Women with Metabolic Syndrome and Unhealthy Lifestyle Factors Are at a Higher Risk for Hyperuricemia.

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.

Implementation of Systematic Bioanalysis of Antibody-Drug Conjugates for Preclinical Pharmacokinetic Study of Ado-Trastuzumab Emtansine (T-DM1) in Rats.

Antibody-drug conjugates (ADCs) are composed of monoclonal antibodies covalently bound to cytotoxic drugs by a linker. They are designed to selectively bind target antigens and present a promising cancer treatment without the debilitating side effects of conventional chemotherapies. Ado-trastuzumab emtansine (T-DM1) is an ADC that received US FDA approval for the treatment of HER2-positive breast cancer. The purpose of this study was to optimize methods for the quantification of T-DM1 in rats. We optimized four analytical methods: (1) an enzyme-linked immunosorbent assay (ELISA) to quantify the total trastuzumab levels in all drug-to-antibody ratios (DARs), including DAR 0; (2) an ELISA to quantify the conjugated trastuzumab levels in all DARs except DAR 0; (3) an LC-MS/MS analysis to quantify the levels of released DM1; and (4) a bridging ELISA to quantify the level of anti-drug antibodies (ADAs) of T-DM1. We analyzed serum and plasma samples from rats injected intravenously with T-DM1 (20 mg/kg, single dose) using these optimized methods. Based on these applied analytical methods, we evaluated the quantification, pharmacokinetics, and immunogenicity of T-DM1. This study establishes the systematic bioanalysis of ADCs with validated assays, including drug stability in matrix and ADA assay, for future investigation on the efficacy and safety of ADC development.

Altered Risk of Incident Gout According to Changes in Metabolic Syndrome Status: A Nationwide, Population-Based Cohort Study of 1.29 Million Young Men.

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.

Increased risk of incident gout in young men with metabolic syndrome: A nationwide population-based cohort study of 3.5 million men.

Background: To date, few studies have focused on risk factors for gout in young people, and large-scale studies on the relationship between metabolic syndrome (MetS) and gout are lacking. We aimed to investigate the association between gout and MetS in a large nationwide population-based cohort of young men who participated in national health examination. Materials and methods: Cohort included men aged 20-39 years who participated in a health check-up in 2009-2012. A total of 3,569,104 subjects was included in the study, excluding those who had a previous diagnosis of gout or had renal impairment. The outcome was the occurrence of gout, which was defined using the diagnosis code of gout in the claims database. Cox proportional hazard model was used to evaluate the association between MetS and incident gout. Results: Mean follow-up duration was 7.35 ± 1.24 years and the incidence rate of gout was 3.36 per 1,000 person-years. The risk of gout in subjects with MetS was 2.4-fold higher than subjects without MetS. Among the components of MetS, hypertriglyceridemia and abdominal obesity showed the greatest association with gout. As the number of MetS components increased, the risk of gout increased. The association between gout and MetS was more pronounced in relatively young subjects and in low- or normal-weight subjects. Conclusion: Metabolic syndrome is an important risk factor for the gout in young men. In particular, the association between MetS and gout was greater in young and non-obese men. Management of MetS in young men will be important for future gout prevention.

Increased risk of malignancy in patients with Takayasu's arteritis: a population-based cohort study in Korea.

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.

Associations between Cardiovascular Outcomes and Rheumatoid Arthritis: A Nationwide Population-Based Cohort Study.

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.

Cardiovascular risk associated with allopurinol or benzbromarone treatment in patients with gout.

Background: In previous studies, cardiovascular (CV) risk was increased in patients with gout. The effects of uric acid-lowering therapy on CV risk in gout patients have been investigated in numerous studies; however, allopurinol and benzbromarone have rarely been compared. Objectives: To compare CV risk based on allopurinol and benzbromarone treatment in Korean gout patients. Design: A nationwide population-based retrospective cohort study. Methods: We used South Korea database of the Health Insurance Review and Assessment (HIRA) service to identify gout patients ⩾18 years of age who newly started allopurinol or benzbromarone between 2009 and 2015. The primary outcome of the study was the occurrence of a composite CV endpoint, which included coronary revascularization, hospitalization due to myocardial infarction, ischemic stroke, and transient ischemic attack. Cox proportional hazard regression analysis and Kaplan-Meier curves were used for analysis. Results: The study included 257,097 allopurinol initiators and 7868 benzbromarone initiators. Compared with allopurinol initiators, the adjusted hazard ratio (aHR) of the composite CV endpoint of benzbromarone initiators was 1.01 [95% confidence interval (CI): 0.83-1.21], which was not significantly different. The results did not change even when 1:3 propensity score matching was performed for baseline characteristics. In subgroup analysis of high-risk patients with CV disease, significant difference was not observed between allopurinol and benzbromarone initiators. Conclusion: In this study, significant difference was not found in CV risk between allopurinol and benzbromarone initiators. In the high-CV-risk group, the incidence of CV events did not differ between allopurinol and benzbromarone initiators.

Immunomodulatory Effect of Hispolon on LPS-Induced RAW264.7 Cells and Mitogen/Alloantigen-Stimulated Spleen Lymphocytes of Mice.

Hispolon is a potent anticancer, anti-inflammatory, antioxidant, and antidiabetic agent isolated from Phellinus linteus, an oriental medicinal mushroom. However, the immunomodulatory mechanisms by which hispolon affects macrophages and lymphocytes remain poorly characterized. We investigated the immunomodulatory effects of hispolon on oxidative stress, inflammatory responses, and lymphocyte proliferation using lipopolysaccharide (LPS)-treated RAW264.7 macrophages or mitogen/alloantigen-treated mouse splenocytes. Hispolon inhibited LPS-induced reactive oxygen and nitrogen species (ROS/RNS) generation and decreased total sulfhydryl (SH) levels in a cell-free system and RAW264.7 cells. Hispolon exerted significant anti-inflammatory effects by inhibiting production of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) and activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) in LPS-treated RAW264.7 cells. Hispolon also modulated NF-κB and STAT3 activation by suppressing the NF-κB p65 interaction with phospho-IκBα and the STAT3 interaction with JAK1, as determined via coimmunoprecipitation analysis. Additionally, hispolon significantly decreased lymphocyte proliferation, T cell responses and T helper type 1 (Th1)/type 2 (Th2) cytokines production in mitogen/alloantigen-treated splenocytes. We conclude that hispolon exerts immunomodulatory effects on LPS-treated macrophages or mitogen/alloantigen-treated splenocytes through antioxidant, anti-inflammatory, and antiproliferative activities. Thus, hispolon may be a therapeutic agent for treating immune-mediated inflammatory diseases.

Clinical characteristics and radiographic outcomes of vascular Behçet's disease involving the aorta or its major branches.

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.

Adverse postnatal developmental effects in offspring from humidifier disinfectant biocide inhaled pregnant rats.

Inhalation exposure to polyhexamethylene guanidine phosphate (PHMG-P), one of the primary biocides used in humidifier disinfectants, caused a fatal pulmonary disease in Korea. Pregnant women were also exposed to PHMG-P, and subsequent studies showed that PHMG-P inhalation during pregnancy adversely affects their health and embryo-fetal development. However, the postnatal developmental effects after birth on prenatally PHMG-P-exposed offspring have not yet been investigated. Therefore, in this study, we aimed to examine the postnatal development of prenatally PHMG-P-exposed offspring. Pregnant rats (22 or 24 females per group) were exposed to PHMG-P during pregnancy in a whole-body inhalation chamber at the target concentrations of 0, 0.14, 1.60, and 3.20 mg/m3. After parturition, the prenatally exposed offspring were transferred to non-exposed surrogate mothers to minimize the secondary effects of severe maternal toxicities. Postnatal development of offspring was then examined with a modified extended one-generation reproductive toxicity study design. At 3.20 mg/m3 PHMG-P, increased perinatal death rates and decreased viability index (postnatal survival of offspring between birth and postnatal day 4) were observed. In addition, F1 offspring had lower body weight at birth that persisted throughout the study. PHMG-P-exposed pregnant rats also had severe systemic toxicities and increased gestation period. At 1.60 mg/m3 PHMG-P, a decreased viability index was also observed with systemic toxicities of PHMG-P-exposed pregnant rats. These results indicate that prenatal PHMG-P exposure adversely affects the offspring's future health and could be used for human risk assessment.

Association between female reproductive factors and gout: a nationwide population-based cohort study of 1 million postmenopausal women.

BACKGROUND: Previous studies have shown that the incidence and risk factors of gout differs according to sex. However, little research has been done on the association between reproductive factors and gout. We conducted an analysis of a large nationwide population-based cohort of postmenopausal women to determine whether there is an association between reproductive factors and the incidence of gout. METHODS: A total of 1,076,378 postmenopausal women aged 40-69 years who participated in national health screenings in 2009 were included in the study. The outcome was the occurrence of incident gout, which was defined using the ICD-10 code of gout (M10) in the claim database. Cox proportional hazard models were used for the analyses and stratified analyses according to body mass index (BMI) and the presence/absence of chronic kidney disease (CKD) were performed. RESULTS: The mean follow-up duration was 8.1 years, and incident cases of gout were 64,052 (incidence rate 7.31 per 1000 person-years). Later menarche, earlier menopause, and a shorter reproductive span were associated with a high risk of gout. No association between parity and gout incidence was observed. Use of oral contraceptives (OC) and hormone replacement therapy (HRT) were associated with an increased risk of gout. The association between reproductive factors and gout was not statistical significant in the high BMI group. The effects of OC and HRT usage on gout were not significant in the CKD group. CONCLUSION: Shorter exposure to endogenous estrogen was associated with a high risk of gout. Conversely, exposure to exogenous estrogen such as OC and HRT was associated with an increased risk of gout.

A cluster analysis of patients with axial spondyloarthritis using tumour necrosis factor alpha inhibitors based on clinical characteristics.

BACKGROUND: This study aimed to classify the distinct group of patients with axial spondyloarthritis (SpA) on tumour necrosis factor alpha inhibitors (TNFi) according to the baseline characteristics using a clustering algorithm. METHODS: The clinical characteristics and demographic data of patients with axial SpA included in the Korean College of Rheumatology Biologics and Targeted Therapy registry were investigated. The patterns of disease manifestations were examined using divisive hierarchical cluster analysis. After clustering, we compared the clinical characteristics of patients and the drug survival of TNFi between the classified groups. RESULTS: A total of 1042 patients were analysed. The cluster analysis classified patients into two groups: axial group predominantly showing isolated axial manifestations (n = 828) and extra-axial group more frequently showing extra-axial symptoms (n = 214). Almost all extra-axial symptoms (peripheral arthritis, enthesitis, uveitis, and psoriasis) were more frequently observed in the extra-axial group than in the axial group. Moreover, patients in the extra-axial group had shorter disease duration, later disease onset, and higher disease activity than those in the axial group. The disease activity was comparable between the two groups after 1 year of treatment with TNFi. Interestingly, the extra-axial group had a lower drug survival with TNFi than the axial group (p = 0.001). CONCLUSIONS: Cluster analysis of patients with axial SpA using TNFi classified two distinct clinical phenotypes. These clusters had different TNFi drug survival, clinical characteristics, and disease activity.

Machine learning-based prediction model for responses of bDMARDs in patients with rheumatoid arthritis and ankylosing spondylitis.

BACKGROUND: Few studies on rheumatoid arthritis (RA) have generated machine learning models to predict biologic disease-modifying antirheumatic drugs (bDMARDs) responses; however, these studies included insufficient analysis on important features. Moreover, machine learning is yet to be used to predict bDMARD responses in ankylosing spondylitis (AS). Thus, in this study, machine learning was used to predict such responses in RA and AS patients. METHODS: Data were retrieved from the Korean College of Rheumatology Biologics therapy (KOBIO) registry. The number of RA and AS patients in the training dataset were 625 and 611, respectively. We prepared independent test datasets that did not participate in any process of generating machine learning models. Baseline clinical characteristics were used as input features. Responders were defined as those who met the ACR 20% improvement response criteria (ACR20) and ASAS 20% improvement response criteria (ASAS20) in RA and AS, respectively, at the first follow-up. Multiple machine learning methods, including random forest (RF-method), were used to generate models to predict bDMARD responses, and we compared them with the logistic regression model. RESULTS: The RF-method model had superior prediction performance to logistic regression model (accuracy: 0.726 [95% confidence interval (CI): 0.725-0.730] vs. 0.689 [0.606-0.717], area under curve (AUC) of the receiver operating characteristic curve (ROC) 0.638 [0.576-0.658] vs. 0.565 [0.493-0.605], F1 score 0.841 [0.837-0.843] vs. 0.803 [0.732-0.828], AUC of the precision-recall curve 0.808 [0.763-0.829] vs. 0.754 [0.714-0.789]) with independent test datasets in patients with RA. However, machine learning and logistic regression exhibited similar prediction performance in AS patients. Furthermore, the patient self-reporting scales, which are patient global assessment of disease activity (PtGA) in RA and Bath Ankylosing Spondylitis Functional Index (BASFI) in AS, were revealed as the most important features in both diseases. CONCLUSIONS: RF-method exhibited superior prediction performance for responses of bDMARDs to a conventional statistical method, i.e., logistic regression, in RA patients. In contrast, despite the comparable size of the dataset, machine learning did not outperform in AS patients. The most important features of both diseases, according to feature importance analysis were patient self-reporting scales.

Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models.

Human granulocyte colony-stimulating factor (G-CSF, this study used Fc-fused recombinant G-CSF; GX-G3) is an important glycoprotein that stimulates the proliferation of granulocytes and white blood cells. Thus, G-CSF treatment has been considered as a crucial regimen to accelerate recovery from chemotherapy-induced neutropenia in cancer patients suffering from non-myeloid malignancy or acute myeloid leukemia. Despite the therapeutic advantages of G-CSF treatment, an assessment of its immunogenicity must be performed to determine whether the production of anti-G-CSF antibodies causes immune-related disorders. We optimized and validated analytical tools by adopting validation parameters for immunogenicity assessment. Using these validated tools, we analyzed serum samples from rats and monkeys injected subcutaneously with GX-G3 (1, 3 or 10 mg/kg once a week for 4 weeks followed by a 4-week recovery period) to determine immunogenicity response and toxicokinetic parameters with serum concentration of GX-G3. Several rats and monkeys were determined to be positive for anti-GX-G3 antibodies. Moreover, the immunogenicity response of GX-G3 was lower in monkeys than in rats, which was relevant to show less inhibition of toxicokinetic profiles in monkeys, at least 1 mg/kg administrated group, compared to rats. These results suggested the establishment and validation for analyzing anti-GX-G3 antibodies and measurement of serum levels of GX-G3 and anti-GX-G3 antibodies, which was related with toxicokinetic profiles. Taken together, this study provides immunogenicity assessment which is closely implicated with toxicokinetic study of GX-G3 in 4-week repeated administrated toxicological studies.

How much does fat mass change affect serum uric acid levels among apparently clinically healthy Korean men?

OBJECTIVE: The aim of this study was to examine the impact of fat mass alteration on serum uric acid (SUA) levels in apparently clinically healthy men. METHODS: We evaluated 27,387 men who consecutively underwent health check ups between 2015 and 2017. We assessed the likelihood of achieving a SUA level of <0.41 mmol/L and compared the SUA levels according to fat mass changes. RESULTS: Compared with those without fat mass change (the reference group), the odds ratios (95% confidence interval) of achieving a SUA level of <0.41 mmol/L for fat mass decreases of ⩾2.5, 1.5-2.5, and 0.5-1.5 kg were 1.63 (1.45-1.82), 1.19 (1.06-1.34), and 1.07 (0.97-1.18), respectively, while those for a fat mass increase of ⩾2.5, 1.5-2.5, and 0.5-1.5 kg were 0.71 (0.64-0.78), 0.87 (0.79-0.97), and 0.95 (0.86-1.04), respectively. The corresponding beta-coefficients of SUA levels (mmol/L) were -0.26 [-0.29-(-0.23)], -0.12 [-0.16-(-0.09)], and -0.09 [-0.12-(-0.06)] for fat mass decreases of ⩾2.5, 1.5-2.5, and 0.5-1.5 kg, respectively. Every 1-kg fat mass reduction was associated with 9% increased odds of achieving the target SUA level. The multivariate SUA level difference per 1-kg fat mass gain was 2.97 µmol/L. Similar levels of association persisted among the prespecified subgroups. CONCLUSION: We quantitatively demonstrated that fat mass reduction contributes to a clinically relevant decrease in SUA levels and a significant increase in the likelihood of achieving target SUA levels. Our findings may help to provide clear clinical guidance on fat mass alteration to reduce SUA levels in patients with hyperuricemia.

Factors associated with radiographic progression in patients with Takayasu's arteritis.

OBJECTIVES: To identify the factors related to radiographic progression in patients with Takayasu's arteritis (TAK). METHODS: A retrospective cohort study was conducted among patients with TAK who underwent computed tomography angiography (CTA) at least twice in a 2-5-year interval. Radiographic progression was defined as newly developed and/or aggravated (more than 20%) characteristic CTA findings. Correlation analysis was performed using a multivariate Cox regression model. RESULTS: The cohort included 153 TAK patients with a mean CTA interval of 3.53 years, and 24 (15.7%) showed radiographic progression. Those with progression showed higher acute-phase reactant levels (erythrocyte sedimentation rate [ESR], 26.06 vs. 35.72 mm/h, p=0.040; C-reactive protein [CRP], 0.45 vs. 1.13 mg/dL, p<0.001), were younger at the initial CTA (43.70 vs. 31.81 years, p<0.001), and were more likely to be receiving immunosuppressants (14 [10.9%] vs. 7 [29.2%] patients, p=0.038). Multivariate Cox regression analysis revealed age at the initial CTA (hazard ratio [HR]=0.945, confidence interval [CI]=0.898-0.995, p=0.030) and area under the curve (AUC) of CRP levels (HR=2.126, CI=1.046-4.319, p=0.037) as significant factors for radiographic progression. In a subgroup of patients with high CRP levels, 30.4% (14/24) showed progression; only age at the initial CTA was significantly different (37.03 vs. 27.10 years, p=0.012) between those with and without progression. CONCLUSIONS: Higher CRP levels and younger age were risk factors of radiographic progression in patients with TAK. In the high CRP group, younger patients are more prone to progression and may need aggressive anti-inflammatory treatment.

The Effects of Sex and Estrogen on Radiographic Progression of Ankylosing Spondylitis in Korean Patients.

Objective: Ankylosing spondylitis (AS) is a chronic inflammatory disease with obvious male preponderance Males show more severe radiographic manifestations compared with females This study aimed to evaluate the effects of sex and estrogen on the radiographic progression of AS. Methods: A total of 101 patients with AS were included in this study All of the radiographs were scored using the modified Stoke AS Spine Score (mSASSS) Serum levels of 17ß-estradiol (E2), dickkopf-1 (Dkk1), and leptin were detected by enzyme-linked immunosorbent assay The generalized estimating equations model was used to evaluate factors associated with spinal radiographic progression. Results: The mean age at disease onset was 273±107 years, and 16 patients (158%) were female In the multivariable analysis, body mass index (ß-coefficient=012; p=0047) and levels of Dkk1 (ß-coefficient=-011; p<0001), and female (ß-coefficient=-140; p=0001) were associated with radiographic progression Among male patients with AS, baseline C-reactive protein (ß=011; p=0005) and mSASSS (ß=021; p=0030) were also associated with radiographic progression E2 and leptin levels were not significantly related to the radiographic progression. Conclusion: Although female patients were associated with less radiographic progression in AS, there was no significant relationship between serum estrogen level and radiographic progression Results of current study suggests that genetic factors or other environmental factors associated with female may influence radiographic progression in patients with AS.

KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities.

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

Machine learning to predict early TNF inhibitor users in patients with ankylosing spondylitis.

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.

Increased Overall Heart Rate Irregularity Risk by Hyperuricemia in the General Population: Results from the Korean National Health and Nutrition Examination Survey.

Background and objectives: Hyperuricemia is one of the well-known cardiovascular risk factors. There is a growing interest in the association between hyperuricemia and arrhythmia. We used the representative sample data of Korean population to study the association between hyperuricemia and heart rate irregularity (HRI) that reflects total arrhythmia. Materials and Methods: We performed weighted multivariate logistic regression analysis to assess the association between hyperuricemia and HRI. Results: Of the 10,827 subjects, 1308 (13.2%) had hyperuricemia and 130 (1%) had HRI. In the presence of hyperuricemia, HRI was three times higher than that in the absence of hyperuricemia (OR 2.98, 95% CI 1.71-5.18). The risk of HRI was highest in subjects with both hypertension and hyperuricemia. In the subgroup analysis, the association of hyperuricemia with HRI was most pronounced in the smoker group. Conclusions: Hyperuricemia was highly correlated with HRI in adult Korean representative sample data. Hyperuricemia was associated with a nearly tripled risk for HRI. Hypertension has a synergistic effect with hyperuricemia on HRI. Further research is warranted to clarify the relationship between hyperuricemia and arrhythmia and its mechanism.