Association of podocyte injury with clinical features and prognosis in patients with mesangial proliferative lupus nephritis.

OBJECTIVES: The aim of this study is to explore the association of podocyte injury with clinical features and outcomes in mesangial proliferative (Class II) lupus nephritis (LN). METHODS: We conducted a retrospective and clinicopathologic analysis with 576 LN patients with renal biopsy and screened 58 patients with Class II LN. Then, the 58 cases were divided into 4 groups based on the degree of podocyte damage and immune complex (IC) deposits on light microscope (histological and immunofluorescence) and electron microscope: Podocyte Injury Group, IC deposits Group, Podocyte Injury and IC Group, and Less-lesion Group. Clinical and pathologic information was collected from the patients' medical records at the time of the kidney biopsy and at follow-up. The data of demography, clinical parameters, therapy, remission, and relapse rates were analyzed and compared across groups. RESULTS: A significant difference was observed in the ages of patients among four Class II LN groups. The onset age of patients with FPE ≥ 50% was significant later. The frequency of thrombocytopenia was statistically different among the four groups and the patients with FPE ≥ 50% had lower frequency of thrombocytopenia. Patients with FPE ≥ 50% had lower serum albumin, eGFR, and elevated proteinuria and serum lipids. In this study, most patients received glucocorticoids in combination with immunosuppressants. Among the 4 groups, the use of ACEI/ARBs was highest in the podocyte injury group. There was a statistical difference in the renal relapse rates among the 4 Class II LN groups. Moreover, the recurrence rate was higher in the FPE ≥ 50% group. CONCLUSION: Our data identified Class II LN patients with podocyte injury (FPE ≥ 50%) present prominent renal damage and higher rate of renal relapse, suggesting more aggressive treatment and close follow-up for these patients.

High levels of platelet-to-lymphocyte ratio may predict reduced risk of end stage of renal disease in Chinese patients with MPO-ANCA associated vasculitis. / 血小板/淋巴细胞比率比值升高可能预示中国MPO-ANCAç›¸å ³æ€§è¡€ç®¡ç‚Žæ‚£è€ è¿›å±•è‡³ç»ˆæœ«æœŸè‚¾ç— çš„é£Žé™©è¾ƒä½Ž.

OBJECTIVES: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality. METHODS: The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. RESULTS: A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801). CONCLUSIONS: PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.

Risk factors for serious infections in inpatients with systemic lupus erythematosus. / ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®ä½é™¢æ‚£è€ åˆå¹¶ä¸¥é‡æ„ŸæŸ“çš„å±é™©å› ç´ .

OBJECTIVES: To investigate the risk factors for serious infections among hospitalized systemic lupus erythematosus (SLE) patients, and to provide the advice for preventing serious infections in SLE patients. METHODS: Information of SLE patients hospitalized from March 2017 to February 2019 at the Department of Rheumatology and Immunology, Xiangya Hospital, Central South University was obtained. The patients were assigned into a serious infection group and a non-serious infection group. The risk factors for serious infections among SLE inpatients were identified by comparison between the 2 groups and multivariate logistic regression analysis. RESULTS: There were 463 SLE inpatients in total, and 144 were in the serious infection group and 319 in the non-serious infection group. Multivariate logistic regression analysis showed that age ≥54.50 years old (OR=4.958, P<0.001), cardiovascular involvement (OR=6.287, P<0.001), hematologic involvement (OR=2.643, P=0.003), serum albumin <20 g/L (OR=2.340, P=0.036), C-reaction protein (CRP)/erythrocyte sedimentation rate (ESR)≥0.12 (OR=2.430, P=0.002), glucocorticoid dose ≥8.75 mg/d prednisone-equivalent (OR=2.465, P=0.002), and the combined use of immunosuppressive agents (OR=2.847, P=0.037) were the risk factors for serious infections in SLE inpatients. CONCLUSIONS: SLE patients with older age, cardiovascular involvement, hematologic involvement, low serum albumin are prone to suffering serious infections. Increased CRP/ESR ratio indicates serious infections in SLE inpatients. High-dose glucocorticoid and the combined use of immunosuppressive agents can increase the risk of serious infections in SLE inpatients.

Clinical characteristics and prognosis in 269 patients with antineutrophil cytoplasimc antibody associated vasculitis. / 269ä¾‹æŠ—ä¸­æ€§ç²’ç»†èƒžèƒžæµ†æŠ—ä½“ç›¸å ³æ€§è¡€ç®¡ç‚Žæ‚£è€ çš„ä¸´åºŠç— ç†ç‰¹å¾åŠé¢„åŽ.

OBJECTIVES: To investigate the clinic-pathological characteristics, prognosis and its risk factors for antineutrophil cytoplasimc antibody (ANCA)-associated vasculitis (AAV). METHODS: The basic information and clinic-pathological characteristics of AAV patients, who was diagnosed from January 2010 to January 2018 in Xiangya Hospital, Central South University, were retrospectively collected. The renal survival and patient survival were regular followed up, and their clinical pathological, prognosis data and risk factors for renal were analyzed. RESULTS: Among 269 AAV patients, 225 patients (83.64%) were microscopic polyangiitis (MPA), 33 patients (12.27%) were granulomatosis with polyangiitis (GPA), and 11 patients (4.09%) were eosinophilic granulomatosis with polyangiitis (EGPA). Male-to-female ratio was almost 1∶1 for MPA (147/122), but GPA and EGPA was more frequent among man. The medium time from disease onset to diagnosis was 64.0 (32.5, 148.5) days, 65 patients (24.16%) were diagnosed within 30 days. A total of 94.67% patients had kidney involvement in MPA patients, which was significantly higher than that in patients with GPA (63.63%), but ear, nose, and throat manifestations were more frequent in GPA patients. The 1-year kidney survival rates of GPA and MPA patients in this study were 75% and 59.3%, respectively. The 1-year death rates were 16.7% and 16.9%, respectively. The multivariable logistic regression analysis revealed that the low platelet level, low globulin level, low immunoglobin G, and high serum creatinine level were independent risk factors for the 1-year renal survival rate in AAV patients. Multiple factor logistic regression analysis showed that the serum creatinine level was an independent risk factor for all-cause mortality. CONCLUSIONS: MPA is the priority in the AAV patients. The proportion of patients with advanced end-stage renal disease and mortality is still high, and the early diagnosis and treatment in time is crucial for the improvement of prognosis for AAV.

[Clinical characteristics for connective tissue disease complicated with cryptococcal meningitis].

OBJECTIVE: To investigate the clinical characteristics and prognosis for connective tissue disease (CTD) with cryptococcal meningitis (CM). 
 Methods: Clinical data of 18 patients with CTD complicated with cryptococcal meningitis diagnosed by Rheumatology and Immunology Department, Xiangya Hospital, Central South University from January 2000 to January 2017, were retrospectively analyzed.
 Results: The common symptoms of CTD patients with CM were headache, fever, nausea, and vomiting. Patients with severe clinical manifestations, such as convulsions and disturbance of consciousness, all died. Logistic regression analysis showed that disturbance of consciousness and decreased peripheral blood lymphocyte count might be the related factors of poor prognosis of CTD patients with CM (P<0.05). The mortality rate of CTD with CM was 61.11%, and the effective rate of treatment for this disease was 38.89%.
 Conclusion: CTD patients with cryptococcal meningitis have a high risk of death. Severe clinical symptoms, such as disturbance of consciousness and lower peripheral blood lymphocyte count, are associated with its poor prognosis.

Increased levels of serum histone H4 and activated protein C in patients with active rheumatoid arthritis.

OBJECTIVES: We aimed to examine the levels of serum H4 and activated protein C (APC) in rheumatoid arthritis (RA) and other autoimmune conditions, and investigate the associations between H4 or APC levels and disease activity indicators in RA. METHODS: Serum H4 and APC distribution was examined in samples from patients with RA, systemic lupus erythematosus (SLE), polymyositis (PM), and ankylosing spondylitis (AS), as well as in samples from healthy controls, using commercial ELISA kits. Associations of serum H4 or APC levels with disease variables in patients with RA were evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminant capacity of APC against RA and non-RA. RESULTS: The patients with RA, PM, and AS showed higher serum levels of H4 and APC than those from the healthy control individuals, while the SLE patients showed higher serum levels of APC only. Moderate positive correlations between H4 levels and absolute neutrophil count (ANC), platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), brinogen (FIB), D-dimer (DD), and complement fraction 3 (C3) were observed. Positive correlations between APC levels and PLT, RF, DD, or DAS28 were additionally found. ROC curve analysis revealed that APC discriminated well between RA and non-RA. CONCLUSIONS: H4 and APC concentrations are elevated in patients with chronic in ammatory autoimmune diseases. The observed associations between H4 and APC and disease variables in patients with RA support a role for H4 and APC in the in ammatory process of the disease.

Comparison of soluble urokinase plasminogen activator receptor, soluble triggering receptor expressed on myeloid cells 1, procalcitonin and C-reactive protein in distinguishing concurrent bacterial infection from idiopathic inflammatory myopathy.

The aim of the study was to measure the diagnostic values of biomarkers of bacterial infection in idiopathic inflammatory myopathy (IIM) patients. The serum and clinical data of 82 IIM patients with/without bacterial infection were collected. Concentrations of soluble urokinase plasminogen activator receptor (suPAR), soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), procalcitonin (PCT) and C-reactive protein (CRP) were measured in IIM patients and healthy controls. There were no significant differences in serum suPAR and sTREM-1 levels between healthy controls and non-infection IIM patients. Serum levels of suPAR, sTREM-1, PCT and CRP measured in this study were significantly higher in the IIM patient group with concurrent infection than in the non-infection IIM patient group (p < 0.05). The biomarker suPAR showed the highest diagnostic value with sensitivity, specificity, positive predictive value and negative predictive value of 81.6, 77.3, 75.6 and 82.9%, respectively. Combining suPAR negative and CRP negative to rule out bacterial infection in IIM patients provides a very high specificity of 97.4%. Both suPAR and CRP positive to confirm bacterial infection give the specificity of 90.9%. The inflammatory biomarkers suPAR, sTREM-1, PCT and CRP offer diagnostic accuracy in detecting bacterial infection in IIM patients. Particularly, suPAR is the most sensitive and specific biomarker to predict bacterial infection in IIM patients. Combination of suPAR and CRP serum levels provides an even better confirmation of bacterial infection.

Mortality trend of inpatients with connective tissue diseases: 2005-2014.

OBJECTIVE: To analyze the trend relevant factors leading to death and their patterns over a 10-year period in inpatients with connective tissue diseases (CTDs).
 Methods: All clinical data about death in inpatients with CTDs were retrospectively reviewed between 2005 and 2014 at the Department of Rheumatology and Immunology in Xiangya Hospital of Central South University.
 Results: In the 10-year time period, the overall hospital mortality was 15.68‰. The disease itself accounted for 44.71% of the total causes of death, infection accounted for 42.94%, and comorbidities accounted for 12.35%. The constituent ratio of deaths and the average hospital mortality caused by the disease itself declined gradually year by year, and the constituent ratio of deaths caused by infection and comorbidities increased gradually year by year (P<0.05). In 2013-2014, infection was the leading cause of death, which accounted for 51.06%. The survival time for CTDs inpatients with interstitial lung disease (ILD) was shorter than that of CTDs inpatients without ILD, and even the risk of death was 1.722 times of the latter. The proportion of deaths caused by the disease itself was the highest in systemic sclerosis and systemic lupus erythematosus, that by infection was the highest in idiopathic inflammatory myopathy (IIM), and that by comorbidities was the highest in rheumatoid arthritis.
 Conclusion: The proportion of deaths and the hospital mortality in CTDs inpatients caused by the disease itself show a declining trend, while the proportion of deaths caused by infection and comorbidities increase. CTDs patients with ILD have shorter survival time and an increase in risk of death.

Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients' clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the "dominant" phenotype in idiopathic double-positive AAV.

MicroRNA-21 in scleroderma fibrosis and its function in TGF-ß-regulated fibrosis-related genes expression.

Uncontrolled fibrosis in multiple organs is the main cause of death in systemic sclerosis (SSc), and transforming growth factor-ß (TGF-ß) activation plays a fundamental role in the process. Our previous study demonstrated that miR-21 was significantly up-regulated in SSc fibroblasts. Here, we found that TGF-ß regulated the expression of miR-21 and fibrosis-related genes, and decreased Smad7 expression. Over-expression of miR-21 in fibroblasts decreased the levels of Smad7, whereas knockdown of miR-21 increased its expression. Further study using a reporter gene assay demonstrated Smad7 was a direct target of miR-21. Similar to human SSc, the expression of miR-21 increased in the bleomycin induced skin fibrosis. Inhibition of fibrosis by treatment with anti-fibrosis drug bortezomib restored the levels of miR-21 and Smad7. MiR-21 may function in an amplifying circuit to enhance TGF-ß signaling events in SSc fibrosis, and suggesting that miR-21 may act as a potential therapeutic target.

[Clinical study of invasive fungal infection secondary to systemic lupus erythematosus].

OBJECTIVE: To study the clinical characteristics of invasive fungal infection secondary to systemic lupus erythematosus (SLE). METHODS: We observed the clinical features and experimental examination in 91 patients treated in Xiangya Hospital in recent years, of which 48 patients with invasive fungal infection and 41 patients without invasive fungal infection. RESULTS: The invasive fungal infection secondary to SLE mainly occurred in the lungs, nervous system, and urinary system. The fungi were mainly Candida albins and Aspergillus. The rate of invasive fungal infection in SLE patients and the level of CRP and TNF-α in these patients were significantly increased. The occurrence of invasive fungal infection was positively correlated with the prolonged course of disease, long-term use of immunosuppressants and antibiotics, and occurrence of complications, such as hypoproteinemia, leukocytopenia, and so on. The levels of C-reactive protein (CRP) and tumor necrosis factor-α(TNF-α) were increased in SLE patients with invasive fungal infection. CONCLUSION: The clinical features of SLE patients with invasive fungal infections are long course of disease, long-time use of immunosuppressants or antibiotics, and occurrence of complications, such as hypoproteinemia or leukopenia. The level of CRP and TNF-α can be used as an important reference index for diagnosing invasive fungal infections.

Development of a radiomics nomogram to predict the treatment resistance of Chinese MPO-AAV patients with lung involvement: a two-center study.

Background: Previous studies from our group and other investigators have shown that lung involvement is one of the independent predictors for treatment resistance in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV). However, it is unclear which image features of lung involvement can predict the therapeutic response in MPO-AAV patients, which is vital in decision-making for these patients. Our aim was to develop and validate a radiomics nomogram to predict treatment resistance of Chinese MPO-AAV patients based on low-dose multiple slices computed tomography (MSCT) of the involved lung with cohorts from two centers. Methods: A total of 151 MPO-AAV patients with lung involvement (MPO-AAV-LI) from two centers were enrolled. Two different models (Model 1: radiomics signature; Model 2: radiomics nomogram) were built based on the clinical and MSCT data to predict the treatment resistance of MPO-AAV with lung involvement in training and test cohorts. The performance of the models was assessed using the area under the curve (AUC). The better model was further validated. A nomogram was constructed and evaluated by DCA and calibration curves, which further tested in all enrolled data and compared with the other model. Results: Model 2 had a higher predicting ability than Model 1 both in training (AUC: 0.948 vs. 0.824; p = 0.039) and test cohorts (AUC: 0.913 vs. 0.898; p = 0.043). As a better model, Model 2 obtained an excellent predictive performance (AUC: 0.929; 95% CI: 0.827-1.000) in the validation cohort. The DCA curve demonstrated that Model 2 was clinically feasible. The calibration curves of Model 2 closely aligned with the true treatment resistance rate in the training (p = 0.28) and test sets (p = 0.70). In addition, the predictive performance of Model 2 (AUC: 0.929; 95% CI: 0.875-0.964) was superior to Model 1 (AUC: 0.862; 95% CI: 0.796-0.913) and serum creatinine (AUC: 0.867; 95% CI: 0.802-0.917) in all patients (all p< 0.05). Conclusion: The radiomics nomogram (Model 2) is a useful, non-invasive tool for predicting the treatment resistance of MPO-AAV patients with lung involvement, which might aid in individualizing treatment decisions.

The effect of discontinuation of maintenance therapy in Chinese patients with MPO-ANCA associated vasculitis who were in long-term stable remission.

There is a consensus that maintenance therapy should be used to prevent relapse of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV), but there is a debate about the optimal duration of maintenance therapy. Therefore, the purpose of this study was to determine whether discontinuation of maintenance therapy in MPO-AAV patients who were in long-term stable remission affects relapse, renal survival and patient survival. Seventy-nine patients with MPO-AAV diagnosed at Xiangya hospital from June 2010 to June 2019 who were in stable remission for at least 18 months following maintenance therapy were included. Patient records were retrospectively reviewed, and based on whether patients discontinued maintenance therapy 18 months after commencing maintenance therapy, patients were assigned into either the withdrawal group (n = 26) or maintenance group (n = 53). The endpoint was the percentage of relapse, relapse-free survival, renal survival and patient survival during follow-up. Ten relapses (38.5%) occurred in the withdrawal group (n = 26) and 8 relapses (15.1%) occurred in the maintenance group (n = 53) (p = 0.020). Compared to the withdrawal group, the maintenance group had similar relapse-free survival (log-rank test p = 0.099). But maintenance group had a better renal survival (p = 0.035), with no difference in patient survival or adverse events. This study suggests that discontinuing maintenance therapy at 18 months following induction of sustained remission leads to a significant increase in the percentage of relapse, and decreases renal survival in patients with MPO-AAV, but does not decrease relapse-free survival or patient survival.

Sex disparities in clinicopathological features and outcomes of patients with myeloperoxidase-ANCA-associated vasculitis: a retrospective study of 366 cases in a single Chinese center.

There are a few studies that reported sex disparities in clinical features, pathological features and outcomes among ANCA-associated vasculitis (AAV) patients, but studies focusing on sex-specific differences of myeloperoxidase (MPO)-AAV patients are scarce. Therefore, the purpose of this study was to analyze sex differences in clinicopathological features and outcomes of MPO-AAV. Patients diagnosed with MPO-AAV in Xiangya Hospital from January 2010 to June 2021 were included in the study and separated into female and male groups. The differences in clinical manifestations, laboratory parameters, pathological features and prognosis between the two groups were retrospectively analyzed. Three hundred and sixty-six patients were included and divided into female group (n = 176) and male group (n = 190). The age of the male group was 62.41 ± 10.49 years, significantly higher than that of the female group (58.69 ± 16.39, p = 0.011). Compared with the female group, the male group had a shorter duration of disease, higher levels of hemoglobin, eosinophil count, proteinuria, serum C4, and lower levels of serum globulin, serum IgG and serum IgM (p < 0.05). No significant differences in kidney pathological features were observed between the two groups. During a median follow-up of 37.6 months, there was no significant difference in renal survival and patient survival between the two groups, but male patients had a worse composite outcome of renal and patient survival compared with the female patients (p = 0.044). This study found that male patients with MPO-AAV had a higher age of onset, shorter duration of disease, higher levels of hemoglobin, eosinophil count, proteinuria, serum C4, and lower levels of serum globulin, serum IgG and serum IgM. Male patients fared worse than female patients in terms of the composite outcome of renal and patient survival.

MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma.

Scleroderma (systemic sclerosis, SSc) is a complex autoimmune disease caused by progressive fibrotic replacement of normal tissue architecture, a progressive and ultimately fatal process that currently has no cure. Although dysregulation of microRNAs (miRNAs) is known to be involved in a variety of pathophysiologic processes, the role of miRNAs in SSc is unclear. In comparison with the normal skin tissues, miRNAs were aberrantly expressed in limited cutaneous scleroderma and diffuse cutaneous scleroderma skin tissues. We also identified miRNAs whose expressions were correlated with SSc fibrosis: miR-21, miR-31, miR-146, miR-503, miR-145, and miR-29b were predicted to be involved. This study further confirmed that miR-21 was increased whereas miR-145 and miR-29b were decreased both in the skin tissues and fibroblasts. As predicted target genes, SMAD7, SAMD3, and COL1A1 were regulated by these miRNAs. After stimulation with transforming growth factor ß, the expression of miR-21 was increased and that of SMAD7 mRNA was decreased. MiR-145 was upregulated whereas the mRNA level of SMAD3 was downregulated. The downregulation of miR-29b was correlated with the upregulation of COL1A1 mRNA. MiRNAs might play an important role in the pathogenesis of SSc and suggest a potential therapy.

Nicotine inhibits tumor necrosis factor-α induced IL-6 and IL-8 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis.

It was recently demonstrated that the cholinergic anti-inflammatory pathway can modulate host inflammatory responses via cholinergic mediators or via electrical stimulation of the vagus nerve. Here, we investigated whether nicotine, a selective cholinergic agonist, plays any anti-inflammatory role in rheumatoid arthritis fibroblast-like synoviocytes (FLS). We observed that low concentrations (0.1-100 µM) of nicotine did not affect FLS viability in lactate dehydrogenase release test or the MTT assay. Nicotine at concentrations of 0.1-10 µM dose reduced the protein and mRNA expression of IL-6 and IL-8 induced by tumor necrosis factor-α (TNFα). Nicotine also inhibited nuclear factor (NF)-κB (p65) translocation from the cytoplasm to the nucleus, based on Western blotting and immunocytochemical analysis. In conclusion, nicotine can inhibit the TNFα dependant inflammatory pathway in synoviocytes by suppressing the activation of the NF-κB pathway.

Case Report: An Unusual Presentation of Cardiovascular Involvement in Eosinophilic Granulomatosis With Polyangiitis.

Background: Because eosinophilic granulomatosis with polyangiitis (EGPA) is so rare and the symptoms so varied, it can be a challenge to get a correct diagnosis in clinical practice. Cardiovascular involvement is the main cause of death of EGPA. We are the first to report of cardiac magnetic resonance (CMR) findings about right-sided heart involvement in EGPA. Patient Findings: The initial abnormalities detected by CMR were Löffler endocarditis with extensive thrombosis and left ventricular (LV) dysfunction. After active treatment, LV systolic function recovered and endocarditis with thrombosis significantly improved, but there was rapidly progressive pulmonary hypertension, enlargement of right atrium and right ventricle and persistent right-sided heart failure. The patient eventually died of sudden cardiac death 6 months after hospital discharge. Conclusions: Löffler endocarditis and right-sided heart involvement are both rare presentations in patients with EGPA. CMR is a reliable non-invasive tool to precisely and comprehensively assess cardiovascular involvement in EGPA.

Clinical features and prognosis of MPO-ANCA and anti-GBM double-seropositive patients.

Background: Several lines of evidence implicate that there are distinct differences between patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody double-seropositive patients (DPPs) and single-positive patients. Hence, we conducted a retrospective study from a single center in China to analyze the clinical and pathological features, and prognosis of DPPs. Methods: 109 patients with MPO-ANCA-associated vasculitis (MPO-AAV), 20 DPPs and 23 patients diagnosed with anti-GBM disease from a large center in China were included in this study. The ratio of patients with renal biopsy in three groups were 100%, 50% and 100%, respectively. Their clinical and pathological characteristics, and outcomes were analyzed. The intensity of immune deposits in the kidney at diagnosis was detected by immunofluorescence (IF). Furthermore, multivariate Cox hazard model analysis was used to assess the clinical and histological predictors of end-stage renal disease (ESRD) and death for DPPs. Results: In our study, we found that patients in the DPPs group were older than the other two groups (p = 0.007, MPO-AAV vs. DPPs; p < 0.001, DPPs vs. anti-GBM). The DPPs group had a higher value of serum creatinine (p = 0.041) and lower estimated glomerular filtration rate (eGFR) (p = 0.032) compared with MPO-AAV patients. On the contrary, the DPPs group had a lower serum creatinine (p = 0.003) compared with patients with anti-GBM group. The proportion of patients with cardiac system involvement in the DPPs group was higher than anti-GBM patients (p = 0.014). Cellular crescents could be generally observed in renal biopsy of DPPs and patients with anti-GBM glomerulonephritis. In addition, Bowman's capsule rupture was more common in DPPs than MPO-AAV patients (p = 0.001). MPO-AAV had a better renal and overall survival outcome than DPPs (p < 0.001). There was no significant difference of renal and overall survival outcome between DPPs and patients with anti-GBM disease. The incidence of ESRD in DPPs was negatively associated with lymphocyte count (HR 0.153, 95% CI 0.027 to 0.872, p = 0.034) and eGFR (HR 0.847, 95% CI 0.726 to 0.989, p = 0.036). Elevated serum creatinine was confirmed as a risk factor of both renal (HR 1.003, 95% CI 1.000 to 1.005, p = 0.019) and patient survival in DPPs (HR1.461, 95% CI 1.050 to 2.033, p = 0.024). Conclusion: In summary, compared with anti-GBM disease, DPPs tended to involve multi-organ damage rather than limited to the kidney. It is highlighted that serologic DPPs have a worse renal and patient prognosis than MPO-AAV. Moreover, we found that the risk factors of renal survival of DPPs include low lymphocyte count, elevated serum creatinine and reduced eGFR, and serum creatinine can predict patient survival.

Clinical features and outcomes of anti-neutrophil cytoplasmic autoantibody-associated vasculitis in Chinese childhood-onset patients.

Data on anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are limited in children. This study is to determine the clinical features and outcomes of childhood-onset AAV. A retrospective study was performed on patients who were diagnosed with AAV before 18 years old in Xiangya Hospital. Their medical records were analyzed by retrospective review. Sixteen patients were diagnosed with AAV before 18 years old in the past 9 years, with an average age of 13.3 ± 3.3 years and 13 of them were female. There were 15 patients with microscopic polyangiitis (MPA) and 1 with Wegener's granulomatosis. The interval between onset of disease and diagnosis of AAV was 2 (1.5-3) months. Most patients (15/16, 93.8%) had multi-organ involvement, and all patients had renal involvement with 7 (43.8%) patients requiring dialysis at presentation. Eleven patients underwent a renal biopsy, of which mixed class and sclerotic class were the most two common histological types. All patients received immunosuppressive therapy for induction therapy including intravenous administrations of methylprednisolone (MP) pulse therapy for 8 patients. 8 patients (50%) achieved remission after induction therapy. After a median follow-up of 46.3 ± 36.1 months, nine (56.3%) patients progressed to end-stage renal disease (ESRD) and 5 (31.3%) patients died. Childhood-onset AAV showed similar clinical and pathological features compared to those of adults, except that it usually occurs in girls. The most commonly involved organ was the kidney, and it had a high risk of progression to ESRD. Early diagnosis and initiation of appropriate immunomodulatory therapy would be important to improve outcomes.

ECMO Rescues Patients With Acute Respiratory Failure Related to GPA.

Granulomatosis with polyangiitis (GPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis with a wide range of clinical symptoms related to the systemic involvement of small blood vessels. The respiratory system is one of the most frequently involved, and life-threatening acute respiratory failure could occur due to diffusive alveolar hemorrhage and tracheal stenosis. When maximum mechanical ventilation is unable to maintain oxygenation, extracorporeal membrane oxygenation (ECMO) should be considered as the final respiratory supportive method, if available. Here we present a 32-year-old male patient with acute respiratory failure (ARF) related to GPA, who was rescued by winning time for accurate diagnosis and appropriate treatment. Additionally, we reviewed more than 60 GPA-related ARF cases on multiple online databases, summarized the clinical manifestations of these patients, and concluded that ECMO plays an important role in further respiratory support for ARF patients with GPA and assists in accurate and timely diagnosis and appropriate treatment, thus helping them recuperate.