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To explore the etiology of risk factors and quantify the mortality differences in systemic lupus erythematosus (SLE) patients with different initial disease activity. The Jiangsu Lupus database was established by collecting medical records from first-hospitalized SLE patients during 1999–2009 from 26 centers in Jiangsu province, China, and their survival status every five years. The initial SLEDAI scores [high (>12) vs. low–moderate (≤12)] differences in mortality attributable to risk factors were quantified using population attributable fraction (PAF), relative attributable risk (RAR) and adjusted relative risk (ARR). Among 2446 SLE patients, 83 and 176 deaths were observed in the low–moderate and high activity groups, with mortality rates of 7.7 and 14.0 per 1000 person years, respectively. Anemia was the leading contributor to mortality, with PAFs of 40.4 and 37.5 in the low–moderate and high activity groups, respectively, and explained 23.2% of the mortality differences with an ARR of 1.66 between the two groups. Cardiopulmonary involvement caused the highest PAFs in the low–moderate (20.5%) and high activity (13.6%) groups, explaining 18.3% of the mortality differences. The combination of anemia and cardiopulmonary involvement had the highest RAR, causing 39.8% of the mortality differences (ARR = 1.52) between the two groups. In addition, hypoalbuminemia and a decrease in the creatinine clearance rate accounted for 20–30% of deaths and explained 10–20% of the mortality differences between the two groups, while antimalarial drug nonuse accounted for about 35% of deaths and explained 3.6% of the mortality differences. Anemia, cardiopulmonary involvement and hypoalbuminemia may cause substantial mortality differences across disease activity states, suggesting additional strategies beyond disease activity assessment to monitor SLE outcomes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status. Methods: In this study, based on 1999–2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients' survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression. Results: The overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment. Conclusions: The proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association and dose–response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients. Methods Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999–2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI. Results We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose–response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements. Conclusion Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs. [ABSTRACT FROM AUTHOR]

The article discusses a study on a rare but high-risk pathogenic variants within several ankylosing spondylitis (AS) families by whole-exome sequencing and whether the rare variants exist in a larger sample population. Topics include clinical characteristics and relationships of six patients in the study from different families, finding on the number of osteoclasts present in the sample treated with interferon (IFN)ß stimulation, and mutant that plays a pathogenic role in AS.

Objective: To identify early signs associated with poor prognosis in Chinese patients with systemic lupus erythematosus (SLE) through a large population-based follow-up study. Methods: Medical records of > 2,500 SLE patients that first hospitalized between 1999–2009 were collected from 26 centers across Jiangsu province, China, and entered into a database. These patients were followed-up for 5 to 15 years, and those remained contact and had known survival status in 2015 were assessed for the association of factors presented at the initial hospitalization with mortality at two time points (≤1year and > 1year). The independency of mortality factors was evaluated using multivariate Cox regression analysis. Results: Among 1,372 patients we assessed, 92.3% were women and 17.2% were deceased in 2015. The main causes of death were infection (30.1%), neuropsychiatric impairment (14.8%), renal failure (14.4%) and cardiopulmonary involvement (8.5%). Hazard ratios (HR) of independent predictors for mortality (≤1year and > 1year, respectively) included hospital presentation of neuropsychiatric involvement (2.03 and 1.91), cardiopulmonary involvement (1.94 and 1.61) and increased serum creatinine (2.52 and 2.58). Patients older than 45 years and with disease durations more than 2 years at admission had unfavorable short-term outcome (HR 1.76 and 1.79), while the presence of anti-dsDNA and anti-Sm antibodies indicated diverse prognosis after 1 year (HR 1.60 and 0.45). Treatment with cyclophosphamide was beneficial for patient’s first-year outcome (HR 0.50), and anti-malarial drugs significantly reduced the risk of mortality over different time points (HR 0.48 and 0.54). SLEDAI score, proteinuria or hypocomplementemia was not independently associated with the outcome in this cohort. Conclusion: SLE patients presented with vital organ damages rather than active disease at initial hospitalization are likely to have a poor outcome, especially for those with neuropsychiatric, cardiopulmonary involvements and renal insufficiency. Early and effective intervention with the use of anti-malarial drugs may decrease mortality. [ABSTRACT FROM AUTHOR]

In an effort to enhance the linear range of anti-CCP we developed a new immunoassay based on time-resolved fluoroimmunoassay. The precision, sensitivity, specificity, and stability of the assay were evaluated ELISA set as control. The anti-CCP IgG TRFIA kit we established had a wider detectable range than commercial ELISA ones. With regard to intra- and inter-assay precision, the TRFIA kit was better than threee commercial ELISA ones. The mean recovery rate was 101.0%. The TRFIA we developed for anti-CCP IgG detection yielded a more sensitive and reliable method for RA diagnosis and large-scale screening programs as well. [ABSTRACT FROM PUBLISHER]

We demonstrate herein a novel time-resolved fluoroimmunoassay (TRFIA) with high sensitivity and wide range for quantitative detection of ANA-Ig(GAM) antibodies using a biotin-avidin amplification system. The immunoassay was conducted by following procedures for a typical sandwich immunoreactions with cell nucleus form Hela and the Eu3+-labeled biotin combined with biotinylated mouse anti-human Ig(GAM) served as the solid nuclear antigen for ANA and the tracer, respectively. The sensitivity, specificity, and stability of the kit were evaluated and comparison with the classical enzyme-linked immunosorbent assay (ELISA) kit was also made. The average intra-assay and interassay CVs detected by the established ANA-Ig(GAM) biotin-avidin-TRFIA were 4.21% and 6.34%, respectively. The lower detection limit was 2.24 U/mL, and the mean recovery rate was 100.74%. The good measurable range of the established biotin-avidin-TRFIA was within 1.95–64,000 U/mL, while it was only within 32.5–4000 U/mL using an ELISA kit. The values determined by the biotin-avidin-TRFIA and ELISA correlated well (R2 = 0.989). The positive rate of healthy volunteers and patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary biliary cirrhosis (PBC), Sjögren's syndrome (SS), scleroderma, and mixed connective tissue disease (MCTD) was 0, 100%, 18.5%, 100%, 37.9%, 90.9%, and 92%, respectively. We conclude that the biotin-avidin-TRFIA we developed gives promise for greater sensitivity and accurate detection for ANA-Ig(GAM) in diagnosing and monitoring autoimmune disorders. [ABSTRACT FROM PUBLISHER]

Iguratimod (IGU) is a novel disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA). Like other DMARDs, IGU exhibited significant differences in effectiveness and safety., Aim: The aim of this study was to identify genetic predictorsof efficacyand toxicity of IGU in patients with RA., Materials & Methods: Seven SNPs from IGU-metabolizing genes were genotyped in 272 IGU-treated patients with RA. Results: ABCG2 rs2231142 A allele conferred a higher response to IGU, while NAT2 rs1495742 G carriersconferred a lower response to IGU. CYP2C19*2 rs4244285 A carriers had higher risk for IGU-induced toxicity compared to the GG carriers., Conclusion: Our study suggests that the polymorphisms of ABCG2 (rs2231142), NAT2 (rs1495741)and CYP2C19*2 (rs4244285) may help to predict thetherapeutic effectiveness and toxicity of IGU in patients with RA.

Objective: Left atrial function plays a key role in maintaining an optimal cardiac output. Left ventricular diastolic dysfunction has been reported in systemic lupus erythematosus (SLE), but its effect on left atrial function has been largely overlooked. Our aim was to assess left atrial performance using real-time 3-D echocardiography (RT3DE) technology in patients with SLE., Methods: Our study included 102 patients with SLE without any cardiac symptoms, and 32 healthy controls. According to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), all subjects were classified into 3 groups: healthy controls, patients with an SDI = 0, and patients with an SDI ≥ 1., Results: Left atrial volume indexed to body surface area was dilated in subjects with SLE, whereas the left atrial passive emptying fraction (EF) was lower. Left atrial active EF was significantly higher in the SDI = 0 group than in controls (46.4 ± 9.1% vs 30.0 ± 10.3%, p < 0.05); however, it was significantly lower in the SDI ≥ 1 group than in the SDI = 0 group (41.2 ± 9.8% vs 46.4 ± 9.1%, p < 0.05). By multivariate linear analysis, the SDI was independently and positively associated with left atrial volume index and inversely associated with left atrial total function., Conclusion: Our study demonstrated that left atrial mechanical function and volume are impaired in SLE, particularly in patients with an SDI ≥ 1 and disease activity. RT3DE may have better diagnostic value than traditional echo indexes in detecting subclinical cardiac dysfunction in patients with SLE.

Background: Bone damage around the joints is one of the major pathophysiological mechanisms that leads to rheumatoid arthritis (RA) chronic disability. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) is secreted by osteoclasts, its activity can be used as a clinically relevant bone resorption marker. The aim of this study was to test whether the measurement of serum levels of TRACP-5b in patients with RA would correlate with measures of disease activity and with responses to therapy., Methods: Fifty-six patients were randomly assigned to receive recombinant human cytotoxic tlymphocyte-associated antigen-4 immunoglobulin (RhCTLA4-Ig), infliximab or methotrexate (MTX). The clinical and serologic indicators of RA activity were evaluated at baseline and at 24 weeks. Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay (ELISA) at 0, 12 and 24 weeks. Hand X-rays were obtained at baseline., Results: At baseline, the levels of TRACP-5b correlated with the severity of X-ray damage, disease duration (r = 0.332, P = 0.012), and tender joint count (r = 0.408, P = 0.002). The 24 weeks values of TRACP-5b for RhCTLA4-Ig group and infliximab group differed significantly from the baseline values in each group (P < 0.05; P < 0.05), whereas only the value for RhCTLA4-Ig group differed significantly from the 24 weeks value for the MTX group (P < 0.01). Considering the two biologics-treated groups together, the TRACP-5b levels at 24 weeks differed significantly from the baseline values only in those patients who reached an ACR70 level (P < 0.05)., Conclusions: Measurement of serum TRACP-5b in RA patients reflects clinical and radiological measures of disease activity, treatment with certain biologics, and degree of response to therapy. TRACP-5b should be investigated further as a potential biomarker to predict response to therapy, including slowing of radiographic progression.

Objective: To investigate the mortality of hospitalized patients with systemic lupus erythematosus (SLE) and determine the influential factors associated with poor prognosis., Methods: Medical records of 1956 SLE inpatients from 15 hospitals during the period January 1, 1999, to December 31, 2009, were reviewed. All patients were followed up in January 2010. Potential factors associated with mortality were analyzed, comparing patients who were living with those who were deceased. The independency of those factors significantly related to death was determined by Cox regression analysis., Results: Male to female ratio was 1:15 in this cohort; median age at disease onset was 30 years. Hematologic (70.0%), mucocutaneous (68.2%), musculoskeletal (57.9%), and renal (48.7%) involvements were most often seen in these patients at time of admission. The overall mortality was 8.5% (n = 166), with infection (25.9%), renal failure (19.3%), and neuropsychiatric lupus (18.7%) the leading 3 causes of death. Independent predictors for mortality in this cohort of SLE patients were neuropsychiatric involvement [hazard ratio (HR) 2.19], anemia (HR 1.69), SLEDAI score > 8 at discharge (HR 1.64), increased serum creatinine (HR 1.57), low serum albumin (HR 1.56), cardiopulmonary involvement (HR 1.55), and patient untreated before admission (HR 1.48), whereas the use of antimalarial drugs (HR 0.62) and positive anti-Sm antibody (HR 0.60) were shown to be protective factors., Conclusion: SLE patients with delayed treatment and refractory disease have poorer prognosis. A high incidence of death would be expected if they have neuropsychiatric involvement, anemia, azotemia, or cardiopulmonary involvement. Combination therapy with antimalarial drugs may provide some benefit to patients with SLE.