Tissue Ischemia During Aortic Repair: The Point of View of the Perfusionist

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Spotlight on landmark oncology trials: the latest evidence and novel trial designs

The era of precision oncology is marked with prominent successes in the therapy of advanced soft tissue sarcomas, breast cancer, ovarian cancer and haematological neoplasms, among others. Moreover, recent trials of immune checkpoint inhibitors in melanoma, non-small cell lung carcinoma, and head and neck cancers have significantly influenced the therapeutic landscape by providing promising evidence for immunotherapy efficacy in the adjuvant setting in high-risk locoregional disease. To speed up the introduction of targeted therapy for cancer patients, novel phase II trials are being designed, and may likely form the basis for the 'landmark trials' of the future. A special article collection in BMC Medicine, "Spotlight on landmark oncology trials", features articles from invited experts on recent clinical practice-changing trials

Performance of the CryoValve* SG human decellularized pulmonary valve in 342 patients relative to the conventional CryoValve at a mean follow-up of four years

Objective: This study compared clinical outcomes of patients receiving CryoValve SG decellularized pulmonary valves with those of patients receiving conventionally processed CryoValve pulmonary valves. Methods: All consecutive patients undergoing Ross procedures and right ventricular outflow tract reconstructions with SG valves at 7 institutions (February 2000-November 2005) were assessed retrospectively (193 Ross procedures, 149 right ventricular outflow tract reconstructions). Patient, procedural, and outcome data were compared with those from 1246 conventional implants (665 Ross procedures, 581 right ventricular outflow tract reconstructions). Hemodynamic function was assessed at latest follow-up. Results: Follow-up was complete for 99% in SG group and 94% in conventional group, with mean follow-ups of 4.0 years (range, 0-6.7 years) for SG and 3.7 years (range, 0-6.7 years) for conventional. Five-year cumulative survivals and freedoms from adverse events were comparable between SG and conventional valves. Among patients undergoing Ross procedures, peak gradient at last follow-up was lower with SG valves (P<.01); no difference was observed in the right ventricular outflow tract reconstruction population. Pulmonary insufficiency was significantly reduced with SG valves in patients undergoing both Ross procedures (P<.01) and right ventricular outflow tract reconstructions (P<.01). Valve type was not a significant predictor of valve-related failure in propensity-adjusted analysis of either procedure. Conclusions: CryoValve SG decellularized pulmonary valves have acceptable clinical outcomes and favorably compare with conventionally processed valves. Improved hemodynamic function observed with SG valves could signify improved long-term outcomes and may be due to the decreased antigenicity of these valves. (J Thorac Cardiovasc Surg 2010; 139: 339-48

Lysosomal membrane permeabilization in cell death

18 páginas, 3 figuras, 2 tablas -- PAGS nros. 6434-6451Mitochondrial outer membrane permeabilization (MOMP) constitutes one of the major checkpoint(s) of apoptotic and necrotic cell death. Recently, the permeabilization of yet another organelle, the lysosome, has been shown to initiate a cell death pathway, in specific circumstances. Lysosomal membrane permeabilization (LMP) causes the release of cathepsins and other hydrolases from the lysosomal lumen to the cytosol. LMP is induced by a plethora of distinct stimuli including reactive oxygen species, lysosomotropic compounds with detergent activity, as well as some endogenous cell death effectors such as Bax. LMP is a potentially lethal event because the ectopic presence of lysosomal proteases in the cytosol causes digestion of vital proteins and the activation of additional hydrolases including caspases. This latter process is usually mediated indirectly, through a cascade in which LMP causes the proteolytic activation of Bid (which is cleaved by the two lysosomal cathepsins B and D), which then induces MOMP, resulting in cytochrome c release and apoptosome-dependent caspase activation. However, massive LMP often results in cell death without caspase activation; this cell death may adopt a subapoptotic or necrotic appearance. The regulation of LMP is perturbed in cancer cells, suggesting that specific strategies for LMP induction might lead to novel therapeutic avenuesResearch in our labs is supported by grants from Ministry of Science (BFU-2006-00508) and from Fundación La Caixa (BM06-125-1) to PB and Ligue Nationale contre le Cancer (Equipe labellisée), European Commission (Active p53, Apo-Sys, RIGHT, TransDeath, ChemoRes, DeathTrain), Agence Nationale pour la Recherche, Institut National contre le Cancer, Cancéropôle Ile-de-France and Fondation pour la Recherche Médicale to GKPeer reviewe