Search

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 p = 0.073), especially among patients whose with an inactive disease activity was 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.

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder with clinical heterogeneity. Although tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, is an effective treatment for AOSD, the evidence regarding its efficacy on systemic or articular subtypes is conflicting. Furthermore, the predictors of therapeutic response are still elusive and worthy of exploration. This two-center retrospective study analyzed the effectiveness and safety profile of TCZ treatment in 28 patients with refractory AOSD. The 28-joint disease activity score (DAS28) and systemic activity score were assessed before and during TCZ treatment period at weeks 12, 24, 36, and 48. Plasma levels of proinflammatory cytokines at baseline were determined using ELISA method. Among the systemic subtype patients, 10 (58.8%), 13 (76.5%), 14 (82.4%), and 15 (88.2%) patients achieved complete remission at week 12, 24, 36, and 48, respectively, in comparison to 2 (22.2%), 5 (55.6%), 6 (66.7%), and 7 (77.8%) who achieved disease remission (DAS28

Background 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). Methods 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. Results The number of annual outpatient visits increased after ASDAS assessment (5.8 ± 3.4 vs. 5.4 ± 3.4, p

BackgroundTo 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).MethodsWe 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.ResultsThe number of annual outpatient visits increased after ASDAS assessment (5.8 ± 3.4 vs. 5.4 ± 3.4, p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (8.7 ± 3.8 vs. 9.2 ± 4.4 min, p = 0.030), especially among patients whose ASDAS-C-reactive protein (CRP) was ConclusionThe use of an EMRMS increased the frequency of ambulatory visits among AS patients with 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.Trial registrationInstitutional Review Board (IRB) of Taichung Veterans General Hospital (TCVGH-IRB No.: CE20145B)

Adult-onset Still’s disease (AOSD) is a rare and inflammatory disorder characterized by spiking fever, rash, arthritis, and multisystemic involvement. HLA has been shown to be associated with AOSD; however, it could not explain the innate immunity and autoinflammatory characteristics of AOSD. To assess the genetic susceptibility of AOSD, we conducted a genome-wide association study (GWAS) on a cohort of 70 AOSD cases and 688 controls following a replication study of 36 cases and 200 controls and meta-analysis. The plasma concentrations of associated gene product were determined. The GWAS, replication, and combined sample analysis confirmed that SNP rs11102024 on 5′-upstream of CSF1 encoding macrophage colony-stimulating factor (M-CSF) was associated with AOSD (P=1.20×10-8, OR (95% CI): 3.28 (2.25~4.79)). Plasma levels of M-CSF increased in AOSD patients (n=82, median: 9.31 pg/mL), particularly in the cases with activity score≥6 (n=42, 10.94 pg/mL), compared to the healthy donors (n=68, 5.31 pg/mL) (P<0.0001). Patients carrying rs11102024TT genotype had higher M-CSF levels (median: 20.28 pg/mL) than those with AA genotype (6.82 pg/mL) (P<0.0001) or AT genotype (11.61 pg/mL) (P=0.027). Patients with systemic pattern outcome were associated with elevated M-CSF and frequently observed in TT carriers. Our data suggest that genetic variants near CSF1 are associated with AOSD and the rs11102024 T allele links to higher M-CSF levels and systemic outcome. These results provide a promising initiative for the early intervention and therapeutic target of AOSD. Further investigation is needed to have better understandings and the clinical implementation of genetic variants nearby CSF1 in AOSD.

ObjectivesThe 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.MethodsFrom 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).ResultsIn 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.ConclusionWe 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.

Background: We aimed to investigate the change of hepatitis B virus (HBV) viral loads and HBV reactivation (HBVr) in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Methods: This two-center analysis retrospectively investigated the virological and biochemical evidence of HBVr in RA patients who underwent b/tsDMARD dose reduction. Serum levels of viral loads were determined using real-time PCR. Serum levels of alanine transaminase (ALT) were determined using spectrophotometry. Results: Among a total of 40 HBsAg+ RA patients who tapered b/tsDMARDs, 14 (35%) used tocilizumab; 12 (30%) used tumor necrosis factor (TNF)-α inhibitors; and the rest used either abatacept or tofacitinib. We found that patients who had detectable HBV DNA before tapering achieved a one-log reduction in HBV DNA levels, in contrast to the findings in the other 12 patients who did not taper b/tsDMARDs (no change in HBV DNA levels with time). The incidence of HBVr (increased viral loads with hepatitis) was 4.62 (95%CI: 2.08, 10.28) and 2.26 (95%CI: 0.56, 9.02) events per 100 person-years before and after b/tsDMARD tapering, respectively. Conclusions: The HBV viral load decreased after the tapering of b/tsDMARDs in RA patients with detectable HBV DNA. Dose reduction in b/tsDMARDs might be beneficial.

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.

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12–1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29–3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07–1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06–1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01–19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41–24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.

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. Keywords: Hepatitis B, Rheumatoid arthritis, Safety and effectiveness, Tocilizumab, Tuberculosis

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with clinical heterogeneity. Although tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, is an effective treatment for AOSD, the evidence regarding its efficacy on systemic or articular subtypes is conflicting. Furthermore, the predictors of therapeutic response are still elusive and worthy of exploration.This two-center retrospective study analyzed the effectiveness and safety profile of TCZ treatment in 28 patients with refractory AOSD. The 28-joint disease activity score (DAS28) and systemic activity score were assessed before and during TCZ treatment period at weeks 12, 24, 36, and 48. Plasma levels of proinflammatory cytokines at baseline were determined using ELISA method.Among the systemic subtype patients, 10 (58.8%), 13 (76.5%), 14 (82.4%), and 15 (88.2%) patients achieved complete remission at week 12, 24, 36, and 48, respectively, in comparison to 2 (22.2%), 5 (55.6%), 6 (66.7%), and 7 (77.8%) who achieved disease remission (DAS28 2.6) at weeks 12, 24, 36, and 48, respectively, among articular subtype patients. The systemic activity scores and inflammatory parameters were significantly decreased after 12-week TCZ therapy, and TCZ could significantly reduce corticosteroid dose in AOSD patients. Multivariate analysis reveals that baseline IL-18 level is a significant predictor of poor therapeutic response at week 24 (odds ratio 7.86, p 0.05).AOSD patients refractory to high-dose corticosteroids and methotrexate may respond well to TCZ treatment with a steroid-sparing effect and an acceptable safety. A high baseline IL-18 level may be a predictor of poor therapeutic response. Key Points • Tocilizumab may be effective and well-tolerated in refractory AOSD patients regardless of disease subtypes. • High plasma levels of IL-18 may predict poor response to tocilizumab in AOSD patients.

The pathogenic role of autophagic immune regulation in adult-onset Still's disease (AOSD) is unclear. We investigated the relative levels of autophagy in AOSD patients and healthy controls, its association with disease activity or course, and the change in autophagy after 6 months of therapy. Autophagosome levels were determined from the mean fluorescence intensity of autophagosomotropic dye incorporated into circulating immune cells. The fluorescent signal from lymphocytes, monocytes, and granulocytes from AOSD patients was greater than from controls. Levels of p62 fluorescence measured using flow cytometry in lymphocytes and granulocytes from AOSD patients was greater than in the corresponding cells from healthy controls. Expression of Atg5 and LC3-II mRNA and protein levels of p62 and LC3-II were elevated in AOSD patients. Moreover, AOSD activity scores correlated positively with autophagosome levels in monocytes and granulocytes, p62 levels in circulating immune cells, and levels of Beclin-1, Atg5, and LC3-II mRNA. Autophagosome levels and Atg mRNA expression decreased with disease remission in AOSD patients. Elevated autophagosome formation and p62 levels suggest impaired autophagic flux in AOSD.

Objective.The dysregulation of the NLRP3 (NLR containing a pyrin domain) inflammasome is involved in autoinflammatory diseases. Adult-onset Still disease (AOSD) is regarded as an autoinflammatory disease. However, the pathogenic involvement of NLRP3 inflammasome in AOSD remains unclear and NLRP3 activators in AOSD are currently unknown.Methods.The mRNA expression of NLRP3 inflammasome signaling in peripheral blood mononuclear cells (PBMC) from 34 patients with AOSD and 14 healthy subjects was determined using quantitative-PCR (qPCR). The changes in mRNA and protein levels of NLRP3 inflammasome signaling in PBMC treated with the potential activator [imiquimod (IMQ)] or inhibitor of NLRP3 were evaluated using qPCR and immunoblotting, respectively. The supernatant levels of interleukin (IL)-1β and IL-18 were determined by ELISA.Results.Significantly higher mRNA levels of NLRP3 inflammasome signaling were observed in patients with AOSD compared with healthy controls. NLRP3 expressions were positively correlated with disease activity in patients with AOSD. IMQ (an effective Toll-like receptor 7 ligand; 10 µg/ml and 25 µg/ml) stimulation of PBMC from patients with AOSD induced dose-dependent increases of mRNA expression of NLRP3 (mean ± standard error of the mean, 2.06 ± 0.46 and 6.05 ± 1.84, respectively), caspase-1 (1.81 ± 0.23 and 4.25 ± 0.48), IL-1β (5.68 ± 1.51 and 12.13 ± 3.71), and IL-18 (2.32 ± 0.37 and 4.81 ± 0.51) compared with controls (all p < 0.005). IMQ stimulation of PBMC from patients similarly induced greater increases in protein expressions of NLRP3 inflammasome compared with controls. The protein expressions of NLRP3, IL-1β, and IL-18 on PBMC significantly decreased after treatment with NLRP3 inhibitor in patients with AOSD.Conclusion.Increased expression of NLRP3 inflammasome and its positive correlation with disease activity in AOSD suggest its involvement in disease pathogenesis. IMQ upregulated expressions of NLRP3 inflammasome signaling, and IMQ might be an activator of NLRP3 inflammasome in AOSD.

The image-based virtual try-on system has attracted a lot of research attention. The virtual try-on task is challenging since synthesizing try-on images involves the estimation of 3D transformation from 2D images, which is an ill-posed problem. Therefore, most of the previous virtual try-on systems cannot solve difficult cases, e.g., body occlusions, wrinkles of clothes, and details of the hair. Moreover, the existing systems require the users to upload the image for the target pose, which is not user-friendly. In this paper, we aim to resolve the above challenges by proposing a novel FashionOn network to synthesize user images fitting different clothes in arbitrary poses to provide comprehensive information about how suitable the clothes are. Specifically, given a user image, an in-shop clothing image, and a target pose (can be arbitrarily manipulated by joint points), FashionOn learns to synthesize the try-on images by three important stages: pose-guided parsing translation, segmentation region coloring, and salient region refinement. Extensive experiments demonstrate that FashionOn maintains the details of clothing information (e.g., logo, pleat, lace), as well as resolves the body occlusion problem, and thus achieves the state-of-the-art virtual try-on performance both qualitatively and quantitatively.

The image-based virtual try-on system has raised research attention recently, but it still requires to upload an image of a user with the target pose. We present a novel learning model, Fit-Me network, to seamlessly fit in-shop clothing into a person image and simultaneously transform the pose of the person image to another given one. The proposed Fit-Me network helps users not only save the time used to change clothes physically but also provide comprehensive information about how suitable the clothes are. By facilitating the arbitrary pose transformation, we can generate consecutive poses to help users get more information for deciding whether to buy the clothes or not from different aspects.

Background: The Assessment of Spondyloarthritis international Society Health Index (ASAS HI) has been develop and validated to assess health and function in patients with spondyloarthritis. However, whether ASAS HI differs between men and women is unknown. The aim of this study was to compare ASAS HI between men ans women in patients with ankylosing spondylitis (AS). Objectives: The aim of this study was to compare ASAS HI between men ans women in patients with ankylosing spondylitis (AS). Methods: Since November 2016, we measured and recorded data of demography, comorbidity, family history, medication use, 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 for AS patients in clinical practice using an electronic patient reported data system linked to an electronic medical record system in Taichung Veterans General hospital (TCVGH). We retrieved the last recorded data of AS patients in TCVGH during 2017/11–2018/10. We assessed the association between gender and the ASAS HI using a multivariable linear regression model. Variables from the univariable linear regression analysis with p 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. Female patients had an older age at onset (29.2 ± 12.6 vs 24.9 ± 9.6 years, p = 0.015), a shorter symptom duration (15.7 ± 11.6 vs 21.8 ± 12.0 years, p Conclusion: This single center, cross-sectional study revealed that male gender was significantly associated with lower ASAS HI in AS patients. Reference: [1] Kiltz U, van der Heijde D, Boonen A, Akkoc N, Bautista-Molano W, et al. 2018. Measurement properties of the ASAS Health Index: results of a global study in patients with axial and peripheral spondyloarthritis. Annals of the rheumatic diseases 77:1311-7. Disclosure of Interests: Hsin-Hua Chen Speakers bureau: Johnson & Johnson, Novartis, Pfizer, Abbvie, Roche, UCB, Bristol-Myers Squibb, Chugai, Ting-I Pan: None declared, Yi-Ming Chen Grant/research support from: GSK, Pfizer, BMS, Astra & Zeneca, Consultant for: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Sanofi, MSD, Guigai, Astellas Inova Diagnostics, UCB Agnitio Science Technology, United Biopharma, Thermo Fisher, Paid instructor for: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Astra& Zeneca, Sanofi, MSD, Guigai, Astellas UCB Thermo Fisher, Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra& Zeneca, Sanofi, MSD, Guigai, Astellas UCB Thermo Fisher, Kuo-Lung Lai: None declared, Tsu-Yi Hsieh: None declared, Ching-Tsai Lin: None declared, Wei-Ting Hung: None declared, Yin-Yi Chou: None declared, Chih-Wei Tseng: None declared, Yi-Da Wu: None declared, Chia-Wei Hsieh: None declared, Wen-Nan Huang: None declared, Yi-Hsing Chen: None declared, Der-Yuan Chen: None declared

Background: The Bath ankylosing Spondylitis Disease activity index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS). However, the cut-off of BASDAI used to indicate high disease activity (i.e., ≥4) was determined arbitrarily and was suggested as a criterion to initiate biological therapy for aS patients. The ankylosing Spondylitis Disease activity Score (ASDAS) has been developed as a new composite index to assess aS disease activity. The cut-off values for disease activity states has been defined and validated. ASDAS≥2.1 was selected as a criterion of starting biological therapy. However, the BASDAI cut-off values corresponding to the aSDAS cut-off values for disease activity states were unknown. Objectives: The purpose of this study was to estimate the corresponding BASDAI and aSDAS cut-off in a Taiwanese aS cohort. Methods: Since November 2016, we assessed the ankylosing Spondylitis Disease activity Score (ASDAS) and the Bath ankylosing Spondylitis Disease activity index (BASDAI) regularly and recorded demographic data, comorbidity, family history, medication use for aS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient reported data system linked to an electronic medical record system. We identified 489 aS patients with complete baseline demographic and assessment data from the TCVGH electronic data system during 2016/11–2018/10. We used receiver operating characteristic (ROC) curves with Youden’s J statistic to determine the cut-off values of BASDAI that correspond to aSDAS disease activity cut-offs (i.e., 1.3, 2.1 and 3.5). Results: We included a total of 489 aS patients [114 (23.3%) females, mean age 44.1 years (S.D. 13.9), mean symptom duration 18.0 years (S.D. 11.9), 152 (31.1%) current biologic users]. Mean BASDAI, aSDAS-ESR and aSDAS-CRP scores were 2.1 (S.D. 1.5), 1.6 (S.D. 0.8) and 1.5 (S.D. 0.9) respectively. Mean levels of CRP and ESR were 0.6 (S.D. 1.5) mg/dl and 12.2 (S.D. 14.0) mm/hr respectively. Based on aSDAS-CRP, the numbers (%) of aS patients with inactive disease ( Conclusion: The estimated optimal BASDAI value that corresponds to the recommended aSDAS cut-off ≥2.1 for biologial therapy initiation was lower than the recommended BASDAI cut-off of ≥4 in this Taiwanese aS cohort. References [1] Machado P, et al. 2011. Ankylosing Spondylitis Disease activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis2011;70:47-53. Disclosure of interests: Hsin-Hua Chen Speakers bureau: Johnson & Johnson, Novartis, Pfizer, abbvie, Roche, UCB, Bristol-Myers Squibb, Chugai, Ting-I Pan: None declared, Yi-Ming Chen Grant/research support from: GSK, Pfizer, BMS, astra & Zeneca, Consultant for: Pfizer, Novartis, abbvie, Johnson & Johnson, BMS, Roche, Sanofi, MSD, Guigai, astellas, inova Diagnostics, UCB, agnitio Science Technology, United Biopharma, thermo Fisher, Paid instructor for: Pfizer, Novartis, abbvie, Johnson & Johnson, BMS, Roche, astra& Zeneca, Sanofi, MSD, Guigai, astellas, UCB, thermo Fisher, Speakers bureau: Pfizer, Novartis, abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, astra& Zeneca, Sanofi, MSD, Guigai, astellas, UCB, thermo Fisher, Yi-Hsing Chen: None declared, Wen-Nan Huang: None declared, Tsu-Yi Hsieh: None declared, Kuo-Lung Lai: None declared, Wei-Ting Hung: None declared, Yin-Yi Chou: None declared, Chih-Wei Tseng: None declared, Yi-Da Wu: None declared, Chia-Wei Hsieh: None declared, Ching-Tsai Lin: None declared

Adult-onset Still’s disease (AOSD) is a rare autoinflammatory disease, which has elevated autophagosome levels regulated by autophagy-related gene (ATG) expression. We investigated the associations of ATG polymorphisms with AOSD susceptibility, clinical manifestations, and disease course. The six-candidate single-nucleotide polymorphisms (SNPs) involved in autophagy were genotyped using direct sequencing on samples from 129 AOSD patients and 129 healthy participants. The differentially expressed gene products were quantified using PCR and ELISA. Significant linkage disequilibrium was noted in three SNPs of autophagy-related 16-like 1 (ATG16L1) gene (rs10210302, rs2241880, and rs1045100). Although the AA/CC/TT haplotype of ATG16L1 was not associated with the susceptibility of our AOSD patients compared with other haplotypes, those carrying this haplotype had lower mRNA expression levels of LC3-II, reflecting by autophagosome formation (p = 0.026). Patients carrying AA/CC/TT haplotype also have a significantly higher proportion of skin rash and a lower proportion of arthritis compared with other haplotypes. The AA/CC/TT haplotype was significantly associated with systemic pattern (odds ratio, 3.25, 95% confidence interval, 1.15–9.14, p = 0.026). In summary, the AA/CC/TT haplotype encoded lower levels of autophagosome formation and was associated with a higher proportion of skin rash and systemic pattern of AOSD compared with other haplotypes.

Background:Lupus nephritis is a significant complication of systemic lupus erythematosus and is associated with increased risks of end-stage kidney disease and mortality.Objectives:The retrospective observational study aims to investigate which component of the National Institutes of Health activity and chronic indices of lupus nephritis can predict mortality.Methods:We identified 528 SLE patients with biopsy-proven lupus nephritis between 2006 and 2019. Two patients with class VI lupus nephritis were excluded, and a total of 526 patients were analyzed. Serum creatinine, urine protein-to-creatinine ratio (UPCR), and serologic markers for SLE disease activity were measured at the time of the renal biopsy. The histopathologic findings of renal biopsies were classified by utilizing the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification.Results:Among 526 patients enrolled, 64 expired, and 44 were female (68.8%, p=0.004). Class IV (± V) comprised the most (n= 39, 60.9%), followed by class V (n= 18, 29.7%). Lower eGFR was observed in the death group, compared with the survival group (median: 24.7 vs. 80.5, pIn the univariable analysis, age, male sex, eGFR, activity index scores, cellular crescents, chronicity index scores, and all CI components (global obsolete glomeruli, tubular atrophy, interstitial fibrosis, fibrous crescents) and tubulointerstitial nephritis were significantly associated with an increased risk of death. When patient characteristics and NIH activity/ chronicity indices were jointly examined in a multivariable analysis, fibrous crescents were significantly associated with increased risk of death in females (HR 5.23 [95% CI: 1.51, 18.09]) (Table 1). In males, the risks of death increased with cellular crescents (HR 1.73 [95% CI: 1.10, 2.73]) but decreased with global obsolete glomeruli (HR 0.12 [95% CI: 0.02, 0.91]).Conclusion:In this single-center observational study, fibrous crescents in females and cellular crescents in males were significantly associated with increased risks of mortality.References:[1]Doria A, Iaccarino L, Ghirardello A, et al. Long-term prognosis and causes of death in systemic lupus erythematosus. Am J Med 2006; 119: 700–706.[2]Faurschou M, Starklint H, Halberg P, Jacobsen S. Prognostic factors in lupus nephritis: diagnostic and therapeutic delay increases the risk of terminal renal failure. J Rheumatol. 2006;33(8):1563-1569.[3]Chen YM, Hung WT, Liao YW, et al. Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study. Lupus. 2019;28(5):658-666.Table 1.Logistic regression of predictors for mortality in patients with lupus nephritisUnivariableMultivariable (Female)Multivariable (Male)HR95% CIp valueHR95% CIp valueHR95% CIp valueAge1.03(1.01-1.05)0.0021.02(0.98-1.07)0.2671.01(0.95-1.08)0.670Male sex2.10(1.23-3.55)0.006UPCR1.02(0.95-1.09)0.616eGFR0.97(0.96-0.99)0.99(0.96-1.00)0.1830.98(0.96-1.00)0.086Activity Index1.06(1.01-1.11)0.027Cellular crescents1.29(1.12-1.50)1.03(0.63-1.67)0.9171.73(1.10-2.73)0.017Chronicity Index1.16(1.07-1.26)global obsolete glomeruli1.37(1.08-1.76)0.0111.24(0.55-2.77)0.6060.12(0.02-0.91)0.040Tubular atrophy1.65(1.28-2.13)0.41(0.06-2.82)0.3624.77(0.30-75.32)0.267Interstitial fibrosis1.71(1.32-2.23)3.70(0.52-26.24)0.1911.37(0.07-27.40)0.837Fibrous crescents2.38(1.40-4.03)0.0015.23(1.51-18.09)0.0090.00(0-extremely large)0.989Tubulointerstitial nephritis1.70(1.03-2.80)0.037Disclosure of Interests:None declared

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, pp= 0.037). TNF-α inhibitors were associated with lower cumulative incidence of discontinuation due to inefficacy and adverse events (bothp

Adult-onset Still’s disease (AOSD), an autoinflammatory disorder, is related to the dysregulation of NLR3-containing a pyrin domain (NLRP3)-inflammasome signaling. We aimed to investigate the associations of genetic polymorphisms of NLRP3-inflammasome signaling with AOSD susceptibility and outcome and to examine their functional property. Fifty-three candidate single-nucleotide polymorphisms (SNPs) involved in NLRP3-inflammasome response were genotyped using Sequenom MassArray on the samples from 66 AOSD patients and 128 healthy controls. The significant SNPs were validated by direct sequencing using a TaqMan SNP analyzer. Serum levels of associated gene products were examined by ELISA. One SNP rs11672725 of CARD8 gene was identified to be significantly associated with AOSD susceptibility by using MassArray and subsequent replication validation (p = 3.57 × 10−7, odds ratio 3.02). Functional assays showed that serum CARD8 levels were significantly lower in AOSD patients (median, 10,524.6 pg/mL) compared to controls (13,964.1 pg/mL, p = 0.005), while levels of caspase-1, IL-1β and IL-18 were significantly higher in patients (107.1 pg/mL, 2.1 pg/mL, and 1495.8 pg/mL, respectively) than those in controls (99.0 pg/mL, 1.0 pg/mL, and 141.4 pg/mL, respectively). Patients carrying rs11672725CC genotype had significantly higher serum caspase-1 and IL-18 levels (121.3 pg/mL and 1748.6 pg/mL) compared to those with CT/TT genotypes (72.6 pg/mL, p = 0.019 and 609.3 pg/mL, p = 0.046). A higher proportion of patients with rs11672725CC genotype had a systemic pattern of disease outcome, which was linked to low CARD8 levels. A novel variant, rs11672725, of the CARD8 gene was identified as a potential genetic risk for AOSD. Patients carrying the rs11672725CC genotype and C allele had low CARD8 levels, and were predisposed to a systemic pattern with an elevated expression of inflammasome signaling.

ObjectiveTo 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).MethodsFrom 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.ResultsA 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 5 than females (odds ratio = 0.15, 95% CI, 0.07-0.36, p ConclusionThis single-center, cross-sectional study revealed that a higher ASAS HI score was significantly associated with female gender and higher disease activity measures.

Background Systemic sclerosis (SSc) is an autoimmune disease characterised with proximal scleroderma and internal organ involvement. Observational studies demonstrated increased incidences of cancer in SSc patients1. Nailfold capillaroscopy is useful for the diagnosis and disease activity assessment of SSc. However, whether the nailfold capillaroscopy pattern is distinct in SSc patients with malignancy remained unknown. Objectives The aim of this study was to investigate the incidence rate of malignancy in SSc patients. Nailfold capillaroscopy morphology patterns in SSc patients with cancer were also compared to those without cancer. Methods During 2004 to 2014, consecutive 310 SSc patients who visited outpatient clinics at Taichung Veterans General Hospital, Taiwan were enrolled. Nailfold capillaroscopy was performed at a magnification of 200x. Abnormal morphology description were analysed and categorised by the scoring system proposed by Dr. Cutolo2. SSc with malignancy was defined if the subject had a cancer diagnosis during the follow-up period. Results Among 310 SSc patients, 28 (10.9%, 13 males, 25 females) patients had cancer. The mean age of SSc with malignancy is 62±10.9 years. Sixty-four percent SSc patients with cancer is diffuse type, but only 42% of them were tested positive for anti-Scl-70 antibodies. The most common cancer were genitourinary tract and gastrointestinal tract, accounting for almost two-thirds patients. Cancer and SSc were frequently diagnosed at the same year. In SSc patients with cancer, 19 patients received nailfold capillary microscope exams when SSc was diagnosed. The assessment of nailfold capillaroscopy morphology patterns in SSc patients with cancer demonstrated neither enlarged loop, giant loop, microhemorrhage nor angiogenesis. However, prominent avascular areas could be observed universally in SSc patients with malignancy. Conclusions Rheumatologists should be aware of malignancy in SSc patients, especially those with diffuse type and within the 1st year of symptoms onset. SSc patients with malignancy tend to present atypical capillaroscopic pattern of prominent avascular area without loop dilatation, microhemorrhage and angiogenesis. References [1] Bonifazi M, et al.,Rheumatology (Oxford). 2013Jan;52(1):143–54 [2] Maurizio Cutolo (2010) Atlas of Capillaroscopy in Rheumatic diseases chapter 11 page 77–86 Disclosure of Interest None declared

Aim To assess the association between periodontitis (PD) and inadequate disease control (IDC) in patients with rheumatoid arthritis (RA) receiving biological therapy. Materials and methods In total, 111 RA patients receiving biological therapy for at least 3 months were assessed for periodontal disease at baseline. RA disease activity was assessed at baseline and at 3 months of follow-up. A multivariable logistic regression analysis was used to estimate the association between PD and IDC, adjusting for age, sex, smoking, diabetes, and baseline RA disease activity. An additional exploratory model further controlled for disease characteristics and other medications. Results Among 111 patients, 84 (75.7%) had PD, of whom 37 (44.0%) received periodontal treatment. Thirty-four (40.5%) of PD patients had IDC; 12 (32.4%) of treated PD patients and 22 (46.8%) of untreated patients had IDC, respectively. The ORs (95% CIs) for IDC were 1.45 (0.50-4.23) in PD patients and 1.84 (0.59-5.76) in untreated PD patients. In the exploratory model, the ORs (95% CIs) for IDC were 5.00 (1.19-21.03) in PD patients and 6.26 (1.34-29.34) in untreated PD patients. Conclusion This single-centre, prospective study failed to demonstrate a consistently positive correlation between PD and IDC in RA patients receiving biological treatment.

The high affinity immunoglobulin E (IgE) receptor-FcεR1 is mainly expressed on the surface of effector cells. Cross-linking of IgE Abs bound to FcεR1 by multi-valent antigens can induce the activation of these cells and the secretion of inflammatory mediators. Since FcεR1 plays a central role in the induction and maintenance of allergic responses, this study aimed to investigate the association of FcεR1 with the allergic phenotype of Cε expression and cytokine and histamine release from peripheral leukocytes. Peripheral leukocytes from 67 allergic and 50 non-allergic subjects were used for genotyping analysis. Peripheral mononuclear cells (PBMCs) were used for Cε expression and ELISpot analysis, while polymorphonuclear cells (PMNs) were used for histamine release. The association between genotype polymorphism of the FcεR1α promoter region (rs2427827 and rs2251746) and allergic features of Cε expression and histamine were analyzed, and their effects on leukocytes function were compared with wild type. The genotype polymorphisms of FcεR1α promoter region with CT and TT in rs2427827 and TC in rs2251746 were significantly higher in allergic patients than in non-allergic controls. Patients with single nucleotide polymorphism (SNP) of FcεR1α promoter region had high levels of total IgE, mite-specific Der p 2 (Group 2 allergen of Dermatophagoides pteronyssinus)-specific IgE and IgE secretion B cells. The mRNA expression of FcεR1α was significantly increased after Der p2 stimulation in PBMCs with SNPs of the FcεR1α promoter region. Despite the increased Cε mRNA expression in PBMCs and histamine release from PMNs and the up-regulated mRNA expression of interleukin (IL)-6 and IL-8 secretions after Der p2 stimulation, there was no statistically significant difference between SNPs of the FcεR1α promoter region and the wild type. SNPs of FcεR1α promoter region were associated with IgE expression, IgE producing B cells, and increased Der p2-induced FcεR1α mRNA expression. These SNPs may be used as a disease marker for IgE-mediated allergic inflammation caused by Dermatophagoides pteronyssinus.

Dysregulation of inflammasomes serves a pathogenic role in autoinflammatory diseases (AIDs) and adult-onset Still's disease (AOSD) has been categorized as an AID. The present study investigated the expression of NLR family pyrin domain containing proteins (NLRPs) inflammasome in patients with AOSD, the effect of inflammasome inhibitors on NLRP3 signaling and whether human parvovirus B19‑associated antigens can activate NLRP3 in patients with AOSD. mRNA expression levels of NLRPs in peripheral blood mononuclear cells (PBMCs) from 34 patients with AOSD and 14 healthy individuals were determined using reverse transcription‑quantitative polymerase chain reaction. Protein expression of NLRP3 was evaluated by western blotting. Supernatant cytokine levels were measured by ELISA. Among the NLRPs investigated in the present study, NLRP3 transcripts were markedly elevated and expression of NLRP2, NLRP7 and NLRP12 was decreased in patients with AOSD compared with the controls. Treatment with NLRP3 inhibitors significantly reduced downstream NLRP3 signaling in PBMCs form patients with AOSD. B19‑nonstructural protein (NS)1 stimulation of PBMCs from patients with AOSD induced significant upregulation of transcript levels of NLRP3, caspase‑1 and interleukin (IL)‑1β compared with PBMCs from healthy controls. B19‑NS1 stimulation of PBMCs from patients with AOSD induced significant increase in supernatant levels of IL‑1β and protein expression of NLRP3, caspase‑1, IL‑1β, and IL‑18 compared with healthy controls. Elevated expression of NLRP3 and its downstream inflammasome signaling components in patients with AOSD indicated a potential pathogenic role of B19‑NS1. Thus, B19‑NS1 may induce expression of IL‑1β and IL‑18 through activation of caspase‑1‑associated NLRP3‑inflammasome in AOSD.

This article presents a convenient means to inter-relate appliances in an intelligent living space. While more and more wireless devices are phased in, a user can barely familiarize herself with managing these devices. This is because wireless devices often operate in some form of binding relationships among themselves, which are typically set up at startup in a self-organizing fashion, leaving the user little room for intervention. As a remedy, we propose a software-hardware codesign and implementation that enable the user to adapt network operations to certain needs anytime without knowledge of low-level details. Binding manipulation is done straightaway with simple mouse clicking and dragging on icons in our graphical user interface. We demonstrate example applications in green power systems as well. A practical platform over which to inspire other applications, this study elegantly lends itself to generic wireless network environments.

There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (FcεRIα) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (–344C/T) and rs2251746 (–66T/C) gene polymorphisms of FcεRIα in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (–344C>T, –66C>T) were similar to the normal controls. The allele frequency of –344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p = 0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5 ± 5.2 vs. 103.3 ± 3.3 respectively, (p < 0.05), and the percentages of histamine release were 31.3% ± 7.4% vs. −24.0% ± 17.5%, (p < 0.05) respectively. Although the mean fluorescence intensity of CD203c expression and the percentage of histamine release were significantly up-regulated by aspirin, they were not affected by anti-IgE antibodies. These results suggest that a single SNP of FcεRIα (–344C>T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU.

Introduction studies have shown that high-mobility group box 1 (HMGB1) may play a role in the propagation of inflammatory response in infectious and autoimmune diseases. However, its utility in the differentiation between infections and disease flares in systemic lupus erythematosus (SLE) patients has not been investigated. Methods we prospectively recruited 38 hospitalized patients from Taiwan with SLE. Among them, 13 patients suffered from superimposed bacterial infections while the other 25 patients experienced disease flares. SLE disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Serum levels of HMGB1 were measured by an enzyme-linked immunosorbent assay (ELISA). Additionally, serum levels of high-sensitivity C-reactive protein (hsCRP) were determined among 34 of the SLE patients. Results there was no significant difference between the serum HMGB1 levels in SLE patients with disease flares and patients with bacterial infections. Among SLE patients with disease flares, serum HMGB1 levels were significantly higher in patients with mild to moderate flares (3.53 ng/ml) compared to those with severe flares (1.72 ng/ml, p Conclusion the determination of serum HMGB1 level is not useful in the differentiation between disease flares and bacterial infections in SLE patients.

The annual ACM Multimedia Conference was held in Nice, France during October 21st to 25th, 2019. Being the 27th of its series, it attracted approximately 800 participants from all over the World. Among them were the student volunteers who supported the smooth organization of the Conference.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mardi 30 decembre 2014

Background Autophagy is a highly conserved cellular catabolic pathway for degradation and recycling of intracellular components in response to nutrient starvation or environmental stress. Endoplasmic reticulum (ER) homeostasis can be disturbed by physiological and pathological influences, resulting in accumulation of misfolded and unfolded proteins in the ER lumen, a condition referred to as ER stress. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, possesses anti-tumor and anti-viral activities in vitro and in vivo. Objective IMQ has been reported to promote the apoptosis of THP-1-derived macrophages through an ER stress-dependent pathway. However, the role of ER stress in IMQ-induced autophagy is unknown. In this study, we investigated the relationship between ER stress and IMQ-induced autophagy. Methods The expression of LC3, P62, p-PERK, Grp78, p-elF2α and IRE1α proteins were determined by immunoblotting. The relationship between ER stress and IMQ-induced autophagy were analyzed by ER stress inhibitors, a PERK inhibitor and the genetic silencing of PERK. The role of double-strand RNA-dependent protein kinase (PKR) activation in IMQ-induced autophagy was assessed by inhibiting PKR and genetically silencing PKR. The IMQ-induced autophagy was evaluated by immunoblotting and EGFP-LC3 puncta formation. Results IMQ induced reactive oxygen species (ROS) production in cancer cells. Additionally, IMQ markedly induced ER stress via ROS production and increased autophagosome formation in a dose- and time-dependent manner in both TLR7/8-expressing and TLR7/8-deficient cancer cells. Pharmacological or genetic inhibition of ER stress dramatically reduced LC3-II expression and EGFP-LC3 puncta formation in IMQ-treated cancer cells. IMQ-induced autophagy was markedly reduced by depletion and/or inhibition of PKR, a downstream effector of ER stress. Conclusion IMQ-induced autophagy is dependent on PKR activation, which is mediated by ROS-triggered ER stress. These findings might provide useful information for basic research and for the clinical application of IMQ.

QuantiFERON-TB-Gold (QFT-G) conversion is frequently observed in rheumatoid arthritis (RA) patients receiving biologic therapy. However, there have not been any known biomarkers available for detecting tuberculosis (TB) in QFT-G converters. We aimed to evaluate clinical utility of cytokines/chemokines for detecting TB in patients with QFT-G conversion. Among a total of 227 RA patients who underwent QFT-G assay, 187 QFT-G-negative patients received biologic therapy without isoniazid prophylaxis. QFT-G assay was repeated at week 52 of biologic therapy or at the time of TB diagnosis. Levels of cytokines/chemokines were determined by magnetic bead array or ELISA in QFT-G converters and 12 non-RA patients with TB (non-RA TB). QFT-G conversion was found in 54 (28.9%) of 187 baseline QFT-G-negative patients, of which 7 (13.0%) developed active TB during the one-year follow-up period. Among the examined cytokines/chemokines, non-stimulated and TB-antigen-stimulated neopterin levels were significantly higher in RA patients who developed TB (RA-TB) (median, 24.5pg/ml and 23053pg/ml, respectively) and non-RA TB patients (12.2pg/ml and 9633pg/ml, respectively) compared with QFT-G converters without TB (3.0pg/ml and 2720pg/ml, respectively, both p

Objectives The risk of active tuberculosis increases in rheumatoid arthritis (RA) patients receiving antitumour necrosis factor alpha (TNFα) therapy. Longitudinal data concerning serial interferon γ (IFNγ) assays for detecting tuberculosis have been limited. This study investigated the time course of the development of active tuberculosis, and evaluated the utility of serial QuantiFERON-TB Gold (QFT-G) assays for detecting its emergence in RA patients undergoing long-term anti-TNFα therapy. Methods 242 RA patients who received anti-TNFα therapy and serial QFT-G assays were prospectively evaluated. QFT-G was performed by measuring IFNγ levels in whole blood treated with tuberculosis-specific antigens. Results Among 242 RA patients, 75 (31.0%) had a positive tuberculin skin test (TST) and 45 (18.6%) had positive QFT-G results, with another nine (3.7%) showing indeterminate QFT-G assay. Isoniazid prophylaxis was given to 37 patients with TST+/QFT-G+ results and 24 TST+/QFT-G− patients with TST induration diameter ≧10 mm. Four patients (three with baseline QFT-G+ results) developed tuberculosis within the first 3 months of anti-TNFα therapy, whereas five patients with baseline TST−/QFT-G− results developed active tuberculosis after 20–24 months9 anti-TNFα therapy. Progressively rising levels of released IFNγ (2.17±0.98 vs 5.93±2.92 IU/ml in early secretory antigenic target-6-stimulated well; 1.12±0.84 vs 2.96±1.02 IU/ml in culture filtrate protein-10-stimulated well) were observed in those who developed tuberculosis early in anti-TNFα therapy. QFT-G conversion was found in baseline QFT-G-negative patients who developed tuberculosis late in treatment. Conclusion The emergence of active tuberculosis follows a biphasic pattern. Persistently high levels of released IFNγ or QFT-G conversion strongly indicate the development of active tuberculosis in patients undergoing long-term anti-TNFα therapy.

ObjectiveTo investigate the kinetics of hepatitis B virus (HBV) viral loads and HBV reactivation in rheumatoid arthritis (RA) patients undergoing therapy with tumour necrosis factor alpha (TNFα) inhibitors.MethodsThe authors investigated the virological, serological and biochemical evidence of HBV reactivation in 88 RA patients receiving anti-TNFα therapy. Levels of HBV surface (HBs) antigen (Ag), anti-HBV core (HBc)-IgG and anti-HBs antibody (Ab) were detected by electrochemiluminescence immunoassay, and viral loads were determined by real-time PCR assay.ResultsIn a total of 88 HBcAb-positive patients, 18 (20.5%) patients were HBsAg-positive, 12 (13.6%) patients were HBsAg-negative/HBsAb-negative and 58 (65.9%) patients were HBsAg-negative/HBsAb-positive before starting anti-TNFα therapy. Among HBsAg-positive patients receiving anti-TNFα therapy, HBV reactivation was documented in none of 10 patients who received lamivudine pre-emptive therapy and serum viral loads significantly decreased (mean±SEM, 153 860±80 120 IU/ml at baseline vs 313±235 IU/ml after 12 months antiviral therapy, pConclusionHBV reactivation can occur in both HBsAg-positive and HBsAg-negative/HBcAb-positive patients with detectable HBV DNA, so-called occult HBV infection, during anti-TNFα therapy. Antiviral prophylaxis may effectively reduce HBV reactivation in HBsAg-positive RA patients undergoing anti-TNFα therapy.

Polymyositis (PM) and dermatomyositis (DM) are associated with high risk of nasopharyngeal carcinoma (NPC) in Asian countries. Epstein-Barr virus (EBV) might induce autoimmunity and malignancies in susceptible individuals.To investigate the association of EBV with PM/DM and NPC in PM/DM patients.Serum levels of anti-EBV viral capsid antigens (VCA) and anti-EBV-coded nuclear antigens-1 (EBNA-1) antibodies were measured by ELISA, and EBV DNA loads were determined using real-time PCR for 98 PM/DM patients, 94 systemic lupus erythematosus (SLE) patients and 370 healthy controls (HC). Anti-transfer-RNA synthetase antibodies (ASA) were determined by radioimmunoprecipitation for PM/DM patients.Thirteen (13.3%) of PM/DM patients vs. none of SLE patients had detectable NPC. ASA were detectable in 31.7% of PM/DM without malignancy, while lack of ASA in any PM/DM patient with NPC. IgA anti-EBNA-1 were detectable in 30.6% of PM/DM patients and 31.9% of SLE patients, but only in 4.1% of HC (odds ratio [OR] 10.44 and 11.12 respectively, both p0.001). Significantly higher positivity for IgA anti-EBNA-1 were observed in PM/DM with NPC than in those without malignancy (OR 44.7, p0.01). Significantly higher positivity for EBV genome were observed in PM/DM with NPC than in those without malignancy (OR 43.9, p0.01), in SLE patients (OR 13.2, p0.05) and in HC (OR 99.4, p0.001). EBV DNA loads were significantly higher in PM/DM with NPC compared with those without malignancy and HC.Our results showed a positive association of EBV with PM/DM and NPC. PM/DM patients who have IgA anti-EBNA-1 or increased EBV DNA loads should be highly suspected to have occult NPC.

Objective. To investigate the potential role of Th type 17 (Th17) cells and Th17-related cytokines in the pathogenesis of adult-onset Still’s disease (AOSD). Methods. The frequencies of circulating Th17 cells in 24 patients with active untreated AOSD, 16 patients with active SLE and 12 healthy volunteers were determined using intracellular cytokine staining and flow cytometry. Serum levels of Th17-related cytokines, including IL-1b, IL-6, IL-17, IL-18, IL-21 and IL-23 were measured by ELISA. Results. Significantly higher median frequencies of circulating Th17 cells were found in active untreated AOSD patients (1.01%) and active SLE patients (1.26%) than in healthy volunteers (0.12%, both P < 0.001). The frequencies of circulating Th17 cells were positively correlated with activity score (r = 0.527, P < 0.01) and serum ferritin levels (r = 0.724, P < 0.001) in AOSD patients, and correlated with SLEDAI (r = 0.663, P < 0.01) in SLE patients. Additionally, the frequencies of circulating Th17 cells were positively and significantly correlated with serum levels of IL-1b, IL-6, IL-17, IL-18, IL-21 and IL-23 in both AOSD and SLE patients. The frequencies of circulating Th17 cells and serum IL-17 levels significantly decreased after effective therapy in AOSD patients (both P < 0.001). Conclusion. Elevated frequencies of circulating Th17 cells and a positive correlation with disease activity in our AOSD patients suggest that Th17 cells contribute to the pathogenesis of this disease. Dysregulation of Th17 cells may be a common pathogenic mechanism that underlies the development of both AOSD and SLE.

We investigated whether sonography and anti-cyclic citrullinated peptide (anti-CCP) antibodies in Chinese patients with palindromic rheumatism (PR) during active episodes are of predictive value for development of rheumatoid arthritis (RA). Clinically involved regions of 84 PR patients during active episodes were examined with ultrasonography using a 6–13 MHz linear transducer. Serum levels of anti-CCP antibodies were determined by enzyme-linked immunosorbent assay. All patients were followed up monthly for 3 years after investigation. Thirteen (15%) of the PR patients had progressed to RA after a mean of 1.4 years (range, 0.4–3.0 years). Of these 13 patients, 11 patients (85%) had sonographic features of synovitis and 8 patients (62%) had a positive anti-CCP antibody test. The absence of sonographic features of synovitis during active episodes provided a very high 3-year predictive value in excluding the possibility of progression to RA for PR patients with a negative anti-CCP antibody test. Both the sonographic findings of synovitis and a positive anti-CCP antibody test were significant predictors for progression of PR to RA within 3 years by backward stepwise logistic regression analysis. Sonographic examination together with an anti-CCP antibody test during active episodes is useful for predicting the progression of PR to RA.

Accumulating evidence indicates that interleukin (IL)-18 has a central role in the pathogenesis of lupus nephritis (LN). Although two recent studies showed that IL-18 promoter gene polymorphisms might be associated with systemic lupus erythematosus (SLE), to our knowledge, there have not been any reports concerning their association with LN. The aim of our study was to investigate the association of IL-18 promoter polymorphisms with World Health Organization pathological classes and identify their functional correlations. Sequence-specific primer polymerase chain reaction and the restriction fragment length polymorphism method were used to analyse the genotypes of IL-18 promoter polymorphism at the position −607 in 101 unrelated patients with LN, 64 non-renal patients with SLE and 174 ethnically matched healthy controls. Serum IL-18 levels were determined using enzyme-linked immunosorbent assay during the active phase. Immunohistochemical analysis was performed for IL-18 expression on renal biopsies from 72 patients with LN. Our results showed that patients with non-renal SLE had significantly higher frequencies of SNP−607/AA when compared to patients with LN (37.5% vs 18.8%, P

The cauda equina syndrome (CES) is a rare neurological complication of ankylosing spondylitis (AS). Imaging diagnosis of CES in long-standing AS patients (CES-AS) using myelography, computed tomography (CT), and magnetic resonance imaging (MRI) were reported in the literature. They, however, demonstrate only the chronic abnormalities of CES-AS, i.e., dural ectasia, dorsal dural diverticula, and selective bone erosion at the posterior elements of the vertebrae. To our knowledge, imaging features of acute intradural inflammation in CES-AS were not described. We report a patient of CES-AS in whom MRI disclosed acute transverse myelitis and arachnoiditis along the lower spinal cord, and discuss the pathogenesis of CES-AS and the role of MRI in clinical management.

Objective To evaluate the impact of adalimumab (ADA) dose-halving on therapeutic responses and drug levels, the differences in drug levels among patients with different therapeutic responses and the optimal baseline cut-off ADA levels for predicting persistent remission or low disease activity (LDA) at week 24 of dose-halving therapy in 64 RA patients who had already achieved LDA or remission at baseline. Methods Anti-ADA antibody levels were determined by bridging ELISA, ADA levels were evaluated using sandwich ELISA and therapeutic responses were assessed by the 28-joint DAS change. The optimal cut-off drug levels for predicting persistent remission were determined by receiver operating characteristic curve analysis. Results At baseline, 25 (39.1%) and 39 (60.9%) patients had achieved remission and LDA, respectively. After 24 week ADA dose-halving, persistent remission was observed in 23 patients, remission turned LDA in 2 patients, persistent LDA in 24 patients and disease flare in 15 (23.5%) patients. Three patients who developed anti-ADA antibodies at week 24 of dose-halving had very low drug levels and disease flare. Among 61 anti-ADA antibody-negative patients, ADA levels declined by half after 24 weeks of dose-halving (median 5.5 vs 2.6 μg/ml). Baseline ADA levels were significantly higher in patients with persistent remission (median 10.5 μg/ml) or LDA (4.5 μg/ml) than in those with disease flare (0.9 μg/ml), indicating associations of ADA levels with therapeutic responses. An ADA level above the cut-off value of 6.4 μg/ml might predict persistent remission after dose-halving with high sensitivity and specificity. Conclusion ADA dose-halving is feasible for patients who have achieved remission and sufficient drug levels. Drug level monitoring may help clinicians optimize the dosing regimen and prevent overtreatment for patients receiving anti-TNF-α therapy.

Background Sarcoidosis is still considered a rare multisystem disorder in Taiwan, and data on the disease course and outcome are limited. We analyzed the clinical manifestations, disease course and complications in Taiwanese patients with sarcoidosis. Methods A retrospective cohort design was used. Fifty-six patients with sarcoidosis diagnosed between 1985 and 2004 were included. Their clinical features, laboratory findings at initial presentation, disease course, and complications were analyzed. Results Forty-three patients (76.8%) were female. The mean age at symptom onset was 47 years. The most common clinical symptoms were pulmonary (82.1%), cutaneous (23.2%), ophthalmic (19.6%), and articular (17.8%). Only two patients presented with Lofgren's syndrome. There was a seasonal variation in disease onset, with higher incidence in winter and early spring. No advanced pulmonary involvement was noted. Elevated levels of serum angiotensin converting enzyme (sACE) were found in 72.5% (29/40) of patients with active sarcoidosis, and significantly higher levels of sACE were found in patients with lung involvement (27.98 ± 1.71 IU/L vs. 18.2 ± 2.76 IU/L; p 0.01). In 50% (20/40) of patients, sACE levels declined significantly in parallel with clinical remission (24.75 ± 1.53 IU/L vs. 16.33 ± 1.21 IU/L; p 0.05). Spontaneous complete remission was found in 20.7% of patients, whereas 39.6% of patients with multiple extrapulmonary involvement responded poorly to intensive corticosteroids plus various immunosuppressants. Conclusion In this series, the mean age of disease onset was in middle age (mean, 47 years old), there was a low incidence of Lofgren's syndrome (3.6%), and no patients had advanced pulmonary syndrome. The results of this study also suggest that sACE might be a marker of pulmonary involvement that is also useful in monitoring disease activity.

The objective of this study is to determine the risk of tuberculosis (TB) disease in biologics users among rheumatoid arthritis (RA) patients in Taiwan from 2000 to 2015. This retrospective cohort study enrolled adult RA patients initiated on first biologics at Taichung Veterans General Hospital. TB risks were determined as hazard ratio (HR) with 95% confidence interval (CI) using cox regression. A total of 951 patients were recruited; etanercept (n = 443), adalimumab (n = 332), abatacept (n = 74), golimumab (n = 60), tocilizumab (n = 31) and tofacitinib (n = 11). Twenty-four TB cases were identified; 13 in etanercept and 11 in adalimumab group with the TB incidence rate of 889.3/ 100,000 and 1055.6/ 100,000 patient-years respectively. There was no significant difference in TB risk between adalimumab and etanercept users with an incidence rate ratio of 1.27 (p = 0.556 by Poisson model). Significant 2-year TB risk factors included elderly patient >65 year-old (HR: 2.72, 95% CI: 1.06–6.99, p = 0.037), history of TB (HR: 6.24, 95% CI: 1.77–22.00, p = 0.004) and daily glucocorticoid use ≥5mg (HR:5.01, 95% CI: 1.46–17.21, p = 0.010). Sulfasalazine treatment appeared to be protective (HR: 0.32, 95% CI: 0.11–0.97, p = 0.043). Risk management plan (RMP) for TB before initiation of biologics commenced in 2012. The 2-year TB risks after RMP was compared with that before 2012 (HR:0.67, 95% CI: 0.30–1.49, p = 0.323). Elderly RA patients with a history of previous TB infection and concomitant moderate dose glucocorticoid were at higher risk of TB disease. Concurrent sulfasalazine treatment appeared to be a protective factor against TB disease.

Background Suicide is a global health issue, and an increase in suicide risk has been found in patients with systemic lupus erythematosus (SLE) when compared with the general population. However, only a few studies have described suicide attempts in patients with SLE in detail. Objective The aim of this study is to describe the suicide attempts in patients with SLE in a tertiary hospital in Taiwan. Methods A total of 8 patients with SLE, 7 women and 1 man, with 12 suicide attempts among them were identified among 2469 patients visiting a tertiary medical center in Taiwan, from March 1, 2003 to November 30, 2013. Their demographic data, lupus manifestations throughout their disease course, laboratory data, and details of their suicide attempts were retrospectively documented. We also searched the MEDLINE database and found 4 articles in English describing suicide attempts in 14 patients with SLE. Results The median age of the 8 patients with SLE in our hospital who attempted suicide was 33 years (range: 19–77 years). Neuropsychiatric SLE developed in 5 (63%) of these patients before the attempts, and psychiatric disorders were diagnosed in 5 (63%) of them. We also observed a high prevalence of neuropsychiatric SLE (71%) and psychiatric disorders (86%) in patients with SLE in the literature who had attempted suicide. Conclusion We demonstrated that previous neuropsychiatric SLE and comorbid psychiatric disorders are prevalent in patients with SLE who attempt suicide. If a rheumatologist suspects that a patient with SLE has a psychiatric disorder, he or she should refer the patient to a psychiatrist.

Revue du rhumatisme - In Press.Proof corrected by the author Available online since vendredi 9 janvier 2015

A new approach of determining the permissible capacity of grid-connected distributed generation in a distribution feeder is proposed. The method takes the existing operation profile of a power system into consideration, and the outcomes of real systems correspond with practical scenarios. These test results support the method for DG capacity validation that is considered.

We aimed to compare the use of computer-aided quantification methods with 3 different power Doppler ultrasonography (PDUS) modes to assess wrist inflammation in patients with rheumatoid arthritis (RA).This study enrolled 49 patients (60 hand joints) with RA. Clinical parameters (rheumatoid factor [RF], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]) were measured and pain was evaluated by a visual analogue scale (VAS, range: 0 to 10). Imaging of the affected wrist joints was performed with 2D- and 3D-PDUS imaging. The 2D imaging used a volumetric transducer and a linear transducer and the 3D imaging employed a volumetric transducer. Software was used to calculate the vascularisation index (VI), flow index (FI), and vascularisation flow index (VFI) under different measurement conditions.There were 8 males and 41 females, with an average age of 47.59±15.17 years, and average VAS score of 3.63±2.22. In 2D-PDUS with a linear probe, there were significant correlations of ESR with VI and VFI, and of CRP with area, VI, and VFI (p0.05 for all comparisons). In 3D-PDUS, there was a significant correlation of CRP with VFI (p0.05). In all 3 measurement modes, there were moderate or high levels of inter- and intra-operator agreement in measurement of area/volume, VI, FI, and VFI.All 3 PDUS measurement modes had high accuracy and reliability in assessment of wrist inflammation. These results suggest that use of a 3D transducer, which is more expensive and time-consuming, is not necessary for assessment of wrist inflammation.