Acellular Perfusate is an Adequate Alternative to Packed Red Blood Cells During Normothermic Human Kidney Perfusion.

Background: Brief normothermic machine perfusion is increasingly used to assess and recondition grafts before transplant. During normothermic machine perfusion, metabolic activity is typically maintained using red blood cell (RBC)-based solutions. However, the utilization of RBCs creates important logistical constraints. This study explored the feasibility of human kidney normothermic perfusion using William's E-based perfusate with no additional oxygen carrier. Methods: Sixteen human kidneys declined for transplant were perfused with a perfusion solution containing packed RBCs or William's E medium only for 6 h using a pressure-controlled system. The temperature was set at 37 °C. Renal artery resistance, oxygen extraction, metabolic activity, energy metabolism, and histological features were evaluated. Results: Baseline donor demographics were similar in both groups. Throughout perfusion, kidneys perfused with William's E exhibited improved renal flow (P = 0.041) but similar arterial resistance. Lactic acid levels remained higher in kidneys perfused with RBCs during the first 3 h of perfusion but were similar thereafter (P = 0.95 at 6 h). Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding oxygen consumption (P = 0.41) and reconstitution of ATP tissue concentration (P = 0.55). Similarly, nicotinamide adenine dinucleotide levels were preserved during perfusion. There was no evidence of histological damage caused by either perfusate. Conclusions: In human kidneys, William's E medium provides a logistically convenient, off-the-shelf alternative to packed RBCs for up to 6 h of normothermic machine perfusion.

Nationwide utilization of cardiopulmonary bypass in cardiothoracic trauma: A retrospective analysis of the National Trauma Data Bank.

BACKGROUND: The American College of Surgeons Committee on Trauma requires that all level I trauma centers have cardiopulmonary bypass (CPB) capabilities immediately available. Despite this mandate, there are limited data on the utilization and clinical outcomes among trauma patients requiring CPB in the management of injuries. The aim of this study was to evaluate the current use of CPB in the care of trauma patients. METHODS: This is a retrospective analysis of the National Trauma Data Bank from 2010 to 2015. Adult patients sustaining cardiothoracic injuries who underwent surgical repair within the first 24 hours of admission were included. Propensity score matching was used to compare outcomes (in-hospital mortality, hospital length of stay (LOS), intensive care unit LOS, and complications) between patients who underwent CPB within the first 24 hours of admission and those with similar injuries who did not receive CPB. RESULTS: A total of 28,481 patients who met the inclusion criteria were identified, of whom 319 underwent CPB. Three-hundred three CPB patients were matched to 895 comparison patients who did not undergo CPB. Overall in-hospital mortality was 35%. Patients who were not treated with CPB had a significantly higher in-hospital mortality compared with those treated with CBP (odds ratio, 1.57; 95% confidence interval, 1.16-2.12; p = 0.003); however, complications were significantly lower in those who did not receive CPB (odds ratio, 0.63; 95% confidence interval, 0.47-0.86; p = 0.003). Hospital LOS (non-CPB: mean, 13.4 ± 16.3 days; CPB: mean, 14.7 ± 15.1 days; p = 0.23) and intensive care unit LOS (non-CPB: mean, 9.9 ± 10.7 days; CPB: mean, 10.1 ± 9.7 days; p = 0.08) did not differ significantly between groups. CONCLUSION: The use of CPB in the initial management of select cardiothoracic injuries is associated with a survival benefit. Further investigation is required to delineate which specific injuries would benefit the most from the use of CPB. LEVEL OF EVIDENCE: Therapeutic, level IV.

Split-Liver Ex Situ Machine Perfusion: A Novel Technique for Studying Organ Preservation and Therapeutic Interventions.

Ex situ machine perfusion is a promising technology to help improve organ viability prior to transplantation. However, preclinical studies using discarded human livers to evaluate therapeutic interventions and optimize perfusion conditions are limited by significant graft heterogeneity. In order to improve the efficacy and reproducibility of future studies, a split-liver perfusion model was developed to allow simultaneous perfusion of left and right lobes, allowing one lobe to serve as a control for the other. Eleven discarded livers were surgically split, and both lobes perfused simultaneously on separate perfusion devices for 3 h at subnormothermic temperatures. Lobar perfusion parameters were also compared with whole livers undergoing perfusion. Similar to whole-liver perfusions, each lobe in the split-liver model exhibited a progressive decrease in arterial resistance and lactate levels throughout perfusion, which were not significantly different between right and left lobes. Split liver lobes also demonstrated comparable energy charge ratios. Ex situ split-liver perfusion is a novel experimental model that allows each graft to act as its own control. This model is particularly well suited for preclinical studies by avoiding the need for large numbers of enrolled livers necessary due to the heterogenous nature of discarded human liver research.

Ex vivo perfusion-based engraftment of genetically engineered cell sensors into transplantable organs.

Cellular rejection of liver transplant allografts remains a concern despite immunosuppressant use. Existing transplant biomarkers are often not sensitive enough to detect acute or chronic rejection at an early enough stage to allow successful clinical intervention. We herein developed a cell-based sensor that can potentially be used for monitoring local events following liver transplantation. Utilizing a machine perfusion system as a platform to engraft the cells into a donor liver, we effectively established the biocompatibility of the biosensor cells and confirmed efficient delivery of cells distributed throughout the organ. This work proves an innovative concept of integrating synthetic reporter cells ex vivo into organs as a transplant-within-a-transplant during functional organ preservation with a vision to use cell biosensors as a broad way to monitor and treat tissue transplants.

Normothermic liver preservation, current status and future directions.

PURPOSE OF REVIEW: Normothermic machine perfusion (NMP) is an emerging technology for liver preservation. Early clinical results demonstrate beneficial effects in reconditioning high-risk grafts. This review discusses the role of normothermic perfusion as a tool to assess graft viability and as a platform for graft intervention and modification. RECENT FINDINGS: The potential benefits of NMP extend far beyond organ reconditioning. Recent pilot studies have identified clinically relevant viability criteria, which now require validation in large randomized control trials prior to implementation. Furthermore, preclinical studies demonstrate tremendous potential for NMP as a method to extend the preservation period, thus improving transplant logistics as well as serve as a platform for graft-targeted interventions to optimize the preservation period. SUMMARY: NMP is a multifunctional tool with potential to transform liver preservation and the field of transplantation. Large clinical trials are necessary to optimize perfusion protocols, clarify indications for NMP therapy and justify use as the standard preservation modality.

The dawn of liver perfusion machines.

PURPOSE OF REVIEW: Despite high demand, a severe shortage of suitable allografts limits the use of liver transplantation for the treatment of end-stage liver disease. The transplant community is turning to the utilization of high-risk grafts to fill the void. This review summarizes the reemergence of ex-vivo machine perfusion for liver graft preservation, including results of recent clinical trials and its specific role for reconditioning DCD, steatotic and elderly grafts. RECENT FINDINGS: Several phase-1 clinical trials demonstrate the safety and feasibility of machine perfusion for liver graft preservation. Machine perfusion has several advantages compared with static cold storage and may provide superior transplantation outcomes, particularly for marginal grafts. Ongoing multicenter trials aim to confirm the results of preclinical and pilot studies and establish the clinical utility of ex-vivo liver machine perfusion. SUMMARY: Mounting evidence supports the benefits of machine perfusion for preservation of liver grafts. Thus, machine perfusion is a promising strategy to expand the donor pool by reconditioning and assessing viability of DCD, elderly and steatotic grafts during the preservation period. Additionally, machine perfusion will serve as a platform to facilitate graft intervention and modification to further optimize marginal grafts.

Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy.

Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options.