BACKGROUND

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammatory arthritis and extra-articular involvement. Comorbidities are highly prevalent in patients with RA, in particular cardiovascular disease (CVD), which is responsible for over 50% of premature deaths. This study aimed to describe cardiovascular diseases and their risk factors among patients with rheumatoid arthritis in the Philippine General Hospital (PGH).

To describe cardiovascular (CV) diseases and their risk factors among patients with rheumatoid arthritis.

A retrospective descriptive cross-sectional study was done in the University of the Philippines – Philippine General Hospital (UP-PGH) inpatient and outpatient services. The study included patients 18 years old and above diagnosed with RA and fulfills the 1987 American College of Rheumatology or 2010 American College of Rheumatology-European League Against Rheumatism (ACR/EULAR) classification criteria with no overlap features with other autoimmune connective tissue diseases and with complete records of the information required for the study from January 2019-December 2022. The primary outcomes of interest were the prevalence of CV diseases and CV risk factors. Descriptive statistics were used to summarize the data.

There were 123 patients in the study, 93.4% outpatients, and 95.1% females, with a mean age and disease duration of 51.3 and 9.8 years, respectively. Disease activity was moderate in 35% and high in 9.7%, based on disease activity score (DAS 28) or clinical disease activity index (CDAI) scores. Methotrexate (54%) was the most commonly used conventional synthetic disease-modifying antirheumatic drug (csDMARD). Glucocorticoid use was observed in 51.2%. None of the patients were receiving a biologic DMARD. There were 24 (19.5%) patients with CV diseases, namely myocardial infarction, heart failure, and stroke. There were 87 (70%) patients with at least one CV risk factor and 62 (50.4%) with multiple risk factors. The risk factors identified were: dyslipidemia (43.1%), hypertension (40.7%), elevated body mass index (35.7%), and diabetes mellitus (15.4%). There were f ive deaths in the hospitalized patients (4%), one due to a myocardial infarction.

The majority (70%) in our cohort had at least one CV risk factor, 19.5% had an identified CV disease, and one died from a myocardial infarction. Dyslipidemia was the most common CV risk factor. The high proportion of patients with CV disease and CV risk factors highlights the need to add the screening and management of CV diseases and risk factors as a priority among patients with rheumatoid arthritis.

Rheumatoid arthritis is a multisystem disorder that affects not only the musculoskeletal system but also other vital organ systems. This report tackles a case of a Filipino adult female with a 28-year history of rheumatoid arthritis on chronic DMARD and steroid use who developed symptoms of heart failure. This report will review the perioperative implications of a patient with rheumatoid arthritis for triple valve surgery.
Arthritis, Rheumatoid

Introduction: Chinese medicine (CM) external therapy is commonly used to treat rheumatoid arthritis (RA) in combination with conventional drug. This study aims to provide a comprehensive synthesis on the efficacy of CM external therapy combined with conventional drug treatment in RA. Methods: Randomised controlled trials (RCTs) experimenting the efficacy of CM external therapy (acupuncture, moxibustion and CM fumigation) combined with conventional drug in comparison with conventional drug only in RA patients were collected from PubMed, Medline, Cochrane Central of Controlled Trials (CENTRAL), ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and Wanfang databases. Quality was assessed using the Cochrane Risk of Bias Tool. The outcome measures which include Disease Activity Score-28 (DAS28), Visual Analogue Scale (VAS), Swollen Joint Count (SJC), Tumour Necrosis Factor (TNF-α), serum levels of C-reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) were analysed using Review Manager 5.4.1 and GRADEpro GDT online software. Results: Fifty RCTs fulfilling the criteria were included. Although some level of efficacy was statistically noted on the use of CM external therapies, their certainty levels are mixed, ranging only in between moderate and low. Conclusions Mixed levels of certainty has hindered the drawing of conclusion. The addition of CM external therapies to conventional drug treatment may provide some benefits in RA. Further clinical trials with considerations in minimising the risk of bias are recommended to provide more high-quality evidence in the effect of CM external therapies as a complementary treatment in RA.
Medicine, Chinese Traditional ; Fumigation ; Meta-Analysis [Publication Type] ; Moxibustion ; Arthritis, Rheumatoid ; Systematic Review [Publication Type]

OBJECTIVE: To observe the effects of different suspension moxibustion methods on the syndrome characteristics and inflammatory factors of rats with rheumatoid arthritis (RA) of heat bi syndrome and to prove the concept of "moxibustion can be used for heat syndrome". METHODS: Among seventy Wistar rats, 12 rats were randomly selected as a normal group, and the remaining rats were induced by collagen combined with wind, dampness, and heat environmental stimulation to establish the RA model of heat bi syndrome. Forty-eight rats with successful model establishment were further randomly divided into a model group and three moxibustion groups (mild moxibustion group, rotating moxibustion group and sparrow-pecking moxibustion group), with 12 rats in each group. The acupoints "Quchi" (LI 11), "Dazhui" (GV 14) and ashi point were used in all moxibustion groups, with mild moxibustion, rotating moxibustion, and sparrow-pecking moxibustion intervention given respectively, each acupoint was treated with moxibustion for 10 min a day, and 6 days were considered one course of treatment, with a total of three courses. After the intervention, the arthritis index (AI), the Evans blue (EB) extravasated volume in the soft tissue of the right hind paw, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in the serum were measured by ELISA in each group. The volume of the bilateral hind paw was measured; the infrared thermal imaging was collected to analyze the temperature of the plantar area of the bilateral foot pads, and the reaction time of plantar heat pain was calculated before and after modeling, as well as after the 1st, 2nd and 3rd courses of interrention. The ankle dorsiflexion angle of the right hind foot was also measured before and after modeling, as well as after the intervention. RESULTS: After modeling, compared with the normal group, the rats in the model group had more high-temperature areas in the bilateral hind limbs, abnormal AI score, abnormal bilateral hind paw volume, abnormal temperature of the plantar area of the bilateral foot pads, abnormal foot pain response time, abnormal right hind ankle dorsiflexion angle, abnormal right hind paw soft tissue EB extravasation, and abnormal serum TNF-α and IL-10 levels (P<0.01, P<0.05). After the intervention, compared with the model group, the rats in each moxibustion group had decreased or disappeared high-temperature areas in the bilateral hind limbs, EB extravasated volume in the soft tissue of the right hind paw was reduced (P<0.05), and the right ankle dorsiflexion angle was increased (P<0.05), serum level of TNF-α was reduced, and level of IL-10 increased (P<0.05); the AI scores in the mild moxibustion group and the sparrow-pecking moxibustion group was decreased (P<0.01, P<0.05). After the 1st, 2nd and 3rd courses of intervention, compared with the model group, the bilateral hind paw volume of rats in each moxibustion group was decreased (P<0.05, P<0.01), and plantar heat pain reaction time was increased (P<0.05). After the 2nd course and the 3rd course of intervention, the temperature of the right hind paw pad area was decreased in each moribustion group (P<0.05); after the 3rd courses of intervention, the temperature of the left hind paw pad area was decreased in the mild moxibustion group (P<0.05). CONCLUSION Suspension moxibustion could adjust the serum levels of TNF-α and IL-10 to improve the syndrome characteristics of RA rats of heat bi syndrome, such as joint redness, swelling, heat, pain and activity restriction. The effect of mild moxibustion is the most prominent. The findings could provide scientific basis for "moxibustion can be used for heat syndrome".
Animals ; Rats ; Arthritis, Rheumatoid/therapy* ; Evans Blue ; Hot Temperature ; Interleukin-10/genetics* ; Moxibustion ; Rats, Wistar ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVES: To observe the clinical efficacy of moxibustion as an adjunctive treatment for rheumatoid arthritis (RA) based on conventional medication and its effects on serum sclerostin (SOST) and β-catenin levels, exploring the potential mechanisms by which moxibustion may protect joint bones in RA patients. METHODS: Seventy-six RA patients were randomly divided into an observation group (38 cases, 3 cases dropped out) and a control group (38 cases, 4 cases were eliminated, 2 cases dropped out). The patients in the control group were treated with conventional oral medication; based on the treatment of the control group, the patients in the observation group were treated with moxibustion. The direct moxibustion was applied at Zusanli (ST 36) on both sides and ashi points around small joints, and indirect moxibustion was applied at Shenshu (BL 23) on both sides and ashi points around large joints. The treatment was given three times a week for a total of 5 weeks. The count of pain and swollen joint, morning stiffness score, disease activity score of 28 joints (DAS28), visual analogue scale (VAS) score, health assessment questionnaire (HAQ) score, and serum levels of SOST, β-catenin, and tumor necrosis factor-α (TNF-α) were evaluated before and after treatment in the two groups. RESULTS: Compared those before treatment, after treatment, both groups showed a reduction in pain and swollen joint count (P<0.01, P<0.05), morning stiffness, DAS28, VAS, and HAQ scores (P<0.01, P<0.05), with the observation group having lower scores than the control group (P<0.01). Serum levels of SOST, β-catenin, and TNF-α after treatment in the observation group were lower than those in both before treatment and the control group (P<0.01, P<0.05). There was a positive correlation between the difference in serum β-catenin levels before and after treatment and the difference in serum SOST (r=0.578, P<0.001) and TNF-α (r=0.403, P<0.05) levels in the observation group. CONCLUSIONS In addition to medication, moxibustion as an adjunctive treatment could significantly alleviate joint pain and reduce disease activity in RA patients, suggesting a potential role in joint protection. This mechanism may be related to the inhibition of the inflammatory factor TNF-α, regulation of β-catenin levels, and reduction in the production of the endogenous negative regulator protein SOST within the Wnt/β-catenin signaling pathway.
Humans ; Moxibustion ; Tumor Necrosis Factor-alpha ; beta Catenin ; Acupuncture Points ; Arthritis, Rheumatoid/therapy* ; Arthralgia ; Adaptor Proteins, Signal Transducing

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
Humans ; Arthritis, Rheumatoid ; Cohort Studies ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; East Asian People ; Prospective Studies ; Vaccination/adverse effects*

Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthritis, Rheumatoid/surgery* ; Risk Factors ; Patients ; Arthroplasty, Replacement, Hip/adverse effects*

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that poses a major healthcare challenge. In China, approximately 5 million patients are reported to have RA. Notably, Chinese patients with RA often experience a prolonged disease course and increased disease activity, leading to a substantial disease burden. The Chronic Disease Management Group of the Special Committee on Rheumatology and Immunology of Cross-Straits Medicine Exchange Association has advocated for an all-encompassing, continuous, and proactive scientific management approach for RA. This initiative has culminated in the formulation of the "Expert Recommendations for the Chronic Disease Management of Rheumatoid Arthritis", a comprehensive guideline developed through extensive consultations and consideration of the unique characteristics of RA. We have outlined 16 expert recommendations, addressing 10 key aspects central to RA management. We aim to enhance treatment outcomes for patients, streamline the distribution of medical resources, and reduce treatment-related burden on society, families, and individuals affected by this condition.
Humans ; Rheumatic Fever ; Arthritis, Rheumatoid/drug therapy* ; Rheumatology ; Chronic Disease ; Disease Management ; Antirheumatic Agents/therapeutic use*

This study aims to investigate the effect and mechanism of total triterpenes of Euphorbium in treating rheumatoid arthritis(RA). The rat model of RA was established with Freund's complete adjuvant(FCA). Male rats were randomly assigned into control, model, Tripterygium glycosides(7.5 mg·kg~(-1)), and low-, medium-, and high-dose total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1), respectively) groups, with 10 rats in each group. In other groups except the control group, 0.2 mL FCA was injected into the right hind toe. Rats in the intervention groups were administrated with corresponding drugs by gavage, and the control group and the model group with the same volume of 0.5% CMC-Na solution once a day. During the treatment period, the swelling degree of the hind paw was measured and the arthritis was scored until day 30. At the end of drug administration, the pathological changes of the joint tissue were observed by hematoxylin-eosin staining. The content of malondialdehyde(MDA), glutathione(GSH), and Fe~(2+) and the activity of superoxide dismutase(SOD) in the joint tissue were measured by biochemical colorimetry. RT-PCR was performed to determine the mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), and acyl-CoA synthetase long chain family member 4(ACSL4) in the joint tissue. Western blot was employed to determine the protein levels of Nrf2, Kelch-like ECH-associated protein 1(Keap1), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), SOD2, GPX4, and ACSL4 in the joint tissue. The results showed that the treatment with Tripterygium glycosides(7.5 mg·kg~(-1)) and total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1)) alleviated the swelling degree of bilateral hind limbs, decreased the arthritis score, reduced joint tissue lesions and the content of MDA and Fe~(2+) in the joint tissue, and increased GSH content and SOD activity. Furthermore, the interventions up-regulated the protein and mRNA levels of Nrf2 and GPX4, down-regulated the protein and mRNA levels of ACSL4, and up-regulated the protein levels of Keap1, NQO1, HO-1, and SOD2 in the Nrf2/HO-1/GPX4. In summary, the total triterpenes of Euphorbium can treat RA by inhibiting lipid peroxidation and abnormal ferroptosis, which may involve the Nrf2/HO-1/GPX4 signaling pathway.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Triterpenes/pharmacology* ; Oxidative Stress ; Arthritis, Rheumatoid/genetics* ; Glutathione ; Superoxide Dismutase/metabolism* ; Glycosides/pharmacology* ; RNA, Messenger/metabolism*

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
Animals ; Mice ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Molecular Docking Simulation ; Arthritis, Rheumatoid/genetics* ; Tumor Necrosis Factor-alpha ; NF-kappa B ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional