We present the main findings of the 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia (AAGA). Incidences were estimated using reports of accidental awareness as the numerator, and a parallel national anaesthetic activity survey to provide denominator data. The incidence of certain/probable and possible accidental awareness cases was ~1:19,600 anaesthetics (95% confidence interval 1:16,700-23,450). However, there was considerable variation across subtypes of techniques or subspecialities. The incidence with neuromuscular block (NMB) was ~1:8200 (1:7030-9700), and without, it was ~1:135,900 (1:78,600-299,000). The cases of AAGA reported to NAP5 were overwhelmingly cases of unintended awareness during NMB. The incidence of accidental awareness during Caesarean section was ~1:670 (1:380-1300). Two-thirds (82, 66%) of cases of accidental awareness experiences arose in the dynamic phases of anaesthesia, namely induction of and emergence from anaesthesia. During induction of anaesthesia, contributory factors included: use of thiopental, rapid sequence induction, obesity, difficult airway management, NMB, and interruptions of anaesthetic delivery during movement from anaesthetic room to theatre. During emergence from anaesthesia, residual paralysis was perceived by patients as accidental awareness, and commonly related to a failure to ensure full return of motor capacity. One-third (43, 33%) of accidental awareness events arose during the maintenance phase of anaesthesia, mostly due to problems at induction or towards the end of anaesthesia. Factors increasing the risk of accidental awareness included: female sex, age (younger adults, but not children), obesity, anaesthetist seniority (junior trainees), previous awareness, out-of-hours operating, emergencies, type of surgery (obstetric, cardiac, thoracic), and use of NMB. The following factors were not risk factors for accidental awareness: ASA physical status, race, and use or omission of nitrous oxide. We recommend that an anaesthetic checklist, to be an integral part of the World Health Organization Safer Surgery checklist, is introduced as an aid to preventing accidental awareness. This paper is a shortened version describing the main findings from NAP5--the full report can be found at http://www.nationalauditprojects.org.uk/NAP5_home.

Exosomes are nanometer-sized vesicles released by a number of cell types including those of the immune system, and often contain numerous immune recognition molecules including MHC molecules. We demonstrate in this study that exosomes can display a significant proportion of their MHC class I (MHC I) content in the form of disulfide-linked MHC I dimers. These MHC I dimers can be detected after release from various cell lines, human monocyte-derived dendritic cells, and can also be found in human plasma. Exosome-associated dimers exhibit novel characteristics which include 1) being composed of folded MHC I, as detected by conformational-dependent Abs, and 2) dimers forming between two different MHC I alleles. We show that dimer formation is mediated through cysteine residues located in the cytoplasmic tail domains of many MHC I molecules, and is associated with a low level of glutathione in exosomes when compared with whole cell lysates. We propose these exosomal MHC I dimers as novel structures for recognition by immune receptors.

The coronavirus disease 2019 (COVID-19) pandemic has had a major global impact on solid organ transplantation (SOT). An estimated 16% global reduction in transplant activity occurred over the course of 2020, most markedly impacting kidney transplant and living donor programs, resulting in substantial knock-on effects for waitlisted patients. The increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and excess deaths in transplant candidates has resulted in substantial effort to prioritize the safe restart and continuation of transplant programs over the second year of the pandemic, with transplant rates returning towards prepandemic levels. Over the past 2 y, COVID-19 mortality in SOT recipients has fallen from 20%–25% to 8%–10%, attributed to the increased and early availability of SARS-CoV-2 testing, adherence to nonpharmaceutical interventions, development of novel treatments, and vaccination. Despite these positive steps, transplant programs and SOT recipients continue to face challenges. Vaccine efficacy in SOT recipients is substantially lower than the general population and SOT recipients remain at an increased risk of adverse outcomes if they develop COVID-19. SOT recipients and transplant teams need to remain vigilant and ongoing adherence to nonpharmaceutical interventions appears essential. In this review, we summarize the global impact of COVID-19 on transplant activity, donor evaluation, and patient outcomes over the past 2 y, discuss the current strategies aimed at preventing and treating SARS-CoV-2 infection in SOT recipients, and based on lessons learnt from this pandemic, propose steps the transplant community could consider as preparation for future pandemics.

The NAP5 methodology may be used to assess new reports of AAGA in a standardized manner, especially for the development of an ongoing database of case reporting. This paper is a shortened version describing the protocols, methods, and data analysis from NAP5--the full report can be found at http://www.nationalauditprojects.org.uk/NAP5_home.

BackgroundThe development of HLA antibodies towards a failing renal allograft is a barrier to retransplantation. This study aimed to compare the formation of HLA donor-specific antibodies (DSA) in patients undergoing graft nephrectomy and in those with a failed graft left in situ who had maintenance immunosuppression (IS) stopped, and assess the relative impact of IS cessation and graft nephrectomy on future relative chance of transplant (R-CoT).MethodsA single-center retrospective study of patients with failed grafts between 2005 and 2015 was performed. Samples were tested for DSA pre-IS wean, post-IS wean, and post-IS cessation. Nephrectomy patients additionally had samples tested for DSA before and after nephrectomy. Calculated reaction frequency (cRF) was determined at each timepoint and entered into the UK Organ Donation and Transplant R-CoT calculator.ResultsForty-one patients were included in the study: 24 with nephrectomy and 17 with a failed graft in situ. Patient demographics and duration of IS wean were similar between groups. There was a higher rate of blood transfusion (54% vs 24%) in nephrectomy patients. In patients whose graft remained in situ, cRF rose from 13% pre-IS wean to 40% post-IS wean and 62% after IS cessation. This equated to a reduction in mean R-CoT from 54% to 46% at 5 years. In patients undergoing nephrectomy mean cRF rose from 31% pre-IS wean to 69% post-IS wean and 89% post-IS cessation. Mean R-CoT fell from 54% to 42% at 5 years.ConclusionsA stepwise increase in cRF with reduced chance of transplant was observed in both groups as IS was withdrawn, with a similar pattern irrespective of graft nephrectomy. Calculated reaction frequency was higher in the nephrectomy group. The risks and benefits of stopping IS need to be carefully considered on an individual basis to maximize chance of future transplant.

Background The COVID-19 pandemic is placing a significant strain on healthcare. We conducted a national survey of the UK nephrology workforce to understand its impacts on their working lives. Methods An online questionnaire incorporating the Maslach Burnout Inventory Score was distributed between 31st March and 1st May 2021, with a focus on COVID-19 and long COVID incidence, vaccine uptake, burnout, and working patterns. Data were analysed qualitatively and quantitatively; multivariable logistic regression was used to identify associations. Results 423 responses were received. 29% had contracted COVID-19, more common among doctors and nurses (OR 2.18, 95%CI 1.13–4.22), and those under the age of 55 (OR 2.60, 95%CI 1.38–4.90). 36% of those who contracted COVID-19 had symptoms of long COVID, more common among ethnicities other than White British (OR 2.57, 95% CI 1.09–6.05). 57% had evidence of burnout, more common amongst younger respondents (OR 1.92, 95% CI 1.10–3.35) and those with long COVID (OR 10.31, 95% CI 1.32–80.70). 59% with reconfigured job plans continue to work more hours. More of those working full-time wished to retire early. 59% experienced remote working, with a majority preference to continue this in the future. 95% had received one dose of a COVID-19 vaccine; 86% had received two doses by May 2021. Conclusions Burnout and long COVID is prevalent with impacts on working lives. Some groups more at risk. Vaccination uptake is high, and remote and flexible working were well received. Institutional interventions are needed to prevent workforce attrition.

Collection and determinants of patient reported outcome measures in haemodialysis patients in ScotlandNimmo, A.; Bell, S.; Brunton, C.; Campbell, J.; Doyle, A.; Mackinnon, B.; Peel, R. K.; Robertson, S.; Shilliday, I.; Spalding, E.; Traynor, J. P.; Metcalfe, W.; On behalf of the Scottish Renal Registry General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain.• You may freely distribute the URL identifying the publication in the public portal. There were significant differences in PROMs with age, SIMD quintile and primary renal diagnosis. Achieving a urea reduction ratio of >65% and dialysing through arteriovenous access were associated with significantly higher PROMs. PROMs were not affected by haemoglobin or phosphate concentration. Conclusions:Routine collection of PROMs is feasible and can identify potentially under-recognised and treatable determinants to quality of life. The association between attaining recommended standards of care and improved PROMs is striking. Individual and population-wide strategies are required to improve PROMs.

BackgroundMice expressing fluorescent proteins in neurons are one of the most powerful tools in modern neuroscience research and are increasingly being used for in vivo studies of neurodegeneration. However, these mice are often used under the assumption that the fluorescent proteins present are biologically inert.Methodology/Principal FindingsHere, we show that thy1-driven expression of yellow fluorescent protein (YFP) in neurons triggers multiple cell stress responses at both the mRNA and protein levels in vivo. The presence of YFP in neurons also subtly altered neuronal morphology and modified the time-course of dying-back neurodegeneration in experimental axonopathy, but not in Wallerian degeneration triggered by nerve injury.Conclusions/SignificanceWe conclude that fluorescent protein expressed in thy1-YFP mice is not biologically inert, modifies molecular and cellular characteristics of neurons in vivo, and has diverse and unpredictable effects on neurodegeneration pathways.