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.

Weber-Christian Disease (WCD), or relapsing febrile nodular panniculitis is a rare form of subcutaneous fat inflammation commonly affecting women aged 40-75 years old. It is rarer in children with only 1 previously reported case in the Philippines. It presents as erythematous nodules, frequently affecting the lower extremities. There is no standard treatment, but reportedly improves with steroid therapy, cyclosporine, and immunomodulators.

This is a case of a 12-year-old-female, who presented with a 4-month history of palpable facial nodules, thigh pains, and recurrent fever. Work-up for hypersensitivity reaction, autoimmune condition, hematologic problem, or infectious etiology yielded unremarkable findings, and corresponding management had no significant response. Patient developed firm lesions on the abdomen which was sent for biopsy and showed results consistent with WCD. Steroid, hydroxychloroquine, and topical indomethacin were then started and noted gradual improvement of the lesions. Patient was then discharged improved with lesions noted to progressively decrease in size and with no appearance of newer lesions upon follow-up.

WCD is a rare form of nodular panniculitis, more so in the younger age group. It is characterized by presence of cutaneous lesions associated with systemic symptoms. Skin biopsy is necessary to confirm its diagnosis. Visceral organ involvement and failure to respond to treatment may result to poor prognosis, and occasionally leads to death.

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.

OBJECTIVES: Patients with connective tissue diseases (CTD) have a high incidence of cardiac involvement, which often presents insidiously and can progress rapidly, making it one of the leading causes of death. Multiparametric cardiovascular magnetic resonance (CMR) provides a comprehensive quantitative evaluation of myocardial injury and is emerging as a valuable tool for detecting cardiac involvement in CTD. This study aims to investigate the correlations between CMR features and serological biomarkers in CTD patients, assess their potential clinical value, and further explore the impact of pre-CMR immunotherapy intensity on CMR-specific parameters, thereby evaluating the role of CMR in the early diagnosis of CTD-related cardiac involvement. METHODS: A retrospective analysis was conducted on 72 consecutive CTD patients who underwent CMR at Xiangya Hospital of Central South University between September 2019 and March 2024. Clinical data, serological markers, and CMR parameters were collected. Differences in CMR parameters were compared between CTD patients with positive and negative serological markers. Correlations between serological biomarkers and CMR parameters were analyzed, with subgroup analyses performed for different CTD subtypes. Logistic regression (univariate and multivariate) was applied to explore the effects of pre-CMR immunotherapy intensity on CMR parameters, and receiver operating characteristic (ROC) curve analysis was used to determine cutoff values. RESULTS: In differential analyses, CTD patients with elevated interleukin (IL)-1β and IL-6 levels exhibited significantly higher myocardial T₂ values compared with those with normal levels (<i>Pi>=0.014, <i>Pi>=0.012). Elevated IL-10 was associated with a higher prevalence of microvascular lesions on CMR (<i>Pi>=0.038). Correlation analysis revealed a significant positive association between high-sensitivity cardiac troponin T (hs-cTnT) and T₂ values (<i>ri>=0.371, <i>Pi>=0.009). ROC analysis indicated that when the hs-cTnT threshold was 0.01 ng/mL, the sensitivity and specificity for predicting elevated left ventricular T₂ values were 85.71% and 61.11%, respectively [area under the curve (AUC)=0.767, <i>Pi>=0.001]. hs-cTnT and creatine kinase (CK) were also positively correlated with native T₁ values (<i>ri>=0.371, <i>Pi>=0.009; <i>ri>=0.364, <i>Pi>=0.032). Erythrocyte sedimentation rate (ESR) showed a positive correlation with the percentage of the late gadolinium enhancement (LGE) (<i>ri>=0.236, <i>Pi>=0.047). Conversely, hs-cTnT correlated negatively with global radial strain (GRS) (<i>ri>=-0.297, <i>Pi>=0.034), while CK correlated negatively with both GRS and global circumferential strain (GCS) (<i>ri>=-0.292, <i>Pi>=0.022; <i>ri>=-0.282, <i>Pi>=0.027). Among patients with elevated hs-cTnT, the cumulative glucocorticoid dose prior to CMR was negatively associated with elevated T₂ values (<i>ORi>=0.997, <i>Pi>=0.018), and this correlation remained significant after adjusting for duration of steroid use (<i>ORi>=0.997, <i>Pi>=0.044). ROC analysis showed that when the cumulative glucocorticoid dose did not exceed 613 mg/mL (prednisone equivalent), the sensitivity and specificity for predicting elevated T₂ values were 90.48% and 77.78%, respectively (AUC=0.862, <i>Pi><0.001). CONCLUSIONS Several inflammatory biomarkers demonstrate correlations with specific CMR parameters, with hs-cTnT showing the strongest associations across multiple indices. Elevated hs-cTnT suggests a high likelihood of cardiac involvement in CTD patients. Furthermore, pre-CMR immunotherapy intensity significantly influences the specificity of T₂ mapping, indicating its importance in interpreting CMR results. These findings provide critical insights for clinicians in the early recognition, timely intervention, and disease evaluation. Future research should further explore the role of CMR in the assessment of CTD-related cardiac assessment of CTD-related cardiac involvement. Future studies should further explore the role of CMR in evaluating CTD cardiac manifestations and its integration with other clinical data to optimize patient management.
Humans ; Retrospective Studies ; Male ; Female ; Connective Tissue Diseases/blood* ; Middle Aged ; Adult ; Biomarkers/blood* ; Magnetic Resonance Imaging/methods* ; ROC Curve ; Interleukin-6/blood* ; Troponin T/blood*

OBJECTIVES: Rheumatoid arthritis (RA) imposes a heavy burden on individuals, families, and society. This study analyzed the incidence and mortality trends of RA in China from 1990 to 2023 to provide epidemiological evidence for precise prevention and control. METHODS: Data on RA incidence, age-standardized incidence rate (ASIR), deaths, and age-standardized mortality rate (ASMR) in China by sex and age group from 1900 to 2021 were extracted from the Global Burden of Disease (GBD) 2021 database. Joinpoint regression was used to analyze trends in ASIR and ASMR. An age-period-cohort model was constructed using R4.3.1 to evaluate longitudinal age trends and estimate relative risk (RR) values for period and cohort effects. RESULTS: In 2021, the number of RA cases, ASIR, deaths, and ASMR in China were 247 300, 13.70 per 100 000, 10 300, and 0.54 per 100 000, respectively. From 1990 to 2021, the ASIR of RA increased annually among both females and males, with average annual percentage changes (AAPCs) of 0.44% and 0.72%, respectively. Over the same period, ASMR declined in the total population and among females, with AAPCs of -0.78% and -1.19%, while the change in males was not statistically significant. Age-period-cohort analysis showed that the peak incidence occurred in women aged 60-64 years and men aged 75-79 years, and mortality increased with age. The period effect for incidence rose in both sexes, reaching 1.10 [95% confidence interval (<i>CIi>) 0.94 to 1.27] for females and 1.14 (95% <i>CIi> 1.02 to 1.27) for males during 2017 to 2021, compared with 2002 to 2006. The mortality period effect <i>RRi> exhibited a downward-upward-downward pattern, decreasing to 0.56 (95% <i>CIi> 0.52 to 0.61) in females and 0.75 (95% <i>CIi> 0.68 to 0.82) in males in 2017 to 2021. Cohort analysis indicated that the highest incidence risk occurred in individuals born during 2012 to 2016, while the cohort effect <i>RRi> for female RA mortality showed a continuous decline beginning with the 1922 to 1926 birth cohort. CONCLUSIONS The incidence and mortality risks of RA in China have continued to decline. However, with the aging of the population, the incidence and mortality risks among the elderly have increased. Middle-aged women and elderly men should receive focused attention. Health authorities should strengthen education, prevention, and screening among middle-aged women and enhance disease monitoring in elderly populations to reduce the national burden of RA.
Humans ; China/epidemiology* ; Arthritis, Rheumatoid/epidemiology* ; Incidence ; Male ; Female ; Middle Aged ; Adult ; Aged ; Cohort Studies ; Mortality/trends* ; Age Distribution ; Age Factors ; Aged, 80 and over ; Adolescent

The wrist joint is a highly mobile functional joint. Wrist conditions including traumatic and degenerative arthritis, rheumatoid arthritis, and giant cell tumors of the distal radius, cause significant pain and mobility impairment. In joint surgery, the decision to use joint prostheses to reconstruct joint function is greatly influenced by the characteristics of the prosthesis (Mok et al., 2016). However, traditional implants have limitations such as shape mismatch, inadequate implant-bone interface strength which causes loosening, and poor bone ingrowth (Zhang et al., 2014).
Humans ; Joint Prosthesis ; Wrist Joint/surgery* ; Prosthesis Design ; Arthroplasty, Replacement ; Arthritis, Rheumatoid/surgery*

Rheumatoid arthritis (RA), an autoimmune disease characterized by chronic inflammation of synovial tissue, is divided into two subtypes-anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. While the pathogenic mechanisms of ACPA-positive RA are well-understood, the etiology of ACPA-negative RA remains largely unknown. The association between RA and periodontitis (PD) has been observed since the early 1900s, with the two diseases sharing common genetic and environmental risk factors that lead to the progressive destruction of bone and connective tissue. However, the associations between PD and the two subtypes of RA differ. This comprehensive review aims to provide an updated understanding of the epidemiological association between RA and PD, explore potential pathogenic mechanisms linking the two diseases, and highlight the key distinctions between the subtypes of RA and their respective associations with PD. We also discuss the possibility of early intervention or the treatment of the two diseases. Ultimately, this review aims to provide valuable insights for future research in this field.
Humans ; Arthritis, Rheumatoid/complications* ; Periodontitis/complications* ; Anti-Citrullinated Protein Antibodies/immunology* ; Risk Factors

OBJECTIVES: To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of <i>Buyang Huanwui> Decoction (BYHWT) on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients (FLS-RA) cultured under a hypoxic condition. METHODS: Forty normal Wistar rats were randomized into two groups (<i>ni>=20) for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera. FLS-RA were cultured in routine condition or exposed to hypoxia (10% O₂) for 24 h wigh subsequent treatment with IL-1β, followed by treatment with diluted BYHWT-medicated serum (5%, 10% and 20%) or control serum. AnnexinV-APC/7-AAD double staining and T-AOC kit were used for detecting apoptosis and total antioxidant capacity of the cells, and the changes in ROS, ATP level, mitochondrial membrane potential and Ca²⁺ homeostasis were analyzed. The changes in mRNA and protein expressions of BNIP3, PI3K and AKT and mRNA expressions of LC3, Beclin-1 and P62 were detected using RT-qPCR and Western blotting. RESULTS: Treatment with BYHWT-medicated serum dose-dependently lowered apoptosis rate of IL-1β-induced FLS-RA with hypoxic exposure. The treatment significantly decreased T-AOC concentration, increased ROS production, autophagosome formation and ATPase levels, and lowered mitochondrial membrane potential and Ca²⁺ level in the cells. In IL-1β-induced FLS-RA with hypoxic exposure, treatment with BYHWT-medicated serum significantly increased BNIP3 protein expression, decreased the protein expressions of PI3K and AKT, increased the mRNA expressions of BNIP3 and P62, and lowered the mRNA expressions of PI3K, AKT, LC3 and Beclin-1 without significantly affecting Beclin-1 protein expression. The cells treated with 5% and 10% BYHWT-medicated serum showed no significant changes in LC3 expression. CONCLUSIONS BYHWT inhibits mitochondrial autophagy in IL-1β-induced FLS-RA with hypoxic exposure possibly by inhibiting BNIP3-mediated PI3K/AKT signaling pathway.
Drugs, Chinese Herbal/pharmacology* ; Arthritis, Rheumatoid/pathology* ; Animals ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Autophagy/drug effects* ; Humans ; Fibroblasts/cytology* ; Rats, Wistar ; Membrane Proteins/metabolism* ; Rats ; Phosphatidylinositol 3-Kinases/metabolism* ; Mitochondria/metabolism* ; Cells, Cultured ; Proto-Oncogene Proteins/metabolism* ; Apoptosis/drug effects* ; Cell Hypoxia ; Synovial Membrane/cytology* ; Male ; Mitochondrial Proteins

OBJECTIVES: To investigate the regulatory effect of LINC00837/miR-671-5p/SERPINE2 functional axis on pathological processes of fibroblast-like synovial cells (FLS) in rheumatoid arthritis (RA). METHODS: RA-FLS were transfected with a LINC00837 overexpression plasmid (pcDNA3.1-LINC00837), a LINC00837 interference plasmid (siRNA-LINC00837), or their respective negative control plasmids (pcDNA3.1-NC and siRNA-NC). Dual luciferase was used to verify the targeting relationship between LINC00837 and miR-671-5p and between miR-671-5p and SERPINE2. RT-qPCR was used to detect the expression levels of LINC00837, miR-671-5p and SERPINE2 in normal FLS or the transfected cells, whose proliferation and migration abilities were assessed using Edu assay and scratch healing assay and by detecting the expression levels of Ki-67, PCNA, E-cadherin and N-cadherin with Western blotting. The changes in cellular secretion of the inflammatory cytokines (TNF‑α, IL-17, IL-4 and IL-10) were examined using ELISA. RESULTS: Dual luciferase reporter gene assay showed that LINC00837 was capable of binding to the 3'-UTR of miR-671-5p, and the latter bound to the 3-UTR of SERPINE2 at specific binding sites between them. Compared with normal FLS, RA-FLS showed significantly increased expressions of LINC00837 and SERPINE2, lowered miR-671-5p expression and enhanced proliferation and migration abilities with increased expressions of pro-inflammatory cytokines and reduced expressions of anti-inflammatory cytokines. Transfection of RA-FLS with pcDNA-LINC00837 further enhanced cell proliferation and migration and the changes in the inflammatory cytokines, while transfection with si-LINC00837 produced the opposite changes. CONCLUSIONS RA-FLS have a LINC00837/miR-671-5p/SERPINE2 functional axis, which regulates cell proliferation, migration and secretion of inflammatory factors, and interventions targeting LINC00837 may provide a potential strategy to regulate the pathological processes in RA-FLS.
Arthritis, Rheumatoid/metabolism* ; MicroRNAs/metabolism* ; Humans ; Cell Proliferation ; Cell Movement ; Synovial Membrane/pathology* ; RNA, Long Noncoding/genetics* ; Fibroblasts/metabolism* ; Synoviocytes/metabolism* ; Cells, Cultured ; Transfection

OBJECTIVES: To explore the role of oxidative stress and immune infiltration in rheumatoid arthritis (RA). METHODS: RA datasets GSE55235 (10 RA <i>vsi> 10 normal samples) and GSE55457 (13 RA <i>vsi> 10 normal samples) from the GEO database were merged as the test set to identify the differentially expressed genes (DEGs) in RA using R. The DEGs were intersected with oxidative stress-related genes to obtain oxidative stress-associated DEGs. KEGG and GO enrichment analyses of the DEGs were performed, and the RA-related pathways and biological processes were analyzed using GSEA. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape, and the top 10 key genes were obtained using the Degree algorithm. The validation dataset GSE1919 from GEO database was used for ROC analysis of the key genes to obtain the core genes, and their correlations with infiltrating immune cells were analyzed using CIBERSORT. The results were verified by RT-qPCR for detecting expression levels of the core genes in RA and normal joint samples. RESULTS: We identified 89 oxidative stress-associated DEGs. Enrichment analysis suggested that these DEGs were involved in the biological processes including oxidative stress, chemical stress response, reactive oxygen species response, and lipopolysaccharide response. ROC analysis showed that the 5 core genes (STAT1, MMP9, MYC, CCL5, and JUN) all had AUC values >0.7, indicating their high diagnostic sensitivity and specificity for RA. These genes were closely correlated with immune cells, particularly T cells. RT-qPCR confirmed significant differential expressions of the core genes between RA and normal samples. CONCLUSIONS Oxidative stress and diverse immune responses are features of RA, and the immune responses contribute to activation of oxidative stress. The identified core genes can potential serve as new diagnostic markers for RA.
Arthritis, Rheumatoid/genetics* ; Oxidative Stress/genetics* ; Humans ; Computational Biology ; Protein Interaction Maps ; Gene Expression Profiling ; Gene Regulatory Networks