Developing an Injury-Free 15 Hour Preservation Protocol of Donor Porcine Kidneys Using Normothermic Machine Perfusion.

Normothermic machine perfusion (NMP) offers a superior alternative to hypothermic preservation but is currently time limited. Extending this time could electivise transplantation and enable physiologic assessments of functionality. Porcine kidneys were retrieved, stored on ice for 3.

The contribution of the donor vascularised hand and face allograft in transplant rejection: An immunological perspective.

Overcoming immunological rejection remains a barrier to the safe adoption of Vascularised Composite Allotransplantation (VCA). To mitigate this risk, clinical protocols have been derived from solid organ transplantation, targeting recipient immunomodulation, yet VCA is unique. Face and hand composite allografts are composed of multiple different tissues, each with their own immunological properties.

Bionic Prostheses: The Emerging Alternative to Vascularised Composite Allotransplantation of the Limb.

Twenty years have surpassed since the first vascularised composite allotransplantation (VCA) of the upper limb. This is an opportunity to reflect on the position of VCA as the gold standard in limb reconstruction. The paucity of recipients, tentative clinical outcomes, and insufficient scientific progress question whether VCA will remain a viable treatment option for the growing numbers of amputees.

The Use of Hemoglobin-Based Oxygen Carriers in Ex Vivo Machine Perfusion of Donor Organs for Transplantation.

There has been significant progress in the development of ex vivo machine perfusion for the nonischemic preservation of donor organs. However, several complications remain, including the logistics of using human blood for graft oxygenation and hemolysis occurring as a result of mechanical technology. Recently, hemoglobin-based oxygen carriers, originally developed for use as blood substitutes, have been studied as an alternative to red blood cell-based perfusates.

Hemodynamics and Metabolic Parameters in Normothermic Kidney Preservation Are Linked With Donor Factors, Perfusate Cells, and Cytokines.

Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of the kidney has been studied extensively during the last two decades and implemented in clinical trials. Biomarker research led to success in identifying molecules with diagnostic, predictive and therapeutic properties in chronic kidney disease.

Renal hemofiltration prevents metabolic acidosis and reduces inflammation during normothermic machine perfusion of the vascularized composite allograft: A preclinical study.

Introduction: Recent experimental evidence suggests normothermic machine perfusion of the vascularized composite allograft results in improved preservation compared to static cold storage, with less reperfusion injury in the immediate post-operative period. However, metabolic acidosis is a common feature of vascularized composite allograft perfusion, primarily due to the inability to process metabolic by-products. We evaluated the impact of combined limb-kidney perfusion on markers of metabolic acidosis and inflammation in a porcine model.

Understanding immunological response to desensitisation strategies in highly sensitised potential kidney transplant patients.

Sensitisation to human leukocyte antigen (HLA) represents a significant barrier to kidney transplantation. Antibody removal and immune modulation strategies, known as 'desensitisation', aim to reduce levels of circulating HLA antibodies and increase transplant opportunities for highly sensitised patients (HSPs). However, the effects of desensitisation are generally transient and maintaining low or absent HLA antibody levels remains a substantial challenge.

Modifying dietary patterns in cardiothoracic transplant patients to reduce cardiovascular risk: The AMEND-IT Trial.

Background: Cardiovascular disease (CVD) is common after cardiothoracic transplantation and causes substantial morbidity.

Aims: To assess feasibility and potential effectiveness of dietary interventions to reduce CVD risk.

Materials And Methods: In a pilot intervention, we recruited patients from a tertiary hospital and randomly allocated them to a Mediterranean or low-fat diet for 12 months.

A post-preservation vascular flush removes significant populations of donor leukocytes prior to lung transplantation.

Background: Donor leukocytes are intrinsically involved in acute lung allograft rejection, via self-presentation of donor antigens to recipient leukocytes. Therapeutic modalities to remove donor leukocytes are currently unavailable. We evaluated if a vascular flush immediately following preservation can be used for this purpose.

Pro-IL-1β Is an Early Prognostic Indicator of Severe Donor Lung Injury During Ex Vivo Lung Perfusion.

Background: Ex vivo lung perfusion (EVLP) is used to evaluate and recondition extended criteria donor lungs for transplantation. Interleukin-1β (IL-1β) has been identified as a prognostic indicator of nonrecovery during EVLP. This may be an effect of inflammasome activation or cellular necrosis following donation and graft preservation.

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation.

Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation. Isolated porcine hearts underwent hypothermic, cardioplegic perfusion for 8 h.

Ex Vivo Lung Perfusion Improves the Inflammatory Signaling Profile of the Porcine Donor Lung Following Transplantation.

Background: Primary graft dysfunction and allograft rejection represent major caveats to successful lung transplantation. Reducing inflammation in donor lungs before transplantation may improve outcomes. Evidence exists that ex vivo lung perfusion (EVLP) can alter the donor lung environment, although the mechanisms remain unclear.

Substrate for the Myocardial Inflammation-Heart Failure Hypothesis Identified Using Novel USPIO Methodology.

Objectives: The purpose of this study was to identify where ultrasmall superparamagnetic particles of iron oxide (USPIO) locate to in myocardium, develop a methodology that differentiates active macrophage uptake of USPIO from passive tissue distribution; and investigate myocardial inflammation in cardiovascular diseases.

Background: Myocardial inflammation is hypothesized to be a key pathophysiological mechanism of heart failure (HF), but human evidence is limited, partly because evaluation is challenging. USPIO-magnetic resonance imaging (MRI) potentially allows specific identification of myocardial inflammation but it remains unclear what the USPIO-MRI signal represents.

The future application of nanomedicine and biomimicry in plastic and reconstructive surgery.

Plastic surgery encompasses a broad spectrum of reconstructive challenges and prides itself upon developing and adopting new innovations. Practice has transitioned from microsurgery to supermicrosurgery with a possible future role in even smaller surgical frontiers. Exploiting materials on a nanoscale has enabled better visualization and enhancement of biological processes toward better wound healing, tumor identification and viability of tissues, all cornerstones of plastic surgery practice.

A Randomized Study Comparing the Incidence of Postoperative Pain After Phrenic Nerve Infiltration Vs Nonphrenic Nerve Infiltration During Thoracotomy.

Thoracotomy is a common surgical procedure performed worldwide for lung disease. Despite major advances in analgesia, patients still experience severe shoulder, central back and surgical incision site pain in the postoperative period. This study aimed to assess whether intraoperative phrenic nerve infiltration reduces the incidence of postoperative pain and improves peak flow volume measurements during incentive spirometry.

Adherence to Mediterranean and low-fat diets among heart and lung transplant recipients: a randomized feasibility study.

Background: Heart and lung transplant recipients are at a substantially increased risk of cardiovascular disease (CVD). Since both low-fat and Mediterranean diets can reduce CVD in immunocompetent people at high risk, we assessed adherence among thoracic transplant recipients allocated to one or other of these diets for 12 months.

Methods: Forty-one transplant recipients (20 heart; 21 lung) randomized to a Mediterranean or a low-fat diet for 12 months received diet-specific education at baseline.

Ex-vivo flush of the limb allograft reduces inflammatory burden prior to transplantation.

Background: Passenger leucocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia.

Methods: Bilateral forelimbs from the same pig were procured and infused with preservation flush and stored on ice.

The effect of 1.5 T cardiac magnetic resonance on human circulating leucocytes.

Aims: Investigators have proposed that cardiovascular magnetic resonance (CMR) should have restrictions similar to those of ionizing imaging techniques. We aimed to investigate the acute effect of 1.5 T CMR on leucocyte DNA integrity, cell counts, and function in vitro, and in a large cohort of patients in vivo.

Strategies to Reduce Ischemia Reperfusion Injury in Vascularized Composite Allotransplantation of the Limb.

An important and often underinvestigated contributor to solid organ transplant rejection is ischemia reperfusion injury. This pathophysiological response releases damaging reactive oxygen species and cell stress signals that initiate inflammation, which has a critical role in priming the immune system for allorecognition. In time, this renders graft dysfunction and how this response is mediated in composite tissues remains unknown.

Randomized Study Comparing the Effect of Carbon Dioxide Insufflation on Veins Using 2 Types of Endoscopic and Open Vein Harvesting.

Objective: The aim of the study was to assess whether the use of carbon dioxide insufflation has any impact on integrity of long saphenous vein comparing 2 types of endoscopic vein harvesting and traditional open vein harvesting.

Methods: A total of 301 patients were prospectively randomized into 3 groups. Group 1 control arm of open vein harvesting (n = 101), group 2 closed tunnel (carbon dioxide) endoscopic vein harvesting (n = 100) and Group 3 open tunnel (carbon dioxide) endoscopic vein harvesting (open tunnel endoscopic vein harvesting) (n = 100).

Study Comparing Vein Integrity and Clinical Outcomes in Open Vein Harvesting and 2 Types of Endoscopic Vein Harvesting for Coronary Artery Bypass Grafting: The VICO Randomized Clinical Trial (Vein Integrity and Clinical Outcomes).

Background: Current consensus statements maintain that endoscopic vein harvesting (EVH) should be standard care in coronary artery bypass graft surgery, but vein quality and clinical outcomes have been questioned. The VICO trial (Vein Integrity and Clinical Outcomes) was designed to assess the impact of different vein harvesting methods on vessel damage and whether this contributes to clinical outcomes after coronary artery bypass grafting.

Methods: In this single-center, randomized clinical trial, patients undergoing coronary artery bypass grafting with an internal mammary artery and with 1 to 4 vein grafts were recruited.

The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion.

Background: Extended criteria donor lungs deemed unsuitable for immediate transplantation can be reconditioned using ex vivo lung perfusion (EVLP). Objective identification of which donor lungs can be successfully reconditioned and will function well post-operatively has not been established. This study assessed the predictive value of markers of inflammation and tissue injury in donor lungs undergoing EVLP as part of the DEVELOP-UK study.

Characterizing the early inflammatory contribution of the donor kidney following reperfusion.

Background: Donor kidneys contain a large reservoir of passenger leucocytes that contribute to acute rejection via direct alloantigen presentation and pro-inflammatory cytokine secretion. However, the early contribution of these cells following revascularization has not previously been described. We performed a secondary, high-volume preservation flush following cold storage to characterize the inflammatory contribution of the donor kidney upon reperfusion.

Normothermic Perfusion Induces Donor-Derived Leukocyte Mobilization and Removal Prior to Renal Transplantation.

Introduction: normothermic perfusion offers an alternative method of organ preservation, allowing donor kidneys to be reanimated and evaluated prior to transplantation. Beyond preservation, it can be used to characterize the immunological contribution of the donor kidney in isolation. Furthermore, it has the potential to be used as an immunomodulatory strategy to manipulate donor kidneys prior to transplantation.

Myocardial recovery with mechanical circulatory support.

Mechanical circulatory support (MCS) is instituted in patients with advanced heart failure, some of who may experience sufficient recovery in cardiac function to allow withdrawal of mechanical support. The incidence of left ventricular recovery with MCS is unclear as reported series in the literature demonstrate widely divergent rates. A number of clinical parameters (including echocardiographic, haemodynamic and physiological) are used to indicate likely left ventricular recovery during pump speed reduction but no internationally agreed definition exists.