Comparison of clinical characteristics between patients with axial spondyloarthritis with and without acute anterior uveitis: a multicentre study of the Chinese Spondyloarthritis Registry.

OBJECTIVES: This study explores the clinical characteristics associated with the occurrence of acute anterior uveitis (AAU) in patients with axial spondyloarthritis (axSpA) within a large, multicentre database. METHODS: This observational, cross-sectional study of patients with axSpA used data from the Chinese Spondyloarthritis Registry between August 1, 2018, and March 31, 2020. The demographic and clinical features of patients with and without AAU were compared. Univariate and multivariate analyses were performed to determine the association between variables and uveitis. RESULTS: A total of 4304 patients were included in this study. The prevalence of AAU in patients with axSpA was 10.59%. Multivariate logistic regression analysis revealed a positive correlation between AAU and age at diagnosis (odds ratio [OR], 1.026; p<0.001), disease duration (OR, 2.117; p<0.001), current or past Achilles tendinitis (OR, 1.692; p<0.001), current or past dactylitis (OR, 1.687; p=0.002), current or past psoriasis (OR, 3.932; p<0.001), presence of human leukocyte antigen-B27 (HLA-B27) (OR, 2.787; p<0.001), and a good response to non-steroidal anti-inflammatory drugs (NSAIDs) (OR, 1.343; p=0.027). CONCLUSIONS: AAU was the most common extra-articular manifestation in the Chinese Spondyloarthritis Registry. In Chinese patients with axSpA, older age at diagnosis, longer disease duration, presence of HLA-B27, current or past Achilles tendinitis, current or past dactylitis, current or past psoriasis, and a good response to NSAIDs were positively associated with AAU.

Clinical characteristics of axial spondyloarthritis patients in China: results from ChinaSpA, the Chinese Spondyloarthritis Registry.

OBJECTIVES: The objective of this study is to describe the clinical features of patients with axial spondyloarthritis (axial SpA) in the ChinaSpA registry. METHODS: Patients with clinical diagnosis of ankylosing spondylitis (AS) or axial SpA were enrolled into the registry. Patients with a complete set of pelvis radiograph, pelvis MRI and HLA-B27 (Complete Set group, CS group) were further categorised based on classification criteria into AS, radiographic axial SpA (r-axSpA) and non-radiographic axial SpA (nr-axSpA). Early axial SpA was defined as symptom duration of less than three years. Descriptive statistics were used to describe clinical characteristics of enrolled patients. ANOVA analyses were used to compare patients in different groups. RESULTS: A total of 5270 patients were enrolled in the study, and 3223 patients had complete sets of pelvis radiographs, MRIs and HLA-B27 status. Among them, more than 80% patients met both the ASAS criteria for r-axSpA and the modified New York criteria for AS. Among those with early axial SpA, 92% of patients had sacroiliitis on pelvis radiograph, 3.8% had sacroiliitis only on pelvis MRI, and 3.8% were in the clinical arm without any sacroiliitis on imaging studies. Patients in nr-axSpA clinical arm had less diagnosis delay, lower inflammatory markers and ASDAS, compared topatients in the r-axSpA, nr-axSpA MRI arm. CONCLUSIONS: In the ChinaSpA registry, patients in nr-axSpA clinical arm had the shortest diagnostic delay, lower inflammatory markers and ASDAS, but no difference in extra-articular manifestation, compared to patients in the r-axSpA and nr-axSpA MRI arm.

Efficacy and safety of certolizumab pegol in combination with methotrexate in methotrexate-inadequate responder Chinese patients with active rheumatoid arthritis: 24-week results from a randomised, double-blind, placebo-controlled phase 3 study.

OBJECTIVES: To evaluate the efficacy and safety of certolizumab pegol (CZP) in combination with methotrexate (MTX) in Chinese patients with active rheumatoid arthritis (RA) and an inadequate response to MTX. METHODS: This 24-week, phase 3, double-blind, placebo-controlled study was conducted in 30 centres across China. A total of 430 patients were randomised 3:1 to receive CZP 200 mg every 2 weeks (loading dose: 400 mg CZP at Weeks 0, 2 and 4) plus MTX or placebo (PBO) plus MTX. The primary endpoint was ACR20 response at Week 24, for which the superiority of CZP+MTX over PBO+MTX was evaluated. Additional parameters for clinical efficacy, health outcomes, immunogenicity and safety were assessed. RESULTS: At Week 24, 54.8% of CZP+MTX patients and 23.9% of PBO+MTX patients achieved ACR20 (odds ratio: 3.9, p<0.001). CZP+MTX patients also achieved greater improvements in HAQ-DI, higher ACR50/70 responses and higher DAS28(ESR) remission rate at Week 24. Rapid onset of response to CZP+MTX was observed as early as Week 1 for most of the clinical, functional and patient-reported outcomes. Incidences of treatment-emergent adverse events (TEAEs) were similar between treatment arms. Serious TEAEs were reported by 6.3% of CZP+MTX patients and 2.7% of PBO+MTX patients. No new safety signals were observed. CONCLUSIONS: CZP in combination with MTX showed an acceptable safety profile, a rapid onset of response and sustained effects in reducing the signs and symptoms of RA and improving physical function in Chinese patients with RA and an inadequate response to MTX.

An increased major vessel uptake by 18F-FDG-PET/CT in NIH criteria inactive patients with Takayasu's arteritis.

OBJECTIVES: The commonly adopted method of defining active disease in Takayasu's arteritis (TAK) is the definition used by the US National Institutes of Health (NIH). A gold standard in imaging techniques for assessing disease activity in TAK has not been clearly established and the creation of practical and valid tools represents a challenge. To assess whether 18F-FDG-PET/CT and NIH criteria show a good level of agreement in assessing disease activity of TAK patients. METHODS: 18F-FDG-PET/CT was performed in 17 patients with TAK. All 17 patients fulfilled the clinical criteria according to the American College of Rheumatology criteria. Two nuclear physicians visually assessed the degree of 18F-FDG uptake in the inflammatory vascular lesion. 18F-FDG-PET/CT and the inflammatory vascular lesion were evaluated by using the standardised uptake value (SUV) of 18F-FDG accumulation were interpreted as active vasculitic lesions. RESULTS: Of the 17 patients, 6 were in the active stage and 11 were in the inactive stage according to the level of disease activity as clinically assessed by the NIH criteria. No significant 18F-FDG accumulation was observed in the patients with inactive disease (SUV≤1.2). 18F-FDG-PET/CT localised 18F-FDG accumulation in the inflammatory lesion in the patients with TAK who had inactive disease (n=3) assessed by the NIH criteria. 18F-FDG PET/CT revealed intense 18F-FDG accumulation (SUV max 2.88) in the vasculature of 3 patients in the inactive stage of TAK. The other 8 patients in the active stage showed weak 18F-FDG accumulation (SUV ≤1.2). CONCLUSION: 18FDG-PET/CT appears to be a promising technique for the diagnosis and assessment of disease activity in patients of TAK, even those considered to be inactive by the NIH criteria. However, it needs to be validated in larger groups for cost-effectiveness and sensitivity to change.

Chinese registry of rheumatoid arthritis (CREDIT): I. Introduction and prevalence of remission in Chinese patients with rheumatoid arthritis.

OBJECTIVES: To introduce the Chinese Registry of rhEumatoiD arthrITis (CREDIT), which is the first nationwide, multicentre, online rheumatoid arthritis (RA) registry in China, and to depict major cross-sectional data and treatment strategies of Chinese RA patients. METHODS: RA patients who fulfilled the 2010 ACR/EULAR classification criteria for rheumatoid arthritis were recruited into the registry by their rheumatologists from 144 clinical centres in China. Data, including demographics, disease characteristics, co-morbidities, treatment, and adverse reactions, were collected and documented through the predefined protocol. RESULTS: 8071 registered patients (F:M = 4.03:1) were registered up to May 2017. Mean age at symptom onset and at diagnosis was 46.15±14.72y and 48.68±14.54y, respectively. Point prevalence of remission (95% CIs) was 14.88% (14.10-15.66%), 4.23% (3.79-4.66%), 4.25% (3.81-4.69%), and 4.27% (3.83-4.72%) according to DAS28-CRP, CDAI, SDAI, and the 2011 ACR/EULAR remission criteria, respectively. 38.84% and 38.11% of treatment-naïve patients (n=3262) were in moderate (3.25.1) disease activity, respectively. Among treatment-naïve patients, those who were initiated on treatment with bDMARDs had higher disease activity than those who were treated with csDMARDs (p<0.05). Three months after initiating bDMARDs, 19.29% (n=38) of patients achieved remission (DAS28-CRP<2.6). CONCLUSIONS: The CREDIT registry is an effective tool for real-world study of RA patients in China. By providing information for diagnosis and treatment regimen, the CREDIT registry can enhance the application of treat-to-target (T2T) strategy and improve patient outcomes in China.

Urinary Albumin Levels are Independently Associated with Renal Lesion Severity in Patients with Lupus Nephritis and Little or No Proteinuria.

BACKGROUND Systemic lupus erythematosus (SLE) leads to renal lesions, which may be clinically silent in patients with little or no proteinuria. Early detection of these lesions may improve prognosis, but early markers are controversial. This study aimed to determine renal marker proteins associated with renal lesion severity in patients with lupus nephropathy (LN) and little or no proteinuria. MATERIAL AND METHODS Patients with LN and little or no proteinuria (<0.5 g/24 hours) (n=187) that underwent kidney biopsy were grouped according to: low severity (Class I or II; n=116) versus high severity (Class III, IV, or V; n=71). Disease status was determined according to the SLE disease activity index (SLEDAI). Renal marker proteins (serum ß2-macroglobulin, urinary ß2-macroglobulin, albumin, IgG, and α1-macroglobulin) were measured using radioimmunoassay. RESULTS Compared with the low severity group, patients in the high severity group had higher urinary albumin (11.60±8.94 versus 7.08±10.07 µg/mL, p=0.008) and urinary IgG (13.21±9.35 versus 8.74±8.90 µg/mL, p=0.007) levels. Multivariate conditional logistic regression analysis showed that urinary albumin (odds ratio (OR)=1.417, 95% confidence interval (95% CI): 1.145-1.895, p=0.001) and SLEDAI (OR=2.004, 95% CI: 1.264-3.178, p=0.003) were independently associated with severe renal lesions in these patients. Using an optimal cutoff point of urinary albumin of 7.53 µg/mL resulted in 67% sensitivity and 82% specificity for the detection of high severity renal lesions. CONCLUSIONS Urinary albumin levels and SLEDAI were independently associated with histological severity of renal lesions in patients with LN and little or no proteinuria. These parameters could be used to help select patients for renal biopsy.

Metastasis-associated protein 1 (MTA1) signaling in rheumatoid synovium: Regulation of inflammatory response and cytokine-mediated production of prostaglandin E2 (PGE2).

Abnormal perpetual inflammatory response and sequential cytokine-induced prostaglandin E2 (PGE2) play important roles in the pathogenesis of rheumatoid arthritis (RA). The underlying regulatory mechanism, however, remain largely unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), an important chromatin modifier that plays a critical role in transcriptional regulation by modifying DNA accessibility for cofactors, was upregulated in human rheumatoid synovial tissues. Furthermore, a knockdown of MTA1 by siRNA in the human fibroblast-like synovial cell line MH7A was found to impair the 4-hydroxynonenal (4-HNE)-induced transcriptional expression levels of certain proinflammatory cytokines including IL-1ß, TNF-α and IL-6. Moreover, endogenous MTA1 was required for the cytokines-induced PGE2 synthesis by rheumatoid synoviocytes. Collectively, the coordinated existence of MTA1 inside distinct cascade loops points to its indispensable role in the modulation of the integrated cytokine network along the pathogenesis of RA. Further exploration of the functional details of this master transcriptional regulator should be an attractive strategy to identify novel therapeutic target for RA and warrants execution.

Protection of murine spermatogenesis against ionizing radiation-induced testicular injury by a green tea polyphenol.

Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol in green tea, exerts antiapoptotic activity and prevents tissue damage against different stimuli. Herein, we investigated the effects of EGCG treatment to simultaneously improve spermatogenesis following ionizing radiation (IR) (at a dose of 2 Gy). Mice were intraperitoneally injected with 50 mg/kg EGCG or vehicle control 3 days prior to the irradiation, and the treatment lasted intermittently for 24 days. Supplement with exogenous EGCG protected against short-term germ cell loss and attenuated IR-elicited testicular oxidative stress. Mechanistically, prosurvival effects of EGCG treatment upon IR stress were regulated, at least in part, via the mitogen-activated protein kinase/BCL2 family/caspase 3 pathway. Consistently, at post-IR Day 21, histological analyses revealed tubule damage, desquamation of germ cells, and impairment of caudal parameters in irradiated testis, which could be significantly improved by intermittent EGCG treatment. In addition, long-term EGCG application ameliorated the IR-induced blood-testicular barrier permeability and suppressed testicular steroidogenesis, thus exerting a stimulatory effect on the spermatogenic recovery. Collectively, EGCG appeared to efficiently prevent germ cells from radiation-induced cell death via multiple mechanisms. Employment of this bioactive polyphenol should be an attractive strategy to preserve fertility in males exposed to conventional radiation therapy and warrants further investigation.

Kinetic changes of regulatory B10 cells in collagen-induced arthritis could be regulated by cytokines IFN-γ and TGF-ß1.

OBJECTIVE: The status of B10 cells in patients with rheumatoid arthritis (RA) has not been consistently reported. In this study, we observed the kinetic changes of the B10 cells in collagen-induced arthritis (CIA) mice and the influence of multiple cytokines on the B10 cells to investigate the potential mechanism underlying the changes of B10 cells. METHODS: The kinetic changes of frequency and function of the CD19(+)CD1d(hi)CD5(+) cells in splenic cells were observed during the complete progress of CIA mice. The kinetic changes of cytokines IL-4, IL-6, IL-17A, IL-18, TNF-α, IFN-γ and TGF-ß1 were also detected. Then influence of these cytokines on the status of B10 cells was investigated both in vitro and in vivo. RESULTS: The frequency and suppressive ability of the CD19(+)CD1d(hi)CD5(+) cells increased to its peak on the 14th day while gradually decreased subsequently. IFN-γ showed a similar tendency with the CD19(+)CD1d(hi)CD5(+) cells, whereas IL-6, IL-17A, IL-18, TNF-α, and TGF-ß1 reached its peak on the 28-35th day. In addition, IFN-γ up-regulated while TGF-ß1 down-regulated the frequency and function of the CD19(+)CD1d(hi)CD5(+) cells both in vitro and in vivo. CONCLUSION: The B10 cells in CIA mice could be regulated by IFN-γ and TGF-ß1, suggesting that the status of B10 cells in RA may be influenced by the balance of pro-inflammatory and anti-inflammatory factors, and the impaired B10 cells could be recovered in vitro by adequate treatment before being used for a therapeutic method in clinical practice.

Gastric presentation (vasculitis) mimics a gastric cancer as initial symptom in granulomatosis with polyangiitis: a case report and review of the literature.

Granulomatosis with polyangiitis (GPA), formerly called Wegener's Granulomatosis, is characterized by necrotizing granulomatous inflammation and belongs to the family of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. The main clinical symptoms of GPA are vasculitis primarily involving upper and lower respiratory tracts, as well as kidneys. Gastrointestinal manifestations of GPA are less common (0-20 %), with gastric presentation mimicking a gastric cancer as an initial symptom. This is a descriptive case report of one patient, together with systematic review of the literature. We described a 31-year-old Chinese woman who presented with complaints of abdominal distention, anorexia for 2 months. Gastroscopy was carried out for three times, and stomach cancer was suspected. However, histopathology of gastric biopsy revealed a chronic inflammation with mucosal ulceration, frequent neutrophils and lymphocytes infiltration, and local granulomatous formation, whereas no sign of stomach carcinoma was observed. In view of the positive cANCA test, a diagnosis of GPA was considered. From the onset of the GPA in the patients, no other organs have been involved in the disease. The patient was successfully treated with corticosteroids and cyclophosphamide. As shown in the report, patients who present only with gastrointestinal manifestations represent challenges to diagnosis. ANCA testing can serve as a decisive diagnostic tool. Although uncommon, GI involvement may be a major feature in GPA, sometimes presenting as gastric tumor-like lesions. Diagnosis should be considered in patients presenting with GI symptoms accompanied by evidence of systemic vasculitis, and ANCA test should be used as a diagnostic measurement to clarify differential diagnosis.

α,ß-Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress.

Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,ß-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,ß-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism.

CD147 up-regulates calcium-induced chemotaxis, adhesion ability and invasiveness of human neutrophils via a TRPM-7-mediated mechanism.

OBJECTIVES: We aimed to investigate whether CD147 can up-regulate the chemotactic, adhesive and invasive properties of human neutrophils and to determine the mechanism underlying this process. METHODS: Human promyelocytic leukaemia cells (HL-60) cells and peripheral blood or synovial fluid neutrophils were isolated from RA patients. Under cyclophilin A (CypA) stimulation, chemotaxis, adhesion potential and invasion ability were assessed using chemotaxis, adhesion and invasiveness assays. Lipid raft isolation and western blot were used to determine the mechanism underlying the effects of CypA stimulation. RESULTS: CD147 up-regulates the calcium-induced chemotaxis, adhesion ability and invasiveness of human neutrophils in RA patients. Transient receptor potential melastatin 7 may be responsible for this phenomenon. CONCLUSION: These findings suggest that in RA patients, abundant CypA up-regulates the calcium-induced chemotactic, adhesive and invasive properties of neutrophils via direct binding to CD147. Cyclophilin-CD147 interactions might contribute to the destruction of cartilage and bone in RA.

α,ß-Unsaturated aldehyde crotonaldehyde triggers cardiomyocyte contractile dysfunction: role of TRPV1 and mitochondrial function.

Recent evidence has suggested that cigarette smoking is associated with an increased prevalence of heart diseases. Given that cigarette smoking triggers proinflammatory response via stimulation of the capsaicin-sensitive transient receptor potential cation channel TRPV1, this study was designed to evaluate the effect of an essential α,ß-unsaturated aldehyde from cigarette smoke crotonaldehyde on myocardial function and the underlying mechanism with a focus on TRPV1 and mitochondria. Cardiomyocyte mechanical and intracellular Ca2+ properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90), fura-2 fluorescence intensity (FFI), intracellular Ca2+ decay and SERCA activity. Apoptosis and TRPV1 were evaluated using Western blot analysis. Production of reactive oxygen species (ROS) and DNA damage were measured using the intracellular fluoroprobe 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and 8-hydroxy-2'-deoxyguanosine (8-OHdG), respectively. Our data revealed that crotonaldehyde interrupted cardiomyocyte contractile and intracellular Ca2+ property including depressed PS, ±dL/dt, ΔFFI and SERCA activity, as well as prolonged TR90 and intracellular Ca2+ decay. Crotonaldehyde exposure increased TRPV1 and NADPH oxidase levels, promoted apoptosis, mitochondrial injury (decreased aconitase activity, PGC-1α and UCP-2) as well as production of ROS and 8-OHdG. Interestingly, crotonaldehyde-induced cardiac defect was obliterated by the ROS scavenger glutathione and the TRPV1 inhibitor capsazepine. Capsazepine (not glutathione) ablated crotonaldehyde-induced mitochondrial damage. Capsazepine, glutathione and the NADPH inhibitor apocynin negated crotonaldehyde-induced ROS accumulation. Our data suggest a role of crotonaldehyde compromises cardiomyocyte mechanical function possibly through a TRPV1- and mitochondria-dependent oxidative stress mechanism.

Anemia and Low Body Mass Index in Axial Spondyloarthritis: Results from ChinaSpA, the Chinese Spondyloarthritis Registry.

INTRODUCTION: Anemia and malnutrition are recognized indicators of suboptimal physical condition in chronic inflammatory diseases. This study aimed to examine the association between anemia, low body mass index (BMI), and clinical outcomes in axial spondyloarthritis (axSpA). METHOD: This cross-sectional analysis utilized data from the multicenter ChinaSpA cohort. A total of 4146 participants with axSpA were categorized into four groups based on BMI and hemoglobin levels: those with both anemia and low BMI, those with anemia only, those with low BMI only, and those with neither condition. Logistic regression analyses were performed to analyze the association between anemia, low BMI, inflammation status, functional impairment, and disease activity. RESULTS: Anemia was present in 13.94%, low BMI in 11.99%, and both conditions in 2.15% of axSpA participants. Those with both anemia and low BMI showed significantly higher levels of inflammation (hypersensitive C-reactive protein [hsCRP] 30.60 mg/L vs. 8.44 mg/L), functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI] 3.80 vs. 2.10), and disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 4.52 ± 2.04 vs. 3.67 ± 2.21; Ankylosing Spondylitis Disease Activity Score calculated with C-reactive protein [ASDAS_CRP] 3.51 ± 1.10 vs. 2.62 ± 1.21) compared to those without these conditions. After adjusting for sex and age, significant associations were observed between elevated hsCRP levels and the presence of low BMI (odds ratio [OR] 1.44, 95% CI 1.17-1.78), anemia (OR 1.91, 95% CI 1.56-2.32), and their concurrent presence (OR 3.59, 95% CI 2.22-5.80). Similarly, increased BASFI was significantly associated with low BMI (OR 1.57, 95% CI 1.25-1.97), anemia (OR 1.47, 95% CI 1.19-1.80), and their combination (OR 3.11, 95% CI 2.02-4.78). CONCLUSION: All-cause anemia and low BMI are prevalent complications in patients with axSpA, exhibiting a significant correlation with elevated inflammation status and functional impairment. The simultaneous occurrence of anemia and low BMI particularly exacerbates clinical outcomes, emphasizing the critical role of comprehensive nutritional assessment and management in the therapeutic strategy for axSpA.

Ticagrelor: positive, negative and misunderstood properties as a new antiplatelet agent.

Dual antiplatelet therapy is essential for the management of acute coronary syndrome. In particular, combination therapy using aspirin with a platelet ADP (i.e. P2Y12 ) receptor inhibitor, such as clopidogrel, prasugrel or, more recently, ticagrelor, has been recommended for patients with acute coronary syndrome. Pharmacological agents that reversibly inhibit platelet aggregation without metabolic activation in the liver are believed to reduce cardiovascular mortality compared with the current drug of choice for antiplatelet therapy, namely clopidogrel. These findings are based on a multicentre, double-blind, double-dummy, randomized controlled trial. Numerous factors are postulated to contribute to the improved survival of patients who take ticagrelor compared with those taking clopidogrel, including the risk of myocardial infarction, heart failure, arrhythmia and bleeding. In addition, clopidogrel may lead to a much higher incidence of infection. Although ticagrelor has recently been approved for use in the US and exhibits superiority over other antiplatelet agents, certain concerns remain regarding its use, including lung injury and dyspnoea, thus raising the issue of its true superiority over clopidogrel or prasugrel. Recent studies into ticagrelor report conflicting data, with certain aspects of its mechanisms of action still not fully understood. Ticagrelor has beneficial effects following its clinical application, such as achieving overall higher reductions in mortality compared with the use of clopidogrel and prasugrel. Harmful effects associated with the use of ticagrelor include a higher incidence of dyspnoea and major bleeding compared with clopidogrel.

[Influencing factors of recurrence of systemic lupus erythematosus: An update].

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple tissues and organs. Frequent flare has been regarded as one of the main problems in the diagnosis and treatment of SLE, while the causes for frequent flare has remained to be unclear. We summarized the survival status and the situation of recurrence of SLE patients. The research progress regarding the recurrence and its mechanism will be reviewed from the aspects of genetic factors, environmental factors (i.e. infection, ultraviolet, vitamin D, chemical pollutants), drug and patient compliance, systemic damage and disease status, sex hormones and pregnancy, and social psychology. The implication is to explore effective clinical intervention to alleviate the SLE disease and improve the living quality of the patients.

Alterations of CD8+ T cells in the blood and salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVE: To identify the alterations of CD8+ T cells in blood and labial salivary glands (LSGs) of patients with Primary Sjögren's syndrome (pSS). METHODS: Blood samples from 24 pSS patients were assayed for CD38+ HLA-DR+ CD8+ (activated CD8+, aCD8+) T cells and serum IFN-γ and TNF-α, using flow cytometry and ELISA respectively, and compared with samples from 27 healthy controls. Immunohistochemistry was used to count CD8+ T cells in LSG tissues of 24 pSS patients and of 6 control patients with normal pathology. RESULTS: pSS patients had more aCD8+ T cells than aCD4+ T cells (medians 33.13% vs. 9.43%, p < 0.0001), and had an increased level of aCD8+ T cells (medians 33.13% vs. 16.48%, p < 0.0001) and serum IFN-γ (medians 1026 pg/mL vs. 0.00 pg/mL, p < 0.0001) compared to the healthy controls. The levels of aCD8+ T cells and IFN-γ were both significant positively correlated with European League Against Rheumatism Sjögren's Syndrome Disease Activity Index, IgG, anti-nuclear antibodies, rheumatoid factor. The LSGs focus score (FS) ≥1 group had more CD8+ T cell counts than 0≤ FS <1 group and control group (medians 256/mm2 vs. 126/mm2 and 256/mm2 vs. 64/mm2 respectively, both p < 0.05). CONCLUSION: The aCD8+ T cells and IFN-γ are positively correlated with each other, and predominantly elevated in the blood of pSS patients. In the LSG tissues of pSS, CD8+ T cell counts increase with severity of the lesions. CD8+ T cells may play crucial role in the pathogenesis of pSS. Key Points • Primary Sjögren's syndrome (pSS) is a chronic and systemic autoimmune disease. pSS patients had elevated blood levels of CD38 + HLA-DR+ CD8+ T cells and IFN-γ. • The CD38 + HLA-DR+ CD8+ T cells positively correlated with disease parameters and serum IFN-γ. • The salivary glands of pSS patients had appreciable CD8 + lymphocyte infiltration. CD8+ T cells may play crucial role in the pathogenesis of pSS.

Predictors of relapse in Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TAK) is a large-vessel vasculitis with high relapse rate. Longitudinal studies identifying risk factors of relapse are limited. We aimed to analyze the associated factors and develop a risk prediction model for relapse. METHODS: We analyzed the associated factors for relapse in a prospective cohort of 549 TAK patients from the Chinese Registry of Systemic Vasculitis cohort between June 2014 and December 2021 using univariate and multivariate Cox regression analyses. We also developed a prediction model for relapse, and stratified patients into low-, medium-, and high-risk groups. Discrimination and calibration were measured using C-index and calibration plots. RESULTS: At a median follow-up of 44 (IQR 26-62) months, 276 (50.3%) patients experienced relapses. History of relapse (HR 2.78 [2.14-3.60]), disease duration <24 months (HR 1.78 [1.37-2.32]), history of cerebrovascular events (HR 1.55 [1.12-2.16]), aneurysm (HR 1.49 [1.10-2.04], ascending aorta or aortic arch involvement (HR 1.37 [1.05-1.79]), elevated high-sensitivity C-reactive protein level (HR 1.34 [1.03-1.73]), elevated white blood cell count (HR 1.32 [1.03-1.69]), and the number of involved arteries ≥6 (HR 1.31 [1.00-1.72]) at baseline independently increased the risk of relapse and were included in the prediction model. The C-index of the prediction model was 0.70 (95% CI 0.67-0.74). Predictions correlated with observed outcomes on the calibration plots. Compared to the low-risk group, both medium and high-risk groups had a significantly higher relapse risk. CONCLUSIONS: Disease relapse is common in TAK patients. This prediction model may help to identify high-risk patients for relapse and assist clinical decision-making.

Risk factors for avascular necrosis in patients with systemic lupus erythematosus: a multi-center cohort study of Chinese SLE Treatment and Research Group (CSTAR) Registry XXII.

BACKGROUND: Avascular necrosis is a common organ damage in SLE patients, which can influence patients' life quality. Conflicting results exist in risk factors of AVN in SLE patients. The aim of this study was to illustrate risk factors predicting the occurrence of avascular necrosis (AVN), also known as osteonecrosis, in systemic lupus erythematosus (SLE) patients in Chinese SLE Treatment and Research Group (CSTAR), a multi-center cohort of Chinese SLE patients. METHODS: SLE patients in CSTAR without existing AVN at registration were included. At least two follow-ups and an observation period of no less than 2 years for AVN event were required. Univariate and multivariate Cox regression analyses were used to evaluate risk factors for AVN in SLE patients. Coefficient B was transformed to risk score for the development of a risk stratification model. RESULTS: One hundred six (2.59%) of 4091 SLE patients were diagnosed AVN during follow-ups of no less than 2 years. Multi-variate Cox regression analysis suggested that SLE onset age ≤ 30 (HR 1.616, p 0.023), arthritis (HR 1.642, p 0.018), existing organ damage (SDI ≥ 1) at registration (HR 2.610, p < 0.001), positive anti-RNP (HR 1.709, p 0.006), and high glucocorticoid maximum daily dose at registration (HR 1.747, p 0.02) were independent risk factors. A risk stratification system was developed according to the risk factors, and patients were divided into high risk (3-6) and low risk (0-2). The AUC of 0.692 indicated moderate discrimination. The calibration curve in internal validation was drawn. CONCLUSION: Patients with SLE onset age ≤ 30, arthritis, existing organ damage (SDI ≥ 1) at registration, positive anti-RNP, and high glucocorticoid maximum daily dose at registration are at high risk for AVN and require attention.

Management of Rheumatoid Arthritis With a Digital Health Application: A Multicenter, Pragmatic Randomized Clinical Trial.

IMPORTANCE: Digital health applications have been shown to be effective in the management of chronic diseases with simple treatment targets. The potential clinical value of digital health applications in rheumatoid arthritis (RA) has not been well studied. OBJECTIVE: To investigate whether assessing patient-reported outcomes using digital health applications could result in disease control for patients with RA. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, open-label randomized clinical trial in 22 tertiary hospitals across China. Eligible participants were adult patients with RA. Participants were enrolled from November 1, 2018, to May 28, 2019, with a 12-month follow-up. The statisticians and rheumatologists who assessed disease activity were blinded. Investigators and participants were not blind to group assignment. Analysis was conducted from October 2020 to May 2022. INTERVENTIONS: Participants were randomly assigned at a 1:1 ratio (block size of 4) to a smart system of disease management group (SSDM) or a conventional care control group. Upon the completion of the 6-month parallel comparison, patients in the conventional care control group were instructed to use the SSDM application for an extension of 6 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of patients with disease activity score in 28 joints using the C-reactive protein (DAS28-CRP) of 3.2 or less at month 6. RESULTS: Of 3374 participants screened, 2204 were randomized, and 2197 patients with RA (mean [SD] age, 50.5 [12.4] years; 1812 [82.5%] female) were enrolled. The study included 1099 participants in the SSDM group and 1098 participants in the control group. At month 6, the rate of patients with DAS28-CRP of 3.2 or less was 71.0% (780 of 1099 patients) in the SSDM group vs 64.5% (708 of 1098 patients) in the control group (difference between groups, 6.6%; 95% CI, 2.7% to 10.4%; P = .001). At month 12, the rate of patients with DAS28-CRP of 3.2 or less in the control group increased to a level (77.7%) that was comparable with that (78,2%) in the SSDM group (difference between groups, -0.2%; 95% CI, -3.9% to 3.4%; P = .90). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of RA, the use of a digital health application with patient-reported outcomes was associated with an increase in disease control rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03715595.