Surgical Perfusion and Isolation of the Porcine Pancreas for Islet Isolation.

Pancreatic islet transplantation is an emerging treatment for type I diabetes; however, it is limited by donor matching and availability. Porcine islet xenotransplantation offers a promising alternative to allotransplantation, with the potential for large-scale production of on-demand, functional islets. The yield and viability of isolated islets is highly susceptible to the quality of the donor pancreas and the method of procurement, particularly the duration of warm-ischemia time. To improve organ preservation and subsequent islet yield and viability, we have developed a protocol for surgical perfusion and resection of the porcine pancreas. This protocol employs direct infrarenal aortic cannulation and organ perfusion to both minimize warm-ischemia time and simplify the procedure for operators who do not have extensive surgical expertise. Subsequent arterial perfusion of the pancreas via the aorta flushes stagnant blood from the microvasculature, thereby reducing thrombosis and oxidative damage to the tissue. This manuscript provides a detailed protocol for surgical perfusion and resection of the porcine pancreas, followed by islet isolation and purification.

Percutaneous decannulation reduces procedure length and rates of groin wound infection in patients on venoarterial extracorporeal membrane oxygenation.

Objective: Open decannulation from femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) carries high risk of morbidity, including groin wound infection. This study evaluated the impact of percutaneous decannulation on rates of groin wound infection in patients decannulated from femoral VA-ECMO. Methods: Between January 1, 2022, and April 30, 2023, 47 consecutive patients received percutaneous femoral VA-ECMO and survived to decannulation. A percutaneous suture-mediated closure device was used for decannulation in patients with relatively smaller arterial cannulas. Patients with larger arterial cannulas or unsuccessful percutaneous closures underwent surgical cutdown and repair of the femoral artery. The primary outcome was arterial site wound infection following decannulation. Results: Among the 47 patients who survived to decannulation from VA-ECMO, 21 underwent percutaneous decannulation and 27 underwent surgical cutdown. One patient underwent 2 VA-ECMO runs, one with percutaneous decannulation and one with surgical cutdown. Percutaneous decannulation was attempted in 22 patients, with 21 of 22 (95.5%) success rate. Decannulation procedure length was significantly shorter in the percutaneous group (79 minutes vs 148 minutes, P = .0001). The percutaneous group had significantly reduced rates of groin wound complications (0% vs 40.7%, P = .001) and groin wound infections (0% vs 22.2%, P = .03) when compared with the surgical cutdown group. Three patients (14.3%) in the percutaneous group experienced vascular complications, including pseudoaneurysm at the distal perfusion catheter site and nonocclusive thrombus of the common femoral artery. Conclusions: Percutaneous decannulation may reduce decannulation procedure length and rate of groin wound infection in patients who survive to decannulation from VA-ECMO.

Vaso-Lock for sutureless anastomosis in a pig arteriovenous loop model.

A vascular anastomosis is a critical surgical skill that involves connecting blood vessels. Traditional handsewn techniques can be challenging and resource intensive. To address these issues, we have developed a unique sutureless anastomotic device called Vaso-Lock. This intraluminal device connects free vascular ends using anchors to maintain traction and enable a rapid anastomosis. We tested the anastomotic capability of Vaso-Locks in a pig common carotid-internal jugular arteriovenous model. The use of Vaso-Lock allowed us to accomplish this procedure in less than 10 min, in contrast to the approximately 40 min required for a handsewn anastomosis. The Vaso-Lock effectively maintained patency for at least 6 weeks without causing significant tissue damage. Histological analysis revealed that the device was successfully incorporated into the arterial wall, promoting a natural healing process. Additionally, organ evaluations indicated no adverse effects from using the Vaso-Lock. Our findings support the safety and effectiveness of the Vaso-Lock for arteriovenous anastomosis in pigs, with potential applicability for translation to humans. Our novel sutureless device has the potential to advance surgical practice and improve patient outcomes.

In Vivo Porcine Model of Acute Iliocaval Deep Vein Thrombosis.

CLINICAL IMPACT: The study establishes a rapid, technically straightforward, and reproducible porcine large animal model for acute iliocaval deep vein thrombosis (DVT). The procedure can be performed with basic endovascular skillsets. With its procedural efficiency and consistency, the platform is promising for comparative in vivo testing of venous thrombectomy devices in a living host, and for future verification and validation studies to determine efficacy of novel thrombectomy devices relative to predicates.

Continuous renal replacement therapy and extracorporeal membrane oxygenation: implications in the COVID-19 era.

The novel severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus Disease 19 (COVID-19)) was identified as the causative agent of viral pneumonias in Wuhan, China in December 2019, and has emerged as a pandemic causing acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. Interim guidance by the World Health Organization states that extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy in COVID-19-related ARDS. International registries tracking ECMO in COVID-19 patients reveal a 21%-70% incidence of acute renal injury requiring renal replacement therapy (RRT) during ECMO support. The indications for initiating RRT in patients on ECMO are similar to those for patients not requiring ECMO. RRT can be administered during ECMO via a temporary dialysis catheter, placement of a circuit in-line hemofilter, or direct connection of continuous RRT in-line with the ECMO circuit. Here we review methods for RRT during ECMO, RRT initiation and timing during ECMO, anticoagulation strategies, and novel cytokine filtration approaches to minimize COVID-19's pathophysiological impact.

Quantification of the flexural rigidity of endovascular surgical devices using three-point bending tests.

Endovascular surgical procedures require the navigation of catheters and wires through the vasculature to reach distal target sites. Quantitative frameworks for device selection hold the potential to improve the tracking of endovascular devices through vascular anatomy by personalizing the device flexural rigidity to an individual's anatomy. However, data are lacking to facilitate this technology, in part because typical endovascular devices have intricate spatial variations in mechanical properties that are challenging and tedious to quantify repeatably. We therefore developed a three-point bend test methodology using a custom rig and applied it to measure lengthwise flexural rigidity profiles of endovascular devices that are used to target the cerebral vasculature. The methodology demonstrated high repeatability and was able to characterize transition zones. We applied the methodology to generate the first comprehensive, quantitative library of device flexural rigidities, spanning guidewires, intermediate guides, and long sheaths. We observed that these three classes of device have properties that fall into distinct ranges. Additional plots examining relationships between flexural rigidity, device diameter, and length revealed application-specific trends in flexural properties. This methodology and the data allow for standardized characterization and comparisons to aid device selection, and have the potential to both enhance surgical planning and inform future innovation.

Disparities in Lung Transplantation.

Since the initial report of long-term survival after lung transplantation (LT) in 1983, there has been remarkable progress in the field and LT is now the gold-standard therapy for patients with end-stage lung disease. It confers a significant survival advantage and improves the quality of life in patients who often have few other treatment options. However, LT remains a complex undertaking and establishing and maintaining an LT program is resource intensive with multiple potential barriers. In this article, we focus on disparities in LT and the potential solutions to improving access to LT.

Microbiota in heart and lung transplantation: implications for innate-adaptive immune interface.

PURPOSE OF REVIEW: Transplantation continues to be the only treatment option for end-stage organ failure when other interventions have failed. Although short-term outcomes have improved due to advances in perioperative care, long-term outcomes continue to be adversely affected by chronic rejection. Little is known about the role microbiota play in modulating alloimmune responses and potentially contributing to graft failure. Initial data have identified a correlation between specific changes of the recipient and/or donor microbiota and transplant outcomes. In this review, we will focus on recent findings concerning the complex interplay between microbiota and the innate immune system after heart and lung transplantation. RECENT FINDINGS: Gut microbiome derangements in heart failure promote an inflammatory state and have lasting effects on the innate immune system, with an observed association between increased levels of microbiota-dependent metabolites and acute rejection after cardiac transplantation. The lung allograft microbiome interacts with components of the innate immune system, such as toll-like receptor signalling pathways, NKG2C+ natural killer cells and the NLRP3 inflammasome, to alter posttransplant outcomes, which may result in the development of chronic rejection. SUMMARY: The innate immune system is influenced by alterations in the microbiome before and after heart and lung transplantation, thereby offering potential therapeutic targets for prolonging allograft survival.

Up-regulation of thrombospondin-2 in Akt1-null mice contributes to compromised tissue repair due to abnormalities in fibroblast function.

Vascular remodeling is essential for tissue repair and is regulated by multiple factors, including thrombospondin-2 (TSP2) and hypoxia/VEGF-induced activation of Akt. In contrast to TSP2 knock-out (KO) mice, Akt1 KO mice have elevated TSP2 expression and delayed tissue repair. To investigate the contribution of increased TSP2 to Akt1 KO mice phenotypes, we generated Akt1/TSP2 double KO (DKO) mice. Full-thickness excisional wounds in DKO mice healed at an accelerated rate when compared with Akt1 KO mice. Isolated dermal Akt1 KO fibroblasts expressed increased TSP2 and displayed altered morphology and defects in migration and adhesion. These defects were rescued in DKO fibroblasts or after TSP2 knockdown. Conversely, the addition of exogenous TSP2 to WT cells induced cell morphology and migration rates that were similar to those of Akt1 KO cells. Akt1 KO fibroblasts displayed reduced adhesion to fibronectin with manganese stimulation when compared with WT and DKO cells, revealing an Akt1-dependent role for TSP2 in regulating integrin-mediated adhesions; however, this effect was not due to changes in ß1 integrin surface expression or activation. Consistent with these results, Akt1 KO fibroblasts displayed reduced Rac1 activation that was dependent upon expression of TSP2 and could be rescued by a constitutively active Rac mutant. Our observations show that repression of TSP2 expression is a critical aspect of Akt1 function in tissue repair.