Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many—sometimes contradictory—observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device.

Pressure overload-induced impairment in fatty acid oxidation precedes the onset of congestive heart failure but mitochondrial respiratory capacity is maintained until the EF decreases in vivo. These temporal relations suggest a tight link between impaired substrate oxidation capacity in the development of heart failure and contractile dysfunction and may imply therapeutic and prognostic value.

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The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) encodes a dual specific protein and phospholipid phosphatase that affects cell proliferation, apoptosis and migration. In our study, we examined protein expression of PTEN in renal carcinogenesis. PTEN protein levels were examined in 42 clear cell renal cell carcinomas (ccRCC) and oncocytomas as well as in the corresponding normal renal tissue of the same patients using Western blot analysis. Cellular localization was analyzed by immunohistochemistry. PTEN was highly expressed in all investigated normal renal tissue specimens. Immunohistochemical analysis showed an almost exclusive staining of proximal tubulus epithelial cells known to be precursor cells of ccRCC. Within the proximal tubulus cells, PTEN exhibited a membrane predominant immunostaining pattern. In ccRCCs PTEN expression was markedly reduced to an average of less than 10% compared with normal tissue as evidenced by Western blot analysis (p < 0.001). The degree of reduction was similar in highly differentiated (G1) carcinomas and in less differentiated (G2-G4) carcinomas. Key words: PTEN; renal cell carcinoma; oncocytoma; proximal tubulus epithelial cellThe human tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) located on chromosome 10q23 1 encodes a dual specific protein and phospholipid phosphatase that is involved in regulation of a variety of signal transduction pathways. PTEN inhibits Shc (Src-homology collagen) phosphorylation following epidermal growth factor (EGF) stimulation and therefore blocks the activation of the Ras/MAPkinase pathway. This has been proposed as an explanation for the tumor suppressive effect of PTEN. 2 Another mechanism that involves the protein phosphatase activity of PTEN is dephosphorylation and inactivation of focal adhesion kinase (FAK), thus implying a crucial role of PTEN for the interaction between extracellular matrix and the cytoskeleton. This mechanism may lead to negative regulation of integrin mediated cell spreading, migration and invasion. 3,4 Besides its function as a protein phosphatase, PTEN acts as a phospholipid phosphatase with phosphatidylinositol 3,4,5-triphosphate (PIP3) as a substrate. [5][6][7] One of the direct downstream targets of PIP3, protein kinase B (Akt/PKB), is continually activated by phosphorylation in cells lacking functional PTEN and the elevated levels of activation can in turn be reduced to normal levels by expression of wild-type PTEN. 8 These data suggest that the tumor suppressive properties of PTEN relate in part to its ability to downregulate the Akt/PKB pathway and hence inhibit cell proliferation and facilitate apoptosis. PTEN is frequently deleted or mutated in advanced cancers, thus suggesting a crucial role in tumor development. Loss of PTEN has been implicated in the carcinogenesis in a wide variety of tissues including prostate, bladder, melanoma, breast and brain. 9,10 However, in renal cancer, PTEN has not yet been shown to play a rol...