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Satellite cells are the main source of myogenic progenitors in postnatal skeletal muscle, but their use in cell therapy for muscle disorders is limited because these cells cannot be delivered through circulation and they are rapidly exhausted in severe myopathies. The search for alternative donor cells is ongoing, but none of the candidates so far show all the features required for successful colonization and repair of diseased muscle. In this study, we show that bisperoxovanadium, a phospho-tyrosine phosphatase inhibitor, induces myogenic cells to acquire a gene expression profile and a differentiation potential consistent with the phenotype of a circulating precursors, while maintaining their myogenic potential. These effects are mediated, at least in part, by NF-κB activation through the Tyr42-IκB-α phosphorylation, as shown by the expression of the dominant negative mutant form of the p50 NF-κB subunit. Moreover, when bisperoxovanadium-treated cells are injected into the femoral artery of α-sarcoglican null dystrophic mice, they are able to circulate and to reach muscle tissue; importantly, they contribute to muscle regeneration, as shown by the expression of α-sarcoglican in some fibers. Our observations indicate that bisperoxovanadium, or similar compounds, may prove very valuable to obtain and to expand, from committed cells, multipotent cell populations suitable for gene-cell therapy applications and may help to understand the molecular basis of genome reprogramming and "stem-ness." [ABSTRACT FROM AUTHOR]

Aim To study the influence of peripheral neuropathy on intermittent claudication in patients with Type 2 diabetes (T2DM). Methods Twenty-five patients with T2DM were grouped according to the ankle/brachial index (ABI): 10 with ABI > 0.9 without peripheral artery disease (PAD; group T2DM) and 15 with ABI < 0.9 with PAD (group T2DM + PAD). Twelve individuals without T2DM with PAD (group PAD without T2DM) were also enrolled. Tests for peripheral neuropathy were performed in all patients. ABI, rate pressure product, prothrombin fragments 1 + 2 (F1+2), thrombin-anti-thrombin complex (TAT), andd-dimer were measured before and after a treadmill test. During exercise both initial and absolute claudication distance and electrocardiogram readings were recorded. Results We found mild peripheral neuropathy in 20% of group T2DM and 46.7% of group T2DM + PAD ( P < 0.01). After exercise, the rate pressure product increased in each group; ABI fell in T2DM + PAD ( P < 0.0001) and in PAD without T2DM ( P = 0.0005); the fall was greater in the latter group. Initial and absolute claudication distances were similar in PAD patients. In group T2DM + PAD, absolute claudication distance was longer in the subgroup without peripheral neuropathy ( P < 0.05), whereas ABI and rate pressure products were similar. F1+2 values at rest were higher in group T2DM + PAD. After exercise, F1+2 values and TAT increased only in group PAD without T2DM. Conclusion Only group PAD without T2DM experienced muscular ischaemia, whereas group T2DM + PAD did not. Mild peripheral neuropathy may have prevented them from reaching the point of muscular ischaemia during the treadmill test, because they stopped exercising with the early onset of pain. Reaching a false absolute claudication distance may induce ischaemic preconditioning. These findings suggest a possible protective role of mild peripheral neuropathy in T2DM patients with intermittent claudication, by preventing further activation of coagulation during treadmill testing. [ABSTRACT FROM AUTHOR]

Background: Veno-venous extracorporeal life support (V-V ECLS or V-V ECMO) has been adopted as a rescue support in severe cases of COVID-19 ARDS. Initial reports on the use of V-V ECLS in COVID-19 patients reported very high mortality rates (57%-94%), but subsequent studies showed much lower rates (30%-40%). The aim of this study is to analyze demographic features, clinical course and outcomes of COVID-19 treated with V-V ECLS during the Italian 'third wave', in which the alpha variant was prevalent in the country., Methods: Single-center, retrospective observational study conducted at the ECLS referral center of a teaching hospital in Italy from January 1st, 2021 and October 31st, 2021., Results: Between January and October 2021, 18 consecutive adult patients who underwent V-V ECLS for severe ARDS due to COVID-19 were enrolled. Thirteen patients (72.2%) were male, and their median age was 50 years; the median P/F ratio before V-V ECLS initiation was 43 mm Hg (IQR, 40; 56), and the median RESP score was 0.5 (IQR, -2.25; 1.0). The mortality rate at 90 days was 55.6, compared to 55.7% in non-COVID patients in our center (p > 0.05); the median duration of ECLS was 29 days (IQR, 11; 32), compared to 10 days (IQR, 8; 15), in non-COVID patients (p = 0.004). Incidence of complications was high., Conclusions: In patients with COVID-19 ARDS receiving V-V ECLS, unadjusted mortality was similar to pre-pandemic V-V ECLS cases, while the duration of ECLS was almost three times longer and with frequent complications. This could be partly explained by the selection of very sick patients at the baseline that evolved to multiorgan failure during the course of ECLS., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

The use of extracorporeal membrane oxygenator instead of standard cardiopulmonary bypass during lung transplantation is debatable. Moreover, recently, the concept of prolonged postoperative extracorporeal membrane oxygenator (ECMO) support has been introduced in many transplant centers to prevent primary graft dysfunction (PGD) and improve early and long-term results. The objective of this study was to review the results of our extracorporeal life support strategy during and after bilateral sequential lung transplantation (BSLT) for pulmonary artery hypertension. We review retrospectively our experience in BSLT for pulmonary artery hypertension between January 2010 and August 2018. A total of 38 patients were identified. Nine patients were transplanted using cardiopulmonary bypass (CPB), in eight cases CPB was followed by a prolonged ECMO (pECMO) support, 14 patients were transplanted on central ECMO support, and seven patients were transplanted with central ECMO support followed by a pECMO assistance. The effects of different support strategies were evaluated, in particular in-hospital morbidity, mortality, incidence of PGD, and long-term follow-up. The use of CPB was associated with poor postoperative results and worse long-term survival compared with ECMO-supported patients. Predictive preoperative factors for the need of intraoperative CPB instead of ECMO were identified. The pECMO strategy had a favorable effect to mitigate postoperative morbidity and mortality, not only in intraoperative ECMO-supported patients, but even in CPB-supported cases. In our experience, ECMO may be considered as the first choice circulatory support for lung transplantation. Sometimes, in very complex cases, CBP is still necessary. The pECMO strategy is very effective to reduce incidence of PGD even in CPB-supported patients., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)