Andrew Bradley

Face Transplantation: A Review of the Technical, Immunological, Psychological and Clinical Issues with Recommendations for Good Practice

Three years ago, the Working Party on Facial Transplantation concluded that until there was more information available about risks any potential patient would be exposed to, it would be unwise to proceed with transplantation of the human face. Over the last three years, there has been a deepening understanding of the potential psychological problems of facial transplantation as well as a very considerable debate on the ethical aspects of the procedure. Further data on experimental work in animal models of facial transplantation as well as medium-term follow-up data from 24 hand and forearm transplants in 18 patients has now become available. Furthermore, a partial facial transplantation has been performed in France and a second one in China. In this second edition of the report, the technical, immunological, psychological, and ethical issues are discussed again in the light of this developing knowledge. In particular, there has been a major expansion of the sections on the psychological and societal issues, as well as the ethical and legal problems of facial transplantation. The working party still has considerable reservations about facial transplantation. Although it accepts that on balance the risks cannot be precisely quantified, they remain substantial. Therefore, if patients are allowed to make an informed choice to proceed, they must be very carefully selected and protected in the process, along with the families of both the donors and the recipients. To achieve this, the working party insists that 15 minimum requirements, described at the end of this report, must be fulfilled before it would be appropriate for a research ethics committee/institutional review board to approve of a proposal to undertake facial transplantation.

Cytomegalovirus β2.7 RNA transcript protects endothelial cells against apoptosis during ischemia/reperfusion injury

BACKGROUND Ischemia/reperfusion (I/R) injury causes endothelial cell (EC) dysfunction and can precipitate apoptosis. Complex I of the mitochondrial respiratory chain is a target for I/R injury. The beta2.7 RNA transcript encoded by human cytomegalovirus (CMV) has been shown to stabilize Complex I by direct physical interaction. In this study, we investigated whether stabilizing Complex I in EC in an in vitro model of ischemia could prevent apoptosis. METHODS Lentiviral vectors expressing a full-length beta2.7 RNA were generated from a human immunodeficiency virus-1 (HIV-1) construct, in which the viral promoter had been inactivated and virtually all the viral accessory proteins deleted in order to maximize safety. beta2.7 gene expression in transduced endothelial cells was examined by reverse transcript-polymerase chain reaction (RT-PCR). EC were prepared from rat aorta. An in vitro hypoxia/reperfusion (H/R) and I/R injury models were set up and apoptosis was assessed using caspase-3 activity. Reactive oxygen species (ROS) production in the endothelial cells was assessed by the capacity to oxidize non-fluorescent dihydrorhodamine-123 (DHR-123) to fluorescent rhodamine-123 and measured by flow cytometry. RESULTS H/R and I/R injury induced formation of ROS and EC apoptosis. Overexpression of the viral beta2.7 RNA, which stabilizes Complex I, reduced ROS production and inhibited EC apoptosis. CONCLUSIONS beta2.7 RNA is a novel effector molecule that can protect rat aortic endothelial cells from I/R injury causing apoptosis. As a non-coding RNA, beta2.7 RNA will not induce an immune response in the recipient. We have shown that overexpression of beta2.7 RNA can protect RAEC from H/R- or I/R-mediated apoptosis by reduction of ROS formation.

Questioning the added value of Luminex single antigen beads to detect C1q binding donor HLA-specific antibodies.

Luminex single antigen bead (SAB) technology enables highly sensitive and rapid characterization of immunoglobulin G (IgG) human leukocyte antigen (HLA)-specific antibodies. It is widely used to determine antibody compatibility for renal transplantation and to aid the diagnosis of antibody-mediated rejection and response to therapy. HLA-specific antibodies may contribute to allograft rejection through a variety of mechanisms, including activation of the classical complement pathway, endothelial cell activation, and recruitment of Fc-dependent effector cells. Of these, complement-mediated cytotoxicity has long been associated with hyperacute rejection and, more recently, antibody-mediated rejection for which the deposition of the complement component C4d on peritubular capillaries is a diagnostic marker. In the standard SAB assay, patient serum is incubated with microbeads coated with purified HLA proteins. Human leukocyte antigenYspecific IgG antibody binding is then detected using a fluorescent anti-IgG detection antibody. Increasing levels of donor HLA-specific antibodies detected by this assay predict inferior long-term graft outcome, but not all patients with IgG donor-specific HLA antibodies (DSA) have a poor graft outcome (1, 2). This observation is consistent with the notion that HLA antibodies with the same specificity may differ in their ability to cause graft injury, and this variability may be related to differences in complement fixing activity. In an effort to improve the clinical utility of the IgG

Barriers to living donor kidney transplantation in the United Kingdom: A national observational study

ABSTRACT Background. Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. Methods. A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. Results. Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08–0.17], P < 0.0001 for 65–75 years versus 18–34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39–0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42–0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46–0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42–0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37–0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85–0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. Conclusions. Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation.

Variation in Practice Patterns for Listing Patients for Renal Transplantation in the United Kingdom: a National Survey.

Background Despite the availability of guidelines for the evaluation of candidates for renal transplantation, variation in access to transplantation exists. This national survey investigates whether center variation exists in the assessment of patients for renal transplantation in the United Kingdom. Methods An online survey, informed by qualitative interviews, was distributed to all UK renal centers. This survey examined center approaches to chronic kidney disease service provision, transplant recipient assessment, education provision, and waitlisting decision making processes. Center reevaluation policies for patients already listed and priorities for future development were also examined. Results All 71 renal centers responded. Of these, 83% reviewed predialysis patients in a low clearance clinic. In 26% of the centers, transplantation was not discussed as a treatment option with all patients. Fourteen centers reported having a dedicated transplant assessment clinic, whereas 28% did not have a formal assessment protocol. Age was an exclusion criterion for listing in 3 centers, all of which had a cutoff at 75 years. Eighty-three percent of the centers excluded patients with a high body mass index. Cardiac investigations were risk-stratified in 90% of centers. Surgical involvement varied with 11% of centers listing patients without formal surgical review. There was no formal protocol in place to reevaluate listed patients in 62% of centers. Conclusions There is wide variation in UK practice patterns for listing patients for renal transplantation, though its impact on access to transplantation is unclear. The extent to which center-specific and patient-specific factors affect access to transplantation requires further analysis in a prospective cohort of patients.