肝移植术后认知与脑改变的多模态神经成像

肝性脑病是终末期肝硬化的重要并发症,导致病人出现一系列神经及认知功能改变。肝移植术后病人在肝功能恢复的同时其认知功能也可明显改善。MRI可以从脑代谢、结构及功能方面更进一步揭示肝硬化病人移植术后认知及脑改变情况。综述肝移植术后认知改变的研究现状以及最新的多模态MRI技术在术后脑改变中的应用,及其在揭示术后认知恢复及残存损害的神经机制中的价值。     

Innovative immunosuppression in kidney transplantation: A challenge for unmet needs

Due to the optimal results obtained in kidney transplantation and to the lack of interest of the industries, new innovative drugs in kidney transplantation are difficult to be encountered. The best strategy to find the new drugs recently developed or under development is to search in the sections of kidney transplantation still not completely covered by the drugs on the market. These unmet needs are the prevention of delayed graft function (DGF), the protection of the graft over the long time and the desensitization of preformed anti human leukocyte antigen antibodies and the treatment of the acute antibody-mediated rejection. These needs are particularly relevant due to the expansion of some kind of kidney transplantation as transplantation from non-heart beating donor and in the case of antibody-incompatible grafts. The first are particularly exposed to DGF, the latter need a safe desensitization and a safe treatments of the antibody mediated rejections that often occur. Particular caution is needed in treating these drugs. First, they are described in very recent studies and the follow-up of their effect is of course rather short. Second, some of these drugs are still in an early phase of study, even if in well-conducted randomized controlled trials. Particular caution and a careful check need to be used in trials launched 2 or 3 years ago. Indeed, is always necessary to verify whether the study is still going on or whether and why the study itself was abandoned.     

围手术期外科之家模式在肝移植中的应用

围手术期外科之家（PSH）是一种以病人为中心的创新性围手术期管理模式，强调以医生为主导、以多学科团队为基础，基于循证医学证据，协调医疗资源，促进病人接受不同专业处理时平稳过渡，围手术期始终获得正确的处理方案，尤其适合存在器官功能障碍的外科病人。肝移植病人大多病情危重，手术复杂，围手术期管理困难。将PSH引入肝移植，可以为这类高手术风险的特殊病人群体提供一种全新的围手术期管理方式。     

自体骨髓移植联合MHC单倍体相合淋巴细胞治疗急性髓性白血病的临床疗效

目的:自体骨髓移植联合MHC单倍体相合淋巴细胞治疗急性髓性白血病的治疗效果和安全性。方法:以40例急性髓性白血病患者作为研究对象，随机分为两组各20例，研究组患者使用自体骨髓移植联合MHC单倍体相合淋巴细胞进行治疗，对照组单用自体骨髓移植进行治疗。结果:两组患者的造血系统都得到重建，重建时间以及并发症的发生均没有显著差异。而研究组患者复发率显著降低，且复发时间明显地长于对照组患者。研究组患者3年累积无病生存率明显地高于对照组患者，且差异具有统计学意义。结论:自体骨髓移植联合MHC单倍体相合淋巴细胞治疗能够有效控制急性髓性白血病病情，降低其复发，延长患者生存期。     

Mortality,length of stay and costs associated with acute graft-versus-host disease during hospitalization for allogeneic hematopoietic stem cell transplantation

Objective: Acute graft-versus-host disease (aGVHD) is a common and life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The extent to which aGVHD increases inpatient costs associated with allo-HSCT has not been thoroughly evaluated. In this analysis, mortality, hospital length of stay (LOS) and costs associated with aGVHD during allo-HSCT admissions are evaluated.

Methods: This is a retrospective analysis of discharge records from the National Inpatient Sample database for patients receiving allo-HSCT between 1 January 2009 and 31 December 2013. Allo-HSCT discharges with an aGVHD diagnosis were included in the aGVHD group and those without any graft-versus-host disease (GVHD) diagnosis comprised the non-GVHD group. Mortality, LOS and costs were compared between the two groups, as well as within subgroups, including age (<18 vs. ≥18 years) and survival status (alive vs. deceased) at discharge.

Results: Overall, mortality (16.2% vs. 5.3%; p?<?.01), median hospital LOS (42.0 vs. 26.0 days; p?<?.01) and median total costs ($173,144 vs. $98,982; p?<?.01) were significantly increased in patients with aGVHD versus those without GVHD during hospitalizations for allo-HSCT, irrespective of age group. Patients with aGVHD who were <18 years of age had a lower mortality rate but greater hospital LOS and total costs versus patients aged ≥18 years. Patients who died during allo-HSCT hospitalization had longer LOS and incurred greater costs than those who survived in both the aGVHD and non-GVHD groups.

Conclusion: Occurrence of aGVHD during allo-HSCT admissions resulted in a tripling of the mortality rate and a near doubling of hospital LOS and total costs. In addition, death during allo-HSCT hospitalizations was associated with greater healthcare utilization and costs. Effectively mitigating aGVHD may improve survival and substantially reduce hospital LOS and costs for allo-HSCT.     

Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation

Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT). When myeloablated BALB/c MyD88 knock-out recipients were transplanted with C57BL/6 (B6) donor cells, they developed significantly more severe GVHD than wild-type (WT) BALB/c hosts. The increased morbidity and mortality in MyD88^–/– mice correlated with increased serum levels of lipopolysaccharide and elevated inflammatory cytokines in GVHD target organs. Additionally, MyD88 deficiency in BMT recipients led to increased donor T cell expansion and more donor CD11c⁺ cell intestinal infiltration with apoptotic cells but reduced proliferation of intestinal epithelial cells compared with that in WT BMT recipients. Decreased expression of tight junction mRNA in epithelial cells of MyD88^–/– mice suggested that MyD88 contributes to intestinal integrity. Cox-2 expression in the GVHD-targeted organs of WT mice is increased upon GVHD induction, but this enhanced expression was obviously inhibited by MyD88 deficiency. The present findings demonstrate an unexpected role for host MyD88 in preventing GVHD after allogeneic BMT.     

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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