BACKGROUNDTransplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.
BackgroundIslet cell transplantation can cure type 1 diabetes (T1D), but only a minority of recipients remains insulin–independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.Methodology/Principal FindingsTwenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG) induction and tacrolimus plus mycophenolate mofetil (MMF) maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters - including time until insulin independence, insulin independence at one year, and C-peptide levels over one year- remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively) and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively). Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.Conclusions/SignificanceIn this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular islet autoreactivity may be required. Monitoring cellular immune reactivity can be useful to identify factors influencing graft survival and to assess efficacy of immunosuppression.Trial RegistrationClinicaltrials.gov NCT00623610
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process. Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3, superiority trial. Authorship Ina Jochmans (PhD), Aukje Brat (Medical degree), Lucy Davies (PhD) 4 , H. Sijbrand Hofker (Medical degree), Fenna E.M. van de Leemkolk (Medical degree), Henri G.
Background Tumor recurrence after radical resection of hepatic tumors is not uncommon, suggesting that malignant lesions are missed during surgery. Intraoperative navigation using fluorescence guidance is an innovative technique enabling real-time identification of (sub)capsular liver tumors. The objective of the current study was to compare fluorescence imaging (FI) and conventional imaging modalities for laparoscopic detection of both primary and metastatic tumors in the liver. Methods Patients undergoing laparoscopic resection of a malignant hepatic tumor were eligible for inclusion. Patients received standard-of-care, including preoperative CT and/or MRI. In addition, 10 mg indocyanine green was intravenously administered one day prior to surgery. After introduction of the laparoscope, inspection, FI, and laparoscopic ultrasonography (LUS) were performed. Histopathological examination of resected suspect tissue was considered the gold standard. Results Twenty-two patients suspected to have hepatocellular carcinoma (n=4), cholangiocarcinoma (n=2) or liver metastases from colorectal carcinoma (n=12), uveal melanoma (n=2) and breast cancer (n=2) were included. Two patients were excluded because their surgery was unexpectedly postponed several days. Twenty-six malignancies were resected in the remaining 20 patients. Sensitivity for various modalities was 80% (CT), 84% (MRI), 62% (inspection), 86% (LUS) and 92% (FI), respectively. Three metastases (12%) were identified solely by FI. All 26 malignancies could be detected by combining LUS and FI (100% sensitivity). Conclusion This study demonstrates added value of FI during laparoscopic resections of several hepatic tumors. Although larger series will be needed to confirm long-term patient outcome, the technology already aids the surgeon by providing real-time fluorescence guidance.
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