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A vision-based autonomous driving system can usually fuse information about object detection and steering angle prediction for safe self-driving through real-time recognition of the environment around the car. If an autonomous driving system cannot respond fast to driving control appropriately, it will cause high-risk problems with regard to severe car accidents from self-driving. Therefore, this study introduced GhostConv to the YOLOv4-tiny model for rapid object detection, denoted LW-YOLOv4-tiny, and the ResNet18 model for rapid steering angle prediction LW-ResNet18. As per the results, LW-YOLOv4-tiny can achieve the highest execution speed by frames per second, 56.1, and LW-ResNet18 can obtain the lowest prediction loss by mean-square error, 0.0683. Compared with other integrations, the proposed approach can achieve the best performance indicator, 2.4658, showing the fastest response to driving control in self-driving.

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.

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 &lt, 0.01) and CA-153 (16.4 vs. 72.9, p &lt, 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.

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.

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

The implications of boosting Omalizumab treatment (OT) in patients with severe allergic asthma (SAA) remain unclear. The study aimed to explore and compare the 12-month effectiveness between continuous, at least 10-month OT (continuation group) and four-month boost of Omalizumab (boost group) in adult patients with SAA. In this retrospective cohort study, clinical data were collected for further analysis. Of all participants (n = 124), a significant reduction in annual exacerbations (baseline = 0.8 ± 1.5, follow-up = 0.5 ± 1.0, p = 0.047 *) and improvement in small airway ventilation as evaluated by forced expiratory flow at 25–75% (baseline = 55.1 ± 11.1%, follow-up = 59.4 ± 8.4%, p &lt, 0.001 *) were found in the continuation group (n = 110). By contrast, the boost group (n = 14) had significantly increased annual exacerbations (baseline = 0.7 ± 1.4, follow-up = 2.9 ± 3.6, p = 0.031 *) and impaired small airway function (baseline = 55.3 ± 12.9, follow-up = 52.1 ± 12.5, p = 0.026 *). Furthermore, the continuation group rather than the boost group had significant decreases in the frequency of oral corticosteroid (OCS) use as controllers (baseline = 32.7%, follow-up = 20.0%, p = 0.047 *, baseline = 50.0%, follow-up = 21.4%, p = 0.237, respectively) and OCS maintenance dose (mg/month) (baseline = 85.9 ± 180.8, follow-up = 45.8 ± 106.6, p = 0.020 *, baseline = 171.4 ± 221.5, follow-up = 50.0 ± 104.3, p = 0.064, respectively), and increases in asthma control test scores (baseline = 16.0 ± 3.0, follow-up = 19.8 ± 4.4, p &lt, 0.001 *, baseline = 14.6 ± 3.8, follow-up = 19.7 ± 4.7, p = 0.050, respectively). Continuous OT would be beneficial for adult patients with SAA, while boost of Omalizumab would worsen their long-term outcomes.

The virtual try-on task is so attractive that it has drawn considerable attention in the field of computer vision. However, presenting the three-dimensional (3D) physical characteristic (e.g., pleat and shadow) based on a 2D image is very challenging. Although there have been several previous studies on 2D-based virtual try-on work, most 1) required user-specified target poses that are not user-friendly and may not be the best for the target clothing, and 2) failed to address some problematic cases, including facial details, clothing wrinkles and body occlusions. To address these two challenges, in this paper, we propose an innovative template-free try-on image synthesis (TF-TIS) network. The TF-TIS first synthesizes the target pose according to the user-specified in-shop clothing. Afterward, given an in-shop clothing image, a user image, and a synthesized pose, we propose a novel model for synthesizing a human try-on image with the target clothing in the best fitting pose. The qualitative and quantitative experiments both indicate that the proposed TF-TIS outperforms the state-of-the-art methods, especially for difficult cases., Accepted by IEEE TNNLS (2021). 14 pages including 2 pages of reference

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.

Adult-onset Still’s disease (AOSD) is a multi-systemic inflammatory disorder of unknown etiology. To date, no single diagnostic test is available for AOSD. Herein, we investigated the pathogenic role of microRNAs in AOSD. MicroRNA profiles in plasma from AOSD patients and healthy controls were analyzed by microarray analysis, followed by quantitative reverse transcription PCR validation. The biological functions of microRNAs were evaluated using in vitro cell-based assay. Among the differentially expressed microRNAs, microRNA-134 (miR-134) expression was positively correlated with AOSD activity scores and significantly decreased after effective treatment. An increased miR-134 level is significantly associated with the activation of Toll-like receptor 3 (TLR3). The reporter assay identified IL-18 binding protein (IL-18BP) as the target of miR-134. A negative correlation between miR-134 expression and IL-18BP mRNA levels were detected in peripheral blood cells following TLR3 ligand treatment. Lower plasma IL-18BP levels and higher IL-18 levels were also observed in active AOSD patients who had higher miR-134 expression than inactive patients. Upregulation of circulating miR-134 was associated with elevated IL-18 levels by targeting IL-18BP in AOSD patients and was positively correlated with disease activity, suggesting its involvement in AOSD pathogenesis. MiR-134 may be a novel activity indicator or potential prognostic biomarker in AOSD.

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 Increasing evidence indicates a pathogenic role of deregulated autophagy in rheumatoid arthritis (RA). We examined the relationship between autophagy and inflammatory parameters in patients with RA receiving biologic therapy. Methods In 72 patients with RA and 20 healthy control subjects (HC), autophagosome levels were determined by the mean fluorescence intensity (MFI) of autophagosomotropic dye incorporated into circulating immune cells, and p62 expression levels in immune cells were measured by flow cytometry. We used immunoblotting to examine protein expression of LC3-II and p62 in peripheral blood mononuclear cells. Results Patients with RA had significantly higher levels of autophagosome reflected by MFI of Cyto-ID in circulating lymphocytes, monocytes, and granulocytes (median values, 3.6, 11.6, and 64.8, respectively) compared with HC (1.9, 6.0, and 35.8; respectively) (all p

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

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.

Rheumatoid arthritis (RA) is associated with a high risk of osteoporosis and fracture. Interleukin (IL)-6 inhibitors may suppress osteoclast activation. Anticitrullinated protein antibody (ACPA) titers are inversely associated with bone mineral density (BMD). However, the differential effect of ACPA on bone turnover marker (BTM) and BMD changes after IL-6 inhibition remains unclear. This prospective study recruited patients with active RA with inadequate response to methotrexate or biologics. BMD was measured before and after 2-year tocilizumab (TCZ) treatment. Serum osteocalcin, N-terminal propeptide of type I collagen (P1NP), and C-terminal cross-linking telopeptide of type I collagen (CTX) levels were assessed at the baseline and after treatment. We enrolled 76 patients with RA (89.5% women, age: 57.2 ± 13.3 years) receiving TCZ. The 28-joint disease activity score was negatively correlated with BMD and T-scores of the lumbar spine and bilateral femoral neck. ACPA-positive patients had lower lumbar spine and femoral neck T-scores. After 2-year TCZ treatment, CTX levels significantly decreased (0.32 ± 0.21 vs. 0.26 ± 0.17, p = 0.038). Femoral neck BMD increased significantly (0.71 ± 0.22 vs. 0.69 ± 0.55, p = 0.008). Decreased CTX levels and improved BMD were observed only in ACPA-positive patients. After treatment, femoral neck BMD significantly increased only in patients receiving a glucocorticoid dose of ≥5 mg/day. Two-year TCZ treatment reduced bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that strict inflammation control might affect bone metabolism.

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.

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

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.

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.