Donor-derived infections among Chinese donation after cardiac death liver recipients

AIM To investigate blood cultures of deceased donors and report the confirmed transmission of bacterial infection from donors to liver recipients.METHODS We retrospectively studied the results of blood cultures among our donation after cardiac death(DCD) donors and calculated the donor-derived bacterial infection rates among liver recipients. Study participants underwent liver transplantation between January 1, 2010 and February 1, 2017. The study involved a total of 67 recipients of liver grafts from 67 DCD donors. We extracted the data of donors' and patients' characteristics, culture results and clinical outcomes, especially the post-transplant complications in liver recipients, from electronic medical records. We analyzed the characteristics of the donors and the corresponding liver recipients with emphasis put on donor-derived infections.RESULTS Head trauma was the most common origin of death among our 67 DCD donors(46.3%). Blood taken prior to the procurement operation was cultured for 53 of the donors, with 17 episodes of bloodstream infections developing from 13 donors. The predominant organism isolated from the blood of donors was Gram-positive bacteria(70.6%). Only three(4.5%) of 67 liver recipients developed confirmed donor-derived bacterial infections,with two isolates of multidrug-resistant Klebsiella pneumoniae and one isolate of multidrug-resistant Enterobacter aerogenes. The liver recipients with donorderived infections showed relation to higher crude mortality and graft loss rates(33.3% each) within 3 mo post transplantation, as compared to those without donor-derived infections(9.4% and 4.7%, respectively). All three liver recipients received appropriate antimicrobial therapy.CONCLUSION Liver recipients have high occurrence of donor-derived infections. The liver recipients with donor-derived multidrug-resistant Enterobacteriaceae infections can have good outcome if appropriate antimicrobial therapy is given.

Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats

BACKGROUND： Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum （ER） stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death （DCD） liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid （TUDCA） and 4-phenyl butyric acid （PBA）, on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS： Male Sprague-Dawley rats （8-10 weeks） were randomly divided into control group： liver grafts without warm ischemia were implanted; DCD group： warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups： based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS： Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation （P〈0.01, 0.01 and 0.05, respectively） and oxidative indices （P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine）, more severe liver damage （P〈0.01） and up-regulated ER stress signal expressions （P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12）. All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels （P〈0.05）, increased superoxide dismutase activities （P〈0.01）, alleviated liver damage （P〈0.01）, down-regulated ER stress signal expressions （P〈0.01） and improved postoperative survivals （P〈0.01）. CONCLUSIONS： ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.

Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death

AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.

Kidney donation after cardiac death

There is continuing disparity between demand for and supply of kidneys for transplantation. This review describes the current state of kidney donation after cardiac death(DCD) and provides recommendations for a way forward. The conversion rate for potential DCD donors varies from 40%-80%. Compared to controlled DCD, uncontrolled DCD is more labour intensive, has a lower conversion rate and a higher discard rate. The super-rapid laparotomy technique involving direct aortic cannulation is preferred over in situ perfusion in controlled DCD donation and is associated with lower kidney discard rates, shorter warm ischaemia times and higher graft survival rates. DCD kidneys showed a 5.73-fold increase in the incidence of delayed graft function(DGF) and a higher primary non function rate compared to donation after brain death kidneys, but the long term graft function is equivalent between the two. The cold ischaemia time is a controllable factor that significantly influences the outcome of allografts, for example, limiting it to < 12 h markedly reduces DGF. DCD kidneys from donors < 50 function like standard criteria kidneys and should be viewed as such. As the majority of DCD kidneys are from controlled donation, incorporation of uncontrolled donation will expand the donor pool. Efforts to maximise the supply of kidneys from DCD include: implementing organ recovery from emergency department setting; improving familyconsent rate; utilising technological developments to optimise organs either prior to recovery from donors or during storage; improving organ allocation to ensure best utility; and improving viability testing to reduce primary non function.

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

AIM To identify objective predictive factors for donor after cardiac death(DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index(DCD-RI) to help in prospective decision making on organ use.METHODS The model included objective data from a single institute DCD database(2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated.RESULTS DCD graft survival predictors were primary indication for transplant(P = 0.066), retransplantation(P = 0.176), MELD > 25(P = 0.05), cold ischemia > 10 h(P = 0.292) and donor hepatectomy time > 60 min(P = 0.028).According to the calculated DCD-RI score three risk classes could be defined of low(DCD-RI < 1), standard(DCD-RI 2-4) and high risk(DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively.CONCLUSION The DCD-RI score independently predicted graft loss(P < 0.001) and the DCD-RI class predicted graft survival(P < 0.001).

Potential approaches to improve the outcomes of donation after cardiac death liver grafts

There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death(DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods:(1) different ex vivo perfusion techniques;(2) persufflation with oxygen; and(3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft's for transplantation, improve the outcomes, and decrease the mortality on the waiting list.

Current situation of mechanical CPR devices in donors after cardiac death

Mechanical CPR (cardiopulmonary resuscitation) devices help performing correct chest compressions in the event of a cardiorespiratory arrest. These devices are comfortable and useful, they keep chest compression following the recommendations as they do not depend on interpersonal variability, they do not get tired, their use is simple and one of the rescuers is released from this task, thus facilitating the assistance. Besides, their use in transport conditions makes it safer. However, when coming to results, these mechanical CPR devices have not clearly demonstrated such an advantage, neither in the field of cardiac arrest, nor in organ preservation in the case of donors after cardiac death. In donors after cardiac death they are widely used by most of the emergency services involved, but a number of injuries produced in lungs during the early years of their use have made it controversial. In this paper we make a review of the road traveled by mechanical CPR devices and of the main articles which mark the way.

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

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.

Current attitudes toward organ donation after cardiac death in northwest China

Background People＇s attitude toward organ donation after cardiac death （DCD） has not come to an agreement in different countries and regions.Influenced by the local culture in China for thousands of years,the general public has different ideas about this issue.The purpose of this study was to investigate the current attitudes trend and characteristics of transplantation with organs donated after cardiac death in northwest China.Methods This largest single-center cohort study was performed by an interview or by telephone using a questionnaire.The family members of potential DCD donors were recruited from the First Affiliated Hospital,medical college of Xi＇an Jiaotong University located in a metropolitan area of northwest China.The 12-item attitude questionnaire was specifically developed from the literature review with coordinator,physician,and donor＇s family feedback.The participants were asked to rate the queries on a 5-point Likert intensity scale.Results The 174 participants included 56 （32.2％） women and 118 （67.8％） men.Most people were aged between 41 and 50 years （n=63,36.2％）,31 and 40 years （n=59,33.9％）,and less than 30 years （n=36,20.7％）.The top five attitudes of participants were the best person to suggest organ donation to a family was ranked as the DCD coordinator of Red Cross Organization （RCO,n=160,92％）,donor is a hero （n=143,82.2％）,honor to be a donor＇s family member （n=136,78.2％）,improved relationship with colleagues （n=124,71.3％）,and with recipient after donation （n=123,70.7％）.The best person to suggest organ donation to a family was ranked as the coordinator of RCO （n=160,92％）,doctor unrelated to transplantation （n=104,59.8％）,social worker （n=36,20.7％）,and doctor related to transplantation （n=25,14.4％）.The top two reasons for non-consent to donation were that the family insisted on intact body after patient death and did not want to have surgery again （n=51,41.5％）,and feared that they would be misunderstood by neighbors,relatives,and friends about donation （n=28,22.8％）.Conclusions This study revealed initial attitudes toward DCD in China.Some data afford insight into the decision-making procedure.The concerns of potential DCD donors and their families may help professionals provide better interventions in the future.

Successful Abdominal Organ Donation after Brain Death in a Patient with a Biventricular Assist Device: Extending Extended Criteria

Few studies address the potential for donation after brain death (DBD) in the limited population of patients with ongoing mechanical circulatory support (MCS). A case study was conducted reviewing available records of both donor and recipient, and available literature. The donor was a young female with an acute myocardial infarction precipitating emergent off-pump 2-vessel bypass graft complicated by profound cardiogenic shock refractory to inotropes and intra-aortic balloon pump. A heparin drip was started following percutaneous placement of a left ventricular-assist device (TandemHeart?) which improved her hemodynamics to stabilize for transfer. She ultimately required surgical placement of biventricular assist device (CentraMag?) to normalize hemodynamics. Two days post-operatively, she developed a cerebellar hemorrhage and was declared brain dead. Pre-donation blood chemistry showed adequate end-organ function. Both kidneys were placed locally. The liver was rejected for two regional status 1 patients and by all other local centers. We accepted the liver for a patient with polycystic liver disease with a MELD exception score of 20. The recipient is now 4 years post-transplant with excellent graft function. Extending donor criteria to include MCS patients can result in successful transplantation and should be considered in selected circumstances once satisfactory donor end-organ function is established.

人体器官捐献中的死亡标准问题

死亡后捐献是开展公民逝世后器官捐献工作最重要的伦理原则。新修订的《人体器官捐献和移植条例》未定义死亡,且回避了“是否承认脑死亡”这一关键性问题,器官捐献工作中可能存在一定的法律风险或损害捐献者权益的情况。死亡是人类生命过程最终无法避免的事实,任何时代都需要而且只能通过一些具体的标准来判定死亡。死亡标准的建立基础是人们所持有的死亡观,并受到生产力发展水平和其他社会因素制约。中西方死亡判定标准的认定上存在明显差异。为了规范器官捐献和移植工作,推进器官捐献高质量发展,必须坚持动机纯正原则,以知情同意为前提,尊重捐献者及其近亲属的死亡标准自主选择权,严格遵循死亡判定程序和操作规范,确保死亡认定的科学性、准确性和公正性。

边缘供肝面临的机遇与挑战

随着手术技术和术后免疫抑制治疗的不断突破与成熟,肝移植受者和移植物存活率显著提高,供肝短缺已成为限制肝移植临床发展的主要阻碍,如何扩大供肝来源也成为了当前迫切需要解决的问题。高龄供肝、脂肪变性供肝、病毒性肝炎供肝、心脏死亡器官捐献供肝等常见边缘供肝在临床肝移植中的使用已经取得了一定的突破性进展,但边缘供肝的使用仍存在较多限制。因此,本文对边缘供肝的定义,几种常见边缘供肝的应用及研究进展进行综述,探讨目前边缘供肝面临的机遇与挑战,旨在为临床肝移植供者池的扩大提供参考,造福更多终末期肝病患者。

加速康复外科在老年肝移植受者围手术期临床应用中的效果

目的探索加速康复外科(ERAS)指导下的围手术干预策略在老年肝移植受者中的应用价值。方法回顾性分析405例肝移植受者的临床资料,根据年龄分为老年组(≥60岁,122例)和非老年组(<60岁,283例),所有患者均进行ERAS指导下的围手术期干预处理,分析两组受者术中、术后相关指标,并发症发生情况及出院情况。结果两组受者麻醉时间,手术时间,无肝期,出血量,输血量,关腹前乳酸水平,呼吸机辅助时间,重症监护室(ICU)入住时间,Caprini评分,CHIPPS评分,胃管、尿管、引流管拔除时间,首次饮水时间,首次下地活动时间和首次肛门排气时间差异均无统计学意义(均为P>0.05),老年组首次进食时间晚于非老年组(P<0.05)。两组受者发热、腹腔积液、肺部感染、胃排空障碍、出血、非活动性静脉血栓发生率差异均无统计学意义(均为P>0.05)。两组受者出院前天冬氨酸转氨酶、总胆红素、直接胆红素、血清肌酐水平及总住院时间差异均无统计学意义(均为P>0.05);老年组受者丙氨酸转氨酶值比非老年组低,差异有统计学意义(P<0.05)。非老年组与老年组受者术后30 d内均无非计划再次手术发生,出院后30 d内再入院率差异无统计学意义(P>0.05)。结论ERAS干预策略有助于老年肝移植受者围手术期的恢复,达到与非老年肝移植受者同等的术后恢复水平。

心脏移植的发展现状和新挑战

心脏移植是终末期心力衰竭患者的首选治疗。供者不足一直以来都是限制心脏移植数量增长的主要问题,随着新技术的不断更新和引入,供者池被不断扩大,比如使用年龄较大的供者、丙型肝炎病毒感染的供者、毒品过量致死的供者或心脏死亡器官捐献(DCD)供者的心脏等。与此同时,高龄、多器官功能不全、机械循环支持及人类白细胞抗原抗体致敏受者的比例近几年明显增加。供者数量的不足、受者状况的复杂化、免疫抑制治疗的个体化管理和远期移植物血管病的防治等都是心脏移植领域面临的挑战。本文通过概述现今全球在扩大供者库、提高受者质量、加强排斥反应的诊治和心脏移植物血管病变的预防等方面的新进展,以期有助于改善在等待或已经接受心脏移植的终末期心力衰竭患者的生存时间和生活质量。

Predictive Score Model for Delayed Graft Function Based on Easily Available Variables before Kidney Donation after Cardiac Death

Background： How to evaluate the quality of donation after cardiac transplantation in China. Hence, the aim of this study was to develop kidneys before DCD. death （DCD） kidneys has become a critical problem in kidney a simple donor risk score model to evaluate the quality of DCD Methods： A total of 543 qualified kidneys were randomized in a 2：1 manner to create the development and validation cohorts. The donor variables in the development cohort were considered as candidate univariate predictors of delayed graft function （DGF）. Multivariate logistic regression was then used to identify independent predictors of DGF with P 〈 0.05. Date from validation cohort were used to validate the donor scoring model. Results： Based on the odds ratios, eight identified variables were assigned a weighted integer; the sum of the integer was the total risk score for each kidney. The donor risk score, ranging from 0 to 28, demonstrated good discriminative power with a C-statistic of 0.790. Similar results were obtained from validation cohort with C-statistic of 0.783. Based on the obtained frequencies of DGF in relation to different risk scores, we formed tour risk categories of increasing severity （scores 04, 5 9, 10-14, and 15 28）. Conclusions： The scoring model might be a good noninvasive tool for assessing the quality of DCD kidneys before donation and potentially useful for physicians to make optimal decisions about donor organ offers.

心脏死亡器官捐献供肾与亲属活体捐献供肾的移植效果

目的 探讨心脏死亡器官捐献(donation after cardiac death,DCD)供肾与亲属活体捐献(livingdonor,LD)供肾移植术后短期效果的差异,评估DCD供肾移植的可行性及安全性,以便更好地利用DCD来源供肾。方法 选取2017年12月至2023年1月在临沂市人民医院泌尿外科行肾脏移植术后患者,根据供者的来源分为DCD组和LD组。收集两组的临床资料,并比较两组术后不同时间血肌酐变化及术后并发症等发生情况。结果 共纳入患者70例,其中DCD为50例,LD为20例。两组均恢复顺利,术后2周内血肌酐均降至200μmol/L以下,手术时间、住院时间及术后并发症发生率均差异无统计学意义。但DCD组术后2周内血肌酐水平要高于LD组,其中第1~7天及第9天两组血肌酐水平比较差异有统计学意义(P <0.05)。结论 DCD肾移植效果确切,但在术后短期肾功能恢复与LD供肾存在一定的差异,需要加强术前评估。

小香猪DCD边缘供体模型的构建及其供肾病理学观察

目的建立一种小香猪心脏死亡后器官捐献(donation after cardiac death,DCD)供体模型,并对DCD供肾进行病理学评价。方法7只4~6月龄的雄性小香猪(13~17 kg)分为标准供体对照组(C组,n=3)和DCD组(n=4),两组肌注苯巴比妥钠麻醉诱导后,建立耳缘静脉通道,行血压、心电图和氧饱和度(SaO_(2))监测,同时注射丙泊酚、舒芬太尼强化麻醉诱导效果。C组气管插管后机械通气,丙泊酚、瑞芬太尼和顺阿曲库铵维持麻醉,行开腹术摘取肾脏;DCD组静脉推注肝素(300 IU/kg)抗凝,后注射丙泊酚600 mg和顺阿曲库铵10 mg使猪心跳呼吸停止,待心停跳30 min时摘取肾脏。2组肾脏均切成小块组织,4%多聚甲醛固定,行石蜡包埋,采用HE染色,光镜下观察正常肾脏和DCD边缘供体肾脏的病理结果变化并进行组织损伤评分。结果DCD组共成功建模4只猪在注射过量麻醉药后SaO_(2)下降至80%的平均时间为(3.25±1.89)min,心脏骤停平均时间为(7.75±3.10)min;热缺血30 min后获取的DCD边缘供肾与C组供肾相比,肾小管损伤评分增高(P<0.05),肾小球损伤评分均值增高,但差异无统计学意义。结论采用静脉注射过量丙泊酚和顺阿曲库铵的方法可有效建立猪DCD边缘供体模型。

右美托咪定与氙气改良的UW液对猪心脏死亡供肺的保护作用

目的探讨右美托咪定(Dexmedetomidine,DEX)与氙气(Xenon,Xe)添加改良的威斯康星大学保存液(university of Wisconsin solution,UW液)对猪心脏死亡器官捐献(donation after cardiac death,DCD)供肺的保护作用。方法4~6月龄雄性小香猪4只,体质量为13~17 kg,采用静推顺式阿曲库铵及停止供氧建立猪心脏停跳模型,待热缺血(warm ischemia,WI)1 h后取肺并将其切成薄片。其中部分切片被命名为WI组,剩余切片则置于N_(2)/DEX/Xe添加的4种UW液中4℃冷缺血(cold ischemia,CI)24 h,并分别命名为WI+CI+N_(2)组、WI+CI+DEX组、WI+CI+DEX+30%Xe组、WI+CI+DEX+50%Xe组。5组肺组织切片行HE染色及组织损伤评分;TUNEL法检测细胞凋亡;Western blot检测cleaved Caspase-3、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)表达;免疫组化检测GPX4、高迁移率族蛋白1(high mobility group protein 1,HMGB1)表达。结果与WI组比较:HE染色显示各组肺泡结构均无明显破坏,肺水肿及炎症细胞浸润不明显,肺损伤评分无显著变化;WI+CI+N_(2)组TUNEL阳性细胞数、cleaved Caspase-3蛋白表达显著增加(P<0.05);各组肺组织GPX4蛋白表达无显著变化;WI+CI+N_(2)组HMGB1蛋白表达量显著增多(P<0.05)。与WI+CI+N_(2)组比较:WI+CI+DEX组、WI+CI+DEX+30%Xe组和WI+CI+DEX+50%Xe组的TUNEL阳性细胞数显著减少(P<0.001,P<0.05,P<0.05);WI+CI+DEX+30%Xe组HMGB1蛋白表达显著降低(P<0.01)。结论DEX单独或联合Xe添加改良的UW液可通过抑制细胞凋亡、下调HMGB1表达及细胞质内弥散对猪DCD供肺发挥更好的细胞保护效果。

心脏机械灌注技术的研究现状

高质量的供心是移植成功的先决条件和根本保障,合理的供心保存技术对提升供心质量、改善心脏移植预后具有关键作用。静态冷保存(SCS)是目前移植心脏的标准保存技术,但该技术易造成供心严重的冷缺血损伤,且保存过程中无法评估心脏功能。机械灌注技术作为当前器官保存的重要新型技术,比SCS更符合生理状态,能够在器官保存过程中清除代谢废物、提供代谢需求的基本物质,一定程度延长保存时间、提升保存效果;也能有效评估器官功能,改善心脏移植预后;同时还能修复器官损伤,显著优化器官质量,提高供器官利用率。本文就心脏机械灌注技术的研究现状展开综述。