Precautions before starting tofacitinib in persons with rheumatoid arthritis

Tofacitinib is an immunosuppressive and disease-modifying therapy in rheumatoid arthritis. It may result in many infections flaring up. It is important to take precautions of all kinds (cardiovascular, malignancy, infections etc.) before starting tofacitinib. In this article, we have highlighted important steps where we need to take precautions before starting tofacitinib.     

IL-37b作用于树突状细胞CD39/ATP轴抑制类风湿性关节炎大鼠炎症反应的作用及机制

目的探讨白细胞介素37b重组蛋白(rmIL-37b)通过调节CD39/ATP轴抑制树突状细胞(DC)诱导类风湿性关节炎(RA)大鼠炎症反应的机制。方法将SD大鼠随机分为空白对照组(CTL)、CIA模型组、rmIL-37b 5μg/kg组、rmIL-37b 10μg/kg组,每组各10只。除了空白对照组外,其余大鼠采用含有卡介苗的完全弗氏佐剂和牛Ⅱ型胶原混合乳液免疫刺激,建立CIA模型。确定建模成功当天(D0),rmIL-37b组分别尾静脉注射5μg/kg、10μg/kg rmIL-37b;CTL组和CIA模型组注射相同体积的(1 ml/kg)生理盐水,连续给药15 d。免疫组化法检测滑膜组织Nod样受体蛋白3(NRPL3)炎症小体的表达,流式细胞术检测DC表型,另外试剂盒检测血清三磷酸腺苷(ATP)和免疫学指标。结果与CIA模型组相比,rmIL-37b 10μg/kg组大鼠足容积、AI值、NLRP3炎症小体表达量、血清ATP、IL-1β、IL-18、肿瘤坏死因子α(TNF-α)、抗Ⅱ型胶原抗体亚型(anti-ColⅡ-IgG、anti-ColⅡ-IgG2a)水平均降低,同时DC表面CD...     

Visual fixations and visually induced dizziness: An exploratory study

BackgroundVisually induced dizziness can develop as a sequala of a vestibular disorder and is characterized by symptoms of nausea, dizziness, and imbalance in rich visual environments such as supermarkets and shopping malls. To date the mechanisms underlying visually induced dizziness are poorly understood.Research questionWhat are the characteristics of visual fixations and postural sway in adults with visually induced dizziness compared to healthy adults when exposed to increasingly complex visual environments?MethodsWe recruited 20 adults with visually induced dizziness and 20 healthy adults to this cross-sectional exploratory study. Participants were instructed to maintain gaze on letters projected on a large screen with backgrounds of differing visual complexity. The number of visual refixations, movement of the centre of pressure, and movement of the head and body centres of mass were recorded.ResultsAdults with visually induced dizziness showed a significantly higher number of visual refixations (F= 10.592, p < 0.01), and increased mean velocity of head and body centres of mass movement (F= 14.034, p < 0.01 and F= 6.553, p < 0.05 respectively) compared to healthy adults.SignificanceAdults with visually induced dizziness exhibited visual fixational instability and increased postural and head sway compared to healthy adults. This was mainly observed in conditions with complex and moving backgrounds. This may account for reports from adults with visually induced dizziness of worsening symptoms in busy environments. The results from the study may assist in guiding intervention development to reduce symptoms of visually induced dizziness.     

HLA-DRB typing among polyarticular juvenile idiopathic arthritis and progressive pseudorheumatoid dysplasia patients

Juvenile Idiopathic Arthritis (JIA) is a multi-factorial disease influenced both by environmental and genetic factors. Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive genetic disorder affecting multiple joints, mimicking JIA. Aim of the work: to reveal the frequency of HLA-DR types among the studied patients and to correlate the different allele variations clinically. Patients and methods: Thirty JIA patients, in addition to 15 molecularly diagnosed PPD patients were subjected to full history taking and clinical examination. HLA-DRB1 typing was performed to 24/30 JIA and 12/15 PPD cases and thirty healthy age and sex matched children who were included as a control group. Results: The JIA patients were 22 females and 8 males with mean age of 15.8 ± 1.96 years and disease duration 5.3 ± 4.4 years. PPD patients were 8 males and 7 females with mean age of 8.7 ± 3.06 years and disease duration 3.95 ± 2.68 years. A significant frequency of HLA-DRB 04 (p = 0.049) among JIA patients was present in comparison to the controls (OR = 2.81, CI:1.02–7.75), other risky alleles were HLA-DRB 10, 13 and 15. However, HLA-DRB 01, 03, 07, 11 and 14 were found to be protective. HLA-DRB 01, 04, 10 and 13 were found to be risky alleles in PPD. However, HLA 03, 07, 11 and 15 were found to be protective alleles among PPD patients. Conclusion: HLA-DRB 04 was found in a higher frequency in JIA patients with a significant difference in comparison to the controls, denoting that it may play a role in the genetic pathogenesis of JIA.     

Rheumatoid arthritis occurring after coronavirus disease 2019 (COVID-19) infection: Case based review

IntroductionRheumatoid arthritis (RA) is a multifactorial disease. Genetic predisposition and environmental triggers including infections are the major players of autoimmunity. We present a case of rheumatoid arthritis occurring after the coronavirus disease 2019(COVID-19) infection.Case presentationA 72-year-old woman with a medical history of hypertension and atrial fibrillation presented for a 2-month history of bilateral symmetric polyarthritis starting 2 weeks after asymptomatic COVID-19 infection. Physical examination showed swelling and tenderness of the metacarpophalangeal and proximal interphalangeal joints, wrists, and knees. She had increased inflammatory biomarkers (C-reactive protein:108 mg/L, erythrocyte sedimentation rate: 95 mm, alpha-2 and gamma-globulins, interleukin 6: 16.5 pg/mL). Immunological tests revealed positive rheumatoid factor (128 UI/mL), anti-cyclic citrullinated peptide antibodies (200UI/mL), anti-nuclear antibodies (1:320), and anti-SARS-CoV-2 IgG (12.24U/mL). She had the genotype: HLA-DRB1*04:11, HLA-DQB1*03:01, and HLA-DQB1* 03:02. Hands and feet radiographs did not show any erosion. Ultrasonography showed active synovitis and erosion of the 5th right metatarsal head. The diagnosis of RA was made. The patient received intravenous pulses of methylprednisolone (250 mg/day for 3 consecutive days) then oral corticosteroids (15 mg daily) and methotrexate (10 mg/week) were associated, leading to clinical and biological improvement.ConclusionDespite its rarity, physicians should be aware of the possibility of the occurrence of RA after COVID-19 infection. This finding highlights the autoimmune property of this emerging virus and raises further questions about the pathogenesis of immunological alterations.     

Surgically treated reactive arthritis of the ankle after COVID-19 infection: A case report

A 37-year-old man developed right ankle pain and swelling six days after being diagnosed with coronavirus disease (COVID-19). Despite conservative treatment, his ankle symptoms persisted. Magnetic resonance imaging and computed tomography showed synovial hypertrophy and bone erosion in the ankle. Following arthroscopic synovectomy, performed 69 days after the COVID-19 diagnosis, the pain improved significantly. The clinical course was consistent with that of reactive arthritis following severe acute respiratory syndrome coronavirus 2 infection. The pathological findings resembled rheumatoid nodules. The bone erosion may have originated from the inflammatory pathway, which resembles the mechanism of rheumatoid arthritis.     

Organoids in modelling infectious diseases

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection.Teaser.Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.