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Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge

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World Journal of Translational Medicine 2014年第2期3卷 58-68页

作者： Fateh Bazerbachi Nazia selzner John B Seal markus selzner Department of Medicine University of Minnesota Department of Medicine University of TorontoMultiorgan Transplant Program Toronto General Hospital Department of Surgery University of Toronto Multiorgan Transplant Program Toronto General Hospital

The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusionmodels, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.

关键词： Transplant hepatology Liver transplantation Organ donation Extended criteria donors Donation after cardiac death Ex-vivo liver perfusion Normothermic machine perfusion Hypothermic machine perfusion

3D U-Net Segmentation Improves Root System Reconstruction from 3D MRI Images in Automated and Manual Virtual Reality Work Flows

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Plant Phenomics 2023年第3期5卷 598-611页

作者： Tobias selzner Jannis Horn Magdalena Landl Andreas Pohlmeier Dirk Helmrich Katrin Huber Jan Vanderborght Harry Vereecken Sven Behnke Andrea Schnepf Forschungszentrum Juelich GmbH Agrosphere(IBG-3)JuelichGermany Autonomous Intelligence Systems Group University of BonnBonnGermany Forschungszentrum Juelich GmbH Juelich Supercomputing CenterJuelichGermany

Magnetic resonance imaging(MRI)is used to image root systems grown in opaque ***,reconstruction of root system architecture(RSA)from 3-dimensional(3D)MRI images is *** resolution and poor contrast-to-noise ratios(CNRs)hinder automated ***,manual reconstruction is still widely ***,we evaluate a novel 2-step work flow for automated RSA *** the first step,a 3D U-Net segments MRI images into root and soil in *** the second step,an automated tracing algorithm reconstructs the root systems from the segmented *** evaluated the merits of both steps for an MRI dataset of 8 lupine root systems,by comparing the automated reconstructions to manual reconstructions of unaltered and segmented MRI images derived with a novel virtual reality *** found that the U-Net segmentation offers profound benefits in manual reconstruction:reconstruction speed was doubled(+97%)for images with low CNR and increased by 27%for images with high *** root lengths were increased by 20%and 3%,***,we propose to use U-Net segmentation as a principal image preprocessing step in manual work *** root length derived by the tracing algorithm was lower than in both manual reconstruction methods,but segmentation allowed automated processing of otherwise not readily usable MRI ***,model-based functional root traits revealed similar hydraulic behavior of automated and manual *** studies will aim to establish a hybrid work flow that utilizes automated reconstructions as scaffolds that can be manually corrected.

关键词： Root utilize otherwise

Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis

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World Journal of Gastroenterology 2017年第15期23卷 2673-2684页

作者： Agata Bartczak Jianhua Zhang Oyedele Adeyi Achiya Amir David Grant Reginald Gorczynski Nazia selzner Andrzej Chruscinski Gary A Levy Multi Organ Transplant Program University Health Network Department of Laboratory Medicine and Pathology University Health Network Gastroenterology Hepatology and Nutrition DivisionThe Hospital for Sick Children

AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1-/- *** and Teff cells from fgl2-/-, fgl2+/+, and fgl2Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1-/- *** vitro, fgl2Tg Treg had enhanced immunosuppressive activity, and fgl2Tg Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice (fgl2+/+) into Rag1-/- mice produced both clinical and histologic colitis with dense infiltrates of CD3+ T cells, crypt abscesses and loss of goblet cells. Fgl2Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/- Treg were only partially protective. In mice that received fgl2Tg Treg, the ratio of Foxp3+ to CD3+ cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2Tg mice did not produce *** we show that fgl2Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2Tg Treg prevent colitis in contrast to fgl2+/+ Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.

关键词： Fibrinogen-like protein 2 Colitis Regulatory T cells Transgenic mouse Inflammatory bowel disease

Divergent trajectories of lean vs obese non-alcoholic steatohepatitis patients from listing to post-transplant:A retrospective cohort study

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World Journal of Gastroenterology 2022年第26期28卷 3218-3231页

作者： Fakhar Ali Qazi-Arisar Raj Uchila Catherine Chen Cathy Yang Shi-Yi Chen Ravikiran Sindhuvalada Karnam Amirhossein Azhie Wei Xu Zita Galvin Nazia selzner Leslie Lilly Mamatha Bhat Ajmera Transplant Program Toronto General HospitalUniversity Health NetworkToronto M5G 2N2OntarioCanada Division of Gastroenterology and Hepatology Department of MedicineUniversity of TorontoToronto M5G 2N2OntarioCanada National Institute of Liver and GI Diseases Dow University of Health SciencesKarachi 75330Pakistan Department of Biostatistics Princess Margaret Cancer CenterUniversity Health NetworkToronto M5G 2C1OntarioCanada Division of Biostatistics Dalla Lana School of Public HealthUniversity of TorontoToronto M5G 2C1OntarioCanada

BACKGROUND Non-alcoholic steatohepatitis(NASH)cirrhosis is the second most common indication for liver transplantation(LT).The role of body mass index(BMI)on outcomes of NASH cirrhosis has been *** To compare the longitudinal trajectories of patients with lean vs obese NASH cirrhosis,from listing up to post-transplant,having adjusted their BMI for *** We retrospectively reviewed all adult NASH patients listed for LT in our program from 2012 to ***-Gray Competing Risk analyses and Cox Proportional-Hazard Models were performed to examine the cumulative incidence of transplant and survival outcomes *** Out of 265 NASH cirrhosis listed patients,176 were *** age was 61.0 years;46%were females.111 patients underwent *** robust patients had better waitlist survival[hazard ratio(HR):0.12;95%CI:0.05–0.29,P<0.0001]with higher instantaneous rate of transplant(HR:5.71;95%CI:1.26–25.9,P=0.02).Lean NASH patients had a substantially higher risk of graft loss within 90 d post-LT(1.2%vs 13.8%,P=0.032)and death post-LT(2.4%vs 17.2%,P=0.029).1-3-and 5-year graft survival was poor for lean NASH(78.6%,77.3%and 41.7%vs 98.6%,96%and 85%respectively).Overall patient survival post-LT was significantly worse in lean NASH(HR:0.17;95%CI:0.03–0.86,P=0.0142)with 83%lower instantaneous rate of death in obese *** Although lean NASH is considered to be more benign than obese NASH,our study suggests a paradoxical correlation of lean NASH with waitlist outcomes,and graft and patient survival post-LT.

关键词： Outcomes Frailty Waitlist Liver transplant Survival

一氧化碳通过调节CD36表面表达控制小胶质细胞的红细胞吞噬作用减轻出血性损伤

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神经损伤与功能重建 2020年第6期15卷 F0003-F0003页

作者： Sandra Kaiser Lisa selzner JanickWeber Nils Schallner 杜一星(编译) Department of Anesthesiology&Critical Care Medicine Medical CenterUniversity of FreiburgGermany Faculty of Medicine University of FreiburgGermany 不详

小胶质细胞的红细胞吞噬作用在出血性卒中后的损伤反应中至关重要。我们假设通过HO-1/CO调节小胶质细胞的红细胞吞噬作用依赖于涉及活性氧(ROS)和CD36表面表达的信号通路。我们在有/无血液和有/无一氧化碳(CO)暴露条件下孵育小胶质细胞B... 详细信息

小胶质细胞的红细胞吞噬作用在出血性卒中后的损伤反应中至关重要。我们假设通过HO-1/CO调节小胶质细胞的红细胞吞噬作用依赖于涉及活性氧(ROS)和CD36表面表达的信号通路。我们在有/无血液和有/无一氧化碳(CO)暴露条件下孵育小胶质细胞BV-2细胞系和原代小胶质细胞(PMG)。我们用从组织特异性HO-1缺陷(LyzM-Cre-Hmoxlfl/fl)和CD36-/-小鼠中分离出的PMG,或针对AMPK(AMP激活的蛋白激酶)的siRNA来检验我们的假设。在鼠蛛网膜下腔出血(SAH)模型中,我们比较了野生型和CD36-/-小鼠的神经元损伤。观察指标包括血管痉挛、小胶质细胞活化、神经元凋亡和空间记忆。我们观察到在血液暴露后,小胶质细胞HO-1表达增加。CO暴露后,ROS产生显著增加,导致磷酸化的AMPK数量增加,随后CD36表面表达增强。来自LyzM-CreHmoxlfl/fl小鼠的PMG表现出ROS产生和CD36表面表达均降低,并且CO不能诱导其CD36表面表达增加。缺乏HO-1和CD36导致的红细胞吞噬作用降低无法用CO逆转。在存在外源性CO的情况下,BV-2细胞的红细胞吞噬作用增强,而在经AMPK的siRNA处理的细胞中没有发现该现象。经历SAH的CD36-/-小鼠神经元细胞死亡增加,空间记忆功能受损。我们证明,小胶质细胞的吞噬功能部分与HO-1相关通路有关,该通路涉及ROS产生、磷酸化的AMPK和CD36的表面表达的变化。CD36为出血后血液清除的关键因子之一,与神经元的预后密切相关。这些结果需要进一步研究以明确CO潜在的神经保护特性。

关键词：脑出血一氧化碳血红素氧化酶小胶质细胞吞噬作用