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.

Pathological Characteristics of Liver Allografts from Donation after Brain Death Followed by Cardiac Death in Pigs

Donation after brain death followed by circulatory death （DBCD） is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs （25-30 kg） were allocated randomly into donation after brain death （DBD）, donation after circulatory death （DCD） and DBCD groups. Brain death was induced by aug- menting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were col- lected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [（0.56±0.30）%] and DBCD [（0.50 ±0.11）%] groups was much lower than that in DCD group [（3.78±0.33）%] （P〈0.05）. And there was no significant difference between DBD group and DBCD group （P〉0.05））. The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

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 con-trolled 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 signifcantly infuences the outcome of allografts, for example, limiting it to 〈 12 h markedly reduces DGF. DCD kidneys from donors 〈 50 function like stan-dard criteria kidneys and should be viewed as such. As the majority of DCD kidneys are from controlled dona-tion, incorporation of uncontrolled donation will expand the donor pool. Efforts to maximise the supply of kid-neys from DCD include： implementing organ recovery from emergency department setting; improving family consent 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.

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.

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.

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.

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.

全球DCD发展趋势及临床实践的要点

器官移植给许多终末期器官衰竭患者带来了治愈希望。但人体器官来源不足已成为严重制约人体器官移植发展的重要因素之一。心脏死亡器官捐献(DCD)是扩充供者来源的一种安全途径,各国在努力提高脑死亡器官捐献(DBD)数量的同时,在条件允许的情况下不应错失DCD的机会。本文从DCD历史背景和全球发展趋势、可控型DCD实施的基本条件、可控型DCD实践中的关键问题以及伦理审查等方面进行探讨。

亲属活体供肾和DCD供肾肾移植的临床疗效比较

目的:比较亲属活体供肾与心脏死亡器官捐献(donation after cardiac death,DCD)供肾肾移植的临床效果。方法:回顾性分析2011-04～2018-01兰州大学第二医院肾移植科同期完成的45例亲属活体供肾(亲属活体供肾组)和21例DCD供肾肾移植受者(DCD供肾组)的临床资料,比较两组患者移植肾一般情况、肾功能、人肾累积存活率及并发症情况。结果:两组患者性别、BMI、手术时间、住院时长比较,差异无统计学意义(P>0.05),供、受者年龄和透析时间比较,差异有显著统计学意义(P<0.01)。亲属活体供肾组和DCD供肾组受者急性排斥反应分别发生2例(4.4%)和6例(28.6%),两组间差异有统计学意义(P<0.05);移植肾功能延迟恢复分别发生1例(2.2%)和2例(9.5%),两组间差异无统计学意义(P>0.05)。术后1周两组患者血肌酐比较,差异均有统计学意义,且术后患者血肌酐恢复至正常的时间比较,差异有统计学意义(P<0.05或P<0.01);术后2周、1个月、2个月两组患者血肌酐差异均无统计学意义。两组整个随访期的人、肾累积存活率比较,差异无统计学意义。结论:亲属活体供肾与DCD供肾肾移植早期效果类似,活体肾移植在移植肾术后急性排斥反应及肾功能短期恢复方面具有一定优势,但随访期间的人、肾累积存活率相同。

DCD角膜移植术后角膜内皮细胞的变化

目的探讨心脏死亡供体器官捐献(donation after cardiac death,DCD)来源角膜植片行穿透性角膜移植后角膜内皮细胞变异情况.方法用角膜内皮显微镜对心脏死亡供体来源角膜植片行穿透性角膜移植191例眼术后角膜植片分别于术后1~4周;5~12周;4~6月;7~12月行角膜内皮镜检查.结果 (1)191例患者中有48例患者角膜内皮镜检出,143例患者角膜内皮镜无法检出,检出率占25%;(2)48例患者术后1~4周、2~3月、4~6月及7~12月的内皮细胞细胞密度(2271.15±321.47)个/mm^2、(1971.33±358.18)个/mm^2、(1826.59±303.92)个/mm^2、及(1753.14±306.31)个/mm^2.平均细胞面积由术前的(388.45±95.26)μm增加到术后7~12月的(638.63±124.73),细胞大小变异系数(cv值)由30.15%增加到65.04%,六角形细胞比例由(52.59±7.26)%下降到(40.01±11.35)%.结论 (1)角膜内皮镜检查对于早期角膜移植术后患者内皮细胞识别率较低,敏感度差,角膜移植术后早期内皮镜无法测出结果时可选择共焦显微镜评价观察角膜内皮细胞的变化;(2)穿透性角膜移植术后供眼角膜内皮细胞密度逐渐减少,六角形细胞比例渐变小平均细胞面积和cv值均渐增大.(3)DCD角膜移植术后1 a,尤其是术后3月应加强术后随访,当发现有早期排斥反应的征象时,及时进行抗排斥治疗对于减少早期排斥反应尤为重要.

DCD供体质量对肝移植术后感染的危险因素分析

目的研究心脏死亡后器官捐献(DCD)供体质量对肝移植术后感染的危险因素。方法选取我院2015年1月至2017年1月128例DCD肝移植受者为研究对象,统计肝移植术受者住院期间感染发生率,根据有无术后感染将受者分组。对所有受者进行为期1年随访,比较感染组与未感染组术后1年生存情况。收集DCD供体年龄、性别、体重指数、有无脂肪肝、热缺血时间、冷缺血时间、血钠、血钾、白蛋白、总胆红素、谷丙转氨酶、谷草转氨酶。结果 128例肝移植受者在住院期间,共63例发生术后感染,感染率为49. 2%。共分离151株病原菌,革兰阳性菌65株,占43. 0%;革兰阴性菌71株,占47. 0%;真菌15株,占9. 9%。术后1年随访中,感染组累积生存率显著低于未感染组(P <0. 05)。感染组体重指数≥24kg/m^2、中或重度脂肪肝供体比例显著高于未感染组(P <0. 05),白蛋白显著低于未感染组(P <0. 05),冷缺血时间、总胆红素显著高于未感染组(P <0. 05)。经Logistic回归分析显示,供体脂肪肝、冷缺血时间、总胆红素是肝移植术后感染的独立危险因素,白蛋白是其独立保护因素。结论供体体重指数、脂肪肝、冷缺血时间、白蛋白、总胆红素等DCD供体质量因素对肝移植术后感染有显著影响。

间充质干细胞体外修复DCD供肝的研究

目的探讨体外心脏死亡器官捐献(DCD)供肝的修复方法,采用大鼠骨髓间充质干细胞(BMMSCs)联合常温机械灌注(NMP),研究其对DCD肝脏的影响。方法体外培养BMMSCs,建立心脏死亡后热缺血45分钟的模型。将Wistar大鼠随机分成3组:A组(冷保存组)、B组(单纯NMP组)和C组(NMP+BMMSCs组),4小时为各组研究时间点(n=5)。血生化仪检测循环液中的丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST),苏木素-伊红(HE)染色观察肝脏的病理情况,血气分析仪检测灌注组的耗氧量。结果 C组ALT和AST的量明显低于B组(ALT:F=177.98,P<0.05;AST:F=284.38,P<0.05);C组ALT和AST的量明显低于A组(ALT:F=3 100.39,P<0.05;AST:F=192.88,P<0.05)。C组的耗氧量在1小时后明显高于B组(4小时:F=22.90,P<0.05)。肝脏病理显示C组的修复作用明显优于其他两组。结论 BMMSCs联合NMP对DCD肝脏功能、病理及细胞活性均具有明显保护作用,为修复DCD供肝提供了新的方法。

DCD角膜移植术后角膜内皮细胞与排斥反应的相关性分析

目的:探讨心脏死亡供体器官捐献(donation after cardiac death,DCD)来源角膜植片术后排斥反应与角膜内皮细胞的相关性。方法:用角膜内皮显微镜对心脏死亡供体来源角膜植片行穿透性角膜移植术后发生排斥反应的28例28眼角膜植片分别于术后<1、2~3、4~6、7~12mo行角膜内皮镜检查。结果:28例患者术后<1、2~3、4~6、7~12mo的角膜内皮细胞变异系数分别为38.23%、49.56%、57.18%、65.04%;角膜内皮细胞密度分别为2071.15±311.47、1771.33±348.18、1626.59±353.92、1553.14±307.31个/mm2;角膜内皮细胞变异系数与排斥反应呈正相关关系(r=0.95,P<0.05);术后角膜内皮细胞密度与排斥反应呈负相关关系(r=-0.93,P<0.05)。结论:DCD穿透性角膜移植术后发生排斥反应时有角膜内皮细胞变异系数逐步增高,角膜内皮细胞密度逐步降低的趋势;角膜内皮细胞变异系数、角膜内皮细胞密度可作为早期检测术后排斥反应的指标。

不同肾脏替代治疗方式在DCD供肾移植中的临床分析

目的探讨腹膜透析、间断性血液透析(intermittent hemodialysis,IHD)、连续肾脏替代治疗(continuous renal replacement therapy,CRRT)3种肾脏替代治疗方式在公民逝世器官捐献(donation after citizen’s death,DCD)供肾移植中的临床应用。方法选择2013年1月-2017年12月期间DCD供肾移植术后58例行肾脏替代治疗受者,回顾分析腹膜透析(18例)、IHD(30例)、CRRT(10例)3种肾脏替代治疗方式的治疗效果及并发症。结果 3组透析治疗后血BUN、Crea、血钾的浓度较治疗前明显下降(P<0.05),IHD及CRRT组治疗前后Crea、BUN差值高于腹膜透析组(P<0.05),IHD与CRRT组比较差异无统计学意义(P>0.05)。其中发生心功能衰竭8例,发生率为13.79%(8/58);肺部感染11例,18.97%(11/58);急性肺水肿1例,发生率为1.72%(1/58);腹腔感染3例,发生率为5.17%(3/58);胃肠道功能紊乱、心律失常均为4例,6.90%(4/58);低血压6例,发生率为发生率为10.34%(6/58);诱发出血5例,发生率为发生率为8.62%(5/58)。结论 DCD供肾移植术后肾脏替代治疗选择恰当的肾脏替代治疗方式是保护移植肾功能甚至挽救患者生命的关键。

极低龄DCD供肝在婴儿肝移植中的疗效分析

目的评估极低龄儿童心脏死亡器官捐献（DCD）供肝在婴儿肝移植中的疗效。方法收集我院2013年12月~2015年4月应用极低龄DCD供肝行肝移植的11例患儿临床资料,包括供体资料、受体资料及随访资料。结果所有供者年龄均小于2月,11例婴儿肝移植受者年龄4~11月。术后有5例患儿出现并发症,其中肝动脉血栓形成4例,门静脉血栓形成1例,肝性脑病3例,肺炎1例,经治疗后均痊愈出院。所有患者随访均长期健康存活。结论极低龄DCD供肝可以作为婴儿肝移植肝源,但并发症发生率偏高。

DCD供肾肾移植及免疫诱导的单中心经验总结

目的探讨DCD捐献肾脏移植的经验及免疫诱导的临床效果观察。方法分析本院于2011年12月至2013年12月完成的40例DCD捐献肾移植患者的临床资料,根据免疫诱导药物的不同,分为舒莱组(10例)、ATG组(15例)和ATG-F组(15例)。结果 40例患者中除3例出现DGF外,其余患者术后血肌酐均平稳下降,恢复正常;3组患者中均有1例发生DGF,ATG组发生急排1例,其余组无急排发生;所有组均无原发肾无功能发生;CMV发生率:舒莱组4例(40%),ATG组10例(71%),ATG-F组11例(73%);ATG组发生肺部感染1例,其余组均无肺炎发生;ATG、ATG-F组分别有5、6例出现血小板及血红蛋白下降,无其他不良反应;除ATG组肺炎患者死亡外,其余均带功存活;术后恢复正常的肾脏病理表现为肾小球及肾小管结构清晰,而DGF的活检病理表现为肾小管肿胀,部分肾小管变性坏死。结论 DCD是解决我国器官移植界瓶颈的重要手段,中国三类(DBCD)是较理想的DCD供者。免疫诱导能够有效预防急性排斥的发生,但可引起机体广泛抑制,导致潜伏的CMV复活;取肾过程中尽量缩短热缺血时间,DGF发生率较低。供肾零点活检应该成为DCD供肾肾脏移植的常规检查项目,但慎重决定取舍。

适应新形势下的我国DCD器官移植教学对策探讨

鉴于我国的特殊国情及器官移植的特殊性,加之自2015年1月1日开始,我国逐步建立健全了各项法规,完全停止死刑犯器官使用,旨在创建一个与世界接轨的、合法的和可持续发展的自愿器官捐献系统。适应这种新时代变更下的器官移植教学模式的探讨就成为当务之急。如何在新的形势下提高器官移植教学的质量,是摆在医学教育工作者面前的严峻课题。

机械灌注与单纯冷保存对猪DCD供胰影响的对比研究

目的对比研究机械灌注与单纯冷保存对猪心脏死亡器官捐献(DCD)供胰的影响。方法健康猪10只,随机分为单纯冷保存组和机械灌注组两组(每组各5只)。制备DCD猪模型,胰腺切取后采用威斯康星大学保存液(UW液)保存。单纯冷保存组给予单纯UW液冷保存,机械灌注组给予机械灌注保存。分别于保存1、2、3、4、6、24 h时点在胰尾部取材,制作组织切片,予苏木素-伊红(HE)染色。两组进行胰腺组织病理学检查,并对病理学评分进行比较。结果猪DCD供胰在机械灌注180 min时胰腺微血栓已被清除,又避免了过度灌注对胰岛的损害。机械灌注组病理学评分为(4.2±0.8)分,单纯冷保存组病理学评分为(8.4±1.1)分,比较差异有统计学意义(P<0.05)。结论机械灌注可以有效清除胰腺血管内血栓。与单纯冷保存比较,保存相同时间后,机械灌注组更能维持胰岛的完整性。