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This article discusses a case study of a 25-year-old woman who presented with symptoms of chronic leg edema, erythema nodosum, cough, and numbness in her limbs. Further investigation revealed pneumonia, empyema, subclavian artery thrombosis, spleen and kidney infarctions, and left ventricular thrombi. The patient was diagnosed with Takayasu's arteritis, a systemic vasculitis, and received treatment with anticoagulation and immunosuppression. The article emphasizes the importance of considering Takayasu's arteritis as a potential cause of unexplained heart failure in young women. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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)-1ß compared with PBMCs from healthy controls. B19-NS1 stimulation of PBMCs from patients with AOSD induced significant increase in supernatant levels of IL-1ß and protein expression of NLRP3, caspase-1, IL-1ß, 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-1ß and IL-18 through activation of caspase-1-associated NLRP3-inflammasome in AOSD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still’s disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome. Methods: Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites. Results: Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05). Conclusion: Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis. [ABSTRACT FROM AUTHOR]

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<0.001). Rising levels of neopterin relative to baseline (non-stimulated levels, 4.4pg/ml vs. 24.5pg/ml; TB-antigen-stimulated levels, 1801pg/ml vs. 23053pg/ml) were observed in QFT-G converters who developed TB. A high proportion (85.7%) of QFT-G converters with high plasma neopterin levels developed TB during the one-year follow-up period. In conclusion, RA patients with QFT-G conversion during the period of biologic therapy should be carefully monitored for elevation of neopterin levels, which is associated with TB risk in QFT-G converters, particularly in TB-endemic areas. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigates the role played by high-mobility group box 1 (HMGB1) chromatin-binding protein in the differentiation between disease flares and infections in patients with systemic lupus erythematosus (SLE). The study used an enzyme-linked immunosorbent assay (ELISA) to measure the serum levels of HMGB1. Results show no significant difference between the serum HMGB1 levels in patients with bacterial infections with SLE patients with disease flares.

Objective. To determine circulating levels of CD4+CD25high regulatory T (Treg) cells and transforming growth factor-β (TGF-β) in patients with adult-onset Still's disease (AOSD) and to examine the associations with disease activity and clinical course of this disease. Methods. The frequencies of circulating CD4+CD25high Treg cells in 52 active AOSD patients, 42 active systemic lupus erythematosus (SLE) patients, and 22 healthy controls (HCs) were determined using flow cytometry analysis. Levels of serum TGF-β and soluble interleukin-2 receptor (sIL-2R) were measured by enzyme-linked immunosorbent assay. Results. Significantly lower levels of circulating CD4+CD25high Treg cells and serum TGF-β were found in AOSD patients and SLE patients than those found in HCs. Levels of circulating CD4+CD25high Treg cells and TGF-β were inversely correlated with disease activity scores for AOSD patients and SLE patients. Circulating CD4+CD25high Treg cell frequencies were positively correlated with serum TGF-β levels for patients with both diseases. Levels of circulating CD4+CD25high Treg cells and TGF-β significantly increased, paralleling clinical remission and the decrease in levels of C-reactive protein and soluble interleukin-2 receptor after effective therapy in AOSD patients. AOSD patients with monocyclic course had significantly higher levels of circulating CD4+CD25high Treg cells and TGF-β compared to those with polycyclic and chronic articular course. Conclusion. Diminished levels of circulating CD4+CD25high Treg cells and TGF-β, and inverse correlation with disease activity in patients with AOSD and SLE might be involved in the pathogenesis of both diseases. Increased levels of circulating CD4+CD25high Treg cells or TGF-β might be associated with a favorable clinical course in AOSD patients. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Background/purpose: Adalimumab is a fully humanized monoclonal antibody that blocks tumor necrosis factor (TNF)-alpha, which is effective in the treatment of patients with rheumatoid arthritis (RA). The purpose of this study was to compare the efficacy and safety of adalimumab plus methotrexate (MTX) and MTX alone in Taiwanese patients with active RA.Methods: Forty-seven patients with active RA who were maintained on MTX therapy at a stable dose of 10-15 mg/week for 4 weeks were randomized blindly to receive adalimumab 40 mg (n = 35) or placebo (n = 12) by subcutaneous injection every other week over a period of 12 weeks. The primary endpoint was a reduction in tender and swollen joint counts of 20% (ACR20), 50% (ACR50) and 70% (ACR70), as determined by the American College of Rheumatology criteria in week 12. The occurrence of treatment-emergent adverse events (TEAEs) was the primary safety variable.Results: Addition of adalimumab to MTX resulted in a significant reduction in the number of swollen joints (12.6 vs. 5.6; p = 0.011), patients' global assessment of disease activity (18.0 vs. 4.8; p = 0.040), pain visual analog scale (18.3 vs. 1.3; p = 0.015), and disability indices of the Health Assessment Questionnaire (0.6 vs. 0.2; p = 0.031), compared with MTX alone after 12 weeks of therapy. Overall improvement in disease activity was assessed by ACR20 (54.3% vs. 33.3%), ACR50 (34.3% vs. 16.7%) and ACR70 (14.3% vs. 0%), and all favored the adalimumab plus MTX group. TEAEs were comparable between the treatment groups, except for a slightly higher incidence of severe infection in the adalimumab plus MTX group.Conclusion: Adalimumab in combination with MTX is well tolerated and provides significantly more clinical benefits than MTX alone in Taiwanese patients with active RA. [ABSTRACT FROM AUTHOR]

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

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

Sarcoidosis is a granulomatous multisystem disorder that rarely involves muscle. Although characteristic ultrasound features of nodular-type muscular sarcoidosis have been reported, observations for such lesions at different disease stages are limited. We report ultrasonographic findings for nodular-type muscular sarcoidosis at 3 months and 1 year after the onset of disease in the left medial gastrocnemius muscle of a 35-year-old woman. A hypoechoic mass was initially detected in the involved muscle, and central echogenicity appeared later. It is, therefore, considered that ultrasonography can be a valuable tool in detecting and following up nodular-type muscular sarcoidosis lesions. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 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 < 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Abstract: Background: 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. Objectives: To investigate the association of EBV with PM/DM and NPC in PM/DM patients. Study design: 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. Results: 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 p <0.001). Significantly higher positivity for IgA anti-EBNA-1 were observed in PM/DM with NPC than in those without malignancy (OR 44.7, p <0.01). Significantly higher positivity for EBV genome were observed in PM/DM with NPC than in those without malignancy (OR 43.9, p <0.01), in SLE patients (OR 13.2, p <0.05) and in HC (OR 99.4, p <0.001). EBV DNA loads were significantly higher in PM/DM with NPC compared with those without malignancy and HC. Conclusions: 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. [ABSTRACT FROM AUTHOR]