Current Opinion in Organ Transplantation最新文献

Purpose of review: The United States (US) liver transplant community is processing changes to the allocation system and developing a new proposal that will result in even greater change. This review evaluates the ethical implications of these decisions, focusing on two sets of competing ethical principles (Urgency vs. Utility and Justice vs. Pragmatism).

Recent findings: About four years ago, the Organ Procurement and Transplantation Network (OPTN) implemented the Acuity Circle Model to replace the geographic boundaries of organ procurement organizations (OPOs). Here, we review how effectively this model reduced regional variation in access and improved waitlist survival. Likewise, the OPTN is planning to transition to a continuous distribution model which will redefine the scoring systems for allocation. We will discuss how the ethical priorities discussed above should be considered while developing the new system.

Summary: Every change in organ allocation policy must balance competing ethical imperatives. Although our community's emphasis on urgency over utility is appropriate, we should study the potential benefits of considering utility in the system. Meanwhile, our push for more Justice in the system should remain our imperative and Pragmatism should only be considered to minimize the costs of these changes.

Purpose of review: As the volume and complexity of solid organ and hematopoietic stem cell transplantation continue to see rapid growth, the training of a specialized transplant infectious diseases physician workforce is of increasing interest and importance. This review provides an overview of the evolution of transplant infectious diseases training programs, essential elements of training, as well as future needs.

Recent findings: Despite the first publication of a transplant infectious diseases curriculum in 2010, more recent surveys of infectious diseases trainees have identified gaps in didactic curriculum, donor and recipient assessment, and safe living practices.

Summary: This review of transplant infectious diseases training summarizes growth through the decades, the current landscape of recommend training elements, suggested areas for continued development and expansion in training as well as novel methodologies to reach a modern trainee audience.

Purpose of review: Rebalanced hemostasis describes the precarious balance of procoagulant and antithrombotic proteins in patients with severe liver failure. This review is aimed to discuss currently available coagulation monitoring tests and pertinent decision-making process for plasma coagulation factor replacements during liver transplantation (LT).

Recent findings: Contemporary viscoelastic coagulation monitoring systems have demonstrated advantages over conventional coagulation tests in assessing the patient's coagulation status and tailoring hemostatic interventions. There is increasing interest in the use of prothrombin complex and fibrinogen concentrates, but it remains to be proven if purified factor concentrates are more efficacious and safer than allogeneic hemostatic components. Furthermore, the decision to use antifibrinolytic therapy necessitates careful considerations given the risks of venous thromboembolism in severe liver failure.

Summary: Perioperative hemostatic management and thromboprophylaxis for LT patients is likely to be more precise and patient-specific through a better understanding and monitoring of rebalanced coagulation. Further research is needed to refine the application of these tools and develop more standardized protocols for coagulation management in LT.

Purpose of review: A major hurdle hindering more widespread application of reconstructive transplantation is the very limited cold ischemia time (CIT) of vascularized composite allografts (VCAs). In this review, we discuss cutting edge machine perfusion protocols and preservation strategies to overcome this limitation.

Recent findings: Several preclinical machine perfusion studies have demonstrated the multifactorial utility of this technology to extend preservation windows, assess graft viability prior to transplantation and salvage damaged tissue, yet there are currently no clinically approved machine perfusion protocols for reconstructive transplantation. Thus, machine perfusion remains an open challenge in VCA due to the complexity of the various tissue types. In addition, multiple other promising avenues to prolong preservation of composite allografts have emerged. These include cryopreservation, high subzero preservation, vitrification and nanowarming. Despite several studies demonstrating extended preservation windows, there are several limitations that must be overcome prior to clinical translation. As both machine perfusion and subzero preservation protocols have rapidly advanced in the past few years, special consideration should be given to their potential complementary utilization.

Summary: Current and emerging machine perfusion and preservation technologies in VCA have great promise to transform the field of reconstructive transplantation, as every extra hour of CIT helps ease the complexities of the peri-transplant workflow. Amongst the many advantages, longer preservation windows may allow for elective procedures, improved matching, establishment of novel immunomodulatory protocols and global transport of grafts, ultimately enabling us the ability to offer this life changing procedure to more patients.

Purpose of review: Antibody-mediated rejection (AMR) after solid organ transplantation remains an unsolved problem and leads to poor early and late patient outcomes. The complement system is a well recognized pathogenic mediator of AMR. Herein, we review the known molecular mechanisms of disease and results from ongoing clinical testing of complement inhibitors after solid organ transplant.

Recent findings: Activation and regulation of the complement cascade is critical not only for the terminal effector function of donor-specific antibodies, but also for the regulation of T and B cell subsets to generate the antidonor humoral response. Donor-specific antibodies (DSA) have heterogenous features, as are their interactions with the complement system. Clinical testing of complement inhibitors in transplant patients have shown good safety profiles but mixed efficacy to date.

Summary: The complement cascade is a critical mediator of AMR and clinical trials have shown early promising results. With the steady emergence of novel complement inhibitors and our greater understanding of the molecular mechanisms linking complement and AMR, there is greater optimism now for new prognostic and therapeutic tools to deploy in transplant patients with AMR.

Purpose of review: The potential for transmission of donor-derived infections (DDIs) is impossible to eliminate, but a thoughtful and systematic approach to donor evaluation can mitigate the risk. Prevention is a key issue and clinicians must maintain a high index of suspicion and remain vigilant in staying up to date on emerging infections. COVID-19 and Monkeypox have represented a new challenge for infectious disease screening and recommendations have been evolving, as knowledge in the field has grown. Additional considerations for pretransplant deceased donor screening include testing for neglected and endemic infectious diseases such as strongyloidiasis and HTLV 1/2. Molecular diagnostic tests have improved awareness on pathogenicity of mollicutes and fungi in the setting of DDIs. The aim of this review is to provide an update on the most recent literature on DDI with a special focus on these emerging hot topics.

Recent findings: Donor screening for uncommon pathogens must be guided by knowledge of changing epidemiology of infectious disease and availability of new diagnostic methods.

Summary: Appropriate screening, early recognition, timely reporting, close monitoring, and appropriate management are essential to help reducing the risk of emerging DDIs.

Purpose of review: Heart transplant is the gold standard treatment for patients with end-stage heart failure, improving both quality of life and survival. Despite advances in donor and recipient management, primary graft dysfunction (PGD) remains the most common cause of morbidity and mortality in the early posttransplant period. This review summarizes recent discoveries in the underlying pathophysiology, risk prediction and management of PGD.

Recent findings: The incidence of PGD appears to be rising and it is not clear whether this is due to better recognition or secular changes in transplant practice. The utilization of donation after circulatory death organs for transplant is a further consideration for the development of PGD. Organ transport systems and preservation techniques may help to prevent PGD. As some of the risk factors for developing PGD remain modifiable, we summarize the current evidence for prevention and management of PGD.

Summary: A better understanding will allow us to appropriately manage donors and recipients to reduce the complex interactions that lead to PGD. The development of an international consortium provides the opportunity for deep phenotyping and development of contemporary risk prediction models for PGD, which may reduce the incidence and consequent early mortality associated with heart transplantation.

Purpose of review: The implementation of highly sensitive immune assays measuring anti-human leukocyte antigen (HLA) antibodies has modified alloimmune risk stratification and diagnosis of rejection. Nonetheless, anti-HLA antibodies represent the downstream effector mechanism of the B-cell response. Better characterizing the cellular components of the humoral immune response (including memory B cells (mBCs) and long-lived plasma cells) could help to further stratify the alloimmune risk stratification and enable discovery of new therapeutic targets. Several tests that characterize HLA-specific mBCs, either functionally or phenotypically, have been developed in the last years, showing promising applications as well as some limitations.

Recent findings: Functional assays involving ex vivo polyclonal activation of mBC have been refined to allow the detection of HLA-specific mBC capable of producing anti-HLA Abs, using different and complementary detection platforms such as multiplex Fluorospot and single antigen bead assay on culture supernatants. Detection of circulating HLA-specific B cells by flow cytometry remains hindered by the very low frequency of HLA-specific mBC.

Summary: Technological refinements have allowed the development of tests detecting HLA-specific mBC. Further evaluation of these assays in clinical trials, both for immune risk stratification and to assess treatment efficacy (desensitization strategies, rescue therapies for ABMR) are now urgently needed.

Purpose of review: The revised United States heart organ allocation system was launched in October 2018. In this review, we summarize this United Network for Organ Sharing (UNOS) policy and describe intended and unintended consequences.

Recent findings: Although early studies published after the change suggested postheart transplant survival declined at 6 months and 1 year, recent publications with longer follow-up time have confirmed comparable posttransplant survival in adjusted models and several patient cohorts. Moreover, the new allocation decreased overall waitlist time from 112 to 39 days ( P  < 0.001). Mean ischemic time increased because of greater distances traveled to acquire donor hearts under broader sharing. Despite the intention to decrease exception requests by expanding the number of priority tiers to provide more granular risk stratification, ∼30% of patients remain waitlisted under exception status. Left-ventricular assist device (LVAD) implants are declining and the number of LVAD patients on the transplant list has decreased dramatically after the allocation system change.

Summary: As the next allocation system is developed, it is imperative to curtail the use of temporary mechanical support as a strategy solely for listing purposes, identify attributes that more clearly stratify the severity of illness, provide greater oversight of exception requests, and address concerns regarding patients with durable LVADs.