Although pulmonary hypertension (PH) and interstitial lung disease (ILD) are major contributors to mortality in patients with connective tissue disease (CTD), data on concomitant PH specifically in those with CTD-associated ILD (CTD-ILD) remain limited. We aimed to identify predictors for PH development in CTD-ILD patients, and assess their impact on survival in this population. This retrospective observational study included 224 patients with CTD-ILD, confirmed through multidisciplinary discussion, including patients with inflammatory myopathy-associated ILD (IIM-ILD, n = 88), systemic sclerosis-associated ILD (SSc-ILD, n = 57), rheumatoid arthritis-associated ILD (RA-ILD, n = 55), and primary Sjögren’s syndrome-associated ILD (pSS-ILD, n = 24). PH was diagnosed using right heart catheterization (RHC) or, in patients unable to undergo RHC, by transthoracic echocardiography. Autoantibodies related to IIM and SSc were assessed using Euroimmun immunoblot assays. Among CTD-ILD patients, 28 (12.5

Formyl peptide receptor 1 (FPR1), activated by N-formyl peptides, significantly contributes to neutrophil activation and the development of acute respiratory distress syndrome (ARDS). This study showed that butyrolactone I (BLI), a secondary metabolite of Aspergillus terreus, effectively blocks FPR1 and reduces the severity of ARDS. BLI selectively inhibited superoxide anion production, elastase release, cluster of differentiation molecule 11b (CD11b) expression, and chemotaxis in human neutrophils activated by N-formyl peptides derived from bacteria and mitochondria. The FPR1 receptor-binding and molecular docking assays confirmed that BLI acted as an FPR1 inhibitor. Pharmacological experiments demonstrated that BLI selectively inhibited FPR1 downstream signals in human neutrophils, including calcium mobilization and phosphorylation of protein kinase B (Akt), c-Jun N-terminal kinases (JNK), extracellular regulated protein kinases (ERK), and p38 mitogen-activated protein kinases (p38). In a mouse model of ARDS, treatment with BLI reduced neutrophil infiltration, oxidative damage, and levels of elastase and interleukin-1 beta (IL-1β) in the lungs. The fungal compound BLI could serve as a potential treatment for ARDS by blocking FPR1 and reducing neutrophil-induced injury.

BackgroundAngiostrongylus cantonensis is a zoonotic nematode that causes eosinophilic meningitis and central nervous system injury in humans; 3-hydroxybenzaldehyde (3-HBA) is a benzaldehyde compound that exhibits antioxidant and anti-inflammatory activities. Brain injury promotes Ca²⁺ influx and mitochondrial Ca²⁺ loading via voltage-dependent anion channel 1 (VDAC1) and the mitochondrial Ca²⁺ uniporter (MCU), leading to mitochondrial dysfunction and cytochrome c-mediated apoptosis.Methodology/principal findingsThis study aimed to evaluate the therapeutic effects of 3-HBA combined with albendazole on brain injury and the expression of mitochondria-related molecules in A. cantonensis-infected mice. In BALB/c mice infected with A. cantonensis, the infection significantly increased glial fibrillary acidic protein expression in five regions: the cerebral cortex, hippocampus, subcortical areas, cerebellum, and brainstem and elevated the expression of MCU and cytochrome c in the cerebral cortex and hippocampus. Hematoxylin and eosin staining revealed pathological changes, such as meningitis, hemorrhage, and vascular congestion. However, combined treatment with 3-HBA and albendazole reduced these pathological changes and the expression of mitochondria-related molecules, including glial fibrillary acidic protein, VDAC1, MCU, and cytochrome c. In cultured mouse astrocytes, soluble antigens from fifth-stage larval-activated astrocytes induced mitochondria-related molecule expression, but 3-HBA suppressed these effects.Conclusions/significanceThese results suggest that the combination of 3-HBA and albendazole downregulates astrocyte activation and VDAC1/MCU-associated mitochondrial pathways following A. cantonensis infection. These findings support the use of 3-HBA as a promising adjuvant to albendazole in the treatment of angiostrongyliasis.

Abstract The role of zinc finger protein 334 (ZNF334) in immunological processes remains unknown. We identified a ZNF334 truncation mutation (p.Thr399fs) in a rare case of late-onset cold-induced autoinflammatory disease with elevated TNF-α, IL-1β, IL-6, and extracellular heat shock protein 90 (eHsp90) plasma levels and progressive sensorineural hearing loss. Using patient-derived monocytes and CRISPR/Cas9-edited THP-1 monocytes with a ZNF334 truncation mutation, we discovered that the mutation reduced the interaction between ZNF334 and Hsp90, diminished the endogenous levels of the cold stress regulators Hsp90 and transient receptor potential melastatin 8 (TRPM8), disrupted ER protein folding response and redox homeostasis, and increased cold-induced NF-κB activation and secretion of the proinflammatory TRPM8+ mitochondria-containing extracellular vesicles in monocytes. Long-term cold avoidance alleviated the patient’s cold-induced symptoms. In addition, treatment of ZNF334-truncated THP-1 cells with an Hsp90 inhibitor prevented cold-induced TNF and NLRP3 upregulations. Our findings suggest ZNF334 as an essential regulator of cold-induced inflammation and oxidative stress, and Hsp90 ATPase inhibitors might be effective in the treatment of autoinflammatory diseases induced by repeated mild cold exposure.

Background: The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides derived from the medicinal fungus Hirsutella sinensis produced anti-inflammatory, anti-diabetic and anti-obesity effects by modulating the gut microbiota and increasing the abundance of the commensal Parabacteroides goldsteinii in mice fed with a high-fat diet. Methods: We examined the effects of the prebiotics, H. sinensis polysaccharides, and probiotic, P. goldsteinii, in a mouse model of imiquimod-induced systemic lupus erythematosus. Results: The fungal polysaccharides and P. goldsteinii reduced markers of lupus severity, including the increase of spleen weight, proteinuria, and serum levels of anti-DNA auto-antibodies and signal transducer and activator of transcription 4 (STAT4). Moreover, the polysaccharides and P. goldsteinii improved markers of kidney and liver functions such as creatinine, blood urea nitrogen, glomerulus damage and fibrosis, and serum liver enzymes. However, the prebiotics and probiotics did not produce consistent improvements in gut microbiota composition, colonic histology, or expression of tight junction proteins in colon tissues. Conclusions: Our results indicate that H. sinensis polysaccharides and the probiotic P. goldsteinii can reduce lupus markers in imiquimod-treated mice. These prebiotics and probiotics may therefore be added to other interventions conducive of a healthy lifestyle in order to counter autoimmune diseases.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. Serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ-inducible protein-10 (IP-10) were measured by ELISA. Among the 66 enrolled RA patients, 24 developed new-onset HZ. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21 pg/mL, interquartile range (IQR) 77.63–150.30 pg/mL versus 142.3 pg/mL, IQR 106.7–175.6 pg/mL, p < 0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8 ng/mL, IQR 21.0–38.2 ng/mL versus 10.5 ng/mL, IQR 9.9–15.0 ng/mL, p < 0.005). Our results suggest an association between reduced MCP-1 levels and HZ development in JAKi-treated RA patients. High-titer anti-IFN-γ autoantibodies may be related to severe HZ in these patients.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is prevalent among rheumatoid arthritis (RA) patients, but its pathogenesis has rarely been explored. Galectin-9 (Gal-9) interacts with T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3) expressed on hepatocytes and thus regulates T cell proliferation in a murine model of NAFLD. We aimed to examine the pathogenic role of the Gal-9/TIM-3 pathway in RA-NAFLD.MethodsSerum levels of Gal-9, soluble TIM-3 (sTIM-3), fatty acid-binding proteins (FABP)1, and FABP4 were determined by ELISA in forty-five RA patients and eleven healthy participants. Using Oil-red O staining and immunoblotting, we examined the effects of Gal-9 and free fatty acid (FFA) on lipid accumulation in human hepatocytes and FABP1 expression.ResultsSerum Gal-9, sTIM-3 and FABP1 level were significantly higher in RA patients (median 5.02 ng/mL, 3.42 ng/mL, and 5.76 ng/mL, respectively) than in healthy participants (1.86 ng/mL, 0.99 ng/mL, and 0.129 ng/mL, all p < 0.001). They were also significantly higher in patients with moderate-to-severe NAFLD compared with none-to-mild NAFLD (p < 0.01; p < 0.05; and p < 0.01, respectively). Serum Gal-9 levels were positively correlated with sTIM-3, FABP1, FABP4 levels, and ultrasound-fatty liver score, respectively, in RA patients. Multivariate regression analysis revealed that Gal-9 (cut-off>3.30) was a significant predictor of NAFLD development, and Gal-9 and sTIM-3 were predictors of NAFLD severity (both p < 0.05). The cell-based assay showed that Gal-9 and FFA could upregulate FABP1 expression and enhance lipid droplet accumulation in hepatocytes.ConclusionElevated levels of Gal-9 and sTIM3 in RA patients with NAFLD and their positive correlation with NAFLD severity suggest the pathogenic role of Gal-9 signaling in RA-related NAFLD.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p<0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p<0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

What Is Known and Objective. Given that autoantibodies are relatively abundant and easily measured, the detection of antibody biomarkers would be ideal for predicting therapeutic responses. Although anti‐Ro60/SSA (anti‐TROVE2) antibody has been identified as a useful predictor for the development of immunogenicity and therapeutic failure to adalimumab in RA patients, autoantibodies with similar predictive potentials are not yet sufficiently validated. Methods. We aimed to investigate the baseline autoantibodies, including rheumatoid factor (RF)‐IgM, anti‐citrullinated peptide antibodies (ACPA), antinuclear antibody (ANA), anti‐Ro60/SSA antibody, and anti‐La/SSB antibody, for their relationships with drug immunogenicity and therapeutic responses in RA patients assessed at week 48 of adalimumab therapy. We also compared adalimumab drug survival between participants with or without these autoantibodies. Results and Discussion. Our results showed that poor EULAR responders had significantly higher positive rates of baseline ANA, anti‐Ro60/SSA antibody, and anti‐La/SSB antibody than moderate or good responders. However, no significant differences in circulating levels of RF‐IgM or ACPA were observed among groups with different responses. The multivariate logistic regression analysis revealed that ANA and anti‐Ro60/SSA antibodies were significant predictors of developing immunogenicity to adalimumab (both p < 0.001). The presence of ANA, anti‐Ro60/SSA, and anti‐SSB antibodies could significantly predict poor EULAR response in adalimumab‐treated RA patients (odds ratio, 4.98, 5.60, and 8.08, respectively, all p < 0.01). In Kaplan–Meier analysis, the adalimumab drug survival rate was significantly lower in RA patients with positivity for ANA, anti‐Ro60/SSA, anti‐SSB, and anti‐drug antibodies than in the seronegative group. What Is New and Conclusion. Our results suggest that baseline ANA and anti‐Ro60/SSA antibodies are potential predictive markers of drug immunogenicity and poor EULAR response in adalimumab‐treated RA patients.

ObjectiveThe risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) remains inadequately defined. Consequently, this study aims to evaluate the predictive value of remnant cholesterol (RC) for assessing CVD risk in RA patients.MethodsPlasma RC levels were measured in 114 RA patients and 41 healthy controls, calculated as total cholesterol minus HDL-C and LDL-C. These levels were further analyzed using 1H-NMR lipid/metabolomics. Meanwhile, the 28-joint Disease Activity Score (DAS28) assessed RA activity.ResultsRC levels were significantly elevated in RA patients (19.0 mg/dl, p < 0.001) compared to healthy controls (14.5 mg/dl). Furthermore, RC levels were significantly elevated at 37.4 mg/dl in patients who experienced cardiovascular event (CVE) compared to 17.4 mg/dl in those without CVE (p < 0.001). To enhance the precision and reliability of RC measurements, RC concentrations were further validated using 1H-NMR spectroscopy. Additionally, a positive correlation was observed between RC levels and DAS28. Multivariate analysis identified RC as a significant predictor of CVE (odds ratio = 1.82, p = 0.013). ROC curve analysis revealed superior predictive capability of RC for CVE (AUC = 0.919, p < 0.001) compared to LDL-C (AUC = 0.669, p = 0.018), with a high sensitivity of 94.7% and a specificity of 82.1%.ConclusionElevated RC levels demonstrate greater accuracy in predicting CVE occurrence in RA patients compared to traditional measures such as LDL-C. These findings suggest that elevated RC levels may serve as a novel predictor for occurrence of CVE in RA patients, facilitating early intervention strategies based on the risk stratification.

Background Although the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in patients with RA and identified the potential risk factors.Design Retrospective study.Setting Taiwan.Participants 2281 newly diagnosed patients with RA and selected 91 240 individuals without RA to match with patients with RA (1:40) by age, gender, income status and urbanisation level of the residence.Outcomes In this retrospective study using the 2000–2018 claim data from two-million representative Taiwanese population, we identified and compared the incidence rates (IRs) of NAFLD and alcoholic fatty liver disease (AFLD) between RA and non-RA groups. Using multivariable regression analyses, we estimated adjusted HR (aHR) of NAFLD development in patients with RA compared with individuals without RA, with 95% CIs.Results The incidences of NALFD and AFLD were not significantly different between individuals with RA and without RA during the 17-year follow-up period. However, patients with RA had significantly increased NAFLD risk during the first 4 years after RA diagnosis, with IR ratio of 1.66 fold (95% CI 1.18 to 2.33, p<0.005), but the risk was reduced after the first 4 years. Multivariable regression analyses revealed that aHR was 2.77-fold greater in patients not receiving disease-modifying anti-rheumatic drugs therapy than in non-RA subjects (p<0.05). Old age, women, low-income status and obesity could significantly predict NAFLD development.Conclusions We demonstrated elevated risk of NAFLD in patients with RA during the first 4 years after RA diagnosis, and old age, women, low-income status and obesity were significant predictors of NAFLD.

Background Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to adult-onset immunodeficiency and opportunistic infections. Methods To explore whether anti-IFN-γ autoantibodies are associated with disease severity of coronavirus disease 2019 (COVID-19), we examined the titers and functional neutralization of anti-IFN-γ autoantibodies in COVID-19 patients. In 127 COVID-19 patients and 22 healthy controls, serum titers of anti-IFN-γ autoantibodies were quantified using enzyme-linked immunosorbent assay, and the presence of autoantibodies was verified with immunoblotting assay. The neutralizing capacity against IFN-γ was evaluated with flow cytometry analysis and immunoblotting, and serum cytokines levels were determined using the MULTIPLEX platform. Results A higher proportion of severe/critical COVID-19 patients had positivity for anti-IFN-γ autoantibodies (18.0%) compared with non-severe patients (3.4%, p < 0.01) or healthy control (HC) (0.0%, p < 0.05). Severe/critical COVID-19 patients also had higher median titers of anti-IFN-γ autoantibodies (5.01) compared with non-severe patients (1.33) or HC (0.44). The immunoblotting assay could verify the detectable anti-IFN-γ autoantibodies and revealed more effective inhibition of signal transducer and activator of transcription (STAT1) phosphorylation on THP-1 cells treated with serum samples from anti-IFN-γ autoantibodies-positive patients compared with those from HC (2.21 ± 0.33 versus 4.47 ± 1.64, p < 0.05). In flow-cytometry analysis, sera from autoantibodies-positive patients could also significantly more effectively suppress the STAT1 phosphorylation (median,67.28%, interquartile range [IQR] 55.2–78.0%) compared with serum from HC (median,106.7%, IQR 100.0–117.8%, p < 0.05) or autoantibodies-negative patients (median,105.9%, IQR 85.5–116.3%, p < 0.05). Multivariate analysis revealed that the positivity and titers of anti-IFN-γ autoantibodies were significant predictors of severe/critical COVID-19. Compared with non-severe COVID-19 patients, we reveal that a significantly higher proportion of severe/critical COVID-19 patients are positive for anti-IFN-γ autoantibodies with neutralizing capacity. Conclusion Our results would add COVID-19 to the list of diseases with the presence of neutralizing anti-IFN-γ autoAbs. Anti-IFN-γ autoantibodies positivity is a potential predictor of severe/critical COVID-19.

OBJECTIVES:Although 1H-nuclear magnetic resonance (NMR)-based lipid/metabolomics has been used to detect atherosclerosis, data regarding lipid/metabolomic signature in rheumatoid arthritis (RA)-related atherosclerosis are scarce. We aimed to identify the distinct lipid/metabolomic profiling and develop a prediction score model for RA patients with subclinical atherosclerosis (SA).METHODS:Serum levels of lipid metabolites were determined using 1H-NMR-based lipid/metabolomics in 65 RA patients and 12 healthy controls (HCs). The occurrence of SA was defined as the presence of carotid plaques revealed in ultrasound images.RESULTS:Compared with HC, RA patients had significantly higher levels of phenylalanine and glycoprotein acetyls (GlycA) and lower levels of leucine and isoleucine. RA patients with SA had significantly higher levels of phenylalanine, creatinine, and glycolysis_total and lower levels of total lipid in HDL(HDL_L) than RA patients without SA. The Lasso logistic regression analysis revealed that age, creatinine, HDL_L, and glycolysis_total were significant predictors for the presence of SA. The prediction scoring algorithm was built as ( -0.657 + 0.011*Age + 0.004*Creatinine -0.120*HDL_L + 0.056*glycolysis-related measures), with AUC 0.90, sensitivity 83.3%, and specificity 87.2%. Serum phenylalanine levels were significantly decreased, and the levels of HDL_L and HDL_Particle were significantly increased in 20 RA patients, paralleling the decrease in disease activity score for 28-joints.CONCLUSIONS:With 1H-NMR-based lipid/metabolomics, distinct profiling of lipid metabolites was identified between RA patients and HC or between RA patients with and without SA. We further developed a scoring model based on lipid/metabolomics profiling for predicting RA-associated SA.

ObjectiveNeutralizing anti-interferon (IFN)-γ autoantibodies are linked to opportunistic infections (OIs). To explore the association between anti-IFN-γ autoantibodies and OIs in patients with adult-onset Still's disease (AOSD), we aimed to examine the ability of these autoantibodies to blockade signal transducer and activator of transcription (STAT1)-phosphorylation and chemokines production.MethodsSerum titers of anti-IFN-γ autoantibodies were quantified using ELISA in 29 AOSD and 22 healthy controls (HC). The detectable autoantibodies were verified with immunoblotting assay, and their neutralizing capacity against IFN-γ-signaling was evaluated with flow-cytometry analysis and immunoblotting. IFN-γ-mediated production of supernatant chemokines, including monocyte chemoattractant protein-1 (MCP-1) and IFN-γ inducible protein-10 (IP-10), were measured by ELISA.ResultsAmong 29 AOSD patients, high titers of anti-IFN-γ neutralizing autoantibodies were detectable in two patients with OIs. Immunoblotting assay revealed more effective inhibition of STAT1-phosphorylation in THP-1 cells treated with sera from autoantibody-positive AOSD patients (56.7 ± 34.79%) compared with those from HC (104.3 ±29.51%), which was also demonstrated in flow-cytometry analysis (47.13 ± 40.99 vs. 97.92 ± 9.48%, p < 0.05). Depleted serum IgG from anti-IFN-γ autoAbs-positive AOSD patients with OIs restored phosphorylated STAT-1 upon IFN-γ treatment. Sera from autoantibody-positive AOSD patients more effectively inhibited IFN-γ-mediated production of MCP-1 (45.65 pg/ml) and IP-10 (22.44 pg/ml) than sera from HC (263.1 pg/ml and 104.0 pg/ml, both p < 0.05). Serum samples showing the strongest inhibition of IFN-γ-signaling were from two patients with high-titer autoantibodies and OIs.ConclusionAOSD patients have a high positive rate and titers of anti-IFN-γ autoantibodies. The remarkable blockade effect of high-titer autoantibodies on IFN-γ-mediated STAT1-phosphorylation and chemokines could make these patients susceptible to OIs.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of SMN1 is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, Mir34 family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.

Background The OMERACT-EULAR Synovitis Scoring (OESS) system is worldwide used to evaluate arthritis severity on ultrasound (US) images. Because of inter-observer and intra-observer variability, deep learning (DL) has been applied in high-quality image interpretation and analysis. Previous studies mostly focused on Doppler US (DUS) classification by convolutional neural network (CNN), which could provide objective assessment. However, the reports of DL intervention in grey scale (GS) US image automatic measurements are limited. Objectives The aim of this study was to develop an integrated multiple CNN model in precise scoring GS US images from rheumatoid arthritis (RA) patients. Methods The standard US images from patients of RA were retrospectively selected by three 10-years US experienced rheumatologist together and were graded according to the OESS system. Six different joints data were taken, including proximal interphalangeal, metacarpophalangeal, wrist, elbow, knee and ankle joints. We conducted the DL model integrating three binary CNNs to predict four-class GS US scoring (Figure 1). The accuracy of the trained model was tested by an independent test data. Results Total 678 images from 447 patients of RA were used in this study. These images were divided into training (n=611) and testing (n=67) sets. The integrated multiple CNNs model could achieve a four-class accuracy of 77.6%. The individual accuracy of grades 0, 1, 2 and 3 were 68.4%, 77.3%, 73.3% and 100%, respectively (Table 1). Furthermore, we found that adding on anatomic site parameters or labeling areas of interest would establish a better average area under curve (AUC) with 92.6% and 89.0%. Conclusion Our study suggests the possibility of using the integrated multiple CNNs model in grading synovial hypertrophy of RA, which is critical in RA healthcare. External validation would be required to confirm the predictive ability of this model. References [1]D'Agostino MA et al. RMD Open. 2017 Jul 11;3(1):e000428.[2]Andersen JKH et al. RMD Open. 2019 Mar 30;5(1):e000891.[3]Christensen ABH et al. Ann Rheum Dis. 2020 Sep;79(9):1189-1193.[4]Shin Y et al. Ultrasonography. 2021 Jan;40(1):30-44.[5]Zhou Z et al. Patterns (N Y). 2022 Sep 29;3(10):100592. Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1The proposed integrated multiple CNNs model to predict grade 3 synovium hypertrophy in rheumatoid arthritis. CNN: convolutional neural network.Table 1Prediction results of the integrated model for grey scale ultrasound scoresIntegrated modelAccuracyRheumatologist0123Total(%)0134201968.41417102277.32121111573.330001111100Total182314126777.6

OBJECTIVES:This study investigates the efficacy and adverse events of beta-3 agonists and antimuscarinic agents for managing overactive bladder syndrome in Sjogren syndrome.METHODS:Sjogren's syndrome patients with an Overactive Bladder Symptom Score (OABSS) >5 were enrolled and were randomly assigned to mirabegron 50 mg/day or solifenacin 5 mg/day. Patients were evaluated on the recruitment day and reassessed at Week 1, 2, 4, and 12. The study's primary endpoint was to have a significant change in OABSS at Week 12. The secondary endpoint was the adverse event and crossover rate.RESULTS:A total of 41 patients were included in the final analysis, with 24 in the mirabegron group and 17 in the solifenacin group. The study's primary outcome was a change of the OABSS at Week 12. We found that both mirabegron and solifenacin significantly reduce patients' OABSS after 12 weeks of treatment. The evolution of the OABSS was -3.08 for mirabegron and -3.71 for solifenacin (p = .56). Six out of 17 patients from the solifenacin group crossed over to the mirabegron arm due to severe dry mouth or constipation, while none from the mirabegron arm crossed over to the solifenacin group. Sjogren's syndrome-related pain was also improved in the mirabegron group (4.96-1.67, p = .008) compared to the solifenacin group (4.39-3.4, p = .49).CONCLUSIONS:Our study showed that mirabegron is equally effective as solifenacin in treating Sjogren's syndrome patients with overactive bladder. Mirabegron is superior to solifenacin in terms of treatment-related adverse events.

OBJECTIVES:Monocyte distribution width (MDW) correlates with volume modifications of circulating monocytes upon activation. Given the crucial role of monocyte activation in the pathogenesis of adult-onset Still's disease (AOSD), we aimed to examine the associations between MDW and disease activity or inflammatory parameters in this disease.METHODS:In 58 AOSD patients and 95 other patients with coronavirus disease 2019 (COVID-19) as disease control, MDW and complete blood count were determined using a UniCel DxH800 analyser. C-reactive protein (CRP) levels were measured by nephelometry, and ferritin levels by chemiluminescent immunoassay. AOSD activity was assessed using a modified Pouchot score.RESULTS:MDW was significantly higher in active AOSD patients (median 28.3, interquartile range [IQR] 23.3-32.1) compared with inactive AOSD (19.2, IQR 18.0-20.6, p<0.001) or non-severe COVID-19 patients (23.2, IQR 21.0-25.2, p<0.01). MDW was positively correlated with AOSD activity scores, CRP, and ferritin levels (all p<0.001). Longitudinal follow-up evaluation revealed that median MDW significantly declined (28.3 versus 18.5, p<0.001) along with disease activity, paralleling a decrease in CRP and ferritin levels. Severe COVID-19 and sepsis patients had elevated MDW, which were not different from active AOSD patients. Multivariate analysis revealed MDW as a significant predictor of active AOSD, and MDW threshold at 21.7 could predict an active status with a high sensitivity of 91.3% and specificity of 94.3%.CONCLUSIONS:Elevated MDW and its positive correlation with inflammatory parameters in AOSD patients indicate MDW as a novel activity indicator, with a high MDW value above 21.7 linked to a high probability of active AOSD.