Simultaneous blockade of the CD40 and CD28 costimulatory pathways is an effective treatment strategy to promote allograft acceptance but does not lead to indefinite allograft survival. The immune mechanisms responsible for costimulation-independent rejection are not defined. Here we have studied the rejection responses of murine C57BL/6 recipients, which we show to be relatively resistant to inhibition by combined CD40/CD28 blockade. We demonstrate that asialo GM1 + CD8 + cells play a critical role in this costimulation blockade-resistant rejection. These results provide new insights into the costimulatory requirements for T-cell subsets and demonstrate for the first time that combined blockade of the CD40 and CD28 pathways does not adequately inhibit CD8-mediated skin allograft rejection. Furthermore, we provide evidence that asialo GM1 is a potentially important therapeutic target for CD8-dependent immune responses.

Blockade of the CD40 pathway with anti-CD40 mAb is immunosuppressive in a large animal, preclinical renal transplant model. The potential effect of this therapy on viral immune responses will be important to consider for the design of safe clinical trials.

The aim of this study was to assess the long-term safety and clinical outcomes associated with the utilization of highly steatotic donor livers utilizing a specific donor/recipient matching algorithm. This was a prospective, observational, single-center, 10-yr follow-up study. Highly steatotic livers were utilized according to a donor/recipient algorithm that guided the surgeon to use highly steatotic donor organs judiciously in low-risk recipients. This study initially compared fat assessment based on frozen-section Ehrlich's hematoxylin and eosin (H&E) to reperfusion biopsy fat assessment and demonstrated that H&E is an insensitive analysis to determine degree of steatosis. Patients were divided into three groups based on donor steatosis (group 1: <30% steatosis, group 2: 30-60% steatosis, group 3: >60% steatosis), and clinical outcomes were assessed. One hundred and sixteen patients were included in the analysis. Patients that received severely steatotic livers (>60% fat) showed increased reperfusion liver injury and delayed return of liver function in the early postoperative period, demonstrated by biochemical markers. However, there were no differences in primary non-function, postoperative complications, length of stay, and patient and graft survival. Using rigorous donor/recipient matching through a detailed algorithm, these data demonstrate that normal liver allograft outcomes are not superior to those in highly steatotic grafts.

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.

Combination therapy with AICAR and NAC attenuates renal I/R injury and improves the outcome of the transplanted kidney after prolonged cold preservation.

No abstract

The primary outcome measure of DGF was not statistically different for the two treatment groups. Regarding longer-term rejection and graft survival, the intensively treated participants were at higher risk for a rejection episode.

Hepatic artery thrombosis (HAT) is the most common vascular complication after orthotopic liver transplantation (OLT) and has traditionally been managed with re-OLT. However, several reports have shown that urgent revascularization is frequently an effective means of graft salvage. This most often involves hepatic artery (HA) thrombectomy and thrombolysis, with reestablishment of arterial inflow through a donor iliac artery conduit based on the supraceliac or infrarenal aorta. We report a 46-year-old man who developed HAT 13 days after OLT after angiographic splenic artery embolization to reduce splenic artery steal. A suitable donor iliac artery was not available for arterial reconstruction and could not be obtained from neighboring transplant centers. The patient underwent urgent HA thrombectomy, intrahepatic arterial thrombolysis, and revascularization using an autologous radial artery (RA) conduit based on the supraceliac aorta. The patient is alive more than 1 year after revascularization, with normal liver function and documented flow in the arterial conduit by Doppler ultrasound and arteriography. He has not developed late biliary complications or adverse sequelae of RA harvest. Autologous RA can be safely and successfully used as an aortic-based arterial conduit in urgent revascularization of HAT after OLT. RA should be considered for use in HA revascularization if an adequate donor iliac artery is not available and other potential conduits are not usable or desirable. The availability of autologous RA expands the armamentarium of vascular conduits that can be used in HA revascularization and may help minimize re-OLT for otherwise potentially salvageable liver allografts. (Liver Transpl 2001;7:913-917.) H epatic artery (HA) thrombosis (HAT) is the most common vascular complication in orthotopic liver transplantation (OLT), with an incidence of 2% to 5% in adults and 10% to 33% in children. 1 Although interruption of HA flow is frequently well tolerated in a native liver because of the presence of collateral arterial blood supply, it is often a morbid and life-threatening event after OLT because of the lack of collateral vessels. Although it has been speculated that as many as one third of all early cases of HAT after OLT may be asymptomatic, 2 many episodes of HAT result in either acute hepatic necrosis and liver failure or late biloma and hepatic abscess formation. Traditionally, HAT has been considered an indication for urgent re-OLT, and most cases are still managed in this way. Although re-OLT has significantly reduced the morbidity and mortality attributable to HAT, this option has become limited by the decreasing availability of organs for transplantation. Over the past decade, several reports have shown the effectiveness of urgent revascularization for early HAT. [2][3][4][5][6] Although HA thrombectomy with primary reanastomosis is well described, revascularization usually requires the use of a donor iliac artery as a vascular conduit between the aorta and allograft HA.We report a novel approach ...