Effect of alginate matrix engineered to mimic the pancreatic microenvironment on encapsulated islet function.

Islet transplantation is emerging as a therapeutic option for type 1 diabetes, albeit, only a small number of patients meeting very stringent criteria are eligible for the treatment because of the side effects of the necessary immunosuppressive therapy and the relatively short time frame of normoglycemia that most patients achieve. The challenge of the immune-suppressive regimen can be overcome through microencapsulation of the islets in a perm-selective coating of alginate microbeads with poly-l-lysine or poly- l-ornithine. In addition to other issues including the nutrient supply challenge of encapsulated islets a critical requirement for these cells has emerged as the need to engineer the microenvironment of the encapsulation matrix to mimic that of the native pancreatic scaffold that houses islet cells. That microenvironment includes biological and mechanical cues that support the viability and function of the cells. In this study, the alginate hydrogel was modified to mimic the pancreatic microenvironment by incorporation of extracellular matrix (ECM). Mechanical and biological changes in the encapsulating alginate matrix were made through stiffness modulation and incorporation of decellularized ECM, respectively. Islets were then encapsulated in this new biomimetic hydrogel and their insulin production was measured after 7 days in vitro. We found that manipulation of the alginate hydrogel matrix to simulate both physical and biological cues for the encapsulated islets enhances the mechanical strength of the encapsulated islet constructs as well as their function. Our data suggest that these modifications have the potential to improve the success rate of encapsulated islet transplantation.

Stenting the carotid artery from radial access using a Simmons guide catheter.

BACKGROUND: Carotid artery stenting (CAS) is a procedure for stroke prevention, usually done from femoral artery access. Reports of CAS using radial artery access have adopted techniques similar to those used for transfemoral CAS. Initial experience with a simpler and lower profile technique for transradial carotid stenting is described here. METHODS: Of 55 consecutive elective CAS cases with standard (not bovine) arch anatomy performed during a 15 month time period by the same operator, 20 were selected for transradial treatment using a 6 F Simmons 2 guide catheter. This was a retrospective analysis of those initial 20 patients compared with the 35 patients treated with elective transfemoral CAS. The CAS database was reviewed for clinical indications, technique, procedure and fluoroscopy times, and clinical outcomes. RESULTS: All procedures were technically successful (no crossovers). No patient had a decline in National Institutes of Health Stroke Scale score or modified Rankin Scale score within 30 days. Mean (95% CI) procedural times for transradial CAS were slightly higher than transfemoral CAS (29.4 (26.0 to 32.7) vs 23.8 (21.2 to 26.4) min, p=0.0098). Mean (95% CI) fluoroscopy times were also higher for transradial CAS compared with transfemoral CAS (9.6 (8.0 to 11.2) vs 6.4 (5.4 to 7.4), p=0.0006). One patient developed a radial artery pseudoaneurysm which required elective surgical repair. CONCLUSION: Transradial carotid stenting using the described lower profile technique provides another effective option in the array of surgical procedures for the treatment of carotid artery stenosis. Relative procedural and fluoroscopy times may initially be longer compared with transfemoral carotid stenting for experienced CAS operators, although absolute differences are small.

Major complications of dural venous sinus stenting for idiopathic intracranial hypertension: case series and management considerations.

BACKGROUND: Venous sinus stenting (VSS) is a safe, effective, and increasingly popular treatment option for selected patients with idiopathic intracranial hypertension (IIH). Serious complications associated with VSS are rarely reported. METHODS: Serious complications after VSS were identified retrospectively from multicenter databases. The cases are presented and management strategies are discussed. RESULTS: Six major acute and chronic complications after VSS were selected from a total of 811 VSS procedures and 1466 venograms for IIH. These included an acute subdural hematoma from venous extravasation, cases of both intraprocedural and delayed stent thrombosis, an ultimately fatal cerebellar hemorrhage resulting in acute obstructive hydrocephalus, venous microcatheter perforation during venography and manometry, and a patient who developed subarachnoid hemorrhage and subdural hematoma after cerebellar cortical vein perforation. The six cases are reviewed and learning points regarding complication avoidance and management are presented. CONCLUSION: We report on six rare, major complications after VSS for IIH. Familiarity with these potential complications and appropriate timely management may allow for good clinical outcomes.

Carotid stenosis, stroke, and carotid artery revascularization.

Atherosclerotic disease of the carotid artery places patients at risk of ischemic stroke and consequently is a target of medical, endovascular and open surgical management. Various imaging modalities are used to characterize anatomy/severity of carotid disease and justify intervention, each having advantages and disadvantages. Carotid revascularization techniques including carotid artery stenting, carotid endarterectomy, and transcarotid artery revascularization vary in invasiveness and are not equally suitable for certain subsets of patients. As such, providing quality care for patients with carotid disease requires a multidisciplinary team of experts in clinical diagnosis, image interpretation, medical management, endovascular intervention, and surgical treatment.

Islet cell encapsulation - Application in diabetes treatment.

In this minireview, we briefly outline the hallmarks of diabetes, the distinction between type 1 and type 2 diabetes, the global incidence of diabetes, and its associated comorbidities. The main goal of the review is to highlight the great potential of encapsulated pancreatic islet transplantation to provide a cure for type 1 diabetes. Following a short overview of the different approaches to islet encapsulation, we provide a summary of the merits and demerits of each approach of the encapsulation technology. We then discuss various attempts to clinical translation with each model of encapsulation as well as the factors that have mitigated the full clinical realization of the promise of the encapsulation technology, the progress that has been made and the challenges that remain to be overcome. In particular, we pay significant attention to the emerging strategies to overcome these challenges. We believe that these strategies to enhance the performance of the encapsulated islet constructs discussed herein provide good platforms for additional work to achieve successful clinical translation of the encapsulated islet technology.