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Hepatocellular carcinoma recurrence after liver transplant:An Australian single-centre study

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World Journal of Transplantation 2025年第1期15卷 105-114页

作者： Matthew G Garas Luis calzadilla-Bertot Briohny W Smith Luc Delriviere Byron Jaques Lingjun Mou Leon A Adams Gerry c MacQuillan George Garas Gary P Jeffrey Michael c Wallace Medical School University of Western AustraliaNedlands 6009Western AustraliaAustralia Department of Hepatology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia Department of Surgery Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia

BAcKGROUND Hepatocellular carcinoma(Hcc)is a leading cause of cancer-related deaths *** transplantation(LT)offers the most effective *** recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for *** rate of Hcc recurrence is generally reported as 8%-20%in the *** predictors of Hcc have already been researched,however,to our knowledge there are no published studies on this topic using Australian *** To determine the rate and identify predictors of Hcc recurrence in a contemporary Western Australian LT *** We performed a retrospective cohort study of all liver transplants in patients with Hcc at Sir charles Gairdner Hospital between 2006 and *** was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of *** survival of Hcc patients post-LT,stratified for recurrence,was calculated by Kaplan Meier *** and multivariate cox regression was used to determine predictors of Hcc recurrence *** Between 1/1/2006 and 12/31/2021,119 patients were transplanted with Hcc.8.4%of subjects developed recurrent Hcc after LT with median follow-up time of 5.4 *** median time to recurrence was 2.9 years±0.75 *** comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated Hcc(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with Hcc recurrence compared to those without Hcc recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank PcONcLUSION Hcc recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT *** studies are requir

关键词： Liver cancer Recurrence Liver transplantation Hepatocellular carcinoma Predictors Post-transplant survival Australian data

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon c.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Hepatitis c Virus, Insulin Resistance, and Steatosis

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Journal of clinical and Translational Hepatology 2016年第1期4卷 66-75页

作者： Dominik Kralj Lucija Virovi(c) Juki(c) Sanja Stojsavljevi(c) Marko Duvnjak Martina Smoli(c) Ines Bili(c) (c)ur(c)i(c) Department of Gastroenterology and Hepatology Sisters of Charity University Hospital Center Zagreb Croatia Department of Pharmacology Faculty of Medicine University of Osijek Osijek Croatia Department of Pharmacology Faculty of MedicineUniversity of Osijek Department of Endocrinology and metabolism disorders University Hospital Center Osijek Osijek Croatia

Hepatitis c virus (HcV) is one of the main causes of liver disease *** steatosis is a common finding in many hepatic and extrahepatic disorders,the most common being metabolic syndrome (MS).Overtime,it has been shown that the frequent coexistence of these two conditions is not coincidental,since many epidemiological,clinical,and experimental studies have indicated HcV to be strongly associated with liver steatosis and numerous metabolic ***,we present an overview of publications that provide clinical evidence of the metabolic effects of HcV and summarize the available data on the pathogenetic mechanisms of this *** has been shown that HcV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple *** research has suggested that HcV interferes with insulin signaling both directly and indirectly,inducing the production of several proinflammatory *** replication,assembly,and release from hepatocytes require close interactions with lipid droplets and host *** modulation of lipid metabolism in host cells can induce hepatic steatosis,which is more pronounced in patients with HcV genotype *** risk of steatosis depends on several viral factors (including genotype,viral load,and gene mutations) and host features (visceral obesity,type 2 diabetes mellitus,genetic predisposition,medication use,and alcohol consumption).HcV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HcV infection and quality of life,due to their association with resistance to antiviral therapy,progression of hepatic fibrosis,and development of hepatocellular ***,HcV-induced IR,oxidative stress,and changes in lipid and iron metabolism lead to glucose intolerance,arterial hypertension,hyperuricemia,and atherosclerosis,resulting in increased cardiovascular mortality.

关键词： Hepatitis c virus Metabolic syndrome Insulin resistance Steatosis

Influence of B4c and ZrB2 reinforcements on microstructural,mechanical and wear behaviour of AA 2014 aluminium matrix hybrid composites

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Defence Technology（防务技术） 2024年第10期40卷 242-254页

作者： Ramesh Babu R Rajendran c Saiyathibrahim A Rajkumar Velu Department of Mechanical Engineering Karpagam Institute of TechnologyCoimbatore 641105India Department of Mechanical Engineering Sri Krishna College of Engineering and TechnologyCoimbatore 641008India Department of Mechanical Engineering Indian Institute of Technology JammuJammu and Kashmir 181221India

considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace *** research effort aims to develop novel hybrid composites based on AA 2014 alloy through the use of liquid metallurgy stir casting to reinforce dual ceramic particles of Zirconium Diboride(ZrB_(2))and Boron carbide(B4c).The weight percentage(wt%)of ZrB_(2) was varied(0,5,10,and 15),while a constant 5 wt%of B4c was maintained during this *** as-cast samples have been assessed using an Optical Microscope(OM)and a Scanning Electron Microscope(SEM)with Energy Dispersive Spectroscopy(EDS).The properties such as hardness,tensile strength,and wear characteristics of stir cast specimens were assessed to examine the impact of varying weight percentages of reinforcements in AA 2014 *** particular,dry sliding wear behaviour was evaluated considering varied loads using a pin-on-disc *** the weight%of ZrB_(2) grew and B4c was incorporated,hybrid composites showed higher hardness,tensile strength,and wear ***,the incorporation of a cumulative reinforcement consisting of 15 wt%ZrB_(2) and 5 wt%B4c resulted in a significant 31.86%increase in hardness and a 44.1%increase in tensile strength compared to AA 2014 *** addition,it has been detected that wear resistance of hybrid composite pin(containing 20 wt%cumulative reinforcement)is higher than that of other stir cast wear test pins during the whole range of applied *** surfaces of tensile specimens showed ductile fracture in the AA 2014 matrix and mixed mode for hybrid *** surfaces obtained employing higher applied load indicated abrasive wear with little plastic deformation for hybrid composites and dominant adhesive wear for matrix ***,the superior mechanical and tribological performance of hybrid composites can be attributed to dual reinforcement pa

关键词： AA 2014 alloy Stir casting Hybrid composite Hardness Tensile strength Specific wear rate

Treatment modalities for hypersplenism in liver transplant recipients with recurrent hepatitis c

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World Journal of Gastroenterology 2009年第40期15卷 5010-5013页

作者： Lena Sibulesky Justin H Nguyen Ricardo Paz-Fumagalli c Burcin Taner Rolland c Dickson Division of Transplant Surgery and Transplant Hepatology Division of Interventional Radiology

Hepatitis c is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis c recurs universally in the transplanted liver and is the major cause of decreased graft and patient survival. The combination therapy of interferon and ribavirin has been shown to be the most effective therapy for recurrent hepatitis c. However, pre-and post-transplant hypersplenism often precludes patients from receiving the antiviral therapy. Splenectomy and partial splenic embolization are the two invasive modalities that can correct the cytopenia associated with hypersplenism. In this report we review the two treatment options, their associated outcomes and complications.

关键词： Hypersplenism Leukopenia Recurrenthepatitis c Thrombocytopenia Liver transplant

Genetic diversity of the hepatitis c virus: Impact and issues inthe antiviral therapy

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World Journal of Gastroenterology 2007年第17期13卷 2416-2426页

作者： H Le Guillou-Guillemette S Vallet c Gaudy-Graffin c Payan A Pivert A Goudeau F Lunel-Fabiani Laboratory of Virology University Hospital of Angers France and Laboratory HIFI UPRES EA 3859 University of Angers France Department of Microbiology EA 3882 CHU Morvan University Hospital of Brest France Université Francois Rabelais INSERM ERI 19 et CHRU de Tours Tours France

The hepatitis c Virus (HcV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The re- sulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the pre- dictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic suc- cess. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antivi- ral therapy in patients infected by the same HcV geno- type. Both structural and non structural genomic regions of HcV have been suggested to be involved in the Inter- feron pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HcV diversity. Then, the HcV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non- structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

关键词： Hepatitis c virus Genetic diversity Therapyresistance E2 NS3 NSSA NSSB

c_c(X)Spaces with X Locally compact

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Acta Mathematica Sinica,English Series 2007年第9期23卷 1593-1600页

作者： J.c.FERRANDO S.MOLL centro de Investigación Operativa Universidad Miquel Hernández Departamento de Matemática Aplicada Universidad Politécnica

In this paper, we show, among other results, that if X is a [separable] locally compact space X [satisfying the first countability axiom] then the space cc （X） has countable tightness [if and only if it has bounding tightness] if and only if it is Frechet-Urysohn, if and only if cc （X） contains a dense （LM） subspace and if and only if X is a-compact.

关键词： Frechet-Urysohn space countable [bounding] tightness (LM)-space

Fabrication and Properties of SiB6-B4c with Phenolic Resin as a carbon Source

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Journal of Materials Science & Technology 2008年第1期24卷 102-104页

作者： G. c.Hwang J.Matsushita United Graduate School of Science and Engineering Tokai University 1117 Kitakaname Hiratsuka 259-12921 Japan

Si-B-c ceramic composites were synthesized using SiB-6,B-4c,and phenolic resin as a carbon source by pressureless sintering in an Ar ***,the Si-B-c ceramic composites were fabricated to determine their potential for applications as high hardness and high temperature *** X-ray diffraction patterns of sintered bodies of SiB-6-B-4c with carbonized phenolic resin can be seen that SiB-6 and c changed to B-4c and *** this study,it is obtained that carbonized phenolic resin is good addition material as a reaction material comparing to carbon powder at 1683 K for 1 h by pressureless sintering in an Ar atmosphere.

关键词： Silicon boride Boron carbide Phenolic resin

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer c.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury