Explore the vast range of titles available.

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality. Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.

Background Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. Methods In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). Discussion This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. Trial registration ISRCTN ISRCTN14957538. Registered in October 2022.

Background A shortage of organs available for transplantation is causing loss of life. Increasing the number of individuals on the National Health Service (NHS) Organ Donor Register (ODR) is one way to address the shortage of organs. In Great Britain, new drivers registering for their driving licence are invited to join the ODR. A further 17 million drivers renew their road tax online each year, presenting an additional opportunity to prompt drivers to join the ODR. This trial explores the effect of adding persuasive messages to a prompt to join the ODR at the end of road tax payment transactions. Methods In this pragmatic, parallel group, quasi-randomised controlled trial, drivers renewing their road tax or registering for a driving licence were alternately allocated, using a JavaScript randomisation code embedded in the GOV.UK website, to view a control prompt inviting sign-ups to the ODR or the same prompt plus one of seven theoretically informed persuasive messages; (i) social norms alone, (ii) social norms plus the NHS ODR logo, (iii) social norms plus an image, (iv) loss frame, (v) gain frame, (vi) reciprocity and (vii) cognitive dissonance. The trial took place over a 4-week period in June 2013. The primary outcome measure was participants completing the online registration form (sign-ups). Results Altogether, 1,085,322 website users were included in the study. Further, 1171 more sign-ups were completed under the most effective message (reciprocity) compared to the control prompt alone (reciprocity: n  = 4256, control: n  = 3085; odds ratio, OR 1.38, 95% confidence interval 1.32–1.45, p  < 0.001). The loss-framed message was as effective. All messages increased sign-ups compared to the control prompt apart from the social norms message plus image ( n  = 2879; OR 0.94, 95% confidence interval 0.89–0.99, p  < 0.05). Conclusions Short persuasive messages alongside a prompt can persuade more ODR sign-ups for individuals renewing their road tax than a prompt alone. The most effective message remains in place today. Since the trial in 2013, the same message has been implemented across 25 government end-of-transaction websites on GOV.UK, resulting in 529,000 new registrations to the ODR up to 31st October 2017.

Background The gap between the supply and demand of organ donors is substantial, causing patients to suffer from long waiting times. Moreover, the lack of registrations places a burden on family members and medical professionals when an unregistered individual dies. This article describes a cluster randomized controlled trial (CRCT) study to assess the effectiveness and quality of implementation of a web-based program aimed at encouraging lower-educated adolescents to register a well-informed choice about organ donation, regardless of it being as a donor or not. Methods/design The program will be delivered by teachers at schools for Intermediate Vocational Education in the Netherlands. The effectiveness will be assessed in a CRCT design with post-test only using self-administered questionnaires for the primary outcome (i.e. intention to register). Classes will be matched to improve equivalence of groups. From each pair of matched classes, one class will be randomly assigned to the experimental condition, and the other assigned to the control condition. Students in the control groups will fill in the questionnaire before receiving the program, while the experimental groups will do this afterwards. A post-test design prevents the risk of testing bias. The required sample size is 14 schools, with 10 classes per school and 13 unregistered students per class. The questionnaire assesses demographics, behavioural determinants (attitude, self-efficacy, knowledge and social outcomes), intention to register (as a donor) and registration status. Six months after delivery, registration status will be assessed again. Additionally, a process evaluation will be conducted to evaluate the quality of implementation using both qualitative (i.e. semi-structured interviews) and quantitative (i.e. logbooks, questionnaires, Google Analytics to track user behaviour at the website) methods. Discussion Findings of the study can help to further improve the program and serve as a basis for a solid dissemination plan. Moreover, the study will provide insight into (change in) determinants of registration and donorship and the translation of research into practice of school-based health promotion interventions, which can serve as an example for others. Trial registration The Dutch Trial Register, NTR6771 . Registered on 24 October 2017. This is version 2 of the protocol (5 November 2017).

The continuing shortage of deceased donor organs for transplantation, and the limited number of potential donors after brain death, has led to a resurgence of interest in donation after circulatory death (DCD). The processes of warm and cold ischemia threaten the viability of DCD organs, but these can be minimized by well-organized DCD pathways and new techniques of in situ organ preservation and ex situ resuscitation and repair post-explantation. Transplantation survival after DCD is comparable to donation after brain death despite higher rates of primary non-function and delayed graft function. Countries with successfully implemented DCD programs have achieved this primarily through the establishment of national ethical, professional and legal frameworks to address both public and professional concerns with all aspects of the DCD pathway. It is unlikely that expanding standard DCD programs will, in isolation, be sufficient to address the worldwide shortage of donor organs for transplantation. It is therefore likely that reliance on extended criteria donors will increase, with the attendant imperative to minimize ischemic injury to candidate organs. Normothermic regional perfusion and ex situ perfusion techniques allow enhanced preservation, assessment, resuscitation and/or repair of damaged organs as a way of improving overall organ quality and preventing the unnecessary discarding of DCD organs. This review will outline exemplar controlled and uncontrolled DCD pathways, highlighting practical and logistical considerations that minimize warm and cold ischemia times while addressing potential ethical concerns. Future perspectives will also be discussed.

Approximately three million people have immigrated to the state of Israel since it was founded. Consequently, the immunogenetic profile of the younger generation may consist of a genetic mixture of formerly distinct population groups. We aimed to investigate whether HLA profiles in the Israeli population are age dependent and how this influences representation of various age groups in local donor registries. We determined HLA-A*, HLA-B*, and HLA-DRB1* low-resolution phenotypes of three age groups ( n  = 4,169 in each): (1) cord blood units collected between 2009 and 2013 (BABIES) and adult registry donors (2) aged 18–28 years (YOUNG) and (3) aged 49–60 years (OLD). We compared the results with virtual groups that simulate the offspring of the actual study groups. None of the three actual age groups were in Hardy-Weinberg equilibrium. The YOUNG presented four HLA-B alleles that were absent in the OLD and BABIES. A significantly higher percentage among the OLD and BABIES had a “matched” individual within their group in comparison to the YOUNG. In the YOUNG, the 10 most common haplotypes account for 16.7 % of the population, in comparison to 18.2 % in the OLD or 19.8 % in the BABIES group. The BABIES group was genetically remote from all other groups. Further disparities were found between the actual and the corresponding virtual groups. We conclude that discrete age groups in Israel present distinct immunogenetic profiles, where the younger generation is more heterogeneous. The population dynamics of the age-dependent HLA profile is multifactorial: gradual intersubgroup admixture, nonrandom mating, and entry of new alleles.

Key Points The autoimmune response in type 1 diabetes combined with the response to allogeneic cell transplantation remains a formidable barrier to transplant success that currently requires the use of powerful immunosuppressive drugs. Encapsulation strategies have the potential to ameliorate these responses to promote survival post-transplantation, with modifications to the biomaterial chemistry, the incorporation of biologics or cell co-transplantation being used to avoid lifelong immunosuppression. Allogeneic islets are the current standard for clinical use; however, the supply of these islets is insufficient to meet the need for patients. Alternative sources such as human embryonic stem cell-derived β-cells and porcine islets have the potential to satisfy demand, although efficacy, safety and regulatory issues remain to be addressed. Vascularization of the transplant site is being developed to enhance islet function post-transplantation by providing the nutrients necessary for survival, while also allowing the sensing of glucose and the distribution of insulin. Oxygen is frequently the limiting factor and oxygen delivery systems are also being developed to complement the vascularization process. A small number of islet encapsulation systems have been applied clinically, all of which have demonstrated good safety profiles, although it is too early to evaluate functional outcomes. Islet transplantation can be an effective therapy for patients with type 1 diabetes, but its widespread use is limited by the need for lifelong immunosuppression. Here, Desai and Shea discuss the emerging potential of islet cell encapsulation including new strategies, assess key challenges facing the human translation of this technology and highlight encapsulation devices that have entered the clinic. Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. Although islet transplantation has proved to be successful for some patients with type 1 diabetes, its widespread use is limited by islet donor shortage and the requirement for lifelong immunosuppression. An encapsulation strategy that can prevent the rejection of xenogeneic islets or of stem cell-derived allogeneic islets can potentially eliminate both of these barriers. Although encapsulation technology has met several challenges, the convergence of expertise in materials, nanotechnology, stem cell biology and immunology is allowing us to get closer to the goal of encapsulated islet cell therapy for humans.

Solid-organ transplantation is the treatment of choice for many patients with end-stage diseases, but the supply of organs is limited. Recent advances are improving the quality and supply of organs for transplantation.

The use of amniotic membrane in ophthalmic surgery and other surgical procedures in the fields of dermatology, plastic surgery, genitourinary medicine and otolaryngology is on the increase. Furthermore, amniotic membrane and its epithelial and mesenchymal cells have broad use in regenerative medicine and hold great promise in anticancer treatment. Amniotic membrane is a rich source of biologically active factors and as such, promotes healing and acts as an effective material for wound dressing. Amniotic membrane supports epithelialization and exhibits anti-fibrotic, anti-inflammatory, anti-angiogenic and anti-microbial features. Placentas utilised in the preparation of amniotic membrane are retrieved from donors undergoing elective caesarean section. Maternal blood must undergo serological screening at the time of donation and, in the absence of advanced diagnostic testing techniques, 6 months postpartum in order to cover the time window for the potential transmission of communicable diseases. Amniotic membrane is prepared by blunt dissection under strict aseptic conditions, then is typically transferred onto a nitrocellulose paper carrier, usually with the epithelial side up, and cut into multiple pieces of different dimensions. Amniotic membrane can be stored under various conditions, most often cryopreserved in glycerol or dimethyl sulfoxide or their mixture with culture medium or buffers. Other preservation methods include lyophilisation and air-drying. In ophthalmology, amniotic membrane is increasingly used for ocular surface reconstruction, including the treatment of persistent epithelial defects and non-healing corneal ulcers, corneal perforations and descemetoceles, bullous keratopathy, as well as corneal disorders with associated limbal stem cell deficiency, pterygium, conjunctival reconstruction, corneoscleral melts and perforations, and glaucoma surgeries.

The National Marrow Donor Program (NMDP) has increased the availability of suitable HLA-matched donors of bone marrow and cord blood, such that more than 90% of people of European or African American ancestry in need of a donor will have one. Hematopoietic stem-cell transplantation (HSCT) is a potentially curative therapy for several life-threatening blood cancers and other diseases. Although an HLA-matched sibling is the preferred donor, only about 30% of patients who may benefit from HSCT have such a donor available. To address this issue, registries of adult volunteers and, more recently, umbilical cord–blood banks have been developed around the globe. In the United States, the National Marrow Donor Program (NMDP) was established in 1986 and has grown to include more than 10.5 million adult volunteers and nearly 200,000 cord-blood units. With contracts from the federal government, the NMDP currently operates . . .