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Limb replantation and transplantation is the optimal treatment for traumatic limb amputation. Safe and effective limb preservation is the key factor to determine the success of limb replantation and transplantation. Currently, static cold storage is the gold standard of limb preservation. However, the preservation time is short, which may no longer meet clinical requirements. With rapid development of organ preservation in recent years, novel preservation technologies, such as ultra-low temperature preservation, supercooling preservation and mechanical perfusion preservation, have successively emerged. However, at present, these techniques are primarily applied to the preservation of solid organs rather than composite tissue allografts with blood vessels including limbs. In this article, research status and progress on the application of static cold storage and mechanical perfusion preservation in limb preservation were reviewed, aiming to provide reference for clinical application of limb preservation technology and promote the development of limb replantation and transplantation.
ABSTRACT
As an effective treatment for end-stage liver disease, liver transplantation has been widely carried out worldwide and gradually captivated widespread recognition. With the advancement of liver transplantation techniques, the incidence of postoperative complications has been gradually declined, and the short-term and long-term prognosis of recipients have been constantly improved. However, a huge gap has existed between the supply and demand of donor organs, which is a major factors restricting the development of liver transplantation. The amount of liver transplantation operation in China is increasing year by year, the shortage of donor liver is becoming more and more prominent, and marginal donor liver is increasingly used in clinic. In recent years, the selection criteria of donor organs, organ preservation and functional maintenance have been continuously improved. In this article, the application and development trend of different techniques were reviewed from the perspectives of donor liver preservation and functional maintenance, and recent technical development and research results were summarized, aiming to provide reference for further enhancing the survival rate of grafts and recipients and promoting the development of liver transplantation in China.
ABSTRACT
High-quality donor heart is the prerequisite and fundamental guarantee for successful heart transplantation. Reasonable donor heart preservation technique plays a key role in improving the quality of donor heart and the prognosis of heart transplantation. Static cold storage (SCS) is currently the standard preservation technique for cardiac allograft. However, it is prone to cause severe cold ischemia injury to the donor heart, and it is impossible to evaluate heart function during SCS. As an important emerging technique of organ preservation, machine perfusion better matches with physiological conditions compared with SCS, which may remove metabolic wastes and provide basic substances for metabolic needs during organ preservation, prolong the preservation time and improve the preservation effect to a certain extent. Besides, it may also effectively evaluate organ function and improve clinical prognosis of heart transplantation. Meantime, it can also repair organ damage, significantly optimize organ quality and improve the utilization rate of donor organs. In this article, research status of machine perfusion of donor heart was reviewed.
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Objective To evaluate the effect of hypothermic machine perfusion (HMP) on the expression levels of inflammatory cytokines in rat kidney. Methods Thirty male rats were randomly divided into the control (Control group), static cold storage group (SCS group) and HMP group, with 10 rats in each group. The velocity, intrarenal resistance and pH value of perfusion effluent were recorded during HMP. The expression levels of CXC chemokine ligand (CXCL)1, CXCL2, interferon (IFN)-β1, IFN-α4, CC chemokine ligand (CCL)2, CCL20, interleukin (IL)-17α, IL-17C and tumor necrosis factor (TNF)-α messenger RNA (mRNA) in renal tissues were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Pathological changes of the kidney were observed by hematoxylin-eosin (HE) staining. Results During HMP, the velocity and intrarenal resistance remained stable, and the pH value of perfusion effluent was decreased slowly. RT-PCR showed that the relative expression levels of CXCL1, CXCL2, CCL2, CCL20, IL-17α, IL-17C and TNF-α mRNA in the SCS and HMP groups were higher compared with those in the Control group. Compared with the SCS group, the relative expression levels of CXCL1, CXCL2, CCL2, CCL20, IL-17α and TNF-α mRNA were up-regulated in the HMP group (all P<0.05). HE staining revealed that the morphology of renal cells was normal in the Control group, whereas evident epithelial necrosis, cytoplasmic vacuolation, brush border loss and epithelial shedding were observed in the SCS group. Compared with the SCS group, pathological changes in the HMP group were alleviated. Conclusions HMP may activate renal inflammation, and inhibiting the activation of inflammation during HMP is expected to further improve the effect of allograft preservation.
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Heart transplantation is the primary therapeutic option for patients with end-stage heart failure. The shortage of donors has been the main limiting factor for the increasing quantity of heart transplantation. With persistent updating and introduction of novel technologies, the donor pool has been increasingly expanded, such as using the heart from older donors, donors infected with hepatitis C virus, donors dying from drug overdose or donation after cardiac death (DCD) donors, etc. Meantime, the proportion of recipients with advanced age, multiple organ dysfunction, mechanical circulatory support and human leukocyte antigen antibody sensitization has been significantly increased in recent years. The shortage of donors, complication of recipients' conditions, individualized management of immunosuppressive therapy and prevention and treatment of long-term cardiac allograft vasculopathy are all challenges in the field of heart transplantation. In this article, novel progresses on donor pool expansion, improving the quality of recipients, strengthening the diagnosis and treatment of rejection, and preventing cardiac allograft vasculopathy were reviewed, aiming to prolong the survival and enhance the quality of life of patients with end-stage heart failure on the waiting list or underwent heart transplantation.
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To increase the utilization rate of expanded criteria donor (ECD) kidney, the kidney preservation methods have been ever advancing in recent years. The application of normothermic machine perfusion (NMP) promotes the preservation, evaluation and repair of ex vivo donor kidneys and accelerates the innovation of surgical approaches of kidney transplantation. Ischemia-free kidney transplantation (IFKT), which initiated by Organ Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University, keeps the blood flow and oxygen supply of the donor kidney with NMP machine during the entire process of acquisition, preservation and transplantation, thereby fundamentally avoiding ischemia-reperfusion injury (IRI) of the donor kidney and reducing the risk of delayed graft function (DGF) and acute rejection after surgery. In this article, recent progresses upon the kidney NMP, surgical procedures and short-term outcomes of IFKT were reviewed, aiming to provide reference for enhancing the utilization rate of ECD donor kidney and resolving the issue of organ shortage.
ABSTRACT
Organ donation after citizen's death has become the main source of organ donation in China. However, the complexity of donor quality and the increasing proportion of expanded criteria donor (ECD) exert significant impact upon the availability of donor kidney and the long-term prognosis of recipients after kidney transplantation. Strengthening the quality maintenance and evaluation of donor kidney is of great significance for improving the quality of donor kidney, increasing the procurement and utilization of donor kidney and prolonging the long-term survival of recipients and kidney allografts. As one of the major approaches of organ preservation, machine perfusion preservation may not only prolong the preservation time and improve the quality of donor kidney, but also play a critical role in the repair and function evaluation of donor kidney. Based on literature review, several hot issues, corresponding treatment strategies and research progress on machine perfusion in the quality maintenance of donor kidney from organ donation after citizen's death were reviewed in this article, aiming to provide reference for selecting the optimal preservation method of donor kidney and enhancing the quality and utilization rate of ECD donor kidney.
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Organ transplantation is the most effective treatment for end-stage organ failure, and voluntary donation after citizen's death is the only source of transplant organ in China. Clinically, transplant organ protection technique plays a critical role in improving the quality of transplant organs and the prognosis of recipients. On the basis of domestic and worldwide basic research and clinical practice of transplant organ protection and according to the Oxford evidence classification and GRADE system, the experts organized by Branch of Organ Transplant Physicians of Chinese Medical Doctor Association, Branch of Transplantation Group of Surgery of Chinese Medical Association and China Liver Transplant Registry Scientific Committee had compiled and published the Chinese Expert Consensus on Organ Protection of Transplantation (2016 edition) for liver, kidney, pancreas, small intestine, heart, lung transplant organs. With the support of China Liver Transplant Registry, National Trauma Medical Center, National Quality Control Center for Human Donated Organ Procurement, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation and National Center for Healthcare Quality Management in Liver Transplant combined with recent domeatic and worldwide clinical practice and research progress for organ transplantation and organ protection, the Chinese Expert Consensus on Organ Protection of Transplantation (2022 edition) has been published recently. This consensus focuses on updating the technical progress and evidence-based medicine of organ procurement, preservation, transport, and quality evaluation in clinical practice. Additionally, the content of composite tissue transplantation mainly including limb transplantation has also been covered. The aim is to promote the the scientific and standardized clinical organ transplantation.
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Objective To explore the feasibility of biomarkers in static cold storage (SCS) perfusate of donor kidney from donation after cardiac death (DCD) for predicting delayed graft function (DGF) after renal transplantation. Methods Clinical data of 64 recipients and 47 donors undergoing DCD renal transplantation were retrospectively analyzed. All recipients were divided into the DGF group (n=7) and immediate graft function (IGF) group (n=57) according to the incidence of postoperative DGF in the recipients. The levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), interleukin -18(IL-18) and kidney injury molecule-1 (KIM-1) in the SCS perfusate were statistically compared between two groups, and the correlation with DGF was analyzed. The predictive value of each biomarker in the occurrence of DGF in recipients after renal transplantation was analyzed. Results The incidence of DGF in the recipients undergoing DCD renal transplantation was 11% (7/64). The NGAL level in the donor kidney perfusate of the DGF group was significantly higher than that in the IGF group (P=0.009). The NGAL level in the donor kidney perfusate was positively correlated with the incidence of DGF in recipients after renal transplantation (r=0.430, P < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the increased levels of NGAL and KIM-1 in the perfusate yielded certain predictive value for DGF in recipients after renal transplantation (both P < 0.05). The area under the curve (AUC) of combined detection of NGAL and KIM-1 for predicting DGF in recipients after renal transplantation was 0.932 [95% confidence interval (CI) 0.850-1.000]. The sensitivity was calculated as 1.000 and 0.754 for the specificity (P < 0.05). Conclusions The NGAL level in the SCS perfusate of DCD donor kidney is associated with the occurrence of DGF in recipients after renal transplantation. Combined detection of NGAL and KIM-1 levels in the perfusate may accurately predict the occurrence of DGF in recipients after renal transplantation.
ABSTRACT
The main purpose of organ preservation in organ transplantation is to maintain tissue and cell activity of donor organs so as to gain time for allocation and transportation of the organ, preparation of the recipient and organization of staff and facilities. The main principles of organ preservation can be divided into normothermic mechanical perfusion and cryopreservation. Cryopreservation is the favourite organ preservation method in clinical practice currently. However, the metabolic activity still exists in donor organs preserved with current cryopreservation technique, which makes the long-term preservation of organs extremely difficult. The supercooling organ preservation is a new type of cryopreservation technology, which greatly prolongs the preservation time of organs. It is expected to become an important organ preservation technique in the future, and it will provide technical support for the establishment of "organ bank".
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Objective To evaluate the clinical effect of hypothermic machine perfusion (HMP) in the storage of renal grafts from deceased donor (DD) with high-risk delayed graft function (DGF). Methods Clinical data of 52 donors with high-risk DGF were collected in this prospective randomized controlled study. Two renal grafts from each donor were randomly divided into the HMP group (n=52) and static cold storage (SCS) group (n=52). In the HMP group, the renal grafts were stored by LifePort under HMP, whereas the renal grafts in the SCS group were preserved in University of Wisconsin solution (UW solution). The incidence of DGF and primary nonfunction (PNF) after renal transplantation was statistically compared between two groups. The recovery of renal graft function, the survival rates of the recipients and renal grafts within postoperative 1 year were observed in two groups. Results The incidence of DGF in the HMP group was 4%(2/52), significantly lower than 17% (9/52) in the SCS group (P < 0.05). No PNF was reported in the HMP group and 1 case of PND was noted in the SCS group, the difference was not statistically significant (P > 0.05). The recovery time of graft function of the recipients in the HMP and SCS groups were (7.2±0.6) d and (7.7±1.0) d with no statistical significance (P > 0.05). In the HMP group, the urine volume of the recipients on the day of operation, postoperative 1 and2 d was significantly larger than that in the SCS group (all P < 0.05). In the HMP group, the levels of serum creatinine at each time point after operation were significantly lower than those in the SCS group (all P < 0.05). The 1-year survival rates of the recipient and kidney were 98.1%, 92.3% and 100%, 96.2% in the HMP and SCS groups with no statistical significance (all P > 0.05). Conclusions HMP can significantly reduce the incidence of DGF after renal transplantation from DD with high-risk DGF and promote the early recovery of graft function.
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Objective To evaluate the effect of Lifeport and static cold storage (CS)on preservation of donor kidney. Methods Medline,Embase,Cochrane library,CBMdisc,China National Knowledge Infrastructure,Wanfang database and VIP database were searched by computer,and relevant clinical studies on the effect of Lifeport and CS on preservation of transplant kidney were collected,with the search period from database construction to December 31,2015. According to the inclusion and exclusion criteria,relevant references were selected,quality was evaluated,information was extracted,and risk of bias in the study was evaluated.In addition,Meta analysis was conducted using software Stata 12. Results A total of 16 studies were included with 5 randomized controlled trials (RCT)and 11 retrospective cohort studies (RCS).The results of Meta analysis showed that:compared with Group CS,(1 )for total deceased donor (TDD), incidence of delayed graft function (DGF)decreased in Group Lifeport after transplantation,duration of DGF and average length of stay decreased,and 1﹣year survival rate of kidney increased after operation.The incidence of postoperative acute rejection (AR)and 1﹣year survival rate of patients were similar in two groups.(2)for donor after cardiac death (DCD):postoperative incidence of DGF and average length of stay decreased in Group Lifeport;there was no statistical significance in incidence of primary nonfunction (PNF)and AR,1﹣year survival rate of kidneys and patients between two groups.(3)for expanded criteria donor (ECD):postoperative incidence of PNF decreased and 1﹣year survival rate of kidney increased in Group Lifeport;there was no statistical significance in postoperative incidence of DGF and AR and 1﹣year survival rate of kidney between two groups. Conclusions Application of Lifeport in preservation of donor kidney has certain advantages. However,more high﹣quality studies should be further conducted to verify the study findings due to limited quantity and quality of the study.