Search

Background: Clinical manifestations and risk factors associated with systemic lupus erythematosus (SLE) flares, including recurrent lupus nephritis (LN), in patients with LN who undergo kidney transplantation have been unclear. Methods: Kidney transplant recipients with LN from January 1995 to December 2021 were included in this study. A disease flare was defined as either an increase in the non‐renal SLE disease activity index score or the presence of biopsy‐proven recurrent LN. Results: Among a total of 93 patients with LN who underwent kidney transplantation, 11 patients (11.8%) experienced SLE flares during a median follow‐up period of 76.9 months (IQR, 43.0–122.4). The most common clinical manifestations of SLE flares were recurrent LN (4/11, 36.4%) and hematologic manifestations (4/11, 36.4%). Patients who had flares had significantly higher anti‐double‐stranded DNA (anti‐dsDNA) antibody titers both before and after transplantation. Furthermore, an increased anti‐dsDNA antibody level before transplantation was associated with a high risk of an SLE flare (HR, 1.030; p =.008). Conversely, preemptive transplantation was associated with a lower risk of a flare (HR, 0.617; p =.026). The rate of patient death‐censored graft survival was found to be considerably lower in patients with recurrent LN than in those without LN. Conclusions: Approximately 10% of patients with LN experienced an SLE flare after transplantation, with recurrent LN being the most frequent manifestation. Anti‐dsDNA antibody titers before transplantation were significantly related to the risk of an SLE flare. Notably, preemptive transplantation was associated with a reduced risk of flares following transplantation. [ABSTRACT FROM AUTHOR]

This article discusses a study that aimed to classify the progression of asthma by analyzing longitudinal data on lung function, eosinophilic status, and steroid use. The study utilized electronic medical record data from 350 adults with asthma over a 5-year period. The researchers identified six clusters based on the trajectories of these factors and found significant differences in exacerbation risk among the clusters. The study suggests that this multi-trajectory analysis may be a useful method for studying the complex progression of asthma over time. [Extracted from the article]

This study aimed to investigate the clinical features of splenomegaly, mainly focussing on cytopenia, in patients with systemic lupus erythematosus (SLE). Cytopenia was commonly observed in 111 SLE patients with splenomegaly (n = 79, 71.2%). During the follow‐up period, two patients developed haematologic malignancy after the diagnosis of SLE and splenomegaly, but no patients experienced severe complications (e.g. splenic rupture) related to splenomegaly. [ABSTRACT FROM AUTHOR]

Aim: Predicting radiographic progression is vital for assessing the prognosis of patients with radiographic axial spondyloarthritis, and C‐reactive protein (CRP) may be a valuable biomarker for this purpose. This study aimed to investigate the relationship between changes in the CRP level and spinal radiographic progression in patients with radiographic axial spondyloarthritis who were initially treated with non‐biologics. Methods: Patients with radiographic axial spondyloarthritis who were followed up for 18 years at a single center and initially treated with nonsteroidal anti‐inflammatory drugs and/or conventional disease‐modifying antirheumatic drugs for 3 months were included. Patients with a CRP level of <0.8 mg/dL or 50% of the baseline CRP at 3 months were assigned to the controlled CRP group (n = 351), and the remaining patients were assigned to the uncontrolled CRP group (n = 452). A generalized estimating equation was used to analyze the differences in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between the 2 groups. Results: The increase in the mSASSS was slower in the controlled CRP group than in the uncontrolled CRP group (interaction term β = −.499, 95% confidence interval −0.699 to −0.300). Conclusion: Controlled CRP achieved in response to initial treatment with non‐biologic agents for 3 months was significantly associated with a slower rate of spinal radiographic change in patients with radiographic axial spondyloarthritis. The CRP level at 3 months after initial non‐biologic treatment is a good predictor of radiographic progression. [ABSTRACT FROM AUTHOR]

Aim: To evaluate clinical characteristics and natural history of non‐radiographic axial spondyloarthritis (nr‐axSpA) using KOrean Nonradiographic Axial SPondyloArthritis (KONASPA) data. Methods: Data were collected from 11 centers in South Korea. A total of 278 patients with nr‐axSpA from January 2018 to July 2020 were included. Demographic data, clinical features, comorbidities, disease activity, medications, and laboratory results were collected. Results: Mean age at symptom onset was 28.2 ± 14.2 years. Of 278 patients, 152 (54.7%) were male. Mean Bath Ankylosing Spondylitis Disease Activity Index at diagnosis was 3.5 ± 2.1. Dyslipidemia was the most common comorbidity (8.4%), followed by hypertension (6.1%). Mean age at diagnosis of nr‐axSpA was older in female patients than in male patients (31.8 ± 15.8 years vs 24.9 ± 12.0 years, P < 0.001). Enthesitis and uveitis were more frequently found in female patients than in male patients. Thirty‐one (11.1%) participants with nr‐axSpA progressed to ankylosing spondylitis. The median follow‐up duration was 48 months. In multivariable Cox regression analysis, age at symptom onset (hazard ratio [HR] 0.93, 95% confidence interval (CI) 0.88‐0.97, P = 0.006), body mass index (BMI) (HR 1.24, 95% CI 1.06‐1.44, P = 0.005) and sacroiliitis grade (HR 1.86, 95% CI 1.19‐2.92, P = 0.006) were associated with progression to ankylosing spondylitis. Conclusions: Results of nationwide data revealed that women with nr‐axSpA showed a late disease onset and more extra‐articular manifestations than men. Young age at symptom onset, high BMI, and presence of radiographic sacroiliitis at diagnosis were risk factors for progression to AS. [ABSTRACT FROM AUTHOR]

This study assesses the performance of the Coupled Model Intercomparison Project (CMIP) models for simulating summer heatwaves in Korea during a historical simulation period (1979–2014) using four diagnostic indices that represent the teleconnection mechanism of summer heatwaves in Korea. Four skill metrics are used for the model evaluation, namely, relative error (RE), interannual variability skill‐score (IVS), correlation coefficient (CC), and total ranking (TR) based on daily maximum temperature (TMAX) in Korea and the four diagnostic indices. The results show that the REs of CMIP5 models do not differ significantly from those of the CMIP6 models while the IVSs in the CMIP6 models are significantly improved compared with the CMIP5 models. Observations show that the heatwave circulation index (HWCI) contributes more to the interannual variability in TMAX in Korea than that of the Indian Monsoon Rainfall Index (IMRI), indicating that the teleconnection from the northwestern Pacific is more important than that from northwestern India. Interestingly, the CMIP6 models simulate this property better than the CMIP5 ensemble. The higher TR of CMIP6 models than CMIP5 supports that CMIP6 models are better overall in simulating heatwaves in Korea and the associated diagnostic indices. Key Point: Model performance of CMIP6 models is better than that of CMIP5 models in simulating heatwaves in Korea and the associated diagnostic indices [ABSTRACT FROM AUTHOR]

Drug repositioning is an effective way to mitigate the production problem in the pharmaceutical industry. Electronic medical record (EMR) databases harbor a large amount of data on drug prescriptions and laboratory test results and may thus be useful for finding new indications for existing drugs. Here, we present a novel high‐throughput data‐driven algorithm that identifies and prioritizes drug candidates that show significant effects on specific clinical indicators by utilizing large‐scale EMR data. We chose four laboratory tests as clinical indicators: hemoglobin A1c (HbA1c), low‐density lipoprotein (LDL) cholesterol, triglycerides (TGs), and high‐density lipoprotein (HDL) cholesterol. From a 5‐year EMR database, we generated datasets consisting of paired data with averaged measurement values during on and off each drug in each patient, adjusted for co‐administered drug effects at each timepoint, and applied one sample t‐test with the Bonferroni correction for statistical analysis. Among 1,774 drugs, 45 were associated with increases in HDL cholesterol, and 41, 146, and 65 were associated with reductions in HbA1c, LDL cholesterol, and TGs, respectively. We compared the list of candidate drugs with that of drugs indicated for relevant clinical conditions and found that the algorithm had high values for both sensitivity (range 0.95–1.00) and negative predictive value (range 0.95–1.00). Our algorithm was able to rediscover well‐known drugs that are used for diabetes and dyslipidemia while revealing potential candidates without current indications but have shown promising results in the literature. Our algorithm may facilitate the repositioning of drugs with proven safety profiles. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the disease flare rate in patients with rheumatoid arthritis (RA) who achieved low disease activity following long‐term methotrexate (MTX) treatment and the factors related to flare. Methods: This retrospective longitudinal cohort study included patients with RA and low disease activity who were exposed to MTX for >10 years. Disease flare was defined as an increase in Disease Activity Score of 28 joints (DAS28) of >1.2 within 6 months of discontinuation of MTX. Logistic regression analysis was performed to identify the factors associated with flare. Results: In total, 97 patients with RA were included in the study. The mean baseline DAS28 was 1.96 ± 0.56. The median cumulative MTX dose was 11.7 g; the median duration of exposure to MTX was 19 years. Following MTX discontinuation, flare occurred in 43 (44.3%) patients; the median time to flare was 99 (28‐168) days. According to univariate logistic regression analysis, C‐reactive protein, erythrocyte sedimentation rate (ESR) at discontinuation, the average ESR in the 6 months before discontinuation of MTX, a weekly dose of MTX before discontinuation, and use of other conventional synthetic disease‐modifying antirheumatic drugs were associated with a higher risk of disease flare. In multivariable analysis, a weekly dose of MTX before discontinuation (odds ratio 1.014; 95% CI 1.014‐1.342; P =.031) was significantly associated with flare risk. Conclusion: Among patients with RA who achieved low disease activity with long‐term treatment with MTX, more than half remained flare free after MTX discontinuation. A higher MTX dose before discontinuation was associated with a high flare risk. [ABSTRACT FROM AUTHOR]

We investigate the impact of the diabatic heating (Q1) over the Indian subcontinent and Tibetan Plateau (TP) sensible heat on the heat waves in South Korea in July and August over a recent 42‐year period. In particular, we emphasize the role of the convective activity across the region from northeastern Pakistan to northwestern India (PWI) induced by the heat from the TP, especially over the western and eastern TP. A composite analysis indicates that the composite differences between the heat‐wave summers (HWS) and non‐heat‐wave summers (NHWS) resemble the circum‐global teleconnection (CGT) pattern, which generates a high‐pressure anomaly over the Korean Peninsula, producing favourable conditions for heat waves in South Korea. The first coupled mode of the geopotential height at 250 hPa with the daily maximum temperature (TM) for July and August in South Korea is consistent with the composite pattern, suggesting that the diabatic heating over the Indian subcontinent induces a high‐pressure anomaly over the Korean Peninsula through a CGT‐like mechanism. The regression analysis of the wind vectors in the upper troposphere also indicates that the diabatic heating over the PWI region and associated TP sensible heating generates the strong convection over the PWI region, which corresponds to the anomalous anticyclonic circulation at 250 hPa over the western TP and the cyclonic circulation at 850 hPa over the PWI region. Moreover, the correlation patterns of the 250‐hPa geopotential height with the normalized rainfall amount index (IMRI) over the PWI region and the wave activity flux pattern confirm that the strong convective activity over the PWI region contributes to the anomalous high pressure and heat waves over the Korean Peninsula. It is found that the PWI diabatic heating triggers anomalous South Asian High shifted to the western TP and then it stimulates stationary Rossby wave propagation and finally generates anomalous high pressures over the Korean Peninsula through stationary Rossby wave propagation, which contribute to the heat waves in South Korea. [ABSTRACT FROM AUTHOR]

Objective: Interleukin-32 (IL-32) induces various inflammatory molecules in human monocytes and differentiation of monocytes into macrophage-like cells. This study was undertaken to evaluate the effects of IL-32gamma, the most biologically active isoform, on the differentiation and activation of osteoclasts., Methods: CD14+ monocytes were obtained from healthy volunteers, and samples of synovial tissue and synovial fluid were obtained from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). The concentration and expression levels of IL-32gamma in RA and OA samples were evaluated by enzyme-linked immunosorbent assay and immunoblotting, respectively. To examine the osteoclastogenic effects and functional activities, isolated monocytes were treated with either IL-32gamma or IL-17 in the presence or absence of soluble RANKL (sRANKL) on a culture system and on Osteologic disks. The expression of RANKL and osteoprotegerin (OPG) messenger RNA (mRNA) in RA fibroblast-like synoviocytes (FLS) was measured using reverse transcription-polymerase chain reaction (PCR) and real-time PCR., Results: The concentration and expression levels of IL-32gamma were higher in the RA samples than in the OA samples. Upon costimulation with sRANKL, the osteoclast count and resorbed area increased more significantly in the IL-32gamma-stimulated cultures than in those stimulated with IL-17. In the IL-32gamma-treated group without sRANKL stimulation, osteoclasts were differentiated, but the cells displayed low resorption activity. In RA FLS, RANKL mRNA expression increased in the presence of both IL-32gamma and IL-17. However, transcription of OPG decreased following IL-32gamma stimulation, resulting in a significant increase in the RANKL:OPG ratio., Conclusion: Our results suggest that IL-32gamma is a potent mediator of active osteoclast generation in the presence of sRANKL. Moreover, this novel cytokine creates more favorable conditions for osteoclastogenesis in the RA joint by increasing the RANKL:OPG ratio in FLS.