Current Opinion in Organ Transplantation最新文献

Purpose of review: Transplant oncology encompasses and utilizes liver transplantation (LT) in combination with other aspects of cancer care to offer improved long-term outcomes for patients with liver cancer, but not all patients have equal access and ability to undergo LT. Social determinants of health may negatively impact a patient's ability to receive liver-related oncologic care, including LT. This review highlights recent work exposing gaps in access to LT, including transplant oncology, and interventions to ameliorate these disparities.

Recent findings: Members of racial and ethnic minorities and indigenous groups, females, socioeconomically disadvantaged persons, and patients from rural areas are less likely to undergo LT. Recent studies have also described programs that have successfully mitigated some of the barriers in access to transplant oncology that these patients experience, including targeted outreach programs and access to virtual healthcare.

Summary: Disparities in access to LT for liver cancer are increasingly well described, but additional research is needed to find effective ways to ameliorate these differences.

Purpose of review: With advances in the field of congenital cardiac surgery and in the management of congenital heart defects in early life, the population of adult congenital heart disease (ACHD) patients is increasing. End-stage heart failure is currently the main cause of cardiovascular mortality and is expected to increase in the coming years. This review summarizes recent innovations in transplant techniques, with special attention to what is known in the population of ACHD recipients.

Recent findings: The use of machine perfusion for heart preservation enables longer preservation times. Normothermic (organ care system - OCS) and hypothermic (hypothermic oxygenated perfusion - HOPE) machine perfusion will alleviate the time pressure associated with heart transplantation in the ACHD population, may allow for expansion of the geographical range in which donors can be matched and may improve graft quality. Donation after circulatory death (DCD) heart transplantation, either through direct procurement-machine perfusion (DP-MP) or thoraco-abdominal normothermic regional perfusion (TA-NRP) is a viable strategy to further expand the donor pool.

Summary: The use of machine perfusion and DCD donors in ACHD is feasible and shows promise. Time pressure and shortage of donors is even more critical in ACHD than in other patient populations, making these innovations particularly relevant. Further clinical experience and research is needed to elucidate their impact.

Purpose of review: Prehabilitation, defined as preparing the body physically and psychologically for upcoming surgery is of increasing prominence in presurgical care. The aim of this review is to discuss the evidence base around prehabilitation in solid organ transplantation, the use of digital health as a tool to deliver these interventions, and consider future directions.

Recent findings: Prehabilitation is of increasing interest as an adjunct to pretransplant care for individuals working up for solid organ transplantation. To date, research has shown that prehabilitation is acceptable and feasible; however, the literature base remains small. The majority of research has been delivered using in-person rehabilitation programmes, and the evidence base utilizing digital health as a means to deliver prehabilitation is limited.

Summary: To date, the research evidence base in prehabilitation for solid organ transplantation is limited. Evidence in other surgical populations has demonstrated promising results, particularly in aerobic capacity, physical function and postoperative complications. Further high-quality randomized controlled clinical trials are required to strengthen the evidence base, understand how digital health can be harnessed and utilized to deliver multimodal prehabilitation with an aim to see how this may form part of routine care in the solid organ transplantation pathway.

Purpose of review: This review delves into the intricate landscape of airway complications post lung transplantation. With the rising prevalence of end-stage lung disease and the increasing number of lung transplantation worldwide, understanding and effectively managing airway complications are crucial. Given the nuanced nature of these complications and the array of treatment options available, this review aims to provide a comprehensive overview of how to identify, classify, mitigate risk factors for, and manage these complications.

Recent findings: Several donor, recipient, and surgical risk factors are associated with the increased risk of airway complications. In managing these complications, bronchoscopic interventions, notably balloon dilation and stenting, are pivotal. Although self-expanding metallic stents offer versatility, silicone stents are preferred in certain scenarios for their durability. Emerging techniques such as biodegradable stents and advancing imaging modalities show promise in mitigating complications and improving outcomes.

Summary: These findings underscore the significance of a multidisciplinary approach and personalized treatment algorithms in managing airway complications post lung transplantation. By elucidating specific indications and complications of treatment modalities, this review serves as a valuable resource for optimally managing airway complications. Ongoing research into novel interventions holds promise for further enhancing outcomes in this challenging clinical setting.

Purpose of review: Although lung transplantation stands as the gold standard curative therapy option for end-stage lung disease, the scarcity of available organs poses a significant challenge in meeting the escalating demand. This review provides an overview of recent advancements in ambulatory respiratory assist systems, selective anticoagulation therapies that target the intrinsic pathway, and innovative surface coatings to enable permanent respiratory support as a viable alternative to lung transplantation.

Recent findings: Several emerging ambulatory respiratory assist systems have shown promise in both preclinical and clinical trials. These systems aim to create more biocompatible, compact, and portable forms of extracorporeal membrane oxygenation that can provide long-term respiratory support. Additionally, innovative selective anticoagulation strategies, currently in various stages of preclinical or clinical development, present a promising alternative to currently utilized nonselective anticoagulants. Moreover, novel surface coatings hold the potential to locally prevent artificial surface-induced thrombosis and minimize bleeding risks.

Summary: This review of recent advancements toward permanent respiratory support summarizes the development of ambulatory respiratory assist systems, selective anticoagulation therapies, and novel surface coatings. The integration of these evolving device technologies with targeted anticoagulation strategies may allow a safe and effective mode of permanent respiratory support for patients with chronic lung disease.

Purpose of review: Mechanical circulatory support is used frequently as a method of stabilizing patients with end stage heart failure who are unable to safely await allograft availability. While this technology has been fundamentally important in supporting patients with normal cardiac anatomy, it is still used infrequently in adult patients with congenital heart disease and end-stage heart failure. Here, we review the data on mechanical circulatory support technology in this small but growing population of patients with chronic heart disease prone to the development of circulatory failure.

Recent findings: Mechanical circulatory support (MCS) has been increasingly employed in adults with congenital heart disease (ACHD) as a bridge to transplant. The new United Network for Organ Sharing listing system favoring temporary MCS use with a higher listing status offers another tool to stabilize ACHD patients and potentially shorten wait times. Both temporary and Durable MCS could help improve transplant candidacy and posttransplant outcomes in select groups of ACHD patients.

Summary: Durable and temporary MCS have the potential to significantly improve access to transplant and overall transplant outcomes in ACHD patients.

Purpose of review: Advancements in preclinical xenotransplant studies have opened doors for clinical heart and kidney xenotransplantation. This review assesses recent progress in lung xenotransplantation research and its potential clinical implications.

Recent findings: The efficacy of the humanized von Willebrand factor in reducing platelet sequestration in ex-vivo and in-vivo lung xenotransplant models was showcased. Combining human tissue factor pathway inhibitor and CD47 expression with selectin and integrin inhibition delayed neutrophil and platelet sequestration. Enhanced expression of human complement regulatory proteins and thrombomodulin in genetically engineered pig lungs improved graft survival by reducing platelet activation and modulating coagulation disruptions. Knocking out the CMAH gene decreased antibody-mediated inflammation and coagulation activation, enhancing compatibility for human transplantation. Furthermore, CMAH gene knockout in pigs attenuated sialoadhesin-dependent binding of human erythrocytes to porcine macrophages, mitigating erythrocyte sequestration and anemia. Meanwhile, in-vivo experiments demonstrated extended survival of xenografts for up to 31 days with multiple genetic modifications and comprehensive treatment strategies.

Summary: Experiments have uncovered vital insights for successful xenotransplantation, driving further research into immunosuppressive therapy and genetically modified pigs. This will ultimately pave the way for clinical trials designed to improve outcomes for patients with end-stage lung disease.

Purpose of review: Blastocyst complementation represents a promising frontier in next-generation lung replacement therapies. This review aims to elucidate the future prospects of lung blastocyst complementation within clinical settings, summarizing the latest studies on generating functional lungs through this technique. It also explores and discusses host animal selection relevant to interspecific chimera formation, a challenge integral to creating functional human lungs via blastocyst complementation.

Recent findings: Various gene mutations have been utilized to create vacant lung niches, enhancing the efficacy of donor cell contribution to the complemented lungs in rodent models. By controlling the lineage to induce gene mutations, chimerism in both the lung epithelium and mesenchyme has been improved. Interspecific blastocyst complementation underscores the complexity of developmental programs across species, with several genes identified that enhance chimera formation between humans and other mammals.

Summary: While functional lungs have been generated via intraspecies blastocyst complementation, the generation of functional interspecific lungs remains unrealized. Addressing the challenges of controlling the host lung niche and selecting host animals relevant to interspecific barriers between donor human and host cells is critical to enabling the generation of functional humanized or entire human lungs in large animals.

Purpose of review: The number of adult congenital heart disease (ACHD) patients presenting for consideration of heart transplantation continues to grow. Comprehensive pretransplant assessment and thoughtful patient selection are of critical importance to mitigate perioperative and posttransplant morbidity and mortality in this population.

Recent findings: There is increasing evidence that patient outcomes after the onset of heart failure in the ACHD population are poor while overall transplant outcomes for ACHD patients have improved over time. Delineation of factors associated with better versus worse posttransplant outcomes is an area of ongoing research. Several studies have found that delayed patient referral, anatomic complexity and the presence of noncardiac organ dysfunction may increase peri-transplant and posttransplant risk.

Summary: Pretransplant assessment and patient selection in ACHD patients should focus on mitigating perioperative and early posttransplant risk. Anatomic complexity, noncardiac organ dysfunction, and referral timing after the onset of heart failure can contribute to poor posttransplant outcomes and should inform patient selection.