BackgroundBiological disease modifying antirheumatic drugs (bDMARDs) are frequently used in combination with other drugs. Very limited data are available on concomitant therapy with bDMARDs in China.ObjectivesTo investigate the usage patterns and safety of concomitant drugs in Chinese RA patients receiving bDMARDs.MethodsPatients from 15 Chinese hospitals were recruited in this cross-sectional study. Consenting patients (aged ≥18 years) diagnosed with RA receiving bDMARDs were included.ResultsData collected from 802 patients with a mean (SD) age of 49.0 (13.9) years (81.3% women) were analyzed. Among these patients, 89.5%, 56.1%, 29.7%, and 19.1% were receiving concomitant conventional DMARDs (cDMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GC), and drugs for local application (LA drugs), respectively. In total, 718 patients were receiving concomitant cDMARDs. The proportion of patients using 1, 2, and 3 concomitant cDMARDs was 49.3%, 41.2%, and 9.5%, respectively. The most common cDMARDs were methotrexate, hydroxychloroquine, leflunomide, and sulfasalazine; used by 65.9%, 41.8%, 41.5%, and 6.3% patients at a mean (SD) daily dose (mg) of 1.4 (0.4), 340.3 (96.3), 15.4 (5.2), and 1753.3 (693.3), respectively. The respective mean (SD) duration of treatment (days) was 443.7 (845.8), 261.3 (409.4), 413.4 (578.5), and 429.1 (1039.9). Among the 238 patients on concomitant GC, 73.1% and 23.1% patients were receiving oral prednisone and methylprednisolone at a mean (SD) weekly dose (mg) of 57.8 (31.9) and 59.7 (151.6), respectively. In total, 17.6% patients reported at least one GC-associated adverse event (AE) at a mean (SD) duration of treatment (weeks) of 12 (28.3); the most common AEs were moon face (13.9%) and weight gain (4.2%). Among the 450 patients receiving concomitant NSAIDs, 43.1%, 20.2%, and 12.0% patients were receiving celecoxib, meloxicam, and loxoprofen sodium at a mean (SD) daily dose (mg) of 306.2 (100.1), 12.8 (3.5), and 143.9 (45.3), respectively. Most NSAID users were receiving NSAIDs at a dose lower than the daily maximum, except 2 patients using diclofenac acid at higher than daily maximum dose (150 mg). Only 3.6% NSAID users reported at least one AE; the most common AE was gastrointestinal discomfort (3.1%). A total of 153 patients were receiving concomitant LA drugs. The most common LA drugs were ketoprofen, diclofenac acid, and a Chinese herb medicine “Jia Wei Shuang Bai San”, used by 30.1%, 20.9%, and 10.5% patients, respectively. The corresponding mean (SD) treatment duration (weeks) was 2.0 (4.1), 7.8 (26.4), and 16.9 (28.0), respectively. The predominant reason (62.9% patients) for not using LA drugs was the lack of physician-directed prescription.ConclusionsThe usage patterns of concomitant cDMARDs and NSAIDs in Chinese RA patients receiving bDMARDs are similar to those in Western countries. The 17.6% concomitant GC users who reported at least one AE are receiving GC for longer time (12 weeks on average). LA drugs including traditional Chinese medicine offer a broad...

improve the detection of ITC compared with routine pathological examination.Background: Accurate TNM staging plays an important role in the diagnosis, treatment, and prognosis of lung cancer. In current clinical practice, the staging of lung cancer is usually decided by physicians. We aim to develop an automated lung cancer staging system using machine learning and verify the staging correctness. Method: In this work, we constructed a feature generalizing and automatically extracting model using NLP techniques. The parameters required for Tumor (T), Lymph nodes (N) and Metastases (M) categories of the eighth edition of the International Lung Cancer Research Association (IASLC) TNM staging system were automatically extracted from de-identified electronic medical records of pathology, operation note, CT scan, PET/CT scan, cranial MRI, bone scan, and ultrasound. A technical solution using Bayesian reasoning network was developed for automated staging. The stage was automatically predicted while the reasoning basis was given. All the reports were reviewed by thoracic surgeons to obtain the gold standard for evaluation. Result: Five hundred de-identified reports were collected as training dataset to construct the model by learning from stage given by physicians. Five hundred and thirteen de-identified reports were collected as validation dataset. The current overall recall rate was 96.88%, and the agreement rate between machine prediction and physicians's diagnosis was 93.70%. Conclusion: Natural language processing is a useful technique for encoding medical reports in order to detect the TNM descriptors. Automatic lung cancer staging process using Bayesian reasoning network achieve acceptable accuracy. This system is extendable and can be applied to large database processing.

Background:Behcet’s disease (BD) is a chronic and relapsing vasculitis, in which major vessel involvement is a main cause of mortality and morbidity. The therapeutic arsenal is mainly composed of classical immunosuppressants. However, when faced with resistance to these drugs, no alternative therapeutic strategy is currently recommended.Objectives:To assess the efficacy and safety of interleukin 6 receptor inhibitor tocilizumab (TCZ) in refractory arterial involvement of BD in a real-life observational setting.Methods:10 patients were enrolled in our center between 2014 and 2019. All patients met the international criteria for BD and had severe arterial involvement evaluated by echocardiography, angio-Computerized Tomography scan and vascular Doppler. The diagnosis of refractory arterio-BD was based on objective vascular symptoms not explained by any other known disease and non-response to conventional immunosuppressants combined with glucocorticoids therapy. All patients underwent TCZ infusions at 8mg/kg every 4 weeks. Concomitant therapy with immunosuppressants and glucocorticoids was continued. Clinical and imaging findings were assessed before and after TCZ therapy. All adverse events were recorded during follow-up.Results:All the patients were males, with a mean age of 44.3±10.5 years in this study. The mean age at presentation of arterial involvement was 40.8±9.2 years old. The patterns of arterial involvement were aneurysm (n=9), stenosis (n=3) and aortic valve lesion (n=2). After a mean follow-up of 26.8±7.2 months, TCZ yielded rapid and maintained clinical improvement in 9 patients, with complete remission in 6 of them and partial response in 3 of them. Discontinuation of TCZ treatment due to relapse occurred in one case as the enlargement of abdominal aortic aneurysm. The mean glucocorticoid dosage was tapered from 54.5±20.6mg/d to 8.3±3.6mg/d (p<0.001). And the use of immunosuppressants was tapered in 4 (40.0%) patients. As for serological improvement, the median ESR and CRP levels decreased from 50 (2-82) mm/h and 32.9 (2.1-62.3) mg/dL to 4 (1-10) mm/h (p<0.001) and 2.9 (0.2-12.1) mg/dL (p<0.001), respectively. Radiologic improvement of artery lesion was demonstrated in 4(40%) patients. None of the patients had serious adverse events during follow-up.Conclusion:TCZ was a safe and effective therapeutic option for refractory arterial involvement of BD, with a favorable steroid-sparing effect.References:[1]G Hatemi, R Christensen, D Bang, et al. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis. 2018;77(6):808-818.[2]Y Ozguler, P Leccese, R Christensen, et al. Management of major organ involvement of Behcet’s syndrome: a systematic review for update of the EULAR recommendations. Rheumatology (Oxford). 2018;57(12):2200-2212.[3]M Akiyama, Y Kaneko, T Takeuchi. Effectiveness of tocilizumab in Behcet’s disease: A systematic literature review. Semin Arthritis Rheum. 2020;50(4):797-804.Table 1.Tocilizumab therapy in ten cases of refractory arterio-BDPatientAge, yearDisease duration, monthsClinical features*Arterial lesionsPrevious therapyResponse at week 24134228O, G, P, S, IStenosis of CA/ SMA/RA/SCA, aortic valve prolapsePred/CYC/MMFCR22024O, SDissecting aneurysm of AA (Debakey I)Pred/MMFPR367276O, G, P, S, Athoracoabdominal aortic aneurysmPred/CYC/TACCR46775O, S, UStenosis of LAD/LCX/RCAPred /CYCCR55080O, G, AAbdominal and coronary aortic aneurysmsPred /CYCRelapse64826O, GAortic insufficiencyPred /CYCPR726147O, P, S, VIliac artery aneurysmPred /MMFCR849466O, S, VThoracoabdominal and coronary aortic aneurysmsPred /CYC/AZACR927181O, P, SPseudoaneurysm of CCAPred /CYCPR10Male/55354O, P, SAbdominal aneurysm, stenosis of LAD/LCX/RCAPred /CYC/AZACR*O: oral ulcer; G: genital ulcer; P: pathergy test; S: skin lesions; I: intestinal ulcer; A: arthritis; U: uveitis; V: venous thrombosisFigure 1.Changes from baseline in BSAS, BDCAF, ESR, CRP and steroid daily dose at 24 weeksDisclosure of Interests:None declared

BackgroundBiological disease modifying antirheumatic drugs (bDMARDs) have been increasingly prescribed for RA in mainland China. Large scale epidemiological studies are needed to understand the treatment patterns and experience of bDMARD therapy in China.ObjectivesTo characterize bDMARD therapy in Chinese RA patients in routine clinical practice.MethodsFifteen Chinese hospitals participated in this multi-center cross-sectional observational study. Consenting patients aged ≥18 years diagnosed with RA and receiving marketed bDMARDs were included.ResultsIn total, 802 patients (81.3% women) met the inclusion criteria. The mean age (SD) was 49.0 (13.9) years. Analysis of available data of dosage and treatment duration of bDMARDs for all patients revealed that 66.6% patients were receiving ETN at a mean (SD) weekly dose of 38.2 (15.6) mg for 25.5 (47.0) weeks. The second most common bDMARD was tocilizumab administered to 17.0% patients at a mean weekly dose of 94.5 (21.9) mg for 4.7 (7.5) weeks. Only 7.5% and 6.6% patients were receiving adalimumab and infliximab, respectively. Using DAS28 score as the evaluation index, 32.8%, 42.2%, 12.4%, and 12.6% patients showed high, medium, low disease activity, and disease remission, respectively. Compared with patients (62.7%) receiving bDMARDs for <3 months, whose DAS28 score was 4.6 (1.5), those receiving bDMARDs for ≥3 months exhibited significantly lower DAS28 scores (P<0.0001). In particular, patients (14.6%) receiving bDMARDs for ≥12 months exhibited DAS28 scores of 3.2 (1.4). In total, 89.5% patients were receiving a combination of bDMARDs and cDMARDs whereas 10.5% patients were receiving bDMARD monotherapy. Among the 84 patients receiving bDMARD monotherapy, 75.0%, 10.7%, 9.5%, and 4.8% were receiving etanercept (ETN), infliximab, tocilizumab, and adalimumab respectively; for ETN, 8.3% and 66.7% patients were using original ETN (Enbrel®) and ETN biosimilar (Yi Sai Pu®), respectively. Patients receiving concomitant therapy exhibited significantly lower DAS28 than patients receiving bDMARD monotherapy (4.3 vs. 4.8, P=0.011). Reasons for discontinuing or switching bDMARDs varied. For patients (n=58) who had received the same bDMARDs previously, the main reasons for discontinuing the bDMARDs were improvement of disease condition (31%), financial burden (24.1%), and adverse reactions (13.8%). For patients (n=93) switching to different bDMARDs, the main reasons were unsatisfactory efficacy of the previous bDMARDs (58.1%), adverse reactions (14.0%), improvement of disease condition (10.8%), and financial burden (10.8%).ConclusionsThis is the first large scale multi-center study to characterize bDMARD therapy in China. Patients receiving bDMARDs ≥3 months showed significantly lower DAS28 scores than patients receiving bDMARDs <3 months, although the treatment target was not achieved within 12 months in routine practice. Currently, ETN and tocilizumab are the most commonly used bDMARDs in China, and the proportion of patients receiving bDMARD monotherapy is lower than that in Eur...

BackgroundBehcet’s syndrome (BS) is an autoimmune disease characterized by recurrent mucocutaneous ulcerations, vascular and nervous system involvement. While there have been a lot of researches proving that immune cells play a vital role in rheumatic disease, opinions on the effect of different immune cell subsets on BS is inconsistent. Therefore, we performed this real-world study to explore the role of immune cells in the pathogenesis of BS.ObjectivesTo investigate the changes in the levels of several immune cell subsets in BS, and the correlation between the levels of different immune cell subsets and clinical features in patients with BS.MethodsThis is a retrospective, single-center study conducted in Beijing. 136 patients diagnosed with BS in rheumatology and immunology department of Peking University People’s Hospital from 2018 to 2021 and 114 healthy controls (HCs) were enrolled. All patients met the International Criteria for Behcet’s Disease (ICBD). We utilized flow cytometry to test the levels of CD4+T cells, CD8+T cells, B cells, NK cells and several subsets of CD4+T cells. Wilcoxon rank test and student’st-test were used and a P-value <0.05 was considered statistically significant.ResultsCompared to HCs, there is a decrease in the count of CD4+T cells, B cells and NK cells in BS patients. A significant increase in the frequency of IFN-γ, IL-2 and IL-4 producing CD4+T cell in BS patients were observed, which accompanied by a decreased frequency of Naïve CD4+T cells. The frequency of Foxp3+Treg cells was notably increased while the proportion of CLA+Treg in Treg cells was significantly decreased in BS patients. BS patients’ frequency of follicular helper T cells were apparently lower than HCs. There was a significant reduction of the frequency of Treg in patients with vascular involvement. The frequency of follicular helper T cells were positively correlated with joint involvement and negatively correlated with nerve involvement in BS patients. Patients with gastrointestinal involvement had a increased frequency of TNF-α, IFN-γ, IL-2 and IL-4 producing CD4+T cells and a decreased level of B cell count. Elevated level of NK cell count and decreased frequency of TNF-α, IL-2 producing CD4+T cells were found in patients with skin-mucosa involvement alone.ConclusionOur study confirmed that Th1 cells, Th2 cells, Treg cells, follicular helper T cells, B cells and NK cells contribute a lot to the pathogenesis of BS.References[1]Yazici, Y., Hatemi, G., Bodaghi, B., Cheon, J. H., Suzuki, N., Ambrose, N., & Yazici, H. (2021). Behçet syndrome.Nature reviews. Disease primers,7(1), 67.https://doi.org/10.1038/s41572-021-00301-1Figure: The level of different immune cells in patients with BS and healthy controls.Table: Correlation of immune cells and clinical manifestation in patients with BS.Patients with skin-mucosa involvement alonePatients with more than skin-mucosa involvementPTNF-α（%）33.17±11.3144.20±12.370.010IL-2（%）43.58±14.4652.41±13.630.004NK cell（/μL）302.86±222.00209.89±148.460.006Patients with joint involvementPatients without joint involvementFollicular helper T cell（%）2.97±1.422.18±0.930.002Patients with nerve involvementPatients without nerve involvementFollicular helper T cell（%）1.83±0.842.52±1.150.006Patients with gastrointestinal involvementPatients without gastrointestinal involvementTNF-α（%）49.53±11.7240.74±11.710.002IFN-γ（%）18.94±6.5216.04±5.000.039IL-2（%）56.94±15.2647.81±13.460.005IL-4（%）2.10±0.881.60±0.760.010B cell（/μL）160.48±141.41232.64±177.210.028Patients with vascular involvementPatients without vascular involvementTreg（%）7.75±2.279.14±3.410.019(Results without significance are not listed)Acknowledgements:NIL.Disclosure of InterestsNone Declared.