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ID PMID Title PublicationDate abstract
26025435 Antinuclear antibody-positive cohort constitutes homogeneous entity in juvenile idiopathic 2016 OBJECTIVE: To identify a homogeneous entity for antinuclear antibody (ANA)-positive patients suffering from juvenile idiopathic arthritis (JIA). METHODS: All of the clinical features were recorded retrospectively. ANA positivity was defined as more than twice positive results at a titer of > 1:100. The correlation between ANA positivity and clinical parameters was assessed by multiple logistic regression analysis. RESULT: Of 120 patients, 49 patients were ANA positive (31 oligoarthritis, 18 rheumatoid factor [RF]-negative polyarthritis) and 71 patients were ANA negative (48 oligoarthritis, 23 RF-negative polyarthritis), and were recruited retrospectively to this study according to the International League of Associations for Rheumatology (ILAR) criteria. In ANA-positive cohort, the characteristics of early-onset age, female predominance, and asymmetric arthritis were observed compared with ANA-negative cohort including oligoarthritis and RF-negative polyarthritis. Correspondingly, we found that ANA-positive cohort had higher cumulative number of joints affected at 9 and 12 months after disease presentation than ANA-negative cohort, had lower frequency of occurrence of image change, and had a different pattern of affected arthritis than ANA-negative cohort, which was more likely to have knee involvement and less likely to have hip and shoulder involvement. ANA positivity correlated strongly with asymmetric arthritis, female predominance and wrist involvement. CONCLUSION: This study demonstrates that ANA-positive cohort divided into different subgroups by present ILAR criteria share the similar features and suggests that ANA positivity might serve as a novel potential value for JIA classification.
25065010 The active metabolite of spleen tyrosine kinase inhibitor fostamatinib abrogates the CD4⁠2015 Jan OBJECTIVES: Spleen tyrosine kinase (SYK) is a core signalling protein that drives inflammatory responses and is fundamental to the propagation of signals via numerous immune receptors, including the B cell receptor and Fc receptors (FcRs). Fostamatinib, a small molecule SYK inhibitor, has shown evidence of ameliorating inflammation in RA patients. We sought to understand how the active metabolite of fostamatinib, R406, affects the inflammatory response at the cellular level. METHODS: Antigen-specific in vivo systems and in vitro fluorescence microscopy were combined to investigate the effects of fostamatinib on antigen-specific interactions between dendritic cells (DCs) and CD4(+) T cells. RESULTS: Although it has previously been shown that R406 reduces the response of DCs to immune complexes (ICs), we found that fostamatinib failed to reduce specific CD4(+) T cell proliferation in mice after immunization with ICs. However, we observed in vitro that R406 reduces both the area and duration of cellular interactions between IC-activated DCs and specific CD4(+) T cells during the initial phase of cellular crosstalk. This led to diminished proliferation of antigen-specific CD4(+) T cells after R406 treatment compared with vehicle controls. This decreased proliferative capacity of CD4(+) T cells was accompanied by reduced expression of the co-stimulatory molecules, inducible T cell co-stimulator (ICOS) and PD-1, and abrogation of the production of inflammatory cytokines such as IFN-γ and IL-17. CONCLUSION: Our findings indicate a potential mechanism by which this compound may be effective in inhibiting FcR-driven CD4(+) T cell responses.
26523022 Native Joint Septic Arthritis: Epidemiology, Clinical Features, and Microbiological Causes 2015 Dec OBJECTIVE: To determine the epidemiology, clinical features, and microbiology of adult native joint septic arthritis in Canterbury, New Zealand, over a 5-year period in individuals with and without an underlying rheumatic disorder. METHODS: Patients with native joint septic arthritis were identified retrospectively and classified by Newman's criteria. The clinical characteristics were described and comparisons made between those with and without underlying rheumatic disease. RESULTS: Two hundred forty-eight cases of native joint septic arthritis (mean age 60, range 16-97 yrs) were identified with an overall incidence rate of 12.0/100,000/year (95% CI 10.6-13.6). Yearly incidence increased with age to a maximum of 73.4/100,000 in those > 90 years of age. Septic arthritis was iatrogenic in 16.9% of cases while 27% had an underlying inflammatory arthritis including gout (14.9%), calcium pyrophosphate disease (8.5%), and rheumatoid arthritis (4%). Few patients were taking immunosuppressant therapy, with just 1 taking a biological agent. Staphylococcus aureus was the most commonly identified organism. Those with underlying inflammatory arthritis were significantly older (73.6 yrs vs 55.6 yrs; p < 0.001), more likely to be female (55.2% vs 26.0%; p < 0.001), and to have septic polyarthritis (16.4% vs 4.4%; p = 0.002). The 30-day mortality was 2%, increasing to 6% at 90 days. CONCLUSION: The incidence of septic arthritis in Canterbury, New Zealand, is higher than in previous studies. Crystal arthropathy commonly coexisted with infection although autoimmune arthritis and immunosuppression was less of a factor than anticipated.
28031499 Mid-term outcome of total hip arthroplasty using a short stem. 2016 Dec PURPOSE: To review the outcome of total hip arthroplasty (THA) using a short femoral stem in 33 hips. METHODS: Records of 33 hips in 20 men and 10 women aged 25 to 40 (mean, 30) years who underwent cementless THA using a short femoral stem by a single senior surgeon were reviewed. The diagnosis included avascular necrosis (n=9), ankylosing spondylitis (n=12), rheumatoid arthritis (n=7), posttraumatic arthritis (n=4), and Hurler syndrome (n=1). Clinical outcome was assessed using the Harris Hip Score. Radiological outcome was assessed according to a modified Gruen zoning system. Stem positioning (neutral, varus, valgus) and bone contact wereevaluated, as were fixation and early host response as well as subsidence and changes in the calcar region (zone 5). Trabecular response (trabecular attachment), spot welds, cortical hypertrophy, and pedestal formation were determined. Heterotopic ossification was graded by the Brooker classification. RESULTS: The mean follow-up period was 6.5 years. The mean Harris Hip Score improved from 40 to 90. All hips achieved immediate postoperative stability. No patient had thigh pain. Four hips had varus placement (5º-7º) of the stem; all were asymptomatic and remained stable without any migration. Evidence of proximal load transfer (endosteal spot welds) between the endosteum and the stem in zones 2 and/or 4 was noted in 12 hips on both sides and in 8 hips on the lateral side only. At one year, all stems showed evidence of osseointegration. None had subsidence or progressive varus migration. There was no radiolucent line or osteolysis around the stem, pedestal formation or buttressing at the prosthesis tip, or cortical hypertrophy. One patient had grade I heterotopic ossification that was not clinically significant. One patient had a 1.5 cm leg lengthening. One patient had a discharging sinus, a loosened acetabular component, and intrapelvic migration at 2 years and underwent implant removal and debridement. One patient developed a crack in the proximal femur even with the smallest stem. The stem was fixed with cerclage wiring and remained stable with no migration. CONCLUSION: A short femoral stem design that transfers load proximally through a prominent lateral flare achieved good short-term outcome in younger patients. Nonetheless, the ease of removal and preservation of bone at the time of revision should guide the choice of the design of the short stem.
25681339 CD73 plays a protective role in collagen-induced arthritis. 2015 Mar 15 Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity and mortality. Recent studies suggest that modulation of adenosine signaling, a potent immunosuppressive pathway, is a promising approach for treatment of RA. Extracellular adenosine can come from two sources: transport of intracellular adenosine and hydrolysis of extracellular adenine nucleotides by CD73. In this study, we investigated the susceptibility of CD73-deficient C57BL/6 mice to collagen-induced arthritis (CIA), a well-established mouse model of RA. Our data demonstrated that CD73-deficient mice are significantly more susceptible to CIA than wild-type mice. CD73 deficiency resulted in an increased production of proinflammatory cytokines in the joints, increased Th1 T cell responses, and increased joint destruction. Surprisingly, this was accompanied by delayed anticollagen IgG responses, suggesting defective isotype class switching in CD73-deficient mice. Using bone marrow chimera mice, we demonstrated that CD73 expression on nonhematopoietic cells, but not on hematopoietic cells, was important for protection from CIA. We further demonstrated that administration of a selective A2A adenosine receptor agonist to CD73-deficient mice resulted in arthritis incidence similar to wild-type mice in support of a protective role for A2A signaling. Taken together, our study identifies CD73 as an important regulator of CIA in mice. It also strengthens the notion that CD73-generated adenosine by nonhematopoietic cells plays a protective role in RA and suggests that strategies able to enhance CD73 activity or expression levels may be a valid therapeutic option.
25707864 Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated vir 2015 Aug The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA.
24935412 Methods of assessment of tophus and bone erosions in gout using dual-energy CT: reproducib 2015 Apr This study aims to evaluate the intraobserver and interobserver reproducibility of the tophus urate volume, erosion volume, and the erosion score measurements in patients with gout by using dual-energy CT (DECT) scans comparing their bone erosion volumes against bone erosion scores and also to determine a valid measure of joint destruction in chronic gout. Sixty-six subjects underwent DECT scans of the hands or feet. Two independent observers measured the tophus urate volumes and bone erosion volumes using automated volume assessment software and the erosion scores based on the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). The intraobserver and interobserver reproducibility were analyzed by intraclass correlation coefficient (ICC) and limits of agreements analysis. The relationship between erosion volumes and erosion scores was analyzed. The intraobserver and interobserver ICC for tophus urate volume measurements (n = 636) were 1.000 (95 % confidence interval (95 % CI) 1.000 to 1.000) and 1.000 (95 % CI 1.000 to 1.000), 0.999 (0.999, 0.999) and 0.999 (0.999, 0.999) for bone erosion volumes (n = 350), 0.937 (0.928, 0.946) and 0.899 (0.883, 0.912) for erosion scores (n = 350). Strong positive correlations were demonstrated between individual erosion volumes and scores (r s = 0.914, p < 0.001) as well as total erosion volume and score per patient (r = 0.838-0.867, p < 0.001). This study demonstrated a high reproducibility of tophus urate volumes, erosion volumes, and erosion score measurements using DECT. Erosion volumes show to be a more direct and accurate method to evaluate bone erosion compared with erosion score, strongly supporting it as a superior and standard measure of structural joint damage in gout.
25379815 How good is the coverage and how accurate are exposure data in the Swedish Biologics Regis 2015 OBJECTIVES: To assess the coverage of the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden, ARTIS) across indications, and the accuracy of the registered information on treatment with biologics. METHOD: Through cross-reference of ARTIS to almost complete national health registers on prescriptions (adalimumab and etanercept), outpatient visits, and death/residency during 2008-2010, we assessed: the treatment coverage of ARTIS for each treatment indication, the validity of the registered start and stop dates, ARTIS treatments with no corresponding drug dispensations, and the accuracy of the registered information on concomitant anti-rheumatic therapies. RESULTS: According to the national health registers, 3945 individuals with a spondyloarthropathy (SpA) and 8032 patients with rheumatoid arthritis (RA) had filled at least one adalimumab or etanercept prescription during the study period. Of these, 86% of those with SpAs and 95% of patients with RA were also found in ARTIS with the corresponding treatment. Tumour necrosis factor (TNF) inhibitor prescriptions had been filled by 95% of patients between the ARTIS start and stop dates (allowing a 90-day window). More than 60 days before and more than 60 days after the registered start date in ARTIS, 5% and 4% respectively of patients had filled their first TNF inhibitor prescription. More than 90 days after the registered stop date in ARTIS, 8% of patients had filled one or more TNF inhibitor prescriptions. CONCLUSIONS: We observed a high coverage and accuracy of ARTIS data on biologics exposure, for both SpAs and RA. The combination of data from clinical registers such as ARTIS with data from national health registers offers a high quality measurement of actual treatment.
24493331 Abatacept as a successful therapy for myositis—a case-based review. 2015 Mar Only limited evidence exists on the therapeutic potential of biologic agents in the treatment of myositis. We present a brief review of the literature on off-label experiences of biologic agents in myositis, with a special interest in abatacept. Rituximab has been indicated to be beneficial and well tolerated in one large randomized controlled trial and many smaller studies. Initial data on tumour necrosis factor (TNF) inhibitors are conflicting. There are only a few case reports and mechanistic studies on the treatment of myositis with other biologics, including alemtuzumab, anakinra, tocilizumab and abatacept. We report a patient with severe myositis overlap syndrome, manifesting also as rheumatoid arthritis, peripheral vasculitis and interstitial lung disease. Her myositis was refractory to many conventional and biologic therapies but was well controlled with abatacept. This suggests that abatacept might be a beneficial option for the treatment of refractory myositis and that clinical trials are needed to further investigate its efficacy.
27579476 Therapeutic effect of ergotope peptides on CIA by down-regulation of inflammatory and Th1/ 2016 Oct Rheumatoid arthritis (RA) is a systemic autoimmune disease that results in a chronic and inflammatory disorder. Dynamic balance of helper T cells (Th)1, Th17 and regulatory T cells (Treg) is broken in RA. Since there is no cure for RA at present, it's necessary to find a truly effective and convenient treatment. Several studies intended to induce ergotopic regulation to treat autoimmune diseases. This study was undertaken to find the potential ergotope peptides and investigate its effect in treating the animal model of RA and their underlying regulatory mechanisms. Firstly, we selected the functional ergotope peptides from 25 overlapping peptides derived from interlukin(IL)-2 receptor (IL-2R) α chain, and then used these peptides to treat collagen-induced arthritis (CIA). The study showed ergotope peptides as immunomodulatory factors with great benefits at the clinical and pathologic levels. This effect was associated with the inhibition of type II collagen (CII)-specific proliferation and autoantibody production as well as the induction of anti-ergotypic immune response, the down-regulation of both Th1 and Th17 cells and their related components, and the emergence of Treg cells that had suppressive actions on autoreactive T cells. We also proved that cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and IL-10 are two important mediators which are critical to Treg suppressive function. The inhibition of Th1 and Th17 in established CIA could be attributed to ergotope induced Treg cells. Our findings reveal that ergotope peptides induce regulatory immune responses and restore immune tolerance, suggesting ergotope peptides treatment appears to be a novel approach to the therapy of RA patients and has a good application prospect with cheap, effective, convenient, wide-spectrum features.
27490216 Tendinopathy and Tendon Rupture Associated with Statins. 2016 May 17 Use of statins may be associated with certain tendinopathies and tendon ruptures, especially of the Achilles, quadriceps, and distal biceps tendons. Tendinopathy usually occurs within the first year of statin use and improves after the drug therapy is stopped. Systemic conditions with a higher risk of tendon rupture include diabetes, gout, rheumatoid arthritis, and chronic kidney disease. Certain drugs, such as corticosteroids and fluoroquinolones, have also been implicated in tendon ruptures. Patients with these systemic conditions who are taking statins in combination with other drugs that increase the risk of tendon injury should be educated about this risk and alternative treatments, including diet and exercise.
27381347 Methotrexate induced pneumatosis intestinalis under hemodialysis patient. 2017 Jan Pneumatosis intestinalis (PI) is a rare disorder characterized by the gas within the intestinal mucosa. This is the first report methotrexate (MTX) induced PI under hemodialysis (HD) patient. A 46-year-old man suffered rheumatoid arthritis and underwent HD at local HD center. After the initial induction of MTX, the patient showed epigastralgia and diarrhea. He was referred to our hospital and abdominal computed tomography showed significant large intestinal edema and free intraperitoneal air consistent with PI. Physicians should aware that MTX is contraindication drug for chronic kidney disease and high-flux HD may decrease MTX toxicity and oxidative stress, improving PI.
27190887 Treatment of Resıstant Cyclophosphamide Induced Haemorrhagic Cystıtıs: Revıew of Liter 2016 Apr Haemorrhagic Cystitis (HC) is defined as diffuse inflammatory bladder bleeding due to many aetiologies. Massive HC often arises from anticancer chemotherapy or radiotherapy for the treatment of pelvic malignancies. Phosphamides are the anti-cancer drugs used for treating breast cancer, B-cell lymphoma, leukemia, rheumatoid arthritis and systemic lupus erythaematosis by cross-linking strands of DNA and preventing the cell division. They are also used in bone marrow transplantation for prevention of Graft Versus Host Disease (GVHD). Hepatic metabolism of phosphamide forms acrolein, and acrolein makes ulceration, haemorrhage, edema and necrosis of the urothelium during its excretion by the urine. Infectious causes of HC in immunocomprimesed patients are adenovirus, BK polyoma-virus (BK), JC virus, and Cytomegalovirus (CMV). The present article attempts to make a review of literature for the treatment of intractable HC and report three cases with HC.
26783440 Poncet's disease mimicking rheumatoid arthritis in a patient with suspected Crohn's diseas 2016 Jan Poncet's disease is a rarely reported entity with an unknown pathogenesis. However, because it has a very favorable prognosis with antituberculosis drugs, we believe it should be considered as a differential diagnosis for patients with fever and polyarthritis of unknown cause, particularly if active tuberculosis is suspected.
30289662 [Differential diagnostics of febrile conditions in an emergency care clinic]. 2016 We undertook the analysis of 157 cases of fever at the stages of polyclinic - admission department - hospital treatment for the purpose of elucidating the structure of febrile syndrome. Pneumonia developed in 45 patients, infectious endocarditis in 34, chronic alcoholic hepatitis in 21, rheumatoid arthritis (pseudoseptic variant) in 2, systemic lupus erythematosus in 1, polymyositis in 2, acute pyelonephritis (exacerbation of chronic pyelonephritis) in 15, tumours of different localization in 37 patients. We evaluated the informative value of some acute-phase blood characteristics obtained, results of X-ray and ultrasonic studies for early diagnostics of pneumonia and infectious endocarditis.
26557260 Rituximab-induced interstitial lung disease: five case reports. 2015 Rituximab (RTX), a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody has been effectively used as a single agent or in combination with chemotherapy regimen to treat lymphoma since 1997. In addition, it has been used to treat idiopathic thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Recently, RTX has also been suggested for the treatment of certain connective tissue disease-related interstitial lung diseases (ILD) and hypersensitivity pneumonitis. Rare but serious pulmonary adverse reactions are reported. To raise awareness about this serious side effect of RTX treatment, as the indication for its use increases with time, we report five cases of probable RTX-ILD and discuss the current literature on this potentially lethal association.
26067484 Third Annual Open Meeting of the UK Pharmacogenomics and Stratified Medicine Network Confe 2015 Jul Third Annual Open Meeting of the UK Pharmacogenetics and Stratified Medicine Network 14 January 2015, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK The third Annual Open Meeting of the UK Pharmacogenetics and Stratified Medicine Network was held on 14 January 2015 in association with the Wellcome Trust on the Wellcome Trust Genome Campus at Hinxton, Cambridge, UK. In the morning, speakers from Cancer Research UK, the Medical Research Council, Genomics England, Innovate UK (formerly TSB) and the Department of Health described the current major projects they are funding. In the afternoon, speakers from various universities around the United Kingdom presented data on pharmacogenetics and stratified medicine research covering diverse disease areas including cancers, warfarin dosing, Gaucher disease and rheumatoid arthritis.
26445924 Rosuvastatin improves endothelial function in patients with inflammatory joint diseases, l 2015 Oct 8 INTRODUCTION: Endothelial dysfunction is an early step in the atherosclerotic process and can be quantified by flow-mediated vasodilation (FMD). Our aim was to investigate the effect of long-term rosuvastatin therapy on endothelial function in patients with inflammatory joint diseases (IJD) with established atherosclerosis. Furthermore, to evaluate correlations between change in FMD (ΔFMD) and change in carotid plaque (CP) height, arterial stiffness [aortic pulse wave velocity (aPWV) and augmentation index (AIx)], lipids, disease activity and inflammation. METHODS: Eighty-five statin-naïve patients with IJD and ultrasound-verified CP (rheumatoid arthritis: n = 53, ankylosing spondylitis: n = 24, psoriatic arthritis: n = 8) received rosuvastatin treatment for 18 months. Paired-samples t tests were used to assess ΔFMD from baseline to study end. Linear regression models were applied to evaluate correlations between ∆FMD and cardiovascular risk factors, rheumatic disease variables and medication. RESULTS: The mean ± SD FMD was significantly improved from 7.10 ± 3.14 % at baseline to 8.70 ± 2.98 % at study end (p < 0.001). Improvement in AIx (p < 0.05) and CP height reduction (p = 0.001) were significantly associated with ΔFMD (dependent variable). CONCLUSIONS: Long-term lipid lowering with rosuvastatin improved endothelial function in IJD patients with established atherosclerotic disease. Reduced arterial stiffness and CP regression were longitudinally correlated with the improvement in endothelial function measured by FMD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01389388 . Registered 16 April 2010.
27920815 Early onset acute tubular necrosis following single infusion of zoledronate. 2016 May Zoledronate is a highly potent bisphosphonate widely used in the treatment of postmenopausal osteoporosis. We report the first occurrence of toxic acute tubular necrosis (ATN) following treatment with zoledronate in a patient with osteoporosis. A 63-year-old Caucasian female with rheumatoid arthritis on anti-immune agents received a single dose of zoledronic acid (reclast) for worsening osteoporosis. Twelve days later, she developed renal failure with a rise in serum creatinine from a baseline level of 1.1 mg/dL to 5.5 mg/dL. Renal biopsy showed toxic ATN. Zoledronate was discontinued and the patient had subsequent gradual improvement in renal function with final serum creatinine of 1.8 mg/dL at 1 month of follow up. Careful monitoring of serum creatinine and awareness of the potential nephrotoxicity may avert the development of acute renal failure in osteoporosis patients treated with this agent.
26788808 Clinical data and regulatory issues of biosimilar products. 2015 Dec Biologics are a fast-growing segment of pharmaceutical development. Many are effective in the treatment of illnesses such as cancers, rheumatoid arthritis, and multiple sclerosis. Biologics encompass a range of compounds, including recombinant hormones, growth factors, monoclonal antibodies, recombinant vaccines, and blood products. Many of these drugs are facing patent expiration, and pharmaceutical research is focusing on the development of generic substitutes, or "biosimilars." Because biologics generally exhibit high molecular complexity, the process of development and approval of biosimilars is complicated. Unlike standard small molecule generics where an identical drug copy is expected, variations in biosimilars may be inherent because the sponsor does not have knowledge of the originator's processes. Because of this intricacy, regulatory requirements are needed to ensure biosimilarity, comparability, and interchangeability with respect to efficacy and safety. Clinician awareness of the similarities and differences between original biopharmaceuticals and biosimilars, as well as their impact on efficacy and safety, is imperative.