Endovascular coiling in the treatment of patients with renal artery aneurysms.

Endovascular coiling is a percutaneous endovascular technique used in the management of arterial aneurysms with high success rates and minimal associated morbidity. We present a series of three patients with incidental renal artery aneurysms treated successfully with endovascular coiling, despite comorbidities. One patient had an aneurysm associated with a solitary kidney. The decision to use this technique becomes critical when the aneurysm involves a single functioning kidney. Each renal artery aneurysm was successfully coiled by combining vascular and neurointerventional techniques. The results from the present case series also highlight the challenges faced in therapeutic decision-making in complex situations with limited error margins.

Endovascular Hepatic Artery Stents in the Modern Management of Postpancreatectomy Hemorrhage.

Background: Postoperative hemorrhage is a potentially lethal complication of pancreatoduodenectomy. This study reports on the use of endovascular hepatic artery stents in the management of postpancreatectomy hemorrhage. Methods: This is a retrospective analysis of a prospectively maintained, consecutive dataset of 440 patients undergoing pancreatoduodenectomy over 68 months. Data are presented on bleeding events and outcomes, and contextualized by the clinical course of the denominator population. International Study Group of Pancreatic Surgery terminology was used to define postpancreatectomy hemorrhage. Results: Sixty-seven (15%) had postoperative hemorrhage. Fifty (75%) were male and this gender difference was significant (P = 0.001; 2 proportions test). Postoperative pancreatic fistulas were more frequent in the postoperative hemorrhage group (P = 0.029; 2 proportions test). The median (interquartile range [IQR]) delay between surgery and postoperative hemorrhage was 5 days (2-14 days). Twenty-six (39%) required intervention comprising reoperation alone in 12, embolization alone in 5, and endovascular hepatic artery stent deployment in 5. Four further patients underwent more than 1 intervention with 2 of these having stents. Endovascular stent placement achieved initial hemostasis in 5 of 7 (72%). Follow-up was for a median (IQR) of 199 days (145-400 days) poststent placement. In 2 patients, the stent remained patent at last follow-up. The remaining 5 stents occluded with a median (IQR) period of proven patency of 10 days (8-22 days). Conclusions: This study shows that in the specific setting of postpancreatoduodenectomy hemorrhage with either a short remnant gastroduodenal artery bleed or a direct bleed from the hepatic artery, where embolization risks occlusion with compromise of liver arterial inflow, endovascular hepatic artery stent is an important hemostatic option but is associated with a high risk of subsequent graft occlusion.

Safe nanoengineering and incorporation of transplant populations in a neurosurgical grade biomaterial, DuraGen PlusTM, for protected cell therapy applications.

High transplant cell loss is a major barrier to translation of stem cell therapy for pathologies of the brain and spinal cord. Encapsulated delivery of stem cells in biomaterials for cell therapy is gaining popularity but experimental research has overwhelmingly used laboratory grade materials unsuitable for human clinical use - representing a further barrier to clinical translation. A potential solution is to use neurosurgical grade materials routinely used in clinical protocols which have an established human safety profile. Here, we tested the ability of Duragen Plus™ - a clinical biomaterial used widely in neurosurgical duraplasty procedures, to support the growth and differentiation of neural stem cells- a major transplant population being tested in clinical trials for neurological pathology. Genetic engineering of stem cells yields augmented therapeutic cells, so we further tested the ability of the Duragen Plus™ matrix to support stem cells engineered using magnetofection technology and minicircle DNA vectors- a promising cell engineering approach we previously reported (Journal of Controlled Release, 2016 a &b). The safety of the nano-engineering approach was analysed for the first time using sophisticated data-independent analysis by mass spectrometry-based proteomics. We prove that the Duragen Plus™ matrix is a promising biomaterial for delivery of stem cell transplant populations, with no adverse effects on key regenerative parameters. This advanced cellular construct based on a combinatorial nano-engineering and biomaterial encapsulation approach, could therefore offer key advantages for clinical translation.

Pharmacological characterisation of novel alpha 2-adrenoceptor antagonists as potential brain imaging agents.

Development of suitable imaging ligands to facilitate in vivo characterisation of alpha(2)-adrenoceptors has been limited in its success. In the present study, a series of iodinated derivatives and a fluorinated derivative of the classical alpha(2)-adrenoceptor antagonist, idazoxan, have been evaluated as potential imaging ligands. These compounds are based on the structure of idazoxan but more closely resemble the selective alpha(2)-adrenoceptor antagonists 2-methoxy-idazoxan (RX821002) and 2-ethoxy-idazoxan (RX811059). Preliminary studies, investigating their affinities at alpha(2)-adrenoceptors, using brain membranes prepared from a variety of species, and their ability to antagonise UK14, 304-induced inhibition of twitch in mouse vas deferens highlighted 2-iodopropoxy-idazoxan and 2-fluoroethoxy-idazoxan as the most promising candidates. Further characterisation of these two compounds showed they had a good selectivity for alpha(2)-adrenoceptors compared with imidazoline(2)-binding sites and beta-adrenoceptors. Additional functional studies also showed a lack of intrinsic activity at alpha(2)-adrenoceptors. Following intravenous injection, both compounds were able to cross the blood brain barrier when tested using an ex vivo binding assay. These data show that both 2-iodopropoxy-idazoxan and 2-fluoroethoxy-idazoxan have binding and functional properties suitable for imaging ligands. Further studies using radiolabelled forms of these ligands and a more extensive characterisation of their binding profiles are necessary but these initial evaluations demonstrate their potential.