Our study showed a superior benefit of bone marrow cells and peripheral blood cell treatments of critical limb ischaemia in patients with diabetic foot disease when compared with conservative therapy. There was no difference between both cell therapy groups, and no patient demonstrated signs of systemic vasculogenesis.
The release of proangiogenic cytokines into the circulation after stem cell (SC) therapy and compensatory increase of angiogenesis inhibitors may reflect local vasculogenesis but also can increase the risk of side effects. The aim of our study was to evaluate serum levels of angiogenic cytokines with regard to the assessment of local and systemic vasculogenesis in diabetic patients with no-option critical limb ischemia (NO-CLI). Twentyfive diabetic patients with NO-CLI treated with SCs isolated from bone marrow or stimulated peripheral blood were included in the study. Serum levels of proangiogenic cytokines (VEGF, bFGF, Ang-1, PDGF-AA, and PDGF-BB) and an antiangiogenic cytokine (endostatin) were assessed 6 months after cell treatment, compared to baseline values, and correlated with the number of injected CD34 + cells. The clinical effect of SC therapy (assessed by changes in TcPO 2 ) and potential systemic vasculogenesis (assessed by eye fundus examination) were evaluated after 6 months. Serum levels of angiogenic inhibitor endostatin increased significantly after 1 and 3 months (p = 0.0003), but no significant increase in serum levels of proangiogenic cytokines was observed. A significant correlation between number of injected CD34 + cells and serum levels of endostatin was observed (r = 0.41, p < 0.05); however, proangiogenic cytokines did not correlate with CD34 + cells. No correlation between increase in TcPO 2 after treatment and serum levels of any of the angiogenic cytokines were seen, and no signs of systemic vasculogenesis in the retina were observed after 6 months. Despite the significant increase in the levels of the angiogenic inhibitor endostatin following SC treatment, there was no risk of systemic vasculogenesis after SC therapy as documented by serum levels of proangiogenic cytokines or changes in the retina.
The aim of our study was to analyse inherited thrombotic disorders that influence the long-term outcome of PTA. Methods. Diabetic patients with peripheral arterial disease (PAD) treated by PTA in our centre between 2008 and 2011 were included in the study. Patients were divided into unsuccessful PTA group (75 patients), successful PTA group (58 patients), and control group (65 patients, with diabetes but no PAD). Diagnosis of inherited thrombotic disorders included mutation in factor V (Leiden), factor II (prothrombin), and mutation in genes for methylenetetrahydrofolate reductase—MTHFR (C677T and A1298C). Results. The genotypic frequency of Leiden allele G1691A was significantly associated with a risk of unsuccessful PTA in comparison with successful PTA group and control group (OR 8.8 (1.1–70.6), p = 0.041, and OR 9.8 (1.2–79.2), p = 0.032, resp.). However, we only observed a trend for the association of the prothrombin allele G20210A and risk of PTA failure. The frequencies of alleles of MTHFR 677 or 1298 did not differ significantly among the groups. Conclusion. Our study showed higher frequency of heterozygous form of Leiden mutation in diabetic patients with unsuccessful outcome of PTA in comparison with patients with successful PTA and diabetic patients without PAD.
Evidence regarding the use of bortezomib-containing schemes in primary treatment of antibody-mediated rejection in heart transplant recipients is scarce. This case report presents the clinical experience with upstream use of bortezomib in primary treatment of early antibody-mediated rejection in an adult heart transplant recipient. Two cycles of bortezomib together with methylprednisolone, immunoadsorption, rituximab, and supplementary doses of intravenous immunoglobulin G reversed signs of heart failure, production of donor-specific antibodies, and findings of antibody-mediated rejection in biopsy. This treatment regimen was tolerated with only mild hematologic toxicity and proved to be successful during a 12-month follow-up. Primary treatment with a bortezomib-containing regimen appears to be a new therapeutic option for severe antibody-mediated rejection in heart transplant recipients. However, the efficacy and safety of this treatment need to be tested in prospective trials.
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