Should endovascular approach be considered as the first option for thoraco-abdominal aortic aneurysms?

Open surgical repair has been the gold standard for treatment of thoracoabdominal aortic aneurysms (TAAAs). The technique of open TAAA repair has evolved from the use of "island" patch incorporation to separate branch vessel bypass, from "clamp and go" to routine use of distal perfusion, and towards more extensive repair in patients with connective tissue disorders. Open TAAA repair can be done with excellent results in highly specialized centers. However, these operations continue to carry excessive risk when performed outside large aortic centers, with 30-day mortality estimated on 20% according to statewide and national databases. In octogenarians. the mortality of elective open TAAA repair can be up to 40%. Endovascular repair was introduced as an alternative to open surgical repair in the elderly or higher risk patients using hybrid reconstruction, parallel grafts or fenestrated and branched endografts. Several large aortic centers have developed dedicated clinical programs to advance techniques of fenestrated-branched endovascular repair using patient-specific and off-the-shelf devices. offering a minimally invasive alternative to open repair allowing treatment of increasingly older and sicker TAAA patients. During the last decade, improvements in device design, patient selection, spinal cord injury protocols, and perioperative management have contributed to a continued decline in morbidity and mortality of fenestrated-branched endovascular aortic repair, challenging open surgical repair as the new "gold standard" for treatment of TAAAs. Despite the improved results, endovascular repair is a highly technical procedure that requires vast experience, involves a significant risk of complications, and also, has an impact on patients' physical quality of life. In this article, we review the current technical aspects of endovascular TAAA repair with the main focus on the evidence of open versus endovascular outcomes of TAAA repair

Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo

The Mediator is a conserved transcriptional coregulator complex required for eukaryotic gene expression. In Caenorhabditis elegans, the Mediator subunit mdt-15 is essential for the expression of genes involved in fatty acid metabolism and ingestion-associated stress responses. mdt-15 loss of function causes defects in reproduction and mobility and shortens lifespan. In the present study, we find that worms with mutated or depleted mdt-15 (mdt-15 worms) exhibit decreased membrane phospholipid desaturation, especially in phosphatidylcholine. Accordingly, mdt-15 worms exhibit disturbed endoplasmic reticulum (ER) homeostasis, as indicated by a constitutively activated ER unfolded protein response (UPR(ER)). Activation of this stress response is only partially the consequence of reduced membrane lipid desaturation, implicating other mdt-15-regulated processes in maintaining ER homeostasis. Interestingly, mdt-15 inactivation or depletion of the lipid metabolism enzymes stearoyl-CoA-desaturases (SCD) and S-adenosyl methionine synthetase (sams-1) activates the UPR(ER) without promoting misfolded protein aggregates. Moreover, these worms exhibit wild-type sensitivity to chemically induced protein misfolding, and they do not display synthetic lethality with mutations in UPR(ER) genes, which cause protein misfolding. Therefore, the constitutively activated UPR(ER) in mdt-15, SCD, and sams-1 worms is not the consequence of proteotoxic stress but likely is the direct result of changes in ER membrane fluidity and composition. Together, our data suggest that the UPR(ER) is induced directly upon membrane disequilibrium and thus monitors altered ER homeostasis