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Translational research and innovation in modern transplant practice:Paradigms from Greece and around the world

World Journal of transplantation 2023年第2期13卷 25-27页

作者： Georgios Tsoulfas Ioannis Boletis Vassilios Papalois Department of transplantation Surgery Aristotle University School of MedicineThessaloniki 54124Greece Department of Nephrology EKPA UniversityAthens 11527Greece Department of transplant Surgery Imperial College Renal and Transplant CentreLondon W120HSUnited Kingdom

The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially *** goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the *** from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and *** papers that are part of this Special Issue“Translational Research and Innovation and the current status of transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and *** provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant ***,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational *** as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial *** this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine

关键词： Translational research Non-alcoholic fatty liver disease Immunotherapy Pandemic Liver transplantation Bioengineering Artificial intelligence Immunosuppression transplant oncology Living donor kidney transplantation

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Risk factors and outcomes of delayed graft function in renal transplant recipients receiving a steroid sparing immunosuppression protocol

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World Journal of transplantation 2017年第1期7卷 34-42页

作者： Michelle Willicombe Anna Rizzello Dawn Goodall Vassilios Papalois Adam G Mc Lean David Taube imperial college kidney and transplant centre Hammersmith Hospital

AIM To analyse the risk factors and outcomes of delayed graft function(DGF) in patients receiving a steroid sparing protocol. METHODS Four hundred and twenty-seven recipients of deceased donor kidney transplants were studied of which 135(31.6%) experienced DGF. All patients received monoclonal antibody induction with a tacrolimus based, steroid sparing immunosuppression *** Five year patient survival was 87.2% and 94.9% in the DGF and primary graft function(PGF) group respectively, P = 0.047. Allograft survival was 77.9% and 90.2% in the DGF and PGF group respectively, P transplant period than the group with DGF who received alemtuzumab induction. On multivariate analysis, risk factors for DGF were male recipients, recipients of black ethnicity, circulatory death donation, preformed DSA, increasing cold ischaemic time, older donor age and dialysis *** Alemtuzumab induction may be of benefit in preventing early rejection episodes associated with DGF. Prospective trials are required to determine optimal immunotherapy protocols for patients at high risk of DGF.

关键词： Allograft failure Deceased donors Delayed graft function Cold ischaemic time Rejection Steroid sparing Alemtuzumab

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Renal transplantation in gigantism: A case report

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World Journal of transplantation 2022年第4期12卷 65-71页

作者： Jeevan Prakash Gopal Sotirios Charalampidis Jinpo Xiang Frank JMF Dor Vassilios E Papalois imperial college Renal and transplant Center Imperial College Healthcare NHS TrustHammersmith HospitalLondon W120HSUnited Kingdom imperial college School of Medicine Imperial CollegeLondon W120HSUnited Kingdom Department of Surgery and Cancer Imperial CollegeLondon W120HSUnited Kingdom

BACKGROUND Gigantism,characterized by excessive growth and height is due to increased secretion of growth hormone,most commonly from a pituitary *** addition to the surgical and anesthetic complexity,the extreme stature of these patients presents a unique challenge for kidney transplantation in deciding whether to proceed with a single or dual kidney *** lack of relevant literature further adds to the *** SUMMARY A 45-year-old patient with untreated gigantism and end stage renal failure on renal replacement therapy was waitlisted for a deceased donor dual kidney transplantation due to the extreme physical stature(Height-247 cm and weight-200 kg).He was offered 2 kidneys from a 1-0-1 HLA mismatched 24-year-old DCD donor(Height-179 cm and weight-75 kg),and was planned for a bilateral retroperitoneal implantation into the recipient external iliac *** immunosuppression consisted of alemtuzumab induction(50 mg)and steroidfree maintenance with *** donor’s right kidney was uneventfully implanted extra-peritoneally into the right external iliac *** contralateral exposure,the left common and external iliac arteries were ectatic and frail.A complex vascular reconstruction was not preferred in order to preserve the arterial supply to the left lower limb,to minimise the cold ischemia time and prevent additional warm ischemic insult to the second ***,it was decided not to proceed with dual *** concerns of nephron mass insufficiency,the graft function was remarkable with a serum creatinine of 120μmol/L within a month from transplantation and 94μmol/L at 1-year post transplantation,and without *** To our knowledge,this is the first case report on kidney transplantation in *** it is believed that dual kidney transplantation is ideal,a single kidney transplantation from an appropriately selected donor can provide sufficient functioning nephron mass in patients with

关键词： Gigantism Giantism Renal transplantation kidney transplantation Pituitary adenoma Case report

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Unspecified live kidney donation by urological patients

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World Journal of transplantation 2020年第8期10卷 215-222页

作者： Sebastiaan Ceuppens Hendrikus J A N Kimenai Karel W J Klop Willij C Zuidema Michiel G H Betjes Willem Weimar Jan N M IJzermans Frank J M F Dor Robert C Minnee Division of transplant Surgery Department of SurgeryErasmus MC University Medical CenterRotterdam 3015GDNetherlands Department of Internal Medicine Nephrology and Kidney Transplant UnitRotterdam 3000CANetherlands imperial college Renal and transplant Unit Hammersmith HospitalImperial College Healthcare NHS TrustLondon W120HSUnited Kingdom

BACKGROUND Individuals with benign kidney disorders undergoing nephrectomy have three possibilities:Autotransplantation,with a certain risk of complications,but without a clear benefit;discarding the kidney;or living kidney *** To investigate whether patients with benign kidney disorders and a medical indication for nephrectomy are suitable as unspecified live kidney *** We searched all clinical data from 1994-2019 for unspecified donors and their transplant recipients(n=160).Nine of these 160 donors had pre-existing kidney disorders necessitating nephrectomy and had decided to donate their kidney anonymously after discussing the possibility of kidney *** studied the clinical course of these nine donating patients and their transplant *** Seven of nine donating patients indicated unbearable loin pain as the main complaint,one donating patient refused ureterocutaneostomy and one had two aneurysms of the renal ***,seven donating patients described absence of pain and one a significant reduction after the *** average 1-year creatinine level in the donating patients was 88μmol/L and after a median of 6.9 years the average creatinine level was 86.6μmol/*** the transplant recipients,one major complication occurred which led to death and in one transplant recipient graft function failed to normalize at first but has been stable for nine years ***,all transplant recipients are off *** Our data show that patients undergoing nephrectomy as part of treatment in selected kidney disorders can function as live kidney donors.

关键词： Unspecified donor Live kidney donation Benign kidney disorder Living donors kidney transplantation

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Anticoagulation in simultaneous pancreas kidney transplantation - On what basis?

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World Journal of transplantation 2020年第7期10卷 206-214页

作者： Jeevan Prakash Gopal Frank JMF Dor Jeremy S Crane Paul E Herbert Vassilios E Papalois Anand SR Muthusamy imperial college Renal and transplant Center Imperial College Healthcare NHS TrustHammersmith HospitalLondon W120HSUnited Kingdom Department of Surgery and Cancer Imperial CollegeLondon W120HSUnited Kingdom

BACKGROUND Despite technical refinements,early pancreas graft loss due to thrombosis continues to *** coagulation tests(CCT)do not detect hypercoagulability and hence the hypercoagulable state due to diabetes is left ***(TEG)is an in-vitro diagnostic test which is used in liver transplantation,and in various intensive care settings to guide *** is better than CCT because it is dynamic and provides a global hemostatic profile including *** To compare the outcomes between TEG and CCT(prothrombin time,activated partial thromboplastin time and international normalized ratio)directed anticoagulation in simultaneous pancreas and kidney(SPK)transplant *** A single center retrospective analysis comparing the outcomes between TEG and CCT-directed anticoagulation in SPK recipients,who were matched for donor age and graft type(donors after brainstem death and donors after circulatory death).Anticoagulation consisted of intravenous(IV)heparin titrated up to a maximum of 500 IU/h based on CCT in conjunction with various clinical parameters or directed by TEG *** loss due to thrombosis,anticoagulation related bleeding,radiological incidence of partial thrombi in the pancreas graft,thrombus resolution rate after anticoagulation dose escalation,length of the hospital stays and,1-year pancreas and kidney graft survival between the two groups were *** Seventeen patients who received TEG-directed anticoagulation were compared against 51 contemporaneous SPK recipients(ratio of 1:3)who were anticoagulated based on *** graft losses occurred in the TEG group,whereas 11 grafts(7 pancreases and 4 kidneys)were lost due to thrombosis in the CCT group(P=0.06,Fisher’s exact test).The overall incidence of anticoagulation related bleeding(hematoma/gastrointestinal bleeding/hematuria/nose bleeding/re-exploration for bleeding/post-operative blood transfusion)was 17.65%in the TEG group and 45

关键词： Anticoagulation Pancreas transplantation Thromboelastography Thrombosis Hypercoagulability

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Acute kidney injury following adult lung transplantation

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Chinese Medical Journal 2022年第2期135卷 172-180页

作者： Lei Jing Wenhui Chen Li Zhao Lijuan Guo Chaoyang Liang Jingyu Chen Chen Wang Chinese Academy of Medical Sciences and Peking Union Medical college Beijing 100730China Department of Lung transplantation Centre of Lung TransplantationCentre of Respiratory DiseasesChina-Japan Friendship HospitalBeijing 100029China National Center for Respiratory Medicine Beijing 100029China Institute of Respiratory Medicine Chinese Academy of Medical SciencesBeijing 100029China National Clinical Research Center for Respiratory Diseases Beijing 100029China Wuxi Lung transplant Center Wuxi People's Hospital affiliated to Nanjing Medical UniversityWuxiJiangsu 214023China

Background:Acute kidney injury(AKI)is a common and serious complication following lung transplantation(LTx),and it is associated with high mortality and *** study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical ***:This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December *** outcomes were AKI incidence,risk factors,mortality,and kidney *** analysis was performed to identify independent risk *** analysis was presented using the Kaplan-Meier ***:AKI occurred in 137 of the 191 patients(71.7%),with transient AKI in 43(22.5%)and persistent AKI in 94(49.2%).AKI stage 1 occurred in 27/191(14.1%),stage 2 in 46/191(24.1%),and stage 3 in 64/191(33.5%)of the AKI *** replacement therapy(RRT)was administered to 35/191(18.3%)of the *** sex,older age,mechanical ventilation(MV),severe hypotension,septic shock,multiple organ dysfunction(MODS),prolonged extracorporeal membrane oxygenation(ECMO),reintubation,and nephrotoxic agents were associated with AKI(Pkidney function,and reduced survival(Pkidney function and reduced survival in LTx patients.

关键词： Acute kidney injury Adult lung transplantation Incidence Outcomes Risk factors

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Efficacy and safety of on demand tadalafil in the treatment of East and Southeast Asian men with erectile dysfunction:a randomized double-blind,parallel,placebo-controlled clinical study

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Asian Journal of Andrology 2006年第6期8卷 685-692页

作者： Wai Chun Andrew Yip Han-Sun Chiang Jesus Benjamin Mendoza Hui-Meng Tan Man-Kay Li Wei Christine Wang Vladimir Kopernicky Department of Surgery Kwong Wah HospitalHong KongChina college of Medicine Fu Jen Catholic UniversityTaipei 24205TaiwanChina Department of Urology National Kidney and Transplant InstituteQuezon City 1100the Philippines Department of Urology Subang Jaya Medical CentreSelangor Darul Ehsan 47500Malaysia Department of Urology National University Hospital119074Singapore Lilly Research Laboratories Eli Lilly and CompanyIndianapolisIndiana 46285USA Lilly Area Medical Center Vienna 1030Austria

Aim： To assess the efficacy and safety of tadalafil in comparison to a placebo, when taken on demand for 12 weeks by East/Southeast Asian men with erectile dysfunction （ED）, Methods： This multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted at 17 centers across East and Southeast Asia between August 2002 and February 2003. Men more than 18 years of age with mild to severe ED of various etiologies were randomized to receive a placebo or 20 mg of tadalafil taken as needed （maximum once daily）. Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile diary and Global Assessment Questions. Results： Tadalafil significantly improved erectile function as compared to the placebo （P 〈 0.001）. At the endpoint, the patients receiving 20 mg of tadalafil reported a greater mean per patient percentage of successful intercourse attempts （Sexual Encounter Profile question 3： 70.9% compared to 33.5% in the placebo） and a greater proportion of improved erections （Global Assessment Question： 86.2% compared to 30.1%）. Most （≥3%） treatment emergent adverse events were mild or moderate. The most common treatment emergent adverse events were headache, back pain, dizziness and dyspepsia. Conclusion： Tadalafil was an effective and well-tolerated treatment for ED in East and Southeast Asian men.

关键词： tadalafil phosphodiesterase type 5 inhibitor erectile dysfunction efficacy safety Asian

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Is de novo membranous nephropathy suggestive of alloimmunity in renal transplantation?A case report

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World Journal of transplantation 2022年第1期12卷 15-20页

作者： Prakash I Darji Himanshu A Patel Bhavya P Darji Ajay Sharma Ahmed Halaw Department of Nephrology and Renal transplantation Zydus HospitalsAhmedabad 380059GujaratIndia Internship Department of MedicineGCS Medical CollegeHospital and Research CentreAhmedabad 380025GujaratIndia Faculty of Health and Life Science Institute of Learning and TeachingUniversity of LiverpoolLiverpool L693BXUnited Kingdom Consultant transplant Surgeon Royal Liverpool University HospitalsLiverpool L78XPUnited Kingdom Department of transplantation Sheffield Teaching HospitalsSheffield S102JFUnited Kingdom

BACKGROUND Post-transplant nephrotic syndrome(PTNS)in a renal allograft carries a 48%to 77%risk of graft failure at 5 years if proteinuria *** can be due to either recurrence of native renal disease or de novo glomerular *** prognosis depends upon the underlying *** describe a case of post-transplant membranous nephropathy(MN)that developed 3 mo after kidney *** patient was properly evaluated for pathophysiology,which helped in the management of the *** SUMMARY This 22-year-old patient had chronic *** received a living donor kidney,and human leukocyte antigen-DR(HLA-DR)mismatching was *** was discovered at the follow-up visit 3 mo after the *** histopathology was suggestive of *** the past antibody-mediated rejection(ABMR)might have been misinterpreted as de novo MN due to the lack of technologies available to make an accurate *** researchers have observed that HLA-DR is present on podocytes causing an anti-DR antibody deposition and development of de novo *** also reported poor prognosis in their ***,we excluded the secondary causes of *** was suggestive of IgG1 deposits that favoured the diagnosis of de novo *** patient responded well to an increase in the dose of tacrolimus and angiotensin converting enzyme *** Exposure of hidden antigens on the podocytes in allografts may have led to subepithelial antibody deposition causing de novo MN.

关键词： Post-transplant nephrotic syndrome Recurrent membranous nephropathy Secondary membranous nephropathy Alloimmunity Cryptic antigens Case report

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Helper T Cell(CD4^(+))Targeted Tacrolimus Delivery Mediates Precise Suppression of Allogeneic Humoral Immunity

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Research 2022年第3期2022卷 189-203页

作者： Jia Shen Chang Liu Pengpeng Yan Meifang Wang Luying Guo Shuaihui Liu Jianghua Chen Jessica MRosenholm Hongfeng Huang Rending Wang Hongbo Zhang kidney Disease Center The First Affiliated HospitalCollege of MedicineZhejiang UniversityKey Laboratory of Kidney Disease Prevention and Control TechnologyZhejiang ProvinceChina Pharmaceutical Sciences Laboratory Faculty of Science and EngineeringÅbo Akademi UniversityTurku 20520Finland Turku Bioscience centre University of Turku andÅbo Akademi UniversityTurku 20520Finland Organ Donation and Coordination Office The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Antibody-mediated rejection(ABMR)is a major cause of dysfunction and loss of transplanted *** current treatments for ABMR involve nonspecific inhibition and clearance of T/B cells or plasma ***,the prognosis of patients following current treatment is poor.T follicular helper cells(Tfh)play an important role in allograft-specific antibodies secreting plasma cell(PC)*** cells are therefore considered to be important therapeutic targets for the treatment of antibody hypersecretion disorders,such as transplant rejection and autoimmune ***(Tac),the primary immunosuppressant,prevents rejection by reducing T cell ***,its administration should be closely monitored to avoid serious side *** this study,we investigated whether Tac delivery to helper T(CD4^(+))cells using functionalized mesoporous nanoparticles can block Tfh cell differentiation after alloantigen *** showed that Tac delivery ameliorated humoral rejection injury in rodent kidney graft by suppressing Tfh cell development,PC,and donor-specific antibody(DSA)generation without causing severe side effects compared with delivery through the drug administration *** study provides a promising therapeutic strategy for preventing humoral rejection in solid organ *** specific and controllable drug delivery avoids multiple disorder risks and side effects observed in currently used clinical approaches.

关键词： Tacrolimus treatment donor

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Pre-emptive live donor kidney transplantation-moving barriers to opportunities:An ethical,legal and psychological aspects of organ transplantation view

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World Journal of transplantation 2021年第4期11卷 88-98页

作者： David van Dellen Lisa Burnapp Franco Citterio Nizam Mamode Greg Moorlock Kristof van Assche Willij CZuidema Annette Lennerling Frank JMF Dor Department of Renal and Pancreas transplantation Manchester University NHS Foundation TrustManchester M139WLUnited Kingdom Department of Faculty of Biology Medicine and HealthUniversity of ManchesterManchester M139PLUnited Kingdom Department of transplantation Guy's and St.Thomas'NHS Foundation TrustLondon SE19RTUnited Kingdom Department of Surgery Renal TransplantationCatholic UniversityRome 00153Italy Warwick Medical School University of WarwickCoventry CV47ALUnited Kingdom Res Grp Personal Rights&Property Rights University of AntwerpAntwerp 2000Belgium Departments of Internal Medicine Erasmus Medical CentreRotterdam CE 1015Netherlands The transplant centre Sahlgrenska University HospitalGothenburg S-41345Sweden Institute of Health and Care Sciences The Sahlgrenska AcademyUniversity of GothenburgGothenburg S-40530Sweden imperial college Renal and transplant centre Hammersmith HospitalLondon W21NYUnited Kingdom

Live donor kidney transplantation(LDKT)is the optimal treatment modality for end stage renal disease(ESRD),enhancing patient and graft ***-emptive LDKT,prior to requirement for renal replacement therapy(RRT),provides further advantages,due to uraemia and dialysis *** are a number of potential barriers and opportunities to promoting pre-emptive *** infrastructure is needed to deliver robust programmes,which varies based on socio-economic *** frameworks can impact on national prioritisation of pre-emptive LDKT and supporting education *** on other programme’s components,including deceased kidney transplantation and RRT,can also hamper *** programmes are designed to provide maximal benefit to the recipient,which is specifically true for pre-emptive *** care providers need to be educated to maximize early LDKT *** access for varying population groups,without socioeconomic bias,also requires *** barriers,including religious influence,also need consideration in developing successful *** addition,the benefit of pre-emptive LDKT needs to be emphasised,and opportunities provided to potential donors,to ensure timely and safe work-up *** education and preparation for pre-emptive LDKT needs to ensure increased *** of the benefits of pre-emptive transplantation require prioritisation for this population *** recommend an approach where patients approaching ESRD are referred early to pre-transplant clinics facilitating early discussion regarding pre-emptive LDKT and potential donors for LDKT are prioritized for work-up to ensure *** regarding preemptive LDKT should be the norm for patients approaching ESRD,appropriate for the patient’s cultural needs and physical ***-emptive transplantation maximize benefit to potential recipients,with the potential to occur within successful service *** f

关键词： Pre-emptive kidney transplantation Living donor Ethics End-stage renal disease

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