BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise cr...BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.展开更多
To facilitate the implementation of controlled donation after circulatory death(cDCD)programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation(ECMO)team(Spokes),some countries and Italia...To facilitate the implementation of controlled donation after circulatory death(cDCD)programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation(ECMO)team(Spokes),some countries and Italian Regions have launched a local cDCD network with a ECMO mobile team who move from Hub hospitals to Spokes for normothermic regional perfusion(NRP)implantation in the setting of a cDCD pathway.While ECMO teams have been clearly defined by the Extracorporeal Life Support Organization,regarding composition,responsibilities and training programs,no clear,widely accepted indications are to date available for NRP teams.Although existing NRP mobile networks were developed due to the urgent need to increase the number of cDCDs,there is now the necessity for transplantation medicine to identify the peculiarities and responsibility of a NRP team for all those centers launching a cDCD pathway.Thus,in the present manuscript we summarized the character-istics of an ECMO mobile team,highlighting similarities and differences with the NRP mobile team.We also assessed existing evidence on NRP teams with the goal of identifying the characteristic and essential features of an NRP mobile team for a cDCD program,especially for those centers who are starting the program.Differences were identified between the mobile ECMO team and NRP mobile team.The common essential feature for both mobile teams is high skills and experience to reduce complications and,in the case of cDCD,to reduce the total warm ischemic time.Dedicated training programs should be developed for the launch of de novo NRP teams.展开更多
AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase(iN OS) inhibitor in a model of donation after circulatory death(DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min w...AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase(iN OS) inhibitor in a model of donation after circulatory death(DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min warm ischemia. They were then stored on ice for 18 h before being reperfused ex vivo with oxygenated autologous blood on an isolated organ perfusion system. The selective i NOS inhibitor 1400W(10 mg/kg) was administered before reperfusion(n = 6) vs control group(n = 7). Creatinine(1000 μmol/L) was added to the system, renal and tubular cell function and the level of ischemia reperfusion injury were assessed over 3 h of reperfusion using plasma, urine and tissue samples. RESULTS: Kidneys treated with 1400 W had a higher level of creatinine clearance(CrC l) [area under the curve(AUC) CrC l: 2.37 ± 0.97 mL /min per 100 g vs 0.96 ± 0.32 mL /min per 100 g, P = 0.004] and urine output [Total: 320 ± 96 mL vs 156 ± 82 mL, P = 0.008]. There was no significant difference in levels of fractional excretion of sodium(AUC, Fr ex Na+: Control, 186.3% ± 81.7%.h vs 1400 W, 153.4% ± 12.1%.h, P = 0.429). Levels of total protein creatinine ratio were significantly lower in the 1400 W group after 1 h of reperfusion(1h Pr/Cr: 1400 W 9068 ± 6910 mg/L/mmol/L vs Control 21586 ± 5464 mg/L/mmol/L, P = 0.026). Levels of 8-isoprostane were significantly lower in the 1400 W group [8-iso/creatinine ratio: Control 239 ± 136 pg/L/mmol/L vs 1400 W 139 ± 47 pg/L/mmol/L, P = 0.041].CONCLUSION: This study demonstrated that 1400 W reduced ischaemia reperfusion injury in this porcine kidney model of DCD donor. Kidneys had improved renal function and reduced oxidative stress.展开更多
Background:Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past.But it has seemed to remain controversial in the last decade,as a result of modified c...Background:Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past.But it has seemed to remain controversial in the last decade,as a result of modified clinical protocols,selected recipients,and advanced technology of organ perfusion and preservation.The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death(DCD).Methods:A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups:using graft from older donor(aged≥65 years,n=87)and younger donor(age<65 years,n=857).Propensity score matching(PSM)was applied to eliminate selection bias.Results:A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68%to 15.44%during the study period.The well-balanced older donor(n=79)and younger donor(n=79)were 1:1 matched.There were significantly more episodes of biliary nonanastomotic stricture(NAS)in the older donor group than the younger donor group[15/79(19.0%)vs.6/79(7.6%);P=0.017].The difference did not reach statistical significance regarding early allograft dysfunction(EAD)and primary non-function(PNF).Older livers had a trend toward inferior 1-,2-,3-year graft and overall survival compared with younger livers,but these differences were not statistically significant(63.1%,57.6%,57.6%vs.76.9%,70.2%,67.7%,P=0.112;64.4%,58.6%,58.6%vs.76.9%,72.2%,72.2%,P=0.064).The only risk factor for poor survival was ABO incompatible transplant(P=0.008)in the older donor group.In the subgroup of ABO incompatible cases,it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group[6/8(75.0%)vs.3/14(21.4%);P=0.014].Conclusions:Transplants with grafts from older donors(aged≥65 years)after circulatory death are more frequently associated with inferior outcome compared to those from younger donors.Older grafts from DCD are more likely to develop NAS,especially in ABO incompatible cases.展开更多
AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor tra...AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO<sub>2</sub>, PaO<sub>2</sub>, FiO<sub>2</sub>, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O<sub>2</sub> content was computed as [hemoglobin (gm/dL) × 1.37 (mL O<sub>2</sub>/gm) × SpO<sub>2</sub>%) + (0.003 × PaO<sub>2</sub>)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O<sub>2</sub>/100 mL blood vs 16.8 ± 3.3 mL O<sub>2</sub>/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r<sup>2</sup> = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006).CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.展开更多
AIM: To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS: Pertinent variables for all pediatric deaths(age ≤ 21 years) from 1/2009 to 6/20...AIM: To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS: Pertinent variables for all pediatric deaths(age ≤ 21 years) from 1/2009 to 6/2014 in our pediatric intensive care unit(PICU) were extracted through a detailed review of the medical records. As originally described, a recently developed tool that predicts timing of death in children following withdrawal of life support(dallas predictor tool [DPT]) was used to calculate individual scores for each patient. Individual scores were calculated for prediction of death within 30 min(DPT30) and within 60 min(DPT60). For various resulting DPT30 and DPT60 scores, sensitivity, specificity and area under the receiver operating characteristic curve were calculated.RESULTS: There were 8829 PICU admissions resulting in 132(1.5%) deaths. Death followed withdrawal of life support in 70 patients(53%). After excluding subjects with insufficient data to calculate DPT scores, 62 subjects were analyzed. Average age of patients was 5.3 years(SD: 6.9), median time to death after withdrawal oflife support was 25 min(range; 7 min to 16 h 54 min). Respiratory failure, shock and sepsis were the most common diagnoses. Thirty-seven patients(59.6%) died within 30 min of withdrawal of life support and 52(83.8%) died within 60 min. DPT30 scores ranged from-17 to 16. A DPT30 score ≥-3 was most predictive of death within that time period, with sensitivity = 0.76, specificity = 0.52, AUC = 0.69 and an overall classification accuracy = 66.1%. DPT60 scores ranged from-21 to 28. A DPT60 score ≥-9 was most predictive of death within that time period, with sensitivity = 0.75, specificity = 0.80, AUC = 0.85 and an overall classification accuracy = 75.8%.CONCLUSION: In this external cohort, the DPT is clinically relevant in predicting time from withdrawal of life support to death. In our patients, the DPT is more useful in predicting death within 60 min of withdrawal of life support than within 30 min. Furthermore, our analysis suggests optimal cut-off scores. Additional calibration and modifications of this important tool could help guide the intensive care team and families considering DCD.展开更多
Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasi...Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.展开更多
Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its potential....Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its potential.There is still room for expansion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation.We convened a multidisciplinary transplantation summit to examine various aspects of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transplantation,including abdominal and cardiothoracic surgeons,organ procurement organization directors,hepatologists,and gastroenterologists.The conference focused on identifying barriers to DCD organ utilization and strategies to overcome these barriers.We divide the barriers to DCD utilization into three mains categories:(Ⅰ)policy and process variation;(II)logistical and transportation challenges;and(Ⅲ)higher risk perceptions related to DCD outcomes.For each barrier,we proposed a variety of solutions,providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of DCD.There is a specific focus on ex situ machine perfusion,normothermic regional perfusion,and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.展开更多
Background:Early allograft dysfunction(EAD)is associated with decreased graft and patient survival rates.This study aimed to identify the severity of EAD and develop a predictive model for EAD after donation after cir...Background:Early allograft dysfunction(EAD)is associated with decreased graft and patient survival rates.This study aimed to identify the severity of EAD and develop a predictive model for EAD after donation after circulatory death(DCD)liver transplantation(LT).Furthermore,the influence of operative time on EAD incidence was also evaluated.Methods:In this retrospective,multicentre cohort study,nomograms were established based on a single-centre training cohort(n=321)and validated in a 3-center validation cohort(n=501).Results:The incidence rate of EAD was 46.4%(149/321)in the training cohort and 40.5%(203/501)in the validation cohort.Of the 149 EAD patients in the training cohort,77 patients with either elevated alanine aminotransferase(ALT)or aspartate aminotransferase(AST)were classified as having EAD type A,and the rest of the EAD patients were classified as having EAD type B.Recipients with EAD type B had lower graft and patient survival rates than recipients with EAD type A(P=0.043 and 0.044,respectively).We further developed a nomogram to predict EAD(graft weight,cold ischemia time,donor age,model for end-stage liver disease(MELD)score)and another nomogram to predict EAD type B(graft weight,cold ischemia time,MELD score).The nomograms for the prediction of EAD and EAD type B had good discrimination[concordance index(C-index)=0.712(0.666-0.758),0.707(0.641-0.773)]and calibration[Hosmer-Lemeshow(HL)P=0.384,P=0.425]in the validation cohort.An increased operative time(>6 h)was associated with increased EAD and EAD type B incidence in the high-risk group(P=0.005,P=0.020,respectively).Conclusions:EAD type B was associated with decreased graft and patient survival rates.The novel nomograms effectively predicted the incidence of EAD and EAD type B in DCD LT patients.展开更多
Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications Mach...Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications Machine perfusion(MP) is a beneficial alternative preservation strategy for donor livers, particularly fo those considered to be of suboptimal quality, and could expand the limited donor pool. Data sources: A comprehensive search in Pub Med, EMBASE, Ovid databases and Clinical Trials.gov website was conducted using the medical subject heading terms "machine perfusion", "machine preservation""liver transplantation", combined with free text terms such as "hypothermic", "normothermic" and "sub normothermic". The deadline for the search was September 30, 2017. Results: MP can be classified as hypothermic, subnormothermic, and normothermic with the tempera ture maintained at 0–12 °C, 25–34 °C and 35–38 °C, respectively. Twelve clinical trials of MP have been reported in recent years. MP effectively decreased AST/ALT level and the incidence of early allograft dys function. However, the graft and patient survival rate after MP were similar to static cold storage. The detailed clinical characteristics such as liver function, graft survival, patient survival and early allograf dysfunction were reviewed.Conclusions: Clinical trial results showed that MP improves delayed graft function, primary non-function and biliary strictures. However, MP still requires validation in large clinical trials and the key parameters during MP still require optimization.展开更多
The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or earl...The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.展开更多
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...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 analysed.RESULTS 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 validated.CONCLUSION 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.展开更多
In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of ...In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death(DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease(CKD). Acute kidney injury(AKI) post-LT has been recently recognized as an important risk factor for the occurrence of denovo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome(PRS) that can influence recipient's morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since preLT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A Pub Med search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on Pub Med search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRSinduced AKI, avoiding confounding factors, we have limited our study to "acute kidney injury AND DCD AND liver transplantation". Accordingly, three out of five studies were selected for our purpose.展开更多
文摘BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.
文摘To facilitate the implementation of controlled donation after circulatory death(cDCD)programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation(ECMO)team(Spokes),some countries and Italian Regions have launched a local cDCD network with a ECMO mobile team who move from Hub hospitals to Spokes for normothermic regional perfusion(NRP)implantation in the setting of a cDCD pathway.While ECMO teams have been clearly defined by the Extracorporeal Life Support Organization,regarding composition,responsibilities and training programs,no clear,widely accepted indications are to date available for NRP teams.Although existing NRP mobile networks were developed due to the urgent need to increase the number of cDCDs,there is now the necessity for transplantation medicine to identify the peculiarities and responsibility of a NRP team for all those centers launching a cDCD pathway.Thus,in the present manuscript we summarized the character-istics of an ECMO mobile team,highlighting similarities and differences with the NRP mobile team.We also assessed existing evidence on NRP teams with the goal of identifying the characteristic and essential features of an NRP mobile team for a cDCD program,especially for those centers who are starting the program.Differences were identified between the mobile ECMO team and NRP mobile team.The common essential feature for both mobile teams is high skills and experience to reduce complications and,in the case of cDCD,to reduce the total warm ischemic time.Dedicated training programs should be developed for the launch of de novo NRP teams.
文摘AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase(iN OS) inhibitor in a model of donation after circulatory death(DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min warm ischemia. They were then stored on ice for 18 h before being reperfused ex vivo with oxygenated autologous blood on an isolated organ perfusion system. The selective i NOS inhibitor 1400W(10 mg/kg) was administered before reperfusion(n = 6) vs control group(n = 7). Creatinine(1000 μmol/L) was added to the system, renal and tubular cell function and the level of ischemia reperfusion injury were assessed over 3 h of reperfusion using plasma, urine and tissue samples. RESULTS: Kidneys treated with 1400 W had a higher level of creatinine clearance(CrC l) [area under the curve(AUC) CrC l: 2.37 ± 0.97 mL /min per 100 g vs 0.96 ± 0.32 mL /min per 100 g, P = 0.004] and urine output [Total: 320 ± 96 mL vs 156 ± 82 mL, P = 0.008]. There was no significant difference in levels of fractional excretion of sodium(AUC, Fr ex Na+: Control, 186.3% ± 81.7%.h vs 1400 W, 153.4% ± 12.1%.h, P = 0.429). Levels of total protein creatinine ratio were significantly lower in the 1400 W group after 1 h of reperfusion(1h Pr/Cr: 1400 W 9068 ± 6910 mg/L/mmol/L vs Control 21586 ± 5464 mg/L/mmol/L, P = 0.026). Levels of 8-isoprostane were significantly lower in the 1400 W group [8-iso/creatinine ratio: Control 239 ± 136 pg/L/mmol/L vs 1400 W 139 ± 47 pg/L/mmol/L, P = 0.041].CONCLUSION: This study demonstrated that 1400 W reduced ischaemia reperfusion injury in this porcine kidney model of DCD donor. Kidneys had improved renal function and reduced oxidative stress.
基金the Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine(2013-0022).
文摘Background:Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past.But it has seemed to remain controversial in the last decade,as a result of modified clinical protocols,selected recipients,and advanced technology of organ perfusion and preservation.The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death(DCD).Methods:A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups:using graft from older donor(aged≥65 years,n=87)and younger donor(age<65 years,n=857).Propensity score matching(PSM)was applied to eliminate selection bias.Results:A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68%to 15.44%during the study period.The well-balanced older donor(n=79)and younger donor(n=79)were 1:1 matched.There were significantly more episodes of biliary nonanastomotic stricture(NAS)in the older donor group than the younger donor group[15/79(19.0%)vs.6/79(7.6%);P=0.017].The difference did not reach statistical significance regarding early allograft dysfunction(EAD)and primary non-function(PNF).Older livers had a trend toward inferior 1-,2-,3-year graft and overall survival compared with younger livers,but these differences were not statistically significant(63.1%,57.6%,57.6%vs.76.9%,70.2%,67.7%,P=0.112;64.4%,58.6%,58.6%vs.76.9%,72.2%,72.2%,P=0.064).The only risk factor for poor survival was ABO incompatible transplant(P=0.008)in the older donor group.In the subgroup of ABO incompatible cases,it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group[6/8(75.0%)vs.3/14(21.4%);P=0.014].Conclusions:Transplants with grafts from older donors(aged≥65 years)after circulatory death are more frequently associated with inferior outcome compared to those from younger donors.Older grafts from DCD are more likely to develop NAS,especially in ABO incompatible cases.
文摘AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO<sub>2</sub>, PaO<sub>2</sub>, FiO<sub>2</sub>, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O<sub>2</sub> content was computed as [hemoglobin (gm/dL) × 1.37 (mL O<sub>2</sub>/gm) × SpO<sub>2</sub>%) + (0.003 × PaO<sub>2</sub>)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O<sub>2</sub>/100 mL blood vs 16.8 ± 3.3 mL O<sub>2</sub>/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r<sup>2</sup> = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006).CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.
基金Supported by Health Resources and Services Administration,NO.234-2005-37011C
文摘AIM: To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS: Pertinent variables for all pediatric deaths(age ≤ 21 years) from 1/2009 to 6/2014 in our pediatric intensive care unit(PICU) were extracted through a detailed review of the medical records. As originally described, a recently developed tool that predicts timing of death in children following withdrawal of life support(dallas predictor tool [DPT]) was used to calculate individual scores for each patient. Individual scores were calculated for prediction of death within 30 min(DPT30) and within 60 min(DPT60). For various resulting DPT30 and DPT60 scores, sensitivity, specificity and area under the receiver operating characteristic curve were calculated.RESULTS: There were 8829 PICU admissions resulting in 132(1.5%) deaths. Death followed withdrawal of life support in 70 patients(53%). After excluding subjects with insufficient data to calculate DPT scores, 62 subjects were analyzed. Average age of patients was 5.3 years(SD: 6.9), median time to death after withdrawal oflife support was 25 min(range; 7 min to 16 h 54 min). Respiratory failure, shock and sepsis were the most common diagnoses. Thirty-seven patients(59.6%) died within 30 min of withdrawal of life support and 52(83.8%) died within 60 min. DPT30 scores ranged from-17 to 16. A DPT30 score ≥-3 was most predictive of death within that time period, with sensitivity = 0.76, specificity = 0.52, AUC = 0.69 and an overall classification accuracy = 66.1%. DPT60 scores ranged from-21 to 28. A DPT60 score ≥-9 was most predictive of death within that time period, with sensitivity = 0.75, specificity = 0.80, AUC = 0.85 and an overall classification accuracy = 75.8%.CONCLUSION: In this external cohort, the DPT is clinically relevant in predicting time from withdrawal of life support to death. In our patients, the DPT is more useful in predicting death within 60 min of withdrawal of life support than within 30 min. Furthermore, our analysis suggests optimal cut-off scores. Additional calibration and modifications of this important tool could help guide the intensive care team and families considering DCD.
文摘Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.
文摘Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its potential.There is still room for expansion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation.We convened a multidisciplinary transplantation summit to examine various aspects of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transplantation,including abdominal and cardiothoracic surgeons,organ procurement organization directors,hepatologists,and gastroenterologists.The conference focused on identifying barriers to DCD organ utilization and strategies to overcome these barriers.We divide the barriers to DCD utilization into three mains categories:(Ⅰ)policy and process variation;(II)logistical and transportation challenges;and(Ⅲ)higher risk perceptions related to DCD outcomes.For each barrier,we proposed a variety of solutions,providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of DCD.There is a specific focus on ex situ machine perfusion,normothermic regional perfusion,and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.
基金supported by grants from the National Science and Technology Major Project(Grant number:2017ZX10203205)National Natural Science Funds for Distinguished Young Scholar of China(Grant number:81625003)+1 种基金Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ17H160006)National Natural Science Foundation of China(Grant number.81570589,81800578).
文摘Background:Early allograft dysfunction(EAD)is associated with decreased graft and patient survival rates.This study aimed to identify the severity of EAD and develop a predictive model for EAD after donation after circulatory death(DCD)liver transplantation(LT).Furthermore,the influence of operative time on EAD incidence was also evaluated.Methods:In this retrospective,multicentre cohort study,nomograms were established based on a single-centre training cohort(n=321)and validated in a 3-center validation cohort(n=501).Results:The incidence rate of EAD was 46.4%(149/321)in the training cohort and 40.5%(203/501)in the validation cohort.Of the 149 EAD patients in the training cohort,77 patients with either elevated alanine aminotransferase(ALT)or aspartate aminotransferase(AST)were classified as having EAD type A,and the rest of the EAD patients were classified as having EAD type B.Recipients with EAD type B had lower graft and patient survival rates than recipients with EAD type A(P=0.043 and 0.044,respectively).We further developed a nomogram to predict EAD(graft weight,cold ischemia time,donor age,model for end-stage liver disease(MELD)score)and another nomogram to predict EAD type B(graft weight,cold ischemia time,MELD score).The nomograms for the prediction of EAD and EAD type B had good discrimination[concordance index(C-index)=0.712(0.666-0.758),0.707(0.641-0.773)]and calibration[Hosmer-Lemeshow(HL)P=0.384,P=0.425]in the validation cohort.An increased operative time(>6 h)was associated with increased EAD and EAD type B incidence in the high-risk group(P=0.005,P=0.020,respectively).Conclusions:EAD type B was associated with decreased graft and patient survival rates.The novel nomograms effectively predicted the incidence of EAD and EAD type B in DCD LT patients.
基金supported by grants from the National Natural Science Foundation of China(81470891)China Postdoctoral Science Foundation(2017M610374)+1 种基金Science and Technology Bureau of Zhejiang Province,China(2016C33145)Innovative Research Groups of the National Natural Science Foundation of China(81421062)
文摘Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications Machine perfusion(MP) is a beneficial alternative preservation strategy for donor livers, particularly fo those considered to be of suboptimal quality, and could expand the limited donor pool. Data sources: A comprehensive search in Pub Med, EMBASE, Ovid databases and Clinical Trials.gov website was conducted using the medical subject heading terms "machine perfusion", "machine preservation""liver transplantation", combined with free text terms such as "hypothermic", "normothermic" and "sub normothermic". The deadline for the search was September 30, 2017. Results: MP can be classified as hypothermic, subnormothermic, and normothermic with the tempera ture maintained at 0–12 °C, 25–34 °C and 35–38 °C, respectively. Twelve clinical trials of MP have been reported in recent years. MP effectively decreased AST/ALT level and the incidence of early allograft dys function. However, the graft and patient survival rate after MP were similar to static cold storage. The detailed clinical characteristics such as liver function, graft survival, patient survival and early allograf dysfunction were reviewed.Conclusions: Clinical trial results showed that MP improves delayed graft function, primary non-function and biliary strictures. However, MP still requires validation in large clinical trials and the key parameters during MP still require optimization.
基金funding received in the form of the Catherine Marie Enright research scholarship from the Royal Australasian College of Surgeons to support his program of research
文摘The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.
基金supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trustthe University of Birmingham
文摘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 analysed.RESULTS 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 validated.CONCLUSION 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.
基金Supported by An international research grant 2014 of the Italian Society of NephrologyThe study sponsor provided logistic support but had no role in the collection and analysis of data or in the writing of the review and in the decision to submit the paper for publication+1 种基金The study also received support from the NIHR Birmingham Liver Biomedical Research UnitThe opinions expressed are those of the authors and not necessarily those of the NHS,the NIHR or the Department of Health
文摘In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death(DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease(CKD). Acute kidney injury(AKI) post-LT has been recently recognized as an important risk factor for the occurrence of denovo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome(PRS) that can influence recipient's morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since preLT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A Pub Med search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on Pub Med search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRSinduced AKI, avoiding confounding factors, we have limited our study to "acute kidney injury AND DCD AND liver transplantation". Accordingly, three out of five studies were selected for our purpose.