Aorto-bifemoral bypass using a total laparoscopic approach can be performed safely. As all new techniques, a learning curve is observed. This new technique should be evaluated in a larger randomised trial to assess its clinical value in comparison to conventional surgery.

Individuals born preterm show reduced exercise capacity and increased risk for pulmonary and cardiovascular diseases, but the impact of preterm birth on skeletal muscle, an inherently critical part of cardiorespiratory fitness, remains unknown. We evaluated the impacts of preterm birth-related conditions on the development, growth, and function of skeletal muscle using a recognized preclinical rodent model in which newborn rats are exposed to 80% oxygen from day 3 to 10 of life. We analyzed different hindlimb muscles of male and female rats at 10 days (neonatal), 4 weeks (juvenile) and 16 weeks (young adults). Neonatal high oxygen exposure increased the generation of reactive oxygen species and the signs of inflammation in skeletal muscles, which was associated with muscle fiber atrophy, fiber type shifting (reduced proportion of type I slow fibers and increased proportion of type IIb fast-fatigable fibers), and impairment in muscle function. These effects were maintained until adulthood. Fast-twitch muscles were more vulnerable to the effects of hyperoxia than slow-twitch muscles. Male rats, which expressed lower antioxidant defenses, were more susceptible than females to oxygen-induced myopathy. Overall, preterm birth-related conditions have long-lasting effects on the composition, morphology, and function of skeletal muscles; and these effects are sex-specific. Oxygen-induced changes in skeletal muscles could contribute to the reduced exercise capacity and to increased risk of diseases of preterm born individuals.

Muscle weakness and atrophy are clinical hallmarks of myotonic dystrophy type 1 (DM1). Muscle stem cells, which contribute to skeletal muscle growth and repair, are also affected in this disease. However, the molecular mechanisms leading to this defective activity and the impact on the disease severity are still elusive. Here, we explored through an unbiased approach the molecular signature leading to myogenic cell defects in DM1. Single cell RNAseq data revealed the presence of a specific subset of DM1 myogenic cells expressing a senescence signature, characterized by the high expression of genes related to senescence-associated secretory phenotype (SASP). This profile was confirmed using different senescence markers in vitro and in situ. The excessive accumulation of intranuclear RNA foci in DM1 senescent cells compared to non-senescent cells suggests that RNA-mediated toxicity contribute to senescence induction. High expression of IL-6, a prominent SASP cytokine, in the serum of DM1 patients was identified as a biomarker correlating with muscle weakness and functional capacity limitations. Drug screening revealed that the BCL-XL inhibitor (A1155463), a senolytic drug, can specifically target senescent DM1 myoblasts to induce their apoptosis and reduce their SASP. Removal of senescent cells re-established the myogenic function of the non-senescent DM1 myoblasts, which displayed improved proliferation and differentiation capacity in vitro; and enhanced engraftment following transplantation in vivo. Altogether this study presents a well-defined senescent molecular signature in DM1 untangling part of the pathological mechanisms observed in the disease; additionally, we demonstrate the therapeutic potential of targeting these defective cells with senolytics to restore myogenesis.

Background: Individuals born preterm present left ventricle changes and increased risk of cardiac diseases and heart failure. The pathophysiology of heart disease after preterm birth is incompletely understood. Mitochondria dysfunction is a hallmark of cardiomyopathy resulting in heart failure. We hypothesized that neonatal hyperoxia in rats, a recognized model simulating preterm birth conditions and resulting in oxygen-induced cardiomyopathy, induce left ventricle mitochondrial changes in juvenile rats. We also hypothesized that humanin, a mitochondrial-derived peptide, would be reduced in young adults born preterm. Methods: Sprague-Dawley pups were exposed to room air (controls) or 80% O 2 at postnatal days 3 to 10 (oxygen-induced cardiomyopathy). We studied left ventricle mitochondrial changes in 4 weeks old males. In a cohort of young adults born preterm (n=55) and age-matched term (n=54), we compared circulating levels of humanin. Results: Compared with controls, oxygen-exposed rats showed smaller left ventricle mitochondria with disrupted integrity on electron microscopy, decreased oxidative phosphorylation, increased glycolysis markers, and reduced mitochondrial biogenesis and abundance. In oxygen-exposed rats, we observed lipid deposits, increased superoxide production (isolated cardiomyocytes), and reduced Nrf2 gene expression. In the cohort, left ventricle ejection fraction and peak global longitudinal strain were similar between groups however humanin levels were lower in preterm and associated with left ventricle ejection fraction and peak global longitudinal strain. Conclusions: In conclusion, neonatal hyperoxia impaired left ventricle mitochondrial structure and function in juvenile animals. Serum humanin level was reduced in preterm adults. This study suggests that preterm birth–related conditions entail left ventricle mitochondrial alterations that may underlie cardiac changes perpetuated into adulthood. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03261609.