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The objective of this study was to investigate the effect of transcatheter arterial embolization (TAE) with N-butyl-2-cyanoacrylate (NBCA)-Lipiodol mixture in patients with bronchial artery aneurysm (BAA). From January 2005 to January 2010, five patients presenting hemoptysis with six BAAs were treated with NBCA-Lipiodol mixture, including intra-aneurysm embolization (IAE) in one patient. Adjuvant embolization with spherical polyvinyl alcohol (PVA) embolic microparticles or NBCA was first performed to embolize the distal engorged bronchiectatic arteries. Bronchial arterial angiography showed six BAAs (four in the right lobe and two in the left lobe) and some engorged, tortuous bronchial arteries. TAE through microcatheter was successful in all cases. Postembolization angiogram demonstrated the NBCA cast and total occlusion of BAAs and bronchiectatic engorged vessels. After these procedures, hemoptysis completely disappeared in all patients. Follow-up computed tomography (CT) scan was performed at an average of 3 months (range 2 to 6), which showed no enhancement of BAAs and accumulation of NBCA. TAE is a minimally invasive, effective, and reliable approach for treatment for patients with BAA. NBCA-Lipiodol mixture provides a good choice for treatment of BAA, especially when catheterization of the efferent branches is impossible. [ABSTRACT FROM AUTHOR]

Objectives: To report our initial experience of one-stage flexible ureteroscopic lithotripsy(FURL) with 11/13Fr suctioning ureteral access sheath(UAS) and 8.55Fr single-use digital flexible ureteroscope(SDFU) in upper ureteral or renal calculi., Materials and Methods: We retrospectively collected the clinical data of 900 adult patients with upper ureteral or renal calculi treated by FURL with 11/13Fr suctioning UAS and 8.55Fr SDFU from January 2022 to April 2024. Demographics, peri- and postoperative outcomes were assessed., Results: In all, 40 of 940 cases(4.26%) failed to introduce UAS and required second-stage FURL because of ureterostenosis and were excluded. Mean stones size of the remaining 900 eligible cases was 1.68 ± 0.58 cm in greatest diameter. There were 228 cases of upper ureteral stone, 456 cases of renal stone and 216 cases of concomitant ureteral and renal calculi. The mean operation time was 52.20 ± 20.21 min and the postoperative hospital stay was 2.87 ± 1.37 days. The stone-free rate of 1 month postoperatively was 89.56% and only 2.44% of patients with residue underwent additional reoperation. The rate of postoperative fever, postoperative pain needing analgesic and slight ureteral mucosal injury were 5.11%, 8.22% and 7.78%, respectively. None of patient suffered from severe complications, such as sepsis or ureteral perforation., Conclusion: It's practical and suitable for the vast majority of adult patients to undergo FURL in single session with 11/13Fr suctioning UAS without preoperative stenting. FURL with 11/13Fr suctioning UAS and 8.55Fr SDFU is feasible, reliable, safe, and efficient in the management of renal stone and upper ureteral stone., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The objective of this study was to assess the incidence and risk factors of major adverse cardiovascular events (MACEs) in patients with systemic sclerosis (SSc)., Methods: We conducted a nationwide, population-based, cohort study using Taiwan's National Health Insurance Research Database. We performed propensity score matching (PSM) using a 1:2 ratio, resulting in inclusion of 1379 patients with SSc and 2758 non-SSc individuals in the analysis. We assessed the association between SSc and MACEs, using the multivariable Cox proportional hazard regression model with adjustment of time-dependent covariates, and investigated risk factors for MACEs in patients with SSc, shown as adjusted hazard ratios (aHRs) with 95% CIs., Results: SSc was not significantly associated with the risk of MACEs (aHR 1.04; 95% CI 0.77-1.42). Nevertheless, SSc was associated with increased risk of myocardial infarction [incidence rate ratio (IRR) 1.76; 95% CI 1.08-2.86] and peripheral arterial occlusion disease (IRR 3.67; 95% CI 2.84-4.74) but not of ischaemic stroke (IRR 0.89; 95% CI 0.61-1.29). Factors independently associated with MACEs in SSc patients included age (aHR 1.02), male gender (aHR 2.01), living in a suburban area (aHR 2.09), living in a rural area (aHR 3.00), valvular heart disease (aHR 4.26), RA (aHR 2.14), use of clopidogrel (aHR 26.65), and use of aspirin (aHR 5.31)., Conclusions: The risk of MACEs was not significantly increased in Taiwanese patients with SSc, and our investigation effectively identified the factors independently associated with MACEs in SSc patients. Additionally, patients with SSc exhibited higher risks of myocardial infarction and peripheral arterial occlusion disease but not of ischaemic stroke., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Membranous aplasia cutis congenita (MACC) is the most common clinical subtype of aplasia cutis congenita (ACC). It is typified by a localized skin lesion devoid of hair and features a membranous surface. While most MACC individuals do not present with concurrent abnormalities, it can sometimes co-occur with additional physical anomalies and various malformation syndromes. Moreover, the underlying causes of MACC remain elusive., Case Presentation: We describe a case of a 6-month-old female infant diagnosed with MACC. The patient presented with a midline skin lesion on the occipital scalp, characterized by a glistening surface and a hair collar sign. Dermoscopic examination revealed specific features, including translucency, telangiectasia, and hypertrichosis. The infant had a history of patent foramen ovale, and further examination uncovered an asymptomatic ventricular septal defect. Whole exome sequencing revealed 20 gene variants relevant to the clinical phenotype of the patient, suggesting a possible association with MACC., Conclusion: MACC is a rare and underreported condition, primarily diagnosed based on its distinctive clinical features. It is imperative to emphasize the significance of thorough evaluations in MACC patients, encompassing developmental, cardiac, neurological, and genetic assessments to facilitate early detection and the exclusion of potentially life-threatening comorbidities. Importantly, genetic characterization, as demonstrated in this case, contributes to our understanding of MACC's etiology and highlights the need for further research in this field., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The diagnostic process for fibrotic interstitial lung disease (F-ILD) is notably intricate, necessitating a multidisciplinary discussion to achieve consensus based on both clinical and radiological features. This study investigated the shared and distinctive long-term mortality predictors among the two primary phenotypes of F-ILD, namely idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD)., Methods: We included patients with F-ILD diagnosed from December 2018 to December 2019 and conducted follow-up assessments until February 2023. Age, gender, usual interstitial pneumonia (UIP) pattern, gender-age-physiology (GAP) score, modified Medical Research Council (mMRC) dyspnea score, antifibrotic agent use, pulmonary function test parameters, and six-minute walking test (6MWT) parameters were recorded at baseline and used as mortality predictors in a multivariate Cox regression model., Results: We enrolled 104 ILD patients. The survival rate of non-IPF patients was more than twice that of IPF patients (78.9% vs. 34%, p < 0.001), and the survival rate of patients with a GAP score of 0-2 was more than twice that of patients with a score of > 2 (93.2% vs. 36.6%, p < 0.001). Older age, male gender, definite UIP pattern, higher GAP score, higher mMRC dyspnea score, lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC), shorter 6MWT distance, and lower initial and final SpO2 were also associated with higher long-term mortality (p < 0.05). In multivariable analysis, only a GAP score of > 2 (hazard ratio [HR]:16.7; 95% confidence interval [CI] 3.28-85.14; p = 0.001) and definite UIP pattern (HR: 4.08; 95% CI 1.07-15.5; p = 0.039) were significantly associated with overall mortality., Conclusion: The long-term mortality rate of IPF patients was higher than that of CTD-ILD patients. The GAP score and UIP patterns were significant mortality predictors for both IPF and CTD-ILD patients., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients., Methods: From December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction., Results: We enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80-0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73-0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71-0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67-0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03-2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11-10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis., Conclusion: The clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients., (© 2024. The Author(s).)

Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV., (© 2024. The Author(s).)

Introduction: Atypical anti-neutrophil cytoplasmic antibody (a-ANCA) is characterized by a positive fluorescence staining other than typical cytoplasmic or perinuclear ANCA. ANCA is associated with increased risk of dialysis and mortality in patients with ANCA vasculitis. However, comorbidities related to a-ANCA and whether a-ANCA exhibits an increased risk for renal failure and mortality remain unclear. This study aimed to explore the comorbidities and outcome associated with a-ANCA., Materials and Methods: This retrospective study enrolled 164 and 170 patients with typical ANCA and a-ANCA positivity, respectively, who visited Taichung Veterans General Hospital, Taiwan from January 2016 to March 2021. Logistic regression analysis was used to determine risk factors and the rheumatological diagnosis associated with a-ANCA. Cox proportional hazard regression and Kaplan-Meier curves were employed to identify variables associated with 5-year renal survival and mortality., Results: Patients with a-ANCA had lower chance of ANCA-associated vasculitis (OR: 0.02, 95 % CI: 0.01-0.07 p  < 0.001), and systemic lupus erythematosus (OR: 0.23, 95 % CI: 0.11-0.48, p  < 0.001), but a higher risk of rheumatoid arthritis (OR: 2.99, 95 % CI: 1.15-7.83, p  = 0.025) and ulcerative colitis (OR: 5.50, 95 % CI: 1.20-25.29, p  = 0.028). Patients with a-ANCA had a better renal survival (OR: 0.14, 95 % CI: 0.08-0.24, p  < 0.001) and lower mortality (OR: 0.31, 95 % CI: 0.16-0.60, p  = 0.001) than patents in the typical ANCA group. The 5-year renal survival and mortality was 89.3 % and 8.8 %, respectively, in patients with a-ANCA., Conclusion: Patients with a-ANCA had better renal survival and lower mortality rates compared to patients with typical ANCA. These real-world data provide evidence of the long-term outcome and shed light on avenues for the strategic management of patients with a-ANCA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action., Methods: This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi., Results: In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01-0.12, p = 0.016; right, 0.09, 95% CI 0.04-0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02-0.15, p = 0.008; right, 0.11, 95% CI 0.05-0.18, p = 0.001)., Conclusion: Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points •JAKi therapy inhibits systemic bone loss in patients with RA. •ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. •JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Competing Interests: Conflicts of interest None.

Objectives: To assess the association between antirheumatic drugs and of the risk of nonalcoholic fatty liver disease (NAFLD) in a nationwide rheumatoid arthritis (RA) cohort., Methods: Using claim data from the 2000-2020 National Health Insurance Research Database, we identified 21 457 incident patients with RA from 2002 to 2020 without prior liver diseases. A time-varying multivariable Cox regression model was applied to estimate for the association of NAFLD with the use of antirheumatic drugs after adjusting potential confounders, show as adjusted hazard ratios (aHRs) with 95% confidence interval (CIs). Subgroup analyses were conducted based on age-, sex-, and obesity-related comorbidities., Results: Multivariable time-dependent Cox regression analyses showed that defined daily dose (DDD) of NSAID (aHR, 1.03; 95% CI: 1.02-1.05) and prednisolone equivalent dose >5 mg/day (aHR, 2.39; 95% CI: 1.85-3.09) were risk factors of NAFLD in patients with RA, while prednisolone equivalent dose ≤5 mg/day (aHR of 0.53; 95% CI: 0.40-0.71) and HCQ use (aHR of 0.75; 95% CI: 0.60-0.93) were associated with a decreased risk of NAFLD. In addition, a history of hospitalizations, number of outpatient visits, age, male, and leflunomide use were associated with the development of NAFLD in some subgroups., Conclusion: This study reveals that NSAID use and prednisolone equivalent dose >5 mg/day were associated with an increased risk of NAFLD in patients with RA, while the use of HCQ and prednisolone equivalent dose ≤5 mg/day decreased the risk of NAFLD., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: This study aimed to identify risk factors associated with the development of pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE)., Methods: We conducted a systematic literature review of studies focusing on adult patients classified as having SLE-related PAH by searching the electronic databases Embase, Medline, Medline in-progress, Wanfang, China National Knowledge Infrastructure, Ichushi Web, Kmbase, and KoreaMed. Based on the findings, we conducted a Delphi survey to build expert consensus on issues related to screening for PAH in patients with SLE and on the importance and feasibility of measuring the identified factors in clinical practice., Results: We included 21 eligible studies for data synthesis. Sixteen factors were associated with an increased risk of SLE-PAH: pericardial effusion, serositis, longer duration of SLE, arthritis, acute and subacute cutaneous lupus, scleroderma pattern on nailfold capillaroscopy, diffusion capacity of carbon monoxide in the lungs (DLCO) <70% predicted, interstitial lung disease, thrombocytopenia, and seven serological factors. Six factors were associated with a decreased risk of SLE-PAH: malar/acute rash, hematologic disorder, renal disorder, higher Systemic Lupus Erythematosus Disease Activity Index score, and two serological factors. Among these, there were six risk factors on which the panelists reached strong or general consensus (peak tricuspid regurgitation velocity on echocardiography >2.8 m/s, pericardial effusion, DLCO <70% predicted, scleroderma pattern on nailfold capillaroscopy, brain natriuretic peptide >50 ng/l, and N-terminal pro-brain natriuretic peptide >300 ng/l). The Delphi panel confirmed the need for a screening tool to identify patients with SLE at high risk of developing PAH and provided consensus on the importance and/or practicality of measuring the identified factors., Conclusion: The risk factors we identified could be used in a screening algorithm to identify patients with SLE with a high risk of developing PAH to facilitate early diagnosis, which could improve prognosis and management of these patients., (© 2023 Janssen Asia Pacific and The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Metastasis is commonly occurred in gastric cancer, and it is caused and responsible for one of the major cancer-related mortality in gastric cancer patients. Allyl isothiocyanate (AITC), a natural product, exhibits anticancer activities in human many cancer cells, including gastric cancer. However, no available report shows AITC inhibits gastric cancer cell metastasis. Herein, we evaluated the impact of AITC on cell migration and invasion of human gastric cancer AGS cells in vitro. AITC at 5-20 μM did not induce significant cell morphological damages observed by contrast-phase microscopy but decreased cell viability assayed by flow cytometry. After AGS cells were further examined by atomic force microscopy (AFM), which indicated AITC affected cell membrane and morphology in AGS cells. AITC significantly suppressed cell motility examined by scratch wound healing assay. The results of the gelatin zymography assay revealed that AITC significantly suppressed the MMP-2 and MMP-9 activities. In addition, AITC suppressed cell migration and invasion were performed by transwell chamber assays at 24 h in AGS cells. Furthermore, AITC inhibited cell migration and invasion by affecting PI3K/AKT and MAPK signaling pathways in AGS cells. The decreased expressions of p-AKT Thr308 , GRB2, and Vimentin in AGS cells also were confirmed by confocal laser microscopy. Our findings suggest that AITC may be an anti-metastasis candidate for human gastric cancer treatment., (© 2023 Wiley Periodicals LLC.)

Objective: Lupus nephritis (LN), a common manifestation of systemic lupus erythematosus, is associated with a higher risk of kidney failure and death. The renal pathology of LN helps elucidate the severity of inflammation and the extent of irreversible damage. We aimed to identify histologic variables that correlate with risks of kidney failure and mortality., Methods: Between 2006 and 2019, a total of 526 patients with LN were enrolled. Renal pathology was classified according to the International Society of Nephrology/Renal Pathology Society classification. Components of activity and chronicity indices were analyzed to determine which variables correlated with an increased risk of kidney failure and death, with the adjustment of potential confounders., Results: During the follow-up period (median 7.5, IQR 3.5-10.7 years), 58 patients progressed to kidney failure and 64 died. In the multivariate Cox regression analysis, tubular atrophy (hazard ratio [HR] 2.28, 95% CI 1.66-3.14) and tubulointerstitial inflammation (HR 3.13, 95% CI 1.34-7.33) predicted kidney failure. The renal outcome was even worse if tubular atrophy and tubulointerstitial inflammation coexisted (10-year kidney survival rate: 63.22%). The presence of cellular crescents was associated with an increased risk of death in male patients with LN (HR 1.91, 95% CI 1.02-3.57), whereas the presence of fibrous crescents predicted death in female patients with LN (HR 5.70, 95% CI 1.61-20.25)., Conclusion: Histologic variables of renal biopsy in LN could be regarded as prognostic indicators for kidney failure and mortality., (Copyright © 2023 by the Journal of Rheumatology.)

Introduction: Elderly-onset rheumatoid arthritis (EORA) is associated with an increased mortality risk; however, the effect of conventional synthetic, biologics or targeted synthetic disease-modifying anti-rheumatic drugs (csDMARDs, bDMARDs or tsDMARDs) on the EORA-specific mortality risk is unknown. In this study, we investigated the risk factors for all-cause mortality of patients with EORA., Methods: Data of EORA patients diagnosed with RA at age > 60 years between January 2007 and June 2021 were extracted from the electronic health record of Taichung Veterans General Hospital, Taiwan. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The survival of patients with EORA was analyzed by Kaplan-Meier method., Results: Among the 980 EORA patients who were enrolled (survivors 852 and non-survivor 128), the significant mortality-associated risk factors [HR (95% CI)] included higher age (1.10 [1.07-1.12], p < 0.001), male sex (1.92 [1.22-3.00], p = 0.004), current smoker (2.31 [1.10-4.87], p = 0.027) and underlying malignancy (1.89 [1.20-2.97], p = 0.006). Hydroxychloroquine treatment conferred protection against mortality in patients with EORA (HR 0.30, 95% CI 0.14-0.64, p = 0.002). Patients with malignancy who did not receive hydroxychloroquine treatment had the highest mortality risk compared with their counterparts. Patients with a monthly cumulative dose of hydroxychloroquine dose < 1374.5 mg had the lowest survival rate compared to patients who received hydroxychloroquine 1374.5-5778.5 and ≥ 5778.5 mg., Conclusion: Hydroxychloroquine treatment is associated with survival benefits in patients with EORA, and prospective studies are needed to validate the abovementioned findings., (© 2023. The Author(s).)

Background and Aims: We aimed to evaluate the diagnostic performance and prognostic value of disease-specific antibodies and anti-Ro52 using a commercial line immunoblot assay (LIA) in Taiwanese patients with systemic sclerosis (SSc)., Materials and Methods: We retrospectively enrolledall individuals at the Taichung Veterans General Hospital. We evaluated the diagnostic performance of LIA, anti-nuclear antibody (ANA) by indirect immunofluorescence (IIF) and also the association between the autoantibodies and the clinical phenotype using multivariable logistic regression., Results: The LIA exhibited a sensitivity of 65.4% and a specificity of 65.4%, at the optimal cutoff values of 2 + signal intensity. By taking the result of ANA into consideration, the optimal cutoff point was redefined as 1+. We observed a higher risk of diffuse cutaneous SSc (dcSSc) in those with negative autoantibodies, positive anti-Scl-70, anti-RNA polymerase III, and anti-Ro-52. Interstitial lung disease (ILD) was associated with negative autoantibodies, as well as positive anti-Scl-70 and anti-Ro52. Anti-Ro52 positivity was also associated with pulmonary arterial hypertension (PAH) and gastrointestinal tract involvement., Conclusion: The presence of anti-Ro52 or the absence of SSc-specific autoantibodies may potentially indicate advanced diseases in patients with SSc. The incorporation of both IIF and LIA testing may improve the diagnostic specificity of SSc., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Outdoor air pollution has been found to trigger systemic inflammatory responses and aggravate the activity of certain rheumatic diseases. However, few studies have explored the influence of air pollution on the activity of ankylosing spondylitis (AS). As patients with active AS in Taiwan can be reimbursed through the National Health Insurance programme for biological therapy, we investigated the association between air pollutants and the initiation of reimbursed biologics for active AS., Methods: Since 2011, hourly concentrations of ambient air pollutants, including PM2.5, PM10, NO2, CO, SO2, and O3, have been estimated in Taiwan. Using Taiwanese National Health Insurance Research Database, we identified patients with newly diagnosed AS from 2003 to 2013. We selected 584 patients initiating biologics from 2012 to 2013 and 2336 gender-, age at biologic initiation-, year of AS diagnosis- and disease duration-matched controls. We examined the associations of biologics initiation with air pollutants exposure within 1 year prior to biologic use whilst adjusting for potential confounders, including disease duration, urbanisation level, monthly income, Charlson comorbidity index (CCI), uveitis, psoriasis and the use of medications for AS. Results are shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs)., Results: The initiation of biologics was associated with exposure to CO (per 1 ppm) (aOR, 8.57; 95% CI, 2.02-36.32) and NO2 (per 10 ppb) (aOR, 0.23; 95% CI, 0.11-0.50). Other independent predictors included disease duration (incremental year, aOR, 8.95), CCI (aOR, 1.31), psoriasis (aOR, 25.19), use of non-steroidal anti-inflammatory drugs (aOR, 23.66), methotrexate use (aOR, 4.50; 95% CI, 2.93-7.00), sulfasalazine use (aOR, 12.16; 95% CI, 8.98-15.45) and prednisolone equivalent dosages (mg/day, aOR, 1.12)., Conclusions: This nationwide, population-based study revealed the initiation of reimbursed biologics was positively associated with CO levels, but negatively associated with NO 2 levels. Major limitations included lack of information on individual smoking status and multicollinearity amongst air pollutants., (© 2023. The Author(s).)

Objectives: The majority of the cancelled elective surgeries caused by the COVID-19 pandemic globally were estimated to occur in low- and middle-income countries (LMICs), where surgical services had long been in short supply even before the pandemic. Therefore, minimising disruption to existing surgical care in LMICs is of crucial importance during a pandemic. This study aimed to explore contributory factors to the continuity of surgical care in LMICs in the face of a pandemic., Design: Semistructured interviews were conducted over zoom with surgical leaders of 25 tertiary hospitals from 11 LMICs in South and Southeast Asia in September to October 2020. Key themes were subsequently identified from the interview transcripts using the Braun and Clarke's method of thematic analysis., Results: The COVID-19 pandemic affected all surgical services of participating institutions to varying degrees. Overall, elective surgeries suffered the gravest disruption, followed by outpatient surgical care, and finally emergency surgeries. Keeping healthcare workers safe and striving for continuity of essential surgical care emerged as notable response strategies observed across all participating institutions., Conclusion: This study suggested that four factors are important for the resilience of surgical care against COVID-19: adequate COVID-19 testing capacity and effective institutional infection control measures, designated COVID-19 treatment facilities, whole-system approach to balancing pandemic response and meeting essential surgical needs, and active community engagement. These findings can inform healthcare institutions in other countries, especially LMICs, in their effort to tread a fine line between preserving healthcare capacity for pandemic response and protecting surgical services against pandemic disruption., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Serious infections are an important concern for patients with autoimmune conditions. We sought to estimate serious infection rates among patients with select autoimmune conditions relative to the general population in Taiwan and the USA., Methods: This retrospective cohort study estimated setting-specific standardized serious infection incidence rates and ratios among patients with systemic lupus erythematosus, including extra-renal lupus and lupus nephritis, rheumatoid arthritis and primary membranous nephropathy, compared with the general population using insurance claims for hospitalizations between 2000 and 2013. Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios for serious infections, adjusting for age, sex, index year, prior serious infection, comorbidities and medications., Results: In Taiwan, serious infection rates were 22.7, 28.7, 70.6, 43.4 and 215.3 per 1000 person-years among the general population and among cohorts of patients with primary membranous nephropathy, rheumatoid arthritis, extra-renal lupus and lupus nephritis, respectively. In the USA, serious infection rates were 2.6, 9.0, 15.6, 21.0 and 63.3 per 1000 person-years among the general population and among cohorts of patients with primary membranous nephropathy, rheumatoid arthritis, extra-renal lupus and lupus nephritis, respectively. Patients had significantly higher serious infection rates than the general population in both settings, largely driven by bacterial, respiratory, urinary tract and opportunistic infections. Patients with lupus nephritis had the highest burden of serious infections relative to the general population, with 7- to 25-fold higher adjusted hazard ratios in Taiwan and the USA, respectively., Conclusion: This study identified a significant excess serious infection burden among patients with targeted autoimmune conditions compared with the general populations in Taiwan and the USA., (© 2022. The Author(s).)

Background: Hyperuricemia and gout are risk factors of nephrolithiasis. However, it is unclear whether the ABCG2 gene contributes to the development of nephrolithiasis. We aimed to investigate the interaction between the ABCG2 rs2231142 variant and incident nephrolithiasis in the Taiwanese population., Methods: A total of 120,267 adults aged 30-70 years were enrolled from the Taiwan Biobank data-base in this retrospective case-control study and genotyped for rs2231142. The primary outcome was the prevalence of self-reported nephrolithiasis. The odds ratio (OR) of incident nephrolithiasis was analyzed by multivariable logistic regression models with adjustment for multifactorial confounding factors. Associations of the ABCG2 rs2231142 variant with serum uric acid levels, and the incident nephrolithiasis were explored., Results: The frequency of rs2231142 T allele was 53%, and 8,410 participants had nephrolithiasis. The multivariable-adjusted OR (95% confidence interval) of nephrolithiasis was 1.18 (1.09-1.28) and 1.12 (1.06-1.18) for TT and GT genotypes, respectively, compared with the GG genotype ( p <0.001), specifically in the male population with hyperuricemia. Higher age, male sex, hyperlipidemia, hypertension, diabetes mellitus, hyperuricemia, smoking and overweight were independent risk factors for nephrolithiasis. In contrast, regular physical exercise is a protective factor against nephrolithiasis., Conclusions: ABCG2 genetic variation is a significant risk of nephrolithiasis, independent of serum uric acid levels. For rs2231142 T allele carriers, our result provides evidence for precision healthcare to tackle hyperuricemia, comorbidities, smoking, and overweight, and recommend regular physical exercise for the prevention of nephrolithiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Chen, Chen, Lin, Chang, Wang, Huang, Chen, Chen, Lin and Chen.)

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS., (© 2023. The Author(s).)

Background: Aspergillus diseases are frequently encountered in patients who are immunocompromised. Without a prompt diagnosis, the clinical consequences may be lethal. Aspergillus -specific antibodies have been widely used to facilitate the diagnosis of Aspergillus diseases. To date, universally standardized cut-off values have not been established. This study aimed to investigate the cut-off values of Aspergillus -specific antibodies and perform a narrative review to depict the geographic differences in the Taiwanese population., Methods: We analyzed enrolled 118 healthy controls, 29 patients with invasive aspergillosis (IA), chronic pulmonary aspergillosis (CPA), and allergic bronchopulmonary aspergillosis (ABPA) and 99 with disease control, who were tested for Aspergillus fumigatus and Aspergillus niger -specific IgG and IgE using ImmunoCAP. 99 participants not fulfilling the diagnosis of IA, CPA, and ABPA were enrolled in the disease control group. The duration of retrieval of medical records from June 2018 to September 2021. Optimal cut-offs and association were determined using receiver operating characteristic curve (ROC) analysis., Results: We found that patients with CPA had the highest A. fumigatus -specific IgG levels while patients with ABPA had the highest A. fumigatus -specific IgE, and A. niger -specific IgG and IgE levels. In patients with CPA and ABPA, the optimal cut-offs of A. fumigatus -specific IgG and A. niger -specific IgG levels were 41.6, 40.8, 38.1, and 69.9 mgA/l, respectively. Geographic differences in the cut-off values of A. fumigatus -specific IgG were also noted. Specifically, the levels were different in eco-climatic zones., Conclusion: We identified the optimal cut-offs of Aspergillus -specific antibodies to facilitate a precise diagnosis of aspergillosis. The observed geographic differences of the antibody levels suggest that an eco-climatic-specific reference is needed to facilitate a prompt and accurate diagnosis of aspergillosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hsiao, Yen, Wu, Chen, Chen, Huang, Chen and Chen.)

Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in Azathioprine (AZA) metabolization. Although studies have discussed the association between the TPMT polymorphisms and myelosuppression, the data about the relationship between TPMT genotypes and hepatoxicity in Asian patients remain limited. This study investigated the correlation between TPMT polymorphisms and AZA-related hepatotoxicity. This study enrolled the patients who had prior exposure to AZA from the Taichung Veterans General Hospital (TCVGH)-Taiwan Precision Medicine Initiative (TPMI) cohort. Genetic variants were determined using a single nucleotide polymorphism (SNP) array. Participants were accordingly categorized into normal metabolizer (NM) and non-normal metabolizer (non-NM) groups. From the TCVGH-TPMI cohort, we included 50 TPMT non-NM patients, including 1 poor metabolizer (PM), 49 intermediate metabolizers (IMs), and 1000 NM patients. The non-NM genotype was associated with hepatotoxicity compared with the NM genotype (hazard ratio (HR): 3.85, 95% confidence interval (CI): 1.83−8.10). In the non-NM group, the 3-year cumulative incidence of hepatotoxicity was higher than that in the NM group at 8.5% in the first year and 18.6% in the second and third years (p < 0.001). A TPMT non-NM genotype was associated with the occurrence of hepatotoxicity following AZA therapy. Preemptive testing helps individualize AZA therapy by minimizing the risk of hepatotoxicity.

Objectives: To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq)., Methods: From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis., Results: The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16 - monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group., Conclusions: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16 - monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Cheng, Huang, Chen, Chen, Chen, Lin, Tang, Hung, Hsieh, Chen, Chen and Hsiao.)

There is a gap between medical resources and patient needs, Managers need to obtain productivity information to optimize resources allocation. The value of this research is that the information provided by the dashboard allows hospital managers problems respond to it quickly. We recommend the research could integrate more data (such as temperature data, national death population data record), so as to be closed to hospital operating cost control and to estimate patients' needs.

Objectives: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort., Methods: From November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5)., Results: In our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively., Conclusion: We propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Huang, Chen, Lai, Hsieh, Hung, Lin, Tseng, Tang, Chou, Wu, Huang, Hsieh, Chen, Liao and Chen.)

Background: Potential risk factors for major adverse cardiovascular events (MACE) in patients with ankylosing spondylitis (AS) requiring medical therapy should be investigated. Methods: We identified newly diagnosed AS patients without previous MACE from 2004 to 2012 using the National Health Insurance Research Database, matched MACE cases with non-MACE controls at a 1:4 ratio for age, gender, AS duration, and index date, and included 947 AS patients with MACE and 3896 matched controls for final analyses. By using conditional logistic regression analyses, we examined the associations of MACE with low income, urbanisation, comorbidities, common extra-articular manifestations (EAM), and medications, including nonsteroidal anti-inflammatory drugs (NSAID) of three categories (traditional NSAIDs, selective cyclooxygenase-2 inhibitors (COX-2i), and preferential COX-2is) with their annual cumulative defined daily dose (cDDD) within a year before MACE development. Results: MACE development was associated with the use of selective COX-2is (especially with annual cDDD > 132) and corticosteroids, residence in rural regions, and well-known associated comorbidities, but not with the use of traditional NSAIDs, preferential COX-2i, biologics, methotrexate, sulfasalazine, and common EAMs. Conclusions: The risk factors of MACE in newly diagnosed AS patients include residence in rural regions, well-known associated comorbidities, and the use of corticosteroids and selective COX-2is. A major limitation was the lack of information on individual lifestyle patterns and disease activity.

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Several factors have been found to be predictors of a good response following omalizumab treatment in patients with severe allergic asthma (SAA). However, it remains unclear whether clinical characteristics can predict a minimal clinically important difference (MCID) following omalizumab treatment in this population. Therefore, the aim of this study was to investigate the features associated with an MCID following omalizumab treatment in adult patients with SAA. Of the 124 participants enrolled in this retrospective, cross-sectional study, 94, 103, 20 and 53 achieved the MCID following treatment with omalizumab and were considered to be responders of exacerbation reduction (no exacerbation during the 1-year follow-up period or ≧50% reduction in exacerbations from baseline), oral corticosteroid (OCS) sparing (no use of OCS to control asthma during the study period or a reduction of the monthly OCS maintenance dose to <50% of baseline), lung function (an increase of ≧230 ml in the forced expiratory volume in 1 s from baseline) and asthma control (an increase of ≧3 points in the asthma control test score from baseline), respectively. Normal weight [<25 vs. ≧30 kg/m 2 , odds ratio (OR) = 3.86, p = 0.024] was predictive of a responder of reduction in exacerbations following omalizumab treatment while subjects with a blood eosinophil level of <300 cells/μL (<300 vs. ≧300 cells/μL, OR = 5.81, p = 0.001) were more likely to exhibit an MCID in OCS sparing. No factor was found to be a predictor of lung function or asthma control. When choosing treatment for adult patients with SAA, our findings may help to select those who may benefit the most from omalizumab treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Fu, Chan, Chin, Huang, Lai, Wang, Hung, Wu, Hsieh, Wu, Chen and Hsu.)

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.

This study aimed to compare the test results of anti-double-stranded DNA (anti-dsDNA) antibodies obtained using chemiluminescent immunoassay (CIA) and enzyme-linked immunosorbent assay (ELISA), and investigate predictors of inconsistent results. This retrospective study included 502 patients who underwent CIA and ELISA to determine their anti-dsDNA antibody values within a year. We compared the diagnostic power for SLE, disease activity, and predictive power for lupus nephritis (LN). A multivariate analysis was performed to determine the predictors of inconsistencies. CIA and ELISA were moderately correlated in terms of their consistency (Cronbach's α = 0.571), and yielded comparably favorable results in terms of SLE diagnostic power and SLE disease activity. However, if the patient had LN, CIA displayed higher predictive power than ELISA (0.620 vs. 0.555, p = 0.026). Compared with the CIA/ELISA double-positive group, the inconsistent group had lower anti-C1q circulating immune complexes (CIC) antibody values (OR: 0.42, 95% CI: 0.18-0.94, p = 0.036), and lower SLEDAI scores (≥4) (OR: 0.33, 95% CI: 0.14-0.79, p = 0.013). Anti-dsDNA antibody detection with CIA exhibited higher predictability for diagnosing LN than did ELISA. In the event of inconsistencies between anti-dsDNA methods, SLE disease activity and CIC test values should be considered simultaneously.

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.

The risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after glucocorticoid (GC) pulse therapy remains unclear., Aims: Our study aimed to examine the safety of GC pulse therapy in HBsAg-negative, anti-HBc-positive rheumatic patients., Methods: Medical records of HBsAg-negative, anti-HBc-positive patients receiving GC pulse therapy to treat rheumatic diseases were reviewed. The primary outcome was HBV-associated hepatitis occurring within the first year after GC pulse therapy; the secondary outcome was HBsAg seroreversion occurring during the follow-up period., Results: We identified 5222 HBsAg-negative, anti-HBc-positive patients with rheumatic diseases who had attended Taichung Veterans General Hospital from October 2006 to December 2018. A total of 689 patients had received GC pulse therapy, with 424 patients being analyzed. Hepatitis was noted in 28 patients (6.6%) within the first year after GC pulse therapy, but none had been diagnosed as HBV-associated hepatitis. Three patients (0.7%) later developed HBsAg seroreversion, with a median interval of 97 months from the first episode of GC pulse therapy. These cases concurrently had maintained high dose oral prednisolone (≥20 mg prednisolone daily for over 4 weeks)., Conclusions: Amongst the HBsAg-negative, anti-HBc-positive rheumatic patients treated with GC pulse therapy, the risk of HBV-associated hepatitis within the first year was low. HBsAg seroreversion may have developed in the later stage, but only in those patients who had maintained high-dose oral steroid.

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Antinuclear antibody pattern recognition is vital for autoimmune disease diagnosis but labor-intensive for manual interpretation. To develop an automated pattern recognition system, we established machine learning models based on the International Consensus on Antinuclear Antibody Patterns (ICAP) at a competent level, mixed patterns recognition, and evaluated their consistency with human reading., Methods: 51,694 human epithelial cells (HEp-2) cell images with patterns assigned by experienced medical technologists collected in a medical center were used to train six machine learning algorithms and were compared by their performance. Next, we choose the best performing model to test the consistency with five experienced readers and two beginners., Results: The mean F1 score in each classification of the best performing model was 0.86 evaluated by Testing Data 1. For the inter-observer agreement test on Testing Data 2, the average agreement was 0.849 (κ) among five experienced readers, 0.844 between the best performing model and experienced readers, 0.528 between experienced readers and beginners. The results indicate that the proposed model outperformed beginners and achieved an excellent agreement with experienced readers., Conclusions: This study demonstrated that the developed model could reach an excellent agreement with experienced human readers using machine learning methods.

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.

(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA). The mitochondrial-produced formate is essential for folate-mediated one carbon (1C) metabolism. The impacts of MTX on formate homeostasis in unknown, and rigorously controlled kinetic studies can greatly help in this regard. (2) Methods: Combining animal model (8-week old female C57BL/6JNarl mice, n = 18), cell models, stable isotopic tracer studies with gas chromatography/mass spectrometry (GC/MS) platforms, we systematically investigated how MTX interferes with the partitioning of mitochondrial and cytosolic formate metabolism. (3) Results: MTX significantly reduced de novo deoxythymidylate (dTMP) and methionine biosyntheses from mitochondrial-derived formate in cells, mouse liver, and bone marrow, supporting our postulation that MTX depletes mitochondrial 1C supply. Furthermore, MTX inhibited formate generation from mitochondria glycine cleavage system (GCS) both in vitro and in vivo. Folinate selectively rescued 1C metabolic pathways in a tissue-, cellular compartment-, and pathway-specific manner: folinate effectively reversed the inhibition of mitochondrial formate-dependent 1C metabolism in mouse bone marrow (dTMP, methionine, and GCS) and cells (dTMP and GCS) but not methionine synthesis in liver/liver-derived cells. Folinate failed to fully recover hepatic mitochondrial-formate utilization for methionine synthesis, suggesting that the efficacy of clinical folinate rescue in MTX therapy on hepatic methionine metabolism is poor. (4) Conclusion: Conducting studies in mouse and cell models, we demonstrate novel findings that MTX specifically depletes mitochondrial 1C supply that can be ameliorated by folinate supplementation except for hepatic transmethylation. These results imply that clinical use of low-dose MTX may particularly impede 1C metabolism via depletion of mitochondrial formate. The MTX induced systematic and tissue-specific formate depletion needs to be addressed more carefully, and the efficacy of folinate with respect to protecting against such depletion deserves to be evaluated in medical practice.

Background/purpose: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan., Methods: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR)., Results: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 10 3 /uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353., Conclusion: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: Hyperspectral imaging (HSI) is a novel technology for obtaining quantitative measurements from transcutaneous spatial and spectral information. In patients with SSc, the severity of skin tightness is associated with internal organ involvement. However, clinical assessment using the modified Rodnan skin score is highly variable and there are currently no universal standardized protocols. This study aimed to compare the ability to differentiate between SSc patients and healthy controls using skin scores, ultrasound and HSI., Methods: Short-wave infrared light was utilized to detect the spectral angle mapper (SAM) of HSI. In addition, skin severity was evaluated by skin scores, ultrasound to detect dermal thickness and strain elastography. Spearman's correlation was used for assessing skin scores, strain ratio, thickness and SAM. Comparisons of various assessment tools were performed by receiver operating characteristic curves., Results: In total, 31 SSc patients were enrolled. SAM was positively correlated with skin scores and dermal thickness. In SSc patients with normal skin scores, SAM values were still significantly higher than in healthy controls. SAM exhibited the highest area under the curve (AUC: 0.812, P < 0.001) in detecting SSc compared with skin scores (AUC: 0.712, P < 0.001), thickness (AUC: 0.585, P = 0.009) and strain ratio by elastography (AUC: 0.522, P = 0.510). Moreover, the severity of skin tightness was reflected by the incremental changes of waveforms in the spectral diagrams., Conclusion: SAM was correlated with skin scores and sufficiently sensitive to detect subclinical disease. HSI can be used as a novel, non-invasive method for assessing skin changes in SSc., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.

Objective: To assess interstitial lung disease (ILD) risk among patients newly diagnosed with systemic autoimmune rheumatic diseases (SARDs) including rheumatoid arthritis (RA), dermatomyositis (DMtis), polymyositis (PM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS)., Method: Using the 1997-2013 Taiwanese National Health Insurance Research Database, we identified 62,930 newly diagnosed SARD patients from 2001 to 2013. We selected 251,720 individuals without SARD diagnoses who were matched (1:4) with SARD patients by age, sex and year of index date. We compared the incidence rates (IRs) of ILD (consistent diagnosis with ICD-9 code 515, 516.3, 516.8, 516.9 or 517 after a ILD-related radiological or pathological procedure) between the specific SARD subgroups and the corresponding non-SARD comparison groups. Using multivariable Cox regression analyses, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of ILD in the various SARD groups compared with comparison groups after adjusting for age, sex and Charlson comorbidity index., Results: The IR of ILD was greatest among patients with SSc (1,364 per 10 5 years), followed by DMtis (1,011 per 10 5 years), PM (831 per 10 5 years), pSS (196 per 10 5 years), RA (109 per 10 5 years) and SLE (120 per 10 5 years). Multivariable analyses showed that the risk of ILD was increased among patients with SSc (HR, 172.63), DMtis (HR, 119.61), PM (HR, 84.89), SLE (HR, 32.18), pSS (HR, 17.54), or RA (HR, 8.29)., Conclusion: This population-based, cohort study demonstrates that the risk of ILD is significantly increased in patients with newly diagnosed SARDs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/aim: Demethoxycurcumin (DMC), a derivate of curcumin from natural plants, exerts antitumor effects on various human cancer cells in vitro and in vivo. Nevertheless, no reports have disclosed whether DMC can affect the growth of human cervical cancer cells in vivo. Therefore we investigated the antitumor effects of DMC on a HeLa cell xenograft model in nude mice in this study., Materials and Methods: Twenty-four nude mice were subcutaneously injected with HeLa cells. All mice were randomly divided into control, low-dose DMC (30 mg/kg), and high-dose DMC (50 mg/kg) groups and individual mice were treated intraperitoneally accordingly every 2 days., Results: DMC significantly reduced tumor weights and volumes of HeLa cell xenografts in mice, indicating the suppression of growth of xenograft tumors., Conclusion: These effects and findings might provide evidence for investigating the potential use of DMC as an anti-cervical cancer drug in the future., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Reducing nosocomial transmission within health care facilities is important, but the number of negative-pressure airborne infection isolation rooms for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is limited. It is a daunting challenge to cope with a surge of suspected infectious patients in hospitals. We installed air exhaust fans on the windows to change the pressure direction within the wards rapidly. The best location for the fans was 90 cm from the floor and 90 cm from the edge of bed whether the indoor air conditioners were on or off. The noise level should be <60 dB(A) as per government regulations. General wards can be transformed into makeshift negative-pressure rooms easily and effectively within 24 hours, which is really the simple, fast, and effective way for the transformation being applied.

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Risk factors for sepsis have not been assessed in patients receiving tumor necrosis factor-alpha inhibitors (TNFi) for immune-mediated inflammatory diseases (IMIDs) who are vulnerable to serious/hospitalized infections., Methods: Data from 2003-2017 were obtained from Taiwan's National Health Insurance Research Database to identify patients receiving TNFi, including etanercept, adalimumab, and golimumab, for IMIDs including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis (PsO), psoriatic arthritis (PsA), Crohn's disease (CD), and ulcerative colitis (UC). To investigate risk factors for sepsis, we used the Sepsis-3 definition and calculated hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression analysis., Results: There were 17,764 patients (mean age 49.3 ± 14.3 years; females, 57.6%) receiving TNFi for IMIDs, including RA (58.6%), AS (19.1%), PsO (15.1%), PsA (2.5%), CD (3.0%), and UC (1.7%). The overall incidence rate of sepsis was 1088 per 100,000 person-years. After adjustment for potential confounders, recent sepsis within 3 months before TNFi initiation (HR, 2.35; 95% CI, 1.73-3.20), CD (HR, 3.36; 95% CI 2.11-5.34; reference group: AS) and glucocorticoid use (prednisolone-equivalent dose, mg/day HR, 1.05; 95% CI, 1.05-1.06) were associated with the risk of sepsis. Intriguingly, golimumab users appeared to have a lower risk of sepsis compared with etanercept users (HR, 0.56; 95% CI, 0.38-0.83). In addition, socioeconomic status, including urbanization level and insured amount, was associated with sepsis in a dose-response manner., Conclusions: Recent sepsis, CD, concomitant glucocorticoid use, and low socioeconomic status, which were associated with an increased risk of sepsis, are crucial for individualized risk management plans., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)