Assessment of biological organ age using molecular pathology in pre-transplant kidney biopsies.

Organ shortage is a major challenge in kidney transplantation but the use of older donors, often with co-morbidities, is hampered by inconsistent outcomes. Methods of accurately stratifying marginal donor organs by clinical and histological assessment are lacking. To better understand organ variability, we profiled the transcriptomes of 271 kidneys from deceased donors at retrieval. Following correction for biopsy composition, we assessed molecular pathways that associated with delayed, and sub-optimal one-year graft function. Analysis of cortical biopsies identified an adaptive immune gene-rich module that significantly associated with increasing age and worse outcomes. Cellular deconvolution using human kidney reference single cell transcriptomes confirmed an increase in kidney-specific B and T cell signatures, as well as kidney macrophage, myofibroblast and fibroblast gene sets in this module. Surprisingly, innate immune pathway and neutrophil gene signature enrichment was associated with better outcomes. Thus, our work uncovers cellular molecular features of pathological organ ageing, identifiable at kidney retrieval, with translational potential.

Transplantation of Organs From DCD and DBD Donors Who Died After Ligature Asphyxiation.

BACKGROUND: The United Kingdom transplant registry data demonstrated similar transplant outcomes for recipients of kidneys from donors who died following ligature asphyxiation and those who received organs from donors dying from other causes. The impact that this donor cause of death has on the outcomes of other solid organ transplant recipients remains uncertain. METHODS: The United Kingdom transplant registry analysis was undertaken to determine transplant outcomes in recipients of lungs, hearts, livers' and pancreases from donors who died following ligature asphyxiation. RESULTS: Between January 01, 2003, and December 31, 2016, 2.7% (n = 521) of all potential United Kingdom donors died following ligature asphyxiation (mostly suicide by hanging). Of these, 416 (79.9%; 197 donation after brain stem death and 219 donation after circulatory death [DCD]) donated an organ for transplantation. These donors provided organs for 574 transplants (66 lung transplants, 75 heart transplants, 279 liver transplants, and 154 pancreas transplants). Patient and graft survival were similar for recipients of both donation after brain stem death and DCD hearts, livers, and pancreases from donors who died following ligature asphyxiation. Unadjusted graft and patient survival were significantly worse for recipients of lungs from DCD donors who died following ligature asphyxiation. This detrimental effect persisted after propensity score matching. CONCLUSIONS: Livers, hearts, and pancreases from donors who die following ligature asphyxiation suffer an additional warm ischemic insult, but this does not negatively impact transplant outcomes. Outcomes for recipients of DCD lungs appear to be significantly worse.

Transplantation of kidneys from DCD and DBD donors who died after ligature asphyxiation: The UK experience.

There is uncertainty about whether hypoxic injury accompanying donor death from ligature asphyxiation influences renal transplant outcomes, particularly for recipients of kidneys donated after circulatory death (DCD). The UK Registry analysis was undertaken to determine transplant outcomes in recipients of kidneys from donors who died following ligature asphyxiation. From 2003 to 2016, 2.7% (n = 521) of potential organ donors died following ligature asphyxiation (mostly suicide by hanging). Of these, 409 (78.5%) donated kidneys for transplantation (46.9% donation after brain death [DBD] and 53.1% DCD donors) resulting in 650 kidney transplants. Compared to other deceased donors, those dying from ligature asphyxiation were younger, more often male, and had less hypertension. Unadjusted patient and graft survival were superior for recipients of both DBD and DCD kidneys from donors dying after ligature asphyxiation, although after adjustment for donor/recipient variables, transplant outcomes were similar. A case-control matched analysis confirmed transplant outcomes for those who received kidneys from donors dying after ligature asphyxiation were similar to controls. Although caution is required in interpreting these findings because of potential selection bias, kidneys from donors dying of ligature asphyxiation suffer an additional warm ischemic insult that does not apparently adversely influence transplant outcomes, even for kidneys from DCD donors.

Use of Organs From Hepatitis C Virus-Positive Donors for Uninfected Recipients: A Potential Cost-Effective Approach to Save Lives?

BACKGROUND: Organs from hepatitis C virus (HCV) seropositive (HCVpos) individuals are seldom used for transplantation because of the risk of disease transmission. Because transmitted HCV is now amenable to effective treatment, we estimated the potential impact of using HCVpos deceased donor organs for transplantation. METHODS: The Potential Donor Audit of patients (<80 years) dying in UK critical care units and the UK Transplant Registry was searched to identify HCVpos potential and proceeding deceased donors. Donor organ quality was assessed using validated donor organ quality indices. Cost analysis was performed by comparing the cumulative cost of direct-acting antivirals with hemodialysis and renal transplantation. RESULTS: Between 2009 and 2016, 120 patients identified from the Potential Donor Audit were not considered as potential donors because of the presence of HCV. Between 2000 and 2015, 244 HCVpos potential deceased donors were identified from the UK Transplant Registry, and 76 (31%) proceeded to donation, resulting in 63 liver, 27 kidney, and 2 heart transplants. Recipient and graft survival was not adversely impacted by donor HCVpos status. Most (69%) offered organs were declined because of positive virology although their quality was similar to that of other transplanted organs. The additional costs of treating recipients exposed to HCV by receiving a HCVpos kidney was cost-neutral with dialysis 5 years from transplantation. CONCLUSIONS: HCVpos donors represent a potential source of organs for HCV seronegative recipients as many good quality HCVpos donor organs are not currently used for transplantation. This change in practice may increase access to transplantation without having an adverse effect on transplant outcome.

Deceased Organ Donors With a History of Increased Risk Behavior for the Transmission of Blood-Borne Viral Infection: The UK Experience.

BACKGROUND: Deceased organ donors are routinely screened for behaviors that increase the risk of transmissible blood-borne viral (BBV) infection, but the impact of this information on organ donation and transplant outcome is not well documented. Our aim was to establish the impact of such behavior on organ donation and utilization, as well transplant recipient outcomes. METHODS: We identified all UK deceased organ donors from 2003 to 2015 with a disclosed history of increased risk behavior (IRB) including intravenous drug use (IVDU), imprisonment and increased risk sexual behavior. RESULTS: Of 17 262 potential donors, 659 (3.8%) had IRB for BBV and 285 (1.7%) were seropositive for BBV, of whom half had a history of IRB (mostly IVDU [78.5%]). Of actual donors with IRB, 393 were seronegative for viral markers at time of donation. A history of recent IVDU was associated with fewer potential donors proceeding to become actual organ donors (64% vs 75%, P = 0.007). Donors with IRB provided 1091 organs for transplantation (624 kidneys and 467 other organs). Transplant outcome was similar in recipients of organs from donors with and without IRB. There were 3 cases of unexpected hepatitis C virus transmission, all from an active IVDU donor who was hepatitis C virus seronegative at time of donation, but was found to be viremic on retrospective testing. CONCLUSIONS: Donors with a history of IRB provide a valuable source of organs for transplantation with good transplant outcomes and there is scope for increasing the use of organs from such donors.

Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis.

BACKGROUND: Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients. METHODS: Using the UK Transplant Registry, a retrospective cohort analysis of deceased organ donors in the UK was undertaken to better understand the extent to which organs from deceased donors with meningitis and/or encephalitis (M/E) (of both known and unknown cause) have been used for transplantation, and to determine the associated recipient outcomes. RESULTS: Between 2003 and 2015, 258 deceased donors with M/E were identified and the causative agent was known in 188 (72.9%). These donors provided 899 solid organs for transplantation (455 kidneys and 444 other organs). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at time of transplantation who transmitted a fatal nematode infection to 2 kidney transplant recipients. A further 3 patients (2 liver and 1 heart recipient) died within 30 days of transplantation from a neurological cause (cerebrovascular accident) with no suggestion of disease transmission. Overall, patient and graft survival in recipients of organs from donors with M/E were similar to those for all other types of deceased organ donor. CONCLUSION: Donors dying with M/E represent a valuable source of organs for transplantation. The risk of disease transmission is low but, where the causative agent is unknown, caution is required.

Pharmacological and other interventions for head and neck cancer pain: a systematic review.

OBJECTIVES: Pain is a common complication in head and neck cancer. The aim of this paper is to evaluate the evidence from randomised control trials investigating pharmacological and non-pharmacological methods of pain management in head and neck cancer. MATERIAL AND METHODS: Medline, Embase and the Cochrane library databases were searched. Squamous cell carcinomas of the head and neck excluding nasopharyngeal and salivary gland cancers were included. The limits were "human" and "randomised clinical trials". A quality assessment was carried out. RESULTS: 13 studies were included with a total of 644 participants. The primary outcome for most of these papers was pain control post-treatment. Levels of bias varied between the studies. Majority (12 out of the 13 studies) reported intervention to be superior to the control or standard therapy in pain management. Only 46% of the studies were carried out on an intention to treat basis. Two studies reported high dropout rates, with one at 66%. CONCLUSIONS: There is insufficient evidence from randomised clinical trials to suggest an optimal pharmacological intervention for head and neck cancer pain post-treatment. Further high quality randomised clinical trials should be conducted to develop an optimal management strategy for head and neck cancer pain.