肺移植患者姑息照护的研究进展

肺移植是终末期肺病的有效治疗方法。该文介绍了肺移植患者姑息照护的概念、必要性、开展情况、影响肺移植患者姑息照护的障碍因素、促进肺移植患者姑息照护的策略、姑息照护对肺移植患者的效果等方面，为国内肺移植患者姑息照护的发展提供借鉴，从而提高肺移植患者的生活质量。     

Pneumococcal immunity and PCV13 vaccine response in SOT-candidates and recipients

BackgroundSolid organ transplantation (SOT) candidates and recipients are highly vulnerable to invasive pneumococcal diseases (IPD). Data on which to base optimal immunization recommendations for this population is scant. The national distribution of IPD serotypes led the Swiss Health Authorities to recommend in 2014 one dose of pneumococcal-13-valent-conjugate-vaccine (PCV13), without any subsequent dose of the 23-valent-polysaccharide-pneumococcal-vaccine (PPV23).MethodsThis is a retrospective analysis of pneumococcal immunity using a multiplex binding assay, to assess seroprotection rates against a selection of seven PCV13- and seven PPV23-serotypes in SOT-candidates and recipients evaluated and/or transplanted in 2014/2015 in the University Hospitals of Geneva. Seroprotection was defined as serotype-specific antibody concentration greater than 0.5 mg/l and overall seroprotection when this was achieved for ≥ 6/7 serotypes.ResultsPre-vaccination and at time of transplant sera were available for 35/43 (81%), and 43/43 (100%) SOT-candidates respectively. At listing, 17/35 (49%) SOT-candidates were seroprotected against PCV13 and 21/35 (60%) against PPV23 serotypes. Following one systematic dose of PCV13 at listing, 35/43 (81%) SOT-recipients were seroprotected at day of transplant against PCV13-serotypes and 34/43 (79%) against PPV23 serotypes, compared to 21/41 (51%) and 28/41 (68%) respectively in the controls transplanted in 2013, before the systematic PCV13-vaccination.ConclusionsThe systematic vaccination with PCV13 of all SOT candidates without additional PPV23 is a good strategy as it confers seroprotection against a wide range of pneumococcal serotypes. Indeed, one of five PCV13-vaccinated SOT-candidates was nevertheless not seroprotected at time of transplant, reflecting their partial immune competence, and indicating the need for additional dose of pneumococcal vaccines before transplant.     

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

Implementation of molecular matching in transplantation requires further characterization of both immunogenicity and antigenicity of individual HLA epitopes

Over the past decade, high HLA epitope mismatch scores have been associated with inferior transplant outcomes using several tools, of which HLAMatchmaker is most well-known. This software uses theoretically defined polymorphic amino acid configurations, called eplets, for HLA compatibility analysis. Although consideration of eplet mismatch loads has potential for immunological risk stratification of transplant patients, the use of eplet matching in organ allocation algorithms is hindered by lacking knowledge of the immunogenicity of individual eplets, and the possibility that single mismatched amino acids, rather than complete eplets, are responsible for HLA antibody induction.There are several approaches to define eplet immunogenicity, such as antibody verification of individual eplets, and data-driven approaches using large datasets that correlate specific eplet mismatches to donor specific antibody formation or inferior transplant outcomes. Data-driven approaches can also be used to define whether single amino acid mismatches may be more informative than eplet mismatches for predicting HLA antibody induction.When using epitope knowledge for the assignment of unacceptable antigens, it important to realize that alleles sharing an eplet to which antibodies have formed are not automatically all unacceptable since multiple contact sites determine the binding strength and thus biological function and pathogenicity of an antibody, which may differ between reactive alleles.While the future looks bright for using HLA epitopes in clinical decision making, major steps need to be taken to make this a clinical reality.     

Update on pediatric corneal diseases and keratoplasty

Managing pediatric corneal disorders is challenging as the prognosis of pediatric keratoplasty depends on several factors. Advancements in the genetic basis of congenital corneal diseases and investigations in congenital corneal conditions provide a better understanding of pediatric corneal conditions. Surgeons performing keratoplasty in children now have a choice of various techniques. Evolving surgical techniques of anterior lamellar and endothelial keratoplasties have expanded the management interventions in these pediatric corneal morbidity conditions; however, considerable concerns still exist in association with corneal transplantation in infants and children. Outcomes in pediatric keratoplasty depend upon the preoperative indications, the timing of surgical intervention, intraoperative and postoperative factors including the patient/care givers’ compliance. Factors such as low scleral rigidity, higher rate of graft failure, need for frequent examinations under anesthesia, and difficulty in optimal visual acuity assessment still remain a considerable challenge in pediatric scenarios. In children, deprivation amblyopia as a result of the corneal opacification can adversely affect visual development, causing dense amblyopia. Outcomes to surgical interventions for management of corneal opacification in children are further compromised by the preexisting amblyopia apart from the concerns of refractive outcome of the graft. Graft rejection, graft infection, amblyopia, and glaucoma continue to be serious concerns. In recent years both anterior and posterior lamellar keratoplasty techniques are being increasingly performed in pediatric eyes, which offer advantages in the form of lower risk of graft rejection. The timing of surgery, careful case selection, cautious intraoperative approach, and optimal postoperative management can improve the anatomical and functional outcome in difficult cases.     

Combined hepatic and portal vein embolization as preparation for major hepatectomy: a systematic review

BackgroundSome patients remain deemed unsuitable for resection after portal vein embolization (PVE) because of insufficient hypertrophy of the future remnant liver (FRL). Hepatic and portal vein embolization (HPVE) has been shown to induce hypertrophy of the FRL. The aim of this study was to provide a systematic review of the available literature on HPVE as preparation for major hepatectomy.MethodsThe literature search was performed on online databases. Studies including patients who underwent preoperative HPVE were retrieved for evaluation.ResultsSix articles including 68 patients were published between 2003 and 2017. HPVE was performed successfully in all patients with no mortality and morbidity-related procedures. The degree of hypertrophy of the FRL after HPVE ranged from 33% to 63.3%. Surgical resection after preoperative HPVE could be performed in 85.3% of patients, but 14.7% remained unsuitable for resection because of insufficient hypertrophy of the FRL or tumor progression. Posthepatectomy morbidity and mortality rates were 10.3% and 5.1%, respectively. The postoperative liver failure rate was nil.ConclusionHPVE as a preparation for major hepatectomy appears to be feasible and safe and could increase the resectability of patients initially deemed unsuitable for resection because of absent or insufficient hypertrophy of the FRL after PVE alone.     

2018 ATC/TTS器官移植前沿热点回顾及进展概述

重点概述2018年美国移植大会及第27届国际移植大会有关器官移植基础、临床及转化医学研究的前沿热点及最新进展，包括供者特异性抗体、抗体介导排斥反应、临床免疫耐受、供器官合理利用、供肝保存新技术应用及移植相关病毒感染等概要内容。     

Pump Speed Optimization in Patients Implanted With the HeartMate 3 Device

Background

Pump speed optimization in patients implanted with a ventricular assist device represents a major challenge during the follow-up period. We present our findings on whether combined invasive hemodynamic ramp tests and cardiopulmonary exercise testing (CPX) can help optimize patient management.