Explore the vast range of titles available.

Background Biomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated interstitial lung disease (CTD-ILD). This study aimed to evaluate Krebs von den Lungen 6 (KL-6) as a potential biomarker reflecting the severity of CTD-ILD as assessed through computed tomography (CT) and pulmonary function test (PFT) parameters. Methods This retrospective study included 549 Korean patients with rheumatoid arthritis, systemic sclerosis, inflammatory myositis, and other CTDs with or without concurrent ILD. Serum KL-6 concentration (U/mL) was measured using the latex-enhanced immunoturbidimetric assay method. CT and PFT results were collected within 1 year of serum collection. A semiquantitative grade of ILD extent was evaluated through CT scan (grade 1, 0–25%; grade 2, 26–50%; grade 3, 51–75%; grade 4, 76–100%). Results CTD-ILD patients ( n  = 165) had elevated serum KL-6 levels compared to CTD patients without ILD ( n  = 384) ( p  < 0.001), and those findings were preserved after adjusting for age, sex, and CTD type. The semiquantitative grade of ILD on CT scan was significantly proportional to the KL-6 level, and the optimal cut-off KL-6 value effectively differentiated each ILD grade. The percent diffusing capacity of the lung for carbon monoxide (DLCO) ( p  < 0.001) and forced vital capacity (FVC) ( p  < 0.001) parameters had a moderate, negative correlation with the KL-6 level. Conclusion Serum KL-6 levels were increased in CTD-ILD patients and had a positive correlation with CT grade and a negative correlation with FVC and DLCO. Serum KL-6 levels may reflect CTD-ILD severity.

Background To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea. Methods Using 2009–2019 Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users. Results We included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00–2.80) for HZ, 1.04 (0.71–1.52) for SBI, and 0.25 (0.09–0.73) for OI. Conclusions This population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.

In this study, we introduce a uricase-immobilized paper (UOx­-paper) integrated electrochemical sensor for detection of uric acid (UA) in saliva. The UOx was immobilized on the detection zone in the wax-patterned paper substrate. This UOx-paper was integrated with a Prussian blue­-modified, screen-printed carbon electrode after electropolymerization of o-phenylenediamine to construct an electrochemical cell for small-volume (20 μL) of samples. First, we optimized the fabrication conditions of UOx-paper. Next, the amperometric response of the UOx-paper-based electrochemical UA sensor was analyzed using a known concentration of UA standard solution in artificial saliva at an applied potential of − 0.1 V (versus Ag pseudo-reference electrode). The UOx-­paper based electrochemical UA sensor showed a sensitivity of 4.9 μA·mM −1 in a linear range of 50 to 1000 μM (R 2  = 0.998), high selectivity and good reproducibility, as well as a limit of detection of 18.7 μM (0.31 mg/dL) UA. Finally, we quantified the UA levels in undiluted saliva samples of healthy controls (n = 20) and gout patients (n = 8). The levels were correlated with those measured with conventional salivary UA enzymatic assays as well as serum UA levels. The UOx-paper-based electrochemical UA sensor is a user-friendly and convenient tool to assess salivary UA levels.

Recent studies have suggested that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) are emerging markers of disease activity and prognosis in patients with chronic inflammatory diseases, cardiovascular diseases, or malignancies. Therefore, we investigated the clinical significance and prognostic value of the NLR and CAR in adult patients with polymyositis and dermatomyositis. The medical records of 197 patients with newly diagnosed polymyositis/dermatomyositis between August 2003 and November 2016 were retrospectively reviewed. Survival and causes of death were recorded during an average 33-month observational period. Clinical and laboratory findings were compared between survivors and non-survivors. Using receiver operating characteristic curves, the NLR and CAR cut-off values for predicting survival were calculated. Univariate and multivariate analyses using Cox proportional hazard models were performed to identify factors associated with survival. Twenty-six patients (13.2%) died during the study period, and the 5-year survival-rate was estimated to be 82%. The non-survivor group exhibited older age and a higher prevalence of interstitial lung disease (ILD), acute interstitial pneumonia, and acute exacerbation of ILD compared to that in the survivor group. NLR and CAR values were significantly higher in the non-survivors and in patients with polymyositis/dermatomyositis-associated ILD, and the death rates increased across NLR and CAR quartiles. Furthermore, when stratified according to the NLR or CAR optimal cut-off values, patients with a high NLR (>4.775) or high CAR (>0.0735) had a significantly lower survival rate than patients with low NLR or CAR, respectively. In addition, old age (>50 years), the presence of acute interstitial pneumonia, hypoproteinemia (serum protein <5.5 g/dL), and high NLR (but not high CAR) were independent predictors for mortality. The results indicate that a high NLR is independently associated with worse overall survival. Thus, the baseline NLR level may be a simple, cost-effective prognostic marker in patients with polymyositis/dermatomyositis.

Lung illness encountered in patients with rheumatic diseases bears clinical significance in terms of increased morbidity and mortality as well as potential challenges placed on patient care. Although our understanding of natural history of this important illness is still limited, epidemiologic knowledge has been accumulated during the past decade to provide useful information on the risk factors and prognosis of lung involvements in rheumatic diseases. Moreover, the pathogenesis particularly in the context of genetics has been greatly updated for both the underlying rheumatic disease and associated lung involvement. This review will focus on the current update on the epidemiologic and genetics features and treatment options of the lung involvements associated with four major rheumatic diseases (rheumatoid arthritis, systemic sclerosis, myositis, and systemic lupus erythematosus), with more attention to a specific form of involvement or interstitial lung disease.

Backgrounds Despite the advances of rheumatoid arthritis (RA) therapeutics, several patients do not receive adequate treatment due to the toxicity and/or insufficient response of drugs. The aim of this study is to design photothermally controlled drug release from multifunctional nanoparticles (MNPs) at a near-infrared (NIR) irradiated site to improve therapeutic efficacy for RA and reduce side effects. Methods Au film was deposited onto methotrexate (MTX)-loaded poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles, resulting in MTX-loaded MNPs. The synergistic effects of MTX-loaded MNPs with NIR irradiation were investigated using RA fibroblast-like synoviocytes (FLSs) and collagen-induced arthritis (CIA) mice. Results Upon NIR irradiation, NIR resonance of the Au half-shell generated heat locally, accelerating MTX release from PLGA nanoparticles. In vivo NIR images of MTX-loaded MNPs indicated effective delivery of the MNPs to the inflamed joints. Moreover, in collagen-induced arthritis mice, MTX-loaded MNPs containing 1/1400 of MTX solution (repeated-dose administration) had therapeutic effects comparable to conventional treatment with MTX solution. In vitro experiments showed higher therapeutic efficacy of MTX-loaded MNPs with NIR irradiation than that of chemotherapy alone. Conclusions A combination therapy of MTX-loaded MNP and NIR irradiation showed durable and good treatment efficacy for the suppression of arthritis in a single administration of small dose of MTX. Our results demonstrate that the treatment modality using drug-loaded MNP with NIR irradiation may be a promising therapeutic strategy for the treatment of RA and allow in vivo NIR optical imaging.

Despite recent accumulation on cardiovascular (CV) safety data on xanthine oxidase inhibitors (XOIs) among gout patients, assessment has been largely limited to macro- than micro-vascular disorders, prompting the investigation on the latter outcome. Therefore, we aimed to compare the risk of retinal microvascular disorders between allopurinol and febuxostat initiators among gout patients. Using the 2011–2019 Korean National Health Insurance service database, we conducted a cohort study on gout patients initiating allopurinol or febuxostat. The primary outcome was a composite of retinal microvascular disorders. After 1:1 propensity-score (PS) matching in non-diabetic (non-DM) and diabetic (DM) subgroups, pooled and subgroup-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were reported, comparing allopurinol and febuxostat. We included 118,376 PS-matched pairs of febuxostat and allopurinol initiators (mean 57.3 years, 83.7% male; 89,642 pairs in non-DM and 28,734 pairs in DM subgroup). During a mean follow-up of 223 days, the incidence rate per 100 person-years of the primary outcomes was 0.88 among allopurinol users and 0.93 among febuxostat users. The corresponding HR (95% CI) was 0.98 (0.83–1.15). The HR (95% CI) was 0.94 (0.76–1.15) in non-DM subgroup and 1.05 (0.80–1.39) in DM subgroup. The result for DM retinopathy also showed a similar risk (HR 0.86, 95% CI 0.67–1.11). In this large population-based cohort study on patients with gout, we did not find any difference in the risk of retinal microvascular disorders between allopurinol and febuxostat initiators.

Background/Objectives: Autoimmune thrombocytopenia is a common manifestation of systemic lupus erythematosus (SLE). Its main treatments are glucocorticoids, intravenous immunoglobulin, and immunosuppressants, but thrombopoietin mimetics may be considered with refractory to conventional treatment. Romiplostim, a thrombopoietin receptor agonist, has been approved for increasing platelet counts in corticosteroid-refractory chronic immune thrombocytopenia. However, data on its long-term safety and efficacy in patients with SLE are still lacking. Case Presentation: We present the case of a 55-year-old woman with SLE and refractory immune thrombocytopenia who developed bilateral adrenal hemorrhage and progressed to fatal catastrophic anti-phospholipid syndrome while using romiplostim.

Extracellular PKM2 (exPKM2) levels have been reported to be increased in several cancers and inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to investigate the association of circulating exPKM2 levels with radiographic progression in RA patients and the effect of exPKM2 on osteoclastogenesis. Plasma and synovial fluid exPKM2 levels were significantly elevated in RA patients. Plasma exPKM2 levels were correlated with RA disease activity and were an independent predictor for radiographic progression in RA patients with a disease duration of ≤ 12 months. CD14 + monocytes but not RA fibroblast-like synoviocytes secreted PKM2 upon stimulation with inflammatory mediators. Recombinant PKM2 (rPKM2) increased the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and resorption pit in osteoclast precursors, dose-dependently, even in the absence of receptor activator of nuclear factor-kappa B ligand (RANKL). rPKM2 treatment upregulated the expression of dendrocyte-expressed seven transmembrane protein (DC-STAMP) and MMP-9 via the ERK pathway. Although rPKM2 did not directly bind to RAW264.7 cells, extracellular application of pyruvate, the end-product of PKM2, showed effects similar to those seen in rPKM2-induced osteoclastogenesis. These results suggest that exPKM2 is a potential regulator of RA-related joint damage and a novel biomarker for subsequent radiographic progression in patients with early-stage RA.

ObjectivesTo assess the differences in clinical outcomes between patients with rheumatoid arthritis (RA) with early menopause (EM) (<45 years) and usual menopause (UM) (≥45 years) and to identify the impact of EM on longitudinal changes in RA activity and patient-reported outcomes (PROs).MethodsWe recruited 2878 postmenopausal women with RA from the Korean Observational Study Network for Arthritis. Patients were examined at baseline and for 5 consecutive years using the Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire–Disability Index (HAQ-DI) and other PROs. Generalised estimating equation (GEE) analyses were performed among patients with a baseline SDAI of >11 to evaluate the impact of EM on longitudinal changes in RA activity and PROs.ResultsThe EM group (n=437) was younger than the UM group (n=2441), but the RA duration was similar between the two groups. The EM group was more educated and more likely to be seronegative at enrolment. Moreover, the EM group demonstrated higher disease activity and worse PROs for global assessment, fatigue, sleep disturbance and health-related quality of life (HRQoL) (all p<0.05) at baseline. The GEE model revealed that EM significantly influenced the rate of SDAI change (β=1.265, p=0.004) after adjusting for age, RA duration, biologics use and SDAI at baseline. The EM group was also significantly associated with increased HAQ-DI scores and decreased EQ-5D-utility values during the 5-year follow-up period.ConclusionPatients with RA and EM demonstrate higher disease activity and poorer HRQoL. Furthermore, EM significantly affects the longitudinal changes in disease activity and PROs in patients with RA.