Current Transplantation Reports最新文献

Purpose of review: We examined data from the last 5 years describing extracorporeal life support (ECLS) as a bridge to lung transplantation. We assessed predictors of survival to transplantation and post-transplant mortality.

Recent findings: The number of lung transplants performed worldwide is increasing. This is accompanied by an increase in the type of patients being transplanted, including sicker patients with more advanced disease. Consequently, there is an increase in the need for bridging strategies, with varying success. Several predictors of failure have been identified. Major risk factors include retransplantation, other organ dysfunction, and deconditioning.

Summary: ECLS is a risky strategy but necessary for patients who would otherwise die if not bridged to transplantation. The presence of predictors for failure is not a contraindication for bridging. However, major risk factors should be approached cautiously. Other, more minor risk factors may be considered acceptable. More importantly, the strategy should be individualized for each patient to achieve the best possible outcomes.

Purpose of the review: This is a comprehensive update on failing Fontan physiology and the role of heart and combined heart and liver transplantation in the current era.

Recent findings: Single ventricle physiology encompasses a series of rare congenital cardiac abnormalities that are characterized by absence of or hypoplasia of one ventricle. This effectively results in a single ventricular pumping chamber. These abnormalities are rarely compatible with long-term survival if left without surgical palliation in the first few years of life. Surgical treatment of single ventricle physiology has evolved over the past 60 years and is characterized by numerous creative innovations. These include the development of arteriopulmonary shunts, the evolution of partial cavopulmonary connections, and the eventual development of the "Fontan" operation. Regardless of the type of Fontan modification, the long-term consequences of the Fontan operation are predominantly related to chronic central venous hypertension and the multi-organ consequences thereof. Atrial arrhythmias can further compromise this circulation.Patients with single ventricle physiology represent a special sub-segment of congenital cardiac transplants and are arguably the most challenging patients considered for transplantation.

Summary: This review describes in detail the challenges and opportunities of heart and liver transplantation in Fontan patients, as viewed and managed by the experienced team at the Ahmanson/UCLA Adult Congenital Heart Center.

Purpose of review: Coronavirus disease 2019 (COVID-19) is caused by a complex interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics and host immune responses. Hosts with altered immunity, including solid organ transplant recipients, may be at increased risk of complications and death due to COVID-19. A synthesis of the available data on immune responses to SARS-CoV-2 infection is needed to inform therapeutic and preventative strategies in this special population.

Recent findings: Few studies have directly compared immune responses to SARS-CoV-2 between transplant recipients and the general population. Like non-transplant patients, transplant recipients mount an exuberant inflammatory response following initial SARS-CoV2 infection, with IL-6 levels correlating with disease severity in some, but not all studies. Transplant recipients display anti-SARS-CoV-2 antibodies and activated B cells in a time frame and magnitude similar to non-transplant patients-limited data suggest these antibodies can be detected within 15 days of symptom onset and may be durable for several months. CD4⁺ and CD8⁺ T lymphopenia, a hallmark of COVID-19, is more profound in transplant recipients, but SARS-CoV-2-reactive T cells can be detected among patients with both mild and severe disease.

Summary: The limited available data indicate that immune responses to SARS-CoV-2 are similar between transplant recipients and the general population, but no studies have been sufficiently comprehensive to understand nuances between organ types or level of immunosuppression to meaningfully inform individualized therapeutic decisions. The ongoing pandemic provides an opportunity to generate higher-quality data to support rational treatment and vaccination strategies in this population.

Purpose of review: IL-6 is a pleiotropic, pro-inflammatory cytokine that plays an integral role in the development of acute and chronic rejection after solid organ transplantation. This article reviews the experimental evidence and current clinical application of IL-6/IL-6 receptor (IL-6R) signaling inhibition for the prevention and treatment of allograft injury.

Recent findings: There exists a robust body of evidence linking IL-6 to allograft injury mediated by acute inflammation, adaptive cellular/humoral responses, innate immunity, and fibrosis. IL-6 promotes the acute phase reaction, induces B cell maturation/antibody formation, directs cytotoxic T-cell differentiation, and inhibits regulatory T-cell development. Importantly, blockade of the IL-6/IL-6R signaling pathway has been shown to mitigate its harmful effects in experimental studies, particularly in models of kidney and heart transplant rejection. Currently, available agents for IL-6 signaling inhibition include monoclonal antibodies against IL-6 or IL-6R and janus kinase inhibitors. Recent clinical trials have investigated the use of tocilizumab, an anti-IL-6R mAb, for desensitization and treatment of antibody-mediated rejection (AMR) in kidney transplant recipients, with promising initial results. Further studies are underway investigating the use of alternative agents including clazakizumab, an anti-IL-6 mAb, and application of IL-6 signaling blockade to clinical cardiac transplantation.

Summary: IL-6/IL-6R signaling inhibition provides a novel therapeutic option for the prevention and treatment of allograft injury. To date, evidence from clinical trials supports the use of IL-6 blockade for desensitization and treatment of AMR in kidney transplant recipients. Ongoing and future clinical trials will further elucidate the role of IL-6 signaling inhibition in other types of solid organ transplantation.

Purpose of review: Acute allograft rejection is a common cause of morbidity and mortality in heart and lung transplantation. Unfortunately, the current monitoring gold standard-biopsy plus histopathology-has several limitations. Plasma donor-derived cell-free DNA (dd-cfDNA) has emerged as a potentially valuable biomarker for rejection that addresses some of the limitations of biopsy. This review covers the current state of the evidence and future directions for the use of dd-cfDNA in the monitoring of acute rejection.

Recent findings: The results of several observational cohort studies demonstrate that levels of dd-cfDNA increase in the setting of acute cellular rejection and antibody-mediated rejection in both heart and lung transplant recipients. dd-cfDNA demonstrates acceptable performance characteristics, but low specificity for the detection of underlying injury from rejection or infection. In particular, the high negative predictive value of the test in both heart and lung transplant patients provides the potential for its use as a screening tool for the monitoring of allograft health rather than tissue biopsy alone.

Summary: Existing evidence shows that dd-cfDNA is a safe, convenient, and reliable method of acute rejection monitoring in heart and lung transplant recipients. Further studies are required to validate threshold values for clinical use and determine its role in the diagnosis of alternative forms of allograft injury.

Purpose of review: To summarize the research on effective interventions for preserving cognitive function and prevent cognitive decline in patients with end-stage kidney disease (ESKD) who are undergoing dialysis and/or kidney transplantation (KT).

Recent findings: Among ESKD patients undergoing hemodialysis, exercise training has been administered through home-based and intradialytic interventions. Additionally, one pilot study identified intradialytic cognitive training, electronic brain games, as an intervention to preserve cognitive function among patients undergoing hemodialysis. Fewer studies have investigated interventions to preserver cognitive function among KT recipients. To date, the only randomized controlled trial in this population identified B-vitamin supplements as an intervention to preserve cognitive function. The evidence from these trials support a short-term benefit of cognitive and exercise training as well as B-vitamin supplementation among patients with ESKD. Future studies should: 1) replicate these findings, 2) identify interventions specific to KT candidates, and 3) investigate the synergistic impact of both cognitive and exercise training.

Summary: Cognitive prehabilitation, with cognitive and/or exercise training, may be novel interventions for KT candidates that not only reduces delirium risk and long-term post-KT cognitive decline but also prevents dementia.