Search

IgG4-related disease (IgG4-RD) is a multi-organ fibroinflammatory disorder that may result in organ dysfunction and complications. Glucocorticoids remain the primary treatment for inducing remission, while recently reported disease phenotypes might inform personalized therapeutic strategies. Progress in understanding the pathophysiology of IgG4-RD has led to the identification of novel treatment targets. Ongoing research will further refine the optimal treatment for IgG4-RD. This review offers an update on the latest evidence on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of IgG4-RD.

Background: The aim of this study was to validate the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) in antinuclear antibody (ANA)-positive Chinese patients. Methods: Medical records of all adult patients who attended the rheumatology out-patient clinics between May and September 2019 were reviewed. Patients with ever ANA positive (titre ⩾1:80) were included and evaluated for the fulfilment of the 2019 EULAR/ACR, 2012 Systemic Lupus International Collaborating Clinics (SLICC) and 1997 ACR criteria for SLE classification. The performance of these criteria in predicting a clinical diagnosis of SLE as judged by an independent panel of rheumatologists was studied and compared in different subgroups. Results: A total of 1533 patients (88.2% women; age at first clinic attendance 45.5 ± 15.6 years) were studied and 562 patients were judged to be clinical SLE. The sensitivity and specificity of the EULAR/ACR (⩾10 points), SLICC and ACR criteria for a clinical diagnosis of SLE was 96.1%, 97.9% and 86.1%; and 85.8%, 86.3% and 94.3%, respectively. Applying the attribution rule to the non-SLE controls, the specificity of the three criteria increased to 95.0%, 92.5% and 98.8%, respectively. The specificity of the EULAR/ACR criteria was higher in male patients (97.9%), those aged >50 years (97.0%) and disease duration of ⩽3 years (97.6%). Using a cut-off of 12 points, the specificity of the EULAR/ACR criteria was further increased (96.6%) while a high sensitivity (95.0%) was maintained. Conclusion: In Chinese patients with a positive ANA, the EULAR/ACR criteria for clinical SLE perform equally well to the SLICC criteria. Both the EULAR/ACR and SLICC are more sensitive but less specific than the ACR criteria. The specificity of all the three criteria is enhanced by applying the attribution rule to controls. The specificity of the EULAR/ACR criteria is higher in certain patient subgroups or when the cut-off score is raised.

Objectives: To revisit the trend of survival of systemic lupus erythematosus in a cohort of Chinese patients over 25 years.Methods: Patients who fulfilled the 1997 ACR criteria for SLE and were followed in our hospital since 1995 were included. Patients were stratified into two groups according to the year of diagnosis: (1) 1995–2004 and (2) 2005–2018. Survival of patients was studied by Kaplan–Meier analysis. Organ damage as assessed by the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) and causes of death in the first 10 years of SLE onset was compared between the two groups. Cox regression was used to study factors associated with survival.Results: A total of 1,098 SLE patients were registered in our database. After excluding 157 patients diagnosed outside the time period of 1995–2018, 941 patients were studied (92% women). All were ethnic Chinese. The mean age of SLE onset was 35.1 ± 14.4 years, and the mean duration of observation was 13.1 ± 6.6 years. Seventy-seven (8.2%) patients were lost to follow-up. Groups 1 and 2 consisted of 364 and 577 patients, respectively. The mean SDI score at 10 years of disease onset was significantly higher in group 1 than group 2 patients (1.01 ± 1.43 vs. 0.57 ± 0.94; p < 0.01), particularly in the neuropsychiatric, musculoskeletal, and gonadal domains. Within 10 years of SLE onset, 32 (8.8%) patients in group 1 and 25 (4.3%) patients in group 2 died (p = 0.005). The 5- and 10-year cumulative survival rates were 93.6 and 91.0% in group 1 and 96.5 and 94.2% in group 2 patients, respectively (log-rank test p = 0.048). Infection accounted for more than half of the deaths in both groups. More group 1 than group 2 patients died of vascular events, but the difference was not statistically significant. Cox regression showed that the age of SLE onset and damage score accrued at 10 years, but not the time period in which SLE was diagnosed, were significantly associated with mortality.Conclusions: The improvement in survival of our SLE patients is probably related to the accrual of less organ damage in the past 15 years.

Abstract Surface-enhanced Raman spectroscopy (SERS) is widely utilized in bacterial analyses, with the dominant SERS peaks attributed to purine metabolites released during sample preparation. Although adenosine triphosphate (ATP) and nucleic acids are potential molecular origins of these metabolites, research on their exact contributions remains limited. This study explored purine metabolite release from E. coli and RNA integrity following various sample preparation methods. Standard water washing generated dominant SERS signals within 10 s, a duration shorter than the anticipated RNA half-lives under starvation. Evaluating RNA integrity indicated that the most abundant ribosomal RNA species remained intact for hours post-washing, whereas messenger RNA and transfer RNA species degraded gradually. This suggests that bacterial SERS signatures observed after the typical washing step could originate from only a small fraction of endogenous purine-containing molecules. In contrast, acid depurination led to degradation of most RNA species, releasing about 40 times more purine derivatives than water washing. Mild heating also instigated the RNA degradation and released more purine derivatives than water washing. Notably, differences were also evident in the dominant SERS signals following these treatments. This work provides insights into SERS-based studies of purine metabolites released by bacteria and future development of methodologies.

Abstract Background Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson’s Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. Methods In a case–control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer’s disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. Results The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. Conclusions and Relevance Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.

Background/purpose: Understanding the relationship between maxillary sinus and posterior root apices is critical in preventing dental treatment complications. This study aimed to analyze and showcase the relationship between the posterior root apices and the maxillary sinus floor, the distance to the buccal cortical bone, and their correlation with age, gender, and sides. Materials and methods: Cone-beam computed tomography images were collected from 94 patients with a total of 478 maxillary posterior teeth and 997 roots. The shortest distance from root apices to the closest border of maxillary sinus and the outer buccal cortical bone margin were measured and grouped for statistical analysis for the differences (P

BackgroundSodium-glucose co-transporter-2 inhibitors (SGLT2i) have cardiovascular (CV) benefits, particularly in reducing the risk of heart failure (HF). Pioglitazone (Pio) has shown potential in decreasing the risks of recurrent stroke, non-fatal myocardial infarction (MI), and all-cause mortality but increasing risks of HF. Our study aimed to examine the synergistic effects on CV outcomes in patients with type 2 diabetes mellitus (T2DM) who received the combined treatment of SGLT2i and Pio.Materials and methodsA total of 117,850 patients with T2DM and without a history of HF were selected as the observational study cohort from the Chang Gung Research Database (CGRD) in Taiwan between January 1, 2016, and December 31, 2019. The primary composite outcome was 4-point major adverse CV events (4P-MACE), including CV death, non-fatal MI, non-fatal ischemic stroke, and hospitalization for HF. The study was divided into four groups: a combined treatment group in which SGLT2i and Pio were used, two individual groups in which SGLT2i or Pio was used separately, and a reference group (non-study drugs).ResultsCombined treatment of SGLT2i and Pio had the lowest risk of 4P-MACE (adjusted hazard ratio [aHR], 0.66; 95% confidence interval [CI], 0.54–0.80) compared with the reference group after a mean follow-up of 2.2 years. There was no significant difference in risks of hospitalization for HF (adjusted subdistribution hazard ratio, 0.73; 95% CI, 0.49–1.07) compared with the reference group.ConclusionsIn T2DM patients without HF, the combined treatment with SGLT2i and Pio may synergistically provide CV benefits without increasing risks of HF.

Background As the burden and distribution of calcification within chronic total occlusion (CTO) lesions can be diverse, its effect on CTO recanalization using multiple devices and techniques is debatable. This study investigated the role of calcification in wiring-based intraplaque tracking techniques for CTO recanalization.Methods A modified J-CTO score without counting calcification was used to analyze the procedures of 458 consecutive patients who underwent CTO interventions. Failed guidewire crossing and intraplaque tracking were considered procedural failures. Recanalization time details were analyzed for successful procedures.Results In patients with calcified CTO, the rate of procedural success only significantly declined to be lower than that of noncalcified CTO when the modified J-CTO score was ≥3 (77% vs. 94%, p = 0.008). In 422 patients with successful procedures, the presence of calcification was irrelevant to guidewire crossing time, but was accompanied with longer time from guidewire cross to final angiogram when the modified J-CTO score was 1–2 (53 ± 35 vs. 35 ± 17 [noncalcified] min, p 60 min (OR = 4.8, 95% CI = 2.2–10.2) in successfully recanalized lesions with modified J-CTO score 1–2.Conclusions Using intraplaque guidewire tracking, calcification was unfavorable for very difficult CTO lesions, and caused prolongation of angioplasty time for lesions with moderate complexity. This suggested that the role of calcification in the J-CTO score could be altered when different recanalization techniques were applied for CTO interventions.

In this study, cupric oxide nanowires (CuO NWs) on patterned interdigitated electrodes (PIEs) used as ozone (O3) gas sensors, were successfully fabricated using thermal oxidation and the microelectromechanical systems (MEMS) technique. After the thermal oxidation process, CuO NWs with different heights and densities were fabricated using a pure copper seed layer with a thickness ranging from 0.5 μm to 2 μm. In this experiment, a low temperature, low concentration, and repeatable CuO NWs gas sensor was fabricated, which can detect O3 gas at a low concentration of 50 ppb and low temperature of 100°C with a high sensor response (40%). The concentration response of this gas sensor shows an increasing linear trend, with an increase of O3 concentration in the range of 50 ppb - 300 ppb. Additionally, the results indicated that this CuO NWs gas sensor is more selective for O3 than CO, CO2, C2H5OH, C3H6O, NO2, or NH3. While CuO has been less studied in O3 detection compared with other semiconducting metal oxide materials, CuO NWs show potential applications in gas sensing devices for low-temperature and low-concentration O3 environmental monitoring.