High level of serum complement 3 is a risk factor for vascular stenosis progression in TA patients receiving tocilizumab: a prospective observational study.

BACKGROUND: The IL-6R antibody tocilizumab has been proven effective in treating Takayasu arteritis (TA). However, some patients show silent vascular stenosis progression (VSP) despite treatment with tocilizumab. The aim of the study was to explore the related risk factors of VSP in patients treated with tocilizumab. METHODS: Patients receiving tocilizumab were enrolled from the prospective living ongoing East China Takayasu Arteritis cohort. Their medical information was uniformly recorded with a homogenized evaluation method. Magnetic resonant angiography or computed tomographic angiography was employed to monitor VSP during the follow-up period, and Cox regression analysis was performed to explore the related risk factors. RESULTS: Thirty-eight patients were enrolled, among whom 18 (47.4%) experienced VSP, and seven and three patients experienced new and worsened vascular ischemic symptoms and events (VISE) during follow-up, respectively. The median period for VSP occurrence was 6.9 months during follow-up. Patients with VSP showed higher levels of baseline complement 3 (C3) than those in the patients without VSP. Multivariate Cox regression analysis revealed baseline C3 level (hazard ratio [HR] = 7.05, 95% confidence interval: 1.50-33.07, p = 0.013) was independently associated with VSP, with a cut-off value of 1.22 g/L. CONCLUSIONS: 47.4% of TA patients treated with tocilizumab would suffer VSP. A high C3 level is a risk factor for VSP in TA patients receiving tocilizumab, which may facilitate the option of tocilizumab in the future.

Practice of network platform teaching in standardized residency training of rheumatology and immunology / 中华医学教育探索杂志

This article intends to explore the application and implementation effect of network platform teaching in the standardized residency training of rheumatology and immunology. Through the implementation of online platform teaching (micro-class, online PBL teaching, and air class) for the training residents rotating in the rheumatology and immunology department, the questionnaire survey was carried out. The results showed that the satisfaction of the residents with the online platform teaching reached 96.88% (31/32), and more than 90.00% of the residents believed that their self-learning ability and clinical thinking ability have been improved, and their learning initiative and enthusiasm have also been improved, which deserves further promotion.

Continuation, reduction, or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control: a multicenter, open-label, randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.@*METHODS@#The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months.@*RESULTS@#Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group.@*CONCLUSION@#Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR2000039799.

Clinical and pathological predictors of relapse in IgG4-related disease.

OBJECTIVES: In IgG4-related disease, the relationship between pathological findings and relapse has not been well established. This study aimed to identify the clinical and pathological predictors of disease relapse in IgG4-RD. METHODS: Patients with newly diagnosed IgG4-RD (n = 71) were enrolled between January 2011 and April 2020; all cases were pathologically confirmed. The clinical and pathological features were recorded in a database at baseline and each follow-up visit. Patients were followed up at least once a month via outpatient clinic examinations and telephone calls. Univariate and multivariate Cox regression analyses and receiver operating curve (ROC) analysis were used to identify the predictors of disease relapse and to assess their predictive value. RESULTS: Over a median follow-up of 26 (range, 6-123) months, 3/71 (4.2%) patients died. Of the remaining 68 patients, 47 (69.1%) patients had achieved clinical remission and 21 (30.9%) had suffered relapse at the last follow-up. The independent predictors of relapse were IgG4 ≥ 6.5 g/L (HR = 2.84, 95% CI: 1.11-7.23), IgG ≥ 20.8 g/L (HR = 4.11, 95% CI: 1.53-11.06), IgG4-RD responder index (RI) ≥ 9 (HR = 3.82, 95% CI: 1.28-11.37), and severe IgG4+ plasma cell infiltration (HR = 6.32, 95% CI: 1.79-22.41). A prognostic score developed using three of the identified predictors (IgG ≥ 20.8 g/L, IgG4-RD RI ≥ 9, and severe IgG4+ plasma cell infiltration) showed good value for predicting impending relapse (AUC, 0.806). CONCLUSIONS: In patients with IgG4-RD, IgG4 ≥ 6.5 g/L, IgG ≥ 20.8 g/L, IgG4-RD responder index (RI) ≥ 9, and severe IgG4+ plasma cell infiltration are predictors of relapse.

Recommendations of diagnosis and treatment of Takayasu′s arteritis in China / 中华内科杂志

Takayasu′s arteritis (TAK) mainly involves the aorta and its major branches, which is characterized as a chronic, progressive and inflammatory disease. China belongs to one of the regions with a high prevalence of TAK referring to its global distribution. However, it is insufficient for the spread and update of standardized diagnosis and treatment of TAK. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed the standardized diagnosis and treatment of TAK in China. The purpose is to standardize the methods for diagnosis of TAK, assessment of disease activity and disease severity, strategies of internal treatment and timing of surgical intervention, and further leading to protect the function of important organs and improve the disease prognosis.

Analysis of clinical characteristics and adverse events related factors in patients with giant cell arteritis / 中华风湿病学杂志

Objective:To identify the clinical characteristics and adverse events of patients with giant cell arteritis (GCA).Methods:Patients who were hospitalized and diagnosed with GCA in Zhongshan Hospital, Fudan University, from December 2009 to November 2020 were enrolled into a retrospective study analysis. Baseline data and follow-up data were collected. Adverse events were defined as one of the following events: relapses, ischemic complications and death. Patients with adverse events were analyzed in clinical features and risk factors by univariate and multivariate analysis. Associations with adverse events were assessed using ROC curve and survival curves.Results:A total of 69 patients with GCA were included in this study, with the male: female ratio of 1∶1.03. Fatigue and headache were common symptoms. Finally, 61 patients were followed up at the end of May in 2021. Over the mean follow-up time of (35±20) months, adverse events occurred in 16 cases (26.2%). Patients with adverse events had significantly lower levels of platelet and globulin at baseline than those without adverse events [(325±142)×10 9/L vs (238±112)×10 9/L, t=2.22, P=0.030]; [(31±6) g/L vs (26±6) g/L, t=2.74, P=0.008]. Red cell volume distribution width-coefficient of variation (RDW-CV) was considered an independent risk factor for adverse events [ OR (95% CI)=0.32 (0.14,0.74), P=0.008]. Further, patients especially with RDW-CV<14.75% were prone to have adverse events, which occurred in 2.6%, 20.5%, 25.6%, 33.3%, 41.00% in 1, 2, 3, 5, 10 years. Its risk increased significantly after 2 years ( P=0.042, P=0.021, P=0.002, P=0.001). The incidence of adverse events was much higher in patients with RDW-CV<14.75%(95% CI=0.002). Conclusion:Adverse events are common in patients with GCA. RDW-CV is an independent risk factor for having adverse events. Low level of RDW-CV predicts an increased risk of adverse events by the following years.

Clinical characteristics, imaging phenotypes and events free survival in Takayasu arteritis patients with hypertension.

BACKGROUND: Hypertension occurred in 30-80% of Takayasu arteritis (TAK) patients around the world and the occurrence of hypertension might worsen the disease prognosis. This study aimed to investigate the clinical characteristics and imaging phenotypes, as well as their associations with events free survival (EFS) in Chinese TAK patients with hypertension. METHODS: This current research was based on a prospectively ongoing observational cohort-the East China Takayasu Arteritis (ECTA) cohort, centered in Zhongshan Hospital, Fudan University. Totally, 204 TAK patients with hypertension were enrolled between January 2013 and December 2019. Clinical characteristics and imaging phenotypes of each case were evaluated and their associations with the EFS by the end of August 30, 2020, were analyzed. RESULTS: Severe hypertension accounted for 46.1% of the entire population. Three specific imaging phenotypes were identified: Cluster 1: involvement of the abdominal aorta and/or renal artery (27.5%); Cluster 2: involvement of the ascending aorta, thoracic aorta, the aortic arch, and/or its branches (18.6%); and Cluster 3: combined involvement of Cluster 1 and 2 (53.9%). Clinical characteristics, especially hypertensive severity, differed greatly among the three imaging clusters. In all, 187 patients were followed up for a median of 46 (9-102) months; 72 events were observed in 60 patients (1-3 per person). The overall blood pressure control rate was 50.8%, and the EFS was 67.9% by the end of the follow-up. Multivariate Cox regression indicated that controlled blood pressure (HR = 2.13, 95% CI 1.32-3.74), Cluster 1 (HR = 0.69, 95% CI 0.48-0.92) and Cluster 3 (HR = 0.72, 95% CI 0.43-0.94) imaging phenotype was associated with the EFS. Kaplan-Meier curves showed that patients with controlled blood pressure showed better EFS (p = 0.043). Furthermore, using cases with Cluster 1 imaging phenotype and controlled blood pressure as reference, better EFS was observed in patients with Cluster 2 phenotype and controlled blood pressure (HR = 2.21, 95%CI 1.47-4.32), while the case with Cluster 1 phenotype plus uncontrolled blood pressure (HR = 0.64, 95%CI 0.52-0.89) and those with Cluster 3 phenotype and uncontrolled blood pressure (HR = 0.83, 95%CI 0.76-0.92) suffered worse EFS. CONCLUSION: Blood pressure control status and imaging phenotypes showed significant effects on the EFS for TAK patients with hypertension.

Improved clinical outcomes of tocilizumab versus cyclophosphamide for IgG4-related disease: insights from a prospective IgG4-related disease registry.

OBJECTIVE: To compare the clinical outcomes of patients with active immunoglobulin G (IgG) 4 related disease (IgG4-RD) receiving tocilizumab versus those receiving cyclophosphamide (CYC). METHODS: This IgG4-RD registry study was a prospective cohort study conducted among patients with active IgG4-RD hospitalized at Zhongshan Hospital, Fudan University. Patients who were treated with tocilizumab or CYC along with glucocorticoids (GCs) were enrolled. All participants were followed up at the hospital clinic at 3 and 6 months after discharge. Primary clinical outcomes were measured via the IgG4-RD responder index (RI), complete response (CR), and partial response (PR), as well as side effects. RESULTS: From January 2015 to June 2020, 29 patients enrolled. Fourteen and 15 patients were treated with tocilizumab and CYC, respectively. At the 6-month follow-up, disease activity parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IgG4, and IgG4-RD RI, decreased significantly in both groups. At 6 months, tocilizumab demonstrated its superiority, with 50% of patients achieving CR in the Tocilizumab group versus 20% in the CYC group. However, no statistical significance was identified (p = 0.128). The GC dosage at 6 months was significantly lower in the tocilizumab group than in the CYC group [10 (9.4-15) mg/d versus 15 (15-15) mg/d, p = 0.025]. In the CYC group, two patients experienced lumbar vertebral compression fractures related to GCs. Other patients in both groups showed mild adverse effects. CONCLUSIONS: Tocilizumab could be a better steroid-sparing agent, with a comparable curative effect and tolerance, than CYC, in the treatment of IgG4-RD.

Effect of hydroxychloroquine on angiographic progression in routine treatment of Takayasu arteritis.

OBJECTIVES: Hydroxychloroquine (HCQ), an anti-malarial drug, is widely used in the treatment of rheumatic diseases. However, the benefits of HCQ in the treatment of Takayasu arteritis (TA) remain unclear, especially in terms of alleviation of vascular progression. METHODS: This longitudinal observational retrospective study was based on the East China TA cohort. Patients received routine treatment with prednisone and immunosuppressants. Fifty TA patients who underwent magnetic resonance angiography two times within a 1.5-year follow-up period of monitoring vascular changes were divided into HCQ and non-HCQ groups according to whether HCQ was prescribed. Changes in angiographic features were compared. Multivariate Cox regression analysis was employed to further validate the results. RESULTS: Of 50 TA patients, 21 were prescribed HCQ. The two groups shared a similar disease course, vascular types, prednisone with immunosuppressants intervention strategy, globin level, and disease remission rate at 6 months. The HCQ group showed greater reduction in the inflammatory indices erythrocyte sedimentation rate and C-reactive protein (CRP) level (p < .05), and a significantly lower incidence of angiographic progression than the non-HCQ group (19.0% vs. 51.7%, p = .035). After adjustment for age and usage of tocilizumab, angiographic progression was found to be independently associated with CRP (hazard ratio [95% confidence interval], HR [95% CI]: 1.102 [1.000-1.024], p = .046), and the usage of HCQ (HR [95% CI]: 0.266 [0.075-0.940], p = .040). CONCLUSION: HCQ enhanced the anti-inflammatory effect of routine treatment strategies with prednisone and immunosuppressants, and alleviated angiographic progression in TA.

Prognostic factors in IgG4-related disease: a long-term monocentric Chinese cohort study.

OBJECTIVES: Patients with IgG4-related disease (IgG4-RD) suffer high relapse rates during long-term treatment, but factors that predict relapse outcomes are not well established. In the present study, we aimed to identify predictive factors for treatment resistance and disease relapse in a Chinese IgG4-RD cohort. METHODS: This study enrolled 102 patients newly diagnosed with IgG4-RD. Disease prognosis was determined by evaluating disease activity and dosage of glucocorticoids. Predictive factors for refractory and relapsed disease were identified by univariate analysis and Cox regression. RESULTS: Among the 102 patients, 78 cases received medical treatment with regular follow-up (21 [6-111] months). During the follow-up period, 55 (70.5%) patients sustained clinical remission, and 23 (29.5%) patients suffered refractory or relapsed disease. The relapse rate of the patients with IgG4-RD was significantly higher among patients who stopped taking medicine than among those who continued treatment with glucocorticoids (GC) + immunosuppressor (IM). Serum TNF-α ≥ 13 pg/mL, sIL-2R ≥ 1010 U/mL, total cholesterol < 3.55 mmol/L, low-density lipoprotein < 2.0 mmol/L, IgG ≥ 20.2 g/L, and drug withdrawal were predictive factors for refractory and relapsed IgG4-RD. Multivariate Cox regression revealed that both sIL-2R and TNF-α were independent risk factors for refractory and relapsed disease. The combination of GC and IM treatment was an independent protective factor against refractory and relapsed IgG4-RD. CONCLUSIONS: High serum levels of sIL-2R and TNF-α may be informative risk factors for refractory and relapsed IgG4-RD. Our data suggest that a combination treatment of GC along with IM may be protective against refractory and relapsed IgG4-RD. Key Points • High sIL-2R and TNF-α levels are informative risk factors for refractory and relapsed IgG4-related disease. • Combination treatment of GC with IM protects against refractory and relapsed IgG4-related disease.

Clinical and genetic risk factors for glucocorticoid-associated osteonecrosis of the femoral head: a prospective cohort study / 中华骨科杂志

Objective:To perform a prospective cohort study to identify individual susceptibility of glucocorticoid (GC) -associated osteonecrosis of the femoral head (GA-ONFH) and their clinical and genetic risk factors. Methods:The present prospective cohort study enrolled patients who received their first GC therapy between July 2015 and January 2018 at Zhongshan Hospital. All patients did not receive any GC treatment before enrollment. Further, they planned to start GC treatment with the dose (equivalent prednisone) of ≥30 mg/d, lasted ≥3 weeks, or pulse dose ≥200 mg/d, lasted ≥3 d. Blood samples were collected before GC treatment to evaluate bone metabolism and its released factors. Hip MRI was performed at the 1st, 3rd, 6th, 12th and 24th month to diagnose GA-ONFH. All patients were followed-up for ≥2 years. The endpoint was regarded as diagnosis of GA-ONFH or completion of 2 years follow-up. Lasso regression was performed to determine which clinical features were associated with GA-ONFH. A nested case-control sub-cohort (A, n=12) was established prospectively based on the main cohort by 1∶1 matching. Whole exome sequencing was performed to screen differential and functional candidate single nucleotide polymorphisms and insertion-deletions (SNP/InDels). Another sub-cohort (B, n=50) was constructed retrospectively in patients with GA-ONFH and non-ONFH patients received standard high dose GC treatment for more than two years. The candidate SNP/InDels were verified by Sanger sequencing based on the patients from sub-cohort B. Results:A total of 96 patients were enrolled of which 88 of them (32 males and 56 females, mean age 42.30 years) completed follow-up. Eight cases (9.1%) were diagnosed with GA-ONFH. The median time from the start of GC therapy to the diagnosis of ONFH was 53.00(34.00,13.50) days. The baseline characteristics, such as age, sex and body mass index, indicated no significant difference between the ONFH group and the non-ONFH group. The cumulative GC dose of the ONFH patients in the first month was higher than that of non-ONFH [32.74(29.55, 47.05) mg/kg vs. 24.00(21.10, 29.45) mg/kg, Z=-2.410, P=0.016]. However, there was no significant difference of patients who underwent pulse therapy (37.5% vs. 10.0%, adjusted χ 2=2.829, P=0.093). The ratio of serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) in patients with ONFH was higher than that in non-ONFH group before GC use [0.95(0.80, 1.50) vs. 0.70(0.60, 0.80), Z=-2.875, P=0.000]. Due to the multicollinearity, Lasso regression model was performed to reduce overfitting. All variables were included in the model. The results suggested that higher ApoB/ApoA1 ratio, lower serum β-c-terminal telopeptide (β-CTX) and higher cumulative GC dose in the first month were the top three risk factors of GA-ONFH. This model had an accuracy of 0.982 in internal validation. Seven differential candidate SNP/InDels were found by whole exome sequencing of sub-cohort A. We further verified these SNP/InDels in sub-cohort B. The patients with COLEC12 mutation (rs2305027, G1816A) were at risk of GA-ONFH ( OR=6.00, 95% CI: 1.17, 30.73). Conclusion:Higher first-month GC dose, lower serum β-CTX level before treatment, higher ApoB/ApoA1 ratio and COLEC12 mutation (rs2305027, G1816A) could increase the risk of GA-ONFH.

Study on the value of different diagnostic/classification criteria for the diagnosis of Takayasu's arteritis / 中华风湿病学杂志

Objective:To compare the diagnostic efficacy of Chinese diagnostic model, the 1990 American College of Rheumatology (ACR) classification criteria and the 2018 ACR new classification criteria (draft) for Takayasu arteritis (TA).Methods:A total of 196 TA patients who came to our hospital from January 1, 2009 to May 31, 2019 in the TA database of the department of rheumatology and immunology, Zhongshan Hospital, Fudan University and 131 patients with other vascular diseases visited during the same period were selected. General characteristics, clinical data, laboratory tests and imaging tests of all patients were collected. Categorical variables were presented as numbers and percentages, between-group differences were analyzed using the χ2 test. Continuous variables were presented as the Mean± SD for a normal distribution or median and interquartile range (IQR) for a non-normal distribution. Between-group differences were analyzed using the Student's t-test or Mann- Whitney test, as appropriate. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and receiver operating characteristics of the above diagnostic/classification criteria area under the curve were analyzed. P<0.05 was considered significant. Results:In terms of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under receiver operating characteristic curve (ROC), Chinese diagnostic models was 85.7%, 96.2%, 89.9%, 97.1%, 81.5%, 0.909, 1990 ACR criteria was 47.4%, 97.7%, 67.6%, 96.9%, 55.4%, 0.726, 2018 ACR classification criteria was 79.1%, 98.5%, 86.5%, 98.7%, 75.9%, 0.888. The difference between the Chinese diagnostic model and the 2018 ACR criteria in AUC was not statistically significant ( Z=1.186 , P>0.05). The sensitivity, accuracy and diagnostic efficiency of Chinese diagnostic model was the best, that of the 1990 ACR classification criteria was the worst, and the specificity of the 2018 ACR classification criteria was the highest. The Kappa value of the 2018 ACR classification criteria and the Chinese diagnostic model was 0.719, which had good consistency, and the Kappa value of the consistency between the 1990 ACR classification criteria and the Chinese TA diagnostic model was 0.516. Conclusion:The Chinese diagnostic model, which is based on the clinical characteristics of the Chinese TA population, has a good diagnostic efficacy for the Chinese population. The 2018 ACR classification criteria (draft) is highly consistent with the Chinese TA diagnostic model, and can be promoted and applied in practice.

Clinicial features of Takayasu arteritis: a cohort study / 中华风湿病学杂志

Objective:To analyze the characteristics of patients with Takayasu arteritis (TA) in the east China Takayasu arteritis (ECTA) cohort and their subgroups, and evaluate the disease characteristics.Methods:Patients diagnosed with TA in ECTA cohort from January 2009 to October 2019 were enrolled and their data were analyzed. The characteristics were analyzed and compared within subgroups using t-test or Wilcoxon rank sum test or Chi-square test. Results:A total of 454 patients were included, with the male to female ratio of 1∶4.75(79/375), and the main complaint were dizziness/headache, fatigue, and chest tightness/pain. The type Ⅴ and Ⅰ were the most common angiographic pattern, among which the subclavian artery and carotid artery were most vulnerable, manifested as vascular stenosis. Hypertension, tuberculosis and hepatitis B were common complications. In subgroup comparison, symptoms and inflammation index were much more evident in the active group, female group, <40 years old, and newly diagnosed group. C-reactive protein (CRP)[10(2, 33) mg/L vs 3(1, 14) mg/L, Z=-4.49, P<0.01), erythrocyte sedimentation rate (ESR) [(45±33) mm/1 h vs (25±23) mm/1 h, t=-5.82, P<0.01), in the active group were significantly higher than those in the inactive group, while the ESR in female patients was only higher than that in males, but without statistical significant difference. SAA in the young age group, ESR in the newly diagnosed group was significantly higher than that in the other subgroups [19(6, 95) mg/L vs 10(4, 39) mg/L, Z=2.06, P<0.05] [(44±34) mm/1 h vs (32±28) mm/1 h, t=3.77, P<0.01]. Conclusion:The TA patients are mainly young women, and are in active disease when first being diagnosed. The type Ⅴ and Ⅰ are the most common artery involve-ment pattern. Hypertension and tuberculosis are the most frequent complications.

Classification of patients with gout and their clinical features / 中华风湿病学杂志

Objective:To investigate the classification of patients with gout, and further analyze their clinical features.Methods:Outpatients with gout were enrolled from January 2018 to July 2019 in Depart-ment of Rheumatology, Zhongshan Hospital. Subjects were classified into four groups according to their 24-hour urinaryexcretion and fractional excretion of urate. Clinical features of different groups were analyzed using one-way Analysis of Variance (ANOVA), Kruskal-Wallis H test, or χ2 test. Results:Finally, 378 subjects were enrolled in this cross-sectional study. Among them, 186(49.2%) were renal underexcretion type, 100(26.5%) were combined type, 57(15.1%) were renal overload type, 35(9.3%) were the normal type. Renal underexcretion type was the main subtype in any age-stratified groups. With aging, the proportion of combined type decreased, while the normal type increased. Participants in the combined type were the youngest [(42±14) years of age] with the highest estimated glomerular filtration rate [(94±18) ml·min -1·1.73 m -2], while their serum urate levels were the highest [(554±104) μmol/L]. Subjects in the normal type were the oldest [(60±15) years of age] with the lowest estimated glomerular filtration rate [(71±19) mL·min -1·1.73 m -2], however, their serum urate concentrations were the lowest [(427±118) μmol/L], The difference was statistically significant (age, F=13.98; estimated glomerular filtration rate, F=16.11; urate, F=17.14; P<0.01). Prevalence of urolithiasis were similar among the four groups ( χ2 =2.00, P>0.05). Conclusion:The renal underexcretion type is the main type of gout. Young patients are more likely to suffer from combined type with the highest serum urate levels and the best renal function.

In vitro IL-6/IL-6R Trans-Signaling in Fibroblasts Releases Cytokines That May Be Linked to the Pathogenesis of IgG4-Related Disease.

Background: The remarkable mechanisms of storiform fibrosis and the formation of high levels of IgG4 with a pathogenic germinal center (GC) in the inflammatory tissue of IgG4-RD remains unknown and may be responsible for the unsatisfactory therapeutic effect on IgG4-related diseases when using conventional therapy. Objectives: To investigate the mechanisms of interleukin 6 (IL-6) inducing fibroblasts to produce cytokines for pathogenic GC formation in the development of IgG4-related disease (IgG4-RD). Methods: The clinical data and laboratory examinations of 56 patients with IgG4-RD were collected. IL-6 and IL-6R expression in the serum and tissues of patients with IgG4-RD and healthy controls were detected by ELISA, immunohistochemistry, and immunofluorescence. Human aorta adventitial fibroblasts (AAFs) were cultured and stimulated with IL-6/IL-6 receptor (IL-6R). The effect of IL-6/IL-6R on AAFs was determined by Luminex assays. Results: The serum IL-6 and IL-6R levels were elevated in active IgG4-RD patients and IL-6 was positively correlated with the disease activity (e.g., erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and IgG4-RD responder index). IL-6 and IL-6R expression in the tissue lesions of IgG4-related retroperitoneal fibrosis and IgG4-related sialadenitis patients were also significantly higher than that in the normal tissues. In addition, there is a relative abundance of myofibroblasts as well as IgG4+ plasma cells in the tissues of IgG4-related retroperitoneal fibrosis. α-SMA and B cell differentiation cytokines (i.e., B cell activating factor), and α-SMA and T follicular helper (Tfh) cell differentiation cytokines (e.g., IL-7, IL-12, and IL-23) were co-expressed in the local lesions. In vitro, IL-6/IL-6R significantly promoted the production of B cell activating factor, IL-7, IL-12, and IL-23 in AAFs in a dose-dependent manner. This effect was partially blocked by JAK1, JAK2, STAT3, and Akt inhibitors, respectively. Conclusions:In vitro IL-6/IL-6R trans-signaling in fibroblasts releases Tfh and B cell differentiation factors partially via the JAK2/STAT3, JAK1/STAT3, and JAK2/Akt pathways, which may be linked to the pathogenesis of IgG4-RD. This indicated that IL-6 and fibroblasts may be responsible for GC formation and fibrosis in the development of IgG4-RD. Blocking IL-6 with JAK1/2 inhibitors or inhibiting fibroblast proliferation might be beneficial for IgG4-RD treatment.

Efficacy and safety of leflunomide versus cyclophosphamide for initial-onset Takayasu arteritis: a prospective cohort study.

BACKGROUND: Leflunomide (LEF) has been considered as an alternative treatment for Takayasu arteritis (TA); however, data on its efficacy are still scanty. OBJECTIVE: To investigate the efficacy and safety of LEF versus cyclophosphamide (CYC) for initial-onset TA. METHODS: Initial-onset TA patients with active disease were enrolled in this research. Patients enrolled from 1 January 2009 to 31 December 2015 were treated with glucocorticoids and CYC, while patients enrolled from 1 January 2016 to 31 October 2018 received glucocorticoids and LEF. Treatment response including complete remission (CR), partial remission (PR), and effectiveness rate (ER) and side effects were evaluated at 6 and 12 months. RESULTS AND CONCLUSION: In total, 92 patients were enrolled. A total of 47 patients were treated with LEF, while 45 patients were treated with CYC. The CR and ER rates were 75.55%, and 88.89% at 6 months, and 85.37% and 95.12% at 12 months in the LEF group. The CR and ER rates were 39.02% and 70.73% at 6 months, and 56.41% and 82.05% at 12 months in the CYC group. The CR rate was significantly higher in the LEF group than in the CYC group both at 6 months (75.61% versus 38.24%, p < 0.01) and 12 months (77.42% versus 53.33%, p < 0.05) after adjustment for propensity scores. The incidence of side effects in the LEF group was much lower than that in the CYC group (21.28% versus 44.44%). In conclusion, LEF provided a better treatment response, along with lower reproductive toxicity, compared with CYC in initial-onset TA.

Anti-neutrophil cytoplasmic antibody-associated vasculitis overlap immunoglobulin G4-related diseases: a 4 case series and review of literature / 中华风湿病学杂志

Objective:To summarize the characteristics and treatment outcomes of immunoglobulin G4-related disease (IgG4-RD) overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods:The clinical data of four patients with AAV overlaped with IgG4-RD from Zhongshan Hospital of Fudan University from August 2018 to July 2019 were collected and the related literature were reviewed.Results:Four patients were included, in which two were diagnosed with IgG-RD and granulomatosis with polyangiitis (GPA), one was probable IgG4-RD and microscopic polyangiitis (MPA), and one was probable IgG4-RD and GPA. All patients were female, with an average age of (42±12) (26-56) years, and disease duration was (7±4) (4-13) months. The manifestations were ocular inflammatory pseudotumor, sinusitis, otitis media, mastoiditis, parotitis, meningitis, lung and kidney involvement. After treatment with glucocorticoid and immunosuppressants (including cyclophosphamide, methotrexate, azathioprine, leflunomide), 2 patients failed to achieve remission, and 2 patients relapsed 8-15 months after treatment. One patient was treated withglucocorticoid pulse therapy combined with rituximab and one was treated with glucocorticoid combined with methotrexate and rituximab, and the patient was relieved.Conclusion:AAV and IgG4-RD may be a new overlap syndrome. Hypertrophic meningitis, orbital mass, chronic periaortic inflammation and interstitial glomerulonephritis are reported in the literature. The pathological changes of orbit, nasopharynx, parotid gland and lung are common. Glucocorticoids and immunosuppressive agents have poor treatment response, which indicates that AAV is refractory when combined with elevated IgG4. The induced remission rate is low, and easy to relapse. Glucocorticoid pulse therapy and rituximab treatment are effective.

Chinese expert investigation on diagnosis and disease activity evaluation in Takayasu's arteritis / 复旦学报（医学版）

Objective To investigate the current situation in Chinese rheumatologic physicians' clinical diagnosis and evaluation of Takayasu's arteritis (TA).Methods Nineteen rheumatology experts and three vascular surgery specialists in China were invited to make the nationwide investigation for the first time about the diagnosis and disease activity evaluation of TA in China,through the questionnaire survey on the internet.Weighted average was used to calculate the average scores of corresponding problems.Results Chinese experts mainly adopted 1990 American College of Rheumatology (ACR) classification criteria for clinical diagnosis of TA.In details,symptoms of age,limb claudication and amaurosis,signs including pulselessness or pulse weakening,vascular bruits,increasing bilateral pulse pressure and hypertension and acute phase reactants (APR) were critical to the clinical diagnosis of TA.Besides,noninvasive imaging examinations,such as computed tomography angiography (CTA),magnetic resonance angiography (MRA),vascular ultrasonography,and positron emission tomography (PET) were also of great importance.In the aspect of disease activity assessment,Chinese experts mainly used Kerr scoring tool.APR and noninvasive radiological examinations were considered with vital value.Some TA patients with carotid artery involvement were recommended using vascular ultrasonography,while others with pulmonary artery and thoracic/abdominal aorta trunk involvement were preferred CTA other than MRA.Conclusions APR and noninvasive imaging examinations were thought with great help to make clinical diagnosis and evaluation of TA for Chinese physicians.

The relationship between the muscles edema and skeleton involvement surrounding sacroiliac joint of axial seronegative spondyloarthropathy patients with functional magnetic resonance imaging / 复旦学报（医学版）

Objective To observe the muscles and skeleton involvement surrounding sacroiliac joint (SIJ) of axial seronegative spondyloarthropathy (SPA) patients with magnetic resonance imaging (MRI),and to analyze the relationship between them.Methods A prospective study of 38 patients who meet the 2009 axial SpA diagnostic criteria was conducted.We carried out MRI of the SIJ for these patients to evaluate the muscles and skeleton involvement.Those cases were divided into muscles differences between the two groups of image scores,including Spondyloarthritis Research Consortium of Canada (SPARCC) scores and Spondyloarthritis Research Consortium of Canada MRI Sacroiliac Joint Structural Score (SPARCC SSS).The extent of muscles edema in patients with sacroiliac joints was ranked into twelve grades from 0-12,and we did Spearman rank correlation test of muscles edema scope and two indexes.Results We found that 28 cases (73.68％) of the 38 patients had significant muscle involvement by analyzing the STIR sequence,and found erector spinae in 22 cases (57.89 ％)gluteal muscles in 13 cases (34.21 ％),iliacus muscle in 11 cases (28.95 ％),obturator muscle in 5 cases (13.16％),piriform muscle in 5 cases (13.16％) and other 4 cases (10.53％).SPARCC (t =2.28,P =0.03) and SPARCC SSS (t =3.37,P =0.00) were statistically different between the two groups.SPARCC (P =0.00,r =0.67) and SPARCC SSS (P-0.01,r =0.47) were positively correlated with the extent of muscles edema.Conclusions The muscles edema around sacroiliac joint is an important sign of axial SpA magnetic resonance imaging.Patients who had muscles edema tended to have more serious skeleton changes.

18F-Fluorodeoxyglucose positron emision tomography in the assessment of disease activity of Takayasu arteritis: a meta-analysis / 中华风湿病学杂志

Objective To evaluate the performance of Positron emision tomography (PET) in the assessment of disease activity of Takayasu arteritis (TA). Methods Information retrieval was based on database such as PubMed/Medline and CNKI, etc. The research before Dec 2016 involving Takayasu arteritis and PET were included.The quality of the research was evaluated by diagnostic accuracy studies-2Q(UADAS-2) and the data was analyzed by Meta-disc. Results Among the 70 research, nine studies were included in this study with a total of 126 patients and 254 controls. All patients were diagnosed according to the classification criteria of American College of Rheumatology. The disease activity was mostly assessed by the scoring system of National Institutes of Health and by clinical assessment in one study. The result of PET was evaluated by visual grade and semi-quantitative analysis. The pooled DOR of the 9 studies was 17.54, the pooled sensitivity and specificity was 84% and 73%,respectively.However,the heterogeneity of specificity was 81.4%. Two studies had included one patients repeatedly and suspected active patients were included in the in-active group in one study,which might impact the statistical result of the meta-analysis.After excluded these studies, the pooled DOR was 30.32. The pooled sensitivity and specificity was 86% and 85%, respectively, with better consistency. Conclusion PET shows stable sensitivity and variant specificity in the diagnosis and assess of disease activity of TA, which is a useful method in the clinically evaluation of disease activity of TA.