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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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The use of procedural mechanical support during lung transplantation (LTx) varies between centers and the optimal support strategy is still controversially discussed. The two main questions are if cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) should be preferred and whether mechanical support should be reserved for specific patient groups or a routine use can be recommended., Recent Findings: Recent cohort studies have consistently shown that LTx on CPB leads to inferior outcomes when compared to venoarterial (va)-ECMO. Thus, ECMO should be preferred in lung transplantation except for special indications. Despite its higher invasiveness, ECMO offers some pivotal advantages over off-pump lung transplantation. It has been shown to remarkably reduce rates of primary graft dysfunction, supporting the concept of a routine intraoperative ECMO use in LTx., Summary: Although randomized-controlled trials addressing this question are still lacking, current evidence appears to favor the routine use of ECMO support during lung transplantation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Primary graft dysfunction (PGD) is a devastating complication in the acute postoperative lung transplant period, associated with high short-term mortality and chronic rejection. We review its definition, pathophysiology, risk factors, prevention, treatment strategies, and future research directions., Recent Findings: New analyses suggest donation after circulatory death and donation after brain death donors have similar PGD rates, whereas donors >55 years are not associated with increased PGD risk. Recipient pretransplant diastolic dysfunction and overweight or obese recipients with predominant abdominal subcutaneous adipose tissue have increased PGD risk. Newly identified recipient biomarkers and donor and recipient genes increase PGD risk, but their clinical utility remains unclear. Mixed data still exists regarding cold ischemic time and PGD risk, and increased PGD risk with cardiopulmonary bypass remains confounded by transfusions. Portable ex vivo lung perfusion (EVLP) may prevent PGD, but its use is limited to a handful of centers. Although updates to current PGD treatment are lacking, future therapies are promising with targeted therapy and the use of EVLP to pharmacologically recondition donor lungs., Summary: There is significant progress in defining PGD and identifying its several risk factors, but effective prevention and treatment strategies are needed., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Primary graft dysfunction (PGD) is common early postheart transplantation; however, use of standardized definitions remains inconsistent. This review focuses on understanding the incidence, classification, risk factors, and management of PGD., Recent Findings: The incidence and mortality of PGD in heart transplant varies considerably in the published literature ranging from 1.0% to 31% and 3% to 75%, respectively. There is also considerable variation in management strategies with current data favoring early intervention., Summary: PGD in heart transplantation remains a challenging problem associated with significant mortality and morbidity. There is need for a consistent and accessible definition to better define associated risk factors and optimize management strategies.

Purpose of Review: Organ transplantation and other major surgeries are impacted by ischemia-reperfusion injury (IRI). Mesenchymal stromal cells (MSCs) recently became an attractive alternative therapeutic tool to combat IRI. The present review highlights the effects of MSCs in the preclinical animal models of IRI and clinical trials, and explains their potential modes of action based on the pathophysiological IRI cascade., Recent Findings: The application of MSCs in animal models of IRI show anti-inflammatory and anti-apoptotic effects, particularly for damage to the kidneys, heart and lungs. The mechanism of MSC action remains unclear, but may involve paracrine factors which could include the transfer of microvesicles, RNA or mitochondria. Although few clinical trials have reached completion, adverse effects appear minimal., Summary: MSCs show promise in protecting against IRI-induced damage. They appear to help recovery mainly by affecting the levels of inflammation and apoptosis during the organ repair process. In addition, they may mediate immunomodulatory effects on the innate and adaptive immune processes triggered during reperfusion and reduce fibrosis. Success in preclinical animal models has led to the initiation of ongoing clinical trials.

Purpose of Review: Primary graft dysfunction (PGD) is the primary obstacle to short-term survival for post-lung transplant patients. PGD is a form of acute lung injury secondary to donor brain death and ischemia-reperfusion damage to the allograft affecting 10-25% of all lung transplant recipients. This article reviews the significant role of allograft ischemia in the phenotypic presentation of PGD and the evidence for activation and disruption of normal cellular pathways for the development and long-term sequelae., Recent Findings: Pathways implicated in the pathogenesis of PGD resultant from tissue ischemia include abnormalities in coagulation and fibrinolysis, epithelial cell injury, endothelial cell dysfunction, chemotaxis, and alterations in cell adhesion. Blood and bronchoalveolar lavage fluid biomarkers from these pathways have been increasingly identified as useful for diagnosing and predicting the development of severe PGD., Summary: Future efforts at preventing and treating severe PGD should focus on techniques for altering the pathways involved in PGD pathogenesis. Ex-vivo lung perfusion and transduction with interleukin-10 are promising modalities for preventing PGD and expanding the available lung transplant donor pool.

Purpose of Review: There is increasing disparity between the supply of acceptable donor organs and the number of potential transplant recipients. The shortage of organs for transplantation demands optimal utilization of a wider spectrum of donor organs, including nonheart-beating and other extended criteria donors. In the case of the liver, a substantial number of organs are discarded because of a risk of primary nonfunction., Recent Findings: For many years hypothermic preservation has been the universal standard for organ preservation. Although limited in terms of the duration of preservation it has had the major advantages of simplicity, portability and affordability. Organ preservation by normothermic machine perfusion has repeatedly proven superiority over static cold storage in experimental settings. However, it is complex and costly and its place in clinical transplantation has not yet been established. In liver preservation normothermic perfusion provides the potential: (a) to preserve extended criteria grafts for long periods; (b) to assess the viability of these grafts during perfusion; and (c) to improve the condition of the grafts., Summary: Avoidance of cold ischaemic preservation damage and repair of injury sustained during warm ischaemia and organ procurement would potentially allow many livers from extended criteria donors to be transplanted reliably. The current challenges are, first to confirm the feasibility of the normothermic machine perfusion methodology in human livers and, second, to develop and introduce a functional device into the clinical arena.

Purpose of Review: The critical organ shortage has forced lung transplant teams to extend their donor criteria, thereby compromising a good early outcome in the recipient. Better preservation solutions for longer storage are welcomed to further reduce incidence of primary graft dysfunction. New ex-vivo techniques to assess and to condition lungs prior to transplantation are hoped to increase the number of available pulmonary grafts., Recent Findings: Although no prospective clinical trial has been carried out so far, clinical and experimental evidence suggest that an extracellular solution is currently the preservation fluid of choice for lung transplantation. The combination of an antegrade and retrograde pulmonary flush and technique to control reperfusion and ventilation are becoming common practice, although the evidence to support this method is low. Ex-vivo lung perfusion to assess and to recondition lungs has been demonstrated to be well tolerated and effective in small clinical series., Summary: New extracellular preservation solutions have contributed in decreasing the incidence of primary graft dysfunction over the last decade leaving more room to extend the donor criteria and ischemic time. Ex-vivo lung perfusion is now on the horizon as a potential method to prolong the preservation time and to resuscitate lungs of inferior quality.

Purpose of Review: Biological modulation of renal ischemia-reperfusion injury holds the potential to reduce the incidence of early graft dysfunction and to safely expand the donor pool with kidneys that have suffered prolonged ischemic injury before organ recovery., Recent Findings: In the current review, we will discuss clinical studies that compare kidney transplant recipients with and without early graft dysfunction in order to elucidate the pathophysiology of ischemic acute allograft injury. We will specifically review the mechanisms leading to depression of the glomerular filtration rate and activation of the innate immune system in response to tissue injury., Summary: We conclude that the pathophysiology of delayed graft function after kidney transplantation is complex and shares broad similarity with rodent models of ischemic acute kidney injury. Given the lack of specific therapies to prevent delayed graft function in transplant recipients, comprehensive efforts should be initiated to translate the promising findings obtained in small animal models into clinical interventions that attenuate ischemic acute kidney injury after transplantation.

Purpose of Review: The purpose of the present review is to describe the current kidney preservation techniques for donors after cardiac death and to give insight in new developments that may reduce warm ischemia times and therefore improve graft function after transplantation., Recent Findings: There is still a general reluctance to use donors after cardiac death for kidney donation and transplantation, because of a relatively high incidence of delayed graft function and primary nonfunction compared to conventional donors after brain death. New clinically applicable methods, such as automated chest compression devices and extracorporeal membrane oxygenation, may reduce warm ischemia time., Summary: Kidneys from donors after cardiac death sustain an increased incidence of delayed graft function and primary nonfunction. However, transplanted kidneys that do not experience these complications survive as long as conventional kidneys from donors after brain death. Maintaining adequate organ perfusion after cardiac death by using automated chest compression devices and extracorporeal membrane oxygenation reduces warm ischemia time. Optimal organ preservation and careful selection of kidneys from donors after cardiac death may reduce the risk of delayed graft function and primary nonfunction. Major efforts should continue to be made to improve the quality of kidneys from donors after cardiac death and thereby expand the utilization of this large pool of donor kidneys to its full potential.

Purpose of Review: The history of transplantation of the pancreas, unlike that of transplantation of other abdominal organs, has largely been shaped by the associated surgical complications. After more than three decades of progress, surgical-technical pancreas graft failure rates have decreased to approximately 8%. The most recent developments in this area are systematically reviewed in this article., Recent Findings: Vascular graft thrombosis remains, by far, the most common cause of technical graft failure. Recent reports suggested that pancreas preservation with histidine-tryptophan-ketoglutarate solution (HTK) might be a risk factor for reperfusion pancreatitis, graft thrombosis and decreased short- and long-term graft survival. It remains unclear whether these results are, at least in part, related to HTK flush volumes and extended preservation (e.g.,>12 h). For selected thrombosed pancreas grafts, there has been renewed interest in pharmacological, interventional, and surgical salvage. For selected recipients with early pancreas graft thrombosis not amenable to a salvage intervention, transplant pancreatectomy in conjunction with immediate retransplantation has emerged as a viable option. For graft thrombosis prevention, the enhanced backtable pancreas vascular reconstruction techniques (e.g., gastroduodenal artery revascularization) proposed by some authors await more formal study. For prevention of native vascular complications in high-risk recipients, several technical modifications have been reported. Developments with respect to other surgical complications (wound infection, pancreatitis, leak, and bleeding) have been more incremental., Conclusion: Recent evidence underscores the importance of judicious donor and recipient selection and of optimization of preservation and surgical factors for excellent short- and long-term pancreas transplant outcomes.