Is endovascular treatment with multilayer flow modulator stent insertion a safe alternative to open surgery for high-risk patients with thoracoabdominal aortic aneurysm?

A best evidence topic in cardiothoracic and vascular surgery was written according to a structured protocol. The question addressed was whether endovascular treatment with multilayer flow modulator stents (MFMS) can be considered a safe alternative to open surgery for high-risk patients with thoracoabdominal aortic aneurysm (TAAA). Altogether 27 papers were identified using the reported search, of which 11 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study limitations are tabulated. The outcomes of interest were all-cause survival, aneurysm-related survival, branch vessel patency and major adverse events. Aneurysm-related survival exceeded 78% in almost all studies, with the exception of one where the MFMS was inserted outside the instructions for use. In that study the aneurysm-related survival was 28.9%. The branch vessel patency was higher than 95% in 10 studies and not reported in one. At 12-month follow-up, several studies showed a low incidence of major adverse events, including stroke, paraplegia and aneurysm rupture. We conclude that MFMS represent a suitable and safe treatment for high-risk patients with TAAA maintaining branch vessel patency when used within their instructions for use. However, a number of limitations must be considered when interpreting this evidence, particularly the complete lack of randomised controlled trials (RCTs), short follow-up in all studies, and heterogeneity of the pathologies among the different populations studied. Further innovative developments are needed to improve MFMS safety, expand their instructions for use, and enhance their efficacy.

Miltefosine-loaded lipid nanoparticles: Improving miltefosine stability and reducing its hemolytic potential toward erythtocytes and its cytotoxic effect on macrophages.

The toxic effects of miltefosine on the epithelial cells of the gastrointestinal tract and its hemolytic action on erythrocytes have limited its use as an antileishmanial agent. As part of our search for new strategies to overcome the side effects of miltefosine during the treatment of leishmaniasis, we have developed stable miltefosine-loaded lipid nanoparticles in an attempt to reduce the toxic effects of the drug. We have evaluated lipid nanoparticles containing varying amounts of miltefosine and cholesterol, prepared by sonication, in terms of their physicochemical properties, preliminary stability, hemolytic potential toward erythrocytes, and cytotoxicity to macrophages and to promastigote and amastigote forms of Leishmania (L.) chagasi. Miltefosine loading into lipid nanoparticles was 100% for low drug concentrations (7.0 to 20.0mg/mL). Particle size decreased from 143nm (control) to between 43 and 69nm. From fluorescence studies, it was observed that the presence of miltefosine and cholesterol (below 103µM) promoted ordering effects in the phospholipid region of the nanoparticles. The formulation containing 15mg/mL miltefosine was stable for at least six months at 4°C and in simulated gastrointestinal fluids, and did not promote epithelial gastrointestinal irritability in Balb/C mice. When loaded into lipid nanoparticles, the hemolytic potential of miltefosine and its cytotoxicity to macrophages diminished, while its antiparasitic activity remained unaltered. The results suggested that miltefosine-loaded lipid nanoparticles may be promising for the treatment of leishmaniasis and might be suitable for oral and parenteral use.