Effect of smoking on thrombotic antiphospholipid syndrome: a 10-year prospective cohort study.

OBJECTIVES: Cigarette smoking is an established risk factor for autoimmune diseases. However, whether smoking plays a clear role in thrombotic antiphospholipid syndrome (TAPS) has not been determined. We aimed to investigate the effects of smoking on clinical characteristics and prognosis of TAPS. METHODS: This was a prospective cohort study from 2013 to 2022. During the study period, 297 patients were diagnosed with TAPS, including 82 smokers and 215 non-smokers. After propensity score matching, 57 smokers and 57 non-smokers matched by age and sex were analysed. RESULTS: Overall, smokers with TAPS had more cardiovascular risk factors (CVRFs) than non-smokers, including hypertension (36.59% vs. 14.42%, P<0.001), obesity (15.85% vs. 7.44%, P=0.029), dyslipidaemia (64.63% vs. 48.37%, P=0.012), and hyperhomocysteinaemia (62.20% vs. 36.28%, P<0.001). Arterial thrombotic events were more common in smokers at diagnosis (62.20% vs. 46.05%, P=0.013), especially myocardial infarction, visceral thrombosis, and peripheral vascular thrombosis. After matching, smokers showed balanced CVRFs with non-smokers at baseline, but retained a higher prevalence of arterial thrombosis (59.65% vs. 33.33%, P=0.005), mainly distributed in cerebral vascular, cardiovascular, and retinal vascular territories. During follow-up, smokers presented a tendency for more recurrent arterial thrombosis and less recurrent venous thrombosis. Smokers had significantly poorer outcomes for organ damage with higher DIAPS (median, 2.00 vs. 1.00, P=0.008), especially in the cardiovascular (26.32% vs. 3.51%, P=0.001), gastrointestinal (15.79% vs. 1.75%, P=0.016), and ophthalmologic (10.53% vs. 00.00%, P=0.027) systems. CONCLUSION: Smoking is related to increased arterial events and poor prognosis in TAPS patients. Patients with TAPS should be fully encouraged to avoid smoking.

Immunity and inflammation in pulmonary arterial hypertension: From pathophysiology mechanisms to treatment perspective.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary dysfunctional disease, characterized by progressive vascular remodeling. Inflammation is an increasingly recognized feature of PAH, which is important for the initiation and maintenance of vascular remodeling. High levels of various inflammatory mediators have been documented in both PAH patients and experimental models of PAH. Similarly, multiple immune cells were found to accumulate in and around the wall of remodeled pulmonary vessels and in the vicinity of plexiform lesions, respectively. On the other hand, inflammation is also a bridge from autoimmune diseases to PAH. Autoimmune diseases always lead to chronic inflammation, characterized by the low-level persistent infiltration of immune cells, and elevated levels of several pro-inflammatory cytokines and chemokines. In addition, circulating autoantibodies are found in the peripheral blood of patients, indicating a possible role of autoimmunity in the pathogenesis of PAH. Thus, anti-inflammatory and immunotherapy might be new strategies to prevent or even reverse the process of PAH. Many anti-inflammatory agents and immunotherapies have been confirmed in animal models while some clinical trials employing immunotherapies are completed or currently underway. Here, we review pathological mechanisms associated with inflammation and immunity in the development of PAH, and discuss potential interventions for the treatment of PAH.

[Clinical Features of Relapsing Polychondritis Patients Presented with Arthropathy].

Objective To explore the clinical characteristics of relapsing polychondritis(RP)patients presented with arthropathy. Methods We retrospectively analyzed the clinical data of 201 RP patients who were hospitalized in our center between December 2005 and February 2019.After 16 patients with co-existing other autoimmune diseases and malignancies were ruled out,185 RP patients entered the final analysis,among whom 16 RP patients were presented with arthropathy and 169 without arthropathy.The demographic data,clinical manifestations,laboratory findings,and prognosis were compared between these two groups. Results Five of the 16 RP patients with arthropathy at presentation were misdiagnosed as rheumatoid arthritis.Compared with RP patients without arthropathy at presentation,RP patients with arthropathy at presentation had a longer disease course[(37.50±66.50)months vs.(9.00±11.00)months,z=-3.186,P =0.001],longer time of diagnostic delay[(24.00±41.25)months vs.(7.00±9.00)months,z=-2.890,P=0.004],and higher incidence of eye(62.50% vs. 36.09%,χ2=4.309,P=0.038)and nervous system involvements(43.75% vs. 15.38%,χ2=6.205,P=0.013). Conclusions RP patients with arthropathy at presentation are most likely to be misdiagnosed as rheumatoid arthritis.These patients are characterized by longer disease course and diagnostic delay and more frequrent eye and nervous system involvements.

Telangiectasia as a potential clinical marker of microvascular lesions in systemic sclerosis patients from EUSTAR data in China.

OBJECTIVES: To investigate the prevalence and clinical relevance of telangiectasia in Chinese patients with systemic sclerosis (SSc). METHODS: Data from 230 SSc EUSTAR patients from Peking Union Medical College Hospital (2009-2011) that fulfilled the 1980 American College of Rheumatology SSc classification criteria were prospectively collected. Demographic, clinical, and laboratory data were calculated between groups with and without telangiectasia, and a six-minute walk test, pulmonary function test (PFT), transthoracic echocardiography (TTE), right heart catheterisation (RHC) and modified Rodnan skin score (mRSS) were performed. RESULTS: 96 patients (41.7%) were diagnosed with telangiectasia. There were no significant differences between patients with and without telangiectasia based on gender, age at onset, Raynaud's phenomenon (RP) duration, or SSc classification. Disease duration both from RP onset of patients and from first non-RP manifestation of patients with telangiectasia was significantly longer than patients without (p<0.05). RP (97.9% vs. 90.3%), finger/toe sclerosis (96.9% vs. 88.1%), facial sclerosis (68.8% vs. 53.7%), digital ulcers (DUs; 40.6% vs. 23.1%), digital pitting (49.0% vs. 33.8%), joint contracture (20.8% vs. 10.4%) and erythrocyte sedimentation rate elevation (26.7% vs. 14.8%) were significantly greater in telangiectasia patients (p<0.05). There were no differences in autoantibody development between patients with and without telangiectasia (p>0.05). PFT showed that forced vital capacity (77.0±17.26 vs. 83.05±16.53, p=0.005) and diffusion capacity for CO of the lung (58.9±19.4 vs. 65.7±19.7, p=0.030) were lower, while forced expiratory volume ratio (87.02±7.8 vs. 84.33±7.1, p=0.029) was higher in SSc with telangiectasia. Pulmonary artery hypertension (PAH) prevalence (25.0% vs. 14.2%) was significantly greater in patients with telangiectasia. CONCLUSIONS: Telangiectasia are common in Chinese SSc patients and usually associated with DUs, RP, and PAH. Telangiectasia could be a clinical marker of microvascular disease in SSc.

Clinical characteristics of systemic sclerosis patients with digital ulcers in China.

OBJECTIVES: To investigate the clinical characteristics of SSc patients with DUs in China. METHODS: The data of 267 consecutive SSc patients based on the EUSTAR DATABASE from Peking Union Medical College Hospital from February 2009 to March 2012 were prospectively collected. The patients with DUs were compared to those without DUs. RESULTS: Seventy-nine patients (29.6%) had DUs out of 267 SSc patients analysed. There were significant differences between patients with and without DU based on sex (female/male: 65/14 vs. 174/14), age of onset of SSc (32.3±11.7 vs. 40.4±12.6 y), age of onset of Raynaud's phenomenon (31.8±12.3 vs. 38.7±12.2) (p<0.05). In addition, there was a higher rate of diffuse SSc, gastrointestinal involvement, (especially esophageal involvement), and pericardial effusion, higher mRodnan score, and more anti-scl70 antibody positivity in patients with DU (p<0.05). A multivariate analysis identified anti-Scl70 antibody positivity, gastrointestinal involvement and a younger age at disease onset as three risk factors for developing DUs in SSc patients. CONCLUSIONS: The occurrence of DUs in Chinese SSc patients is frequent. It is possible that SSc patients with DUs were influenced by the disease earlier in life, which should be detected early for effective intervention.

Implementation of the treat-to-target approach and treatment satisfaction in patients with rheumatoid arthritis: perspectives of Chinese rheumatologists.

OBJECTIVE: To investigate the implementation of treat-to-target (T2T) and treatment satisfaction from Chinese rheumatologists' perspectives. METHODS: This retrospective analysis of a cross-sectional database collected from rheumatologists and their adult patients with RA in China using Adelphi Real World Disease Specific Programme™ methodology. Multivariate logistic regression models were used to evaluate factors associated with T2T use, achievement of T2T goals, and physician treatment satisfaction. RESULTS: Sixty physicians provided data for 600 patients, of whom 39.0% (234/600) were being treated using T2T, and 64.9% (366/564) had achieved their T2T goal. Physicians were satisfied with treatment in 74.3% (445/599) of patients. Patients with a higher pain score were more likely to be managed using T2T (odds ratio (OR) 1.25; p = 0.017), but less likely to have achieved the T2T goal (OR 0.76; p = 0.004). T2T use was more likely if patients had a longer time since diagnosis (> 2 vs ≤ 2 years; OR 1.61; p = 0.031) or received targeted synthetic or biologic disease-modifying antirheumatic drugs (tsDMARDs or bDMARDs; OR 6.90; p < 0.001). T2T goal achievement was more likely for patients with higher body mass index (≥ 24 vs < 24 kg/m2; OR 2.73; p = 0.001) or full-time employment (OR 2.11; p = 0.005). Physician treatment satisfaction was more likely if the T2T goal was achieved (OR 4.78; p < 0.001) or tsDMARDs or bDMARDs were used (OR 2.58; p = 0.017), and less likely if pain scores were higher (OR 0.79; p = 0.019). CONCLUSIONS: T2T implementation in China is suboptimal. Our findings provide insight into T2T implementation and physician treatment satisfaction, supporting T2T use in Chinese RA clinical practice. Key Points • T2T implementation in China is currently suboptimal. • Patients with greater pain were more likely to be managed using T2T but were less likely to have achieved their T2T goals. • Physician treatment satisfaction was associated with T2T goal achievement.

Cardiac manifestations in a Chinese cohort of fetuses from mothers with anti-Ro and anti-La antibodies.

Objectives: To analyze the clinical characteristics, echocardiographic features, and prognosis of fetuses based on three groups of cardiac manifestations associated with maternal anti-Ro and anti-La antibodies in China. This study included three groups: the isolated-arrhythmia, isolated-endocardial fibroelastosis (EFE), and mixed groups. Methods: We prospectively evaluated 36 fetuses with cardiac manifestations due to maternal anti-Ro and anti-La antibodies from our center between 2016 and 2020 in China. Clinical and echocardiographic data were collected. Results: There were 13 patients (36%) in the isolated-arrhythmia group, eight (22%) in the isolated-EFE group, and 15 (42%) in the mixed group. All patients in the isolated-EFE group presented with mild EFE. Severe EFE was identified in four patients (27%) in the mixed group. Atrioventricular block (AVB) was more common in the isolated-arrhythmia group (13, 100%) than in the mixed group (6, 40%; p = 0.001). Moderate-severe mitral regurgitation (p = 0.006), dilated cardiomyopathy (DCM, p = 0.017), and low cardiovascular profile scores (p = 0.013) were more common in the mixed group than in the other two groups. Twenty-one mothers decided to terminate the pregnancy and 15 fetuses were born with regular perinatal treatment. They all survived at 1 year of age. One patient in the isolated-arrhythmia group and two in the mixed group required a pacemaker due to third-degree AVB or atrioventricular junctional rhythm. Five patients in the isolated-EFE group and five in the mixed group had no DCM or heart failure and the location of mild EFE was significantly reduced. Conclusion: Fetal cardiac manifestations due to maternal anti-Ro and anti-La antibodies can be divided into three groups, i.e., the isolated-arrhythmia, isolated-EFE, and mixed groups. AVB usually occurs in the isolated-arrhythmia group. Severe EFE, moderate-severe mitral regurgitation, and DCM mainly appear in the mixed group. Location of mild EFE significantly reduces after birth and the outcome of fetuses with mild EFE depends on the presence of arrhythmia and its subtypes.

[The value of brain natriuretic peptide in connective tissue diseases associated with pulmonary arterial hypertension].

OBJECTIVE: To explore the potential role of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the assessment of patients with connective tissue diseases (CTD) associated pulmonary arterial hypertension (PAH). METHODS: Thirty patients with CTD associated PAH were evaluated by WHO function, echocardiography, right heart catheterization and blood biomarkers. All the clinical data was analyzed statistically. RESULTS: All patients [age (39.5 ± 11.6) yr] were female. Both NT-proBNP and BNP were significantly increased and significantly correlated (all P < 0.05) respectively with mean pulmonary arterial pressure (r = 0.53 and r = 0.40), right arterial pressure (r = 0.55 and r = 0.42), pulmonary vascular resistance (r = 0.69 and r = 0.61), cardiac index (r = -0.58 and r = -0.46), mixed venous blood oxygen saturation (r = -0.62 and r = -0.54), pericardial effusion (r = 0.46 and r = 0.43), right atrial sizes (r = 0.40 and 0.53, and r = 0.39 and 0.45) and right ventricular size (r = 0.55 and r = 0.37). Furthermore, NT-proBNP, but not BNP, significantly correlated with WHO function class (r = 0.55). CONCLUSION: Blood NT-proBNP and BNP were elevated in patients with CTD associated PAH and paralleled the extent of function class, pulmonary hemodynamic changes and right ventricular remodeling.

Effectiveness of iguratimod as monotherapy or combined therapy in patients with rheumatoid arthritis: a systematic review and meta-analysis of RCTs.

BACKGROUND: This study aims to evaluate the efficacy and safety of the iguratimod (IGU) as monotherapy or combined therapy in patients with rheumatoid arthritis (RA) by using meta-analysis. METHODS: We searched Medline, EMBASE, Cochrane library, CNKI, Wanfang medical network from initial to 30 June, 2020, for randomized clinical trials (RCTs). Two authors independently screened the studies via reading the title, abstract, and full text. The risk of bias in individual studies was assessed using the Cochrane Risk of Bias tool. STATA 12.0 was used for pooled analysis of all included studies. RESULTS: A total of 23 RCTs were included in this analysis. Meta-analysis showed that patients in the IGU monotherapy or combined therapy group had significantly higher ACR20 (OR = 1.97, 95% CI 1.29 to 3.00, P = 0.002), lower DAS28-CRP (SMD = -3.49, 95% CI -5.40 to -1.58, P < 0.001) and DAS28-ESR (SMD = -2.61, 95% CI -3.64 to -1.57, P < 0.001), as well as shorter duration of morning stiffness (SMD = -2.06, 95% CI -2.86 to -1.25, P < 0.001) and lower HAQ score (SMD = -0.91, 95% CI -1.61 to -0.21, P = 0.011), than those received other disease-modifying antirheumatic drugs (DMARDs) monotherapy (primarily comprising methotrexate). For the safety profile, IGU monotherapy had similar risks for gastrointestinal reactions (P = 0.070), leucopenia (P = 0.309), increment in transaminase (P = 0.321), increase of ALT (P = 0.051), and liver damage (P = 0.182) to methotrexate monotherapy, and IGU combined with other DMARDs therapy did not increase the risks of these AEs (P > 0.05). CONCLUSIONS: Our evidence suggests that IGU is effective and tolerant as monotherapy or combined therapy especially with methotrexate in patients with active RA. IGU may be regarded as a potential alternative to methotrexate, and a preferable choice when combined with other DMARDs for the treatment of RA.

Clinical characteristics and prognosis of patients with isolated thrombotic vs. obstetric antiphospholipid syndrome: a prospective cohort study.

BACKGROUND: Several studies suggested that thrombotic and obstetric antiphospholipid syndromes could be independent identities, but few have systematically compared their clinical characteristics and prognosis. OBJECTIVE: The objective of this study is to identify key differences between thrombotic APS (tAPS) and obstetric APS (oAPS). METHODS: This single-center, prospective study included consecutive patients with primary antiphospholipid syndrome (APS) receiving treatment at the Peking Union Medical College Hospital during a period from 2013 to 2020. RESULTS: Screening of the database yielded a total of 244 women with positive antiphospholipid antibody (aPL). Among the 105 women with primary APS, 39 (37.14%) had isolated tAPS (ItAPS), 44 (41.90%) had isolated oAPS (IoAPS), and 9 (8.57%) had both tAPS and tAPS+oAPS. In comparison to those with IoAPS, patients with ItAPS had older age (41.92 ± 11.97 vs. 33.16 ± 4.22 years, P < 0.01), higher rate of cardiovascular risk (at least one positive of coronary heart disease, hypertension, obesity, diabetes, and hyperlipidemia) (41.03% vs. 6.82%, P < 0.01), and higher frequency of thrombocytopenia (43.59% vs. 20.45%, P < 0.05). Antibody profiles were generally similar among the groups, but isolated anti-ß2GPI positivity was more common in patients with IoAPS (52.27% vs. 17.94% for ItAPS, P = 0.01). Triple aPL positivity was more common in patients with both tAPS and oAPS (66.67% vs. 46.15% for ItAPS vs. 25% for IoAPS, P = 0.022). Blood homocysteine was higher in patients with ItAPS (11.20 vs. 9.90 µmol/L for IoAPS, P < 0.05), but there were no differences in inflammatory markers or complements. Recurrence rate of thrombosis was higher in patients with ItAPS (33.33% vs. 2.27% for IoAPS, P ≤ 0.001) with a mean follow-up of 61 months. CONCLUSION: Despite generally similar antibody and biochemical profiles, patients with ItAPS had much higher risk of recurrent thrombosis than IoAPS, supporting distinct mechanisms of pathogenesis.

Dorsolateral medullary infarction during skin infection by Stenotrophomonas maltophilia in a patient with triple antiphospholipid antibody positivity: a case-based review.

Thrombotic events are the most frequent causes of death in patients with antiphospholipid syndrome (APS). Previous studies have reported infection to be the most important trigger of thrombosis in APS, with molecular mimicry considered to be a major mechanism. Although timely management of infections has been recommended in patients with high suspicion of infection, anti-infective therapy would not take effect in a short time due to the dilemma in determining the origins of infection, especially in patients undergoing immunosuppressive therapy. Here, we describe a 26-year-old patient with systemic lupus erythematosus with triple antiphospholipid antibody positivity who had a stroke involving her dorsolateral medulla, despite timely anti-infective treatment within the context of skin infection caused by Stenotrophomonas maltophilia. To the best of our knowledge, it is the first report about the association between Stenotrophomonas maltophilia infection and thrombotic complications in APS. Thus, solely focusing on anti-infective therapy by the current recommendation for the management of APS may be insufficient within the context of infection; early initiation of effective anticoagulation should also be suggested until the anti-infective therapy becomes effective, especially in patients with high-risk antiphospholipid antibody profiles, in whom the potential benefit would outweigh the risk of bleeding.

Etiologies and outcomes of rheumatology patients with acute respiratory failure requiring intensive care: a single-center medical records review study of 259 patients.

OBJECTIVE: The etiologies of acute respiratory failure in patients with systemic rheumatic diseases (SRDs) requiring intensive care remain unknown. This study was undertaken to investigate the etiologies and outcomes. METHODS: A medical records review study was performed of 259 adult SRDs patients with respiratory failure admitted to medical ICU across a 5-year period. The etiologies were classified as infection, SRD exacerbation, and undetermined. The factors associated with ICU mortality were identified with multivariate logistic regression analysis. RESULTS: The etiologies of respiratory failure included infection (n = 209, 80.7%), SRD exacerbation (n = 71, 27.4%), and undetermined (n = 21, 8.1%). The most common pathogen was Pneumocystis jirovecii (39.8%), followed by Aspergillus spp. (33.2%), and cytomegalovirus (23.2%). The ICU mortality rate was 59.8%. A high acute physiology and chronic health evaluation II score (OR 1.118, 95% CI 1.054 to 1.186, p < 0.001), a PaO2/FiO2 ratio < 100 mmHg (OR 3.918, 95% CI 2.199 to 6.892, p < 0.001), and a diagnosis of dermatomyositis/polymyositis (OR 4.898, 95% CI 1.949 to 12.309, p = 0.001), vasculitis (OR 3.007, 95% CI 1.237 to 7.309, p = 0.015), and Pneumocystis pneumonia (OR 2.345, 95% CI 1.168 to 4.705, p = 0.016) were associated with increased mortality. CONCLUSIONS: Opportunistic infections and SRD exacerbation were the most common etiologies of acute respiratory failure in patients with SRDs requiring ICU admission, with high ICU mortality. Development of a standard protocol for differential diagnosis in this population might help initiate definitive therapy and improve clinical outcome. Key Points • Infections, especially with opportunistic infections, were the leading cause of acute respiratory failure in critically ill rheumatology patients, with high mortality. • Severity of illness, certain types of rheumatic diseases, and opportunistic fungal infections were associated with increased mortality. • Using a comprehensive diagnostic workup might help to confirm the infective etiology and improve outcome.

Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry IX: Clinical Features and Survival of Childhood-Onset Systemic Lupus Erythematosus in China.

BACKGROUND: Approximately 15-20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric-onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult-onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database. METHODS: We made a prospective study of 225 cSLE patients (aged Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI], 0.470-0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512-2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053-2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170-0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log-rank test (0.557, P = 0.455). CONCLUSIONS: cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5- year survival between cSLE and aSLE groups.

Protein-losing enteropathy in systemic lupus erythematosus: 12 years experience from a Chinese academic center.

OBJECTIVE: Protein-losing enteropathy (PLE) is a complication in some systemic lupus erythematosus (SLE) patients that is often misdiagnosed. With this study, we provide insight into clinical characteristics, laboratory characteristics, diagnostic tests, risk factors, treatment, and prognosis of the disease. METHODS: A retrospective, case-control study was performed in 44 patients with SLE-related PLE (PLE group) and 88 patients with active SLE (control group) admitted to our care from January 2000-January 2012. Risk factors for SLE-related PLE were examined, and we analyzed the accuracy of single and combined laboratory characteristics in discriminating SLE-related PLE from active SLE. Serum albumin and C3 levels were measured as outcome during and after treatment with corticosteroids and immunosuppressive agents. RESULTS: The PLE group had lower mean serum albumin and 24-hour urine protein levels, higher mean total plasma cholesterol levels, and greater frequencies of anti-SSA and SSB seropositivity compared with the control group. Anti-SSA seropositivity, hypoalbuminemia, and hypercholesterolemia were independent risk factors for SLE-related PLE. The simultaneous presence of serum albumin (<22 g/l) and 24-hour urine protein (<0.8 g/24 h) had high specificity, positive predictive value, negative predictive value, and positive likelihood ratio, a low negative likelihood ratio and no significant reduction in sensitivity. High dosage of glucocorticosteroid combined with cyclophosphomide were mostly prescribed for SLE-related PLE. CONCLUSION: SLE-related PLE should be considered when an SLE patient presents with generalized edema, anti-SSA antibody seropositivity, hypercholesterolemia, severe hypoalbuminemia, and low 24-hour urine protein levels. Aggressive treatment for lupus might improve prognosis.