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Clinical outcomes of patients with two small hepatocellular carcinomas

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World journal of Hepatology 2021年第10期13卷 1439-1449页

作者： Anh Duy Pham Karl Vaz Zaid S Ardalan Marie Sinclair Ross Apostolov Sarah Gardner Ammar Majeed Gauri Mishra Ning Mao Kam Kurvi Patwala Numan Kutaiba Niranjan Arachchi Sally Bell Anouk T Dev john S Lubel Amanda j Nicoll Siddharth Sood William Kemp Stuart K Roberts Michael Fink Adam G Testro Peter W Angus paul j gow The Victorian Liver Transplant Unit Austin HealthHeidelberg 3084VictoriaAustralia Department of Gastroenterology Alfred HealthMelbourne 3000VictoriaAustralia The Melbourne Liver Group Melbourne 3000VictoriaAustralia The University of Melbourne Parkville 3010VictoriaAustralia Central Clinical School Monash UniversityMelbourne 3004VictoriaAustralia Department of Gastroenterology and Hepatology Monash HealthClayton 3168VictoriaAustralia Department of Radiology Austin HealthHeidelberg 3084VictoriaAustralia Department of Radiology Eastern HealthBox Hill 3128VictoriaAustralia Department of Gastroenterology Western HealthFootscray 3011VictoriaAustralia Department of Gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Department of Gastroenterology Royal Melbourne HospitalParkville 3050VictoriaAustralia

BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or *** transplantation is often considered for multiple small or single large *** of two small HCC whether presenting synchronously or sequentially is less *** To define the outcomes of patients presenting with two small *** Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC≤3 cm between january 2000 and March *** outcomes were overall survival(OS)and transplant-free survival(TFS).RESULTS 104 patients were identified(male n=89).Median age was 63 years(interquartile range 58-67.75)and the most common aetiology of liver disease was hepatitis C(40.4%).59(56.7%)had synchronous HCC and 45(43.3%)had sequential.36 patients died(34.6%)and 25 were transplanted(24.0%).1,3 and 5-year OS was 93.0%,66.1% and 62.3% and 5-year post-transplant survival was 95.8%.1,3 and 5-year TFS was 82.1%,45.85% and 37.8%.When synchronous and sequential groups were compared,OS(1,3 and 5 year synchronous 91.3%,63.8%,61.1%,sequential 95.3%,69.5%,64.6%,P=0.41)was similar but TFS was higher in the sequential group(1,3 and 5 year synchronous 68.5%,37.3% and 29.7%,sequential 93.2%,56.6%,48.5%,P=0.02)though this difference did not remain during multivariate *** TFS in patients presenting with two HCC≤3 cm is poor regardless of the timing of the second *** patients presenting with two small HCC should be considered for transplantation.

关键词： Hepatocellular carcinoma Liver cancer Prognosis Transplantation Transplant-free survival

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

Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease

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World journal of Gastroenterology 2015年第4期21卷 1189-1196页

作者： Christopher Leung Sern Wei Yeoh Desmond Patrick Shara Ket Kaye Marion paul gow Peter W Angus Liver Transplant Unit Austin HospitalHeidelbergVictoria 3084Australia Department of Medicine The University of MelbourneAustin CampusHeidelbergVictoria 3084Australia Statistics and Operations Research Group School of Mathematical and Geospatial Sciences College of ScienceEngineering and HealthRMIT UniversityMelbourneVictoria 3000Australia

AIM: To determine characteristics and prognosticpredictors of patients with hepatocellular carcinoma(HCC) in association with non-alcoholic fatty liver disease(NAFLD).METHODS: We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index(BMI), and the presence of diabetes, hypertension, or ***: Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent(8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of < 25 kg/m2, 25-29 kg/m2 and ≥ 30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤ 1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics(P = 0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of ***: HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis.

关键词： Hepatocellular carcinoma Non-alcoholic fatty liver

Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations

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World journal of Hepatology 2022年第4期14卷 754-765页

作者： Ross Apostolov Emily Gianatti Darren Wong Numan Kutaiba paul gow Mathis Grossmann Marie Sinclair Department of Gastroenterology and Liver Transplant Unit Austin HealthHeidelberg 3084VICAustralia Department of Medicine University of MelbourneParkville 3010VICAustralia Department of Endocrinology Fiona Stanley HospitalMurdoch 6150WAAustralia Department of Radiology Austin HealthHeidelberg 3084VICAustralia Department of Endocrinology Austin HealthHeidelberg 3084VICAustralia

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available *** To explore the effect of testosterone treatment on *** therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly *** This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received *** patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for *** liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo *** ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo *** week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%Pjustified.

关键词： Hepatic steatosis Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Testosterone therapy Testosterone undecanoate Type 2 diabetes

Reduced upper limb lean mass on dual energy X-ray absorptiometry predicts adverse outcomes in male liver transplant recipients

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World journal of Transplantation 2022年第6期12卷 120-130页

作者： Penelope Hey Rudolf Hoermann paul gow Timothy P Hanrahan Adam G Testro Ross Apostolov Marie Sinclair Liver Transplant Unit Austin HealthHeidelberg 3084Australia Department of Medicine University of MelbourneMelbourne 3052Australia

BACKGROUND Pre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation *** limb lean mass(LM)measured by dual-energy X-ray absorptiometry(DEXA)was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for *** To investigate the use of DEXA LM in predicting gender-stratified early posttransplant *** Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were *** included posttransplant mortality and graft failure,bacterial infections,acute cellular rejection(ACR)and intensive care and total hospital length of *** Four hundred and sixty-nine patients met inclusion criteria of which 338 were male(72%).Median age was 55.0 years(interquartile range 47.4,59.7)and model for end-stage liver disease(MELD)score *** time from assessment to transplantation was 7 mo(3.5,12).Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant(hazard ratio=0.42;95%confidence interval:0.20-0.89;P=0.024)in males *** was a negative correlation between upper limb LM and intensive care(τb=-0.090,P=0.015)and total hospital length of stay(τb=-0.10,P=0.0078)in *** women,neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of *** composition parameters,MELD and age were not associated with 90-d mortality or graft failure in either *** were no significant predictors of early *** Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with *** upper limb LM provides a novel measure of muscle wasting that has prognostic value in this *** lack of association in women req

关键词： Dual-energy X-ray absorptiometry Sarcopenia Body composition Liver transplantation Survival

Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

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World journal of Hepatology 2016年第35期8卷 1569-1575页

作者： Siddharth Sood Lijia Yu Kumar Visvanathan Peter William Angus paul john gow Adam Gareth Testro Department of Gastroenterology and Hepatology University of Melbourne Royal Melbourne Hospital Liver Transplant Unit Victoria University of Melbourne Innate Immune Laboratory University of Melbourne St Vincent’s Hospital

AIMTo investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODSAdult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1st February 2014. RESULTSCirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient’s immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM P = 0.01) for infection. A very low QFM P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSIONQFM is lower in cirrhotics, allowing objective determinations of an individual’s unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.

关键词： Infection Biomarker Immune dysfunction Immune function Immunosuppression Liver Immune system Cirrhosis Mortality

Advances in newly developing therapy for chronic hepatitis C virus infection

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Frontiers of Medicine 2014年第2期8卷 166-174页

作者： paul j. Pockros Division of Gastro/Hepatology Scripps Clinic 10666 N Torrey Pines Road N203 La Jolla CA 92067 USA

Chronic hepatitis C virus （HCV） infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral （DAA） agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN ＋ RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA) nucleotide polymerase inhibitors protease inhibitors

The Bemisia tabaci Species Complex:Questions to Guide Future Research

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journal of Integrative Agriculture 2012年第2期11卷 187-196页

作者： paul j De Barro CSIRO Ecosystem Sciences Brisbane QLD 4001Australia

Since 2007 we have began to consider the relationships between the different members of the Bemisia tabaci species complex in a more structured and systematic *** of these relationships has been infered from considerations of a portion of the mitochondrial cytochrome oxidase one（mtCOI）*** this is a quite limited approach which would benefit from the consideration of a much greater diversity of genetic material,it is the only publically available data that spans the diversity of the species *** the limitations,the phylogenetic reconstruction that can be derived from this data is useful and can be used as a basis to frame questions and construct testable hypotheses that will form the basis for future *** study uses the largest available mtCOI dataset,consisting of 383 unique mtCOI haplotypes that spans the full diversity of the *** species complex as we currently know it,to make a range of observations which are then used to develop questions as guide for future research.

关键词： mitochondrial cytochrome oxidase one phylogenetic analysis

The rise of 3D cellular spheroids: efficient culture via upward growth from a superamphiphobic surface

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National Science Review 2019年第6期6卷 1068-1069页

作者： paul j.Dyson Institut des Sciences et Ingénierie Chimiques Ecole Polytechnique Fédérale de Lausanne

Cell culture assays are extensively used in drug discovery and development programs, biomedical research, and in many others areas of science. Currently,2D monolayer cellular assays serve as the gold standard. However, while they provide seemingly indispensable information on drug activity, it is estimated that of the putative drug candidates selected

关键词： The rise of 3D cellular spheroids efficient culture via upward growth from a superamphiphobic surface