Methylene blue treatment for cytokine release syndrome-associated vasoplegia following a renal transplant with rATG infusion: A case report and literature review.

Rabbit anti-thymocyte globulin (rATG) is an infusion of polyclonal rabbit-derived antibodies against human thymocyte markers, which can be used to prevent and treat acute rejection following organ transplantation. However, the product monograph issued by the manufacturer (Sanofi Canada) reports that serious immune-mediated reactions have been observed following the use of rATG, consisting of anaphylaxis or severe cytokine release syndrome (CRS), which is a form of vasoplegic syndrome (VS), in which distributive shock occurs refractory to norepinephrine (NE) and vasopressin (VP). Severe infusion-associated reactions are consistent with CRS and can cause serious cardiac or respiratory problems, or in certain cases, mortality. CRS is a form of systemic inflammatory response syndrome (SIRS). In SIRS, the substantial activation of endothelial inducible nitric oxide synthase (iNOS) and smooth muscle guanylate cyclase (GC) is observed, which can produce severe hypotension that is unresponsive to conventional vasopressors. Methylene blue (MB) is a direct inhibitor of iNOS and GC and has been used as an effective treatment for VS following cardiothoracic surgery. In the present study, the successful use of MB as a rescue therapy for CRS in a patient receiving rATG following a renal transplant was reported. Following an uneventful cadaveric kidney transplant involving the intravenous (IV) administration of rATG for the induction of immunological tolerance, the patient became markedly hypotensive and tachycardic. The patient required high doses of VP and NE infusions. Following the protocol described for treating refractory VS in post-cardiac surgery patients, the decision was made to initiate the patient on an IV MB infusion. This treatment protocol was shown to improve the hemodynamic status of the patient, which enabled the withdrawal of vasopressors and suggests an important role for methylene blue in the management of refractory VS.

Survival after liver transplantation using hepatitis C virus-positive donor allografts: case-controlled analysis of the UNOS database.

BACKGROUND: Numerous reports have documented reduced graft and patient survival after use of hepatitis C (HCV) seropositive allografts in liver transplantation (OLT). We aimed to examine if the use of a HCV+ liver allograft affects patient and graft survivals compared to HCV- donor allografts in a case-controlled analysis of the united network for organ sharing (UNOS) database. METHODS: We examined 63,149 liver transplants (61,905 donors HCV-; 1,244 donors HCV+) from the UNOS standard transplant analysis and research (STAR) file from 1987 to 2007. Donor and recipient demographics and outcomes were collected in which donor HCV serology was complete. A case-controlled cohort from 11 donor and recipient variables comparing donor HCV- and HCV+ allografts (n=540 in each group) was created using propensity scores with a matching algorithm. Graft and patient survival was estimated using Kaplan-Meier survival curves. RESULTS: Significant differences were evident in the unadjusted cohort between recipients who received HCV+ and HCV- allografts, including HCV+ recipients, donor and recipient age, and model for end-stage liver disease (MELD) exception cases. Use of HCV+ allograft resulted in significantly lower graft survival (8.1 vs. 10.6 years; P=0.001) and patient survival (10.2 vs. 12.3 years; P=0.01) after OLT. In the matched cohort, HCV seropositivity had no detrimental effect on the graft (P=0.57) or patient (P=0.78) survival after OLT. CONCLUSIONS: This is the first population-based analysis to show that after adjusting for donor and recipient characteristics there was no difference in graft or patient survival with the use of HCV+ donor liver allografts compared to HCV- donor liver allografts.

Comparison of right lobe donor hepatectomy with elective right hepatectomy for other causes in New York.

INTRODUCTION: Right lobe donor hepatectomy (RLDH) is a potential source of liver allografts given the ongoing shortage of deceased donor organs available. Since there is no live donor registry in the United States, a population-based, unsolicited state-wide analysis has yet to be reported. METHODS: The New York (NY) State Inpatient Database was used to query 1,524 elective liver lobectomies performed from 2001 to 2006. RLDH were identified in this cohort (n = 195; 13%). Most common indications for elective right lobe hepatectomy (ERH) were metastatic colon cancer (50%) and hepatocellular carcinoma (HCC) (34%). Primary outcomes were mortality, perioperative resources and major postoperative complications. RESULTS: After a dramatic drop in 2002, there was a slow increase in RLDH from 2003 to 2006 in New York. Donors were younger (median age 36 vs. 60 years, P < 0.0001) and healthier (75% with no comorbidities vs. 18%, P < 0.0001) than patients undergoing ERH for other causes. Median length of hospital stay was 7 days in both groups. Donors were less likely to require blood transfusion (22.6 vs. 62.8%, P < 0.0001) and received less blood (mean 0.10 units vs. 2.4 units). Major post-operative complications based on the Clavien classification occurred in only 2.6% of donor cases compared to 13.8% in non-donors (P < 0.0001). There was one RLDH in-hospital mortality (0.5%) in New York compared to 4.3% after ERH (P = 0.003). CONCLUSIONS: This study represents one of the first unsolicited regional analyses of donor morbidity and resource utilization for RLDH and further emphasizes the need and utility of a live donor registry.

Disparities in organ allocation and access to liver transplantation in the USA.

Liver transplantation has become the standard of care for the treatment of chronic liver disease. In 1986, the United Network for Organ Sharing (UNOS) was formed to ensure the just and equitable allocation of donor livers. At the time, UNOS decided to use the Childs-Turcotte-Pugh scoring system to determine the degree of liver disease in potential transplant patients. Unfortunately, it was shown that the Childs-Turcotte-Pugh system was easily manipulated and did not provide equal access to donor organs. Owing to this fact, the Model of End Stage Liver Disease (MELD) score was instituted by UNOS in February 2002. While the institution of MELD has shown an improvement in organ allocation and outcomes, disparities still exist. This article discusses UNOS and the MELD allocation system as well as the racial, geographic and gender disparities that occur despite the institution of the MELD system.

Effect of resveratrol and beta-sitosterol in combination on reactive oxygen species and prostaglandin release by PC-3 cells.

The objective of this project was to identify some possible mechanisms by which two common phytochemicals, resveratrol and beta-sitosterol, inhibit the growth of human prostate cancer PC-3 cells. These mechanisms include the effect of the phytochemicals on apoptosis, cell cycle progression, prostaglandin synthesis and the production of reactive oxygen species (ROS). Prostaglandins have been known to play a role in regulating cell growth and apoptosis. PC-3 cells were supplemented with 50 microM resveratrol or 16 microM beta-sitosterol alone or in combination for up to 5 days. Phytochemical supplementation resulted in inhibition in cell growth. beta-Sitosterol was more potent than resveratrol and the combination of the two resulted in greater inhibition than supplementation with either alone. Long-term supplementation with resveratrol or beta-sitosterol elevated basal prostaglandin release but beta-sitosterol was much more potent than resveratrol in this regard. beta-Sitosterol was more effective than resveratrol in inducing apoptosis and the combination had an intermediate effect after 1 day of supplementation. Cells supplemented with resveratrol were arrested at the G1 phase and at the G2/M phase in the case of beta-sitosterol while the combination resulted in cell arrest at the two phases of the cell cycle. beta-Sitosterol increased ROS production while resveratrol decreased ROS production. The combination of the two phytochemicals resulted in an intermediate level of ROS. The observed changes in prostaglandin levels and ROS production by these two phytochemicals may suggest their mediation in the growth inhibition. The reduction in ROS level and increase by resveratrol supplementation in PC-3 cells reflects the antioxidant properties of resveratrol. It was concluded that these phytochemicals may induce the inhibition of tumor growth by stimulating apoptosis and arresting cells at different locations in the cell cycle and the mechanism may involve alterations in ROS and prostaglandin production.