Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation

Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes controlling OA progression is poor. Here, we report the association of OA with increased levels of osteoclast-associated receptor (OSCAR), an immunoglobulin-like collagen-recognition receptor. In mice, OSCAR deletion abrogates OA manifestations, such as articular cartilage destruction, subchondral bone sclerosis, and hyaline cartilage loss. These effects are a result of decreased chondrocyte apoptosis, which is caused by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in induced OA. Treatments with human OSCAR-Fc fusion protein attenuates OA pathogenesis caused by experimental OA. Thus, this work highlights the function of OSCAR as a catabolic regulator of OA pathogenesis, indicating that OSCAR blockade is a potential therapy for OA.ope

Vascular Uptake on 18 F-FDG PET/CT During the Clinically Inactive State of Takayasu Arteritis Is Associated with a Higher Risk of Relapse

Purpose: To evaluate whether vascular uptake on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) during the clinically inactive state of Takayasu arteritis (TAK) is associated with disease relapse. Materials and methods: Patients with TAK who underwent 18F-FDG PET/CT during the clinically inactive state of the disease between 2006 and 2019 were included. Clinically inactive disease was defined as a status not fulfilling the National Institutes of Health (NIH) criteria for active disease in TAK. Relapse was defined as recurrence of clinically active disease after a clinically inactive period, requiring change in the treatment regimen. Vascular uptake on 18F-FDG PET/CT was assessed using target/background ratio (TBR), calculated as arterial maximum standardized uptake value (SUV)/mean SUV in venous blood pool. Multivariable Cox regression analysis was performed to identify factors associated with relapse. Results: A total of 33 patients with clinically inactive TAK were included. During a median observation period of 4.5 (0.9-8.1) years, relapse occurred in 9 (27.3%) patients at median 1.3 (0.7-6.9) years. Notably, TBR [1.5 (1.3-1.8) vs. 1.3 (1.1-1.4), p=0.044] was significantly higher in patients who relapsed than in those who did not. On multivariable Cox regression analysis, the presence of NIH criterion 2 [adjusted hazard ratio (HR): 7.044 (1.424-34.855), p=0.017] and TBR [adjusted HR: 11.533 (1.053-126.282), p=0.045] were significantly associated with an increased risk of relapse. Conclusion: Vascular uptake on 18F-FDG PET/CT and the presence of NIH criterion 2 are associated with future relapse in patients with clinically inactive TAK.ope

Portal Vein Thrombosis Associated with Antiphospholipid Syndrome

Antiphospholipid syndrome is a disorder characterized by the presence of antiphospholipid antibodies, recurrent arterial and/or venous thromboembolism, and spontaneous abortion. Deep vein thrombosis, pulmonary thromboembolism, and cerebral infarction are major thrombotic event, but portal vein thrombosis, especially in young age male, is rarely reported. A 27-year-old man, without prior thrombotic event, presented with severe abdominal pain for 4 days. Extensive portal vein thrombosis was noted on abdominal CT scan and MR angiography. Lupus anticoagulant was suspected and was confirmed according to the guidelines of the International Society on Thrombosis and Hemostasis and the patient was diagnosed as having primary antiphospholipid syndrome associated with portal vein thrombosis. Intravenous heparin infusion was initiated and switched to warfarin upon discharge. Now the patients is being followed in outpatient clinic and treated with warfarin without any evidence suggesting the recurrence of thrombotic event.ope

Cost-effectiveness of Non-steroidal Anti-inflammatory Drugs Adjusting for Upper and Lower Gastrointestinal Toxicities in Rheumatoid Arthritis Patients

Objective : This study was performed to assess the cost-effectiveness of cyclooxygenase-2 (COX2)-selective inhibitor, non-selective non-steroidal anti-inflammatory drugs (NSAIDs), and non-selective NSAID with proton pump inhibitors (PPIs) while considering upper and lower gastrointestinal (GI) safety in patients with rheumatoid arthritis (RA). Methods : A Markov model was used to estimate the costs and effectiveness. Estimates of therapeutic efficacy and upper/lower GI safety were based on results from large randomized controlled trials. The main outcome measure was cost effectiveness, based on the quality-adjusted life years (QALYs) gained. Safety parameters included clinical upper GI symptoms, uncomplicated ulcer, upper GI bleeding, upper GI perforation, clinical lower GI symptoms, lower GI bleeding, and lower GI perforation. Cost data were obtained from patients treated in a tertiary referral center in Korea. Results : The expected three year cost was 3,052,800 Korean won (KRW) for COX2-selective inhibitor, 3,170,800 KRW for nonselective NSAID, and 3,325,900 KRW for non-selective NSAID with PPI. QALYs were 2.87446, 2.85320, and 2.85815, respectively. The total cost for COX2-selective inhibitor use was lower than non-selective NSAID, but QALY was higher, indicating that the incremental cost effectiveness ratio of COX2-selective inhibitor is superior. Conclusion : COX2-selective inhibitor has reasonable cost-effectiveness adjusted for upper and lower GI toxicity for patients with RA in Korea.ope

Correlation between serologic parameters and disease activity of IgG4-related disease: Differences between patients with normal and elevated serum IgG4 concentrations

Objective: We aimed to identify serologic parameters that correlate with the disease activity of IgG4-related disease (IgG4-RD) in patients with normal and elevated serum IgG4 concentrations, respectively. Methods: This retrospective cohort study included 148 patients with IgG4-RD. Patients were categorized into normal (≤201 mg/dL) and elevated (>201 mg/dL) serum IgG4 concentration groups. Disease activity was assessed using the IgG4-RD responder index (RI). The correlations between IgG4-RD RI and serologic parameters (erythrocyte sedimentation rate [ESR], C-reactive protein, C3, C4, IgG4 concentration, IgG concentration, and IgG4/IgG ratio) were evaluated in each group, using Spearman's correlation coefficient. Results: Of the 148 patients with IgG4-RD, 38 (25.7%) and 110 (74.3%) patients were categorized into the normal and elevated serum IgG4 concentration groups, respectively. In the normal serum IgG4 concentration group, IgG concentration was the only serologic parameter that showed a significant correlation with IgG4-RD RI (rho=0.411, p=0.013). However, in the elevated serum IgG4 concentration group, ESR (rho=0.196, p=0.041), C3 (rho=-0.432, p<0.001), C4 (rho=-0.363, p=0.001), IgG4 concentration (rho=0.423, p<0.001), IgG concentration (rho=0.224, p=0.020), and IgG4/IgG ratio (rho=0.328, p=0.001) correlated with IgG4-RD RI. The combination of C3 and IgG4 concentration (rho=0.509, p<0.001) had the strongest correlation with IgG4-RD RI in this group. Conclusion: Among the serologic parameters tested, IgG concentration was the only parameter that correlated with IgG4-RD RI in patients with normal serum IgG4 concentrations, whereas multiple parameters correlated with IgG4-RD RI in those with elevated serum IgG4 concentrations. The combination of C3 and IgG4 concentration had the strongest correlation coefficient in the latter group.ope

Listeria Monocytogenes Meningitis in a Patient with Systemic Lupus Erythematosus -A Case Report-

In systemic lupus erythematosus (SLE) patients, immunosuppressive treatment with cytotoxic drugs or corticosteroids, proteinuria, renal insufficiency, and active SLE itself are known as risk factors for serious bacterial infections and opportunistic infections. Several opportunistic infections such as toxoplasmosis, nocardiosis, and cryptococcal meningitis have been reported to occur in patients with SLE and these can mimic neuropsychiatric lupus. Listeria monocytogenes is one of the pathogens of bacterial meningitis that is less commonly identified than Neisseira meningitidis and Streptococcus pneumoniae in adults, and shows the clinical manifestations, such as headache, fever, nausea, vomiting, neck stiffness, mental changes and seizures similar to symptoms and signs of neuropsychiatric lupus. We report a case of Listeria monocytogenes meningitis in a patient with SLE who was admitted because of headache, nausea, vomiting and poor oral intake.ope

Risk of systemic lupus erythematosus flares according to autoantibody positivity at the time of diagnosis

To estimate the risk of systemic lupus erythematosus (SLE) flares based on the autoantibody positivity at the time of SLE diagnosis. This retrospective cohort study included 228 patients with newly diagnosed SLE. Clinical characteristics including autoantibody positivity at the time of diagnosis of SLE were reviewed. Flares were defined as a new British Isles Lupus Assessment Group (BILAG) A score or BILAG B score for at least one organ system. Multivariable Cox regression analyses were performed to estimate the risk of flares according to autoantibody positivity. Anti-dsDNA, anti-Sm, anti-U1RNP, anti-Ro, and anti-La antibodies (Abs) were positive in 50.0%, 30.7%, 42.5%, 54.8%, and 22.4% of the patients, respectively. The incidence rate of flares was 28.2/100 person-years. Multivariable Cox regression analysis, adjusted for potential confounders, revealed that anti-dsDNA Ab positivity (adjusted hazard ratio [HR]: 1.46, p = 0.037) and anti-Sm Ab positivity (adjusted HR: 1.81, p = 0.004) at the time of diagnosis of SLE were associated with higher risk of flares. To better delineate the flare risk, patients were categorized as double-negative, single-positive, double-positive for anti-dsDNA and anti-Sm Abs. Compared with double-negativity, double-positivity (adjusted HR: 3.34, p < 0.001) was associated with higher risk of flares, while anti-dsDNA Ab single-positivity (adjusted HR: 1.11, p = 0.620) or anti-Sm Ab single-positivity (adjusted HR: 1.32, p = 0.270) was not associated with higher risk of flares. Patients who are double-positive for anti-dsDNA and anti-Sm Abs at the time of the diagnosis of SLE are at higher risk of flares and may benefit from stringent monitoring and early preventive treatment. © 2023, The Author(s).ope

Medical Treatment of Gouty Arthritis

Gout is a heterogenous group of diseases resulting from monosodium urate(MSU) crystal deposition in tissues or from supersaturation of uric acid in extracellular fluids. Clinical manifestations include ① recurrent attacks of articular and periarticular inflammation; ② accumulation of articular, osseous, soft tissue, and cartilagenous crystalline deposits; ③ uric acid calculi in urinary tract; and ④ interstitial nephropathy with renal function impairment. Gout almost always can be treated successfully and without complications. Therapeutic goals include terminating acute attack; providing rapid, safe relief of pain and inflammation; averting future attacks; and preventing such complications as formation of tophi, renal stones, and destructive arthropathy. Treatment of gout can be challenging, given that the disease frequently presents in association with other disorders; patient compliance can be difficult to achieve and the effectiveness and safety of therapies can vary widely from patient to patient. However, with early intervention, careful monitoring, and patient education, the prognosis is excellent.ope

Effect of tumor necrosis factor inhibitors on risk of cardiovascular disease in patients with axial spondyloarthritis

Background: Axial spondyloarthritis (axSpA) is associated with an increased risk of cardiovascular disease. We aimed to evaluate the effect of tumor necrosis factor inhibitors (TNFis) on the risk of cardiovascular disease in patients with axSpA. Methods: This retrospective study included 450 patients with axSpA without pre-existing cardiovascular disease. The outcome was incident cardiovascular disease (myocardial infarction or stroke) after the diagnosis of axSpA. The effect of TNFis on cardiovascular risk was analyzed in the total study population and in an inverse probability of treatment weighting (IPTW)-adjusted population. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular disease, according to exposure to TNFis. Results: Of the 450 patients, 233 (51.8%) and 217 (48.2%) patients were and were not exposed to TNFis, respectively. Twenty cardiovascular diseases occurred during 2868 person-years of follow-up (incidence rate: 6.97/1000 person-years). In the total study population, exposure to TNFis was associated with a reduced cardiovascular risk when adjusted for traditional cardiovascular risk factors (HR 0.30, 95% CI 0.10-0.85, p = 0.024). However, when time-averaged erythrocyte sedimentation rate and C-reactive protein were additionally adjusted, this association was attenuated and lost statistical significance (HR 0.37, 95% CI 0.12-1.12, p = 0.077). Furthermore, in the IPTW-adjusted population, exposure to TNFis showed no significant reduction in cardiovascular risk (HR 0.60, 95% CI 0.23-1.54, p = 0.287). Conclusions: Although controlling inflammation through TNFis could be beneficial in cardiovascular risk reduction, our data indicate no TNFi-specific reduction in cardiovascular risk in patients with axSpA.ope

Rapid onset of efficacy predicts response to therapy with certolizumab plus methotrexate in patients with active rheumatoid arthritis

BACKGROUND/AIMS: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSION: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.ope