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ID PMID Title PublicationDate abstract
30187688 A multicentre observational study comparing patient reported outcomes to assess reliabilit 2019 Jan AIMS: The use of swollen (SJC) and tender joint counts (TJC) for rheumatoid arthritis (RA) disease activity and treatment effectiveness is well established. Patient-reported outcomes (PRO) are important. However, it is unknown if patient scoring is as reliable as that of trained professionals. METHODS: PRO including SJC and TJC were assessed at baseline, 6 and 12 weeks by patients and clinicians. Data were collected using ePRO (electronic) and pPRO (paper). The Least Squares Method (LSM), Pearson correlation (Rs) and weighted Kappa scores were used to assess inter-rater reliability and agreement of responses between the patient, nurse and physician for changes in TJC and SJC from 0 to 12 weeks of treatment. RESULTS: There was a total of 341 evaluable matched joint assessment in 52 patients with RA: 157 nurse, 106 patient and 78 physician. There were matched joint count pairs for 104 patient-nurse, 72 physician-nurse and 21 patient-physician. Correlation (R) of TJC scores were as follows: patient-nurse 0.83 (P < 0.001), physician-nurse 0.85 (P < 0.001) and physician-patient 0.59 (P = 0.005). The inter-rater reliability (agreement) of the patient-nurse pairs had a weighted Kappa of 0.59 (0.53, 0.68). Correlation (R) of SJC scores were as follows: patient-nurse 0.69 (P < 0.001), physician-nurse 0.66 (P < 0.001) and physician-patient 0.42 (P = 0.058). The inter-rater reliability (agreement) of the patient-nurse pairs had a weighted Kappa of 0.48 (0.41, 0.55). CONCLUSIONS: There is a moderate to high level of agreement between clinicians and patient TJC and SJC assessments that suggest it may be a useful option in assessing joints and response in RA. Further evaluation of RA activity tools such as Disease Activity Score of 28 joints, Crohn Disease Activity Index or Simple Disease Activity Index utilizing patient assessments may be worth exploring.
30285532 A high incidence of extensor pollicis brevis insertion into the distal phalanx in rheumato 2019 Nov Objectives: The aim of the current study was to investigate the pattern of extensor pollicis brevis (EPB) insertion macroscopically and histologically using cadaveric thumbs, and to compare the incidence of different insertions with that of thumb boutonnière deformity in rheumatoid arthritis (RA) patients who required surgical reconstruction.Methods: We examined 103 thumbs of 58 adult cadavers with no evidence of RA, and reviewed the surgical records of 28 thumbs of 23 RA patients who underwent surgical reconstruction for thumb boutonnière deformity. The incidence of different insertion patterns of the cadaveric thumbs and the RA thumbs were compared using the Fisher's exact test.Results: Macroscopic and histologic examination revealed that the insertion patterns of EPB could be divided into three groups: insertion into the base of the proximal phalanx (Type P1), integration of EPB into the dorsal fibrocartilage of the MCP joint (Type P2), and insertion into the distal phalanx (Type D). The incidence of Type D was significantly higher in RA patients with thumb boutonnière deformity (64%) than that in the non-RA cadavers (29%; P < .05).Conclusion: EPB is inserted into the distal phalanx more frequently in RA patients who require surgery for thumb boutonnière deformity than non-RA cadavers, suggesting an additional possible mechanism of this deformity.
31541390 The impaired gene expression of adenosine monophosphate-activated kinase (AMPK), a key met 2019 Dec The disturbed immune homeostasis is involved in the pathogenesis of an array of autoimmune diseases like rheumatoid arthritis (RA). The adenosine monophosphate-activated protein kinase (AMPK) with a pivotal role in immunometabolism process, also plays a regulatory function in the immune system. This study aims to evaluate the alteration of AMPK gene expression in peripheral blood leukocytes of RA patients and its effects on disease severity as well as plasma levels of anti-inflammatory cytokines. 60 RA patients, including 30 newly diagnosed and 30 patients whose disease were under controlled with the combinational disease-modifying anti-rheumatic drug (DMARD), as well as 30 healthy subjects, were enrolled in our study. The gene expression of AMPK was evaluated using real-time PCR method. The plasma concentrations of IL-10 and TGF-β1 were measured using sandwich ELISA. The gene expression of AMPK was significantly lower in the newly diagnosed RA patients in comparison with the control group (P = 0.049). Inversely, in RA patients who received DMARD therapy, the gene expression of AMPK was significantly higher than the control group (P = 0.003). There was no significant correlation between AMPK gene expression and plasma levels of IL-10 and TGF-β1. The plasma levels of TGF-β1 was significantly higher in both newly diagnosed and under-treatment patients compared with healthy subjects (P < 0.001). The impaired gene expression of AMPK in peripheral blood leukocytes and elevated levels of plasma TGF-β1 can be contributed in RA pathogenesis.
30928534 Early clinical response and long-term radiographic progression in recent-onset rheumatoid 2019 Oct OBJECTIVES: The primary objective was to evaluate the correlation between 5-year radiographic structural disease progression and early clinical remission in recent-onset rheumatoid arthritis (RA). The secondary objective was to assess the correlation between erosion development in joints free of damage at baseline and early clinical remission. METHODS: A single-center retrospective study was performed in 133 patients meeting ACR criteria for RA of recent onset. Two radiologists independently quantified radiographic structural lesions at the hands and forefeet using the Sharp van der Heijde (SVdH) Score at the diagnosis then 5 years later. The patients were divided into two groups based on whether the lesions were stable (SVdH Score increase ≤ 10 points, Xray-STAB group) or had worsened (SVdH Score increase > 10 points, Xray-PROG group). The clinical response was assessed after 3, 6, and 12 months. Clinical remission was defined based on the DAS28-CRP, SDAI, CDAI, and ACR/EULAR Boolean remission criteria. RESULTS: Of the 133 patients, 90 were in the Xray-STAB group (mean SVdH score increase, 2.4 ± 2.9) and 43 in the Xray-PROG group (22.9 ± 13.4). The 6-month disease activity indices were higher in the Xray-PROG group (P < 0.05). Achieving a 6-month clinical remission had 58.6%, 39.1%, 40.0%, and 32.2% sensitivity for predicting 5-year radiographic stability when the DAS28-CRP, SDAI, CDAI, and Boolean definition were used, respectively; corresponding values for specificity were 73.8%, 85.7%, 83.7%, and 90.5%. CONCLUSION: Achieving a clinical remission within 6 months is key to preventing radiographic structural progression in patients with recent-onset RA.
31829286 Effectiveness of an online self-management tool, OPERAS (an On-demand Program to EmpoweR A 2019 Dec 11 BACKGROUND: Active self-management is a process where patients are fully engaged in managing their health in daily life by having access to contextualized health data and tailored guidance to support a healthy lifestyle. This study aims to determine whether an e-health intervention that incorporates symptom/disease activity monitoring and physical activity counselling can improve self-management ability in patients with rheumatoid arthritis (RA). METHODS: The 'Empowering active self-management of arthritis: Raising the bar with OPERAS (an On-demand Program to EmpoweR Active Self-management)' project is a randomized controlled trial that uses a delayed control design. One hundred thirty-four participants with RA will be randomly assigned to start the intervention either immediately (immediate group) or 6 months later (delayed group). The intervention involves (1) use of a Fitbit-compatible web app to record and monitor their RA disease activity, symptoms, and time spent on physical activity and a Fitbit; (2) group education and individual counselling by a physiotherapist (PT); and (3) six phone calls with a PT. The primary outcome measure is self-management ability measured by the Patient Activation Measure. Secondary outcome measures include disease status, fatigue, pain, depressive symptoms, and characteristics of habitual behavior and also time spent in physical activity and sedentary activity with a wearable multi-sensor device (SenseWear Mini). After the 6-month intervention, we will interview a sample of participants to examine their experiences with the intervention. DISCUSSION: The results of this study will help to determine whether this technology-enhanced self-management intervention improves self-management ability and health outcomes for people living with RA. A limitation of this study is that participants will need to self-report their symptoms, disease status, and treatment use through questionnaires on the OPERAS web app. The user-friendly interface, reminder emails from the research staff, and tailored guidance from PTs will encourage participants to actively engage with the app. TRIAL REGISTRATION: Date of last update in ClinicalTrials.gov: January 2, 2019. ClinicalTrials.gov Identifier: NCT03404245.
30950139 Five-year incidence of common comorbidities, such as hypertension, dyslipidemia, diabetes 2019 Jul AIM: To estimate the 5-year incidence of common comorbidities, including lifestyle-associated diseases, in older Japanese patients with rheumatoid arthritis (RA). METHODS: We enrolled 129 consecutive patients with RA aged ≥65 years in this study. We examined all patients for the presence of hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, cerebrovascular disease and cancer at baseline (in 2013) and 5 years later (in 2018) using clinical records, self-reported questionnaires, interviews and medication records. RESULTS: At baseline, hypertension was prevalent in 37.2% of the patients, dyslipidemia in 18.6%, diabetes mellitus in 9.3%, cardiovascular disease in 14.7%, cerebrovascular disease in 10.1% and cancer in 10.1%. Furthermore, the change of prevalence after 5 years from baseline of hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, cerebrovascular disease and cancer was 4.6%, 3.9%, 0.8%, 4.7%, 2.3% and 1.5%, respectively. The factors associated at baseline and/or after 5 years of hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease and cancer included disease duration and body mass index, body mass index and anti-cyclic citrullinated peptide antibody, corticosteroid use, body mass index, and male and disease duration, respectively. CONCLUSIONS: The Japanese population is aging and so is the population of patients with RA. In older patients with RA, hypertension and cardiovascular disease should be particularly considered. Therefore, although the therapeutic agents for RA have improved, a better understanding of the comorbidities in older patients with RA should impact the treatment of RA. Geriatr Gerontol Int 2019; 19: 577-581.
30999969 Novel optical spectral transmission (OST)-guided versus conventionally disease activity-gu 2019 Apr 17 BACKGROUND: Assessment of disease activity is a critical component of tight-control, treat-to-target treatment strategies of rheumatoid arthritis (RA). Recently, the HandScan has been validated as a novel method for objectively assessing RA disease activity in only 1.5 min, using optical spectral transmission (OST) in hands and wrists. We describe the protocol of a randomized controlled clinical trial (RCT) to investigate whether HandScan-guided treatment aimed at 'HandScan remission' (HandScan arm) is at least as effective as and more cost-effective than clinically guided treatment aimed at ACR/EULAR 2011 Boolean remission (DAS arm). METHODS/DESIGN: The study is a multi-center, double-blind, non-inferiority RCT of 18 months duration. Patients ≥ 18 years with newly diagnosed, disease-modifying antirheumatic drug (DMARD)-naïve RA according to the ACR 2010 classification criteria, will be randomized to the DAS arm or the HandScan arm. The efficacy of the arms will be compared by evaluating Health Assessment Questionnaire (HAQ) scores (primary outcome) after 18 months of DMARD therapy, aimed at remission. The equivalence margin in HAQ scores between study arms is 0.2. Secondary outcomes are differences in cost-effectiveness and radiographic joint damage between treatment arms. The non-inferiority sample size calculation to obtain a power of 80% at a one-sided p value of 0.05, with 10% dropouts, resulted in 61 patients per arm. In both arms, DMARD strategy will be intensified monthly according to predefined steps until remission is achieved; in both arms DMARDs and treatment steps are identical. If sustained remission, defined as remission that persists consistently over three consecutive months, is achieved, DMARD therapy will be tapered. DISCUSSION: The study protocol and the specifically designed decision-making software application allow for implementation of this RCT. To test a novel method of assessing disease activity and comparing (cost-)effectiveness with the contemporary method in treat-to-target DMARD strategies in early RA patients. TRIAL REGISTRATION: Dutch Trial Register, NTR6388. Registered on 6 April 2017 ( NL50026.041.14 ). Protocol version 3.0, 19-01-2017.
29671370 Synovial inflammation analyzed by 3-T magnetic resonance imaging in etanercept-treated pat 2019 May OBJECTIVES: To evaluate joint inflammation using 3-T MRI in rheumatoid arthritis (RA) patients treated with conventional disease modifying anti-rheumatic drugs (cDMARDs) as compared to inhibitors for tumor necrosis factor α (TNFi) over 12 months. METHODS: Prospective epidemiologic clinical pilot study using the RA MRI system (RAMRIS), the visual analog scale (VAS, 0-100) and the Disease Activity Score 28-joint count (DAS28) at baseline, 4, and 12 months after initiation of etanercept (ETA). Ten patients with inadequate response to two cDMARDs were treated with ETA and compared to 10 patients responding to cDMARDs. RESULTS: In cDMARD patients, parameters at baseline and 12 months did not change: VAS: 21.0 ± 11.3 and 20.2 ± 24.6; DAS28: 2.1 ± 0.6 and 2.9 ± 1.0; and RAMRIS: 11.0 ± 2.3 and 11.8 ± 2.8, respectively. In contrast, in the ETA-patients the same parameters were as follows at baseline, 4, and 12 months: VAS: 46.3 ± 7.9, 23.9 ± 7.1, and 24.0 ± 6.3 (each p = .04); DAS28: 3.8 ± 0.4, 2.8 ± 0.3 (ns), and 2.5 ± 0.3 (p = .01); and RAMRIS: 28.9 ± 5.0, 25.8 ± 4.7 (ns), and 24.6 ± 4.5 (ns). Comparing ETA and cDMARD patients, RAMRIS was significantly different. CONCLUSION: The data suggest that synovial inflammation and DAS28 remission are separate entities in RA. MRI scoring before starting a treatment may therefore indicate the requirement for TNFi.
32598674 [Level of N-terminal fragment of brain natriuretic peptide progenitor and atherosclerotic 2019 May 15 The high prognostic significance of the concentration of the N-terminal - pro-B-type natriuretic peptide (NT-proBNP) in the development of cardiovascular diseases (CVD) was identified for rheumatoid arthritis (RA) and general populations. AIM: to investigate the significance of NT-proBNP level in patients (pts) with RA with the ineffectiveness and/or intolerance of basic anti - inflammatory therapy; compare the level of NT-proBNP with atherosclerotic lesion of the brachiocephalic arteries (BCA), traditional risk factors and inflammatory markers. MATERIALS AND METHODS: The investigation enrolled 28 pts (24women/4men) with the lack of efficacy/resistance and/or intolerance of basic anti - inflammatory drugs (DMARDs); median age was 55 [46; 61] years, median disease duration 114 [60; 168] month; DAS28 6,2 [5.1; 7.0]; SDAI 35.0[23.9; 51.0], CDAI 30.0[21.0; 42.0], serum positivity for rheumatoid factor (RF) (100%)/anti - cyclic citrullinated peptide antibodies (ACCP) (86%). The study did not include RA pts with congestive heart failure. High incidence of traditional risk factors was found in RA pts: arterial hypertension - in 75%, dyslipidemia - 61%, smoking - 17%, overweight - 61%, family history of cardiovascular diseases - 36%, hypodynamia - 68%. Coronary artery disease was diagnosed in 11% RA pts. Lack of efficacy of 3 or more DMARDs was found in 46% of pts, intolerance to previous therapy with DMARDs - in 54% pts. 47% were receiving methotrexate (20 [18; 25] mg/week), 11% - leflunomide, 7% - sulfasalazine, 46% - glucocorticoids, 75% - non - steroidal anti - inflammatory drugs. The control group consisted of 20 healthy donors, comparable to pts by age and sex. Serum levels of of NT-proBNP were measured using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland). The determination of the intima - media thickness (IMT) BCA were assessed from duplex scanning. Atherosclerotic lesion of BCA was assessed by the presence of atherosclerotic plaque (IMT ≥1.2 mm). RESULTS: NT-proBNP concentrations in RA pts proved to be higher (78.7 [41.4; 101.3] pg/ml) than those in the control group (55.3 [36.6; 67.3] pg/ml, p100 pg/ml - 1 group (n=6) and ≤100 pg/ml - 2 group (n=22). Groups of RA pts did not differ in gender, age, activity of RA, frequency of detection of traditional risk factors. Atherosclerotic lesion of the BCA was detected in 3 (50%) pts of the 1 group and in 8 (36%) pts of the 2 group (p>0.05). In RA pts the level of NT-proBNP correlated with age (r=0.39; p.
31736366 Transdermal delivery of fluvastatin sodium via tailored spanlastic nanovesicles: mitigated 2019 Dec The current study aimed to encapsulate fluvastatin sodium (FVS), a member of the statins family possessing pleiotropic effects in rheumatoid arthritis (RA), into spanlastic nanovesicles (SNVs) for transdermal delivery. This novel delivery could surmount FVS associated oral encumbrances such as apparent first-pass effect, poor bioavailability and short elimination half-life, hence, accomplishing platform for management of RA. To consummate this objective, FVS-loaded SNVs were elaborated by thin film hydration method, utilizing either Span 60 or Span 80, together with Tween 80 or Brij 35 as an edge activator according to full factorial design (2(4)). Applying Design-Expert(®) software, the influence of formulation variables on SNVs physicochemical properties and the optimized formulation selection were explored. Additionally, the pharmacokinetic studies were scrutinized in rats. Furthermore, in Freund's adjuvant-induced arthritis, rheumatoid markers, TNF-α, IL-10, p38 MAPK, and antioxidant parameters were measured. The optimum SNVs were nano-scaled spherical vesicles (201.54 ± 9.16 nm), having reasonable entrapment efficiency (71.28 ± 2.05%), appropriate release over 8 h (89.45 ± 3.64%) and adequate permeation characteristics across the skin (402.55 ± 27.48 µg/cm(2)). The pharmacokinetic study disclosed ameliorated bioavailability of the optimum SNVs gel by 2.79- and 4.59-fold as compared to the oral solution as well as the traditional gel, respectively. Moreover, it elicited a significant suppression of p38 MAPK expression and also significant improvement of all other measured biomarkers. Concisely, the foregoing findings proposed that SNVs can be auspicious for augmenting FVS transdermal delivery for management of RA.
31653373 Resection Arthroplasty: Current Indications and Tips. 2019 Dec Resection arthroplasty for metatarsalgia is a selective procedure primarily indicated for patients with rheumatoid arthritis. These patients present with significant forefoot deformities, poor bone quality, and loss of soft tissue integrity. Resection of the metatarsal heads and correction of lesser toe deformities improve pain and decrease transfer metatarsalgia. Patients with concurrent hallux valgus may benefit from a lapidus procedure or hallux metatarsophalangeal fusion in an effort to improve outcomes and decrease incidence of recurrent hallux valgus. In rare cases, diabetics with neuropathy may require resection arthroplasty in the setting of forefoot deformities recalcitrant to other modalities.
30948395 Rheumatoid meningitis: a rare cause of unilateral pachymeningitis. 2019 Apr 3 An 87-year-old woman with quiescent rheumatoid arthritis, not on immunosuppressive therapy, presented with unilateral arm weakness, confusion and visual hallucinations. There were no infective symptoms or history of malignancy. Cerebrospinal fluid (CSF) analysis demonstrated lymphocytosis and raised protein, without flow cytometric or cytological abnormalities. Viral, bacterial, mycobacterial and fungal testing of CSF and serum were negative. MRI brain indicated unilateral leptomeningeal enhancement. There was no evidence of occult malignancy on CT imaging of the chest, abdomen and pelvis. Rheumatoid factor and anticyclic citrullinated peptide were strongly positive. The patient declined meningeal biopsy but responded to treatment with corticosteroid therapy.
31368549 Pomegranate supplementation attenuates inflammation, joint dysfunction via inhibition of N 2019 Aug Incisive search of innovative compounds for regulating pain, inflammation, and bone damage, with nominal side effects has focused on nutritional supplements. The endeavor of this research work was to investigate, for first time, the inhibitory effect of pomegranate rind extract in established models of nociception and inflammation. Pomegranate (50, 100, and 200 mg/kg) and indomethacin (3 mg/kg) was assessed in eddy's hot plate-induced algesia, carrageenan, and Complete Freund's adjuvant-induced models in Wistar rats. Results of study conclude that pomegranate at a dose of 200 mg/kg showed significant (p < 0.001) reduction in paw swelling in both inflammatory experimental models. In addition, observations recorded a significant (p < 0.05) increase in nociceptive threshold. Henceforth, we might say that pomegranate (200 mg/kg) decline pain and inflammation by downregulating the activation of TNF-R1, TNF-α, IL-1β, IL-6, NF-κB, oxidative stress markers, and tissue histology. PRACTICAL APPLICATIONS: The research work represents the first report on inhibitory mechanism of NF-κB by pomegranate rind extract, enriched in tannins and flavanoids. The findings of the study provide satisfactory evidence of pomegranate rind in amelioration of adjuvant-induced arthritis. Pomegranate rind, being enrich in bioactive compounds like phenolics and flavanoids possess potent antioxidant activity that might contribute in attenuating rheumatoid arthritis.
30411520 Association between chest computed tomography findings and respiratory adverse events in r 2019 Apr OBJECTIVE: This study aimed to assess the association between chest computed tomography (CT) findings and incidence of respiratory adverse events (RAEs), and to detect risk factors for RAEs, in RA patients treated with long-term biological therapy. METHODS: Clinical and radiological data of 332 RA patients who were treated with biological disease-modifying antirheumatic drugs were collected. CT data were assessed by an experienced radiologist. Patients were categorized into the interstitial lung disease (ILD) group (n = 29), airway disease (AD) group (n = 76), co-existing ILD and AD (Co-existing) group (n = 6), and the group without detectable change (WDC, n = 221) based on CT findings and scores. The incidence of RAEs was calculated for each group, and risk factors for RAEs from CT findings were explored. RESULTS: We identified 41 RAEs, including acute onset or exacerbation of ILD (ILD events, n = 15), respiratory tract infection events (infection events, n = 21), and other events (n = 6). Cumulative incidences of ILD events were 20.2, 3.75, 47.2, and 1.94 (/1000 patient-years: PY) in the ILD, AD, Co-existing, and WDC groups, respectively, and those of infection events were 11.3, 17.6, 23.6, and 2.39 (/1000PY), respectively. Severity, as assessed by CT scores, was correlated with the incidence of RAEs. Risk factors for ILD events were reticular and honeycomb changes, and those for infection events were consolidation, bronchial wall thickening, bronchiectasis, bronchiolitis, air trapping, and atelectasis after adjusting for background factors. CONCLUSION: Our findings highlight particular CT findings that are associated with RAEs in RA patients undergoing long-term biological therapy.
30415439 CIGB-814, an altered peptide ligand derived from human heat-shock protein 60, decreases an 2019 Mar Rheumatoid arthritis (RA) is a chronic T cell-mediated autoimmune disease. Serum autoantibodies against cyclic citrullinated peptides (anti-CCP) are significant markers for diagnosis and prognosis of this disease. Induction of immune tolerance as therapeutic approach for RA constitutes a current research focal point. In this sense, we carried out a phase I clinical trial in RA patients with a new therapeutic candidate (called CIGB-814); which induced mechanisms associated with restoration of peripheral tolerance in preclinical studies. CIGB 814 is an altered peptide ligand (APL), derived from a CD4+ T cell epitope of human heat-shock protein 60 (HSP60), an autoantigen involved in the pathogenesis of RA. Twenty patients with moderate disease activity were included in this open label trial. Sequential dose-escalation of 1, 2.5 and 5 mg of CIGB-814 was studied. Consecutive groups of six, five, and nine patients received a subcutaneous dose weekly of the peptide during the first month and one dose monthly during the next 5 months. The peptide was well tolerated and reduced disease activity. Here, we reported the quantification of anti-CCP antibodies during the treatment with this APL and in the follow-up stage. Anti-CCP antibodies were quantified in the plasma from patients by a commercial enzyme immunoassay at baseline (T0) and at weeks 28 and 48. Results showed that CIGB-814 induced a significant reduction of anti-CCP antibodies. In addition, this decrease correlated with clinical improvement in patients assessed by Disease Activity Score in 28 joints (DAS28) criteria. These findings reinforce the therapeutic potential of CIGB-814.
33087004 A case of acute diffuse large B cell lymphoma in an anti-human T-cell leukaemia virus type 2020 Jul A 70-year-old woman was hospitalised due to jaundice and fever. She was diagnosed with rheumatoid arthritis (RA) at 54 years of age. Treatment with methotrexate (MTX) was successful, and her RA was in remission. Five weeks before the hospitalisation, she was diagnosed with optic neuritis due to a decline in the visual acuity of the right eye. She was treated with methylprednisolone pulse therapy, followed by prednisolone (PSL), before the hospitalisation, which were not effective. Blood tests showed increased C-reactive protein (CRP) levels, liver injury, and thrombocytopenia. Abdominal echo revealed numerous enlarged lymph nodes in the hepatic portal region. Malignant lymphoma was suspected due to high serum levels of soluble interleukin-2 receptor. None of the treatments were effective, and she died on the fifth hospital day. Diffuse large B cell lymphoma was diagnosed during the autopsy, which showed infiltration of CD20-positive atypical lymphocytes in almost all organs. Since she was taking MTX, she was diagnosed with immunosuppressive drug-associated lymphoproliferative disease (LPD). Anti-human T-cell leukaemia virus type 1 (HTLV-1) antibody was detected in her serum after her death; however, adult T cell leukaemia/lymphoma was not observed. LPD develops during the treatment of RA with disease modifying anti-rheumatic drugs; however, a rapid clinical course leading to death is rarely observed. Previous reports suggest that T cell dysregulation observed in HTLV-1 may contribute towards the development of B cell lymphoma. We have discussed the possible roles of HTLV-1 in LPD development in this case.
31699217 Autoimmune diseases in China. 2019 Autoimmune diseases, such as rheumatoid arthritis, systematic lupus erythematosus and Sjögren's syndrome, are a group of diseases characterized by the activation of immune cells and excessive production of autoantibodies. Although the pathogenesis of these diseases is still not completely understood, studies have shown that multiple factors including genetics, environment and immune responses play important roles in the development and progression of the diseases. In China, there are great achievements in the mechanisms of autoimmune diseases during the last decades. These studies provide new insight to understand the diseases and also shed light on the development of novel therapy.
31584316 A novel arthritis model induced by wind, damp, cold and heat in female rats. 2020 Oct Animal models are in constant development to benefit scientific research. Rheumatoid arthritis (RA) is considered a very complex disease due to its complicated pathogenesis, and patients with rheumatic disease around the world are still unable to obtain effective, simple and curable treatment. In order to obtain a clear insight into the pathogenesis of RA, a rat model was established based on the concept of Bi syndrome in Traditional Chinese Medicine by simulating the conditions of RA as much as possible via the change in the physical conditions wind, damp, cold and heat (WDCH). For the first time, a new WDCH-induced RA model in female rats was successfully established and evaluated by body-weight change, paw swelling, blood cells analysis, spleen and thymus coefficients, autoantibodies and serum cytokine changes and histopathology. This model is characterised by its objectivity, no exogenous induction, short modelling time, extremely elevated expression level of autoantibodies and obvious histopathological change. The establishment of such a new model may provide more benefits in the research of the pathogenesis of RA.
30506878 Induction of Krüppel-like factor 2 reduces K/BxN serum-induced arthritis. 2019 Feb Krüppel-like factor 2 (KLF2) critically regulates activation and function of monocyte, which plays important pathogenic role in progressive joint destruction in rheumatoid arthritis (RA). It is yet to be established the molecular basis of KLF2-mediated regulation of monocytes in RA pathogenesis. Herein, we show that a class of compound, HDAC inhibitors (HDACi) induced KLF2 expression in monocytes both in vitro and in vivo. KLF2 level was also elevated in tissues, such as bone marrow, spleen and thymus in mice after infusion of HDACi. Importantly, HDACi significantly reduced osteoclastic differentiation of monocytes with the up-regulation of KLF2 and concomitant down-regulation of matrixmetalloproteinases both in the expression level as well as in the protein level. In addition, HDACi reduced K/BxN serum-induced arthritic inflammation and joint destruction in mice in a dose-dependent manner. Finally, co-immunoprecipitation and overexpression studies confirmed that KLF2 directly interacts with HDAC4 molecule in cells. These findings provide mechanistic evidence of KLF2-mediated regulation of K/BxN serum-induced arthritic inflammation.
30528678 New concepts to reduce glucocorticoid toxicity. 2019 Nov 70 years after their first use, low-dose glucocorticoids are a common part of pharmacological rheumatoid arthritis treatment. This is due to their well-proven capacities in symptom severity and disease activity reduction, in particular when combined with a disease-modifying anti-rheumatic drug, such as methotrexate. Nevertheless, glucocorticoid administration, in long-term especially, is also seen critically because of its potential adverse conditions. In order to achieve a reduction in treatment-related adverse events, modern therapy regimes should take into consideration patients' risk factors and therefore be individual. The Glucocorticoid Toxicity Index is a method to measure side effects of glucocorticoid therapy objectively and will be central in future studies comparing different therapy regimes. Such a new therapy regime is modified-release prednisone, which - thanks to a different time of liberation - seems to capable of reducing morning stiffness much more effectively than conventional prednisone, whilst showing similar properties in disease activity reduction and safety. Still, confirmation of these first data in further trials will be necessary. Eventually, other innovative concepts are liposomal glucocorticoids, dissociated agonists of glucocorticoid receptors and intramuscular application of glucocorticoids. Though these approaches appear to be promising, additional research will be required.