affecting the elderly. Recent research has provided evidence of distinct differences in the gut microbiota of patients with gout and hyperuricemia compared to healthy individuals. However, the link between gut microbiota and age-related gout remained underexplored. Our study found that gut microbiota plays a crucial role in determining susceptibility to age-related gout. Specifically, we observed that age-related gut microbiota regulated the activation of the NLRP3 inflammasome pathway and modulated uric acid metabolism. More scrutiny highlighted the positive impact of ‘younger’ microbiota on the gut microbiota structure of old or aged mice, enhancing butanoate metabolism and butyric acid content. Experimentation with butyrate supplementation indicated that butyric acid exerts a dual effect, inhibiting inflammation in acute gout and reducing serum uric acid levels. These insights emphasize the potential of gut microbiome rejuvenation in mitigating senile gout, unraveling the intricate dynamics between microbiota, aging, and gout. It potentially serves as a therapeutic target for senile gout-related conditions.

Assessment of Carpal Tunnel Syndrome in Patients With Wrist Involvement During the Course of Inflammatory Arthritis. A Cross-Sectional Study.

The aim of the study was to evaluate the ultrasonographic (United States) alterations of the median nerve, the performance of the Kamath screening questionnaire and the clinical examination (Tinel and Phanel test) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) with previous or present inflammatory involvement of the radio-ulno-carpal joint. A cross-sectional study was carried out. Patients with RA and PsA and clinical symptoms suggestive of CTS were consecutively recruited. The main clinical-demographic characteristics were collected in all patients. The Kamath questionnaire was administered to all patients during the clinic visit. The US examination was used as a 'gold-standard' for the diagnosis of CTS (transverse nerve area >12mm2 and morpho-structural alterations) and was used to assess the sensitivity and specificity of the Kamath questionnaire and the Tinel and Phanel clinical tests. 44 patients, 34 patients with RA and 10 patients with PsA were evaluated. 7 (16%) patients had a median nerve cross-sectional area >12mm2, associated with US abnormalities of the nerve. The Kamath questionnaire showed moderate sensitivity values (71.4%) but low specificity (56.7%) for ultrasonographic diagnosis of CTS with a negative predictive value of 91.3%. Clinical tests show low sensitivity but high specificity. No statistically significant correlations were found with the main clinical variables. The screening questionnaire showed moderate sensitivity but low specificity compared to the ultrasound 'gold standard'. Clinical tests may support the diagnosis of CTS in these conditions.

Secreted PD-L1 alleviates inflammatory arthritis in mice through local and systemic AAV gene therapy

IntroductionRheumatoid arthritis (RA) primarily affects the joints but can also affect multiple organs and profoundly impacts patients’ ability to carry out daily activities, mental health, and life expectancy. Current treatments for RA are limited in terms of duration, efficacy, and adverse effects. PD-L1 is a checkpoint protein that plays important roles in immune regulation and has been implicated in the initiation and progression of multiple autoimmune diseases.MethodIn a previous study, we demonstrated that intra-articular injection with adeno-associated virus (AAV) vectors encoding wild type PD-L1 improved local inflammation in the joint in the collagen-induced arthritis (CIA) mouse model of RA. To further improve efficacy, we explored AAV-mediated delivery of the soluble PD-L1 (sPD-L1) to CIA mice.ResultAfter intra-articular injection of AAV6 vectors expressing the optimal isoform of sPD-L1 (shPD-L1), more potency was observed when compared to wild type PD-L1, with a lower dose of AAV6/shPD-L1 needed for arthritis improvement. To study the therapeutic effect of systemic expression of sPD-L1, we administered AAV8/shPD-L1 gene therapy in CIA mice via retro-orbital injection and found significant improvements in joint inflammation and paw swelling, exhibiting similar phenotypes to that in naïve mice. The levels of total immunoglobulin and anti-collagen specific antibodies were lower in AAV8/shPD-L1 treated CIA mice than those in controls. The levels of pro-inflammatory cytokines in blood were also significantly decreased in shPD-L1 treated mice. Additionally, T cell apoptosis rates in the spleen showed a 2-fold increase in treated mice. Finally, we investigated the therapeutic effect of AAV/shPD-L1 via intramuscular injection. After injection of AAV6/shPD-L1, decreased paw swelling, reduced joint inflammation, and lower levels of pro-inflammatory cytokines in blood were achieved. The therapeutic effect of shPD-L1 was dose dependent via intramuscular treatment with AAV vectors.ConclusionIn conclusion, the findings in this study suggest that intra-articular injection of AAV vectors encoding sPD-L1 results in greater therapeutic benefit on arthritis, and systemic AAV/sPD-L1 is able to block the development of inflammatory arthritis with inhibition of the systemic immune response, underlining the potential of gene therapy with systemic delivery of shPD-L1 via AAV vectors in RA.

The role of occupational therapy in providing vocational rehabilitation for people living with inflammatory arthritis: A scoping review.

Inflammatory arthritis significantly impacts work participation resulting in cost to individuals, employers, and society. Vocational rehabilitation seeks to address this need, but its pathways, interventions, and efficacy continue to be under investigation. Contributing variables are complex, identifying the need for a conceptual framework to guide practice. Occupational therapy addresses this complexity, providing theoretical frameworks such as the Person-Environment-Occupation-Performance (PEOP) model to understand the occupation of work supporting well-being and design interventions. The aim of this scoping review is to map the role of occupational therapy in providing vocational rehabilitation for people living with inflammatory arthritis. A scoping review following Arksey and O'Malley's (2005) stages was completed. Major databases and grey literature were systematically searched, and hand-searches completed. Descriptive and thematic analysis mapped the findings to the PEOP model framework. There was no consumer or community involvement in this review. Fourteen studies were included. Major themes aligned to the PEOP model with further analysis synthesised in subthemes. A majority of person-related interventions to support work performance was observed. This framework identifies the domains of focus in vocational rehabilitation and current gaps. Work instability, employment retention, and self-efficacy were used to measure effectiveness. This scoping review presents the evidence regarding vocational rehabilitation for the inflammatory arthritis population in the context of occupational therapy theory to provide a framework for clinical practice. A current focus on person-focused interventions was identified. The PEOP model provides a clear framework to understand the complexity and nuances of vocational rehabilitation across the domains. Outcome measures for vocational rehabilitation are heterogenous and require further exploration as capturing the intricacy of achieving balance with work participation remains unclear. Further research into vocational rehabilitation programs incorporating all domains of the PEOP model is needed. Consideration of work performance measurements to inform effectiveness and the resulting impact on a person's well-being is required.

Thymidine phosphorylase participates in platelet activation and promotes inflammation in rheumatoid arthritis.

The elevated risk of cardiovascular disease (CVD) associated with inflammatory rheumatic diseases has long been recognized. Patients with established rheumatoid arthritis (RA) have a higher mortality rate compared to the general population due to abnormal platelet activation. Thymidine phosphorylase (TYMP) plays a crucial role in platelet activation and thrombosis, following bridging the link between RA and CVD. Data from Gene Expression Omnibus (GEO) database exhibited that TYMP levels were highly expressed in synovial tissues, immune cells, and whole blood of RA patients especially those with high levels of inflammation. Platelet count (PLT) and plateletcrit (PCT) were positively correlated with the severity of inflammation in rheumatoid arthritis while platelet distribution width (PDW) and mean platelet volume (MPV) were adverse. Levels of CD62P and TYMP in platelets of patients with active RA were significantly elevated compared to patients in the inactive phase. In vivo exepriments showed that reducing TYMP expression levels of platelets could relieve inflammation in Adjuvant-Induced Arthritis (AIA) mice. Platelet activation was significantly elevated in AIA model mice, along with increased levels of intracellular calcium (Ca2+), reactive oxygen species (ROS), and decreased Mitochondrial Membrane Potential (ΔΨm). However, treatment with Tipiracil hydrochloride (TPI) or the utilization of Tymp-/- mice reversed these effects. In vitro stimulation of wild type (WT) mouse platelets with tumor necrosis factor-alpha (TNF-α) promoted platelet activation, elevated levels of intracellular Ca2+as well as ROS while decreased ΔΨm. Platelets of WT mice treated with TPI or platelets of Tymp-/- mice exhibited the adverse results. Our study illustrates the vital role of TYMP in promoting RA inflammation and platelet activation, suggesting that TYMP may be a potential therapeutic target for RA.

Resident synovial macrophages in synovial fluid: Implications for immunoregulation.

Resident synovial macrophages (RSMs) are anti-inflammatory, self-renewing macrophages that provide physical immune sequestration of the joint space from the peripheral immune system. Increased permeability of this structure is associated with peripheral immune cells in the synovial fluid (SF). Direct measures of synovial barrier integrity are possible with tissue histology, but after barrier breakdown, if these cells perpetuate or initiate chronic inflammation in SF remains unknown. We sought to identify RSM in human SF as an indirect measure of synovial barrier integrity. To validate findings, we created a novel ex vivo explant model using human synovium. scRNA-seq revealed these SF RSMs upregulated pro-fibrotic and pro-osteoclastic pathways in inflammatory arthritis, but not septic arthritis. Increased frequencies of RSMs in SF was associated with increased sRANKL regardless of underlying pathology. These findings suggest the frequency of RSMs in SF may correlate with synovial barrier damage and in turn, potential damage to joint structures.

The protein tyrosine phosphatase Lyp/PTPN22 drives TNFα-induced priming of superoxide anions production by neutrophils and arthritis.

Neutrophils are essential for host defense against infections, but they also play a key role in acute and chronic inflammation. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes the lymphoid-specific tyrosine phosphatase (Lyp) and a genetic single-nucleotide polymorphism of PTPN22 rs2476601 (R620W) has been associated with several human autoimmune diseases, including rheumatoid arthritis (RA). Here, we investigated the role of Lyp in TNFα-induced priming of neutrophil ROS production and in the development of arthritis using new selective Lyp inhibitors. Results show that Lyp-selective inhibitors (IC-11 and compound 8b), inhibited TNFα-induced priming of neutrophil superoxide anion production. TNFα induced an increase of Lyp protein expression in human neutrophils isolated from healthy donors. Key pathways involved in neutrophil priming were investigated. Lyp-selective inhibitors, inhibited TNFα-induced p47phox phosphorylation on Ser345, ERK1/2 phosphorylation and Pin1 activation. Interestingly, Lyp expression was increased in neutrophils isolated from synovial fluid of RA patients and Lyp inhibitors, I-C11 and compound 8b prevented superoxide anion production by endogenously primed neutrophils isolated from synovial fluid of RA. Moreover, IC-11 significantly prevented collagen antibody-induced arthritis in mice. These results show that Lyp expression is increased in inflammatory neutrophils, Lyp is involved in TNFα-induced excessive ROS production by neutrophils and its inhibition protected mice against arthritis. Inhibition of Lyp could be a therapeutic strategy in inflammatory arthritis.

Aspirin does not confer protection against major ischemic vascular events in patients diagnosed with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammatory arthritis and extra-articular involvement. Patients with RA are at increased risk of developing cardiovascular diseases. This retrospective cohort study aimed to determine whether acetylsalicylic acid (aspirin [ASA]) protects against major ischemic vascular events in patients diagnosed with RA. Patients with RA were recruited from a population of 118, 500 participants who were enrolled into the Kailuan Cohort Study between 2014 and 2016. Information regarding demographic characteristics, anthropometric measures, and medical histories were documented. Patients with RA who underwent ASA therapy were propensity score matched at a ratio of 1:4 with patients with RA who did not receive ASA. The risk of ischemic vascular events (myocardial infarction and ischemic stroke) was examined. The relationship between ASA therapy and major ischemic vascular events was analyzed by Cox proportional hazards regression. A total of 939 patients with RA were included (189 who received ASA and 750 who did not). During the 3.3-year follow-up, six and 35 major ischemic vascular events occurred in the ASA and non-ASA groups, respectively, with no significant between-group difference in the cumulative incidence of such events. Cox proportional hazards regression analysis showed that ASA therapy was not associated with major vascular ischemic events and its subtypes. ASA did not confer protection against major ischemic vascular events in patients diagnosed with RA.

Musculoskeletal manifestations in leprosy.

Leprosy, a chronic infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis, primarily targets the skin and peripheral nerves, frequently leading to dermatological, neurological, and musculoskeletal complications. This review highlights the spectrum of musculoskeletal manifestations in leprosy, including acute arthritis during Type 2 reactions, chronic arthritis mimicking autoimmune diseases like rheumatoid arthritis, and neuropathic arthropathy. These manifestations underscore the complex interplay of inflammatory and immune mechanisms. Acute arthritis often involves both small and large joints, while chronic forms may present diagnostic challenges due to their resemblance to other inflammatory arthritides. Clinical management centers on multidrug therapy (MDT) for infection control, complemented by immunosuppressive or anti-inflammatory agents for reactional episodes. Recent advancements, such as biologics and synthetic immunosuppressants, have demonstrated efficacy in refractory cases, offering new therapeutic avenues. Heightened clinician awareness is essential for timely diagnosis and integrated management, particularly in endemic regions, to mitigate long-term disabilities and improve patient outcomes.

Chinese herbal medicines and its active ingredient wogonin can improve immune inflammation in psoriatic arthritis.

In China, Chinese herbal medicines (CHMs) have been widely used in the treatment of psoriatic arthritis (PsA), showing great therapeutic effects in clinical practice. However, due to the great heterogeneity of PsA and the diversity of CHM combination patterns, there is little high-level evidence-based medical research on the treatment of PsA with CHMs. This study aims to explore the beneficial effects of CHMs on the immune inflammation in PsA and its specific mechanism. The data mining method was performed to analyze the real-world data of 91 PsA clinical cases. Network pharmacology, molecular docking, and cellular experiments were used to explore the mechanism of CHMs and its active ingredient wogonin in improving PsA immune inflammation. Data mining results showed that in PsA, immune inflammation was disturbed and relevant indexes were significantly correlated. After CHM treatment, the level of HCRP, C4, IL-12, IL-17, IL-23, TNF-α, TGF-β1, P65, P50, and IKBα was markedly improved, which was highly correlated with the application of CHMs. In addition, the core prescription containing 10 CHMs was screened, and the action mechanisms of the active ingredient wogonin on the immune inflammation in PsA were identified with network pharmacology and molecular docking. Cell experiments revealed that wogonin reduced M5-induced HaCaT cell viability and TNF-α and IL-1β expressions by blocking the PI3K/AKT pathway in a dose-dependent manner. Our findings strongly confirmed the enormous promise of CHMs as a therapy for PsA and may provide support for developing drugs and targets for PsA treatment.

Facilitators and Barriers to Physical Activity for Patients With Rheumatoid Arthritis and Axial Spondyloarthritis.

Physical activity is important in patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). Current literature suggests they engage in less physical activity compared to healthy controls. Reasons for this discrepancy has not been well studied in Asian populations. We aimed to understand facilitators and barriers to physical activity in patients with RA and axSpA using the validated Inflammatory arthritis FAcilitators and Barriers (IFAB) questionnaire. We conducted a cross-sectional study from 2020 to 2021 and enrolled patients diagnosed with RA and axSpA. Demographics, disease activity, comorbidities, facilitators, barriers and levels of physical activity were collected. Mean time on recreational activity, facilitators and barriers were listed. We enrolled 222 patients (109 RA, 113 axSpA). Mean (SD) age was 48.4 (14.8) years and 42.3% were males. Of all patients, 66.7% met the WHO recommendations on physical activity for health and percentage was similar between patients with RA and axSpA. Mean time spent on recreational-related activities was higher in patients with axSpA. Top three barriers to physical activity included lack of motivation (46.8%), level of symptoms (44.6%) and weather conditions (29.7%). Facilitators included knowledge of the benefits of physical activity for health (68.9%), mood (56.3%), and confidence on how to exercise safely (54.5%). Overall, the facilitators and barriers to physical activity were similar between patients with RA and axSpA. Physicians could address some of these factors during consultations to promote and encourage more physical activity.

145 A notable presentation of inflammatory arthritis in patient on sirolimus

145 A notable presentation of inflammatory arthritis in patient on sirolimus

Fishroesomes show intrinsic anti-inflammatory bioactivity and ability as celecoxib carriers in vivo.

According to the World Health Organization (WHO), chronic inflammatory-related diseases represent the greatest threat to human health. Indeed, failure in the resolution of inflammation leads to serious pathological conditions, such as cardiovascular diseases, arthritis, cancer, diabetes, autoimmune diseases, and neurodegenerative disorders that are often associated with extremely high human suffering and societal and economic burdens. Despite the number and efficacy of available therapeutic agents have been increased, the serious side effects associated with some of them often create a very high risk/benefit ratio for patients. Therefore, herein, a drug delivery system was engineered to overcome important drawbacks of conventional therapies and to have a synergistic action with the incorporated drug. Indeed, it will have an added beneficial role in controlling inflammation. For that, sardine (Sardina pilchardus) roe was used as the lipidic source to produce bioactive liposomes, namely fishroesomes. These spherical vesicles with ≈326 nm in size and a significant negative surface charge (≈-31 mV) were able to encapsulate and control the release of the anti-inflammatory drug celecoxib. Moreover, fishroesomes were cytocompatible for different cell types (chondrocytes and macrophages), at concentrations in which they present anti-inflammatory properties. Importantly, fishroesomes were more effective in reducing pro-inflammatory mediators than the free drug. We also demonstrated that a single intra-articular injection of the fishroesomes encapsulating or not celecoxib in an experimental rat model of inflammatory arthritis was safe and more effective in controlling the pain and reducing the synovial inflammation compared to the free drug. Notably, as the celecoxib concentration in the sardine roe-derived liposomes was less than half of the amount of free drug, this study demonstrates the value of fishroesomes in counteracting inflammation. Therefore, the developed formulations may be considered a promising therapeutic option for inflammatory conditions.