Association between HNF4A rs1800961 polymorphisms and gallstones in a Taiwanese population.

BACKGROUND AND AIM: A large genetic effect of a novel gallstone-associated genetic variant, the hepatocyte nuclear factor 4α (HNF4A) rs1800961 polymorphism, has been identified through recent genome-wide association studies. However, this effect has not been validated in Asian populations. We investigated the association between the rs1800961 variant and gallstones among a Taiwanese population. METHODS: A total of 20 405 participants aged between 30 and 70 years voluntarily enrolled in the Taiwan Biobank. Self-report questionnaires, physical examinations, biochemical tests, and genotyping were used for analysis. The association of the HNF4A rs1800961 variant and other metabolic risks with gallstone disease was analyzed using multiple logistic regression models. RESULTS: The minor T allele of HNF4A rs1800961 was associated with an increased risk of gallstone, and the association remained significant even after adjustment for other risk factors including age, body mass index (BMI), diabetes, hyperlipidemia, hypertension, and cigarette smoking (adjusted odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.31 to 2.75) in male participants. When further stratified by BMI and age, the lithogenic effect was the most significant in male participants with obesity (adjusted OR = 3.55, 95% CI = 1.92 to 6.56) and who were younger (adjusted OR = 2.45, 95% CI = 1.49 to 4.04). CONCLUSION: The novel gallstone-associated HNF4A rs1800961 variant was associated with the risk of gallstone in the Taiwanese men. Screening for the rs1800961 polymorphism may be particularly useful in assessing the risk of gallstone formation in younger or obese men.

Association of Hydroxychloroquine Use with a Dose-Dependent Decrease in Mortality Risk in Patients with Elderly-Onset Rheumatoid Arthritis.

INTRODUCTION: Elderly-onset rheumatoid arthritis (EORA) is associated with an increased mortality risk; however, the effect of conventional synthetic, biologics or targeted synthetic disease-modifying anti-rheumatic drugs (csDMARDs, bDMARDs or tsDMARDs) on the EORA-specific mortality risk is unknown. In this study, we investigated the risk factors for all-cause mortality of patients with EORA. METHODS: Data of EORA patients diagnosed with RA at age > 60 years between January 2007 and June 2021 were extracted from the electronic health record of Taichung Veterans General Hospital, Taiwan. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The survival of patients with EORA was analyzed by Kaplan-Meier method. RESULTS: Among the 980 EORA patients who were enrolled (survivors 852 and non-survivor 128), the significant mortality-associated risk factors [HR (95% CI)] included higher age (1.10 [1.07-1.12], p < 0.001), male sex (1.92 [1.22-3.00], p = 0.004), current smoker (2.31 [1.10-4.87], p = 0.027) and underlying malignancy (1.89 [1.20-2.97], p = 0.006). Hydroxychloroquine treatment conferred protection against mortality in patients with EORA (HR 0.30, 95% CI 0.14-0.64, p = 0.002). Patients with malignancy who did not receive hydroxychloroquine treatment had the highest mortality risk compared with their counterparts. Patients with a monthly cumulative dose of hydroxychloroquine dose < 1374.5 mg had the lowest survival rate compared to patients who received hydroxychloroquine 1374.5-5778.5 and ≥ 5778.5 mg. CONCLUSION: Hydroxychloroquine treatment is associated with survival benefits in patients with EORA, and prospective studies are needed to validate the abovementioned findings.

The ABCG2 rs2231142 polymorphism and the risk of nephrolithiasis: A case-control study from the Taiwan biobank.

Background: Hyperuricemia and gout are risk factors of nephrolithiasis. However, it is unclear whether the ABCG2 gene contributes to the development of nephrolithiasis. We aimed to investigate the interaction between the ABCG2 rs2231142 variant and incident nephrolithiasis in the Taiwanese population. Methods: A total of 120,267 adults aged 30-70 years were enrolled from the Taiwan Biobank data-base in this retrospective case-control study and genotyped for rs2231142. The primary outcome was the prevalence of self-reported nephrolithiasis. The odds ratio (OR) of incident nephrolithiasis was analyzed by multivariable logistic regression models with adjustment for multifactorial confounding factors. Associations of the ABCG2 rs2231142 variant with serum uric acid levels, and the incident nephrolithiasis were explored. Results: The frequency of rs2231142 T allele was 53%, and 8,410 participants had nephrolithiasis. The multivariable-adjusted OR (95% confidence interval) of nephrolithiasis was 1.18 (1.09-1.28) and 1.12 (1.06-1.18) for TT and GT genotypes, respectively, compared with the GG genotype (p<0.001), specifically in the male population with hyperuricemia. Higher age, male sex, hyperlipidemia, hypertension, diabetes mellitus, hyperuricemia, smoking and overweight were independent risk factors for nephrolithiasis. In contrast, regular physical exercise is a protective factor against nephrolithiasis. Conclusions: ABCG2 genetic variation is a significant risk of nephrolithiasis, independent of serum uric acid levels. For rs2231142 T allele carriers, our result provides evidence for precision healthcare to tackle hyperuricemia, comorbidities, smoking, and overweight, and recommend regular physical exercise for the prevention of nephrolithiasis.

The electronic medical record management systems may improve monitoring and control of disease activity in patients with ankylosing spondylitis.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases.

Objectives: To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq). Methods: From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis. Results: The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (ß: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group. Conclusions: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.

The BASDAI Cut-Off for Disease Activity Corresponding to the ASDAS Scores in a Taiwanese Cohort of Ankylosing Spondylitis.

Objectives: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort. Methods: From November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5). Results: In our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively. Conclusion: We propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients.

Comparison of Renal Responses Between Continuous Mycophenolate Mofetil and Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Lupus Nephritis.

BACKGROUND: Mycophenolate mofetil (MMF) is extensively used for induction and maintenance therapy in patients with lupus nephritis (LN). Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the adverse gastrointestinal effects of MMF. However, the therapeutic efficacy of MMF and EC-MPS in LN remains unclear. This study aimed to examine the treatment effects of EC-MPS in LN patients with prior MMF exposure. METHODS: In this medical records review study, we included 54 LN patients, of whom 34 converted from MMF to EC-MPS at equimolar doses in 2016-2018 (nonmedical switching group) and 20 received continuous MMF treatment. Patients achieving complete remission or partial remission before the conversion were categorized as responders, whereas those who had never achieved complete remission or partial remission were categorized as nonresponders. RESULTS: Baseline proteinuria was higher in the nonmedical switching group. Although elevation in proteinuria was observed after nonmedical switching, the serum creatinine concentration and estimated glomerular filtration rate both improved. Responders in the nonmedical switching group had lower proteinuria and higher complement 3 levels. In the subgroup analysis, albeit the modest increase in daily urine protein, anti-double-stranded DNA antibody levels, estimated glomerular filtration rate, and complements 3 and 4 seemed comparable after conversion. CONCLUSION: Switching to EC-MPS demonstrated a similar short-term renal response to continuous MMF treatment in LN patients. Prospective randomized trials are required to verify our findings.

GAP Score and CA-153 Associated with One-Year Mortality in Anti-MDA-5 Antibody-Positive Patients: A Real-World Experience.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. METHODS: We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up. RESULTS: A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality. CONCLUSIONS: Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management.

Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients.

BACKGROUND: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. METHODS: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. RESULTS: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0-1.3), 0.95 (0.9-1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. CONCLUSIONS: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.

Predictors of drug survival for biologic and targeted synthetic DMARDs in rheumatoid arthritis: Analysis from the TRA Clinical Electronic Registry.

In this study we aimed to identify the predictors of drug survival for biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) among patients with rheumatoid arthritis (RA) in a real-world setting. Data from RA patients receiving bDMARDs and tsDMARDs between 2007 and 2019 were extracted from the Taiwan Rheumatology Association Clinical Electronic Registry (TRACER). Patients were categorized into tumor necrosis factor-alpha (TNF-α) inhibitors, non-TNF-α inhibitors, and tofacitinib groups. The primary outcome was 3-year drug retention and the causes of bDMARDs and tsDMARDs discontinuation were recorded. Baseline demographic data before the initiation of bDMARDs and tsDMARDs treatment were analyzed to identify the predictors of 3-year drug survival. A total of 1,270 RA patients were recruited (TNF-α inhibitors: 584; non-TNF-α inhibitors: 535; tofacitinib: 151). The independent protective factors for 3-year drug survival were positive rheumatoid factor (RF) (HR: 0.48, 95% CI: 0.27-0.85, p = 0.013) and biologics-naïve RA (HR: 0.61, 95% CI: 0.39-0.94, p = 0.024). In contrast, positive anti-citrullinated protein antibody (ACPA) (HR: 2.24, 95% CI: 1.32-3.79, p = 0.003) and pre-existing latent tuberculosis (HR: 2.90, 95% CI: 2.06-4.09, p<0.001) were associated with drug discontinuation. RA patients treated with TNF-α inhibitors exhibited better drug retention, especially in the biologics-naïve subgroup (p = 0.037). TNF-α inhibitors were associated with lower cumulative incidence of discontinuation due to inefficacy and adverse events (both p<0.001). Baseline RF and ACPA positivity in abatacept-treated patients were associated with a better 3-year drug survival. However, negative ACPA levels predicted superior drug survival of TNF-α inhibitors and tofacitinib. In conclusion, bio-naïve status predicted better drug survival in TNF-α inhibitors-treated RA patients. RF and ACPA positivity predicted better abatacept drug survival. In contrast, ACPA negativity was associated with superior TNF-α inhibitors and tofacitinib survival.

Flare Rate Thresholds for Patient Assessment of Disease Activity States in Gout.

OBJECTIVE: To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS). METHODS: Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare. A distribution-based approach and extended Youden index identified possible flare count thresholds for each state. RESULTS: Investigators from 17 countries recruited 512 participants. Remission was associated with a median recalled flare count of zero over both 6 and 12 months. Each recalled flare reduced the likelihood of self-perceived remission compared with being in higher disease activity than LDA/PASS, by 52% for 6 months and 23% for 12 months, and the likelihood of self-perceived LDA/PASS by 15% and 5% for 6 and 12 months, respectively. A threshold of 0 flares in preceding 6 and 12 months was associated with correct classification of self-perceived remission in 58% and 56% of cases, respectively. CONCLUSION: Flares are significantly associated with perceptions of disease activity in gout, and no flares over the prior 6 or 12 months is necessary for most people to self-categorize as being in remission. However, recalled flare counts alone do not correctly classify all patients into self-categorized disease activity states, suggesting that other factors may also contribute to self-perceived gout disease activity.

Gender difference in ASAS HI among patients with ankylosing spondylitis.

OBJECTIVE: To assess the associations of the Assessment of Spondyloarthritis International Society Health Index (ASAS HI) with gender and other factors in patients with ankylosing spondylitis (AS). METHODS: From November 2017 to October 2018, we measured the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and the ASAS HI score for AS patients at the Taichung Veterans General Hospital. After adjusting for disease activity (ASDAS-erythrocyte sedimentation rate [ESR], ASDAS- C-reactive protein [CRP], BASDAI+ESR or BASDAI+CRP), mSASSS and other potential confounders including medications, comorbidities, and laboratory data, any associations between gender and the sum score of ASDAS HI were assessed using multiple linear regression analysis, as well as any associations between gender and an ASAS HI score >5 using multivariable logistic regression analysis. RESULTS: A total of 307 AS patients (62 [20.2%] females, mean age 46.4 years [S.D. 13.3], mean symptom duration 20.6 years [S.D. 12.1]) were included. Multiple linear regression analysis showed that the male gender was significantly associated with a lower ASAS HI (B = -1. 91, 95% confidence interval [CI], -2.82--1.00, p <0.001). Multivariable logistic regression analysis revealed that males also had a lower risk of achieving scores of ASAS HI > 5 than females (odds ratio = 0.15, 95% CI, 0.07-0.36, p <0.001). Disease activity measures, including ASDAS-ESR, ASDAS-CRP and BASDAI, had positive correlations with ASAS HI. CONCLUSION: This single-center, cross-sectional study revealed that a higher ASAS HI score was significantly associated with female gender and higher disease activity measures.

Degraded microarchitecture by low trabecular bone score is associated with prevalent vertebral fractures in patients with systemic lupus erythematosus.

PURPOSE: Recently, trabecular bone score (TBS) has emerged as an important supplementary assessment tool in osteoporosis diagnosis and management. The high incidence of fragility fracture within the non-osteoporotic range of bone mineral density (BMD), among systemic lupus erythematosus (SLE) patients, highlights the crucial role of bone microarchitecture in osteoporosis. This study aimed to evaluate whether TBS identified existing vertebral fractures (VF) more accurately than BMD in SLE patients. METHODS: This study enrolled 147 SLE patients from the Asia Pacific Lupus Collaboration (APLC) cohort, who had BMD and TBS assessed from January 2018 until December 2018. Twenty-eight patients sustaining VF and risk factors associated with increased fracture occurrence were evaluated. Independent risk factors and diagnostic accuracy of VF were analyzed by logistic regression and ROC curve, respectively. RESULT: The prevalence of vertebral fracture among SLE patients was 19%. BMD, T-score, TBS, and TBS T-score were significantly lower in the vertebral fracture group. TBS exhibited higher positive predictive value and negative predictive value than L spine and left femur BMD for vertebral fractures. Moreover, TBS had a higher diagnostic accuracy than densitometric measurements (area under curve, 0.811 vs. 0.737 and 0.605). CONCLUSION: Degraded microarchitecture by TBS was associated with prevalent vertebral fractures in SLE patients. Our result suggests that TBS can be a complementary tool for assessing vertebral fracture prevalence in this population.

Hyperspectral imaging for skin assessment in systemic sclerosis: a pilot study.

OBJECTIVE: Hyperspectral imaging (HSI) is a novel technology for obtaining quantitative measurements from transcutaneous spatial and spectral information. In patients with SSc, the severity of skin tightness is associated with internal organ involvement. However, clinical assessment using the modified Rodnan skin score is highly variable and there are currently no universal standardized protocols. This study aimed to compare the ability to differentiate between SSc patients and healthy controls using skin scores, ultrasound and HSI. METHODS: Short-wave infrared light was utilized to detect the spectral angle mapper (SAM) of HSI. In addition, skin severity was evaluated by skin scores, ultrasound to detect dermal thickness and strain elastography. Spearman's correlation was used for assessing skin scores, strain ratio, thickness and SAM. Comparisons of various assessment tools were performed by receiver operating characteristic curves. RESULTS: In total, 31 SSc patients were enrolled. SAM was positively correlated with skin scores and dermal thickness. In SSc patients with normal skin scores, SAM values were still significantly higher than in healthy controls. SAM exhibited the highest area under the curve (AUC: 0.812, P < 0.001) in detecting SSc compared with skin scores (AUC: 0.712, P < 0.001), thickness (AUC: 0.585, P = 0.009) and strain ratio by elastography (AUC: 0.522, P = 0.510). Moreover, the severity of skin tightness was reflected by the incremental changes of waveforms in the spectral diagrams. CONCLUSION: SAM was correlated with skin scores and sufficiently sensitive to detect subclinical disease. HSI can be used as a novel, non-invasive method for assessing skin changes in SSc.

Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout.

OBJECTIVE: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. RESULTS: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). CONCLUSION: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.

Risk of immune-mediated inflammatory diseases in newly diagnosed ankylosing spondylitis patients: a population-based matched cohort study.

OBJECTIVE: To investigate the risk of immune-mediated inflammatory diseases (IMIDs) in patients with ankylosing spondylitis (AS). METHODS: Using 2003-2012 claims data from the Taiwanese National Health Insurance Research Database, we identified 30,911 newly diagnosed AS patients requiring medical therapy from 2006 to 2012. In addition, we randomly selected 309,110 non-AS individuals matching (1:10) the AS patients with regard to age, sex and the year of the index date. After excluding subjects with the corresponding prior IMIDs, we calculated the incidence rates (IRs) of various IMIDs in the AS and non-AS cohorts and estimated the hazard ratios (HRs) with 95% confidence intervals after adjusting for age, sex, the Charlson comorbidity index, the frequency of ambulatory visits during the follow-up period and medications. We conducted sensitivity analyses by excluding those who developed IMIDs within 3 months after the index date. RESULTS: In the follow-up period, we found that newly diagnosed AS patients had significantly increased risks of acute anterior uveitis, psoriasis, Sjögren's syndrome, thromboangiitis obliterans, Behcet's disease and sarcoidosis. However, the risk of Sjögren's syndrome did not increase in AS patients in the sensitivity analysis. In the same period, this study found no significant differences in the risks of Crohn's disease, ulcerative colitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, polymyositis, pemphigus and vitiligo between newly diagnosed AS patients and non-AS individuals. AS patients had a significantly reduced risk of rheumatoid arthritis. CONCLUSION: Newly diagnosed Taiwanese AS patients had increased risks of acute anterior uveitis, psoriasis, thromboangiitis obliterans, Behcet's disease and sarcoidosis, but a reduced risk of rheumatoid arthritis.

Safety and effectiveness of tocilizumab in treating patients with rheumatoid arthritis - A three-year study in Taiwan.

OBJECTIVE: To evaluate the long-term safety and effectiveness of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) in a real-world clinical setting in Taiwan. METHOD: All refractory RA patients who initiated intravenous TCZ between August 2012 and March 2015 were enrolled. Data on patient characteristics, drug safety and effectiveness were collected. RESULTS: A total of 114 RA patients were recruited. Despite the majority of them (93%) had previous biologic failure, 43.75% of the patients were able to reach ACR50 after one year. Serious adverse events commonly found were bacterial pneumonia (4.24/100 patient-years) followed by cellulitis (2.12/100 patient-years). Twenty-three patients had old or latent TB infections, 11 patients had chronic hepatitis B. During the 3 years follow-up, none of them had reactivation of TB, or hepatitis B with concomitant use of isoniazid prophylaxis or pre-emptive antiviral treatment. CONCLUSION: In this 3-year real-world study on RA patients of Taiwan, we found a good long-term effectiveness and similar safety profiles for the TCZ treatment. With prophylactic strategy for latent TB and pre-emptive antiviral treatment for HBV carriers, the risk of reactivation of latent TB and HBV may be reassured.

Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout.

OBJECTIVE: The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. METHODS: Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. RESULTS: There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (≥80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. CONCLUSION: Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.

The clinical application of tumor markers in the screening of malignancies and interstitial lung disease of dermatomyositis/polymyositis patients: A retrospective study.

OBJECTIVE: To examine the clinical utility of tumor markers in dermatomyositis/polymyositis patients in Taiwan. METHOD: Data were collected retrospectively from the database of Taichung Veterans General Hospital in Taiwan from 1998 to 2014. Patients who fulfilled Bohan and Peter criteria of dermatomyositis/polymyositis were recruited. Serum level of tumor markers including carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 125, carbohydrate antigen 19-9 and carbohydrate antigen 15-3 were measured. The occurrence of malignancies and interstitial lung disease was identified. The association of tumor markers with malignancies and interstitial lung disease was examined using Chi-square test or Fisher's exact test. RESULTS: Among the enrolled 151 patients, 98 (64.9%) dermatomyositis and 53 (35.1%) polymyositis, a total of 15 malignancies were detected: breast ductal carcinoma (n = 4), bladder transitional cell carcinoma (n = 2), lung adenocarcinoma (n = 2), cervical intraepithelial neoplasia 3 and papillary squamous cell carcinoma (n = 2), colorectal (colon and rectal adenocarcinoma) (n = 2), uterine adenocarcinoma (n = 1), nasopharyngeal carcinoma (n = 1) and hematological malignancy (myelodysplastic with excess blast cells) (n = 1). Among the patients with malignancies, 13 (86.7%) had dermatomyositis, 2 (13.3%) polymyositis and 3 (20%) interstitial lung disease. The mean duration from dermatomyositis/polymyositis diagnosis to the occurrence of malignancies was 6.05 ± 5.69 years. There was no significant association of raised tumor markers with the occurrence of malignancies (p > 0.085), while a significant association was observed between the elevated levels of carbohydrate antigen 15-3 and the presence of interstitial lung disease (p = 0.006). CONCLUSION: Tumor markers were not useful in malignancy screening or dermatomyositis/polymyositis patients in this tertiary center. The evaluation of the occurrence of malignancy in dermatomyositis/polymyositis patient should include a multidimensional approach. A raised level of carbohydrate antigen 15-3 may be a potential indicator of the presence of interstitial lung disease in dermatomyositis/polymyositis patients.