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Background: New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes., Methods: Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N = 2770) and post-AC (Feb-2020 to Dec-2021, N = 2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival., Results: Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P  < 0.001), and less percentage of MELD exception (4.6% vs 7.7%, P  = 0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period ( P  < 0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P  < 0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56-1.16, P  = 0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41-1.99, P  < 0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods., Conclusions: The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

In blastomycosis, immunosuppression such as that following solid organ transplantation appears to be a risk factor for the development of overwhelming lung infection fulfilling criteria for the acute respiratory distress syndrome. Our transplant center, located outside traditional endemic areas for Blastomyces spp, experienced a case of fatal acute respiratory distress syndrome secondary to blastomycosis pneumonia in a recipient of recent orthotopic liver transplantation. The patient expired despite support with veno-venous extracorporeal membrane oxygenation., Competing Interests: The authors have no conflicts of interest to disclose., (© 2022 The Authors.)

Objectives: The relative roles of liver resection (LR) and liver transplantation (LT) in the treatment of a solitary hepatocellular carcinoma (HCC) remain unclear. This study was conducted to provide a retrospective intention-to-treat comparison of these two curative therapies., Methods: Records maintained at the study centre for all patients treated with LR or listed for LT for hepatitis C-associated HCC between January 2002 and December 2007 were reviewed. Inclusion criteria required: (i) an initial diagnosis of a solitary HCC lesion measuring ≤ 5 cm, and (ii) Child-Pugh class A or B cirrhosis. The primary endpoint analysed was intention-to-treat survival., Results: A total of 75 patients were listed for transplant (LT-listed group) and 56 were resected (LR group). Of the 75 LT-listed patients, 23 (30.7%) were never transplanted because they were either removed from the waiting list (n = 13) or died (n = 10). Intention-to-treat median survival was superior in the LR group compared with the LT-listed group (61.8 months vs. 30.6 months), but the difference did not reach significance. Five-year recurrence was higher in the LR group than in the 52 LT patients (71.5% vs. 30.5%; P < 0.001)., Conclusions: In the context of limited donor organ availability, partial hepatectomy represents an efficacious primary approach in properly selected patients with hepatitis C-associated HCC., (© 2012 International Hepato-Pancreato-Biliary Association.)

Heterologous immunologic memory has been considered a potent barrier to tolerance induction in primates. Induction of such tolerance for a previously transplanted organ may be more difficult, because specific memory cells can be induced and activated by a transplanted organ. In the current study, we attempted to induce tolerance to a previously transplanted kidney allograft in nonhuman primates. The conditioning regimen consisted of low dose total body irradiation, thymic irradiation, antithymocyte globulin, and anti-CD154 antibody followed by a brief course of a calcineurin inhibitor. This regimen had been shown to induce mixed chimerism and allograft tolerance when kidney transplantation (KTx) and donor bone marrow transplantation (DBMT) were simultaneously performed. However, the same regimen failed to induce mixed chimerism when delayed DBMT was performed after KTx. We found that significant levels of memory T cells remained after conditioning, despite effective depletion of naïve T cells. By adding humanized anti-CD8 monoclonal antibody (cM-T807), CD8 memory T cells were effectively depleted and these recipients successfully achieved mixed chimerism and tolerance. The current studies provide 'proof of principle' that the mixed chimerism approach can induce renal allograft tolerance, even late after organ transplantation if memory T-cell function is adequately controlled.

Costimulatory blockade with anti-CD154 monoclonal antibody (aCD154) prolongs allograft survival in nonhuman primates, but has not reliably induced tolerance when used alone. In the current studies, we evaluated the effect of adding CD154 blockade to a chimerism inducing nonmyeloablative regimen in primates. We observed a significant improvement of donor bone marrow (DBM) engraftment, which has been associated with a lower incidence of acute rejection and long-term survival of renal allografts without the need for previously required splenectomy. Among the long-term survivors, four never showed evidence of rejection, with the longest survival exceeding 1700 days following discontinuation of immunosuppression. Nevertheless, late chronic rejection was observed in three of eight recipients, indicating the necessity of further modifications of the regimen. Control recipients receiving no DBM or donor splenocytes in place of DBM rejected their allografts. Thus, DBM engraftment with, at least, transient mixed chimerism appears essential for induction of allograft tolerance using this conditioning regimen. Modification of the original mixed chimerism approach, by the addition of costimulatory blockade, has been shown to enhance mixed chimerism and induce renal allograft tolerance with less morbidity in nonhuman primates., (Copyright 2004 Blackwell Munksgaard)

We investigated changes in the immunoendocrine system during fasting. Ten hospitalized patients aged 14-46 y with psychosomatic disorders fasted for 7 or 10 d. Blood samples were collected before and on days 3 and 7 of the 7-d fasts. When fasting continued to 10 d, an additional sample was taken on day 10. We measured blood cellularity (white blood cells and total lymphocytes), the total number and percentage of lymphocyte subsets (CD2, CD3, CD4, CD8, and CD19), natural killer (NK) cell activity, cytokines (interleukin 1 beta, interleukin 2, interleukin 6, granulocyte-macrophage colony stimulating factor, tumor necrosis factor alpha, and interferon gamma), and soluble interleukin 2 receptors. Corticotropin, cortisol, and dehydroepiandrosterone sulfate (DHEAS) concentrations were also determined. Although the total number of lymphocytes decreased during fasting, NK cell activity increased significantly. Plasma cortisol and DHEAS concentrations also increased significantly whereas changes in corticotropin concentrations were not significant. The total number and percentage of CD4 cells decreased significantly during fasting but no other lymphocyte subsets changed significantly. The percentage of CD4 cells was negatively correlated with cortisol concentrations during fasting. No detectable changes occurred in cytokines or soluble interleukin 2 receptors during the study. All measured immunoendocrine values that changed during fasting returned to prefasting values during the refeeding period. These findings indicate that fasting affects immune variables such as T cell subsets and NK cell activity at least in part through changes in adrenal gland-related hormones.

Stress is known to influence the immune function via an effect on the central nervous system. We previously presented data showing that stress alters the population of T-cell subsets in mice. The variations of T-cell subsets in the thymus, peripheral blood, and spleen in mice similarly stressed by immobilization or by unavoidable and opioid-dependent stress were measured by flow cytometry using the monoclonal antibodies anti-L3T4, anti-Lyt 1, anti-Lyt 2 and anti-Thy 1, 2. Immobilization stress was applied for three days and T-cell subsets were measured on the days 1, 2 and 3, as well as on day 7 after release from immobilization. Lyt 2-positive cells in the thymus were the most sensitive to stress, showing significant variations. The proportion of immature T-cells increased in the thymus, blood and spleen of the stressed mice. When diazepam or naloxone were administered 30 min before the initiation of stress, these variations tended to decrease. Thus, the ratio of T-cell subsets varied with the duration of immobilization stress. This appeared to be partly mediated by the opioid system and the central nervous system.

It is well known that the immune function can be compromised by stress. To investigate immune function in mice stressed by experimental restraint or unavoidable and opioid dependent stress, we evaluated the changes in total body weight and in organ weights (liver, spleen and thymus) of these animals, as well as the phagocytic activity of macrophages, the cytotoxicity of T cells and inhibitory effects on tumor growth and changes in T cell subset populations. At the same time we evaluated the effects of Neurotropin (NSP), a substance extracted from the inflamed skin of rabbits inoculated with the vaccinia virus and which appears to possess neuroimmunomodulating activity. The experimentally stressed group exhibited a reduction of phagocytic activity of macrophages, cytotoxicity of T cells and inhibitory effects on tumor growth. In addition there were changes in the population of T cell subsets. In those animals pretreated with NSP, the immunosuppression induced by stress was ameliorated. As compared with several agents which influence phagocytosis, neurotropin exhibited effects similar to that of agents that blocked the adrenaline receptor and an opioid antagonist rather than tranquilizer (diazepam) and a cholinergic receptor blocker. The pharmacologic effects of neurotropin support a relationship between the actions of the central nervous system and the immune system.