Characterization of virus-mediated autoimmunity and the consequences for pathological process in patients with systemic lupus erythematosus.

INTRODUCTION/OBJECTIVES: This study aimed to identify differentially expressed genes (DEGs) of systemic lupus erythematosus (SLE) using gene expression-based computational methodologies to analyze disease-immune interactions, which affect the development and progression of SLE. METHOD: Twenty-six patients with SLE and 46 healthy controls were selected from the Gene Expression Omnibus (GEO) database. The significantly enriched immune and virus-related gene lists were computed and visualized by using the DEGs from the gene set enrichment analysis (GSEA). Quantification of 38 immune cells was performed in determining the impact of immune cells on the virus mediated immunity in SLE by using ImmQuant algorithm. RESULTS: Thirty-nine upregulated and 57 downregulated were identified in SLE patient compared to the healthy controls. Upregulated genes were significantly implicated in Gene Ontology gene sets as cytokine mediated signaling, secretion, and exocytosis in immune response pathways in 26 female SLE patients. In addition, these genes were enriched in hepatitis C, influenza A, measles, Epstein-Barr virus, and herpes simplex virus 1 infection in Kyoto Encyclopedia of Genes and Genomes pathways. Especially, FCGR1A, IRF7, OAS2, CAMP, MX1, OAS3, OAS1, DEFA3, ISG15, and RSAD2 were involved in virus mediated SLE mechanism, and the expression for OAS1, OAS2, and IRF7 was closely associated with the quantities of colony forming unit-monocyte and colony forming unit-granulocyte. CONCLUSIONS: Identifying virus-mediated SLE genes and quantifies of immune cells were used to understand the pathological process and perform early diagnosis of female SLE, and will lead to clinical tools for treating SLE in patients. Key Points • Using gene expression-based computational methodologies, the 57 immune and viral genes were significantly upregulated in 26 SLE patients. • The identified three key  viral genes such as OAS1, OAS2, and IF7 were closely associated with colony-forming unit-monocytes and colony-forming unit-granulocytes, which affect the virus mediated immunity in SLE. • The viral genes and quantifies of immune cells are useful in understanding pathogenesis of SLE, and this will provide clinical strategies of potential treatment choices in SLE patients.

Effectiveness of paraffin bath therapy for the symptoms and function of hand diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Paraffin bath therapy is noninvasive and is widely used in various hand diseases. Paraffin bath therapy is easy to use, has fewer side effects, and can be applied to various diseases with different etiologies. However, there are few large-scale studies of paraffin bath therapy, and there is insufficient evidence of its efficacy. PURPOSE: The purpose of the study was to investigate the effectiveness of paraffin bath therapy for pain relief and functional improvement in various hand diseases through a meta-analysis. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials. METHODS: We searched for studies using PubMed and Embase. Eligible studies were selected based on the following criteria: (1) patients with any diseases of the hand; (2) comparison between paraffin bath therapy and no paraffin bath therapy; and (3) sufficient data on changes in the visual analog scale (VAS) score, grip strength, pulp-to-pulp pinch strength, or Austrian Canadian (AUSCAN) Osteoarthritis Hand index before and after paraffin bath therapy. Forest plots were drawn to visualize the overall effect. Jadad scale score, I2 statistics, and subgroup analyses were used to assess the risk of bias. RESULTS: A total of five studies included 153 patients who were treated and 142 who were not treated with paraffin bath therapy. The VAS were measured in all 295 patients included in the study, while the AUSCAN index was measured in the 105 patients with osteoarthritis. Paraffin bath therapy significantly reduced the VAS scores (mean difference [MD], -1.27; 95% confidence interval [CI] -1.93 to -0.60). In osteoarthritis, paraffin bath therapy significantly improved grip and pinch strength (MD -2.53; 95% CI 0.71-4.34; MD 0.77; 95% CI 0.71-0.83) and reduced the VAS and AUSCAN scores (MD -2.61; 95% CI -3.07 to -2.14; MD -5.02; 95% CI -8.95 to -1.09). DISCUSSION: Paraffin bath therapy significantly reduced the VAS and AUSCAN scores, and improved grip and pinch strength in patients with various hand diseases. CONCLUSIONS: Paraffin bath therapy is effective for alleviating pain and improving function in hand diseases, thereby improving quality of life. However, owing to the small number of patients included in the study and its heterogeneity, a further large-scale, well-structured study is needed.

Intra-Articular Injection of Rebamipide-Loaded Nanoparticles Attenuate Disease Progression and Joint Destruction in Osteoarthritis Rat Model: A Pilot Study.

OBJECTIVE: Rebamipide has antioxidant effects and is a drug with a local rather than systemic mechanism of action. Oxidative stress and inflammation in chondrocytes are the major factors contributing to the development and progression of osteoarthritis (OA). Since OA is mainly developed in weight bearing or overused joints, the locally sustained therapy is effective for targeting inflammatory component of OA. We investigated the effects of intra-articular injection of rebamipide loaded nanoparticles (NPs) in OA rat model. DESIGN: We fabricated rebamipide-loaded methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-PDLLA) and poly(D, L-lactide-co-glycolide) (PLGA) NPs that allow the sustained release of rebamipide. In vitro, chondrocytes from rat were used to investigate the cytotoxicity and anti-inflammatory effect of rebamipide-loaded NPs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into 7 groups, consisting of healthy control rats and rats injected with MIA alone or in combination with NPs, rebamipide (1 mg)/NPs, rebamipide (10 mg)/NPs, rebamipide (10 mg) solution, or oral administration. RESULTS: In vitro, rebamipide/NPs dose-dependently suppressed the mRNA levels of pro-inflammatory mediators, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, matrix metalloproteinase (MMP)-3, MMP-13, and cyclo-oxygenase-2. In vivo, the mRNA levels of pro-inflammatory components most markedly decreased in the intra-articularly injected rebamipide (10 mg)/NP group compared to other groups. Macroscopic, radiographic, and histological evaluations showed that the intra-articular injection of rebamipide/NPs inhibited cartilage degeneration more than rebamipide solution or rebamipide administration. CONCLUSIONS: Using a chemically induced rat model of OA, intra-articular delivery of rebamipide was associated with decreased local and systemic inflammatory response decreased joint degradation and arthritic progression.

Association between interleukin-10 polymorphisms and juvenile idiopathic arthritis: a meta-analysis.

INTRODUCTION: The aim of this review is to investigate IL-10 polymorphisms (-1082 G/A, -819 C/T, and -592 C/A) and their association with susceptibility to JIA. EVIDENCE ACQUISITION: A meta-analysis was conducted after database search for relevant articles (MEDLINE and EMBASE). EVIDENCE SYNTHESIS: A total of seven studies involving 1495 patients and 1670 controls were considered in the meta-analysis. There was no association between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and JIA in allele contrast and any of the genetic models (allele contrast: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.79-1.02, P=0.09; OR=0.97, 95% CI 0.83-1.13, P=0.68; OR=0.92, 95% CI 0.81-1.06, P=0.24, respectively). In subgroup analysis, none of the subtypes of JIA including systemic, rheumatoid factor (RF)-positive polyarticular, RF-negative polyarticular, and oligoarticular was not significantly associated with IL-10 polymorphism. Meta-analysis of the IL-10 haplotype revealed no association between GCC, ACC, and ATA haplotypes and JIA. CONCLUSIONS: This meta-analysis showed that IL-10 polymorphisms were not associated with risk of JIA.

Association between interleukin-1, interleukin-6, and tumor necrosis factor-alpha polymorphisms and juvenile idiopathic arthritis: a meta-analysis.

INTRODUCTION: In juvenile idiopathic arthritis (JIA), interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are associated with development and progression of JIA. We investigated whether IL-1, IL-6, and TNF-α polymorphisms were associated with susceptibility to JIA. EVIDENCE ACQUISITION: A meta-analysis was conducted on the associations between IL-1α-899 C/T, IL-1ß-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA (PubMed and Embase). EVIDENCE SYNTHESIS: A total of 27 studies involving 4678 JIA patients and 7634 controls were considered in the meta-analysis. There was no association between the IL-1α-899 C/T, IL-1ß-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA in allele contrast or any other genetic models. In subgroup analysis based on subtype, except for the dominant model of TNF-α-238 G/A, systemic JIA was not significantly associated with IL-6 and TNF-α polymorphisms. In Caucasians, the dominant and additive models of IL-1ß-511 C/T were significantly associated with JIA (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.09-2.00, P=0.01; OR 1.46, 95% CI 1.05-2.03, P=0.02, respectively). CONCLUSIONS: This meta-analysis showed no association between IL-1, IL-6, and TNF-α polymorphisms, and JIA, but the TT genotype of IL-1ß -511 C/T was associated with higher prevalence of JIA in Caucasians.

Is Rheumatoid Arthritis Related to Coffee Consumption in Korea? A Nationwide Cross-Sectional Observational Study.

Coffee consumption is gradually increasing in Korea. As a result, interest in the relationship between coffee consumption and various diseases is growing. Several factors affect the development of rheumatoid arthritis (RA), and coffee consumption may be related. We conducted a nationwide cross-sectional study using data from the Korea National Health and Nutrition Examination Survey (2012-2016). A total of 12,465 eligible participants (4819 men and 7646 women) were included in the study. Participants with RA were defined as those who were diagnosed and currently being treated by physicians. Daily coffee consumption amounts were categorized as none, <1 cup, 1-2 cups, 2-3 cups, and ≥3 cups a day based on a self-report. A multivariable logistic regression model was employed, and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for the odds of participants having RA with respect to coffee consumption. Compared to the no-coffee group, the ORs for RA in the <1 cup and 1-2 cups groups were 2.99 (95% CI 0.33-27.28) and 2.63 (95% CI 0.31-22.63) in men, respectively, and the ORs for RA for women in the <1 cup, 1-2 cups, 2-3 cups, and ≥3 cups groups were 0.62 (95% CI 0.31-1.26), 0.67 (95% CI 0.33-1.37), 1.08 (95% CI 0.35-3.36), and 1.43 (95% CI 0.25-8.36), respectively. Our study concludes, therefore, that daily coffee consumption is not related to the prevalence of RA in the general Korean population.

Switching from TNFα inhibitor to tacrolimus as maintenance therapy in rheumatoid arthritis after achieving low disease activity with TNFα inhibitors and methotrexate: 24-week result from a non-randomized, prospective, active-controlled trial.

BACKGROUND: Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX). METHODS: This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period. RESULTS: In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01-1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated. CONCLUSION: This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks. TRIAL REGISTRATION: Korea CDC CRIS, KCT0005868 . Registered 4 February 2021-retrospectively registered.

Prevalence of chronic obstructive pulmonary disease in patients with rheumatoid arthritis: A cross-sectional study.

OBJECTIVE: Rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) are both chronic inflammatory diseases; the prevalence of COPD in RA patients is known to be high. However, the prevalence of both RA and COPD differs according to sex; the relationship between RA and COPD may also vary according to sex. Therefore, we investigated the prevalence of COPD and its association in patients with RA in Korea by sex. METHODS: We conducted a nationwide cross-sectional study using data from the Korea National Health and Nutrition Examination Survey. A total of 12 417 men and 15 878 women were included. In this study, RA was defined as physician diagnosed or currently under RA treatment. COPD was defined based on spirometry results, chronic symptoms, and smoking history. Multivariable logistic regression models were employed and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for COPD prevalence in patients with RA. RESULTS: The prevalence of COPD was 15.5% in men with RA, 3.5% in women with RA, 7.8% in men without RA, and 2.2% in women without RA. After adjustment for potential confounding variables, including smoking status, RA was significantly associated with COPD in men (OR 2.16, 95% CI 1.06-4.40), but not in women (OR 1.58, 95% CI 0.81-3.10). CONCLUSIONS: In Korea, the prevalence of COPD was high in patients with RA of both sexes; RA and COPD was significantly likely to be associated in men, but not in women.

KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities.

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

Associations between interleukin 18 gene polymorphisms and susceptibility to vasculitis: A meta-analysis.

Interleukin 18 (IL18), a pro-inflammatory cytokine, affects the development and progress of vasculitis. The production, expression, and function of this cytokine are affected by polymorphisms of promoter region of the IL18 gene. In this study, a meta-analysis of the associations between several IL18 polymorphisms and susceptibility to vasculitis was performed. Published literature from PubMed and Embase were retrieved. In total, nine studies comprising 1006 patients with vasculitis and 1499 controls combined, and the investigating the rs187238, rs194618, and rs360719 polymorphisms of the promoter region of the IL18 gene, were included in the meta-analysis. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated with fixed-effects model or random-effects model. The recessive model of the rs194618 polymorphism was found to be significantly associated with a high susceptibility to vasculitis (OR = 1.54, 95% CI = 1.02-2.33, P = 0.04), especially in the Mongoloid race, where the A allele of rs194618 was associated with a low risk of the disease (OR = 0.77, 95% CI = 0.62-0.95, P = 0.01). By contrast, the rs187238 and rs360719 polymorphisms were not associated with this inflammatory condition. This meta-analysis showed that some IL18 polymorphisms are associated with susceptibility to vasculitis. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 203-211).

Comparison of the efficacy and safety of CELBESTA® versus CELEBREX® in patients with rheumatoid arthritis: a 6-week, multicenter, double-blind, double-dummy, active-controlled, randomized, parallel-group, non-inferiority phase 4 clinical trial.

OBJECTIVES: Celecoxib is a selective cyclooxygenase (COX)-2 inhibitor that is commonly used to reduce the incidence of gastrointestinal (GI) complications in patients with rheumatoid arthritis (RA). CELBESTA® is a generic equivalent to CELEBREX®, a celecoxib preparation. This study compared the efficacy and safety of CELBESTA® and CELEBREX® in patients with RA. METHODS: This was a multicenter, double-blind, double-dummy, active-controlled, randomized, parallel-group, non-inferiority clinical trial. The primary endpoint was a change from baseline in self-assessed pain intensity determined using a 100-mm visual analog scale after 6 weeks of treatment. RESULTS: After a washout period, 119 eligible subjects were randomized to one of two groups (CELBESTA® group, n = 61; CELEBREX® group, n = 58). CELBESTA® was not inferior to CELEBREX® because the upper limit of two-sided 95% confidence interval (CI) for the difference between the two groups (difference in the least square [LS] mean, -8.68 mm; two-sided 95% CI -16.59 mm to -0.77 mm) was less than the non-inferiority margin (10 mm). There were no significant differences in GI complications and renal toxicity. CONCLUSIONS: CELBESTA® was not inferior to CELEBREX® with regard to the pain relief efficacy in RA patients, and the tolerability and safety profiles were excellent and at similar levels for both preparations.

Correlation between TM joint disease and rheumatic diseases detected on bone scintigraphy and clinical factors.

The aim of this study was to evaluate the effect of rheumatic disease as a risk factor for temporomandibular disease (TMD). A total of 143 outpatients reporting symptoms indicating rheumatic disease at their first visit to the rheumatology clinic were included. We evaluated the temporomandibular joint (TMJ) with scintigraphic images, and standard questionnaires were administered for the symptomatic assessment for all patients. The patients were classified into 'healthy controls' or as per their diagnosis into 'osteoarthritis', 'axial spondyloarthritis', 'peripheral spondyloarthritis', 'rheumatoid arthritis', or 'other rheumatic diseases' groups. The patients were also differentiated depending on the presence or absence of axial involvement. The relation between the rheumatic disease type and findings at the TMJ were evaluated using statistical analyses. Axial spondyloarthritis, peripheral spondyloarthritis, and rheumatic arthritis patients showed significantly higher scintigraphic uptake at the TMJ compared with those in the control and osteoarthritis groups (axial spondyloarthritis: 4.5, peripheral spondyloarthritis: 4.5, rheumatoid arthritis: 4.09, control: 3.5, osteoarthritis: 3.4, p < 0.0001). Compared with patients without axial involvement, patients with axial involvement also showed significantly higher TMJ scintigraphic uptake (axial involvement: 4.24, without axial involvement: 3.50, p < 0.0001) with elevated symptomatic rates in TMD (axial involvement: 17.82, without axial involvement: 9.97, p < 0.005).

A comparative pilot study of oral diacerein and locally treated diacerein-loaded nanoparticles in a model of osteoarthritis.

Diacerein (DIA) is a slow-acting drug for osteoarthritis (OA). Oral DIA administration, however, exerts side effects including diarrhea and urine discoloration. We fabricated DIA-loaded poly(d,l-lactide-co-glycolide) nanoparticles (DIA/PLGA NPs) that allow sustained release of DIA. In vitro, rat synoviocytes were used to investigate the cytotoxicity and anti-inflammatory effects of DIA-loaded NPs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into seven groups that included non-treated healthy control rats and rats injected with MIA alone or in combination with NPs, DIA(5%) solution, DIA(1%)/NPs, DIA(5%)/NPs, or oral DIA. The in vitro studies revealed that DIA/PLGA NPs dose-dependently suppressed mRNA levels of pro-inflammatory cytokines and enzymes, including interleukin-1 (IL-1), IL-6, tumor necrosis factor-α, matrix metalloproteinase-3 (MMP-3), MMP-13, cyclo-oxygenase-2, and a disintegrin and metalloproteinase with thrombospondin motifs-5 in synoviocytes. The in vivo studies demonstrated that intra-articular treatment of OA rat models with DIA-loaded PLGA NPs markedly decreased mRNA levels of these pro-inflammatory factors and increased those of anti-inflammatory cytokines (IL-4 and IL-10). Micro-computed tomography and histological evaluations indicated that intra-articular injection of DIA-loaded NPs was effective in protecting against cartilage degradation. Administration of DIA/PLGA NPs via intra-articular injection is promising for inhibiting inflammation and protecting against cartilage degradation in OA.

A Real-World Experience of Mycophenolate Mofetil for Systemic Sclerosis: A Retrospective Multicenter Observational Study.

OBJECTIVES: This study aims to assess the efficacy and safety of mycophenolate mofetil (MMF) on lung function and skin thickness in Korean patients with systemic sclerosis-interstitial lung disease (SSc-ILD) in a real-world setting. PATIENTS AND METHODS: This retrospective, medical chart-based study was performed at four centers in South Korea and included 34 patients (2 males, 32 females; median age 50.5 years; range, 25 to 72 years) with SSc-ILD. We investigated changes in forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), and modified Rodnan skin score (mRSS) according to MMF treatment for 24 months. RESULTS: The mean dose and treatment duration of MMF were 1,338.2±439.0 mg/day and 13.1±9.3 months, respectively. Although FVC decreased significantly at 15 months, FVC and DLCO did not change significantly during treatment with MMF. Median mRSS decreased significantly from 17.5 (2-40) to 10.5 (2-40) units (p<0.0001). Thirteen patients (38.24%) discontinued treatment with MMF [treatment duration 8.00 (3.0-24.0) months]; the predominant cause of discontinuation was of economic nature (46.15%). No serious adverse events were reported. CONCLUSION: This real-world based study supports the role of MMF in the stabilization of lung function and the improvement in skin thickness with an acceptable safety profile in patients with SSc. Economic burden is the main cause of discontinued treatment with MMF.

Simplified disease activity changes in real-world practice: a nationwide observational study of seropositive rheumatoid arthritis patients with moderate-to-high disease activity.

BACKGROUND/AIMS: The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. METHODS: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. RESULTS: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was -19.0 in the bDMARD group and -12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. CONCLUSION: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Tumour necrosis factor alpha gene polymorphisms in women with recurrent pregnancy loss: a meta-analysis.

Tumour necrosis factor alpha (TNF-α) concentration is associated with recurrent pregnancy loss (RPL). Moreover, TNF-α promoter polymorphisms affect cellular TNF-α concentrations. Although several studies on TNF-α polymorphisms have been reported, these studies only define specific loci and result in conflicting conclusions. The meta-analysis in this study was performed to examine the relationship between various TNF-α polymorphisms and RPL. We searched for articles, using MEDLINE and Embase, and performed meta-analysis of 21 studies involving 3437 cases and 4016 controls. The results demonstrated that the -308G/A polymorphism is positively associated with RPL, particularly in cases involving three or more miscarriages. For -1031T/C, -863C/A, and -376G/A polymorphisms, recessive and homozygote models revealed significant associations with RPL. However, -857C/T, -238G/A, and +488G/A polymorphisms showed no association with RPL. A subgroup analysis with respect to ethnicity demonstrated that the -308G/A and -238G/A polymorphisms are associated with RPL in Asian and Middle Eastern populations, respectively. This meta-analysis showed the associations between TNF-α polymorphisms and RPL. However, further studies of genetic polymorphisms in TNF-α other than -308G/A and -238G/A are required.

Relationship between coffee consumption and serum uric acid level in the general Korean population: A nationwide cross-sectional study.

OBJECTIVE: Coffee is one of the world's most consumed beverages, and its consumption is increasing. Serum uric acid levels are affected by dietary factors, and increased levels can cause a variety of diseases, including gout. This study aimed to investigate the relationship between coffee consumption and serum uric acid levels in the general Korean population. METHODS: A nationwide cross-sectional study was conducted using data from the Korean National Health and Nutrition Examination Survey in 2016. A total of 3005 participants who checked serum uric acid levels and a completed coffee consumption survey were included (1146 men and 1859 women). The amount of coffee consumption was examined via self-reporting and categorized as none, <1 cup, 1-2 cups, 2-5 cups, and ≥5 cups of coffee consumed daily. RESULTS: The mean serum uric acid level of the men was 5.91 ± 1.24 mg/dL and that of women was 4.29 ± 0.97 mg/dL. In the multiple linear regression analysis, there were no significant differences in the serum uric acid levels between the non-coffee-drinking group and the coffee-drinking group (<1 cup, 1-2 cups, 2-5 cups, and ≥5 cups of coffee) in both men and women (P = .569, .258, .466, and .751, respectively, in men; .185, .520, .116, and .302, respectively, in women). CONCLUSIONS: There was no significant relationship between coffee consumption and serum uric acid levels in the general Korean population.

Clinical Findings of Ankylosing Spondylitis With and Without Human Leukocyte Antigen (HLA)-B27 and HLA-B51.

INTRODUCTION: Ankylosing spondylitis (AS) and Behçet's disease are known to be associated with the human leukocyte antigen (HLA)-B27 and HLA-B51 genes, respectively. However, many of their clinical findings-including articular and extra-articular symptoms-are similar, making diagnosis a challenge in the early stage of the disease. The aim of this study was to investigate the differences in clinical findings of AS patients with and without the HLA-B27 gene. MATERIALS AND METHODS: We performed a retrospective chart review of 151 AS patients. The following clinical findings were evaluated: oral ulcer, genital ulcer, skin manifestation, uveitis, peripheral arthritis; and gastrointestinal, cardiac and pulmonary involvement. Patients were divided into 4 groups based on absence or presence of the HLA-B27 and HLA-B51 genes. The number of patients with each clinical finding was subsequently examined in each group. RESULTS: The incidence of uveitis was significantly higher in the HLA-B27-positive group (P = 0.004); however, other clinical findings did not differ significantly according to the absence or presence of the HLA-B27 gene. There were no significant differences in the clinical findings of patients with positive and negative HLA-B51. CONCLUSION: HLA-B27 was associated with the development of uveitis but not with other clinical findings or disease activity in AS patients. HLA-B51 was not associated with the clinical findings or disease activity of AS.

Relationship of rheumatoid arthritis and coronary artery disease in the Korean population: a nationwide cross-sectional study.

BACKGROUND: Rheumatoid arthritis (RA) is known to be associated with coronary artery diseases (CAD). Previous studies of the association between RA and CAD were reported mainly in non-Asian groups. We aimed to examine the prevalence of RA and the relationship between RA and CAD in South Korea. METHODS: We conducted a nationwide cross-sectional study by using the Korea National Health and Nutrition Examination Survey, which collected data for four years between 2008 and 2012. A total of 25,828 eligible participants were included. To balance the distribution of baseline characteristics, we used propensity score-matching. A multivariable logistic regression model was employed and we calculated the odds ratios (ORs) and 95% confidence intervals (CI) for the odds of the participants with RA on CAD prevalence. RESULTS: The prevalence of RA in Korea from 2008 to 2012 was 0.6% and RA was predominant among elderly women. The prevalence of CAD in patients with RA was significantly higher than in general population. After propensity score-matching to balance the confounding factors, RA was significantly associated with CAD (OR 2.97, 95% CI 1.15-7.68, P = 0.02). CONCLUSIONS: The prevalence of RA in South Korea was comparable to the worldwide data, and the presence of CAD in RA patients was more than two-fold.

Comparison of the efficacy and safety of tofacitinib and upadacitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVES: The relative efficacy and safety of tofacitinib and upadacitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic (cs) or biologic (b) disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and upadacitinib in combination with methotrexate (MTX) in RA patients with an inadequate cs- or b-DMARD response. RESULTS: Nine RCTs including 5794 patients met the inclusion criteria. There were 15 pairwise comparisons including 10 direct comparisons of 6 interventions. Upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX were among the most effective treatments for active RA with an inadequate cs- or b-DMARD response, followed by tofacitinib 10 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX had the highest probability of being the best treatment in terms of the American College of Rheumatology 20 response rate (SUCRA = 0.820, 0.762), followed by tofacitinib 10 mg + MTX (SUCRA = 0.623), tofacitinib 5 mg + MTX (SUCRA = 0.424), adalimumab + MTX (SUCRA = 0.371), and placebo + MTX (SUCRA = 0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, upadacitinib + MTX, adalimumab + MTX, or placebo + MTX. CONCLUSIONS: In RA patients with an inadequate response to cs- or b-DMARDs, upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX were the most efficacious interventions and were not associated with significant risks of serious adverse events.