Chinese guideline for the diagnosis and treatment of Takayasu's arteritis (2023).

Takayasu's arteritis (TAK) is a chronic granulomatous inflammatory disease that involves aorta and its primary branches. It is characterized by wall thickening, stenosis/obliteration or aneurysm formation of the involved arteries. In order to standardize the diagnosis and treatment of TAK in China, a clinical practice guideline with an evidence-based approach is developed under the leadership of National Clinical Medical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID). Eleven recommendations for 11 clinical questions that are important to the diagnosis and treatment of TAK are developed based on the latest evidence and expert opinions combined with real clinical practice in China.

Isthmin-1 alleviates cardiac ischemia/reperfusion injury through cGMP-PKG signaling pathway.

AIMS: Ischemia/reperfusion (I/R) injury is an important complication of reperfusion therapy for acute myocardial infarction, extremely compromising the cardiac benefits of revascularization, however, specific and efficient treatment for cardiac I/R injury is still lacking. Isthmin-1 (ISM1) is a novel adipokine, and plays indispensable roles in regulating glycolipid metabolism and cell survival. The present study aims to investigate the potential role and molecular mechanism of ISM1 in cardiac I/R injury using gain- and loss-of-function approaches. METHODS AND RESULTS: Cardiac-specific ISM1 overexpression and silence were achieved using an adeno-associated virus serotype 9 system, and then these mice were subjected to I/R surgery, followed by biochemical test, echocardiography and histopathologic examinations, etc. Meanwhile, neonatal rat cardiomyocytes (NRCMs) with ISM1 silence or overexpression also received simulated I/R (sI/R) injury to further verify its role in vitro. The potential downstream pathways and molecular targets of ISM1 were screened by RNA-sequencing. We also treated injured mice and NRCMs with recombinant ISM1 (rISM1) to explore whether supplementation with ISM1 was sufficient to protect against I/R injury. Furthermore, acute myocardial infarction patients with percutaneous coronary intervention (PCI) and paired healthy controls were included to reveal the clinical relevance of circulating ISM1. Cardiac-specific ISM1 silencing aggravated while ISM1 overexpression alleviated I/R-induced acute cardiac injury and cardiac remodeling and dysfunction. Mechanistically, ISM1 targeted αvß5 integrin to facilitate the nuclear accumulation of nuclear transcription factor Y subunit alpha, transcriptionally increased soluble guanylyl cyclase beta subunit expression, and eventually enhanced cGMP generation. Besides, we confirmed that treatment with rISM1 before or after reperfusion could confer cardioprotective effects in mice. Clinically, lower ISM1 levels post-PCI was associated with worse outcome in patients. CONCLUSION: ISM1 can protect against cardiac I/R injury through cGMP-PKG signaling pathway, and it is a promising therapeutic and predictive target of cardiac I/R injury.

Higher Dietary Inflammatory Index Increases Mortality Rate of Adults With Hyperuricemia: Findings From the National Health and Nutritional Examination Surveys (2001-2018).

OBJECTIVE: This study aimed to assess the association between Dietary Inflammatory Index (DII) score and mortality among adults with hyperuricemia. METHODS: We collected data from the 2001-2018 cohorts of the National Health and Nutritional Examination Surveys (NHANES). Mortality information was obtained based on death certificate records from the National Death Index (NDI) through 31 December 2019. The associations between DII score and all-cause, cardiovascular disease (CVD) and cancer mortality were investigated by using Cox proportional hazards regression models. RESULTS: We enrolled 7786 participants with hyperuricemia in this study. The DII score ranged from -4.42 to 4.61. Higher DII score was significantly associated with higher levels of BMI, glycohemoglobin, glucose, LDL-cholesterol and CRP (all P <0.05). During 67851 person-years of follow-up, 1456 participants were identified death including 532 CVD deaths and 246 cancer deaths. After adjusted for potential variables, significant higher risk of all-cause (HR:1.18, 95% CI: 1.03, 1.36, P =0.01) and CVD (HR:1.30, 95% CI: 1.03, 1.63, P =0.02) mortality was observed for individuals with higher DII score. Considering the DII score as a continuous variable, the risk of all-cause and CVD mortality increases 5% (HR:1.05, 95% CI: 1.01, 1.08) and 8% (HR:1.08, 95% CI: 1.02, 1.15) with each one-unit increment in DII, respectively. Subgroup analysis indicated that the association between DII and all-cause mortality among hyperuricemia participants was more significant in male. CONCLUSION: DII score is found positively associated with all-cause and CVD mortality of adults with hyperuricemia. Controlling the intake of pro-inflammatory food might be potential strategy to reduce mortality.

Serum IL-6 level trajectory for predicting the effectiveness and safety of tocilizumab in the treatment of refractory Takayasu arteritis.

AIM: To explore the value of serial monitoring of serum interleukin-6 (IL-6) levels for predicting treatment response and occurrence of adverse events during tocilizumab (TCZ) treatment in refractory Takayasu arteritis (TAK). METHODS: TAK patients receiving TCZ treatment were prospectively recruited and followed up at 1 month, 3 months and then every 3-6 months. Serum IL-6 levels were measured at each visit. Overall response was the combination of complete and partial response, requiring resolution of signs and symptoms, hsCRP and ESR level decreased at least by half, no progression on imaging and dose of glucocorticoid <15 mg/d. RESULTS: Thirty-five patients with a median follow up duration of 17 [9-44] months were included. The change of IL-6 after TCZ treatment for 6 months compared to the baseline was significantly lower in patients achieved overall response at 6, 12, 18 and 24 months. The ratio of IL-6 at 6 months to baseline could predict overall response at 12 and 24 months after TCZ treatment. With a cutoff value of 1.6, the sensitivity and specificity were 83.3 % and 87.5 % for 12 months, while 100 % and 88.9 % for 24 months. Patients with the ratio less than 1.6 were also 9 times more likely to achieve sustained improvement without treatment intensification. No correlation between IL-6 dynamics and occurrence of adverse events was found. CONCLUSIONS: The change of IL-6 levels after TCZ treatment for 6 months compared to the baseline can predict the overall treatment response at 12 months, 24 months and sustained improvement.

Performance validation of the 2023 American College of Rheumatology/European League Against Rheumatism antiphospholipid syndrome classification criteria in an antiphospholipid syndrome cohort.

BACKGROUND: The 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) antiphospholipid syndrome (APS) classification criteria were developed with higher specificity but lower sensitivity compared with the 2006 Sydney revised classification criteria. OBJECTIVES: To validate the performance of the 2023 ACR/EULAR APS classification criteria in a large Chinese APS cohort. METHODS: This was a single-center cohort study. Inclusion criteria aligned with the entry criteria of 2023 criteria. APS classification by "expert consensus panel" served as the gold standard. Sensitivity and specificity were compared between the 2023 and 2006 criteria. RESULTS: A total of 526 patients with a mean age of 38.55 ± 12.67 years were enrolled, of whom 366 (69.58%) were female and 182 (34.60%) had systemic lupus erythematosus (SLE). Among them, 407 (77.38%) patients were classified as APS by experts. The 2023 criteria demonstrated higher overall specificity than the 2006 criteria (0.983 vs 0.950), while sensitivity was relatively lower (0.818 vs 0.853). The sensitivity of the 2023 criteria improved for patients with SLE (0.860 vs 0.825), microvascular manifestations (0.867 vs 0.786), cardiac valve disease (0.903 vs 0.774), and thrombocytopenia (0.811 vs 0.790). Reduced sensitivity of the 2023 criteria was linked to the omission of certain microvascular manifestations, a stricter definition of pregnancy morbidity, and the exclusion of isolated thrombocytopenia and isolated IgM isotype antiphospholipid antibodies from meeting clinical and laboratory criteria, respectively. CONCLUSION: The 2023 criteria offer higher overall specificity and improved sensitivity in specific patient subsets, such as those with SLE, microvascular manifestations, cardiac valve disease, and thrombocytopenia when compared with the 2006 criteria.

Characterization of kidneys in patients with systemic sclerosis by multi-parametric magnetic resonance quantitative imaging.

PURPOSE: To determine the usefulness of multiparametric magnetic resonance (MR) quantitative imaging in characterizing the kidneys in systemic sclerosis (SSc) patients. MATERIAL AND METHODS: Forty-six SSc patients (47.9 ± 12.8 years, 40 females) and 22 age- and sex- matched healthy volunteers (46.1 ± 13.8 years, 20 females) were recruited and underwent renal MR imaging by acquiring blood oxygen level dependent and saturated multi-delay renal arterial spin labeling (SAMURAI) sequences. The T2* value, T1 value, renal blood flow (RBF), arterial bolus arrival time (aBAT), and tissue bolus arrival time (tBAT) of renal cortex were measured and compared among diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) groups and healthy controls using One-way ANOVA and analyzed by logistic regression. RESULTS: Compared to healthy volunteers, SSc patients with normal estimated glomerular filtration rate (n = 40) had significantly lower T2* value (P = 0.026) in the left renal cortex, longer T1 value (right: P = 0.015; left: P = 0.023), lower RBF (right: P < 0.001; left: P < 0.001), and shorter tBAT (right: P < 0.001; left: P = 0.005) in both right and left renal cortex after adjusting for demographics. The dcSSc patients (n = 23) had significantly lower RBF in both right (226.7 ± 65.2 mL/100 g/min vs. 278.2 ± 73.5 mL/100 g/min, P = 0.022) and left (194.5 ± 71.5 mL/100 g/min vs. 252.7 ± 84.4 mL/100 g/min, P = 0.020) renal cortex compared to the lcSSc patients (n = 23) after adjusting for demographics, but the significance of the difference was attenuated after further adjusting for modified Rodnan skin score and digital ulcers. CONCLUSION: Multi-parametric MR quantitative imaging, particularly multi-delay ASL perfusion imaging, is a useful technique for characterizing the kidneys and classification of SSc patients.

Efficacy and safety of mesenchymal stem cell-derived microvesicles in mouse inflammatory arthritis.

OBJECTIVE: To determine the effective and safe intravenous doses of mesenchymal stem cells (MSCs)-derived microvesicles (MVs) and to elucidate the possible causes of death in mice receiving high-dose MVs. METHODS: MVs were isolated from human MSCs by gradient centrifugation. Mice with collagen-induced arthritis were treated with different doses of intravenous MVs or MSCs. Arthritis severity, white blood cell count, and serum C-reactive protein levels were measured. To assess the safety profile of MSCs and MVs, mice were treated with different doses of MSCs and MVs, and LD50 was calculated. Mouse lungs and heart were assessed by live fluorescence imaging, histopathological measurements, and immunohistochemistry to explore the possible causes of death. Serum concentrations of cTnT, cTnI, and CK-MB were determined by ELISA. With the H9C2 cardiomyocyte cell line,  cellular uptake of MVs was observed using confocal microscopy and cell toxicity was assessed by CCK-8 and flow cytometry. RESULTS: Intravenous treatment with MSCs and MVs alleviated inflammatory arthritis, while high doses of MSCs and MVs were lethal. Mice receiving a maximum dose of MSCs (0.1 mL of MSCs at 109/mL) died immediately, while mice receiving a maximum dose of MVs (0.1 mL of MVs at 1012/mL) exhibited tears, drooling, tachycardia, shortness of breath, unbalanced rollover, bouncing, circular crawling, mania, and death. Some mice died after exhibiting convulsions and other symptoms. All mice died shortly after injecting the maximum dose of MSCs. Histologically, mice receiving high doses of MSCs frequently developed pulmonary embolism, while those receiving high doses of MVs died of myocardial infarction. Consistently, the serum levels of cTnT, cTnI, and CK-MB were significantly increased in the MVs-treated group (P < 0.05). The LD50 of intravenous MVs was 1.60 × 1012/kg. Further, MVs could enter the cell. High doses of MVs induced cell apoptosis, though low concentrations of MVs induced cell proliferation. CONCLUSIONS: Appropriate dosages of MVs and MSCs are effective treatments for inflammatory arthritis while MVs and MSCs overdose is unsafe by causing cardiopulmonary complications.

Prediction of progressive fibrosing interstitial lung disease in patients with systemic sclerosis: insight from the CRDC cohort study.

BACKGROUND: This study aims to establish a reliable prediction model of progressive fibrosing interstitial lung disease (PF-ILD) in patients with systemic sclerosis (SSc)-ILD, to achieve early risk stratification and to help better in preventing disease progression. METHODS: 304 SSc-ILD patients with no less than three pulmonary function tests within 6-24 months were included. We collected data at baseline and compared differences between SSc patients with and without PF-ILD. Least absolute shrinkage and selection operator regularisation regression and multivariable Cox regression were used to construct the prediction model, which were presented as nomogram and forest plot. RESULTS: Among the 304 patients with SSc-ILD included, 92.1% were women, with a baseline average age of 46.7 years. Based on the 28 variables preselected by comparison between SSc patients without PF-ILD group (n=150) and patients with SSc PF-ILD group (n=154), a 9-variable prediction model was constructed, including age≥50 years (HR 1.8221, p=0.001), hyperlipidemia (HR 4.0516, p<0.001), smoking history (HR 3.8130, p<0.001), diffused cutaneous SSc subtype (HR 1.9753, p<0.001), arthritis (HR 2.0008, p<0.001), shortness of breath (HR 2.0487, p=0.012), decreased serum immunoglobulin A level (HR 2.3900, p=0.002), positive anti-Scl-70 antibody (HR 1.9573, p=0.016) and usage of cyclophosphamide/mycophenolate mofetil (HR 0.4267, p<0.001). The concordance index after enhanced bootstrap resampling adjustment was 0.874, while the optimism-corrected Brier Score was 0.144 in internal validation. CONCLUSION: This study developed the first prediction model for PF-ILD in patients with SSc-ILD, and internal validation showed favourable accuracy and stability of the model.

Microstructural abnormality of white matter tracts in rheumatoid arthritis.

BACKGROUND: Structural and functional brain imaging studies have reported abnormalities of gray matter morphology and functional activities in patients with rheumatoid arthritis (RA). However, it is largely unknown whether patients with RA show alterations of white matter microstructural organization. OBJECTIVES: To automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. METHODS: This single-institutional prospective study included 66 participants (33 patients with RA [52 ± 9 years, 29 women] and 33 sex/age-matched healthy controls [53 ± 12 years, 27 women]), who underwent diffusion MRI scan from January 2021 to December 2021. The white matter microstructure was assessed using fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Voxelwise analyses were conducted on white matter skeleton using an automated, observer-independent tract-based spatial statistics analysis. The relationship between white matter microstructural alterations and clinical and neuropsychological variables was evaluated using correlation analysis. RESULTS: Compared with healthy controls, patients with RA exhibited lower fractional anisotropy in several major white matter tracts (threshold-free cluster enhancement at P < 0.05 for multiple comparison correction, permutation test), involving the forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Lower fractional anisotropy values in the patients with RA were significantly associated with pain-related assessments, including tender joint count (r = -0.43, P = 0.015), Clinical Disease Activity Index score (r = -0.36, P = 0.049), pain severity rated through visual analogue scale (r = -0.45, P = 0.012), and Simplified Disease Activity Index score (r = -0.36, P = 0.045). No significant group difference was found in mean diffusivity, axial diffusivity, and radial diffusivity. CONCLUSIONS: We report the first anatomical evidence for aberrant microstructure organization of several major white matter tracts and its associations with pain processing in patients with rheumatoid arthritis.

Baricitinib for refractory Takayasu arteritis: a prospective cohort study in a tertiary referral centre.

OBJECTIVE: To investigate the treatment efficacy and safety of baricitinib in patients with refractory Takayasu arteritis (TAK). METHODS: We performed a prospective cohort study in which baricitinib 4 mg daily was prescribed to patients with refractory TAK, combined with oral glucocorticoids (GCs). RESULTS: 10 patients with refractory TAK were enrolled with a median age of 28 (IQR=22-37) years, median disease duration of 50 (IQR=24-65) months. The median dose of GCs was 10 (IQR=8.1-22.5) mg prednisone or equivalence dosage at baseline. At 6 months of baricitinib treatment, 6/10 (60%) patients had an overall treatment response. During an average follow-up of 15.3 (range 4-31) months, 4/10 (40%) patients maintained overall treatment response. 8/10 (80%) patients tapered or maintained the same dose of GCs with no change of the combined classical synthetic disease-modifying antirheumatic drugs. Two patients discontinued GCs at 18 and 24 months and were in continuous remission till the end of the study. One patient withdrew baricitinib due to liver dysfunction. CONCLUSION: Baricitinib 4 mg daily is effective for refractory TAK and is well tolerated.

Serum proteome analysis identifies a potential biomarker for axial psoriatic arthritis.

BACKGROUND: To identify potential serum biomarkers for differentiating between axial psoriatic arthritis (axPsA) and peripheral psoriatic arthritis (pPsA). METHODS: Serum samples were collected from patients with PsA to create a biomarker discovery cohort and a verification cohort. Patients with PsA were classified into axial or peripheral subtypes based on imaging criteria. Untargeted proteomics technology was used in the discovery phase to screen for biomarkers, and candidate biomarkers were evaluated using enzyme-linked immunosorbent assay (ELISA) in the verification phase. RESULTS: We identified 45 significantly differentially expressed proteins (DEPs) between axPsA (n = 20) and pPsA (n = 20) with liquid chromatography-mass spectrometry. Among these DEPs, serum pigment epithelium-derived factor (PEDF) was identified as a candidate biomarker using the Boruta algorithm and lasso regression. Results of ELISA further confirmed that the level of serum PEDF expression was significantly higher in axPsA (n = 37) than in pPsA (n = 51) at the verification cohort (37.9 ± 10.1 vs. 30.5 ± 8.9 µg/mL, p < 0.001). Receiver operating characteristics analysis showed that PEDF had an area under the curve (AUC) of 0.72. Serum PEDF was positively correlated with body mass index and C-reactive protein. Additionally, there was a tendency towards a positive correlation between PEDF and the Bath Ankylosing Spondylitis Disease Activity Index. CONCLUSIONS: This study provided a comprehensive characterization of the proteome in axPsA and pPsA and identified a candidate biomarker, PEDF, that may contribute to early diagnosis for axPsA.

The development and initial validation of IgG4-related disease damage index: a consensus report from Chinese IgG4-RD Consortium.

OBJECTIVE: To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI). METHODS: A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters. RESULTS: IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91). CONCLUSION: The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.

Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study.

BACKGROUND: To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP). METHODS: This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 109/L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected. RESULTS: A total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 109/L vs. 76.5 × 109/L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 109/L vs. 51.0 × 109/L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories. CONCLUSION: SLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate.

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.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis: acute eosinophilic myocarditis and chronic inflammatory cardiomyopathy.

OBJECTIVES: Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify high-risk population. METHODS: We included EGPA patients hospitalized in our center from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac magnetic resonance imaging, and endomyocardial biopsy results, the patients were divided into 3 groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. RESULTS: A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, p< 0.01), ANCA positivity decreased (41.33/31.82/14.86%, p< 0.01), and lung involvement reduced (73.33/72.73/43.24%, p= 0.02). In EGPA-EM, cardiac troponin further elevated (0.27 vs 6.00 ng/ml, p< 0.01), ejection fractions decreased (57.79 vs 33.20%, p< 0.01), while more ST-T abnormality was observed (41.89 vs 20.45%, p= 0.02). The prognosis of EGPA-EM was significantly worse, with 14.86% death rate, and 2-year event-free survival rate below 50%. Further, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [AUC 0.85 (95%CI 0.78-0.92), sensitivity 0.78, specificity 0.86]. CONCLUSIONS: We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given timely and anti-IL-5 antibodies be tested in trials.

Digital gangrene in systemic sclerosis patients: not only due to the microvascular disease.

OBJECTIVE: This study aims to investigate the characteristics, risk factors, and outcomes of digital gangrenes in SSc patients, and to identify whether vasculitis is one of the causes for digital gangrene. METHODS: A retrospective case-control study was performed from February 2003 to April 2021. Forty-three SSc patients with digital gangrene admitted to Peking Union Medical College Hospital were included. One-hundred forty-six age- and sex-matched SSc patients without gangrene were selected as controls during the same period. Univariate and multivariate logistic regression analysis was used to determine risk factors. RESULTS: Among 43 SSc patients with gangrene, 93.0% had Raynaud's phenomenon (RP) and 32.6% had current or previous digital ulcers (DU). SSc patients with digital gangrene had more ESR elevation (54.8% vs. 34.9%, p = 0.020) and higher level of high-sensitive C reactive protein (median 7.2 mg/L vs. 1.8 mg/L, p = 0.045) compared with controls. In the multivariable logistic regression analysis, smoking history (OR 4.119, p = 0.037), anti-centromere antibody positivity (OR 3.542, p = 0.016), anti-neutrophil cytoplasmic antibody positivity (OR 22.605, p = 0.037), and anti-phospholipid antibody positivity (OR 16.563, p = 0.001), as well as elevated ESR (OR 2.524, p = 0.038) were identified as independent risk factors for gangrenes. Most (79.1%) cases were treated with combination of immunosuppressive and vasodilating therapy, and four cases also got remised after treatment of only glucocorticoid and immunosuppressive agent. CONCLUSION: Smoking history; positive-ACA, ANCA, and anti-phospholipid antibodies; and increased ESR were independent risk factors for digital gangrenes in SSc. Vasculitis and macrovascular disease may contribute to the progression of digital gangrenes. Key Points •18.6% of SSc patients with digital gangrene had macrovascular stenosis. •Smoking, positive-ACA, ANCA, aPL, and increased ESR were indicators for digital gangrenes in SSc. •Vasculitis and macrovascular disease may involve in the pathogenesis.

Withdrawal of immunosuppressants and low-dose steroids in patients with stable IgG4-RD (WInS IgG4-RD): an investigator-initiated, multicentre, open-label, randomised controlled trial.

OBJECTIVES: IgG4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory disease. Induction treatment with glucocorticoid (GC) is usually effective, but its tendency of relapse makes the strategy for maintenance treatment a challenge. The WInS IgG4-RD (withdraw immunosuppressants (IMs) and steroid in stable IgG4-RD) trial tested whether discontinuation of GC and IM was feasible in stable IgG4-RD. METHODS: The WInS IgG4-RD trial was a multicentre, open-label, randomised controlled trial. Patients with IgG4-RD receiving GC+IM as maintenance treatment with clinically quiescent disease for at least 12 months were randomised (1:1:1) into three groups: group 1: withdraw GC+IM; group 2: withdraw GC but maintain IM; group 3: maintain GC+IM. The primary outcome was the relapse rate of disease within 18 months. The secondary outcomes included the changes of IgG4-RD Responder Index (RI), Physician's Global Assessment (PGA), serum IgG4 and IgG, as well as adverse events. RESULTS: One hundred and forty-six patients were randomised, with 48 patients in group 1, 49 patients in group 2 and group 3, respectively. Within the 18-month follow-up period, disease relapse occurred in 25 out of 48 (52.1%) patients in group 1 vs 7 out of 49 (14.2%) in group 2 and 6 out of 49 (12.2%) in group 3 (p<0.001). The changes in RI and PGA were significantly higher in group 1 than in group 2 (p<0.001) or group 3 (p<0.001). CONCLUSIONS: The maintenance of IMs, with or without low-dose GC, was found to be superior to withdraw GC+IM in preventing relapse for long-time stable IgG4-RD. TRIAL REGISTRATION NUMBER: NCT04124861.

Chronic abdominal aortic occlusive disease related to antiphospholipid syndrome: a rare presentation.

OBJECTIVE: Chronic abdominal aortic occlusive disease (CAAOD) is an uncommon manifestation of antiphospholipid syndrome (APS), impacting cardiovascular health and peripheral arterial circulation. We investigated CAAOD in antiphospholipid antibodies (aPL)-positive patients, aimed to offer comprehensive clinical and radiological insights. METHODS: aPL-positive patients with arterial thrombotic events were categorised into CAAOD and non-CAAOD. Extensive data, including clinical features, radiological images and outcomes, were analysed. RESULTS: This case-control study involved 114 patients who experienced arterial events from 2013 to 2021, revealing 12 patients with abdominal aortic stenosis or occlusion. The CAAOD group, predominantly young (36.67±11.83) males (75.00%), exhibited significantly higher rates of critical smoking habits (66.67% vs 25.49%, p=0.006) and hyperhomocysteinaemia (66.67% vs 31.37%, p=0.026). Radiological findings showed long-segment infrarenal aorta stenosis in CAAOD, occasionally involving renal and common iliac arteries. The lesions presented varying degrees of stenosis, including smooth lumen narrow and total vascular occlusion. Treatment modalities typically involved interventions or surgery, complementing anticoagulation therapy. CONCLUSION: The study shed light on the rare occurrence of CAAOD in APS, highlighting the roles of smoking and hyperhomocysteinaemia as notable risk factors. These findings emphasised the significance of early diagnosis and management of CAAOD.

Incidence, risk factors for active tuberculosis infection and changes of IGRA in patients with Takayasu arteritis: a prospective cohort study.

There is limited evidence to support the association between tuberculosis (TB) and the occurrence of Takayasu arteritis (TAK). To investigate the incidence of active TB (ATB) in TAK and explore the impact of anti-rheumatic therapy on the occurrence of ATB or reactivation of Latent TB infection (LTBI) and their effect on interferon-γ release assay (IGRA) results, we conducted a prospective study based on the Chinese Registry for Systemic Vasculitis cohort. The standard incidence ratio (SIR) was calculated and stratified by age. Kaplan-Meier analysis was used to determine the effect of variables on ATB or LTBI reactivation in patients with TAK. Data from 825 patients with TAK in the registry were analysed. During a median follow-up of 5 years, 5 patients developed ATB with a crude incidence of 154 (95%CI:57-381) person-years/100,000. The SIR was 5.59 (95%CI:1.81-13.04). Glucocorticoids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) did not increase the risk of ATB or LTBI reactivation (P > 0.05). However, the use of tumour necrosis factor inhibitor (TNFi) increased the risk of ATB in patients with LTBI (P < 0.001). Furthermore, the value of the IGRA assay decreased after treatment (P < 0.05). In conclusion, the incidence of TB infection is markedly increased in patients with TAK and patients with TAK are at high risk of developing ATB. Treatment with glucocorticoids and cDMARDs does not significantly increase the risk for ATB in patients with TAK. Moreover, IGRA may have limited effectiveness in monitoring ATB infection or LTBI reactivation in patients with TAK.