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World Journal of Gastroenterology 2022年第48期28卷 6922-6934页

作者： Bianca Della Guardia Amanda P C S boteon Celso E l Matielo Guilherme Felga yuri l boteon liver Unit Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil Instituto Israelita de Ensino e Pesquisa Albert Einstein Faculdade Israelita de Ciências da Saúde Albert EinsteinSão Paulo 05652-900Brazil

Acute-on-chronic liver failure(AClF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term *** due to the lack of universal diagnostic criteria,the actual AClF prevalence remains unclear;nevertheless,it is expected to be a highly prevalent condition *** transplantation is an effective protective measure for selected AClF *** liver transplantation,diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of AClF *** new clinical specific therapies have been researched,more studies are necessary to assess safety and ***,future AClF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently ***,an urgent and global discussion about allocation and prioritization for transplantation in critically ill AClF patients is needed because there is evidence suggesting that the current model may not portray their waitlist *** addition,while donor organ quality is meant to be a prognostic factor in the AClF setting,recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.

关键词： Acute-on-chronic liver failure liver cirrhosis liver transplantation Machine perfusion Hypothermic oxygenated machine perfusion

Machine perfusion of the liver: Which is the best technique to mitigate ischaemia-reperfusion injury?

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World Journal of Transplantation 2019年第1期9卷 14-20页

作者： yuri l boteon Simon C Afford liver Unit Queen Elizabeth HospitalUniversity Hospitals Birmingham NHS Foundation Trust Centre for liver and Gastrointestinal Research Institute of Immunology and ImmunotherapyCollege of Medical and Dental SciencesUniversity of Birmingham National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre University of Birmingham and University Hospitals Birmingham NHS Foundation Trust

longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, called ischaemia-reperfusion injury(IRI), leads to parenchymal cell death,microcirculatory failure, and inflammatory immune response. Clinically, IRI is the main factor responsible for the occurrence of posttransplant graft dysfunction and ischaemic-type biliary lesions. While extended criteria donor livers are more vulnerable to IRI, their utilisation is required to address the shortfall in donor organs. Thus, the mitigation of IRI should drive the setting of a new benchmark for marginal organ preservation. Herein, strategies incorporating different modalities of machine perfusion of the liver to alleviate IRI are discussed in conjunction with advantages and disadvantages of individual *** leading to reperfusion of the liver during machine perfusion(in situ normothermic regional perfusion and ex situ normothermic machine perfusion)may mitigate IRI by shortening the ischaemic period of the organs. This benefit potentially escalates from the minimum level, obtained following just partial alleviation of the ischaemic period, to the maximum level, which can be potentially achieved with ischaemia-free organ transplantation. Techniques that do not lead to reperfusion of the liver during machine perfusion(hypothermic,subnormothermic, and controlled-oxygenated rewarming) optimise mitochondrial oxidative function and replenish cellular energy stores, thereby lowering reactive oxygen species production as well as the activation ofdownstream inflammatory pathways during reperfusion. Further mechanistic insights into IRI may guide the development of donor-specific protocols of machine perfusion on the basis of the limitations of individual categories of extended criteria donor organs.

关键词： Machine perfusion of the liver Ischaemia-reperfusion injury liver transplantation Organ preservation Organ reconditioning

Machine perfusion of the liver:Putting the puzzle pieces together

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World Journal of Gastroenterology 2021年第34期27卷 5727-5736页

作者： yuri l boteon Paulo N Martins Paolo Muiesan Andrea Schlegel liver Unit Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil Instituto Israelita de Ensino e Pesquisa Albert Einstein Faculdade Israelita de Ciências da Saúde Albert EinsteinSão Paulo 05652-900Brazil Department of Surgery Transplant DivisionUniversity of Massachusetts Medical SchoolWorcesterMA 01655United States Hepatobiliary Unit Careggi University HospitalUniversity of FlorenceFlorence 50134Italy Department of Visceral Surgery and Transplantation University Hospital ZurichSwiss HPB and Transplant CenterZurich 8091Switzerland

The realm of extended criteria liver transplantation created the'adjacent possible'for dynamic organ *** perfusion of the liver greatly expanded donor organ preservation possibilities,reaching before unattainable goals,including the mitigation of ischemia-reperfusion injury,viability assessment,and organ reconditioning prior to ***,current scientific evidence lacks uniformity between studies,perfusion protocols,and acceptance *** of collaborative research networks for sharing knowledge should,therefore,enable the development of high-level evidence and guidelines for machine perfusion utilization,including donor acceptance ***,this approach shall guarantee conditions for further progress to occur.

关键词： Machine perfusion of the liver liver transplantation Organ donation Extended criteria donors liver preservation Clinical trials

Extended criteria brain-dead organ donors:Prevalence and impact on the utilisation of livers for transplantation in Brazil

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World Journal of Hepatology 2023年第2期15卷 255-264页

作者： Victoria S Braga Amanda P C S boteon Heloisa B Paglione Rafael A A Pecora yuri l boteon Faculdade Israelita de Ciências da Saúde Albert Einstein Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil Transplant Centre Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil

BACKGROUND Despite its association with higher postoperative morbidity and mortality,the use of extended criteria donor(ECD)livers for transplantation has increased globally due to the high demand for the *** To investigate the prevalence of ECD in donation after brain death(DBD)and its impact on organ acceptance for *** Retrospective analysis of DBD organ offers for liver transplantation between 2017 and 2020 in a high-volume transplant *** incidence of the Eurotransplant risk factors to define an ECD(ET-ECD)among DBD donors and the likelihood of organ acceptance over the years were *** relationship between organ refusal for transplantation,the occurrence,and the number of ET-ECD was assessed by simple and multiple logistic regression *** A total of 1619 organ donors were *** these,78.31%(n=1268)had at least one ET-ECD *** was an increase in the acceptance of ECD DBD organs for transplantation(1 criterion:from 23.40%to 31.60%;2 criteria:from 13.10%to 27.70%;3 criteria:From 6.30%to 13.60%).For each addition of one ETECD variable,the estimated chance of organ refusal was 64.4%higher(OR 1.644,95%CI 1.469-1.839,P165 mmol/l(P=0.310),all ET-ECD criteria increased the estimated chance of organ refusal for *** A high prevalence of ECD DBD was *** the increase in their utilisation,the presence and the number of extended donor criteria were associated with an increased likelihood of their refusal for transplantation.

关键词： liver transplantation Extended criteria donors Donation after brain death Organ donation

Update on the management and treatment of viral hepatitis

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World Journal of Gastroenterology 2021年第23期27卷 3249-3261页

作者： Patricia Holanda Almeida Celso E l Matielo lilian A Curvelo Rodrigo A Rocco Guilherme Felga Bianca Della Guardia yuri l boteon liver Unit Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil Instituto Israelita de Ensino e Pesquisa Albert Einstein Faculdade Israelita de Ciências da Saúde Albert EinsteinSão Paulo 05652-900Brazil

This review aims to summarize the current evidence on the treatment of viral hepatitis,focusing on its clinical ***,future treatment options and areas of potential research interest are *** and Scopus databases were searched for primary studies published within the last ten *** included hepatitis A virus,hepatitis B virus(HBV),hepatitis C virus,hepatitis D virus(HDV),hepatitis E virus,and *** reported in the studies were summarized,tabulated,and *** advances in viral hepatitis treatment were accomplished,such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A,hepatitis B,and hepatitis E *** that cure hepatitis B,going beyond viral suppression,are so far unavailable;however,targeted antiviral drugs against HBV(immunomodulatory therapies and gene silencing technologies)are promising approaches to eradicating the ***,high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health *** development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B,albeit further investigation is *** therapeutic options targeting HDV life cycle are currently under clinical investigation.

关键词： Viral hepatitis Hepatitis A virus Hepatitis B virus Hepatitis C virus Hepatitis D virus Hepatitis E virus

Exercise training as an intervention for frailty in cirrhotic patients on the liver transplant waiting list:A systematic review

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World Journal of Hepatology 2023年第10期15卷 1153-1163页

作者： Thais Mellato loschi Melline D T A Baccan Bianca Della Guardia Paulo N Martins Amanda P C S boteon yuri l boteon Transplant Centre Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil Instituto Israelita de Ensino e Pesquisa Albert Einstein Faculdade Israelita de Ciências da Saúde Albert EinsteinSão Paulo 05652-900Brazil Department of Surgery Transplant DivisionUniversity of Massachusetts Medical SchoolWorcesterMA 01655United States

BACKGROUND The existing literature suggests that exercise for cirrhotic patients is safe and favours significant improvement to their physical ***,exercise training for this population and how to deliver activities,especially in severe stages of the disease and while waiting for a liver transplant(lT),remain *** To review the existing exercise prescriptions for cirrhotic patients on the waiting list for lT,their results for frailty evolution and their effect on clinical *** A systematic review was performed following the Preferred Reporting Review and Meta-Analysis guidelines and searching the PubMed,MEDlINE,and Scopus *** keyword“liver transplant”was used in combination with the free terms“frailty”and“exercise”for the literature *** studies that evaluated the effect of a regular training program,independent of supervision or the duration or intensity of physical exercise,in cirrhotic patients on the waiting list for lT were *** data on safe physical activity prescriptions following Frequency,Intensity,Time,and Type recommendations were extracted and *** Nine articles met the inclusion criteria for this *** instruments for frailty assessment were used,frequently in *** studies prescribed physical activity for patients,one in-person and four to be performed remotely and *** remaining four studies only used a self-report instrument to assess the level of physical *** reported adverse events related to exercise *** exercise frequency mainly varied from daily to a minimum of twice per *** intensity depended on frailty and included increasing levels of *** type of exercise was predominantly a combination of aerobic and resistance *** duration of exercise varied from 4 to 12 *** articles evaluated the effect of the exercise program on clinical outcomes,reporting a reduction in 90-d readmission rates post-tran

关键词： End-stage liver disease liver transplant Frailty Exercise Rehabilitation Sarcopenia

Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion

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World Journal of Gastroenterology 2017年第48期23卷 8443-8451页

作者： yuri l boteon Richard laing Hynek Mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal The liver Unit University Hospitals of BirminghamMindelsohn Way The Centre for liver Research Institute for Biomedical ResearchUniversity of Birmingham

Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(lSEC). Recent evidence suggests that lSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular lSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-l) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-l to reduce liver IRI.

关键词： Autophagy liver transplant Ischaemiareperfusion injury Normothermic machine liver perfusion

Impact of machine perfusion of the liver on post-transplant biliary complications: A systematic review

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World Journal of Transplantation 2018年第6期8卷 220-231页

作者： yuri l boteon Amanda PCS boteon Joseph Attard lorraine Wallace Ricky H Bhogal Simon C Afford liver Unit Queen Elizabeth Hospital University Hospitals Birmingham NHS Foundation Trust Centre for liver and Gastrointestinal Research Institute of Immunology and Immunotherapy College of Medical and Dental Sciences University of Birmingham National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre University of Birmingham and University Hospitals Birmingham NHS Foundation Trust

AIM To review the clinical impact of machine perfusion(MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions(ITBl). METHODS This systematic review was performed in accordance with the Preferred Reporting Systematic Reviews and MetaAnalysis(PRISMA) protocol. The following databases were searched: PubMed, MEDlINE and Scopus. The keyword "liver transplantation" was used in combination with the free term "machine perfusion". Clinical studies reporting results of transplantation of donor human livers following ex situ or in situ MP were analysed. Details relating to donor characteristics, recipients, technique of MP performed and post-operative biliary complications(ITBl, bile leak and anastomotic strictures) were critically *** Fifteen articles were considered to fit the criteria for this review. Ex situ normothermic MP was used in 6 studies, ex situ hypothermic MP in 5 studies and the other 4 studies investigated in situ normothermic regional perfusion(NRP) and controlled oxygenated rewarming. MP techniques which have per se the potential to alleviate ischaemia-reperfusion injury: Such as hypothermic MP and NRP, have also reported lower rates of ITBl. Other biliary complications, such as biliary leak and anastomotic biliary strictures, are reported with similar incidences with all MP techniques. There is currently less clinical evidence available to support normothermic MP as a mitigator of biliary complications following liver transplantation. On the other hand, restoration of organ to full metabolism during normothermic MP allows assessment of hepatobiliary function before transplantation, although universally accepted criteria have yet to be *** MP of the liver has the potential to have a positive impact on post-transplant biliary complications, specifically ITBl, and expand extended criteria donor livers utilisation.

关键词： liver transplantation Ex situ machine perfusion of the liver Donation after circulatory death Non-anastomotic intra-hepatic stricture Ischemic-type biliary lesions Extended criteria donors

Parallel Algorithm and Software for Image Inpainting via Sub-Riemannian Minimizers on the Group of Rototranslations

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Numerical Mathematics(Theory,Methods and Applications) 2013年第1期6卷 95-115页

作者： Alexey P.Mashtakov Andrei A.Ardentov yuri l.Sachkov Program Systems Institute Pereslavl-ZalesskyRussia

The paper is devoted to an approach for image inpainting developed on the basis of neurogeometry of vision and sub-Riemannian *** is realized by completing damaged isophotes(level lines of brightness)by optimal curves for the left-invariant sub-Riemannian problem on the group of rototranslations(motions)of a plane SE(2).The approach is considered as anthropomorphic inpainting since these curves satisfy the variational principle discovered by neurogeometry of vision.A parallel algorithm and software to restore monochrome binary or halftone images represented as series of isophotes were *** approach and the algorithm for computation of completing arcs are presented in detail.

关键词： Image inpainting sub-Riemannian geometry neurogeometry of vision group of rototranslations of a plane parallel software

Neurohumoral,cardiac and inflammatory markers in the evaluation of heart failure severity and progression

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Journal of Geriatric Cardiology 2021年第1期18卷 47-66页

作者： Ekaterina A Polyakova Evgeny N Mikhaylov Dmitry l Sonin yuri V Cheburkin Mikhail M Galagudza Almazov National Medical Research Centre Saint-PetersburgRussia

Heart failure is common in adult population,accounting for substantial morbidity and mortality *** main risk factors for heart failure are coronary artery disease,hypertension,obesity,diabetes mellitus,chronic pulmonary diseases,family history of cardiovascular diseases,cardiotoxic *** main factor associated with poor outcome of these patients is constant progression of heart *** the current review we present evidence on the role of established and candidate neurohumoral biomarkers for heart failure progression management and diagnostics.A growing number of biomarkers have been proposed as potentially useful in heart failure patients,but not one of them still resembles the characteristics of the"ideal biomarker."A single marker will hardly perform well for screening,diagnostic,prognostic,and therapeutic management ***,the pathophysiological and clinical significance of biomarkers may depend on the presentation,stage,and severity of the *** authors cover main classification of heart failure phenotypes,based on the measurement of left ventricular ejection fraction,including heart failure with preserved ejection fraction,heart failure with reduced ejection fraction,and the recently proposed category heart failure with mid-range ejection *** could envisage specific sets of biomarker with different performances in heart failure progression with different left ventricular ejection fraction especially as concerns prediction of the future course of the disease and of left ventricular adverse/reverse *** article is intended to provide an overview of basic and additional mechanisms of heart failure progression will contribute to a more comprehensive knowledge of the disease pathogenesis.

关键词： cardiac and inflammatory markers in the evaluation of heart failure severity and progression Neurohumoral