Metabolic syndrome and the decreased levels of uric acid by leflunomide favor redox imbalance in patients with rheumatoid arthritis

Oxidative stress plays a role in the pathophysiology of rheumatoid arthritis (RA). The aim of the present study was to verify the influence of metabolic syndrome (MetS) and disease-modifying antirheumatic drugs on nitrosative and oxidative biomarkers in patients with RA. A total of 177 patients with RA and 150 healthy volunteers participated in this study, which measured lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), carbonyl protein, total radical-trapping antioxidant parameter (TRAP), uric acid (UA), and C-reactive protein (CRP). NOx and the NOx/TRAP ratio were significantly increased in RA, while no significant differences in lipid hydroperoxides, AOPP, UA, and TRAP levels were found between both groups. Treatment with leflunomide was associated with increased levels of carbonyl protein, and lowered levels in TRAP and UA, while the NOx/TRAP ratio further increased. NOx and the NOx/TRAP ratio were significantly higher in women than in men, while TRAP and UA were significantly lower in women. MetS was accompanied by increased AOPP and UA levels. RA was best predicted by increased NOx/TRAP ratio, CRP, and BMI. In conclusion, our data demonstrated that NOx and NOx/TRAP are strongly associated with RA physiopathology. Our findings suggest that inhibition of iNOS may become an interesting therapeutic approach for the treatment of RA. In addition, the presence of MetS and a decrease in levels of UA by leflunomide favor redox imbalance in RA patients. More studies are needed to evaluate the impact of antioxidant capacity reduction on RA progression.     

Eltrombopag for the Treatment of Refractory Pure RBC Aplasia after Major ABO Incompatible Hematopoietic Stem Cell Transplantation

Pure RBC aplasia (PRCS) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many therapeutic options are available to treat this condition, including erythropoietin, rituximab, bortezomib, plasma exchange, immunoadsorption, donor lymphocyte infusion, mesenchymal stem cells, antithymocyte globulin, and high-dose steroids; however, treatment outcomes are often variable and can sometimes lead to disappointing results. In this brief article we report our experience with 2 patients with PRCA after major ABO-incompatible HSCT who were resistant to multiple therapeutic interventions and who eventually benefited from treatment with eltrombopag, a thrombopoietin mimetic approved by the US Food and Drug Administration for the treatment of patients with immune thrombocytopenic purpura or severe aplastic anemia refractory to immunosuppressive agents or not eligible for HSCT. Data from these 2 patients show that eltrombopag was effective in treating erythroid aplasia and transfusion dependence after HSCT in patients who did not benefit from multiple previous treatments. Moreover, eltrombopag was well tolerated, with only a transient thrombocytosis requiring dose adjustment and no evidence of clonal evolution. Based on the positive results obtained in these 2 patients, we suggest that eltrombopag may have a favorable effect on unilineage cytopenias such as PRCA. Further studies in a large proportion of patients are mandatory to confirm these preliminary results.     

“Baby Heart Project”: The Italian Project for Accreditation and Quality Management in Pediatric Cardiology and Cardiac Surgery

Optimization of the relationship between the supply and the demand for medical services should ideally be taken into consideration for the planning within each national Health System. Although government national health organizations embrace this policy specifically, the contribution of expert committees (under the scientific societies’ guarantee in any specific medical field) should be advocated for their capability to collect and analyze the data reported by the various national institutions. In addition, these committees have the competence to analyze the need for the resources necessary to the operation of these centers. The field of pediatric cardiology and cardiac surgery may represent a model of clinical governance of particular interest with regard to programming and to a definition of the quality standards that may be extended to highly specialized institutions and ideally to the entire Health System. The “Baby Heart Project,” which represents a model of governance and clinical quality in the field of pediatric cardiology and cardiac surgery, was born from the spontaneous aggregation of a committee of experts, supported by duly appointed Italian Scientific Societies and guided by a national agency for accreditation. The ultimate aim is to standardize both procedures and results for future planning within the national Health System.