Publications by authors named "John Seal"

Living donor renal transplant involves highly technical operations in both a healthy donor and a recipient with end-stage kidney disease. Contrast-enhanced computed tomography angiography (CTA) is used to assess critical donor anatomy, but its interpretation becomes increasingly difficult as renal anatomy becomes more complex. A related donor was denied because of prohibitive anatomy seen on the pretransplant evaluation CTA.

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Directed blood donation is defined as the donation of blood or its components for the purpose of transfusion into a specified individual. Directed blood donation holds historic significance, and although practices as of 2021 encourage voluntary, nonrenumerated blood donations, public interest in directed donation remains. Requests to discuss the risks and benefits of directed donations are a common inquiry for transfusion medicine, transplant, and hematology/oncology professionals.

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Liver transplantation (LT) using allografts from hepatitis C virus (HCV)-viremic/nucleic acid testing-positive donors' (DNAT+) organs into HCV-aviremic recipients (rHCV-) has been limited owing to nearly universal HCV transmission and concerns regarding availability, safety, and efficacy post-LT with direct-acting antiviral (DAA) therapy. We report our experience of LT using DNAT+ organs into rHCV- as a routine standard of care. Following verification of DAA access, absence of critical drug-drug interactions (DDIs) with DAAs, and informed consent, allocated DNAT+ organs were offered to patients on the waiting list for LT irrespective of recipient HCV status.

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Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest.

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Transplanting donor livers with severe macrosteatosis is associated with increased risk of primary non-function (PNF). The purpose of this study was to identify steatosis-driven biomarkers as a predisposition to severe liver damage and delayed recovery following ischemia reperfusion injury. Wistar rats were fed a methionine- and choline-deficient (MCD) diet for up to three weeks to achieve severe macrosteatosis (>90%).

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Introduction: Early allograft dysfunction (EAD) is a well-defined clinical syndrome that reflects overall graft function within the first week after transplant. The aim of this study was to further refine the definition for EAD.

Method: In this study, 1124 patients were included for analysis.

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Background: Hepatic artery stenosis (HAS) after liver transplantation can progress to hepatic artery thrombosis (HAT) and a subsequent 30% to 50% risk of graft loss. Although endovascular treatment of severe HAS after liver transplantation has emerged as the dominant method of treatment, the potential risks of these interventions are poorly described.

Methods: A retrospective review of all endovascular interventions for HAS after liver transplantation between August 2009 and March 2016 was performed at a single institution, which has the largest volume of liver transplants in the United States.

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Background: Portal vein thrombosis (PVT) is relatively common among candidates for liver transplantation and can present significant intraoperative challenges. Depending on the extent of PVT, thromboendovenectomy (TEV), portal bypass, or systemic inflow may be required to restore portal inflow. While TEV is the most commonly used approach to restore anatomic portal inflow, portal vein injury and life-threatening hemorrhage are risks with this technique.

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Background: Biliary complications remain a significant problem following liver transplantation. Several surgical options can be used to deal with a significant size mismatch between the donor and recipient bile ducts during the biliary anastomosis. We compared biliary transposition to recipient biliary ductoplasty in cadaveric liver transplant.

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Background: Incidence of delirium after liver transplantation (LT) has been reported to occur in 10%-47% of patients and is associated with increased hospital and intensive care unit lengths of stay and poor outcomes.

Methods: Our primary objective was to evaluate the incidence and predisposing risk factors for developing delirium after LT. Our secondary objectives were to describe how delirium is managed in patients after LT, to examine the utilization of resources associated with delirium after LT, and to analyze the outcomes of patients who were treated for delirium after LT.

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Liver transplantation (LT) offers the best chance of survival in selected patients with hepatocellular carcinoma (HCC). Wait-list mortality or dropout due to tumor progression can be significant, and therefore, timely transplantation is critical. Liver grafts discarded by outside organ procurement organizations are a potential source of grafts for low Model for End-Stage Liver Disease tumor patients.

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Background: Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this study was to determine the ability and feasibility of constructing a 3-D model to aid in surgical planning and to predict graft weight prior to an in situ division of the donor liver.

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Objectives: The purpose of this study was to compare the agreement between two heparin assays, Hepcon HMS plus/Kaolin-ACT and Anti-Xa, and their predictive power in detecting circulating heparin levels post-reperfusion of the liver graft when compared with thromboelastogram (TEG) r time ratio in patients undergoing orthotopic liver transplantation (OLT).

Design: Prospective, observational cohort study design.

Setting: Single center, university hospital.

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Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease (NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation.

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This study analyzed how features of a liver graft and the technique of biliary reconstruction interact to affect biliary complications in pediatric liver transplantation. A retrospective analysis was performed of data collected from 2001 to 2011 in a single high-volume North American pediatric transplant center. The study cohort comprised 173 pediatric recipients, 75 living donor (LD) and 98 deceased donor (DD) recipients.

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Liver transplantation (LT) with donation after circulatory death (DCD) donors has been associated with a high rate of ischemic-type biliary strictures (ITBSs) and inferior graft survival. To investigate the impact of an intraoperative tissue plasminogen activator (tPA) on outcomes following DCD LT, we conducted a retrospective analysis of DCD LT at the Toronto General Hospital (TGH) and the Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD LTs were performed with an intraoperative tPA injection (n = 30 at TGH, n = 55 at OMC), and they were compared with 33 DCD LTs without a tPA.

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Background: Pancreas transplant recipient obesity has been associated with increased risk of perioperative complications, graft failure, and death. The imperative to maximize organ utility must be balanced against the need to maintain equity of access, including for the increasing number of obese diabetic patients.

Methods: We compared the outcomes of pancreas transplant recipients with body mass index (BMI) greater than 30 kg/m(2) (n=60, mean ± SD BMI 32.

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Background: There is a paucity of contemporary data describing the results of pancreas retransplantation (PRT). As a measure of utility, we wished to determine whether PRT could produce equivalent short-term and long-term recipient outcomes to primary pancreas after kidney (PAK) transplantation.

Methods: Retrospective analysis of 96 consecutive pancreas only transplants performed from 2003 to May 2012.

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Using a structure based pharmacophore design, a weak inhibitor of RNase H, identified from a small library of two metal binding HIV-1 integrase inhibitors, was optimized for potency and physicochemical properties. This manuscript describes the SAR and in vivo DMPK for the pyridopyrimidinone class of inhibitors.

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Two novel series of spirocyclic piperidine analogs appended to a pyrazolo[1,5-a]pyridine core were designed, synthesized and evaluated for their anti-HCV activity. A series of piperidine ketals afforded dispiro 6p which showed excellent in vitro anti-HCV activities (EC50 of 1.5nM and 1.

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Unlabelled: Background and objective: Insulin and leptin hormones are important regulators of food intake and energy balance. There is limited information about insulin and leptin hormones in neonates. This preliminary study aimed to investigate the concentrations of insulin and leptin in umbilical cord plasma and neonate's saliva and their relationships.

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We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead 1a. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization.

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Background: During organ transplantation, it is inevitable that tissues undergo cold ischemia during harvest and transport before implantation. Polyethylene-based polymers have been proposed and tested as preservation agents, with promising results. We have previously reported that a high molecular weight polyethylene glycol (PEG) (15-20,000 MW; PEG 15-20) protects the intestinal epithelium against a variety of cellular stresses, including radiation injury and microbial invasion, by mechanisms that appear to involve lipid rafts.

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