The drivers and the specification of CD4 + T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique T H -program. Specifically, CD11b + CD103 − DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3 neg tumor-promoting IL-10 + IL-17 + IFNγ + regulatory CD4 + T cells. The balance between this distinctive T H program and canonical FoxP3 + T REGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This T H -signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b + CD103 − DC promote CD4 + T cell tolerance in PDA which may underscore its resistance to immunotherapy.

| INTRODUC TI ONOnce a therapy for neonates with severe respiratory and cardiac impairment, extracorporeal membrane oxygenation (ECMO) is being utilized with greater frequency in the critically ill adult population. 1-4 ECMO has shown encouraging results as a rescue therapy that serves as a replacement for pulmonary and/or cardiovascular function while the heart and lungs recover from a catastrophic insult in the postoperative period. At our center, ECMO has been utilized with increasing frequency in the critically ill adult population. 5 Prior to transplantation, patients with liver failure often have multiple organ system impairment. Coagulopathy, portal hypertension, and an impaired immune system are chief among the maladies associated with acute and chronic liver disease. 6-8 In the perioperative period, the added stress of a rigorous surgery and subsequent liver engraftment may lead to further physiological derangements that predispose patients to cardiopulmonary failure. 9,10 These can lead to intrinsic lung conditions, such as ARDS or to cardiopulmonary failure from right heart impairment and pulmonary thrombosis. Prior to the utilization of adult ECMO, these conditions carried a high mortality rate. 11 The use of veno-venous (VV) ECMO has been Abstract Background: Postoperative severe cardiopulmonary failure carries a high rate of mortality. Extracorporeal membrane oxygenation (ECMO) can be used as a salvage therapy when conventional therapies fail. Methods: We retrospectively reviewed our experience with ECMO support in the early postoperative period after liver transplant between September 2011 and May 2016.Results: Out of 537 liver transplants performed at our institution, seven patients required ECMO support with a median age of 52 and a median MELD score of 28.Veno-venous ECMO was used in four patients with severe respiratory failure while the rest required veno-arterial ECMO for circulatory failure. The median time from transplant to cannulation was 3 days with a median duration of ECMO support of 7 days. All patients except one were successfully decannulated. The median hospital length of stay was 58 days with an in-hospital mortality of 28.6%. Conclusion:Extracorporeal membrane oxygenation can be considered a viable rescue therapy in the setting of severe postoperative cardiopulmonary failure.Extracorporeal membrane oxygenation therapy was successful in saving patients who were otherwise unsalvageable. K E Y W O R D Scardiopulmonary failure, ECMO, liver failure

N-Acetylcysteine (NAC) is reported to have multiple clinical applications in addition to being the specific antidote for acetaminophen toxicity. NAC stimulates glutathione biosynthesis, promotes detoxification, and acts directly as a scavenger of free radicals. It is a powerful antioxidant and a potential treatment option for diseases characterized by the generation of free oxygen radicals. We present a case of postoperative hepatic dysfunction of multifactorial etiology in a patient with therapeutic acetaminophen levels, where hepatic function improved considerably following administration of intravenous NAC. This case suggests that NAC should be considered for treatment of acute liver dysfunction in the postoperative setting, even in the absence of elevated acetaminophen levels.

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