†On behalf of the UK Liver and Cardiothoracic Audit Steering Groups.An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression. In this study on cancer incidence in solid organ transplant recipients in Britain, we describe the incidence of de novo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs. Data in the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland and Wales. Incidence rates in the transplanted population were then compared with the general population, using standardized incidence ratios matched for age, gender and time period. The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater. Nonmelanoma skin cancer, cancer of the lip, posttransplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted. Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient, as well as for different malignancies. These results have implications for a national screening program.
Patients waitlisted for and recipients of solid organ transplants (SOT) are perceived to have a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and death; however, definitive epidemiological evidence is lacking. In a comprehensive national cohort study enabled by linkage of the UK transplant registry and Public Health England and NHS Digital Tracing services, we examined the incidence of laboratory‐confirmed SARS‐CoV‐2 infection and subsequent mortality in patients on the active waiting list for a deceased donor SOT and recipients with a functioning SOT as of February 1, 2020 with follow‐up to May 20, 2020. Univariate and multivariable techniques were used to compare differences between groups and to control for case‐mix. One hundred ninety‐seven (3.8%) of the 5184 waitlisted patients and 597 (1.3%) of the 46 789 SOT recipients tested positive for SARS‐CoV‐2. Mortality after testing positive for SARS‐CoV‐2 was 10.2% (20/197) for waitlisted patients and 25.8% (154/597) for SOT recipients. Increasing recipient age was the only variable independently associated with death after positive SARS‐CoV‐2 test. Of the 1004 transplants performed in 2020, 41 (4.1%) recipients have tested positive for SARS‐CoV‐2 with 8 (0.8%) deaths reported by May 20. These data provide evidence to support decisions on the risks and benefits of SOT during the coronavirus disease 2019 pandemic.
Background Preliminary data suggest that COVID-19 has reduced access to solid organ transplantation. However, the global consequences of the COVID-19 pandemic on transplantation rates and the effect on waitlisted patients have not been reported. We aimed to assess the effect of the COVID-19 pandemic on transplantation and investigate if the pandemic was associated with heterogeneous adaptation in terms of organ transplantation, with ensuing consequences for waitlisted patients.Methods In this population-based, observational, before-and-after study, we collected and validated nationwide cohorts of consecutive kidney, liver, lung, and heart transplants from 22 countries. Data were collected from Jan 1 to Dec 31, 2020, along with data from the same period in 2019. The analysis was done from the onset of the 100th cumulative COVID-19 case through to Dec 31, 2020. We assessed the effect of the pandemic on the worldwide organ transplantation rate and the disparity in transplant numbers within each country. We estimated the number of waitlisted patient life-years lost due to the negative effects of the pandemic. The study is registered with ClinicalTrials.gov, NCT04416256.Findings Transplant activity in all countries studied showed an overall decrease during the pandemic. Kidney transplantation was the most affected, followed by lung, liver, and heart. We identified three organ transplant rate patterns, as follows: countries with a sharp decrease in transplantation rate with a low COVID-19-related death rate; countries with a moderate decrease in transplantation rate with a moderate COVID-19-related death rate; and countries with a slight decrease in transplantation rate despite a high COVID-19-related death rate. Temporal trends revealed a marked worldwide reduction in transplant activity during the first 3 months of the pandemic, with losses stabilising after June, 2020, but decreasing again from October to December, 2020. The overall reduction in transplants during the observation time period translated to 48 239 waitlisted patient life-years lost.Interpretation We quantified the impact of the COVID-19 pandemic on worldwide organ transplantation activity and revealed heterogeneous adaptation in terms of organ transplantation, both at national levels and within countries, with detrimental consequences for waitlisted patients. Understanding how different countries and health-care systems responded to COVID-19-related challenges could facilitate improved pandemic preparedness, notably, how to safely maintain transplant programmes, both with immediate and non-immediate life-saving potential, to prevent loss of patient life-years.
Background. The clinical effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. Methods. We linked 4 national registries to retrospectively identify laboratory-confirmed SARS-CoV-2 infections and deaths within 28 d in England between September 1, 2020, and August 31, 2021, comparing unvaccinated adult SOT recipients and those who had received 2 doses of ChAdOx1-S or BNT162b2 vaccine. Infection incidence rate ratios were adjusted for recipient demographics and calendar month using a negative binomial regression model, with 95% confidence intervals. Case fatality rate ratios were adjusted using a Cox proportional hazards model to generate hazard ratio (95% confidence interval). Results. On August 31, 2021, it was found that 3080 (7.1%) were unvaccinated, 1141 (2.6%) had 1 vaccine dose, and 39 260 (90.3%) had 2 vaccine doses. There were 4147 SARS-CoV-2 infections and 407 deaths (unadjusted case fatality rate 9.8%). The riskadjusted infection incidence rate ratio was 1.29 (1.03-1.61), implying that vaccination was not associated with reduction in risk of testing positive for SARS-CoV-2 RNA. Overall, the hazard ratio for death within 28 d of SARS-CoV-2 infection was 0.80 (0.63-1.00), a 20% reduction in risk of death in vaccinated patients (P = 0.05). Two doses of ChAdOx1-S were associated with a significantly reduced risk of death (hazard ratio, 0.69; 0.52-0.92), whereas vaccination with BNT162b2 was not (0.97; 0.71-1.31). Conclusions. Vaccination of SOT recipients confers some protection against SARS-CoV-2-related mortality, but this protection is inferior to that achieved in the general population. SOT recipients require additional protective measures, including further vaccine doses, antiviral drugs, and nonpharmaceutical interventions. (Transplantation 2022;106: 436-446).
Case fatality ratios for deaths within 28 d of onset in vaccinated compared with unvaccinated transplant recipients Vaccination status (n) SARS-CoV-2 RNA positive, n Deaths in SARS-CoV-2 RNA-positive patients N (%) Unvaccinated (6748) 3473 438 12.6 One dose (1738) 326 39 12.0 Two doses (39 727) 143 11 7.7 SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Objective:To compare the outcomes of livers donated after circulatory death (DCD) and undergoing either in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) with livers undergoing static cold storage (SCS).Summary of Background Data:DCD livers are associated with increased risk of primary nonfunction, poor function, and nonanastomotic strictures (NAS), leading to underutilization.Methods:A single center, retrospective analysis of prospectively collected data on 233 DCD liver transplants performed using SCS, NRP, or NMP between January 2013 and October 2020.Results:Ninety-seven SCS, 69 NRP, and 67 NMP DCD liver transplants were performed, with 6-month and 3-year transplant survival (graft survival non-censored for death) rates of 87%, 94%, 90%, and 76%, 90%, and 76%, respectively. NRP livers had a lower 6-month risk-adjusted Cox proportional hazard for transplant failure compared to SCS (hazard ratio 0.30, 95% Confidence Interval 0.08–1.05, P = 0.06). NRP and NMP livers had a risk-adjusted estimated reduction in the mean model for early allograft function score of 1.52 (P < 0.0001) and 1.19 (P < 0.001) respectively compared to SCS. Acute kidney injury was more common with SCS (55% vs 39% NRP vs 40% NMP; P = 0.08), with a lower risk-adjusted peak-to-baseline creatinine ratio in the NRP (P = 0.02). No NRP liver had clinically significant NAS in contrast to SCS (14%) and NMP (11%, P = 0.009), with lower risk-adjusted odds of overall NAS development compared to SCS (odds ratio = 0.2, 95%CI 0.06–0.72, P = 0.01).Conclusion:NRP and NMP were associated with better early liver function compared to SCS, whereas NRP was associated with superior preservation of the biliary system.
y Shared senior authorship.The objective was to determine whether metabolic goals have been achieved with locally isolated and transported preparations over the first 3 years of the UK's nationally funded integrated islet transplant program. Twenty islet recipients with C-peptide negative type 1 diabetes and recurrent severe hypoglycemia consented to the study, including standardized meal tolerance tests. Participants received a total of 35 infusions (seven recipients: single graft; 11 recipients: two grafts: two recipients: three grafts). Graft function was maintained in 80% at [median (interquartile range)] 24 (13.5-36) months postfirst transplant. Severe hypoglycemia was reduced from 20 (7-50) episodes/patient-year pretransplant to 0.3 (0-1.6) episodes/patient-year posttransplant (p < 0.001). Resolution of impaired hypoglycemia awareness was confirmed [pretransplant: Gold score 6 (5-7); 24 (13.5-36) months: 3 (1.5-4.5); p < 0.03]. Target HbA 1c of <7.0% was attained/maintained in 70% of recipients [pretransplant: 8.0 (7.0-9.6
In 2004, it was agreed that a new allocation scheme for kidneys from deceased heart-beating donors was required in the United Kingdom to address observed inequities in access to transplant. The 2006 National Kidney Allocation Scheme (2006 NKAS) was developed to meet agreed objectives and preparatory work included a review of the criteria for human leukocyte antigen (HLA) matching and simulation evidence about the effectiveness of alternative schemes. ALGORITHM FOR 2006 NKAS: The 2006 NKAS gives absolute priority to all 000 HLA-A, -B, -DR-mismatched patients and well-matched pediatric patients (<18 years), and then a points score defines priorities for allocation with waiting time being most influential. Points for age and HLA mismatch are linked in a novel approach to ensure well-matched transplants for younger patients while recognizing that HLA matching is less important for older patients as retransplantation is less likely to be required. To improve equity for difficult to match patients, rare HLA specificities were defaulted to more common, related specificities. IMPACT OF 2006 NKAS: After 3 years, the scheme is already making good progress in achieving its objectives, with overall results similar to those observed in the simulations. There has been a significant benefit for patients waiting more than 5 years for transplant. A number of other advantages of the scheme are also apparent with equity of access improving in many respects, including the achievement of equity of access to transplant for HLA-DR homozygous patients, but geographical inequity of access will take a number of years to address fully.
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