Current Opinion in Organ Transplantation最新文献

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.

Purpose of review: Solid organ transplantation recipients have an increased risk of infection, exacerbated by immunosuppressant medications that need to finely balance suppression of the immune system to prevent allograft rejection while avoiding over-suppression leading to infections and malignancy. Exercise modulates immune functions, with moderate-intensity activities particularly associated with enhanced antiviral immunity and reduced infection incidence. However, investigations of the effects of exercise and physical activity on immune function and infection risk posttransplantation are scarce. This review highlights areas where the relationship between exercise, immune function and infection risk has greatest potential for benefit for solid organ transplantation and therefore greatest need for investigation.

Recent findings: Moderate and higher intensity exercise do not appear to cause adverse immunological effects in kidney transplantation recipients, although evidence from other organ transplantation is lacking. Evidence from healthy younger and older adults suggests that regular exercise can reduce risk of respiratory infections and latent herpesvirus reactivation and improves antibody responses to vaccination, which is of great importance for organ transplantation recipients.

Summary: There is a strong need for research to investigate the role of exercise on immune function and infection risk in solid organ transplantation to improve both allograft survival and long-term health of the recipient.

Purpose of review: Donor risk factors and events surrounding donation impact the quantity and quality of grafts generated to meet liver transplant waitlist demands. Donor interventions represent an opportunity to mitigate injury and risk factors within donors themselves. The purpose of this review is to describe issues to address among donation after brain death, donation after circulatory determination of death, and living donors directly, for the sake of optimizing relevant outcomes among donors and recipients.

Recent findings: Studies on donor management practices and high-level evidence supporting specific interventions are scarce. Nonetheless, for donation after brain death (DBD), critical care principles are employed to correct cardiocirculatory compromise, impaired tissue oxygenation and perfusion, and neurohormonal deficits. As well, certain treatments as well as marginally prolonging duration of brain death among otherwise stable donors may help improve posttransplant outcomes. In donation after circulatory determination of death (DCD), interventions are performed to limit warm ischemia and reverse its adverse effects. Finally, dietary and exercise programs have improved donation outcomes for both standard as well as overweight living donor (LD) candidates, while minimally invasive surgical techniques may offer improved outcomes among LD themselves.

Summary: Donor interventions represent means to improve liver transplant yield and outcomes of liver donors and grafts.

Purpose of review: Machine perfusion has been adopted into clinical practice in Europe since the mid-2010s and, more recently, in the United States (US) following approval of normothermic machine perfusion (NMP). We aim to review recent advances, provide discussion of potential future directions, and summarize challenges currently facing the field.

Recent findings: Both NMP and hypothermic-oxygenated perfusion (HOPE) improve overall outcomes after liver transplantation versus traditional static cold storage (SCS) and offer improved logistical flexibility. HOPE offers additional protection to the biliary system stemming from its' protection of mitochondria and lessening of ischemia-reperfusion injury. Normothermic regional perfusion (NRP) is touted to offer similar protective effects on the biliary system, though this has not been studied prospectively.The most critical question remaining is the optimal use cases for each of the three techniques (NMP, HOPE, and NRP), particularly as HOPE and NRP become more available in the US. There are additional questions regarding the most effective criteria for viability assessment and the true economic impact of these techniques. Finally, with each technique purported to allow well tolerated use of riskier grafts, there is an urgent need to define terminology for graft risk, as baseline population differences make comparison of current data challenging.

Summary: Machine perfusion is now widely available in all western countries and has become an essential tool in liver transplantation. Identification of the ideal technique for each graft, optimization of viability assessment, cost-effectiveness analyses, and proper definition of graft risk are the next steps to maximizing the utility of these powerful tools.

Purpose of review: Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology.

Recent findings: Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection.

Summary: While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access.