Hepatitis B transmission/reactivation associated with Hepatitis B core antibody and Hepatitis C nucleic acid testing positive organs: A report from the Organ Procurement and Transplantation Network Disease Transmission Advisory Committee.

BACKGROUND: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. AIM: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. METHODS: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. RESULTS: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. CONCLUSION: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.

Building the multidisciplinary team for management of patients with hepatocellular carcinoma.

Optimal care of the patient with hepatocellular carcinoma (HCC) necessitates the involvement of multiple providers. Because the patient with HCC often carries 2 conditions with competing mortality risks (cancer and underlying cirrhosis), no single provider is equipped to deal with all of these patients' needs adequately. Multidisciplinary teams (MDTs) have evolved to facilitate care coordination, reassessments of clinical course, and nimble changes in treatment plans required for this complex group of patients. Providers or sites that elect to manage patients with HCC thus are increasingly aware of the need to build their own MDT or communicate with an established one. The availability of new communication technologies, such as teleconferencing or teleconsultation, offers the possibility of MDT expansion into underserved or rural areas, as well as areas such as correctional facilities. Although the availability of resources for HCC patient care varies from site to site, construction of an MDT is possible in a wide spectrum of clinical practices, and this article suggests a blueprint for assembly of such collaboration. Research strategies are needed to explain how MDTs improve clinical outcomes so that MDTs themselves can be improved.

US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery.

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

Multivariate analysis of prognostic factors for survival following doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: To identify prognostic factors for survival in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads (DEBs). MATERIALS AND METHODS: In a retrospective, single-center analysis, tumor- and patient-related factors were recorded for univariate and multivariate analyses via Kaplan-Meier and Cox regression. Infiltrative HCC phenotype and portal vein invasion (PVI) were correlated, and patients with either or both were classified as having radiographically advanced (RAdv) HCC. The primary endpoint was overall survival, which was calculated from the time of first DEB chemoembolization procedure. RESULTS: A total of 168 patients underwent 248 procedures, of which 215 (86.7%) were outpatient procedures. Mean length of stay was 0.33 days, and 25 patients (10.1%) were readmitted within 30 days. A total of 33 patients underwent liver transplantation and were excluded from survival analyses. A total of 130 had cirrhosis; 62, 50, and 18 had Child class A, B, and C disease, respectively. Forty-one patients had infiltrative HCC phenotype, 28 of whom also had PVI. Multivariate analysis of survival in all patients showed α-fetoprotein (AFP), performance status (PS), RAdv HCC, Child classification, albumin level, and ascites to predict survival. In patients without RAdv HCC, AFP, PS, Child classification, albumin level, and International Normalized Ratio were independent predictors. Increased bilirubin level was not an independent risk factor for death. CONCLUSIONS: Independent prognostic factors in patients with HCC undergoing DEB chemoembolization have been identified. Increased bilirubin level was not an independent risk factor. These data can be used in HCC patient selection and counseling for DEB chemoembolization.

Embolization of hepatocellular carcinoma with drug-eluting beads: doxorubicin tissue concentration and distribution in patient liver explants.

BACKGROUND & AIMS: To follow the local tissue delivery of doxorubicin in HCC explants from patients embolized with drug-eluting beads and to compare it with histologic modifications. METHODS: Six patients with HCC underwent chemoembolization with doxorubicin-eluting beads (caliber 100-300 µm, dose 75-150 mg) followed by liver transplantation at different time points (8 h to 36 days). On sections of the explanted liver, the tissue concentration of doxorubicin was determined radially around bead-occluded vessels with microspectrofluorimetry. The intra/peritumoral location of the beads and the modifications of the surrounding tissue were determined on an adjacent hematein-eosin-saffron-stained section and compared to drug measurements. RESULTS: Doxorubicin was detected in the tissue surrounding the beads at all times of explantation. The drug impregnates an area of at least 1.2 mm in diameter around the occluded vessel. The tissue concentration of drug ranges from 5 µM at 8 h to 0.65 µM at 1 month. In patient transplanted at 8 h, no major tissue modification was observed and we found 42% of the beads occluding intratumoral vessels. Drug concentration was not different around intratumoral and peritumoral occluded vessels. After 9-14 days, necrosis was present around 37% of vessels and at 32-36 days, around 40% of vessels. Necrotic tissue was associated with a deeper penetration and a higher concentration of the drug than non necrotized areas, though statistically significant only at 32-36 days. CONCLUSIONS: Doxorubicin-eluting beads provide a sustained delivery of drug for a period of 1 month and local tissue concentrations above cytotoxic threshold in HCC-bearing livers.

Primary intestinal epithelial cells selectively transfer R5 HIV-1 to CCR5+ cells.

The upper gastrointestinal tract is a principal route of HIV-1 entry in vertical transmission and after oral-genital contact. The phenotype of the newly acquired virus is predominantly R5 (CCR5-tropic) and not X4 (CXCR4-tropic), although both R5 and X4 viruses are frequently inoculated onto the mucosa. Here we show that primary intestinal (jejunal) epithelial cells express galactosylceramide, an alternative primary receptor for HIV-1, and CCR5 but not CXCR4. Moreover, we show that intestinal epithelial cells transfer R5, but not X4, viruses to CCR5+ indicator cells, which can efficiently replicate and amplify virus expression. Transfer was remarkably efficient and was not inhibited by the fusion blocker T-20, but was substantially reduced by colchicine and low (4 degrees C) temperature, suggesting endocytotic uptake and microtubule-dependent transcytosis of HIV-1. Our finding that CCR5+ intestinal epithelial cells select and transfer exclusively R5 viruses indicates a mechanism for the selective transmission of R5 HIV-1 in primary infection acquired through the upper gastrointestinal tract.

Impact of Sarcopenia, BMI, and Inflammatory Biomarkers on Survival in Advanced Hepatocellular Carcinoma Treated With Anti-PD-1 Antibody.

BACKGROUND: Sarcopenia and inflammation are independently associated with worse survival in cancer patients. This study aims to determine the impact of sarcopenia, body mass index (BMI), and inflammatory biomarkers on survival in advanced hepatocellular carcinoma (HCC) patients treated with anti-PD-1 antibody-based immunotherapy. METHODS: A retrospective review of advanced HCC patients treated with immunotherapy at Winship Cancer Institute between 2015 and 2019 was performed. Baseline computed tomography and magnetic resonance images were collected at mid-L3 level, assessed for skeletal muscle density using SliceOmatic (TomoVision, version 5.0) and converted to skeletal muscle index (SMI) by dividing it by height (m2). Sex-specific sarcopenia was defined by the median value of SMI. The optimal cut for continuous inflammation biomarker was determined by bias-adjusted log-rank test. Overall survival (OS) was set as primary outcome and Cox proportional hazard model was used for association with survival. RESULTS: A total of 57 patients were included; 77.2% male, 52.6% Caucasian, 58.5% Eastern Cooperative Oncology Group performance status 0-1, 80.7% Child Pugh A. Treatment was second line and beyond in 71.9% of patients. The median follow-up time was 6 months. Sarcopenia cut-off for males and females was SMI of 43 and 39, respectively. 49.1% of patients had sarcopenia. Median OS was 5 versus 14.3 months in sarcopenic versus nonsarcopenic patients (Log-rank P=0.054). Median OS was 5 and 17.5 months in patients with BMI <25 and BMI ≥25, respectively (Log-rank P=0.034). Median OS was 3.6 and 14.3 months for patients with neutrophil-to-lymphocyte ratio (NLR) ≥5.15 versus NLR <5.15 (Log-rank P<0.001). In multivariable Cox regression model, higher baseline NLR was associated with worse OS (hazard ratio [HR]: 4.17, 95% confidence interval [CI]: 1.52-11.39, P=0.005). Sex-specific sarcopenia showed a trend of worse OS (HR: 1.71, 95% CI: 0.73-4.00, P=0.215) but was not statistically significant. BMI<25 was associated with worse OS (HR: 2.28, 95% CI: 0.92-5.65, P=0.076). In the association with progression free survival, neither baseline BMI nor sex-specific sarcopenia showed statistical significance. CONCLUSION: After controlling for baseline Child Pugh score and NLR, sex-specific sarcopenia does not predict OS. Baseline BMI and NLR together may predict OS in advanced HCC patients treated with anti-PD-1 antibody.

Evaluation of Medium-Term Efficacy of Y90 Radiation Segmentectomy vs Percutaneous Microwave Ablation in Patients with Solitary Surgically Unresectable < 4 cm Hepatocellular Carcinoma: A Propensity Score Matched Study.

OBJECTIVE: To evaluate the efficacy and safety of Y90 radiation segmentectomy (RS) vs. percutaneous microwave ablation (MWA) in patients with solitary HCC ≤ 4 cm. METHODS: From 2014 to 2017, 68 consecutive treatment naïve patients were included (34 per treatment arm). Chi-square and t-test were used to evaluate differences in baseline demographics between groups. Objective response was evaluated using mRECIST and toxicity using CTCAE. Overall survival (OS) and progression free survival (PFS) in the targeted tumor and the remainder of liver from initial treatment was calculated using Kaplan-Meier estimation. Propensity score matching was then performed with n = 24 patients matched in each group. Similar outcome analysis was then pre-formed. RESULTS: In the overall study population, both groups had similar baseline characteristics with the exception of larger lesions in the RS group. There was no difference in toxicity, objective tumor response, OS and non-target liver PFS between the MWA and RS group (p's > 0.05). In the matched cohort, the objective tumor response was 82.6% in MWA vs. 90.9%% in RS (p = 0.548). The mean OS in the MWA group (44.3 months) vs RS (59.0 months; p = 0.203). The targeted tumor mean PFS for the MWA groups was 38.6 months vs. 57.8 months in RS group (p = 0.005). There was no difference overall PFS and toxicity between the 2 matched groups. CONCLUSIONS: Our data suggest Y90 RS achieves similar tumor response and OS with a similar safety compared to MWA in the management of HCC lesions ≤ 4 cm. Additionally, targeted tumor PFS appears to be prolonged in the RS group with similar non-target liver PFS between RS and MWA group.

Clinical outcomes of rare hepatocellular carcinoma variants compared to pure hepatocellular carcinoma.

BACKGROUND: HCC variants are rare primary hepatic tumors. The aim of this study is to compare clinical characteristics and outcomes of HCC variants with pure HCC. METHODS: Patients diagnosed between 2004 and 2013 with ICD-O-3 8180/3 and 8170/3-8175/3 were identified from the National Cancer Database. Univariate and multivariate survival analyses were conducted to analyze the association between histology and overall survival (OS). RESULTS: 80,280 patients were identified; pure HCC 78,461 (97.7%), fibrolamellar (FLHCC) 310 (0.4%), scirrhous 161 (0.2%), spindle cell 72 (0.1%), clear cell 487 (0.6%), pleomorphic 23 (0.0%), and combined HCC and cholangiocarcinoma (mixed HCC) 766 (1.0%). 76.7% were male and 72% Caucasian. Liver transplant was performed in 10.1% of pure HCC, 14.5% of mixed HCC, 16.2% of scirrhous, 6.9% of spindle cell, 8.8% of clear cell, 8.7% of pleomorphic, and 3.2% of FLHCC (p<0.001). Pure HCC (10.6%) underwent surgical resection without transplant less often than variants except for scirrhous (9.9%) (p<0.001). More than a third of patients in each histological type received chemotherapy. FLHCC had the best 5-year OS (38.7%), spindle cell and pleomorphic had the worst (9.6% and 13.0%). In multivariate analysis stratified by histology variants, chemotherapy was associated with improved OS in all histologies except for scirrhous and pleomorphic HCC. CONCLUSION: HCC variants underwent surgical resection more often than pure HCC. FLHCC had the best 5-year OS. Liver transplant was commonly performed in HCC variants.

Deterrents to Organ Donation: A Multivariate Analysis of 766 Survey Respondents.

BACKGROUND: Although successful on many fronts, solid organ transplantation fails patients who die on waitlists. Too few organ donors beget this failure. Dispelling misperceptions associated with donation and transplantation would expectedly increase donation and decrease waitlist mortality; recipients would also receive transplants earlier in their disease process, leading to better post-transplantation outcomes. STUDY DESIGN: Survey responses to 7 questions pertaining to organ donation and transplantation were analyzed to determine their association with willingness to donate. Subgroup analyses according to race, residence status (rural vs nonrural), and education level were performed. RESULTS: There were 766 respondents; 84.6% were willing to be a donor, 76.2% were female, 79.7% were Caucasian, and 16.5% were African-American. Having concerns about getting inadequate medical care if registered as a donor was the strongest independent predictor of willingness to donate overall (odds ratio 0.21; 95% CI 0.13 to 0.36) and in each subgroup; African Americans were more likely than Caucasians to have this concern (20.2% vs 9.5%; p < 0.001). Race (odds ratio 0.41; 95% CI 0.22 to 0.75 for African Americans) and age were also predictive overall, but less so. Willingness to donate a family member's organs depended on whether a discussion about donation had hypothetically occurred: 61.0% would donate if there had been no discussion; 95.2% would donate if the family member had said "yes" to donation; and 11.0% would donate if the family member had said "no" (p < 0.001). If there was no prior discussion, having concerns about getting less-aggressive medical care predicted willingness to donate a family member's organs (odds ratio 0.40; 95% CI 0.25 to 0.65). CONCLUSIONS: The strongest deterrent of willingness to donate one's own or a family member's organs is a misperception that should be correctable. Race and age are less predictive. Efforts to dispel misperceptions and increase donation remain desperately needed to improve waitlist mortality and post-transplantation outcomes.

Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats.

Although approximately 1 million islets exist in the adult human pancreas, current pancreas preservation and islet isolation techniques recover <50%. Presently, cadaveric donors remain the sole source of pancreatic tissue for transplantation. Brain death is characterized by activation of proinflammatory cytokines and organ injury during preservation and reperfusion. In this study, we assessed the effects of brain death on islet isolation yields and functionality. Brain death was induced in male 250- to 350-g Lewis rats by inflation of a Fogarty catheter placed intracranially. The rats were mechanically ventilated for 2, 4, and 6 h before removal of the pancreas (n = 6). In controls, the catheter was not inflated (n = 6). Shortly after brain death induction, a significant increase in serum tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 was demonstrated in a time-dependent manner. Upregulation of TNF-alpha, IL-1beta, and IL-6 mRNA was noted in the pancreas. Brain death donors presented lower insulin release after glucose stimulation assessed by in situ perfusion of the pancreas. Islet recovery was reduced in brain death donors compared with controls (at 6 h 602.3 +/- 233.4 vs. 1,792.5 +/- 325.4 islet equivalents, respectively; P < 0.05). Islet viability assessed in dissociated islet cells and in intact cultured islets was reduced in islets recovered from brain death donors, an effect associated with higher nuclear activities of NF-kappaB p50, c-Jun, and ATF-2. Islet functionality evaluated in vitro by static incubation and in vivo after intraportal transplantation in syngeneic streptozotocin-induced diabetic rats was significantly reduced in preparations obtained from brain death donors. In conclusion, brain death significantly reduced islet yields and functionality. These observations may lead to strategies to reduce the effects of brain death on pancreatic islets and improve the results in clinical transplantation.

Chromophobe renal cell carcinoma in a pediatric living-related kidney transplant recipient.

Renal cell carcinoma can occur in children who have received renal allografts from adults. Chromophobe renal cell carcinoma is a rare variant of renal carcinoma with distinct histochemical, ultrastructural, and genetic characteristics. We describe the incidental finding of a chromophobe renal cell carcinoma in a 13 1/2-year-old boy 5 years after receiving a living-related renal transplant. This tumor was found by serendipity during the evaluation of fever and inguinal lymphadenopathy, with the presumptive diagnosis of posttransplantation lymphoproliferative disorder. The patient was found to have cat-scratch disease. A renal cell carcinoma should be considered in the differential diagnosis of a pediatric recipient of an adult kidney with an incidental finding of a tumor in the graft.

Two-dose daclizumab induction therapy in 209 liver transplants: a single-center analysis.

BACKGROUND: Patient and graft survival after liver transplantation are adversely affected by early posttransplant renal dysfunction. Therefore, our immunosuppressive strategies should be as "renal sparing" as possible. This is the largest published series to date using daclizumab induction therapy in a renal-sparing regimen. METHODS: This is a retrospective, nonrandomized study comparing 209 adult liver transplants with daclizumab induction to 115 transplants with no induction. RESULTS: Patient and graft survival were similar, despite higher pretransplant acuity of illness and older age in the induction group. Acute rejection within the first 6 months occurred less commonly in the induction group (25.4% vs. 39.1%, P=0.01), despite significantly delayed initiation and lower doses of a calcineurin inhibitor. Mycophenolate mofetil was used more commonly in induction patients, but the efficacy of daclizumab in preventing rejection was independent of this. Patients with a pretransplant creatinine concentration 1.5 mg/dL or less had less rejection if they received induction. Renal function worsened in noninduction patients but showed sustained improvement throughout follow-up in induction patients with a pretransplant creatinine concentration greater than 1.5 mg/dL. Induction therapy provided better rejection prophylaxis among those requiring temporary calcineurin inhibitor cessation because of renal dysfunction. The incidences of histologic hepatitis C recurrence and cytomegalovirus infection were similar in each group. CONCLUSIONS: Liver recipients with and without pretransplant renal dysfunction have less acute rejection with daclizumab induction therapy. This is not associated with an increased risk of over-immunosuppression. Sustained renal improvement in recipients with pretransplant renal dysfunction is possible with daclizumab induction.

Expanded-criteria donor kidneys: a single-center clinical and short-term financial analysis--cause for concern in retransplantation.

BACKGROUND: Expanded-criteria donor (ECD) kidneys are associated with a higher risk of posttransplant failure, but they remain a favorable alternative to dialysis. Now that a uniform definition of "expanded criteria" exists, it is more appropriate than ever to evaluate their utility compared with that seen with non-ECD kidneys. METHODS: The authors analyzed 202 cadaveric kidney-only recipients that underwent transplantation from January 1999 to September 2001, including 45 (22%) recipients whose donors met current ECD criteria. RESULTS: ECD and non-ECD kidney recipients had similar pretransplant characteristics except for older age and increased duration of renal failure in the ECD group. Patient, graft, and death-censored graft survival in both groups were similar in primary recipients but significantly worse in retransplant recipients of ECD kidneys. The relative risk of death-censored graft loss was 1.58 in the ECD group (P = 0.45). Overall inpatient charges (minus organ acquisition charge) for 1 year posttransplant were 76,962 US dollars (ECD) versus 71,026 US dollars (non-ECD) (P = 0.53); the same charges in retransplant recipients were 136,596 US dollars (ECD) versus 91,296 US dollars (non-ECD) (P = 0.25). ECD recipients, especially retransplant recipients, had consistently higher creatinine concentrations, although the average current value of all functioning ECD grafts remains less than 2 mg/dL. ECD recipients had a higher incidence of ureteral stricture (4.4% vs. 0%), but this never resulted in graft loss. CONCLUSIONS: Considering the widening disparity between renal allograft availability and need and the fact that ECD kidneys provide superior outcomes compared with dialysis, the authors' data encourage the continued use of ECD kidneys in primary recipients but justify caution in the retransplant setting.

Quercetin inhibits human vascular smooth muscle cell proliferation and migration.

BACKGROUND: The French paradox has been associated with regular intake of red wine, which is enriched with flavonoids. Quercetin, a flavonoid present in the human diet, exerts cardiovascular protection through its antioxidant properties. We hypothesized that the beneficial effect of quercetin also could be related to the inhibition of vascular smooth muscle cell proliferation and migration. METHODS: Human aortic smooth muscle cells (AoSMC) were grown in culture in the presence of serum. Quercetin inhibited the serum-induced proliferation of AoSMC. This inhibition was dose-dependent and not attributed to toxicity. Cell cycle analysis revealed that quercetin arrested AoSMC in the G(0)/G(1) phase. The effect of quercetin on AoSMC migration was examined using explant migration and Transwell migration assays. Quercetin significantly decreased migration in both assays in a consistent manner. Finally, Western blot analysis of AoSMC exposed to quercetin demonstrated a significant reduction in the activation of mitogen-activated protein kinase, a signaling pathway associated with the migration of vascular smooth muscle cells. CONCLUSIONS: Quercetin inhibits the proliferation and migration of AoSMC, concomitant with inhibition of mitogen-activated protein kinase phosphorylation. These findings provide new insights and a rationale for the potential use of quercetin in the prophylaxis of cardiovascular diseases.