Acute effects of air pollution on lupus nephritis in patients with systemic lupus erythematosus: A multicenter panel study in China.

Air pollution may trigger systemic lupus erythematosus (SLE). However, few studies have investigated the associations between air pollution and complications of SLE, such as lupus nephritis (LN). In this study, multicenter longitudinal data from 13 hospitals in China, including 8552 SLE patients with 24,762 visits, were used. Based on the generalized estimating equation (GEE) model, we assessed the associations of LN occurrence with short-term exposures to different air pollutants including particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). We identified 2672 LN patients, and about half of them were from east China. Our results based on the entire data set showed that PM2.5 and NO2 were risk factors for LN within one month after exposure, with odds ratio of 1.16 (95% confidence interval (CI), 1.08-1.19) at lag 18 day and 1.19 (95% CI, 1.12-1.26) at lag 16 day relative to an interquartile range (IQR) increase in PM2.5 and NO2, respectively. This positive association between LN and NO2 was also observed for south, west, and east China. In addition, we found that the short term exposure to CO and O3 was not generally associated with LN. Finally, the negative associations of LN with SO2 were found for the entire region and east China. Our results implied that SLE patients may gain the health benefits of air quality improvement in China. Our work also provided evidence that short-term variations in air pollution may trigger LN, and further studies are needed to confirm these findings and the potential pathogenic mechanisms should be explored.

The presence of P2RX7 single nuclear polymorphism is associated with a gain of function in P2X7 receptor and inflammasome activation in SLE complicated with pericarditis.

OBJECTIVES: A case control study was conducted to evaluate the possible influence of P2RX7 single nuclear polymorphism and P2X7 receptor activity in the susceptibility of SLE with pericarditis in Chinese Han population. METHODS: We studied a cohort of SLE patients with (SLE+PCS) or without (SLE-PCS) history of pericarditis and demographic, therapeutic and clinical data were retrospectively collected. P2RX7 489 C>T (His155Tyr) genotype of each subject was analysed and classified as CC or C>T (CT and TT) variant. After isolation of peripheral blood mononuclear cells and macrophages from whole blood by centrifugation on Ficoll gradient, in vitro macrophage releases of IL-1ß and IL-18 primed by LPS were evaluated by cytometric bead array. NLRP3 expression were evaluated by western blot after normalisation of house-keeping gene α-Tubulin. Finally, P2X7 receptor activity was analysed after stimulation with agonist ATP, by measuring permeability changes using ethidium bromide (EB) uptake fluorescent probe. The Hardy-Weinberg Equilibrium (HWE) analysis was used to detect the association of P2RX7 489C>T SNP with SLE complicated with pericarditis. Spearman linear regression analysis was performed to evaluate the association of macrophages uptake of EB and NLRP3 expression. RESULTS: In total 68 SLE+PCS patients and 72 SLE-PCS patients from the cohort were enrolled. No significant differences in demographic, disease activity and serological features were found between the two subgroups. The HWE analysis detected a significant positive association between SLE+PCS and the 489 C>T SNP (OR=0.65, 95%CI (0.46-0.92), p=0.03). No association was found in SLE-PCS patients carrying either genotype CC or C>T. It was shown that in vitro inflammasome-dependent IL-1ß/IL-18 release from macrophages was higher in SLE+PCS patients compared to SLE-PCS, especially in those bearing the C>T variant genotype, and consequently the WB analysis ofNLRP3 expression in SLE+PCS patients bearing C>T genotype was significantly higher compared to the other genotype carriers (F=13.1, p<0.01). We also detected that macrophages of SLE+PCS patients carrying SNP 489C>T showed a higher EB uptake in response to ATP than subjects carrying wild type (CC). The Spearman linear regression analysis showed a significant association of macrophages EB uptake and NLRP3 expression as well as its dependent IL-1ß and IL-18 in SLE+PCS subjects carrying SNP 489 C>T. CONCLUSIONS: Our results suggest that 489 C>T polymorphism of the P2RX7 gene is associated with activation of inflammasome NLRP3 and an increased release of IL-1ß and IL-18. The EB uptake increase in macrophages of LE+PCS subjects carrying 489C>T displays the functional upregulation of P2RX7, which may be involved in the pathogenesis of SLE complicated with pericarditis in the presence of P2RX7 SNP 489C>T.

Tocilizumab and the risk of respiratory adverse events in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: The purpose of this study is to evaluate the relative risk (RR) of respiratory adverse events (AEs) among patients with RA treated with TCZ. METHODS: Databases (PubMed, Embase and Cochrane Library) were searched for randomised controlled trials (RCT) comparing the use of TCZ with placebo (PBO) or active comparator agents in adults with RA published until October 28, 2017. Statistical analyses were conducted to calculate the RR of infectious and non-infectious respiratory AEs and severe AEs (SAEs) using random-effects or fixed-effects models based on the heterogeneity of the included studies. RESULTS: Eight trials were ultimately included. TCZ was associated with an increased risk of infectious respiratory AEs relative to comparator agents (RR 1.53, 95% confidence interval [95% CI] 1.04-2.25) but was not associated with an increased risk of non-infectious respiratory AEs (RR 1.19, 95% CI 0.86-1.64). A subgroup analysis revealed similar results for non-infectious AEs and SAEs in the comparisons of TCZ with MTX and adalimumab (ADA), whereas increased risks of these AEs but not SAEs were observed compared with the PBO. CONCLUSIONS: Our meta-analysis did not reveal an increase in the risk of non-infectious respiratory AEs in adult patients with RA who were treated with TCZ compared with other csDMARDs and bDMARDs in RCTs.

Combination Therapies of Diacerein and Febuxostat Inhibit IL-1ß Responses and Improve Clinical Symptoms in Patients With Refractory Gout.

There are several therapeutic strategies available for the treatment of an acute gout attack and the prevention of recurrent gout flares, and they include nonsteroid anti-inflammatory drugs. This prospective study was aimed at evaluating the efficiency and safety of diacerein in combination with febuxostat on urate control, global assessments of disease activity, self-monitored gouty acute flare times, inflammatory markers, and clinical symptoms associated with their life quantity in patients with refractory gout. A total of 64 patients with refractory gout were sequentially recruited and prescribed with oral febuxostat alone or febuxostat plus diacerein daily for 12 weeks. The intensity of joint pain, numbers of acute flare, disease activity and the levels of serum amyloid A, mature IL-1ß, IL-18, C-reactive protein, and urate in individual subjects were routine analyzed. In comparison with that treatment with febuxostat alone, treatment with both drugs for 12 weeks had a better therapeutic effect on reducing the values of visual analog scales, acute flares, and healthy assessment questionnaire scores in these gout patients. Furthermore, treatment with both drugs also significantly reduced the mean daily dose of etoricoxib and the levels of serum IL-1ß and serum amyloid A. There was no significant difference in the frequency of patients with adverse effect between these 2 groups of patients. In conclusion, combination of diacerein and febuxostat had better therapeutic effect on reducing acute gout flares, inflammation, and clinical symptoms in patients with refractory gout.

Recent insights into the role of autophagy in the pathogenesis of rheumatoid arthritis.

Autophagy appears to play a dual role in eukaryotic cells. It manifests cytoprotective effects through the regulation of catabolic processes and the clearance of pathogens; however, a correlation between autophagy and the pathogenesis of autoimmune/autoinflammatory conditions has recently been described. Autophagy has emerged as a mediator in the pathogenesis of RA. Autophagy may regulate apoptosis resistance and hyperplasia in synovial fibroblasts, promote osteoclastogenesis and stimulate osteoclast-mediated bone resorption through the delivery of citrullinated peptides to MHC compartments, which results in the activation of the innate and adaptive immune response, thereby resulting in RA. Given the likely importance of autophagy in the pathogenesis of RA, here we reviewed the detailed mechanisms concerning the pathogenicity of autophagy and autophagy proteins in RA.

The impact of rheumatoid arthritis on work capacity in Chinese patients: a cross-sectional study.

OBJECTIVE: To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA. METHODS: A cross-sectional multicentre study was performed in 21 tertiary care hospitals across China. A consecutive sample of 846 patients with RA was recruited, of which 589 patients of working age at disease onset constituted the study population. Information on the socio-demographic, clinical, working and financial conditions of the patients was collected. Logistic regression analyses were used to identify factors associated with work capacity impairment. RESULTS: The rate of work capacity impairment was 48.0% in RA patients with a mean disease duration of 60 months (interquartile range 14-134 months), including 11.7% leaving the labour force early, 33.6% working reduced hours and 2.7% changing job. Multivariable logistic regression analysis showed that reduced working hours was significantly related to current smoking [odds ratio (OR) 2.07 (95% CI 1.08, 3.97)], no insurance [OR 1.94 (95% CI 1.20, 3.12)], in manual labour [OR 2.66 (95% CI 1.68, 4.20)] and higher HAQ score [OR 2.22 (95% CI 1.36, 3.60)]. There was an association of current smoking [OR 3.75 (95% CI 1.54, 9.15)], in manual labour [OR 2.33 (95% CI 1.17, 4.64)], longer disease duration [OR 1.01 (95% CI 1.00, 1.01)] and lower BMI [OR 0.90 (95% CI 0.82, 0.99)] with leaving the labour force early. CONCLUSION: There is a substantial impact of RA on the work capacity of patients in China. Social-demographic, disease- and work-related factors are all associated with work capacity impairment.

A randomized, double-blind, and placebo-controlled multicenter clinical trial of a novel cytotoxic T-lymphocyte antigen-4 fusion protein, Leining, in Chinese active rheumatoid arthritis patients with an inadequate response to methotrexate.

To assess the clinical efficacy as well as safety profiles of Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein, versus placebo in the treatment of Chinese active rheumatoid arthritis (RA) patients with an inadequate clinical response to methotrexate (MTX). In this 24-week, randomized, double-blind, placebo-controlled multicenter study, a total of 440 Chinese patients with active RA with an inadequate response to MTX were randomly assigned to receive Leining (10 mg/kg) or placebo. Clinical response was assessed using the American College of Rheumatology 20 % improvement criteria ACR20, ACR50, and ACR70, with ACR20 as the primary major endpoints. Disease activity scores in 28 joints with erythrocyte sedimentation rate assessment (DAS28-ESR) were used to evaluate disease activity. After 24 weeks of treatment, significantly more patients in Leining group achieved ACR20 response than those in placebo group (70.61 vs. 46.36 %; p < 0.001). Similarly, ACR50 and ACR70 responses of Leining group were significantly higher than those of placebo group (40.30 vs. 22.73 %; p < 0.001 and 16.67 vs. 7.27 %; p < 0.05, respectively). DAS28-ESR in Leining group was significantly reduced compared to that in placebo group, with greater clinically meaningful (>1.2 unit) improvement (54.85 vs. 29.09 %, p < 0.05). Both the rates of remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR < 3.2) were greater in the Leining group than those in the placebo group (12.42 vs. 2.73 %; p < 0.05 and 15.45 vs. 2.73 %; p < 0.05 respectively). The overall incidence of adverse events was similar in both Leining and placebo groups. No neutralizing antibodies were detected. Leining demonstrated clinically meaningful efficacy compared with placebo in Chinese patients with active RA despite MTX therapy. Administration of Leining in combination with MTX for 24 weeks was well tolerated.

[A multi-center retrospective study of organ involvement in adult patients with polymyositis or dermatomyositis].

OBJECTIVE: To explore the prevalence and characteristics of main organ involvement in adult patients with polymyositis (PM) or dermatomyositis (DM) and determine their specific relative factors. METHODS: Using unified questionnaire, we retrospectively collected the medical records of 1 387 confirmed adult PM/DM patients from 2007 to 2012 at 22 rheumatology centers in China. Statistical analyses were performed with chi-square or Fisher exact test and multivariate analyses with logistic regression. RESULTS: A total of 1 387 patients were collected with 460 (33.2%) PM and 927 (66.8%) DM. The female:male ratio was 2.4: 1. Their onset age was ( 47 ± 14) years. A total of 1 031 (74.3%) patients had organ involvement. The prevalence of pulmonary involvement, arthritis, gastrointestinal and cardiac involvement were 44.6%, 32.3%, 21.9% and 20.3% respectively. The multivariate analysis indicated that older onset age (P < 0.01) was positively associated with pulmonary involvement while myalgia (P < 0.05) was negatively associated. Fever (P < 0.05), weight loss (P < 0.05) and Raynaud's phenomenon (P < 0.01) were positively associated with arthritis while muscle weakness (P < 0.05) negatively associated. Weight loss (P < 0.05), Raynaud's phenomenon (P < 0.01) and muscle weakness (P < 0.05) were positively associated with gastrointestinal involvement. Weight loss (P < 0.05) and swollen limbs (P < 0.05) were positively associated with cardiac involvement. CONCLUSION: The prevalence of organ involvement is high in adult PM/DM patients. Our study may aid the diagnosis of organ damage in PM/DM patients.

[A multicenter study of coronary artery disease and its risk factors in rheumatoid arthritis in China].

OBJECTIVE: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). METHODS: Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. RESULTS: In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. CONCLUSION: The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.

[Survey of tumor necrosis factor inhibitors application in patients with rheumatoid arthritis in China].

OBJECTIVE: To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. METHODS: A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. RESULTS: In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). CONCLUSION: About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.

[Sulphasalazine in patients with rheumatoid arthritis in China: a cross-sectional study].

OBJECTIVE: To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect. METHODS: A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy. RESULTS: In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%). CONCLUSION: Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.

Optimizing the protocol for retinal vascular permeability mapping from fluorescein videoangiography data.

An intact blood-retinal barrier is critical to maintaining the function of the retina. Many diseases of the eye have been directly associated with impairment in vascular permeability, and methods to measure vascular permeability could offer a window into early detection of disease; however, there exist no direct measures of vascular permeability that have be translated to the clinic. This work details a complete clinical workflow to quantify vascular permeability and volumetric blood flow from fluorescein videoangiography data, with validation through realistic simulations. For optimizing the protocol, this study carried on frame rate of fluorescein videoangiography to generate a high-resolution image while minimizing the error.

A review on applications of abatacept in systemic rheumatic diseases.

Abatacept is a CTLA-4Ig fusion protein that selectively modulates the CD80/CD86:CD28 costimulatory pathway required for full T-cell activation. The FDA has approved it to be used to treat adult rheumatoid arthritis, juvenile idiopathic arthritis, and adult active psoriatic arthritis. Considering the vital pathogenic role of the CTLA-4 pathway in autoimmune diseases, abatacept could efficiently treat other systemic rheumatic diseases. Here we reviewed the published literature to profile the perspectives about the off-label uses of abatacept, especially in those refractory cases with inadequate responses to conventional therapies and biologic agents. Abatacept can be a promising therapeutic option and contribute to reducing hormone dependence and correlated adverse events.

Rheumatoid arthritis-associated interstitial lung disease: an overview of epidemiology, pathogenesis and management.

Interstitial lung disease (ILD) accounts for the major cause of morbidity and mortality in rheumatoid arthritis (RA). However, little is known of the pathogenesis, diagnosis and treatment of RA-associated ILD. In this review, we describe our present understanding and ongoing research in RA-ILD. Its aetiology does appear to associate with anti-cyclic citrullinated peptide antibodies, MUC5B mutation and smoking. Another focus of this article is on recent diagnostic methods in RA-ILD. Compared with other methods, high-resolution computed tomography (HRCT) imaging is a main method for the evaluation of ILD in RA patients. Pulmonary function is better suited for assessing progression. An important topic relates to therapeutic intervention. Disease-modifying anti-rheumatic drugs (DMARDs) in RA lack strong evidence in the onset or worsening of ILD. The available literature support that methotrexate, leflunomide, abatacept and rituximab play beneficial roles in the prevention and treatment of RA-ILD.

Acute Kidney Injury in Hospitalized Patients Infected with COVID-19 from Wuhan, China: A Retrospective Study.

BACKGROUND: Since the first diagnosed case of infection with the novel coronavirus (SARS-CoV-2), there has been a rapid spread of the disease with an increasing number of cases confirmed every day, as well as a rising death toll. An association has been reported between acute kidney injury (AKI) and mortality in patients infected with SARS-CoV-2. Therefore, our study was conducted to explore possible risk factors of AKI as well as whether AKI was a risk factor for worse outcome, especially mortality among patients with coronavirus disease (COVID-19). METHODS: We included all hospital admissions with confirmed or clinically diagnosed COVID-19 from January 29 to February 25, 2020. We collected demographic and epidemiological information, past medical history, symptoms, laboratory tests, treatments, and outcome data from electronic medical records. A total of 492 patients with diagnosed or clinically diagnosed COVID-19 were included in this study. RESULTS: The prevalence rate of AKI was 7.32%. Among the factors associated with AKI, males versus females (aOR 2.73), chronic kidney disease (aOR 42.2), hypertension (aOR 2.82), increased leucocytes (aOR 6.08), and diuretic use (aOR 7.89) were identified as independent risk factors for AKI among patients infected by SARS-CoV-2. There was a significant difference in hospital fees and death in patients with and without AKI (p < 0.05). The mortality rate in patients with AKI was 63.9%. CONCLUSIONS: AKI was widespread among patients with COVID-19. The risk factors of AKI in COVID-19 patients included sex, chronic kidney disease, hypertension, infection, and diuretic use. AKI may be associated with a worse outcome, especially mortality in COVID-19 patients.

Increased expression of ganglioside GM1 in peripheral CD4+ T cells correlates soluble form of CD30 in Systemic Lupus Erythematosus patients.

Gangliosides GM1 is a good marker of membrane microdomains (lipid rafts) with important function in cellular activation processes. In this study we found that GM1 expression on CD4+ T cells and memory T cells (CD45RO/CD4) were dramatic increased after stimulation with phytohaemagglutinin in vitro. Next, we examined the GM1 expression on peripheral blood CD4+ T cells and CD8+ T cells from 44 patients with SLE and 28 healthy controls by flow cytometry. GM1 expression was further analyzed with serum soluble CD30 (sCD30), IL-10, TNF-alpha and clinical parameters. The mean fluorescence intensity of GM1 on CD4+ T cells from patients with SLE was significantly higher than those from healthy controls, but not on CD8+ T cells. Increased expression of GM1 was more marked on CD4+/CD45RO+ memory T cells from active SLE patients. Patients with SLE showed significantly elevated serum sCD30 and IL-10, but not TNF-alpha levels. In addition, we found that enhanced GM1 expression on CD4+ T cells from patients with SLE positively correlated with high serum levels of sCD30 and IgG as well as disease activity (SLEDAI scores). Our data suggested the potential role of aberrant lipid raft/GM1 on CD4+ T cells and sCD30 in the pathogenesis of SLE.

Platelet Distribution Width Level in Patients With Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension and Its Diagnostic Value.

OBJECTIVES: This study aims to compare the platelet distribution width (PDW) level in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) with that in patients with systemic lupus erythematosus alone (SLE-non-PAH) and to evaluate the clinical value of the PDW level in the early diagnosis of SLE-PAH. PATIENTS AND METHODS: We analyzed 80 SLE-PAH patients (1 males, 79 females; 34.9±12.3 years; range, 19 to 77 years) and 154 sex- and age-matched SLE-non-PAH patients (4 males, 150 females; mean age 36.7±12.4 years; range, 19 to 69 years) hospitalized between June 2011 and April 2018. All patients underwent transthoracic Doppler echocardiography within three months of inclusion in the study. Age, sex, disease course, currently prescribed medications, clinical manifestations, and past history were collected. Pulmonary artery systolic pressure, ejection fraction, white blood cell count, red blood cell count, hemoglobin, platelet count, PDW, mean platelet volume, erythrocyte sedimentation rate, complement 3 (C3), and C4 levels were also obtained. RESULTS: The PDW level was higher in the SLE-PAH group than that in the SLE-non-PAH group (p=0.023). SLE patients were allocated into high systemic lupus erythematosus disease activity index (SLEDAI) group (SLEDAI score, ≥10) (n=121) or low SLEDAI group (SLEDAI score, <10) (n=113). The PDW level was significantly higher in the high SLEDAI group than that in the low SLEDAI group (p=0.030). The receiver operating characteristic curve was used to evaluate the clinical value of the PDW level in diagnosing PAH in SLE patients. The PDW level was valuable for diagnosing PAH in SLE patients [area under the curve (AUC)=0.591, p=0.023]. The optimal critical value of the PDW level was 14.55 fL. Under these conditions, the sensitivity, specificity, and Youden index were 57%, 63% and 0.20, respectively. For newly diagnosed patients, the PDW level had good diagnostic accuracy, with an AUC of 0.626 (p=0.037). The optimal critical value of the PDW level was 14.65 fL. Under these conditions, the sensitivity, specificity, and Youden index were 66%, 67% and 0.33, respectively. CONCLUSION: The PDW level is a good predictor of SLE-PAH, and this parameter is applicable to various clinical settings.

Intracranial hypertension syndrome in systemic lupus erythematosus: clinical analysis and review of the literature.

In order to better understand the clinical manifestation of systemic lupus erythematosus (SLE) with intracranial hypertension syndrome (IHS), we analyzed the clinical features and treatment of a typical SLE patient with IHS. SLE is one of the most unpredictable autoimmune diseases involving multiple organ systems that is defined clinically and associated with antibodies directed against cell nuclei. IHS is an uncommon manifestation of neuropsychiatric SLE (NPSLE) and is characterized by an elevated intracranial pressure, papilledema, and headache with occasional abducens nerve paresis, absence of a space-occupying lesion or ventricular enlargement, and normal cerebrospinal fluid chemical and hematological constituents. IHS has been reported in a few sporadic cases in patients with SLE worldwide, but rarely has been reported in China. In this study, a 34-year-old female SLE patient with IHS was reported and pertinent literature reviewed. The clinical presentation, image logical features, and investigatory findings were discussed.

α-Difluoromethylornithine suppresses inflammatory arthritis by impairing myeloid-derived suppressor cells.

OBJECTIVES: The chemopreventive drug α-difluoromethylornithine (DFMO) has been shown to have an antinociceptive effect on mechanical allodynia in inflammatory arthritis by directly inhibiting ornithine decarboxylase (ODC) and decreasing polyamine production in inflammatory sites. However, little is known about the effect of DFMO on the immune system of inflammatory arthritis. Here, we investigated the effect of DFMO in a well-established collagen-induced arthritis (CIA) mouse model and explored its effect on the immune system. METHODS: The effect of DFMO on the frequency of myeloid-derived suppressor cells (MDSCs) in the spleens of CIA mice and their associations with disease severity, tissue inflammation and the levels of proinflammatory T-helper (Th) 17 cells in lymphoid tissues were investigated. The effects of DFMO on disease severity and Th17 cells were compared with those of antibody depletion of MDSCs. The arthritis severity was also evaluated by adoptive transfer of MDSCs derived from DFMO- or dH2O-treated mice. RESULTS: In this study, we showed that both MDSCs and Th17 cells were significantly expanded in CIA mice. Treatment by DFMO at the onset of CIA suppressed the development of arthritis and decreased the frequency of MDSCs and Th17 cells. MDSC depletion by anti-Gr-1 mAb achieved a similar result, while combination treatment of both methods did not achieve a significant difference compared to either of the single treatments. In addition, the adoptive transfer of MDSCs derived from dH2O-treated mice with CIA restored the arthritis severity of CIA in mice treated with anti-Gr-1 mAb, while the transfer of MDSCs from DFMO-treated mice did not have such an effect. CONCLUSIONS: Our results identified DFMO as a potential therapeutic drug for the treatment of inflammatory arthritis.

A Randomized, Double-Blind, Non-Inferiority Study of Febuxostat Versus Allopurinol in Hyperuricemic Chinese Subjects With or Without Gout.

INTRODUCTION: This 24-week randomized, double-blind, non-inferiority study compared the efficacy and safety of febuxostat, a xanthine oxidase inhibitor, with allopurinol using an up-titration method in hyperuricemic Chinese subjects with or without gout. METHODS: Eligible adults (serum uric acid [SUA] > 7.0 mg/dl with a history of gout, SUA ≥ 8.0 mg/dl with complications or SUA ≥ 9.0 mg/dl without complications) were randomized (1:1:1) to febuxostat 40 mg/day, 80 mg/day, or allopurinol 300 mg/day. Starting doses of febuxostat 20 mg/day and allopurinol 100 mg/day were up-titrated, up to 16 weeks, to the randomized doses and maintained to week 24. Primary endpoint was non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day based on the percentage of subjects with SUA ≤ 6.0 mg/dl at week 24. The same comparison was made between febuxostat 60 mg/day or 80 mg/day versus allopurinol 300 mg/day. Safety assessments included measurement of treatment-emergent adverse events (TEAEs). RESULTS: The per-protocol population comprised 472 subjects. Non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not demonstrated based on the protocol-defined margin of - 10% (44.7 vs. 50.0%; - 5.3% difference; 95% confidence interval [CI]: - 16.4%, 5.8%); however, superiority over allopurinol 300 mg/day was demonstrated for febuxostat 60 mg/day at week 16 (66.3 vs. 51.2%; a 15.0% difference; 95% CI: 4.2%, 25.9%) and febuxostat 80 mg/day at week 24 (70.0 vs. 50.0%; a 20.0% difference; 95% CI: 9.3%, 30.7%). The frequency of TEAEs was similar across groups, with gout flares occurring frequently. CONCLUSIONS: Using a novel dose-titration method, although the primary endpoint of non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not reached, non-inferiority and superiority of febuxostat 60 mg/day and 80 mg/day versus allopurinol 300 mg/day was demonstrated at weeks 16 and 24, respectively. Febuxostat demonstrated an acceptable tolerability profile in the treatment of hyperuricemia in Chinese subjects with or without gout. TRIAL REGISTRATION: JapicCTI-132106. FUNDING: Astellas Pharma Global Development, Inc.