Immunoregulatory Cells and Cytokines Discriminate Disease Activity Score 28-Remission Statuses and Ultrasound Grades in Rheumatoid Arthritis Patients with Non-High Disease Activity.

It is not clear whether immunoregulatory cytokines and cells are associated with Disease Activity Score 28 (DAS28) scores and ultrasound grades/scores. Here, we investigated the relationships between immunoregulatory cytokines or cells and different DAS28 scores or ultrasound grades/scores in patients with rheumatoid arthritis (RA). This study enrolled 50 RA patients (with 147 visits) who had remission/low/moderate DAS28-ESR scores (92% in remission and low disease activity) at baseline. Blood was collected and an ultrasound was performed three times in a year. Percentages of regulatory B cells and T regulatory type 1 cells and M2 macrophage numbers in the blood were examined. Plasma levels of 10 immunoregulatory cytokines IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-35, TGF-ß1, sTNF-R1, and sTNF-R2 and monocyte chemotactic protein-1 (MCP-1) were assessed using ELISA assay. The correlations of cytokines and cells with different DAS28 scores and ultrasound grades were investigated, and cytokines and cells were compared between different categories of DAS28 scores and ultrasound grades. Plasma TGF-ß1 levels were higher in the DAS28-ESR < 2.6 (remission) subgroup than in the DAS28-ESR ≥ 2.6 (nonremission) subgroup (p = 0.037). However, plasma TGF-ß1 levels were higher in the high ultrasound grade subgroup than those in the low ultrasound grade subgroup (p = 0.007). The number of M2 macrophages was lower in the DAS28-MCP-1 < 2.2 subgroup than in the DAS28-MCP-1 ≥ 2.2 subgroup (p = 0.036). The levels of TGF-ß1, sTNF-R2, IL-10, and IL-27 were higher in patients with high ultrasound grades than in those with low ultrasound grades. IL-27 was also higher in the nonremission DAS28-ESR subgroup than the remission one (p = 0.025). Moreover, sTNF-R1 levels in the 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission subgroup were significantly lower than in the 2011 ACR/EULAR nonremission subgroup (p = 0.007). This trend was reflected in that lower sTNF-R1 levels correlated with low DAS28-MCP-1 scores (rho = 0.222, p = 0.007). We conclude that high plasma TGF-ß1 levels indicate the DAS28-ESR remission (<2.6) subgroup and the high ultrasound grade subgroup. IL-27 probably connects the nonremission DAS28-ESR to high ultrasound grades. Low sTNF-R1 levels probably link low DAS28-MCP-1 scores with the 2011 ACR/EULAR remission subgroup. It suggests that incongruent immuno-inflammatory abnormalities exist between DAS28 scores and ultrasound grades, and are also dissimilar among various DAS28-formula categories. Therefore, this study may provide a basis for further research into individual cytokines and immunoregulatory cells behind each DAS28 formula and ultrasound grades/scores.

Predictors of Remission or Combined Remission and Low Disease Activity in Rheumatoid Arthritis Patients in Taiwan: A Prospective Cohort Study.

Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a disease activity score of 28 joints (DAS28) > 3.2 were recruited. Over 1 year of therapy, we conducted blood tests every 6 months to examine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), neuraminidase 3 (Neu3), and α-2,3-sialyltrasnferse I (ST3Gal-1) levels in B cells and monocytes. Additionally, we evaluated physical function by using the Health Assessment Questionnaire-Disability Index (HAQ-DI). Data on demographic and clinical parameters were collected, and musculoskeletal ultrasonography was performed twice a year on 12 specific joints to assess synovial changes. One year later, we compared all collected data and laboratory or ultrasound results between patients achieving remission or LDA and those who did not in order to determine the predictors. Results: Age, the presence or absence of rheumatoid factor, and the number of conventional disease-modifying anti-rheumatic drugs used were not correlated with remission or LDA for DAS28 or Simplified Disease Activity Index formulas. However, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores were associated with a higher likelihood of achieving remission or LDA for DAS28-ESR. Negative anticyclic citrullinated peptide (CCP) and low HAQ-DI scores were predictors of remission or LDA for DAS28-MCP-1. Interestingly, having less than two comorbidities is a good predictor of a combined remission/low disease activity state for SDAI and DAS28-MCP-1. Furthermore, Neu3 and ST3Gal-1 levels and ST3Gal-1/Neu3 ratios in B cells and monocytes had no significant correlation with total ultrasound scores. Nevertheless, monocyte ST3Gal-1 and Neu3 correlated significantly with DAS28-ESR >5.1 and DAS-MCP-1 >4.8 (both categories belong to high disease activity), respectively (rho = 0.609 with p = 0.012, and rho = 0.727 with p = 0.011, respectively). Monocyte ST3Gal-1/Neu3 ratios connected with DAS28-ESR >5.1 and 3.3 < SDAI ≦ 11 (low disease activity), respectively (rho = 0.662 with p = 0.005, and rho = 0.342 with p = 0.048, respectively). Conclusions: In patients with RA in Taiwan, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores are predictors of remission or LDA for DAS28-ESR, which differ from the predictors for DAS28-MCP-1. Moreover, monocyte ST3Gal-1, Neu3, and their ratios correlated with different disease activity categories of DAS28-ESR, DAS28-MCP-1, and SDAI scores.

Clinical and serological factors associated with lupus pericarditis: a case-control study.

OBJECTIVE: Lupus pericarditis, a common manifestation of systemic lupus erythematosus (SLE), can be fatal. We examined the prevalence of lupus pericarditis and its associated factors in a Taiwanese SLE cohort. METHODS: Patients with SLE treated at Change Gung Memorial Hospital between January 2005 and December 2012 were included, and their age, sex, SLE disease duration, SLE disease activity index (SLEDAI) score, laboratory test results, comorbidities, and treatment regimen were noted. Factors related to lupus pericarditis were examined using univariate and multivariate logistic regression analyses. RESULTS: Of the 689 patients, 88.7% were women; age at diagnosis (± standard deviation (SD)) was 40.78 ± 15.59 years, and disease duration at study entry was 11.93 ± 8.21 years. The prevalence of lupus pericarditis was 16.4% (n = 113). Notably, older age at diagnosis (p = 0.0165), longer disease duration (p = 0.009), higher SLEDAI score (p < 0.0001), renal disorder (p = 0.003), lymphocytopenia (p < 0.0001), thrombocytopenia (p = 0.004), and anti-phospholipid antibody (aPL) seropositivity (p = 0.002) were significantly associated with lupus pericarditis. In multivariate analysis, adjusted for sex, SLE disease duration, age, and SLEDAI score, patients with lymphocytopenia and aPL seropositivity were related to a twofold (odds ratio (OR) 2.015, 95% confidence interval (CI) 1.091-3.858) and 1.5-fold (OR 1.569, 95% CI 1.017-2.421) greater prevalence of lupus pericarditis, respectively. CONCLUSIONS: Lupus pericarditis occurred in approximately one fifth of patients in this cohort. Patients with SLE with lymphocytopenia or anti-phospholipid antibody seropositivity were associated with a higher rate of lupus pericarditis. Key Points • Lupus pericarditis is a common manifestation of SLE that occurred in one-fifth patients in this study. • Lymphocytopenia and aPL antibody seropositivity are associated with a higher likelihood of developing lupus pericarditis. • Patients with lupus pericarditis should be identify early and treated with caution to prevent further morbidity and mortality.

Exploring the Risk Factors for Poor Survival in Lupus Pericarditis Patients: A Retrospective Cohort Study.

Patients with systemic lupus erythematosus (SLE) have a higher risk of pericarditis, which could be fatal. The goal of this study was to identify the prognostic factors for mortality in patients with lupus pericarditis. Patients with lupus pericarditis treated at Chang Gung Memorial Hospital were included in this observational cohort study. This study conducted univariate and multivariate COX regression, as well as Kaplan−Meier survival curve analysis, to investigate mortality risk in SLE patients. The average age at admission was 40.78 ± 15.92 years. A total of 113 (16.4%) of the 689 patients had lupus pericarditis. Patients with lupus pericarditis exhibited older age, shorter follow-up, higher disease activities, and higher incidence rates of comorbidities than patients without pericarditis. Cox regression adjusted analysis indicated that lupus pericarditis (hazard ratio = 1.963, 95% CI = 1.315, 2.963, p = 0.001), old age at admission (HR = 1.053, 95% CI = 1.040, 1.065, p < 0.001), high SLEDAI score (HR = 1.079, 95% CI = 1.043, 1.116, p < 0.001), and end-stage kidney disease (ESKD) (HR = 2.533, 95% CI = 1.620, 3.961, p < 0.001) were all linked to increased mortality. Moreover, the Kaplan−Meier survival curve analysis revealed that patients with pericarditis compared to those without pericarditis had a higher mortality rate (log-rank test, p < 0.001). A high proportion of SLE patients have manifestations of lupus pericarditis. Moreover, patients with lupus pericarditis have a greater risk of mortality even if they have no pericardial tamponade. Therefore, these patients need prompt diagnosis and treatment.

Diagnostic Utility of Serum IgG4 in Autoimmune Pancreatitis: An Updated Comprehensive Systematic Review and Meta-analysis.

OBJECTIVES: Despite many studies suggesting an association between serum immunoglobulin G4 (sIgG4) and autoimmune pancreatitis (AIP), the evidence of utility in differentiation between AIP and pancreatic cancer (PC) remain uncertain. METHODS: The analysis based on published studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, diagnostic odds ratios (DOR), areas under summary receiver operating characteristic curves were calculated. RESULTS: In the included thirteen studies, sIgG4 were measured in 594 patients with AIP and 958 patients with PC. The pooled sensitivity, specificity, DOR, and area under the curve were 0.72 [95% confidence interval (CI): 0.68-0.75], 0.93 (95% CI: 0.92-0.95), 51.37 (95% CI: 23.20-113.74), and 0.91 (95% CI: 0.87-0.95). Subgroup analyses of the DORs for region and year: Asia, (112.10; 95% CI: 27.72-453.32), non-Asia (26.01; 95% CI: 12.38-54.65), and year before 2011 (107.61; 95% CI: 39.30-294.68), year after 2011 (26.96; 95% CI: 9.78-74.32). Overall, sIgG4 was associated with AIP, the result revealed a moderate sensitivity 0.72 and high specificity 0.93. In the meta-analysis, the pooled DOR of sIgG4 levels of 2-fold upper limit 50.44 was similar with the DOR 51.37 when 1-fold cut-off value, but the summary receiver operating characteristic was 0.755 and 0.91. The higher specificity (from 93% to 98%) derived from the cut-off value (from 130-140 to 260-280 mg/dL) for sIgG4 occurred at a significant reduction in sensitivity (from 72% to 43%). CONCLUSIONS: The study revealed sIgG4 is a good marker of AIP. Screening of sIgG4 may help clinicians differentiate between AIP and PC, and the best cut-off value should be 140 rather than 280 mg/dL.

Comparison of Orthognathic Surgery Outcomes Between Patients With and Without Underlying High-Risk Conditions: A Multidisciplinary Team-Based Approach and Practical Guidelines.

Orthognathic surgery (OGS) has been successfully adopted for managing a wide spectrum of skeletofacial deformities, but patients with underlying conditions have not been treated using OGS because of the relatively high risk of surgical anesthetic procedure-related complications. This study compared the OGS outcomes of patients with and without underlying high-risk conditions, which were managed using a comprehensive, multidisciplinary team-based OGS approach with condition-specific practical perioperative care guidelines. Data of surgical anesthetic outcomes (intraoperative blood loss, operative duration, need for prolonged intubation, reintubation, admission to an intensive care unit, length of hospital stay, and complications), facial esthetic outcomes (professional panel assessment), and patient-reported outcomes (FACE-Q social function, psychological well-being, and satisfaction with decision scales) of consecutive patients with underlying high-risk conditions (n = 30) treated between 2004 and 2017 were retrospectively collected. Patients without these underlying conditions (n = 30) treated during the same period were randomly selected for comparison. FACE-Q reports of 50 ethnicity-, sex-, and age-matched healthy individuals were obtained. The OGS-treated patients with and without underlying high-risk conditions differed significantly in their American Society of Anesthesiologists Physical Status (ASA-PS) classification (p < 0.05), Charlson comorbidity scores, and Elixhauser comorbidity scores. The two groups presented similar outcomes (all p > 0.05) for all assessed outcome parameters, except for intraoperative blood loss (p < 0.001; 974.3 ± 592.7 mL vs. 657.6 ± 355.0 mL). Comparisons with healthy individuals revealed no significant differences (p > 0.05). The patients with underlying high-risk conditions treated using a multidisciplinary team-based OGS approach and the patients without the conditions had similar OGS-related outcomes.