Endovascular Treatment with Two Overlapping Micromesh-Covered Stents and Balloon Guide Catheter for Symptomatic Carotid Pseudoaneurysm Ten Years after Eversion Endarterectomy.

Pseudoaneurysm is a rare complication after carotid endarterectomy. Herein, we report a successful endovascular exclusion of a symptomatic carotid pseudoaneurysm occurred ten years after an eversion carotid endarterectomy by means of 2 overlapping micromesh stents (InspireMD C-Guard™) and balloon guide catheter (FlowGate2 Balloon Guide Catheter) used as a proximal protection device.

Carotid artery stenting with flow inversion cerebral protection and MicroNet-covered stent.

BACKGROUND: The study aims to evaluate the association of proximal flow-inversion cerebral protection and MicroNet-covered CGuard stents in reducing early and late embolic events in carotid artery stenting procedures. METHODS: From 2018 to 2023, we performed 204 procedures in 180 patients with flow inversion cerebral protection and CGuard stents at the Vascular Surgery Unit of Sant'Eugenio Hospital in Rome. Cerebral protection was achieved with a Flow-Gate2 catheter connected to a peripheral vein. The tip balloon is inflated in the CCA to obtain an effective endoclamping, the pressure difference between the carotid bifurcation and the venous compartment ensures a constant back flow with wash-out in the venous compartment. Inclusion criteria were: life expectancy of >12 months, target lesions indicating treatment according to ESVS Guidelines, increased surgical risk due to comorbidities or anatomic issues. ECD follow-up was performed immediately postoperatively, at 30 days, 6 and 12 months, and subsequently annually. RESULTS: The treatment protocol was successfully implemented in 99% of cases. No major strokes occurred, while one minor stroke (0.5%) occurred within 8 hours of the procedure, regressing in the following months. One perioperative death (0.5%) due to cerebral hemorrhage occurred three hours after the procedure. All patients remained asymptomatic, with no short or medium-term neurological score deterioration. One hemodynamically significant restenosis (0.5%) was detected at the 6-month follow-up. All patients completed the 6 months follow-up, though 6 (3%) were lost at the 12-month appointment. CONCLUSIONS: Our prospective monocentric study has demonstrated the effectiveness and safety of the FlowGate2 flow inversion cerebral protection system in association with MicroNet covered CGuard stent.

The TrkAIII oncoprotein inhibits mitochondrial free radical ROS-induced death of SH-SY5Y neuroblastoma cells by augmenting SOD2 expression and activity at the mitochondria, within the context of a tumour stem cell-like phenotype.

The developmental and stress-regulated alternative TrkAIII splice variant of the NGF receptor TrkA is expressed by advanced stage human neuroblastomas (NBs), correlates with worse outcome in high TrkA expressing unfavourable tumours and exhibits oncogenic activity in NB models. In the present study, we report that constitutive TrkAIII expression in human SH-SY5Y NB cells inhibits Rotenone, Paraquat and LY83583-induced mitochondrial free radical reactive oxygen species (ROS)-mediated death by stimulating SOD2 expression, increasing mitochondrial SOD2 activity and attenuating mitochondrial free radical ROS production, in association with increased mitochondrial capacity to produce H2O2, within the context of a more tumour stem cell-like phenotype. This effect can be reversed by the specific TrkA tyrosine kinase inhibitor GW441756, by the multi-kinase TrkA inhibitors K252a, CEP-701 and Gö6976, which inhibit SOD2 expression, and by siRNA knockdown of SOD2 expression, which restores the sensitivity of TrkAIII expressing SH-SY5Y cells to Rotenone, Paraquat and LY83583-induced mitochondrial free radical ROS production and ROS-mediated death. The data implicate the novel TrkAIII/SOD2 axis in promoting NB resistance to mitochondrial free radical-mediated death and staminality, and suggest that the combined use of TrkAIII and/or SOD2 inhibitors together with agents that induce mitochondrial free radical ROS-mediated death could provide a therapeutic advantage that may also target the stem cell niche in high TrkA expressing unfavourable NB.

TrkAIII promotes microtubule nucleation and assembly at the centrosome in SH-SY5Y neuroblastoma cells, contributing to an undifferentiated anaplastic phenotype.

The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs) and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α -tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.