- The immunomodulatory effects of TNF-α inhibitors on human Th17 cells via RORγt histone acetylation. [Journal Article]
- OOncotarget 2016 Dec 03
- The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA p...
The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification. Human CD4+ T cells from healthy subjects and patients with RA were pretreated with TNF-α inhibitors and then being polarized into IL-17-producing cells. The Th17-related cytokine levels in the culture supernatants were determined with an enzyme-linked immunosorbent assay. Intracellular signalling was investigated by western blot, real-time RT-PCR, and chromatin immunoprecipitation. Th17-polarized cells from patients with RA produced more IL-17A, IL-17F and IL-22 than those from healthy subjects. Etanercept and adalimumab suppressed IL-17A, IL-17F and IL-22 levels in Th17-polarized cells from healthy subjects and patients with RA. Western blot analysis revealed that etanercept and adalimumab decreased mitogen-activated protein kinase-phospho-p38, nuclear factor-κB-phospho-p65, phospho-STAT3 and RORγt levels. Etanercept and adalimumab decreased histone (H)3 and H4 acetylation in the RORγt gene promotor region by decreasing the recruitment of the acetyltransferases p300, CBP and PCAF. The present study broadens our knowledge of the mechanisms underlying the immunomodulatory effects of TNF-α inhibitors in rheumatoid arthritis treatment.
- [Septic arthritis after intra-articular injection is rare: does the Taskforce Infection Prevention use a sledgehammer to crack a nut?] [Journal Article]
- NTNed Tijdschr Geneeskd 2016; 160(0):D789
- CONCLUSIONS: The incidence of SA after a joint puncture can be considered low. Due to the low baseline incidence, we anticipate that it is unlikely that the prescriptive measures outlined by TIF will lead to a cost-effective reduction in incidence of SA.
- Clinical Management of Diabetes Mellitus in the Older Adult Patient. [Journal Article]
- CDCurr Diabetes Rev 2016 Dec 06
- CONCLUSIONS: Providers, patients, caregivers and family members should be vigilant to quickly recognize and manage, micro- and macro-vascular diseases, in order to prevent increased incidence in morbidity and/or mortality, as well as medical costs of diabetes care attributed to this age group.
- Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab-a substudy of the optimized treatment algorithm in early RA (OPERA) trial. [Journal Article]
- CRClin Rheumatol 2016 Dec 05
- This study aims to investigate 1-year hand bone loss (HBL1-year) in early rheumatoid arthritis (RA) patients treated with a methotrexate (MTX) and intra-articular triamcinolone treat-to-target strate...
This study aims to investigate 1-year hand bone loss (HBL1-year) in early rheumatoid arthritis (RA) patients treated with a methotrexate (MTX) and intra-articular triamcinolone treat-to-target strategy +/- adalimumab and to determine if HBL6months is associated with radiographic progression after 2 years. In a clinical trial (OPERA) of 180 treatment-naive early RA patients, bone mineral density (BMD) was estimated from hand radiographs with digital X-ray radiogrammetry (DXR) at baseline, after 6 (n = 90) and 12 months (n = 70) of follow-up. Baseline and 2-year radiographs were scored according to the Sharp/van der Heijde method. Baseline characteristics and HBL6months (0-6 months changes in DXR-BMD) were investigated as predictors of structural damage by univariate linear (∆ total Sharp/van der Heijde score (TSS) as dependent variable) and logistic (+/-radiographic progression (∆TSS >0) as dependent variable) regression analyses. Variables with p < 0.10 were included in multivariable models. In 70 patients with available HBL1-year data, HBL1-year was median (interquartile range (IQR)) -1.9 (-3.3; -0.26 mg/cm(2)) in the MTX + placebo group and -1.8 (-3.6; 0.06) mg/cm(2) in the MTX + adalimumab group, p = 0.98, Wilcoxon signed-rank. Increased HBL (compared to general population reference values) was found in 26/37 and 23/33 patients in the MTX + placebo and MTX + adalimumab groups, chi-squared = 0.99. In 90 patients with HBL6months data and 2-year radiographic data, HBL6months was independently associated with ∆TSS after 2 years (β = -0.086 (95% confidence interval = -0.15; -0.025) TSS unit/mg/cm(2) increase, p = 0.006) but not with presence of radiographic progression (∆TSS >0) (OR 0.96 (0.92-1.0), p = 0.10). In early RA patients treated with a methotrexate-based treat-to-target strategy, the majority of patients had increased HBL1-year, irrespective of adalimumab; HBL6months was independently associated with ∆TSS after 2 years.
- Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone. [Journal Article]
- OIOsteoporos Int 2016 Dec 05
- CONCLUSIONS: Bone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.
- Reasons for Discontinuation and Adverse Effects of TNFα Inhibitors in a Cohort of Patients With Rheumatoid Arthritis and Ankylosing Spondylitis. [Journal Article]
- APAnn Pharmacother 2016 Dec 05
- CONCLUSIONS: The main cause of discontinuation of anti-TNFα is therapeutic failure in both diseases. Etanercept and infliximab have the best survival rates in RA and AS, respectively.
- External Validation of a Prognostic Model for Predicting Nonresponse Following Knee Arthroplasty. [Journal Article]
- JAJ Arthroplasty 2016 Nov 15
- CONCLUSIONS: The external validity of the prognostic instrument was partially supported. While discrimination of the model was very similar to the recently developed instrument, calibration was poor indicating poor agreement between actual vs predicted probabilities of nonresponse. Western Ontario and McMaster Universities Arthritis Index and Kellgren and Lawrence grades show strong potential for use in future prognostic model development. Measurements of general mental health and obesity were not prognostic for nonresponse.
- [Differential diagnosis of monoarthritis]. [Journal Article]
- CLCas Lek Cesk 2016; 155(6):299-304
- Making the diagnosis of monoarthritis can be quite difficult, because in contrast with polyarthritis just a few clinical data is available and wide diagnostic spectrum is present.The diagnosis of inf...
Making the diagnosis of monoarthritis can be quite difficult, because in contrast with polyarthritis just a few clinical data is available and wide diagnostic spectrum is present.The diagnosis of inflammatory rheumatic disease is usually in responsibility of a rheumatologist, but we know from experience that is necessary to carry out the basal differential diagnostic assessment as soon as possible to begin the optimal therapy. General practitioners and orthopaedists are usually first to face this problem.Monoarthritis can be divided into non-inflammatory arthritis where activated osteoarthritis and trauma belongs and inflammatory arthritis, which include gouty arthritis, chondrocalcinosis, infectious arthritis, juvenile idiopathic arthritis, spondylitis, incipient rheumatoid arthritis and many others.The article also focuses on the management of patients with monoarthritis where detailed history, careful clinical joint examination and the nature of arthritis assessment is necessary for differential diagnostic considerations. Our balance sheet further facilitate imaging, arthrocentesis with the analysis of synovial fluid and of course the laboratory examination.
- The cost-effectiveness of HLA-b*5801 screening to guide initial urate-lowering therapy for gout in the United States. [Journal Article]
- SASemin Arthritis Rheum 2016 Nov 01
- CONCLUSIONS: Testing for HLA-B*5801 prior to allopurinol initiation is cost-effective for Asians and African Americans, but not for Caucasians or Hispanics in the United States. Reducing AHS risk by other predictive measures could make HLA-B*5801 testing not cost-effective even among Asians and Blacks.
New Search Next
- Systematic review of rheumatic disease epidemiology in the indigenous populations of Canada, the United States, Australia, and New Zealand. [Review]
- SASemin Arthritis Rheum 2016 Nov 01
- CONCLUSIONS: This comprehensive summary describes rheumatic disease burden in indigenous populations in four countries with similar disparities in social determinants of health, to inform clinical service requirements to meet population need.