The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for <6 months prior to inclusion in the study. Patients with auto-immune or inflammatory diseases other than RA were excluded. Patients treated with glucocorticoids (GCs), disease modifying activity drugs and biologic agents within the past 6 months were also excluded. In the second phase of the study, eRA patients were randomly assigned to standard treatment with methotrexate (MTX) and GCs with (21) or without (18) cholecalcipherol (300,000 IU) and followed for 3 months; the randomization was done by computer generated tables to allocate treatments. Three patients didn’t come back to the follow up visit for personal reasons. None of the patients experienced adverse events. The main outcome measures were T cells phenotypes, OCs precursors and inflammatory cytokines. Secondary outcome measure were clinical parameters. In eRA, 25OH vitamin D levels were significantly lower. CD4+/IFNγ+,CD4+/IL4+, CD4+/IL17A+ and CD4+IL17A+IFNγ+, cells were increased in eRA as well as non-classical OCs precursors, whereas T regulatory cells were not altered. TNFα, TGFβ1, RANKL, IL-23 and IL-6 were increased in eRA. Non-classical OCs, IL-23 and IL-6 correlated with disease severity and activity. Standard treatment with MTX and GC ameliorated clinical symptoms and reduced IL-23, whereas it did not affect CD4+ cells sub-sets nor OCs precursors. After 3 months, the combined use of cholecalcipherol significantly ameliorated the effect of treatment on global health. In eRA, a significant imbalance in T CD4+ sub-types accompanied by increased levels of non-classical OCs precursors and pro-inflammatory cytokines was observed. A single dose of cholecalcipherol (300,000 IU) combined with standard treatment significantly ameliorates patients general health.
The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.
Hybrid imaging procedures such as single-photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT) showed a rapid diffusion in recent years because of their high sensitivity, specificity, and accuracy, due to a more accurate localization and definition of scintigraphic findings. However, hybrid systems inevitably lead to an increase in patient radiation exposure because of the added CT component. Effective doses due to the radiopharmaceuticals can be estimated by multiplying the administered activities by the effective dose coefficients, while for the CT component the dose-length product can be multiplied by a conversion coefficient k. However, the effective dose value is subject to a high degree of uncertainty and must be interpreted as a broad, generic estimate of biologic risk. Although the effective dose can be used to estimate and compare the risk of radiation exposure across multiple imaging techniques, clinicians should be aware that it represents a generic evaluation of the risk derived from a given procedure to a generic model of the human body. It cannot be applied to a single individual and should not be used for epidemiologic studies or the estimation of population risks due to the inherent uncertainties and oversimplifications involved. Practical ways to reduce radiation dose to patients eligible for hybrid imaging involve adjustments to both the planning phase and throughout the execution of the study. These methods include individual justification of radiation exposure, radiopharmaceutical choice, adherence to diagnostic reference levels (DLR), patient hydration and bladder voiding, adoption of new technical devices (sensitive detectors or collimators) with new reconstruction algorithms, and implementation of appropriate CT protocols and exposure parameters.
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