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.

Safety and Effectiveness of Baricitinib in Chinese Patients with Moderate-to-Severe Rheumatoid Arthritis: 24-Week Results from a Post-Marketing Safety Study.

INTRODUCTION: Baricitinib, a JAK1/JAK2 inhibitor, is approved for treatment of moderate-to-severe rheumatoid arthritis (RA) in China. This single-arm, prospective, multi-center, post-marketing safety study (PMSS) evaluated the safety and effectiveness of baricitinib in Chinese patients. METHODS: This study included adult patients with moderate-to-severe active RA who received baricitinib over periods of approximately 12 and 24 weeks. The primary endpoint was safety, defined as week 12 adverse event (AE)/serious AE incidence. Secondary endpoints were week 24 safety and effectiveness (disease activity score with 28 joints/C-reactive protein [DAS28-CRP] and simplified/Clinical Disease Activity Index [SDAI/CDAI]). RESULTS: Safety analyses included 667 patients (female, 82.3%; mean age, 53.3 years; mean RA duration, 86.9 months); 106/667 (15.9%) were 65-74 years old and 19/667 (2.8%) were ≥ 75 years old; 87.0% received baricitinib 2 mg QD. Total exposure was 262.1 patient-years (PY). At week 12, AEs had occurred in 214 (32.1%; exposure-adjusted incidence rate [EAIR], 172.5 per 100 PY) patients (serious AEs: 22 [3.3%; EAIR, 15.0]). At week 24, AEs had occurred in 250 (37.5%; EAIR, 125.9) patients (serious AEs: 28 [4.2%; EAIR, 10.9]). Two patients (0.3%) died (of pneumonia and unknown cause); EAIR for death, 0.77. Serious infection occurred in 1.2% of patients (EAIR, 3.1). Hepatotoxicity occurred in 3.4% of patients (EAIR, 9.0). No patients met potential Hy's law laboratory criteria (alanine/aspartate aminotransferases ≥ 3 × upper limit of normal (ULN) and total bilirubin ≥ 2 × ULN). Malignancy occurred in one patient. No patients experienced venous thromboembolism (VTE) or major adverse cardiovascular events (MACE). At week 24, 52.4%, 27.5%, and 27.6% of patients achieved remission per DAS28-CRP, SDAI, and CDAI, respectively. CONCLUSIONS: This PMSS investigated the safety and effectiveness of baricitinib in clinical practice in China. No VTE/MACE or new safety signals were reported and there was promising effectiveness, supporting the use of baricitinib in Chinese patients with moderate-to-severe active RA. TRIAL REGISTRATION: EU PAS Register: EUPAS34213.

Patterns of renal pathology in Chinese patients with systemic sclerosis undergoing renal biopsy at a tertiary medical center.

OBJECTIVE: We investigated renal injury characteristics in Chinese patients with systemic sclerosis (SSc) who had undergone renal biopsy. METHODS: We searched the medical records of patients with SSc who were hospitalized at Peking Union Medical College Hospital between January 1990 and August 2019. We analyzed the clinical characteristics and pathological results of these patients. RESULTS: We identified 25 patients who had undergone renal biopsy. Of these patients, 10 had scleroderma renal crisis (SRC); one underwent renal biopsy twice (for diffuse mesangial proliferative glomerulonephritis and for SRC); two had antineutrophil cytoplasmic antibody-associated glomerulonephritis; one had immunoglobulin M nephropathy; one had minimal change nephropathy; seven had lupus nephritis; one had scleroderma renal crisis with comorbid lupus nephritis; and two had drug-related kidney injury (caused by aristolochic acid in one and D-penicillamine in the other). Acute tubular necrosis was observed in the patient taking oral aristolochic acid, while minimal change nephropathy was observed in the patient with D-penicillamine-induced renal injury. CONCLUSIONS: SRC was the most commonly encountered renal damage in patients with SSc. We recommend biopsy for patients undergoing treatment for SRC who have persistent renal injury with proteinuria, regardless of hematuria. Rheumatologists in Eastern countries should be aware of aristolochic acid nephropathy.

Preventive and remedial application of etanercept attenuate monocrotaline-induced pulmonary arterial hypertension.

AIM: To evaluate the efficacy of etanercept (ETN) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. METHODS: A PAH rat model was induced by intraperitoneal injection (i.p.) of MCT (60 mg/kg) once and ENT therapy (2.5 mg/kg twice a week i.p.) was initiated on the day following MCT injection (prevention protocol) or after PAH is established (remedial protocol) for 2 weeks. The mean pulmonary arterial pressure (mPAP) was measured using a right heart catheterization technique; quantitative determination of lung small artery blood wall thickening observed by hematoxylin and eosin staining; the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the rat lung tissues were determined using immunohistochemistry. RESULTS: Both preventive (12.53 ± 3.8 vs. model control 28.67 ± 7.57 mmHg, P < 0.01) and remedial (35.95 ± 20.29 vs. model control 66.17 ± 24.29 mmHg, P < 0.01) applications of ETN could significantly reduce mPAP. We obtained similar results when using the R-value to assess the efficacy of ETN in two treatment groups (preventive groups, 0.273 ± 0.018 vs. 0.203 ± 0.036, P < 0.01; remedial groups, 0.227 ± 0.031 vs. 0.124 ± 0.008, P < 0.01). The immunohistochemistry staining showed that there were strong expressions of TNF-α and IL-6 in the lung tissues of model groups and decreased expression in both treatment groups. CONCLUSION: Treatment with TNF-α antagonism ETN prevented and reversed MCT-induced PAH by reducing inflammatory cell infiltration. Our results suggest a critical role of TNF-α and inflammation in MCT-induced PAH progression and targeting the inflammatory environment might be a potential means of PAH treatment.

A preliminary study of acoustic radiation force impulse quantification for the assessment of skin in diffuse cutaneous systemic sclerosis.

OBJECTIVE: To investigate skin elasticity using acoustic radiation force impulse (ARFI) quantification in systemic sclerosis (SSc), and compare the modified Rodnan skin score (mRSS) with measured shear wave velocity (SWV) and thickness of the skin. METHODS: Fifteen patients with diffuse cutaneous SSc (dcSSc) and 15 age-matched and sex-matched healthy controls were evaluated. The SWV and thickness of skin were measured at 17 sites corresponding to those assessed in the mRSS in each participant. The SWV measurements of skin were compared between patients with dcSSc and healthy controls. The correlations between the mRSS and the skin SWV and thickness were explored using Spearman's correlation. RESULTS: The SWV values were higher in patients with dcSSc compared with healthy controls at right hand dorsum, right forearm, left hand dorsum, left forearm, right foot dorsum, and left foot dorsum (p < 0.05). In patients with dcSSc, the SWV values of uninvolved skin were higher than those of controls (p < 0.001), and the SWV values increased with increasing skin scores except for skin score 3 (p < 0.05). The sum of the SWV values correlated with total clinical skin score (r = 0.841, p < 0.001), and the sum of the skin thickness correlated with total clinical skin score (r = 0.740, p = 0.002). CONCLUSION: ARFI quantification is feasible and reliable for assessing the skin involvement in dcSSc. ARFI quantification could identify early skin change that may precede palpable skin involvement, and may be a valuable adjunct to skin evaluation in patients with SSc.

[Importance of salivary gland focus score in the diagnosis of Sjögren's syndrome].

OBJECTIVE: To explore the correlation between labial salivary gland focus score (FS) and severity of Sjögren's syndrome patients. METHODS: From January 2009 to December 2010, a total of 77 patients with primary Sjögren's syndrome were recruited to undergo minor salivary gland biopsy, Schirmer's test, unstimulated whole salivary flow, organ function and serological test. Focus score was calculated for all biopsy samples. And the correlation between focus score and serological test and organ function damage was evaluated. RESULTS: Their pathological examinations revealed focal lymphocytic sialadenitis (n = 62), 10 cases with non-specific or sclerosing chronic sialadenitis (n = 10) and normal features (n = 5). Among 62 cases with focal lymphocytic sialadenitis, 46 cases had FS ≥ 1 and another 16 FS < 1. The median FS was 2.4 ± 2.5 . FS ≥ 1 was strongly associated with unstimulated whole salivary flow rates and ocular staining score (P < 0.05), but not significantly with dry mouth or eyes. FS was significantly correlated with serum immunoglobin G (IgG), immunoglobin M (IgM) and rheumatoid factor level (P < 0.05). Those with positive anti-SSA had higher FS level than those with negative anti-SSA antibody (P < 0.05). In addition, FS level was not significantly associated with organ function damage. CONCLUSION: Prior to determining FS, distinguishing focal lymphocytic sialadenitis from other types of sialadenitis is essential in assessing salivary gland biopsy. And the FS level might be associated with disease activity and positive anti-SSA. No correlation exists between FS and organ function damage.

Clinical and prognostic characteristics of 573 cases of primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is one of the autoimmune diseases with high incidence. There were several clinical investigations in Caucasian but seldom in Chinese. The aim of this study was to compare the difference of clinical manifestations, immunological features and prognosis of pSS between Caucasian and Chinese pSS patients. METHODS: Five hundred and seventy-three patients who fulfilled the 2002 international classification (criteria) for pSS from Peking Union Medical College Hospital between 1985 and 2006 were screened retrospectively and compared with other populations. RESULTS: (1) The study consisted of 524 (91%) female and 49 (9%) male patients (female: male = 10.7:1). Mean age at the onset of the disease was (39.0 ± 13.7) years and in 169 (29.5%) patients the disease onset occurred before the age of 30 years. The average duration from disease onset to pSS diagnosis was 48 months (range, 1 - 552 months). It had been shortened during the recent five years. (2) Dry mouth (84.5%) and dry eyes (70.0%) were the most common symptoms, significantly lower than foreign patients (P = 0.000). Two hundred and seventy-two (47.5%) patients presented with rampant caries, 160 (27.9%) with parotidomegaly. The positivity of xerostomia, xerophthalmia and salivary gland biopsy were 91.9%, 94.8% and 90.7%, respectively. (3) Systemic involvement occurred in 91.4% patients. Compared with studies done outside China, higher prevalence of fever 41.0%, myositis 4.9%, pericardial effusion 14.8%, pulmonary involvement 42.3%, renal involvement 33.5%, thyroid involvement 32.7%, pancrease involvement 5.6% (P < 0.01) and lower prevalence of fatigue, lymphadenectasis and Raynaud's phenomenon (P < 0.01) were seen. (4) Risk factors of death include pulmonary artery hypertension, liver damage and interstitial lung disease. CONCLUSIONS: Chinese pSS differs significantly from the non-Chinese cases in terms of the age of onset, systemic involvement, autoantibodies and proportional mortality rate. Lung and liver damage were found to be the highest risk factors of the disease prognosis.

[An open-label, multicentric clinical trial to evaluate the efficacy and impact on bone metabolism of recombinant human tumor necrosis factor-α receptor II IgG Fc fusion protein with methotrexate in active rheumatoid arthritis: 24-week clinical and radiographic results from ReABLE study].

OBJECTIVE: To evaluate the efficacy, radiographic changes and safety of the combination of recombinant human tumor necrosis factor-α receptor II IgG Fc fusion protein (rhTNFR:Fc) and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: 30 RA patients were treated with rhTNFR:Fc (25 mg subcutaneously twice weekly) and oral MTX (up to 15 mg weekly) in an open-label manner. Clinical response was assessed by American College of Rheumatology (ACR) criteria and Disease Activity Score in 28 joints (DAS28). Radiographs of hands and wrist were assessed by the modified Sharp score. RESULTS: At Week 24, ACR20, ACR50 and ACR70 responses were achieved by 90%, 76.67% and 46.67% respectively. At Week 24, the mean DAS28 was 3.65 ± 1.26 versus 6.41 ± 0.61 at baseline (P < 0.001). And 20% patients achieved remission and 16.67% patients had a low disease activity. At week 24, EULAR good and moderate responses were attained by 36.67% and 60% respectively. Similarly, Health Assessment Questionnaire (HAQ) improved significantly, declining from 1.12 at baseline to 0.36 at week 24 (P < 0.001). No radiographic progression (based on change of total Sharp score) was found in 27 cases. Adverse events were mild. CONCLUSION: rhTNFR:Fc in combination with MTX shows an excellent efficacy of reduced disease activity, improved function and slowed radiographic progression through 24 weeks. A combination therapy for 24 weeks can lead to disease remission and an inhibition of radiographic progression. Further study is warranted.

[The clinico-pathological manifestation of cardiac involvement in eosinophilic diseases].

OBJECTIVE: To investigate the clinical and pathological features of eosinophilic diseases with cardiac involvement. METHODS: We analyzed the clinical and cardiac pathological data of 7 patients with eosinophilic diseases with cardiac involvement under endomyocardial biopsy or autopsy. RESULTS: Seven patients (5 male, average age 51 years) were enrolled. Four patients were diagnosed as idiopathic hypereosinophilic syndrome and three were Churg-Strauss syndrome. Peripheral blood eosinophilia count increased significantly in all patients. Cardiac involvement included angina pectoris, myocardial infarction, heart failure, presyncope and sudden death. Electrocardiogram showed cardiac ischemia, bundle branch block and third degree atrioventricular block. Echocardiography suggested ventricular and atrial enlargement, decreased ventricular systolic function, pulmonary hypertension, valvular prolapse and insufficiency and endocarditis. Pathology displayed infiltration of eosinophils, formation of granulomata, necrotizing vasculitis, myocardial necrosis and endomyocardial fibrosis in heart. Coronary artery could be also affected and led to myocardial infarction. CONCLUSIONS: Cardiovascular complications of eosinophilic diseases are a major source of morbidity and mortality in these disorders. The manifestations are multiple and early recognition and treatment with steroid and immunosuppressant can improve prognosis.

[The diagnostic value of anti-SSA antibody in primary Sjögren's syndrome].

OBJECTIVE: According to international classification criteria (2002) on Sjögren's syndrome, labial pathology was still considered as a major criterion for diagnosis. Standard labial biopsy was hard to be carried out in China. This study is to evaluate whether the invasive labial biopsy could be replaced by noninvasive detection of serum anti-SSA antibody. METHODS: 181 Chinese patients with the initial diagnosis of primary Sjögren's syndrome in Peking Union Medical College Hospital (PUMCH) were enrolled in Sjögren's International Collaborative Clinical Alliance (SICCA). All patients received standard labial biopsies (area of salivary gland tissue ≥ 4 mm²) and focal score (FS) of focal lymphatic sialadenitis were confirmed by pathologists from school of stomatology, University California of San Francisco (UCSF). Anti-SSA antibodies in sera of all patients were detected by double immunodiffusion (DID), Western blot in PUMCH and by enzyme-linked immunosorbent assay (ELISA) in central laboratory of SICCA. The correlation between labial pathological findings and serum anti-SSA antibody was studied by chi² test and the concordance was calculated by unweighted Kappa. RESULTS: (1) Bivariate analysis revealed strong associations of FS > 1 with the presence of anti-SSA antibody by DID (83.9% vs 42.0%, P < 0.0001). The accordance between FS and antibody detection by DID was fine with a kappa value of 0.432. However, there were 16.1% false-positive antibody reports and 42.0% false-negative antibody reports. (2) FS > 1 was strongly associated with the presence of anti-SSA antibody by Western blot (83.0% vs 51.7%, P < 0.0001). But the accordance between FS and antibody detection by Western blot was only fair with a kappa value of 0.316. There were 17.0% false-positive antibody reports and 51.7% false-negative antibody reports. (3) FS > 1 was strongly associated with the presence of anti-SSA antibody by ELISA (81.5% vs 38.6%, P < 0.0001). The accordance between FS and antibody detection by ELISA was fine with a kappa value of 0.427. There were 18.5% false-positive antibody reports and 38.6% false-negative antibody reports. CONCLUSION: In Sjögren's syndrome, labial biopsy with FS > 1 finding is strongly associated with anti-SSA antibody. Positive results of anti-SSA antibodies by DID or ELISA may indicate FS > 1, thus labial biopsy could relatively be avoided, negative results may need further standard labial biopsy procedure to confirm the diagnosis of Sjögren's syndrome.

[Comparison of adenosine versus iloprost by acute vasodilator test in patients of pulmonary arterial hypertension complicated with connective tissue diseases].

OBJECTIVE: To compare the acute hemodynamic effects of adenosine versus iloprost in patients of pulmonary arterial hypertension (PAH) complicated with connective tissue diseases. METHODS: During right heart catheterization, 18 patients of PAH complicated with connective tissue diseases sequentially received intravenous infusion of adenosine and inhaled iloprost. After the baseline hemodynamic data were obtained, an adenosine infusion was started and titrated to the maximal tolerated dose. The hemodynamic parameters were allowed to return to baseline. Then inhalation of iloprost was administered. The effects of both medicines on the patient's hemodynamics were monitored. RESULTS: As compared with the baseline values, the systolic pulmonary artery pressure and pulmonary vascular resistance significantly decreased [(71 +/- 30) vs (80 +/- 29) mm Hg and (712 +/- 440) vs (824 +/- 464) dyn x s x cm(-5) respectively, both P < 0.05) while the heart rate increased significantly [(93 +/- 17) vs (83 +/-16) beat/min, P < 0.05] in the adenosine group. Inhaled iloprost could also lower the systolic pulmonary artery pressure [(66 +/- 29) vs (79 +/- 28) mm Hg, P < 0.05], mean pulmonary artery pressure [(43 +/- 19) vs (52 +/- 19) mm Hg, P < 0.05] and pulmonary vascular resistance [(632 +/- 440) vs (816 +/- 448) dyn x s x cm(-5), P < 0.05] without any effect upon heart rate. Inhaled iloprost exerted more potent effect on lowering mean pulmonary artery pressure and pulmonary vascular resistance than adenosine (P < 0.05). The two medicines did not affect cardiac output, pulse oxygen saturation or systemic blood pressure. The side effects were fewer in the iloprost inhalation group than the adenosine group. CONCLUSION: During acute vasodilator testing, inhaled iloprost was more potent than infused adenosine as a pulmonary vasodilator in PAH complicated with connective tissue diseases.

[Cytophagic histiocytic panniculitis: a report of 6 cases with literature review].

OBJECTIVE: To study the clinical characteristics of cytophagic histiocytic panniculitis (CHP) and increase the understanding of CHP. METHODS: Clinical data of six cases with CHP in our hospital from 1994 were presented with literature review. RESULTS: (1) Six patients including five females, at a mean age of 21.8 year, suffered from the diseases for a mean period of 12.7 months; (2) The major clinical presentations included fever (6/6), subcutaneous nodules (6/6), splenomegaly (5/6) and hepatomegaly (4/6); The laboratory examinations showed elevated hepatic enzymes (4/6), coagulative dysfunction (2/6) and hemocytopenia (3/6); (3) The pathologic examinations revealed benign histiocytes that infiltrated the adipose tissues (6/6) and hemopieotic tissue (3/3), phagocytosing hemocytes; (4) Only one patient was treated with combined chemotherapy. CONCLUSIONS: CHP should be considered based on its unique clinical characteristics and would be diagnosed depending on pathology. The aggressive treatment of combined chemotherapy might improve the prognosis.