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Quantitative hepatitis B surface antigen in predicting recurrence of hepatitis B-related hepatocellular carcinoma after liver transplantation

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Hepatoma Research 2018年第9期4卷 159-170页

作者： James Fung Danny Ka-Ho Wong Yasuhito Tanaka Regina Lo Tiffany Wong kenneth Siu-Ho Chok AIbert Chi-Yan Chan Tan-To Cheung Wing-Chiu Dai KeIvin ng Kevin ng Man Kwan Irene ng Wai-Kay Seto Ching-Lung Lai Man-Fung Yuen Chung-Mau Lo The Liver Transplant Center Queen Mary HospitalHong KongChina Department of Medicine the University of Hong KongHong KongChina State Key Laboratory for Liver Research the University of Hong KongHong KongChina Department of Virology and Liver Unit Graduate School of Medical sciencesNagoya City UniversityNagoya 467-8601Japan Department of Pathology the University of Hong KongHong KongChina Department of Surgery the University of Hong KongHong KongChina

Aim:Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for chronic hepatitis B (CHB) can be associated with reappearance of hepatitis B surface antigen (HBsAg). The current study determined the significance of HBsAg qualitatively and quantitatively using a highly sensitive assay in recurrent HCC after transplantation. Methods:Consecutive patients with HBV-related HCC with LT were included. Oral nucleos(t)ide analogues without hepatitis B immune globulin were used as hepatitis B virus (HBV) prophylaxis. Quantitative HBsAg levels were performed at time of transplant, at 1 month, 3 and 6 months post transplant using a highly sensitive (hs)-HBsAg assay. Results:One hundred and fourteen patients were included, with a median follow-up of 80 months, with 24 cases of HCC recurrence, and a cumulative rate of 20.7% at 5 years. There was significant correlation between time of tumor recurrence and time of HBsAg reappearance (r = 0.551,P = 0.027). Early HCC recurrence was associated with higher median level of hs-HBsAg at the time of transplant (72.85vs. 69.70 IU/mL,P = 0.018). Using a hs-HBsAg cut-off level of 0.0005 IU/mL, patients with levels above this threshold at 3 and 6 months were associated with higher rate of early HCC recurrence (28.6%vs. 3.0% and 26.9%vs. 2.9% respectively, bothP =0.0006). There was no significant difference in HCC recurrence between positive and negative HBsAg using the conventional qualitative HBsAg assay. Conclusion:Serum hs-HBsAg levels of≥ 0.0005 IU/mL at 3 to 6 months after LT is associated with higher rates of early HCC recurrence, and may be useful as an early tumor marker.

关键词： Hepatitis B hepatocellular carcinoma transplantation hepatitis B surface antigen recurrence

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慢即是快——紧凑道路设计思路

城市交通 2013年第2期11卷 91-94页

作者： kenneth A.Small Chen Feng ng 姜洋解建华 kenneth A. Small Chen Feng ng 姜洋(译) 解建华(译) 加州大学尔湾分校经济系美国加州尔湾92697 加州州立大学经济系美国加州长滩90840 宇恒可持续交通研究中心北京100004

按照联邦州际高速公路系统设定的标准修建、扩容快速路耗资巨大,且对环境产生不利影响。然而由于交通拥堵,仅有少数出行者才能体验到快速驾驶的优势。探讨了道路设计的另一种思路——设计更紧凑的道路,或者说车道数更多但车道宽度更窄... 详细信息

按照联邦州际高速公路系统设定的标准修建、扩容快速路耗资巨大,且对环境产生不利影响。然而由于交通拥堵,仅有少数出行者才能体验到快速驾驶的优势。探讨了道路设计的另一种思路——设计更紧凑的道路,或者说车道数更多但车道宽度更窄的道路。对比常规设计和紧凑设计两种思路下快速路车速、通行能力、行程时间指标,结果显示在高峰时段车辆排队严重时,紧凑设计具有较明显的优势。由于紧凑设计对道路安全性的影响尚未定论,建议设置更低的限速并采取措施禁止超速行为。最后指出,紧凑设计可增加道路通行能力以缓解交通拥堵,因此其适用范围得到扩展。

关键词：道路设计通行能力自由流速度

Enhanced propellant performance via environmentally friendly curable surface coating

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Defence Technology（防务技术） 2017年第3期13卷 131-142页

作者： Thelma Manning Jeffrey Wyckoff kenneth Klingaman Viral Panchal Eugene Rozumov John Bolognini Ming Wang Young Subhash Patel US Army RDECOM ARDEC Picatinny Arsenal Polymer Processing Institute

Surface coating of granular propellants is widely used in a multiplicity of propellants for small, medium and large caliber ammunition. All small caliber ball propellants exhibit burning progressivity due to application of effective deterrent coatings. Large perforated propellant grains have also begun utilizing plasticizing and impregnated deterrent coatings with the purpose of increasing charge weights for greater energy and velocity for the projectile. The deterrent coating and impregnation process utilizes volatile organic compounds(VOCs) and hazardous air pollutants(HAPs) which results in propellants that need to be forced air dried which impacts air quality. Propellants undergo temperature fluctuations during their life. Diffusion coefficients vary exponentially with variations in temperature. A small temperature increase can induce a faster migration, even over a short period of time, which can lead to large deviations in the concentration. This large concentration change in the ammunition becomes a safety or performance liability. The presence of both polymeric deterrents and nitroglycerin(ng) in the nitrocellulose matrix and organic solvents leads to higher diffusion rates. This results in continued emissions of VOCs and HAPs. Conventional polymers tend to partition within the propellant matrix. In other words,localized mixing can occur between the polymer and underlying propellant. This is due to solvent induced softening of the polymer vehicle over the propellant grain. In effect this creates a path where migration can occur. Since nitrate esters, like ng, are relatively small, it can exude to the surface and create a highly unstable and dangerous situation for the warfighter. Curable polymers do not suffer from this partitioning due to "melting" because no VOC solvents are present. They remain surface coated. The small scale characterization testing, such as closed bomb testing, small scale sensitivity, thermal stability,and chemical compatibility, will

关键词：推进剂性能表面涂层可固化环境友好挥发性有机化合物有害空气污染物大口径弹药硝酸纤维素

儿童NTRK重排间叶源性肿瘤临床病理学观察

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中华病理学杂志 2020年第7期49卷 675-680页

作者：殷敏智马靖何巧沈萍陈洁枫金晓婷张忠德 Chik Hong Kuick Chen Huiyi Eileen Hui Qi ng Sze Jet Aw kenneth Tou En Chang 上海交通大学医学院附属上海儿童医学中心病理科 200127 Department of Pathology and Laboratory Medicine KK Women′s and Children′s HospitalSingapore 229899Singapore

目的:探讨儿童NTRK重排间叶源性肿瘤临床和病理学特征,以提高对该类疾病的认识。方法:收集上海交通大学医学院附属上海儿童医学中心及新加坡KK Women′s and Children′s Hospital从2017年1月至2019年9月5例手术切除标本,采用EnVision... 详细信息

目的:探讨儿童NTRK重排间叶源性肿瘤临床和病理学特征,以提高对该类疾病的认识。方法:收集上海交通大学医学院附属上海儿童医学中心及新加坡KK Women′s and Children′s Hospital从2017年1月至2019年9月5例手术切除标本,采用EnVision法检测免疫组织化学表型,荧光原位杂交(FISH)检测相关基因并对NTRK基因重排进行克隆性分析。结果:该组5例患儿,3例男性,2例女性。年龄从3个月到13岁,部位包括软组织(膝、胸腔、腹壁)和肾,肿瘤大小为4.5~12.5 cm。组织学检查主要呈梭形细胞肿瘤,浸润性生长,可伴有炎性细胞。免疫表型上,肿瘤细胞阳性表达Pan-TRK,分子检测均存在NTRK基因重排,包括DCTN1-NTRK1的发现。除2例目前接受靶向药物治疗,其余均为无疾病进展病例,随访时间9~29个月。结论:NTRK重排间叶源性肿瘤,其肿瘤发生部位广泛,组织学图像多变。免疫组织化学Pan-TRK可以帮助诊断,NTRK基因检测确认其存在重排是诊断的金标准,对不能完整切除或有复发、转移病例建议靶向药物治疗。

关键词：儿童免疫组织化学分子靶向治疗间叶源性肿瘤

Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5085-5095页

作者： Ye Peng Lin Zhang Chris K.P.Mok Jessica Y.L.Ching Shilin Zhao Matthew K.L.Wong Jie Zhu Chunke Chen Shilan Wang Shuai Yan Biyan Qin Yingzhi Liu Xi Zhang Chun Pun Cheung Pui Kuan Cheong Ka Long Ip Adrian C.H.Fung kenneth K.Y.Wong David S.C.Hui Francis K.L.Chan Siew C.ng Hein M.Tun Microbiota I-Center(MaglC) Hong KongChina Jockey Club School of Public Health and Primary Care The Chinese University of Hong KongHong KongChina Li Ka Shing Institute of Health Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Surgery LKS Faculty of MedicineThe University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina Centre for Gut Microbiota Research The Chinese University of Hong KongHong KongChina

The role of gut microbiota in modulating the durability of cOVID-19 vaccine immunity is yet to be *** this cohort study,we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline,1 month,and 6 months post vaccination(p.v).Neutralisation antibody,plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition.

关键词： vaccine immunity vaccines

Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels

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World Journal of Hepatology 2018年第2期10卷 308-318页

作者： Wong Hoi She Albert Chi Yan Chan Tan To Cheung Chung Mau Lo kenneth Siu Ho Chok Department of Surgery University of Hong Kong Department of Surgery and State Key Laboratory for Liver Research University of Hong Kong

AIM To investigate the impact of alpha-fetoprotein(AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patient *** Data of adult patients who received liver transplant(LT) for hepatocellular carcinoma(HCC) at our hospital from January 2000 to December 2013 were reviewed. Reviewed data included demographic characteristics, preoperative AFP level, operative details, follow-up details, and survival outcomes. Patients were mostly listed for LT based on Milan or UCSF criteria. For the purpose of this study, normal AFP level was defined as AFP value ng/m L, high AFP level was defined as AFP value ≥ 10 to ng/m L, and very highAFP level was defined as AFP ≥ 400 ng/m L. The patients were divided into these 3 groups accordingly. Survival rates were plotted as Kaplan-Meier curves and compared by log-rank analysis. Continuous variables were expressed as median(interquartile range). Categorical variables were compared by Spearman's test. Discriminative analysis was used to define the lowest value of AFP that could affect the overall survival in study population. Statistical significance was defined by a P value of ng-donor LT. The patients were divided into 3 groups: Group A, AFP ng/m L(n = 83); Group B, AFP ≥ 10 to ng/m L(n = 131); Group C, AFP ≥ 400 ng/m L(n = 36). The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar(median, 13 vs 13 vs 12; P = 0.745). The time to operation in Group A was longer(median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality(P = 0.626) and postoperative complication(P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, b

关键词： Alpha-fetoprotein Liver transplantation Recurrence Survival

Outcomes of combination MRI-targeted and transperineal template biopsy in restaging low-risk prostate cancer for active surveillance

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Asian Journal of Urology 2018年第3期5卷 184-193页

作者： kenneth Chen Kae Jack Tay Yan Mee Law Hakan Aydin Henry Ho Christopher Cheng John Shyi Peng Yuen Department of Urology Singapore General HospitalSingapore Department of Diagnostic Radiology Singapore General HospitalSingapore Department of Pathology Singapore General HospitalSingapore

Objective:Active surveillance(AS)offers a strategy to reduce overtreatment and now is a widely accepted treatment option for low-risk prostate *** ideal tool for risk-stratification would detect aggressive cancers and exclude such men from taking up AS in the first *** evaluate if a combination of transperineal template biopsy with magnetic resonance imaging(MRI)-targeted biopsy identifies significant prostate cancer amongst men initially diagnosed with low-risk prostate ***:This prospective,single-blinded study included men with low-risk prostate cancer(D’Amico’s Criteria)diagnosed on conventional transrectal ultrasound-guided *** first underwent multiparametric MRI of the prostate6 weeks after initial *** suspicious lesion is mapped and assigned a Prostate Imaging Reporting and Data System(PIRADS)*** biopsy is first performed with the surgeon blinded to MRI findings followed by MRI-targeted biopsy using a robotic transperineal biopsy ***:The age of the 19 men included is 65.4±4.9 years(mean±SD).Prostate specific antigen(PSA)at diagnosis and at the time of transperineal biopsy were comparable(7.3±1.7 ng/mL and 7.0±1.8 ng/mL,p Z 0.67),so were prostate volumes(34.2±8.9 mL and 32.1±13.4 mL,p Z 0.28).MRI-targeted biopsy had a higher percentage of cancer detection per core compared to template biopsy(11.7%vs.6.5%,p Z 0.02),this was more than 3 times superior for Gleason 7 disease(5.9%vs.1.6%,p<0.01).Four of 18(22.2%)patients with MRI lesions had significant disease with MRI-targeted biopsy *** of 19 patients(15.8%)had significant disease with template biopsy *** combination,both techniques upclassified five patients(26.3%),all of whom underwent radical *** mount histology confirmed tumour location and *** six patients with PIRADS 5 lesions had cancer detected(66.6%significant disease).Conclusion:A combination of MRI-targeted and template biopsy may optimally risk-classi

关键词： Active surveillance Magnetic resonance imaging Targeted biopsy Transperineal prostate biopsy Robotic biopsy Low-risk prostate cancer

Validated model for prediction of recurrent hepatocellular carcinoma after liver transplantation in Asian population

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World Journal of Gastrointestinal Oncology 2019年第4期11卷 322-334页

作者： Ka Wing Ma Wong Hoi She Albert Chi Yan Chan Tan To Cheung James Yan Yue Fung Wing Chiu Dai Chung Mau Lo kenneth Siu Ho Chok Department of Surgery the University of Hong Kong Department of Surgery and State Key Laboratory for Liver Research the University of Hong Kong Department of Medicine and State Key Laboratory for Liver Research The University of Hong Kong

BACKGROUND Liver transplantation(LT) is regarded as the best treatment for both primary and recurrent hepatocellular carcinoma(HCC). Post-transplant HCC recurrence rate is relatively low but significant, ranging from 10%-30% according to different series. When recurrence happens, it is usually extrahepatic and associated with poor prognosis. A predictive model that allows patient stratification according to recurrence risk can help to individualize post-transplant surveillance protocol and guidance of the use of anti-tumor immunosuppressive *** To develop a scoring system to predict HCC recurrence after LT in an Asian *** Consecutive patients having LT for HCC from 1995 to 2016 at our hospital were recruited. They were randomized into the training set and the validation set in a60:40 ratio. Multivariable Cox regression model was used to identity factors associated with HCC recurrence. A risk score was assigned to each factor according to the odds ratio. Accuracy of the score was assessed by the area under the receiver operating characteristic *** In total, 330 patients were eligible for analysis(183 in training and 147 invalidation). Recurrent HCC developed in 14.2% of them. The median follow-up duration was 65.6 mo. The 5-year disease-free and overall survival rates were78% and 80%, respectively. On multivariate analysis, alpha-fetoprotein > 400 ng/mL [P = 0.012, hazard ratio(HR) 2.92], sum of maximum tumor size and number(P = 0.013, HR 1.15), and salvage LT(P = 0.033, HR 2.08) were found to be independent factors for disease-free survival. A risk score was calculated for each patient with good discriminatory power(c-stat 0.748 and 0.85, respectively,in the training and validation sets). With the derived scores, patients were classified into low-(0–9), moderate-(> 9–14), and high-risk groups(> 14), and the risk of HCC recurrence in the training and validation sets was 10%, 20%, 54%(cstat 0.67) and 4%, 22%, 62%(c-stat 0.811), accordin

关键词： Hepatocellular carcinoma Liver transplantation Post-transplant recurrence Predictive model

Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype

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World Journal of Transplantation 2023年第6期13卷 368-378页

作者： Adam Diamond Sunil Karhadkar kenneth Chavin Serban Constantinescu Kwan N.Lau Oscar Perez-Leal Kerry Mohrien Nicole Sifontis Antonio Di Carlo Department of Pharmacy Temple University HospitalPhiladelphiaPA 19140United States Department of Surgery Temple University HospitalPhiladelphiaPA 19140United States Department of Medicine Temple University School of MedicinePhiladelphiaPA 19140United States Department of Pharmaceutical Sciences Jayne Haines Center for Pharmacogenomics and Drug SafetyTemple University School of PharmacyPhiladelphiaPA 19140United States Department of Pharmacy Practice Temple University School of PharmacyPhiladelphiaPA 19140United States

BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant *** requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 *** who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo *** To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 *** Single-arm,prospective,single-center,open-label,observational study(***:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body *** weight is more than 120%of ideal body weight,an adjusted body weight was *** dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/*** analysis of CYP3A5 genotype was performed at study *** Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d *** adverse events were reported for 13(36%)*** Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release

关键词： Immunosuppression Kidney transplant Dosing Tacrolimus Therapeutic drug monitoring Genotype