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Appraisal of the current guidelines for management of cholangiocarcinoma-using the Appraisal of Guidelines Research and Evaluation Ⅱ (AGREE Ⅱ) Instrument

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Hepatobiliary Surgery and Nutrition 2020年第2期9卷 126-135,中插1页

作者： Paschalis Gavriilidis Alan Askari keith j.roberts Robert P.Sutcliffe Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery Queen Elizabeth University Hospitals Birmingham NHS Foundation TrustBirminghamUK Department of Upper Gastro-Intestinal Surgery West Hertfordshire Hospitals NHS TrustWatfordUK

Cholangiocarcinoma(CC)is the second most common primary liver ***-quality guidelines are essential for effective patient stratification and individualised *** study aimed to appraise the methodological quality of existing guidelines for the resection of CC using the Appraisal of Guidelines for Research&Evaluation(AGREE II)instrument.A systematic search of the literature in Cochrane,PubMed,Google Scholar,and Embase was *** of the clinical practice guidelines(CPGs)and consensuses was performed using the AGREE II instrument by four clinicians experienced in surgical practice and the AGREE II appraisal *** searches identified 13 guidelines of highly variable quality according to the AGREE II *** guidelines scored well in certain domains such as scope&purpose(median score across all guidelines;65%),clarity of presentation(76%),and editorial independence(56%).However,they scored poorly for applicability(13%),rigour of development(30%),and stakeholder involvement(39%).None of the 13 guidelines was recommended universally for use without ***,the methodological quality of guidelines on the surgical management of CC is *** updates should address and modify shortcomings detected by the AGREE II instrument,thereby facilitating better patient stratification and individualised treatment strategies.

关键词： Cholangiocarcinoma(CC) clinical practice guidelines(CPGs) Appraisal of Guidelines for Research and Evaluation instrument(AGREE II instrument)

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Distinct risk factors for early and late blood transfusion following pancreaticoduodenectomy

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Hepatobiliary & Pancreatic Diseases International 2018年第4期17卷 349-357页

作者： Sukhchain S.Bansal james Hodson Khalid Khalil Bobby Dasari Ravi Marudanayagam Robert P.Sutcliffe john Isaac keith j.roberts Department of Hepatobiliary Pancreatic Surgery Queen Elizabeth Hospital BirminghamUniversity Hospitals Birmingham Institute of Translational Medicine Queen Elizabeth Hospital BirminghamUniversity Hospitals Birmingham

Background: The International Study Group of Pancreatic Surgery(ISGPS) has defined two periods of postpancreatectomy hemorrhage, early(24 h). A previously published Blood Usage Risk Score(BURS) aimed to predict early and late blood transfusion. The primary aim of this study was to define risk factors for early and late blood transfusion after pancreaticoduodenectomy. Secondary aims were to assess the predictive accuracy of the ***: In this retrospective observational study, multivariable analyses were used to identify independent risk factors for both early and late blood transfusion. The predictive ability of the BURS was then assessed using a receiver operating characteristic(ROC) curve ***: Among 628 patients, 99(15.8%) and 144(22.9%) received early and late blood transfusion, respectively. Risk factors for blood transfusion differed between early and late periods. Preoperative anemia and venous resection were associated with early blood transfusion whilst Whipple’s resection(as opposed to pylorus preserving pancreaticoduodenectomy), lack of biliary stent and a narrow pancreatic duct were predictors of late blood transfusion. The BURS was significantly predictive of early blood transfusion,albeit with a modest degree of accuracy(AUROC: 0.700, P < 0.001), but not of late blood transfusion(AUROC: 0.525, P = 0.360). Late blood transfusion was independently associated with increasing severity of postoperative pancreatic fistula(POPF)(OR: 1.85, 3.18 and 9.97 for biochemical, types B and C POPF,respectively, relative to no POPF).Conclusions: Two largely different sets of variables are related to early and late blood transfusion following pancreaticoduodenectomy. The BURS was significantly associated with early, albeit with modest predictive accuracy, but not late blood transfusion. An understanding of POPF risk allows assessment of the need for late blood transfusion.

关键词： Pancreatic cancer Blood transfusion Pancreaticoduodenectomy

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美国大学的办学理念及其影响

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国家教育行政学院学报 2008年第7期 87-90页

作者： keith j.roberts Y．K．Peter Chan 王永颜(翻译) 美国杨百翰大学学术副校长、博士美国杨百翰大学教育技术副教授、博士河北师范大学成人教育学院在读硕士研究生

美国的大学使用英语作为教学用语,其著名大学的排名位居世界前列,使成千上万的海外学子赴美求学。美国大学对世界的影响在于其先进的理念和良好的学术环境。

关键词：美国大学理念影响

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Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 421-427页

作者： Manish Ahuja Kunal joshi Chris Coldham Paulo Muiesan Bobby Dasari Manuel Abradelo Ravi Marudanayagam Darius Mirza john Isaac David Bartlett Nikolaos A Chatzizacharias Robert P Sutcliffe keith j.roberts Department of HPB and Liver Transplant Surgery University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Immunology and Immunotherapy University of BirminghamBirminghamUK

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor *** median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are *** resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal ***,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.

关键词： hepatectomy surgery mortality

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Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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World journal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： jeffrey A Lowell Michael j Farber keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States Preclinical Studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined *** et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this *** importance of controlled trials should be stressed in establishing new treatment *** prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy

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Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy

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World journal of Gastrointestinal Surgery 2024年第8期16卷 2689-2701页

作者： Lewis A Hall Duncan Loader Santiago Gouveia Marta Burak james Halle-Smith Peter Labib Moath Alarabiyat Ravi Marudanayagam Bobby V Dasari keith j.roberts Syed S Raza Michail Papamichail David C Bartlett Robert P Sutcliffe Nikolaos A Chatzizacharias Department of Hepatopancreatobiliary Surgery and Liver Transplantation University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWUnited Kingdom Institute of Immunology and Immunotherapy University of BirminghamBirmingham B152TTUnited Kingdom College of Medical and Dental Sciences University of BirminghamBirmingham B152TTUnited Kingdom Institute of Clinical Sciences University of BirminghamBirmingham B152TTUnited Kingdom

BACKGROUND The use of neoadjuvant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is *** To synthesise evidence on NAT for dCCA and present the experience of a highvolume tertiary-centre managing dCCA with arterial *** A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received *** patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained *** characteristics,NAT type,progression to surgery and oncological outcomes were *** Twelve studies were *** definition of“unresectable”locally advanced dCCA was *** studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement.R0 resection rate ranged between 0 and 100%but without survival benefit in most *** studies considered either NAT in resectable dCCA or inclusive with extrahepatic *** presented case series includes 9 patients(median age 67,IQR 56-74 years,male:female 5:4)referred for NAT for borderline resectable or locally advanced *** patients progressed to surgery and 2 were *** patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months *** Evidence for benefit of NAT is *** on criteria for uniform definition of resectability for dCCA is *** propose using the established National-Comprehensive-Cancer-Network®criteria for pancreatic ductal adenocarcinoma.

关键词： Cholangiocarcinoma Neoadjuvant therapy Arterial involvement Locally advanced Systematic review

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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell jun Okabe Ishant Khurana Thomas Karagiannis julia j.Liang Lina Mariana Thomas Loudovaris Thomas Kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

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SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation

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World journal of Transplantation 2024年第3期14卷 132-143页

作者： Amr Alnagar Nekisa Zakeri Konstantinos Koilias Rosemary E Faulkes Rachel Brown Owen Cain M Thamara P R Perera keith j.roberts Rebeca Sanabria-Mateos David C Bartlett Yuk Ting Ma Shivan Sivakumar Shishir Shetty Tahir Shah Bobby V M Dasari Department of HBP and Liver Transplantation Surgery Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152GWUnited Kingdom Centre for Liver Research Institute of Biomedical ResearchBirmingham B152TTUnited Kingdom Department of Hepatology Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152GWUnited Kingdom Department of Pathology University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWUnited Kingdom Department of Oncology Queen Elizabeth HospitalUniversity Hospitals of BirminghamBirmingham B152GWUnited Kingdom

BACKGROUND Recurrence of hepatocellular carcinoma(HCC)following liver transplantation(LT)has a devastating influence on recipients’survival;however,the risk of recur-rence is not routinely *** stratification is vital with a long LT waiting time,as that could influence the recurrence despite strict listing *** This study aims to identify predictors of recurrence and develop a novel risk pre-diction score to forecast HCC recurrence following *** A retrospective review of LT for HCC recipients at University Hospitals Bir-mingham between july 2011 and February *** and multivariate analyses were performed to identify recurrence predictors,based on which the novel SIMAP500(satellite nodules,increase in size,microvascular invasion,AFP>500,poor differentiation)risk score was *** 234 LTs for HCC were performed with a median follow-up of 5.3 *** developed in 25 patients(10.7%).On univariate analyses,RETREAT score>3,α-fetoprotein(AFP)at listing 100-500 and>500,bridging,increased tumour size between imaging at the listing time and explant histology,increase in the size of viable tumour between listing and explant,presence of satellite nodules,micro-and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence,based on which,the SIMAP500 risk score is *** SIMAP500 demonstrated an excellent predictive ability(c-index=0.803)and outper-formed the RETREAT score(c-index=0.73).SIMAP500 is indicative of the time to disease *** SIMAP500 risk score identifies the LT recipients at risk of HCC *** stratification allows patient-centric post-transplant surveillance *** validation of the score is recommended.

关键词： Liver transplantation Hepatocellular carcinoma Recurrence Survival

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： jason Philip Appleton Lisa j Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy j England Kailash Krishnan Grant Mair keith W Muir john Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Terlipressin versus placebo in living donor liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2022年第1期21卷 76-79页

作者： Paschalis Gavriilidis Ernest Hidalgo Robert P Sutcliffe keith j.roberts Department of Hepato-Pancreato-Biliary and Liver Transplant surgery Queen Elizabeth University Hospitals Birmingham NHS Foundation TrustBirmingham B152THUK Department of Hepato-Pancreatico-Biliary Surgery and Transplantation Hospital Universitari Vall d’HebronBarcelona 08035Spain

To the Editor:Terlipressin is a long-acting synthetic analogue of vasopressin,demonstrating several potential benefits in the context of living donor liver transplantation(LDLT).During the recipient hepatec-tomy,terlipressin reduces the portal ***,it may mitigate the extent of bowel congestion following portal vein *** decreasing portal hyperperfusion and hypertension,it protects the graft from further injury and improves renal blood flow.

关键词： donor liver Terlipressin

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