Current Opinion in Organ Transplantation最新文献

Purpose of review: Patients undergoing re-transplantation constitute a growing proportion of annual lung transplants. It is necessary to consider ethical considerations of re-transplantation in parallel with clinical progress.

Recent findings: Most clinical data demonstrate patients undergoing re-transplantation have worse survival outcomes; however, there is limited discussion of the ethical principles surrounding re-transplantation. Ethical guidance in re-transplantation trails clinical advancement.

Summary: The four-box model offers a valuable framework for assessing the ethical considerations in re-transplantation. This includes an analysis of medical indications, patient preferences, quality-of-life and contextual factors to support the ethical use of scarce donor lungs.

Purpose of review: The controversial medical procedure of abortion is the subject of this article. It argues that for transplant patients, including recipients, abortion is ethical.

Recent findings: In June 2022, the United States Supreme Court overturned the long-standing decision of Roe v. Wade. This decision has led to a socio-legal environment where obtaining an abortion is impossible for some patients. However, the moral position relating to patients who have undergone transplants or are on a waiting list has been largely overlooked. End-stage renal, liver, and heart disease presents a hazardous situation for pregnancy, posing risks to both the fetus and the pregnant person. The abortion procedure is medically safer and allows a patient to proceed with a transplant. Limiting access to abortion or preventing it altogether will have a significant negative impact on transplant patients. The ethical analysis of abortion can be likened to compelling a relative or loved one of a transplant recipient to donate an organ to their family member or loved one.

Summary: This article emphasizes the importance of maintaining the legal availability of abortion for transplant patients. Allowing abortions in transplant patients upholds ethical parity, as seen in the analogous situation of live organ donation.

Purpose of review: Primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) are the leading causes of graft loss in lung transplant recipients. The development of mouse lung transplant models has allowed for the genetic dissection of cellular and molecular pathways that prevent graft survival. This review provides an overview into recent mechanistic insights into PGD and CLAD.

Recent findings: Mouse orthotopic lung transplant models and investigations of human lung transplant recipeints have revealed new molecular and cellular targets that promote PGD and CLAD. Donor and recipient-derived innate immune cells promote PGD and CLAD. PGD is driven by communication between classical monocytes and tissue-resident nonclassical monocytes activating alveolar macrophages to release chemokines that recruit neutrophils. Products of cell damage trigger neutrophil NET release, which together with NK cells, antibodies and complement, that further promote PGD. The development of CLAD involves circuits that activate B cells, CD8 + T cells, classical monocytes, and eosinophils.

Summary: Effective targeted management of PGD and CLAD in lung transplant recipient to improve their long-term outcome remains a critical unmet need. Current mechanistic studies and therapeutic studies in mouse models and humans identify new possibilities for prevention and treatment.

Purpose of review: As one of the early hand transplant programs in the world, we are often asked to educate other programs on the lessons we have learned and on how to set up a successful hand transplantation program.

Recent findings: Two decades of global experience with vascularized composite allotransplantation (VCA) of the upper limb have demonstrated improved functional outcomes and quality of life for carefully screened patients. Despite initial reticence about VCA, over 30 patients in the USA have benefited from hand transplantation, with around 80% long-term successes. We have experience with four bilateral upper extremity patients who have undergone bilateral upper extremity allotransplants. This review article highlights our personal experience and lessons with respect to VCA team assembly, logistics, patient selection, perioperative planning, the operative procedure, and postoperative management.

Summary: Continual learning and critical evaluation are crucial to maintaining a successful upper extremity VCA program. This will ensure that patients who stand to benefit most from this life-enhancing procedure are identified and are others optimized to achieve the best possible outcomes.

Purpose of review: Despite significant advancements in the field of vascularized composite allotransplantation, challenges, particularly regarding the long-term viability and functionality of vascularized composite allotransplantation (VCA) grafts, persist. This paper provides a review of the current literature on the longevity of VCA grafts, focusing on factors influencing graft survival, immunological considerations and clinical outcomes.

Recent findings: Longevity of VCA grafts is influenced by a variety of peri- and postoperative factors including cold ischemia time, human leukocyte antigen matching, environmental exposure, psychosocial factors, adherence, immunosuppression, and complications. Due to the limited number of VCA transplants performed and heterogenous reporting, direct correlation of single factors with VCA outcomes remains inconclusive. Indirect evidence, however, supports their importance. High immunosuppressive burden, frequent occurrence of acute and accumulating cases of chronic rejection remain a significant challenge of the field.

Summary: Insights gained from this review aim to inform clinical practice and guide future research endeavors with the goal of ameliorating outcomes after VCA transplantation and facilitate wider use of VCA grafts for restoration of tissue defects.

Purpose of review: The purpose of this review is to explore the lessons learned from experimental and human tracheal transplantation to determine if this information may be applied to lung transplantation.

Recent findings: Experimental work in animal models and the recent human tracheal transplantation suggests that a robust tracheal vascular supply prevents anastomotic complications. Further, this work demonstrates that tracheal allografts undergo a progressive chimerism as recipient epithelium repopulates the allograft. In contrast to most vascularized composite allografts such as hand and face transplantation that experience high rates of rejection, the tracheal allograft did not demonstrate rejection. This may suggest that tissue chimerism plays a role in evading immune-mediated allograft rejection.

Summary: While anastomotic complications and chronic allograft rejection are the most common complications related to lung transplantation, the findings associated with tracheal transplantation may have implications for both reducing complications associated with lung transplantation.

Purpose of review: Significant advancements have been made in the field of vascularized composite allotransplantation (VCA); however, like solid organ transplantation, bypassing the recipient's immune response remains a significant obstacle to long-term allograft survival. Therefore, strategies to overcome acute and chronic rejection and minimize immunosuppressive therapy are crucial for the future of VCA. This review highlights recent attempts to induce tolerance in VCA and discusses key findings through a clinical lens.

Recent findings: Promising VCA tolerance protocols are being investigated, with five recent studies illustrating various successes. These preclinical approaches demonstrate a correlation between the presence of donor-derived T cells and VCA tolerance, the importance of using clinically available reagents within preclinical protocols, and the ability to induce sustained tolerance through nonmyeloablative methods. Furthermore, environmental factors, such as NB-UVB light are being investigated for their immunomodulation properties and may influence VCA graft rejection.

Summary: To widen the scope of VCA, minimization of immunosuppression is needed. Overall, tolerance induction protocols should have a low-toxicity level, minimally invasive induction therapies, and utilize short-term immunosuppressive medications. By examining the milestones of recent studies, researchers can gain new technical approaches to immune modulation and make data-driven amendments to tolerance protocols in preparation for clinical translation.

Purpose of review: Allograft vasculopathy in vascularized composite allografts (VCA) remains understudied. This review explores the vascular changes in VCA, focused on recent literature.

Recent findings: Allograft vasculopathy in VCA generally includes progressive concentric myointimal thickening and luminal narrowing of arterial vessels through endothelial deterioration and proliferation of smooth muscle cells. Microvascular changes are also noted, with thrombosis and lumen narrowing in microvessels of the skin even in the absence of large vessel vasculopathy. Histopathologic reports of skin containing VCA rejection document arteriosclerosis in deep vessels that are not always reflected in skin punch biopsies. The first revision of the Banff VCA scoring system 2022 was developed to include vascular changes in VCA. The scoring system for chronic changes and antibody mediated rejection continues to be under development.

Summary: The study of vascular changes in VCA continues to progress. Important data and advances in experimental and clinical VCA have been reported and continue to take place. Challenges ahead include capture of clinical data that will evolve beyond transient report forms and approaching on the problem of graft failure well grounded in sound scientific methodology.

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.