Search

Most of previous works and applications of Bayesian factor model have assumed the normal likelihood regardless of its validity. We propose a Bayesian factor model for heavy-tailed high-dimensional data based on multivariate Student-t likelihood to obtain better covariance estimation. We use multiplicative gamma process shrinkage prior and factor number adaptation scheme proposed in Bhattacharya and Dunson [Biometrika 98(2):291–306, 2011]. Since a naive Gibbs sampler for the proposed model suffers from slow mixing, we propose a Markov Chain Monte Carlo algorithm where fast mixing of Hamiltonian Monte Carlo is exploited for some parameters in the proposed model. Simulation results illustrate the gain in performance of covariance estimation for heavy-tailed high-dimensional data. We also provide a theoretical result that the posterior of the proposed model is weakly consistent under reasonable conditions. We conclude the paper with the application of the proposed factor model on breast cancer metastasis prediction given DNA signature data of cancer cells. [ABSTRACT FROM AUTHOR]

This paper presents a multi-material topology optimization for the design of permanent magnet synchronous motors (PMSMs). Specifically, structural shapes of permanent magnet (PM) and iron core in a PMSM rotor are simultaneously designed together with the orientation of PM magnetization. For a co-design of PM and iron core, relative permeability and residual magnetic flux density are interpolated by the three-field density approach based on the Helmholtz filtering and regularized Heaviside step function. Here, the Helmholtz filtering aims to attain smooth border in design results, and the Heaviside function enables us to acquire a clear border (i.e. zero-one design) without intermediate densities. The optimization goal is set as maximizing the average torque of PMSMs. The average torque is calculated by Maxwell stress tensor (MST) method considering a maximum torque per ampere (MTPA) control. To validate the effectiveness of the proposed multi-material topology optimization approach, a PMSM rotor with 4 poles and 12 slots is designed. In addition, design results at various settings of input current amplitude and PM strength are compared and discussed. When the input current is stronger than the PM strength, rotor PM and iron core are designed for utilizing both PM and reluctance torque components like V-shape interior PMSMs. On the other hand, in the case of stronger PM strength, PM is designed near the air-gap, which utilizes only PM torque component like surface PMSMs. [ABSTRACT FROM AUTHOR]

This paper proposes a topology optimization formulation for the three-dimensional (3-D) design of segmented permanent magnet (PM) arrays. Specifically, the proposed formulation aims to find an optimal 3-D structural topology of PM segments and their discrete magnetization directions. To achieve this, a design variable is defined in the vector form of a Cartesian coordinate system. The magnitude of the design variable vector determines a PM density, and the directional cosines of the vector determine PM magnetization directions. To acquire a segmented PM design with discrete magnetization directions, a PM strength penalization scheme is proposed. In this scheme, a PM strength is controlled using a minimum distance function between a magnetization direction and target discrete directions. Here, the minimum distance function is approximated using the p-norm for sensitivity calculation. To validate the effectiveness of the proposed formulation, three design examples are provided. In the first example, a two-dimensional (2-D) dipole Halbach cylinder is designed to confirm that the proposed formulation can be applied for a 2-D design problem. The second example aims to design 3-D dipole PM arrays with a cuboid cavity. In the third example, a 3-D PM arrays are designed for maximizing the magnetic force acting on a soft ferromagnetic material. [ABSTRACT FROM AUTHOR]

This paper proposes the multi-material topology optimization for the simultaneous design of segmented permanent magnet (PM) arrays, coil, and iron materials in magnetic actuators. Specifically, the proposed approach can find the optimal layout and shape of PM, coil, and iron materials, as well as the optimal border and magnetization direction of segmented PM arrays. For designing the layout and shape of actuator components, the discrete material optimization-type material interpolation scheme is employed in this paper. To attain the design of segmented PM arrays, an orientation design variable in Cartesian coordinate is utilized with the penalization scheme for the discrete PM magnetization directions. To validate the effectiveness of the proposed actuator design approach, two numerical examples are presented. In the examples, the actuator components (i.e., segmented PM arrays, coil winding, and back iron) are designed aiming for maximizing the magnetic force magnitude acting on the actuator plunger. [ABSTRACT FROM AUTHOR]

Aim To investigate the effects of Tubastatin A, a selective histone deacetylase-6 inhibitor, on synovial inflammation and joint destruction in a collagen antibody-induced arthritis ( CAIA) mouse model. Methods Collagen antibody-induced arthritis mice were given daily intraperitoneal injections of various concentrations of Tubastatin A (0, 10, 50, 100 mg/kg). The clinical score and paw thickness were measured. Mice were sacrificed on day 15, and the expression of tumor necrosis factor ( TNF)-α, interleukin ( IL)-1 and IL-6 in the serum were analyzed using enyme-linked immunosorbent assay ( ELISA). Two pathologists independently measured the synovitis score. Micro-computed tomography ( CT) scans of the joints were performed to quantify joint destruction. The expression of IL-6 from human fibroblast-like synoviocytes ( FLSs) after incubation with various doses of Tubastatin A (0, 0.75, 1.5, 3 μmol/L) was measured using ELISA. Results The clinical arthritis score was significantly attenuated and paw thickness was lower in the group treated with 100 mg/kg Tubastatin A compared with those treated with vehicle alone. The synovitis score was significantly reduced in the 100 mg/kg Tubastatin A-treated group compared with the control group. Micro- CT showed that quantitative measures of joint destruction were significantly attenuated in the 100 mg/kg Tubastatin A-treated group compared with the control. The expression of IL-6 in the sera was lower in the mice treated with Tubastatin A compared with the control. The expression of IL-6 in human FLSs decreased dose-dependently after incubation with Tubastatin A without affecting cell viability. Conclusions Tubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL-6 expression. [ABSTRACT FROM AUTHOR]

Requirements engineering (RE) offers the means to discover, model, and manage the requirements of the products that comprise a product line, while software product line engineering (SPLE) offers the means of realizing the products' requirements from a common base of software assets. In practice, however, RE and SPLE have proven to be less complementary than they should. While some RE techniques, particularly goal modeling, support the exploration of alternative solutions, the appropriate solution is typically conditional on context and a large product line may have many product-defining contexts. Thus, scalability and traceability through into product line features are key challenges for RE. Feature modeling, by contrast, has been widely accepted as a way of modeling commonality and variability of products of a product line that may be very complex. In this paper, we propose a goal-driven feature modeling approach that separates a feature space in terms of problem space and solution space features, and establish explicit mappings between them. This approach contributes to reducing the inherent complexity of a mixed-view feature model, deriving key engineering drivers for developing core assets of a product line, and facilitating the quality-based product configuration. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate the effects of benzo[a]pyrene (B[a]P), a major toxic component of cigarette smoke, on the expression of Slug and to determine the effect of B[a]P/Slug on the invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Method: The expression of Slug was measured by real-time PCR following the stimulation of FLS with different concentrations of B[a]P or EGF. The phosphorylation of the key enzymes in the signaling pathway was analyzed by western blots. Inhibitors of PI3K/Akt/mTOR pathway were used to confirm the critical pathway for Slug expression. An in vitro cell invasion assay was performed using RA FLS treated with Slug cDNA, Slug small interference RNA, or control. Results: Slug expression increased significantly following treatment with B[a]P or EGF in a dose-dependent manner. The stimulation of FLS with B[a]P or EGF induced the phosphorylation of Akt kinase, but not in ERK, JNK and p38. The Slug mRNA expression induced by B[a]P and EGF decreased significantly following the treatment with PI3K/Akt/mTOR inhibitors. Slug overexpression using Slug cDNA upregulated the invasive function of FLS, and Slug depletion using siRNA showed the opposite effect compared with the control. In addition, the stimulation with B[a]P increased the invasive function of the control siRNA-treated FLS but not in the Slug siRNA-treated FLS. Conclusion: Our data showed that B[a]P regulates the invasive properties of RA FLS through Slug expression. This mechanism may provide a novel molecular link underlying the association between smoking and increased radiographic progression in RA. [Copyright &y& Elsevier]

The aim of this study is to investigate the effects of CIP2A (Cancerous inhibitor of protein phosphatase 2A) on the apoptosis of RA FLS. Proliferation and apoptotic activity of RA FLS following treatment with CIP2A siRNA or control siRNA were analyzed using MTT assays and Cell Death Detection kit. RA FLS was treated with CIP2A siRNA or control siRNA in 3-, 6-, and 9-day intervals for a Western blot analysis to determine C-Myc expression. To evaluate the signal transduction pathways engaged in apoptosis, caspase-3 activity, caspase-9 activity, PARP, and phosphorylation of the Akt kinase were analyzed by Western blot. Cell viability of RA FLS was significantly lower in the CIP2A siRNA-treated group compared with the control after 7 days ( p = 0.022). Apoptosis of RA FLS was significantly higher in the CIP2A siRNA-treated group compared with the control when incubated for 3, 6, and 9 days ( p = 0.029, p = 0.021, p = 0.043, respectively). C-Myc expression did not change with the different incubation periods. CIP2A siRNA-treated FLS expressed higher level of activated caspase-3, caspase-9, and PARP ( p = 0.014, p = 0.020, p = 0.021, respectively) and lower level of phosphorylated Akt ( p = 0.001) compared with those treated with the control siRNA. Our data show that CIP2A expression in RA FLS is an important mediator of dysfunctional apoptosis independent of c-Myc stabilization. Expression of CIP2A may contribute to apoptotic resistance of RA FLS through the activation of Akt and deactivation of caspase-3, caspase-9, and PARP. Inhibition of CIP2A may therefore constitute a novel, promising therapeutic target in RA. [ABSTRACT FROM AUTHOR]

Abstract: The power loss of a wind turbine due to wakes from upstream turbines is significant for a wind farm. This power loss is usually about 20% of wind turbine power, and this can increase to 40% for an extreme case. Such effects decrease the annual energy production of a wind farm. Thus, it is important to predict the effect of these types of wakes so as to maximize the power output of a wind farm. In this study, we investigate a method to control the pitch angle of turbines to maximize the aerodynamic power of a wind farm. The pitch angle of each wind turbine is controlled by its own pitch schedule or feedback algorithm to optimize the power output. However, these control methods cannot consider the effects of wakes, such as velocity defects and an increase of the turbulent intensity. Thus, controlling the pitch angle of the turbine does not guarantee the maximum aerodynamic power of the wind farm, which is why a comprehensive control method considering all of the wind turbines of a wind farm is needed. The blade element momentum theory (BEM) is used for the aerodynamic analysis. In addition, in order to evaluate the wind turbine wake, the eddy viscosity model (EVM) is used. The wake is assumed to be a two-dimensional Gaussian profile determined by the thrust coefficients of the fore-located turbines and the atmospheric conditions. A genetic algorithm (GA) was applied to calculate the optimal power. The results show that control of the pitch angle can maximize the power output of the wind farm. [Copyright &y& Elsevier]

A service-oriented approach that com- bines feature-oriented analysis with a self- managing quality-of-service framework addresses the challenges associated with dynamic software product lines. [ABSTRACT FROM PUBLISHER]

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells. We aim to investigate CIP2A expression in fibroblast-like synoviocytes (FLS) and its association with the histopathological grade of synovitis and the invasive function of FLS in rheumatoid arthritis (RA). CIP2A protein expression was measured in 8 RA FLS and 8 OA FLS using Western blot analysis. CIP2A mRNA expression from 19 RA FLS and 7 OA FLS was measured using real-time PCR. Synovitis score of RA FLS-matched synovial tissues was semiquantitatively measured by two independent pathologists. An in vitro cell invasion assay was performed using RA FLS treated with CIP2A small interfering RNA (siRNA) or with control vector. Western blot analysis showed that CIP2A is more frequently overexpressed in RA FLS compared with OA FLS. CIP2A mRNA expression was higher in RA FLS compared with those in OA FLS, but did not reach statistical significance ( P = 0.076). In RA, total synovitis score was strongly correlated with FLS CIP2A mRNA expression ( rs = 0.849, P = 0.043). TNF-α treatment induced a robust increase in the invasive function of control FLS ( P = 0.0021), but no significant effect was observed in CIP2A siRNA-treated FLS. Our data demonstrate that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of FLS in RA. These results suggest that CIP2A may play a critical role in the destructive process in RA and warrant further investigation of CIP2A as a therapeutic target. [ABSTRACT FROM AUTHOR]

The aim of this study is to compare the expression of TIM-3 from CD4+ T cells from rheumatoid arthritis (RA) patients and healthy controls and to evaluate the effect of galectin-9 (Gal-9) on apoptosis of CD4+ T cells in these patients. CD4+ T cells from RA patients and healthy controls were isolated from peripheral blood mononuclear cells and were activated. The expression of TIM-3 mRNA in CD4+ T cells was measured using real-time polymerase chain reaction. CD4+ T cells were activated in the presence of graded doses of Gal-9 or control, and Gal-9-induced cytotoxicity and apoptotic activity of CD4+ T cells were analyzed using MTT assays and annexin-V staining, respectively. TIM-3 mRNA expression was significantly lower in CD4+ T cells from RA patients compared with those in healthy controls ( p = 0.028). CD4+ T cell survival as measured by MTT assay when incubated with Gal-9 (15 nM) was significantly higher in RA patients than in healthy controls ( p = 0.002). Apoptotic activity of CD4+ T cells from healthy controls as measured by annexin staining increased with graded doses of Gal-9 (0 nM vs. 30 nM, 0 nM vs. 90 nM, p = 0.016 each). However, apoptotic activity of CD4+ T cells from RA patients did not change despite the stimulation with Gal-9. Gal-9-mediated apoptosis of CD4+ T cells is dysfunctional in RA patients. Blunted Gal-9-mediated apoptosis may be exerted through underexpression of TIM-3 that negatively regulates Th1 response. Our data suggest that TIM-3 and its interaction with Gal-9 may play an important role in the pathogenesis of RA and may represent a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Kirner deformity is characterized by volar and radial incurvature of the distal phalanx of the 5th finger. A proposed causative mechanism includes abnormal distal insertion of the flexor digitorum profundus tendon along the volar surface of the distal phalanx of the 5th finger. A chronic inflammatory process or altered vascularisation of the soft tissues has also been suggested as the underlying causative mechanism based on MRI findings. We present a teenage boy with Kirner deformity, along with supplementary imaging of his father who also has the deformity, to illustrate MRI findings that dispute the above hypotheses. MRI in both son and father show normal insertion of the deep flexor tendon and no signs of inflammation. [ABSTRACT FROM AUTHOR]

• Two-stage staggered time integrator with the Jacobi-Anger expansion is introduced. • The method can be twice as faster than the Taylor expansion based time integrator. • Accuracy condition is obtained to bound error of the solution within a preset level. • Optimal strategy for the method is to use allowable maximum time step length. In this study, we introduce a staggered time integrator with the Fourier pseudospectral method to solve the first-order linear wave equation, which is accelerated by using the Jacobi-Anger expansion. The proposed method can reduce the computational cost by approximately half compared to the scheme whose temporal order of accuracy is extended by the Lax-Wendroff method under the equivalent modeling conditions, such as time step length, grid interval and maximum wave propagation speed. This is because the Jacobi-Anger expansion can effectively approximate the sinusoidal function, which in our case is the sine function in the wavenumber domain. Based on the wavenumber domain analysis of the proposed method, a strategy to optimally design the simulation parameters to maintain a preset level of accuracy is also introduced. According to the strategy, as the time step length increases, not only the computational cost of the simulation is reduced, but also the accuracy of the numerical solution is improved. Numerical simulations are also performed by using both homogeneous and heterogeneous models to validate the introduced strategy, which supports the practicality of the proposed method. [ABSTRACT FROM AUTHOR]

Hyperuricemia (HUA) has become a significant medical concern due to its complications and links to metabolic syndrome (MetS) and cardiovascular disease (CVD), which result in increased mortality. The pathogenic processes associated with unhealthy behaviors, MetS, and HUA can be cooperative and potentially synergistic in the activation of risk factors. Recent research has shown sex-based differences in the relationship between HUA and its associated risk factors. This study aimed to investigate these differences, particularly in the context of MetS and CVD risk factors and unhealthy lifestyles. We also aimed to evaluate the joint effects of these factors based on sex. We conducted a cross-sectional study using nationally representative survey data from the Korean National Health and Nutritional Examination Survey 2016–2018. We performed multivariable logistic regression analysis, calculating adjusted odds ratios (ORs) with their 95% confidence intervals (CIs). We also conducted subgroup analyses based on sex and the presence of MetS with or without unhealthy lifestyle factors (tobacco use, alcohol intake). We found sex-based differences in the relationships between HUA and MetS, CVD risk factors, and lifestyle behaviors. Our major finding was a significant association between MetS and HUA in both men and women, regardless of alcohol consumption and smoking status, and this association was stronger in women. We also observed a synergistic effect of MetS and lifestyle factors on the risk of HUA, particularly in women, in whom the risk of HUA increased up to four times compared to the reference group. A sex-based clinical strategy for HUA is necessary to reduce related complications and their socio-economic burden. [ABSTRACT FROM AUTHOR]

We propose a method to design a discrete fracture network (DFN) model for seismic wave simulations that eliminates complex meshing requirements and poor mesh design. An ant-tracking volume is generated from the original seismic to capture the global fracture geometry. A mesh structure is specified prior to adding fractures. Fractures are then specified on the mesh in the form of small fracture patches following the trend of ant-tracking signals in the previously defined mesh. In the proposed method, the implementation of the DFN model is thus independent of the mesh structure. Also, fracture clusters in the final DFN model are composed of multiple small patches, and each small patch is represented by the linear slip model in the form of a discontinuity of the displacement field. We also performed wave simulations to validate the proposed method of DFN model building, and investigated the wave behavior in the given fracture structure. For efficient implementation of wave modeling, we employed the generalized multiscale finite element method to discretize the elastic wave equation with explicit fractures. The wave simulation results show that a small fracture segment could be ignored when the wavelength is long enough; however, fracture clusters can induce large displacement discontinuities and wave scattering, and these effects become obvious as we apply high source frequency. • A DFN modeling which is independent of mesh structure is proposed. • Seismic wave modeling using multiscale FEM is performed for demonstration. • The proposed method can provide an inference of the seismic waves with fractures. [ABSTRACT FROM AUTHOR]

Objective: Few data are available on whether changes in metabolic syndrome affect incident gout. This study was undertaken to assess associations between metabolic syndrome status and incident gout, as well as changes in the clinical characteristics of metabolic syndrome and incident gout, in a cohort of young men. Methods: This nationwide, population‐based cohort study included 20–39‐year‐old men who participated in serial health check‐ups. The outcome, incident gout, was defined according to the claims database diagnostic code for gout. Associations among changes in metabolic syndrome status and incident gout were analyzed using Cox proportional hazards models. Results: Among 1,293,166 individuals, 18,473 were diagnosed as having gout (incidence rate 3.36 per 1,000 person‐years). Subjects who had chronic metabolic syndrome (defined as metabolic syndrome at all 3 health check‐ups) had a nearly 4‐fold higher risk of incident gout compared to subjects who did not have metabolic syndrome at any of the 3 health check‐ups (adjusted hazard ratio [HRadj] 3.82 [95% confidence interval (95% CI) 3.67–3.98]). Development of metabolic syndrome more than doubled the risk of incident gout (HRadj 2.31 [95% CI 2.20–2.43]). Conversely, recovery from metabolic syndrome reduced the risk of incident gout by nearly half (HRadj 0.52 [95% CI 0.49–0.56]). Among metabolic syndrome components, changes in elevated triglycerides (development of elevated triglycerides, HRadj 1.74 [95% CI 1.66–1.81]; recovery from elevated triglycerides, HRadj 0.56 [95% CI 0.54–0.59]) and abdominal obesity (development of abdominal obesity, HRadj 1.94 [95% CI 1.85–2.03]; recovery from abdominal obesity, HRadj 0.69 [95% CI 0.64–0.74]) showed the greatest association with altered risk of incident gout. Associations between changes in the status and clinical characteristics of metabolic syndrome and incident gout were more pronounced in subjects ages 20–29 years compared to those ages 30–39 years, and in subjects who were underweight or who had a normal weight. Conclusion: Changes in the status and clinical characteristics of metabolic syndrome were associated with altered risk of incident gout. These results suggest that metabolic syndrome is a modifiable risk factor for gout. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the relative risk of malignancy in patients with Takayasu's arteritis compared to that in the general population. This retrospective nationwide cohort study used data from the Korean Health Insurance Review and Assessment Service database. All newly diagnosed patients with Takayasu's arteritis were identified between January 2009 and December 2019. They were observed until the diagnosis of malignancy, death, or end of the observational period, December 2020. The standardized incidence ratios (SIRs) of the overall and site-specific malignancies were estimated and compared with the incidence of cancer in the general population retrieved from the National Cancer Registry. We identified 1449 newly diagnosed patients with Takayasu's arteritis during the observational period (9196 person-years). A total of 74, 66, and 8 patients had overall, solid, and hematologic malignancies, respectively. The risks of overall [SIR, 1.62; 95% confidence interval (CI) 1.27–2.03], solid (SIR, 1.51; 95% CI 1.17–1.92), and hematologic (SIR, 4.05; 95% CI 1.75–7.98) malignancies were increased compared to those in the general population. In solid malignancies, breast (SIR, 2.07; 95% CI 1.16–3.42) and ovarian (SIR, 4.45; 95% CI 1.21–11.39) cancers had an increased risk. In hematologic malignancies, the risk of myelodysplasia increased (SIR, 18.02; 95% CI 3.72–52.66). Immunosuppressive agent use was not associated with malignancy. There was no specific period when cancer more frequently occurred. An increased risk of malignancy was observed in patients with Takayasu's arteritis compared to that in the general population in this large-scale nationwide population study of Korean health insurance data. [ABSTRACT FROM AUTHOR]

Despite a growing burden posed by cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, large-scale studies on the association between the characteristics of RA patients and CVD risks and studies adjusted for various confounding factors are lacking. In this large-scale nationwide cohort study, we aimed to investigate the association between CVD risk and RA and factors that may increase CVD risk using a dataset provided by the Korean National Health Insurance Service (NHIS). We enrolled 136,469 patients with RA who participated in national health examinations within two years of RA diagnosis between 2010 and 2017 and non-RA controls matched by age and sex (n = 682,345). The outcome was the occurrence of myocardial infarction (MI) or stroke. MI was defined as one hospitalization or two outpatient visits with ICD-10-CM codes I21 or I22. Stroke was defined as one hospitalization with ICD-10-CM codes I63 or I64 and a claim for brain imaging (CT or MRI). The Cox proportional hazard model and Kaplan–Meier curve were used for analysis. The mean follow-up duration was 4.7 years, and the incidence rate of CVD was higher in the RA group than the control group (MI: 3.20 vs. 2.08; stroke: 2.84 vs. 2.33 per 1000 person-years). The risk of MI and stroke was about 50% and 20% higher, respectively, in RA patients. The association between RA and CVD was prominent in females after adjusting for confounding variables. The association between RA and risk of MI was significant in individuals without DM. Therefore, appropriate screening for CVD is important in all RA patients including females and younger patients. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical characteristics and radiographic outcomes of vascular Behçet's disease (BD) involving the aorta or its major branches. Methods: This retrospective cohort study was performed in patients with vascular BD involving the aorta or its major branches. All included patients underwent computed tomography angiography (CTA) at least two times with a 2- to 5-year interval. Radiographic progression was defined as newly developed and/or aggravated (> 20%) characteristic features on CTA. Results: The cohort included 22 patients with BD with a median interval of 3.65 years between the initial and follow-up CTA. Five patients (22.7%) showed radiographic progression. Patients with radiographic progression had a longer disease duration at baseline than those without (6.67 vs. 0.26 years, p = 0.028). Of all patients, 21 (95.5%) had vascular aneurysms/pseudoaneurysms and 11 (50.0%) had thrombosis. The most frequently involved artery with aneurysmal change was the abdominal aorta (8/21, 38.1%), followed by the iliac arteries (5/21, 23.8%). In the case of thrombosis, the most frequently involved arteries were the femoral (4/11, 36.4%) and iliac (4/11, 36.4%) arteries. The characteristics and locations of vascular involvement did not significantly differ according to the radiographic outcome. Conclusions: A considerable proportion of patients with BD with arterial involvement showed radiographic progression within 2–5 years. Patients with radiographic progression had a longer disease duration at baseline. The most common form of arterial involvement of BD was aneurysmal change, followed by thrombus formation. Key Points: • This study evaluated for the first time the radiographic outcomes of 22 patients with Behçet's disease involving the aorta or its major branches. • A considerable proportion of patients (5/22, 22.7%) showed radiographic progression. • Patients with radiographic progression had a longer disease duration at baseline than their counterparts; however, no other clinical factors were significantly different. • The most frequent form of vascular involvement was pseudoaneurysm followed by thrombosis. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study is to assess the prevalence and titer of rheumatoid factor (RF) in Korean health screening subjects and consecutive subjects with hepatitis B surface antigen (HBsAg) and to examine the factors influencing RF positivity. Methods: This study was performed in 37,660 patients (23,269 men, 14,391 women) without arthralgia, who participated in a health checkup program in 2009. Results: Approximately 3.7% of health screening subjects (3.3% of males and 4.4% of females) were positive for RF. Among subjects with HBsAg ( n = 1,494) and antibody for hepatitis C virus (HCV) ( n = 132), 11.8 and 10.6% were RF positive, respectively. There was a significant difference in the RF-positive rate between males and females. The RF-positive rate had a significant linear-by-linear association with aging, but there was no significant relationship between RF positivity and aging among subjects with HBsAg or anti-HCV antibody. Presence of HBsAg and anti-HCV antibody, positive C-reactive protein (CRP), and female sex were factors strongly associated with RF positivity. Conclusions: The rate of RF positivity in health screening adults and subjects with HBsAg in Korea can be estimated to be 3.7 and 11.8%, respectively. Clinicians should consider hepatitis B or C virus infection status, CRP positivity, and sex when interpreting RF-positive results. [ABSTRACT FROM AUTHOR]

The classification system for antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis and polyarteritis nodosa had its limitations due to numerous overlapping features of these disease entities. The aim of this study is to investigate the clinical features and outcome of patients diagnosed with microscopic polyangiitis (MPA) according to the newly proposed consensus algorithm of ANCA-associated vasculitides and polyarteritis nodosa. Fifty-five cases of MPA, comprised of 33 men and 22 women, diagnosed according to a new consensus algorithm at a single tertiary hospital were identified for analysis. The main clinical features were constitutional symptoms (78.2%), followed by renal involvement (74.5%), musculoskeletal symptoms (67.3%), skin manifestations (50.9%), neurologic involvement (43.6%), and lung involvement (41.8%). P-ANCA and/or anti-myeloperoxidase antibody were present in 69.1%. Five Factor Score and Birmingham Vasculitis Activity Score (BVAS) at diagnosis were 1.1 ± 0.9 and 10.9 ± 4.9, respectively. Forty-four patients were available for a long-term follow-up, and six patients (13.6%) resulted in death. Mortality was associated with BVAS > 9 at the time of diagnosis, age > 60 years, and presence of cardiomyopathy and interstitial lung disease. The survival rate at 1 and 3 years was 93.9 and 89.2%, respectively. Eight patients (14.5%) required dialysis at the time of diagnosis. This is the first study to demonstrate the clinical features in patients with MPA using a new consensus algorithm. Survival rate was higher than previously reported, and interstitial lung disease was a new risk factor for death in patients with MPA. [ABSTRACT FROM AUTHOR]

Survivin belongs to the family of inhibitor of apoptosis proteins and plays an important role in the hyperplastic growth of tissues and tumors. In this study, we assessed the expression of survivin in rheumatoid synovial fluids (SF) and synovial tissues (ST) of rheumatoid arthritis (RA) patients in order to investigate the role of extracellular survivin in the pathogenesis of RA. The survivin level from SF was significantly higher in RA patients ( n = 38) than in osteoarthritis patients ( n = 18; 10.68 ± 2.76 vs. 1.0 ± 0.56 pg/ml, p = 0.02). In addition, SF survivin level was higher in erosive RA patients ( n = 23) than in non-erosive RA patients ( n = 15; 15.26 ± 4.26 vs. 4.47 ± 1.12 pg/ml, p = 0.05). SF survivin level in RA was positively correlated with disease activity score 28, but did not reach statistical significance ( r = 0.309, p = 0.07). RA SF survivin level was also positively correlated with peripheral blood leukocyte counts ( r = 0.443, p = 0.005). The immunohistochemical staining and Western blot analysis revealed survivin expression in the ST and fibroblast-like synoviocytes of RA patients, respectively. These findings suggest that extracellular survivin may be produced from rheumatoid FLS and may play an important role in the destructive RA process. [ABSTRACT FROM AUTHOR]

The present study aimed at characterizing the phenotype and functions of adherent synovial fluid (SF) cells derived from rheumatoid arthritis (RA), comparing with fibroblast-like synoviocytes (FLS) derived from RA synovial tissue (ST). Adherent SF-derived cells were spindle-shaped from passages 1–6 under light microscopy. The cell surface marker profile in SF-derived cells from passage 1–6 was similar to that of ST-derived FLS. Levels of MMP-1 and MMP-3 were not significantly different between SF-derived cells and ST-derived FLS ( p = 0.20 and p = 0.40, respectively). There was no significant difference in the optical density value between two cell types in the cell invasion assay ( p = 0.10). SF-derived adherent cells have a fibroblast-like phenotype from very early culture passages and have the potential to produce MMPs with the invasive capacity to degrade cartilage, identical to ST-derived FLS. Therefore, these cells could substitute for ST-derived FLS in studying the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

Systematic discovery and exploitation of commonality across related software systems is a fundamental technical requirement for achieving successful software reuse. By examining a class/family of related systems and the commonality underlying those systems, it is possible to obtain a set of reference models, i.e., software architectures and components needed for implementing applications in the class. FORM (Feature-;Oriented Reuse Method) supports development of such reusable architectures and components (through a process called the “domain engineering”) and development of applications using the domain artifacts produced from the domain engineering. FORM starts with an analysis of commonality among applications in a particular domain in terms of services, operating environments, domain technologies, and implementation techniques. The model constructed during the analysis is called a “feature” model, and it captures commonality as an AND/OR graph, where AND nodes indicate mandatory features and OR nodes indicate alternative features selectable for different applications. Then, this model is used to define parameterized reference architectures and appropriate reusable components instantiatable during application development. Architectures are defined from three different viewpoints (subsystem, process, and module) and have intimate association with the features. The subsystem architecture is used to package service features and allocate them to different computers in a distributed environment. Each subsystem is further decomposed into processes considering the operating environment features. Modules are defined based on the features on domain technology and implementation techniques. These architecture models that represent an architecture at different levels of abstraction are derived from the feature hierarchy captured in the feature model. Modules serve as basis for creating reusable components, and their specification defines how they are integrated into the application (e.g., as-;is integration of pre-;coded component, instantiation of parameterized templates, and filling-;in skeletal codes). Our experiences have shown that for the electronic bulletin board and the private branch exchange (PBX) domains, “features” make up for a common domain language and the main communication medium among application users and developers. Thus, the feature model well represents a “decision space” of software development, and is a good starting point for identifying candidate reusable components. [ABSTRACT FROM AUTHOR]

We aim to generate an artificial neural network (ANN) model to predict early TNF inhibitor users in patients with ankylosing spondylitis. The baseline demographic and laboratory data of patients who visited Samsung Medical Center rheumatology clinic from Dec. 2003 to Sep. 2018 were analyzed. Patients were divided into two groups: early-TNF and non-early-TNF users. Machine learning models were formulated to predict the early-TNF users using the baseline data. Feature importance analysis was performed to delineate significant baseline characteristics. The numbers of early-TNF and non-early-TNF users were 90 and 505, respectively. The performance of the ANN model, based on the area under curve (AUC) for a receiver operating characteristic curve (ROC) of 0.783, was superior to logistic regression, support vector machine, random forest, and XGBoost models (for an ROC curve of 0.719, 0.699, 0.761, and 0.713, respectively) in predicting early-TNF users. Feature importance analysis revealed CRP and ESR as the top significant baseline characteristics for predicting early-TNF users. Our model displayed superior performance in predicting early-TNF users compared with logistic regression and other machine learning models. Machine learning can be a vital tool in predicting treatment response in various rheumatologic diseases. [ABSTRACT FROM AUTHOR]

Hyperuricemia and anemia share several comorbidities, but the association between the two conditions remains unclear. The purpose of this study was to investigate the association between hyperuricemia and anemia. Data of 10794 subjects from the Korean National Health and Nutrition Examination Survey conducted in 2016–2017 were analyzed using multivariate logistic regression analyses. An association between anemia and hyperuricemia was not evident in subjects without chronic kidney disease (CKD). In patients with CKD, anemia increased the risk of hyperuricemia by 2-fold. This association remained significant when adjusting for the glomerular filtration rate. In subgroup analyses, the association of anemia with hyperuricemia was significant in subjects aged ≥65 years, and in those with diabetes or hypertension. Subgroup analyses of CKD patients showed similar results. In the current study using data from Korean representative samples, anemia in subjects with CKD was associated with a 2-fold increase in the risk of hyperuricemia, which remained significant even after adjustment for renal function. [ABSTRACT FROM AUTHOR]

Objectives: Spondyloarthritis (SpA) encompasses a group of disorders including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. SpA pathogenesis is still not well understood. Animal models are important for studying disease mechanisms and identifying new therapeutic agents. Recently, a β-glucan-induced SKG mouse was used as an animal model for SpA. The aim of this study was to evaluate the clinical and molecular characteristics of a zymosan-induced SKG mouse.Methods: Zymosan was injected intraperitoneally into SKG mice. Clinical arthritis scores were measured, and fluorine-18 fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed tomography (PET/CT) was performed to quantify joint inflammation. Histologic features of the joints, intestines, skin, and eyes were evaluated. Inflammatory cytokine and Wnt inhibitor expression was measured in mouse serum.Results: Zymosan exposure triggered SpA-like diseases in SKG mice, including peripheral arthritis, spondylitis, dactylitis, enteritis, and psoriatic skin lesions. 18F-FDG uptake was significantly higher in the zymosan-treated mice compared with controls. The expression of tumor necrosis factor α, interleukin (IL)-6, and Dickkopf-1 increased significantly, while IL-4 and sclerostin expression decreased significantly in zymosan-induced mice compared with control mice.Conclusions: Zymosan-induced SKG mice developed articular and extra-articular features as well as molecular changes that resembled those of human SpA. These findings suggest that the zymosan-induced SKG mouse is a good animal model to reflect the complex features of human SpA. [ABSTRACT FROM AUTHOR]

Although many full waveform inversion methods have been developed to construct velocity models of subsurface, various approaches have been presented to obtain an inversion result with long-wavelength features even though seismic data lacking low-frequency components were used. In this study, a new full waveform inversion algorithm was proposed to recover a long-wavelength velocity model that reflects the inherent characteristics of each frequency component of seismic data using a single-frequency component decomposed from the spectrogram. We utilized the wavelet transform method to obtain the spectrogram, and the decomposed signal from the spectrogram was used as transformed data. The Gauss–Newton method with the diagonal elements of an approximate Hessian matrix was used to update the model parameters at each iteration. Based on the results of time–frequency analysis in the spectrogram, numerical tests with some decomposed frequency components were performed using a modified SEG/EAGE salt dome (A–A′) line to demonstrate the feasibility of the proposed inversion algorithm. This demonstrated that a reasonable inverted velocity model with long-wavelength structures can be obtained using a single frequency component. It was also confirmed that when strong noise occurs in part of the frequency band, it is feasible to obtain a long-wavelength velocity model from the noise data with a frequency component that is less affected by the noise. Finally, it was confirmed that the results obtained from the spectrogram inversion can be used as an initial velocity model in conventional inversion methods. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of tumor necrosis factor a inhibitors (TNFi) on spinal radiographic progression in patients with ankylosing spondylitis (AS). Methods: Subjects were selected from patients at a single tertiary hospital between 1995 and 2014. Patients who used TNFi with baseline and paired follow-up radiographic data with a minimum interval of 2 years were included. Time to start TNFi was defined as the time from symptom onset to the start of TNFi use. TNFi index was defined as the ratio of the period of TNFi use to the entire period of disease. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Univariable and multivariable linear regression analyses were used to identify factors associated with radiographic progression. Results: A total of 151 patients were included in the analysis. Seventeen (11.3%) patients were female and mean DmSASSS/year was 1.01 units/year. Mean X-ray follow-up duration was 102.9 ± 54.9 months. Mean time from symptom onset to start of TNFi use was 104.8 ± 83.6 months (median 84 months) and mean TNFi index was 42.9 ± 23.8% (median 40.9%). In multivariable analysis, initial mSASSS, initial C-reactive protein, body mass index, current smoker, and delayed start of TNFi use were associated with radiographic progression. Presence of peripheral arthritis and the TNFi index were negatively associated with radiographic progression. Conclusions: A delay in starting TNFi use and low TNFi index were associated with radiographic progression. Early and long-term use of TNFi appear to reduce spinal radiographic progression in patients with AS. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Chronic periaortitis (CP) is a disease characterized by a fibro‐inflammatory periaortic cuff and adventitia‐predominant fibrosis. CP encompasses idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm (AAA), and recent studies have documented overlap between CP and immunoglobulin G4‐related disease (IgG4‐RD). This study aimed to investigate clinical characteristics and treatment outcomes of patients with CP. Method: CP patients were identified by retrospective review of 1245 patients with International Classification of Diseases 10th edition code of aortitis or aortic disease. Patients were further classified into IgG4‐related and non‐IgG4‐related CP according to the criteria proposed by a Japanese study. Results: A total of 61 CP patients were identified. Patients showed a male predominance (70%) with median age of 61 at diagnosis. The abdominal aorta was most commonly involved (84%), while the thoracic aorta was affected in 46% of patients. Twenty‐three (38%) patients had accompanying aortic aneurysm. Approximately 60% of patients achieved remission without further relapse during the course. Ten patients were classified as IgG4‐related and 25 as non‐IgG4‐related. There was no significant difference in clinical features and outcomes between groups, with the exception of older age and greater pancreas involvement in IgG4‐related patients. Conclusion: We documented 61 CP patients including 10 IgG4‐related cases. CP involved the abdominal aorta in most patients and the thoracic aorta in approximately 50% of patients. IgG4‐related CP patients were older and had greater pancreas involvement, but disease outcomes appeared to be similar between IgG4‐related and non‐IgG4‐related CP. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the association of knee osteoarthritis (OA) with comorbidities and health-related quality of life (HRQOL). Methods: A total of 8,907 (weighted n = 13,687,058) participants aged ≥50 years who had undergone knee radiography were selected from the 2010–2012 Korea National Health and Nutrition Examination Survey. OA was classified into four subgroups based on the presence or absence of pain and radiographic OA (ROA): non-OA (Pain-/ROA-), pain only (Pain+/ROA-), ROA only (Pain-/ROA+), and painful ROA (Pain+/ROA+). ROA was defined as Kellgren–Lawrence grade ≥ 2. HRQOL measurements including EuroQOL visual analogue scale (EQ-VAS) scores and the five dimensions and summary index of the EuroQOL-5 dimension (EQ-5D index) were also analyzed. Multivariable logistic regression and linear regression analyses were performed. Results: After adjustment for socioeconomic and lifestyle characteristics, cardiovascular disease, malignancy, and other comorbidities were not significantly associated with OA. Pain only and painful ROA were each significantly associated with limitations in physical activity (odds ratio (OR) 2.66, 95% CI 2.07–3.44, p < 0.001 and OR 2.83, 95% CI 2.25–3.58, p < 0.001, respectively), lower EQ-VAS (β-coefficient = -10.95, p < 0.001 and β-coefficient = -9.75, p < 0.001, respectively), and EQ-5D index (β-coefficient = -0.10, p < 0.001 and β-coefficient = -0.13, p < 0.001) compared with the non-OA group, whereas ROA only was not associated with limitations in physical activity or lower HRQOL score. Conclusions: Comorbidities were not significantly associated with knee OA after adjustment. Knee OA was associated with physical activity and HRQOL. Painful knee OA, with or without ROA, was more strongly associated with decreased physical activity and lower quality of life than ROA without pain. [ABSTRACT FROM AUTHOR]

Objectives Pulmonary arterial hypertension ( PAH) is a major cause of mortality in connective tissue disease ( CTD). The survival rates and mortality-predictive factors of a nationwide registry of Korean patients with CTD- PH measured by echocardiography were determined. Methods Patients with CTD- PH were enrolled between April 2008 and December 2012. Hemodynamic parameters and clinical data ( WHO-functional class [ FC], organ involvement, laboratory tests and treatment agents) were recorded. Survival rates were calculated by using the Kaplan-Meier method. Mortality-associated factors were examined by Cox proportional hazards regression analysis. Results In total, 174 incident PH cases (61 with systemic lupus erythematosus, 50 with systemic sclerosis, 10 with mixed CTD, 22 with rheumatoid arthritis ( RA) and 31 with other CTDs) were diagnosed by Doppler echocardiography. Of these, 25 (14%) died during the 3.8 ± 2.7 year follow-up period after PH diagnosis. The 1- and 3-year survival rates were 90.7% and 87.3%, respectively. Compared to the other CTD- PHs, RA- PH had the lowest survival rates (56% 3 year survival; P = 0.022). Multiple regression analysis revealed that low diffusion capacity of carbon monoxide ( DLCO), pleural effusion and diabetes mellitus were poor prognostic factors ( P = 0.008, 0.04 and 0.009, respectively). Anti- UI- RNP (ribonucleoprotein) antibody positivity was protective ( P = 0.022). In patients with WHO- FC III/ IV, patients who received vasodilators had lower mortality than those who did not ( P = 0.038). Conclusions In Korean patients with CTD- PH, the 3-year survival rate was 87%. Low diffusion capacity of carbon monoxide ( DLCO), pleural effusion and diabetes mellitus were independent poor prognostic factors. Anti- UI- RNP antibody was protective. Prompt PAH-specific vasodilator therapy may improve the survival of patients with severe CTD- PH. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical effectiveness of two treatment strategies for active rheumatoid arthritis (RA) refractory to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs): starting TNF inhibitors (TNFIs) or changing csDMARDs. Methods: We used two nationwide Korean RA registries for patient selection. TNFI users were selected from the BIOPSY, which is an inception cohort of RA patients starting biologic DMARDs. As a control group, we selected RA patients with moderate or high disease activity from the KORONA database whose treatment was changed to other csDMARDs. After comparing baseline characteristics between the two groups in either unmatched or propensity score matched cohorts, we compared potential differences in the 1-year remission rate as a primary outcome and changes in HAQ-DI and EQ-5D scores as secondary outcomes. Results: A total of 356 TNFI starters and 586 csDMARD changers were identified from each registry as unmatched cohorts, and 294 patients were included in the propensity score matched cohort. In the intention-to-treat analysis, TNFI starters had higher 1-year remission rates than csDMARD changers in both unmatched (19.1 vs. 18.4%, p < 0.01) and matched cohorts (19.7 vs. 15.0%, p < 0.01). In per protocol analysis, TNFI starters had much higher remission rates in unmatched (37.2 vs. 28.0%, p = 0.04) and matched cohorts (35.4 vs. 19.1%, p = 0.04). However, in matched cohorts, no significant differences were observed between two groups in HAQ-DI and EQ-5D scores. Conclusions: We compared the clinical effectiveness of the two treatment strategies for active RA refractory to csDMARDs. TNFI starters showed higher 1-year remission rates than csDMARD changers. [ABSTRACT FROM AUTHOR]

To investigate whether dysregulated selection of autoreactive marginal zone (MZ) B cells is involved in autoimmune diseases, we examined MZ B cell profile in multiple strains of mice, and found that type II collagen (CII)-reactive autoreactive CD80 high MZ B cells spontaneously developed in the DBA/1, but not in C57BL/6 mice. CD80 high MZ B cells that were characteristically found in DBA/1 mice expressed higher levels of TACI, SLAM3, and SLAM6 than the usual CD80 low MZ B cells. Notably, the CD80 high MZ B cells were more sensitive to ibrutinib, a Bruton's tyrosine kinase inhibitor, than CD80 low MZ or follicular B cells and their transient depletion via intravenous injection of ibrutinib significantly delayed the induction of collagen-induced arthritis (CIA). In summary, we suggest that the positive selection of CII-reactive CD80 high MZ B cells is a critical homeostatic process predisposing the DBA/1 mice to the CIA induction. [ABSTRACT FROM AUTHOR]

Despite improved quality of care for rheumatoid arthritis (RA) patients, many still experience treatment failure with a biologic agent and eventually switch to another biologic agent. We investigated patterns of biologic treatment and reasons for switching biologics in patients with RA. Patients with RA who had started on a biologic agent or had switched to another biologic agent were identified from the prospective observational Korean nationwide Biologics (KOBIO) registry. The KOBIO registry contained 1184 patients with RA at the time of initiation or switching of biologic agents. Patients were categorized according to the chronological order of the introduction of biologic agents, and reasons for switching biologics were also evaluated. Of the 1184 patients with RA, 801 started with their first biologic agent, 228 were first-time switchers, and 89 were second-time or more switchers. Second-time or more switchers had lower rheumatoid factor and anti-CCP positivity, and higher disease activity scores at the time of enrollment than the other groups. Among these patients, tocilizumab was the most commonly prescribed biologic agent, followed by adalimumab and etanercept. The most common reason for switching biologics was inefficacy, followed by adverse events, including infusion reactions, infections, and skin eruptions. Furthermore, the proportion of inefficacy, as a reason for switching, was significantly higher with respect to switching between biologics with different mechanisms of action than between biologics with similar mechanisms. In this registry, we showed diverse prescribing patterns and differing baseline profiles based on the chronological order of biologic agents. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010–2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17–2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24–3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05–3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05–2.77), depression (OR 2.38, 95% CI 1.47–3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15–4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the association between rheumatoid arthritis (RA) and hearing impairment in the Korean adult population. Audiometric and laboratory test data from the 2010–2012 Korean National Health and Nutrition Examination Survey (KNHANES) were used for analysis. The relationship between RA and hearing impairment was analyzed, adjusting for various known risk factors associated with hearing impairment. RA was defined in the questionnaire as “RA diagnosed by a physician (yes/no) through a standardized interview.” We defined hearing impairment according to 2 categories of frequency (low/mid and high) as follows (average values in kHz): low/mid frequency, 0.5, 1.0, and 2.0, and high frequency, 3.0, 4.0, and 6.0. Of the subjects, 15,158 (weighted n = 32,035,996) completed the audiometric tests. The overall weighted prevalence of RA was 1.5%. The prevalence of hearing impairment was higher in the subjects with RA than in those without RA, in both, the low/mid- and high-frequency categories (21.1% vs 7.5%, p < 0.001 and 43.3% vs. 26.2%, p < 0.001, respectively). In the multivariable logistic analysis, RA (odds ratios [OR] 1.47, 95% confidence interval [CI] 1.05–2.06, p = 0.025) was an independent risk factor of low/mid-frequency hearing impairment along with age (OR 1.12, 95% CI 1.12–1.13, p < 0.001), current smoking (OR 1.27, 95% CI 1.03–1.56, p = 0.026), and college graduation (OR 0.53, 95% CI 0.39–0.72, p < 0.001). In the multivariable analysis of high-frequency hearing impairment, RA did not show any association with hearing impairment. This study suggests that RA is associated with low/mid-frequency hearing impairment after adjustment for various known risk factors. Further study is needed to verify the hearing impairment in RA. [ABSTRACT FROM AUTHOR]

Bone marrow hemophagocytosis is a frequently observed but not mandatory finding for the diagnosis of hemophagocytic lymphohistiocytosis (HLH). However, the impact of bone marrow hemophagocytosis on the diagnosis of HLH is still not clear in adult patients. Thus, we retrospectively analyzed adult patients with bone marrow hemophagocytosis between 2000 and 2014 to determine its clinical significance. Among 264 patients with bone marrow hemophagocytosis, malignant disorders were the predominant underlying cause (n = 170, 64 %), especially T/NK-cell (n = 88) and B-cell (n = 45) lymphomas compared to infectious disease (48/264, 18 %). The data for HLH-2004 diagnostic criteria was available in 182 patients, and only 29 % (77/264) of patients with ≥ five positive criteria could be diagnosed with HLH. Among the criteria for the diagnosis of HLH, increased serum ferritin (89 %) was more common than hypofibrinogenemia, hypertriglyceridemia, and bicytopenia (<40 %). The median overall survival was worse in patients with malignancy (9.0 months, 95 % confidence interval [CI] 5.6-12.5) than in those with non-malignant disorders (71.8 months, 95 % CI 56.5-87.1, P < 0.001). In patients with malignancy, the overall survival of patients fulfilling the HLH-2004 criteria was significantly worse than patients who did not (P < 0.001). In conclusion, our results suggest that bone marrow hemophagocytosis might be an important finding in the diagnosis of HLH in adult patients. Considering the high incidence of malignancy as a predisposing disorder for HLH, immediate evaluation should be performed in adult patients with bone marrow hemophagocytosis. [ABSTRACT FROM AUTHOR]

Aim To evaluate the clinical characteristics and outcomes of nonradiographic axial spondyloarthritis (nr-axSpA) in Korean patients. Methods A retrospective analysis evaluated 155 patients with nr-axSpA at a single tertiary hospital between January 2001 and January 2011. Baseline characteristics and clinical courses were reviewed and compared with those of patients with ankylosing spondylitis ( AS). Results The mean age at disease onset was 29.5 ± 10.8 years and 52 (33.5%) patients were female. The mean age at symptom onset was older (29.5 ± 10.8 vs 25.9 ± 9.2, respectively, P < 0.001) and the male-to-female ratio was lower (2 : 1 vs 5 : 1, respectively, P = 0.001) in patients with nr-axSpA compared with patients with AS. The proportion of females was higher among patients with late onset SpA than early-onset nr-axSpA (55.0% vs 30.1%, respectively, P = 0.029). Among 74 patients with nr-axSpA, whose follow-up duration was more than 1.5 years, 29 (39.2%) patients progressed to AS during the follow-up period. The proportion of females was lower in progressors that that of non-progressors (13.8% vs 44.4%, respectively, P = 0.010). Presence of syndesmophyte and minimal X-ray changes at baseline were frequently observed in progressors compared with non-progressors (26.7% vs 0.0%, P = 0.006 and 69.0 vs 35.6%, P = 0.005, respectively). Conclusions The predominance of male patients is more prominent among Korean patients with SpA compared with Caucasians. Female nr-axSpA patients had late symptom onset and less progression to AS. X-ray changes at baseline were associated with radiographic progression. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing anti-tumor necrosis factor (TNF) treatment are at an increased risk of reactivating a latent tuberculosis infection (LTBI). This study evaluated the effectiveness of the QuantiFERON-TB Gold In-Tube (QFT) assay for diagnosing LTBI in arthritis patients undergoing anti-TNF treatment. Methods: We enrolled 342 consecutive patients from August 2007 to October 2013: 176 (51.5%) patients with ankylosing spondylitis and 166 (48.5%) with rheumatoid arthritis. Screening tests included tuberculin skin test (TST) and QFT assay. Positive QFT results, regardless of TST results, were considered an indicator for LTBI treatment. Results: Bacillus Calmette-Guérin scars were found in 236 (69.0%) patients. Of 342 patients, TST and QFT were positive in 122 (35.7%) and 103 (30.1%) patients, respectively, and discordant in 101 (29.5%) patients. During a median follow-up duration of 41.7 months, five patients (1.5%) developed TB in a median of 20.8 months after initiation of anti-TNF treatment (428/100,000 person-years). TB did not occur in 62 TST+/QFT+ patients who received LTBI treatment. Of 41 TST−/QFT+ patients who received LTBI treatment, one (2.4%) developed TB 20.5 months after starting anti-TNF treatment (705/100,000 person-years). Of 60 TST+/QFT− patients who did not receive LTBI treatment, two (3.3%) developed TB 20.8 and 22.0 months after starting anti-TNF treatment (871/100,000 person-years). Of 179 TST−/QFT− patients, two (1.1%) developed TB 7.2 and 22.7 months, respectively, after initiating anti-TNF treatment (341/100,000 person-years). TB incidence rate during the follow-up period did not differ among TST−/QFT+, TST+/QFT−, and TST−/QFT− patients (P = 0.661). Conclusion: QFT might be used instead of TST for diagnosing LTBI in patients before starting anti-TNF therapy in countries, such as Korea, where the TB prevalence is intermediate and the BCG vaccination is mandatory at birth. In the absence of a true gold standard test for LTBI, however, there is still a risk of TB development during anti-TNF treatment. [ABSTRACT FROM AUTHOR]

Objectives To evaluates the pregnancy outcomes in systemic lupus erythematosus ( SLE) patients in South Korea and determine the predictive factors for adverse fetal and maternal outcomes. Methods All pregnancies in SLE patients who were seen at the Samsung Medical Center between November 1994 and December 2010 were included and retrospectively analyzed. SLE flares were determined by the Lupus Activity Index-Pregnancy ( LAI-P) score. Results Sixty-two pregnancies were observed in 50 patients. Fifty-one (82.3%) live births and 11 (17.7%) fetal losses were observed. Thirty-eight of the live births (74.5%) were full-term and 13 (25.5%) were preterm births. Fetal losses included three spontaneous abortions, two stillbirths and six therapeutic abortions. Proteinuria during pregnancy was a predictive factor for adverse fetal outcomes (adjusted odds ratio [ OR] 12.50; P = 0.032). An LAI-P score was obtained in 36 pregnancies, and SLE flares occurred in 12 pregnancies (33.3%), primarily during the second trimester (46.2%). Renal involvement (69.2%) was the most common SLE flare during pregnancy. All flares were classified as severe flare according to LAI-P scores. SLE flares during pregnancy were strongly affected by proteinuria prior to pregnancy (adjusted OR 30.28; P = 0.024) and the presence of antiphospholipid antibodies (adjusted OR 6.62; P = 0.047). Conclusion Our study demonstrated a rate of live births and of flares in pregnant lupus patients comparable to recent reports in Western countries. Proteinuria during and prior to pregnancy and presence of antiphospholipid antibodies were predictive factors for poor pregnancy outcome. Preserved renal function prior to pregnancy resulted in favorable outcomes even in patients with a history of lupus nephritis. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the clinical courses and outcomes of patients with monoarthritis and to investigate the predictive factors of clinical outcomes. Methods A retrospective analysis was performed of 171 patients with chronic monoarthritis at a single tertiary hospital between January 2001 and January 2011. Baseline characteristics, radiographic findings and the clinical course were reviewed. Results The most commonly involved joints were the knees (24.0%), followed by the wrists (22.8%) and ankles (18.7%). A final diagnosis was established in 74 (43.3%) patients. Thirty-one (18.1%) patients were diagnosed with rheumatoid arthritis ( RA), 23 (13.5%) with peripheral spondyloarthritis (SpA), and 19 (11.1%) with Behçet's disease ( BD). Among 108 patients who were initially undiagnosed, 85 (78.7%) patients remained with undiagnosed monoarthritis, with relatively shorter symptom durations and requiring less treatment. The initially involved joint was a predictive factor for the final diagnosis: the wrist joint for RA (odds ratio [ OR] 11.58, P < 0.001), the ankle joint for SpA ( OR 6.19, P < 0.001), and the knee joint for BD ( OR 3.43, P = 0.014). Bony erosion at baseline was associated with progression to oligo- or polyarthritis ( OR 2.88, P = 0.030) and with radiographic progression. Conclusions In patients presenting with monoarthritis, a final diagnosis was established in less than half of the patients, and a majority of undiagnosed patients showed benign clinical courses. The initially involved joint and the presence of erosion at baseline were predictors of the final diagnosis and of clinical outcomes. [ABSTRACT FROM AUTHOR]