Withdrawal of life support therapy involves controlled removal of life support modalities including artificial respiration and circulation with intent to provide a comfortable death. Withdrawal of life support therapy is necessary prior to procedures such as organ donation after cardio-circulatory death, but remains poorly explored in current literature. To enhance the current evidence, we conducted a thorough structured review, an observational study, and a qualitative comparison of components comprising withdrawal of life support therapy in both donor and non-donor patient groups. At all stages, we considered how results impacted donation after cardio-circulatory death. Withdrawal of life support therapy processes vary between countries, hospitals, practitioners, and patients. Variability in practice impacts care and outcomes for both donor and non-donor patients. Improved definitions and consensus about the process of withdrawal of life support therapy may improve patient care, success of organ donation after cardio-circulatory death, and uptake of donation protocols.

Withdrawal of life support therapy involves controlled removal of life support modalities including artificial respiration and circulation with intent to provide a comfortable death. Withdrawal of life support therapy is necessary prior to procedures such as organ donation after cardio-circulatory death, but remains poorly explored in current literature. To enhance the current evidence, we conducted a thorough structured review, an observational study, and a qualitative comparison of components comprising withdrawal of life support therapy in both donor and non-donor patient groups. At all stages, we considered how results impacted donation after cardio-circulatory death. Withdrawal of life support therapy processes vary between countries, hospitals, practitioners, and patients. Variability in practice impacts care and outcomes for both donor and non-donor patients. Improved definitions and consensus about the process of withdrawal of life support therapy may improve patient care, success of organ donation after cardio-circulatory death, and uptake of donation protocols.

2017-02-09全文追加 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18453号 / 医博第3908号 / 新制||医||1004(附属図書館) / 31331 / 京都大学大学院医学研究科医学専攻 / (主査)教授 坂田 隆造, 教授 木村 剛, 教授 小池 薫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19226号 / 医博第4025号 / 新制||医||1011(附属図書館) / 32225 / 京都大学大学院医学研究科医学専攻 / (主査)教授 福田 和彦, 教授 木村 剛, 教授 三嶋 理晃 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19556号 / 医博第4063号 / 新制||医||1012(附属図書館) / 32592 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小池 薫, 教授 福田 和彦, 教授 三嶋 理晃 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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La transplantation rénale, thérapie de choix de l'insuffisance rénale chronique terminale, est limitée par une pénurie d'organes. Les greffons issus de donneurs décédés par arrêt cardiaque (DDAC) peuvent contribuer à pallier à cette pénurie au prix de stratégies thérapeutiques visant à améliorer l'issue de la transplantation. Les cellules souches mésenchymateuses (MSC) de l'organisme adulte ont des propriétés de sécrétion, d'immunomodulation et de différenciation intéressantes dans ce contexte.L'objectif de ce travail est d'évaluer, dans un modèle pré-clinique porcin de DDAC, le potentiel thérapeutique de deux populations cellulaires d'intérêt : les MSC issues du liquide amniotique (AFSC) et les cellules de la fraction vasculaire stromale du tissu adipeux (SVF). Les AFSC porcines injectées dans l'artère rénale 7 jours post-greffe, en raison de leur sensibilité à une séquence d'hypoxie réoxygénation (HR) in vitro, accélèrent la reprise de fonction et réduisent l'extension des lésions chroniques du greffon et sont détectées dans le rein 24h après injection. La SVF porcine, phénotypiquement proche de celle de l'Homme, est moins sensible à cette séquence d'HR et peut être injectée dans l'artère du greffon à sa reperfusion sans perturbation du flux sanguin rénal, avec une rétention des cellules dans le rein 24h post injection.Ce travail met en évidence le rôle bénéfique des AFSC dans la réparation des lésions ischémie-reperfusion des greffons issus des DDAC, ainsi que la faisabilité de l'injection de la SVF dans l'artère rénale après transplantation, et ouvre des pistes pour l'optimisation les protocoles d'administration de produits de thérapie cellulaire en transplantation. / Kidney transplantation is the best therapeutic option for end stage chronic kidney failure, but is limited by transplant shortage. Use of transplants from deceased after cardiac death donors (DCD) could represent an additional graft source, but there is a need for developing new therapeutic approaches like cell therapy to increase their recovery. Mesenchymal stem cells (MSC) potentially extracted from many adult tissues have interesting paracrine, immune-modulating, and differentiation properties in this context. This work aims to assess, in a preclinical porcine model DCD donor, the therapeutic potential of two cell populations of interest: amniotic fluid derived MSC (AFSC) and cells from stromal vascular fraction of adipose tissue (SVF). Delayed injection of AFSC 7 days following kidney transplantation because of their sensitivity to a specific Hypoxia Reoxygenation (HR) sequence in vitro, accelerates graft function recovery and limits chronic injuries to the transplanted organ. Cells are detectable into the transplanted kidney 24h after injection. Porcine SVF is phenotypically similar to human. Injected in renal artery simultaneously with organ reperfusion because of its resistance to the HR sequence, porcine SVF does not disturb renal blood flow and allow cell-retention within the organ 24h after injection. This work highlights the protective effect of AFSC against ischemia reperfusion lesions in grafts from DCD donors and the feasibility of SVF injection directly into the renal artery of the graft following kidney transplantation in DCD conditions. Moreover it opens new lines for optimizing injection protocols of cellular products in kidney transplantation.