Gout is the most common inflammatory arthritis. Current urate-lowering therapies have limitations, such as adverse drug reactions or limited efficacy. Epaminurad is a novel selective human urate transporter 1 (hURAT1) inhibitor that has been shown to reduce serum urate (sUA) levels in healthy volunteers and patients with gout. The aims of the current study were to evaluate the urate-lowering efficacy and safety of epaminurad compared with placebo in patients with gout, and to determine the optimal dose. This multicenter, randomized, double-blind, placebo-controlled, dose-finding phase 2b clinical trial, which incorporated a standard-treatment reference arm, enrolled patients aged 19–70 years with gout and sUA level ≥ 0.42 mmol/L. Participants received gout prophylaxis and followed therapeutic lifestyle changes, and were randomized to receive epaminurad 3 mg, 6 mg or 9 mg, or febuxostat 80 mg, or matching placebo, once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sUA level < 0.36 mmol/L at week 4 after initiation of study treatment. Statistical comparisons were performed between the epaminurad and placebo groups. Overall, 169 patients received study medication (99.40

Background/Aims:To compare the efficacy and safety of fexuprazan and lansoprazole for preventing peptic ulcers (PUs) induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Methods:This multicenter, double-blind, randomized, active-controlled study was conducted across 32 hospitals in South Korea. Patients with musculoskeletal disease requiring long-term treatment with celecoxib, naproxen, or meloxicam were randomized to receive either fexuprazan 20 mg/day (n=212) or lansoprazole 15 mg/day (n=211) for 24 weeks. The primary endpoint was the occurrence of PUs, which were confirmed via esophagogastroduodenoscopy (EGD), with a non-inferiority margin of 8.3%. Only ulcers that developed during the treatment period were examined in the analysis. The occurrence of gastroduodenal bleeding was also monitored via EGD, and symptoms were assessed by using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). Adverse events were recorded during the study. Results:The incidence rate of EGD-confirmed PUs at week 24 was 1.16% in the fexuprazan group and 2.76% in the lansoprazole group, with a between-group difference of -1.64% (95% confidence interval, -4.52% to 1.25%), demonstrating non-inferiority. No patients presented with gastroduodenal bleeding. No significant between-group differences were found in the PAGI-SYM scores (leastsquare mean difference in the total score at week 24, -0.42; 95% confidence interval, -2.48 to 1.64; p=0.69). There were low rates of adverse drug reactions in the fexuprazan and lansoprazole groups (8.57% vs 4.78%, respectively p=0.12). Conclusions:Given its non-inferiority to lansoprazole and similar safety profile, fexuprazan is a promising alternative for the prevention of NSAID-induced PUs (ClinicalTrials.gov identifier NCT04784910).

Purpose: Sacroiliitis refers to the inflammatory condition of the sacroiliac joints, frequently causing lower back pain. It is often associated with systemic conditions. However, its signs on radiographic images can be subtle, which may result in it being overlooked or underdiagnosed. This study aims to utilize artificial intelligence (AI) to create a diagnostic tool for more accurate sacroiliitis detection in radiological images, with the goal of optimizing treatment plans and improving patient outcomes. Materials and Method: The study included 492 patients who visited our hospital. Right sacroiliac joint films were independently evaluated by two musculoskeletal radiologists using the Modified New York criteria (Normal, Grades 1–4). A consensus reading resolved disagreements. The images were preprocessed with Z-score standardization and histogram equalization. The DenseNet121 algorithm, a convolutional neural network with 201 layers, was used for learning and classification. All steps were performed on the DEEP:PHI platform. Result: The AI model exhibited high accuracy across different grades: 94.53% (Grade 1), 95.83% (Grade 2), 98.44% (Grade 3), 96.88% (Grade 4), and 96.09% (Normal cases). Sensitivity peaked at Grade 3 and Normal cases (100%), while Grade 4 achieved perfect specificity (100%). PPVs ranged from 82.61% (Grade 1) to 100% (Grade 4), and NPVs peaked at 100% for Grade 3 and Normal cases. The F1 scores ranged from 64.41% (Grade 1) to 95.38% (Grade 3). Conclusions: The AI diagnostic model showcased a robust performance in detecting and grading sacroiliitis, reflecting its potential to enhance diagnostic accuracy in clinical settings. By facilitating earlier and more accurate diagnoses, this model could substantially impact treatment strategies and patient outcomes.

Background/Aims We investigated the effect of rituximab on systemic bone metabolism in patients with seropositive rheumatoid arthritis (RA). Methods Twenty seropositive patients with RA were enrolled and administered one cycle of rituximab. If RA became active for > 6 months after the first rituximab cycle, a second cycle was initiated; otherwise, no additional treatment was administered. Patients were divided into two groups according to the number of rituximab treatment cycles. Results In patients treated with a second cycle, the total hip bone mineral density (BMD) was clinically low, whereas the serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL) were increased at 12 months. BMD in patients treated with one cycle did not change at 12 months, whereas serum RANKL levels decreased at all time points. DAS28 activity improved in both groups from baseline to 4 months; however, from 4 to 12 months, DAS28 activity worsened in the group with the second cycle but remained stable in the group with one cycle. Conclusions Systemic inflammation, reflected by increased disease activity, may be responsible for the increase in RANKL levels, which causes systemic bone loss in rituximab-treated patients with RA. Although rituximab affects inflammation, it does not seem to alter systemic bone metabolism in RA.

BACKGROUND Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen (HLA) B27 haplotype. In regions where conventional polymerase chain reaction for HLA typing is available for antigens such as HLA B27 or HLA B51, it is common to perform the HLA B27 test for evaluation of AS. While HLA B27-associated clustered occurrences of AS have been reported in families, we report the first case series of HLA B51-related occurrences of AS in a family. CASE SUMMARY A father and his daughters were diagnosed with AS and did not have the HLA B27 haplotype. Although they were positive for HLA B51, they exhibited no signs of Behçet’s disease (BD). Of the five daughters, one had AS, and three, including the daughter with AS, were positive for HLA B51. The two daughters with the HLA B51 haplotype (excluding the daughter with AS) exhibited bilateral grade 1 sacroiliitis, whereas the daughters without the HLA B51 haplotype did not have sacroiliitis. Thus, this Korean family exhibited a strong association with the HLA B51 haplotype and clinical sacroiliitis, irrespective of the symptoms of BD. CONCLUSION It is advisable to check for HLA B51 positivity in patients with AS/spondyloarthropathy who test negative for HLA B27.

Little is known about the nature of relationships between sleep disturbance and influencing factors in rheumatoid arthritis. The purpose of this study was to identify factors that influence sleep disturbance and to evaluate mediating effects of depression on sleep disturbance. A nonexperimental, descriptive, correlational study design was adopted. One hundred patients with rheumatoid arthritis were recruited. Inflammatory status and levels of pain, fatigue, functional disability, depression, and sleep disturbance were measured. The factors that directly influenced sleep disturbance were gender, rheumatoid arthritis duration, serum C-reactive protein level, fatigue, and depression. Depression was found to have mediating effects on the relationships between sleep disturbance and arthritis symptoms. Pain, fatigue, and depression were found to have significant direct or indirect impacts on sleep disturbance. Our findings may improve understanding of sleep disturbance and aid the development of effective nursing management strategies for patients with rheumatoid arthritis suffering from sleep disturbance.

Objectives To characterize, using magnetic resonance imaging (MRI), the distribution of blood flow and oxygen transport in human fetuses with subtypes of congenital heart disease (CHD) that present with neonatal cyanosis. Methods Blood flow was measured in the major vessels of 152 late-gestation human fetuses with CHD and 40 gestational-age-matched normal fetuses, using cine phase-contrast MRI. Oxygen saturation (SaO(2)) was measured in the major vessels of 57 fetuses with CHD and 40 controls. Results Compared with controls, we found lower combined ventricular output in fetuses with single-ventricle physiology, with the lowest being observed in fetuses with severe forms of Ebstein's anomaly. Obstructive lesions of the left or right heart were associated with increased flow across the contralateral side. Pulmonary blood flow was reduced in fetuses with Ebstein's anomaly, while those with Ebstein's anomaly and tricuspid atresia had reduced umbilical flow. Flow in the superior vena cava was elevated in fetuses with transposition of the great arteries, normal in fetuses with hypoplastic left heart, tetralogy of Fallot or tricuspid atresia and reduced in fetuses with Ebstein's anomaly. Umbilical vein SaO(2) was reduced in fetuses with hypoplastic left heart or tetralogy of Fallot. Ascending aorta and superior vena cava SaO(2) were reduced in nearly all CHD subtypes. Conclusions Fetuses with cyanotic CHD exhibit profound changes in the distribution of blood flow and oxygen transport, which result in changes in cerebral, pulmonary and placental blood flow and oxygenation. These alterations of fetal circulatory physiology may influence the neonatal course and help account for abnormalities of prenatal growth and development that have been described in newborns with cyanotic CHD. (C) 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Polyarteritis nodosa (PAN) is a systemic vasculitis that can affect multiple organs in its diffuse form and is associated with high rates of morbidity and mortality. From the standpoint of pathology, PAN is necrotizing arteritis predominantly involving medium and small muscular arteries, without glomerulonephritis or vasculitis in the arterioles, capillaries, or venules (1, 2). PAN has protean manifestations, and it may present as a systemic disease or in its limited form, be confined to a single organ (2). The limited form of PAN is rare and may pose a diagnostic challenge; it can mimic other common diseases, and its nonspecific presentation may lead to confusion or delays in diagnosis. Musculoskeletal system involvement in PAN is known to present as myalgia, arthralgia, polymyositis-like syndrome, asymmetric nondeforming polyarthritis, or rarely, as intermittent claudication, acute leg ischemia, or myopathy (2). Muscular involvement in PAN may occur as a component of systemic PAN or as a limited form. Patients with the limited form of PAN are known to present with pain, swelling, and tenderness of the lower leg (3). Magnetic resonance imaging (MRI) findings of muscular involvement in PAN have been reported in other studies, all in cases with the limited form of PAN (4). Most of the previous studies have reported nonspecific edematous signal changes in the affected muscles with hyper-signal intensities on T2-weighted or fat-saturated sequences (5), which may be found in all clinical mimics such as inflammatory or infectious myositis. Ultrasound is particularly useful in the diagnosis of largeand medium-sized vessel vasculitis, as the characteristic wall thickening of the affected arteries allows for the confirmation of a suspected diagnosis. However, only a few studies have reported ultrasonography findings for the limited form of PAN. Herein, we describe a rare case of PAN involving skeletal muscle as indicated on This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: January 16, 2021 Revised: February 22, 2021 Accepted: February 23, 2021

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the axial joints. Altered bone metabolism associated with chronic inflammation leads to both new bone formation in the spine and increased bone loss. It is known that patients with axSpA have a high prevalence of osteoporosis and fractures. However, there is no consensus on which imaging modality is the most appropriate for diagnosing osteoporosis in axSpA. Bone mineral density measurement using dual-energy X-ray absorptiometry is the primary diagnostic method for osteoporosis, but it has notable limitations in patients with axSpA. This method may lead to the overestimation of bone density in patients with axSpA because they often exhibit abnormal calcification of spinal ligaments or syndesmophytes. Therefore, the method may not provide adequate information about bone microarchitecture. These limitations result in the underdiagnosis of osteoporosis. Recently, new imaging techniques, such as high-resolution peripheral quantitative computed tomography, and trabecular bone score have been introduced for the evaluation of osteoporosis risk in patients with axSpA. In this review, we summarize the current knowledge regarding imaging techniques for diagnosing osteoporosis in patients with axSpA.

©2019 Turkish League Against Rheumatism. All rights reserved. Gout is a very common inflammatory arthritis by monosodium urate crystal deposition with increasing incidence.1,2 Tophi appears, on average, 11.6 years after the initial acute attack of gouty arthritis.3 Most patients with digital contractures caused by tophi or tenosynovitis have undergone surgery.3-7 In this article, we report a case of successful medical treatment of extensive gouty digital flexion contractures. A 51-year old male patient presented with an 18-month history of an inability to flex his right second to fourth fingers. There was no family history of gout. Physical examination showed no mass or erythema in his hands, and no sensory deficits. Passive limitations of motion were present. The active range of motion of the right second to fourth metacarpophalangeal (MCP) joints and that of the right second to fourth

As the prevalence of gout and hyperuricemia increases, the comorbidities of gout and hyperuricemia have become a public health burden. In particular, risks of cardiovascular disease (CVD)-related complications are increasing. However, a few guidelines exist for the management of hyperuricemia. This cross-sectional study aimed to investigate the association of serum uric acid with CVD risk in the general population of Korean adults. We examined cross-sectional data from the first and second years of the seventh Korea National Health and Nutrition Examination Survey 2016-2017. Among 16,277 participants, 8781 were analyzed. We estimated the CVD risk using a 10-year CVD risk score prediction formula. There was a significant association of serum uric acid with 10-year CVD risk scores after adjusting for physical activity, body mass index, serum creatinine, and alcohol consumption in both sexes (p < 0.001). In the fitted fractional polynomial model, an approximate U-shaped association between serum uric acid levels and 10-year CVD risk scores was found in men. At the serum uric acid level of 6.9 mg/dL, the CVD risk was lowest. An approximate J-shaped association between serum uric acid levels and 10-year CVD risk scores was found in women. Our study showed that hyperuricemia was associated with an increased CVD risk. Hypouricemia was also associated with an increased CVD risk in men. We, therefore, recommend proper management of uric acid levels in the general population to reduce CVD risks.

Background/Aims: To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) Methods: The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks. Results: Those treated with TCZ showed more favorable outcomes in terms of 20% according to the American College of Rheumatology response criteria (ACR20) and ACR50 responses, individual parameters of ACR core set, disease activity score in 28 joints (DAS28) remission, and European League Against Rheumatism (EULAR) response at week 24. These improvements were maintained or increased during the extension period. DAS28 remission at week 72 was associated with EULAR good response at week 12. The patients who experienced any adverse event (AE) were more frequent in the TCZ group compared to the placebo group. Most AEs were mild or moderate in intensity, although TCZ therapy had possible AEs including serious infection, abnormal liver function, and atherogenic lipid profile. Conclusions: TCZ infusion add-on is highly efficacious and well-tolerated in Korean patients with active RA refractory to conventional DMARDs including MTX. EULAR good response at week 12 could predict DAS28 remission at week 72.

BackgroundPatients with ankylosing spondylitis (AS) have a higher risk of cardiovascular disease. Atherosclerosis is a main pathological process of cardiovascular disease and calcified plaque is a characteristic feature of atherosclerosis. Inflammation plays a potential role in vascular calcification. There is no previous study revealing the mechanism of vascular calcification in AS.ObjectivesWe investigated the relationship between vascular calcification and inflammation in patients with AS.MethodsSixteen male patients aged over 20 years with AS were enrolled. They fulfilled the modified New York criteria and each of their ankylosing spondylitis disease activity score was more than 2.1. Sex and age matched nine healthy controls were also recruited. Mouse MOVAS (American Type Culture Collection, ATCC®, CRL-2797TM) vascular smooth muscle cells were stabilized in maintenance medium for 24 hours. Then the amount of serum equivalent to 10% of maintenance medium from subjects was added and cells were stimulated for another 72 hours. We exchanged this medium with calcification medium every third day and cells were cultured for another 11 days. After 2 weeks, cells were stained with Alizarin Red S and the optical density (OD) was measured while being compensated by cell viability. For Western blotting, cells were stabilized for 24 hours and stimulated for another 72 hours through the same procedure as that of Alizarin Red S staining. Then we measured the level of protein expression in PPAR-gamma, beta-catenin, TNF-a, interleukin (IL)-23, and MMP7.ResultsThe level of OD of MOVAS cells treated with serum from AS patients (19.503 ± 6.422, mean ± SD) was significantly higher than that from controls (12.724 ± 5.746) (P=0.027, Mann-Whitney test). The level of MMP7 expression of MOVAS cells treated with serum from AS patients (1.921 ± 0.702) was significantly higher than that from controls (0.779 ± 0.191) (P=0.000, Mann-Whitney test). The level of beta-catenin expression of MOVAS cells treated with serum from AS patients (1.292 ± 0.356) was significantly higher than that from controls (0.887 ± 0.310) (P=0.025). There was negative correlation between PPAR-gamma and TNF-a (rho=-0.762, p=0.028, Spearman rank correlation coefficient), and between PPAR-gamma and IL-23 (rho=-0.601, p=0.039); positive correlation between MMP7 and TNF-a (rho=0.833, p=0.010), and between MMP7 and IL-23 (rho=0.797, p=0.002).ConclusionSerum from AS patients showed increased calcification of vascular smooth muscle cells than serum from controls. The level of vascular calcification marker from vascular smooth muscle cells treated with serum from AS patients was significantly higher than that from controls. There were negative relationship between inflammatory markers and inhibitory marker of vascular calcification but positive relationship between inflammatory markers and stimulatory marker of vascular calcification. These findings suggest that vascular calcification by inflammation could be an important cause of cardiovascular disease in AS patients.AcknowledgementThis research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03030825)Disclosure of InterestsSeung Yun Lee: None declared, Seong-Ryul Kwon: None declared, Su-Ah Yoon: None declared, Kyong-Hee Jung: None declared, Won Park Consultant for: Celltrion, Inc, Shin-Goo Park: None declared, Mie Jin Lim: None declared