Does Time to Asystole in Donors After Circulatory Death Impact Recipient Outcome in Liver Transplantation?

BACKGROUND: The agonal phase can vary following treatment withdrawal in donor after circulatory death (DCD). There is little evidence to support when procurement teams should stand down in relation to donor time to death (TTD). We assessed what impact TTD had on outcomes following DCD liver transplantation. METHODS: Data were extracted from the UK Transplant Registry on DCD liver transplant recipients from 2006 to 2021. TTD was the time from withdrawal of life-sustaining treatment to asystole, and functional warm ischemia time was the time from donor systolic blood pressure and/or oxygen saturation falling below 50 mm Hg and 70%, respectively, to aortic perfusion. The primary endpoint was 1-y graft survival. Potential predictors were fitted into Cox proportional hazards models. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. RESULTS: One thousand five hundred fifty-eight recipients of a DCD liver graft were included. Median TTD in the entire cohort was 13 min (interquartile range, 9-17 min). Restricted cubic splines revealed that the risk of graft loss was significantly greater when TTD ≤14 min. After 14 min, there was no impact on graft loss. Prolonged hepatectomy time was significantly associated with graft loss (hazard ratio, 1.87; 95% confidence interval, 1.23-2.83; P = 0.003); however, functional warm ischemia time had no impact (hazard ratio, 1.00; 95% confidence interval, 0.44-2.27; P > 0.9). CONCLUSIONS: A very short TTD was associated with increased risk of graft loss, possibly because of such donors being more unstable and/or experiencing brain stem death as well as circulatory death. Expanding the stand down times may increase the utilization of donor livers without significantly impairing graft outcome.

Robotic versus laparoscopic versus open nephrectomy for live kidney donors.

BACKGROUND: Waiting lists for kidney transplantation continue to grow. Live kidney donation significantly reduces waiting times and improves long-term outcomes for recipients. Major disincentives to potential kidney donors are the pain and morbidity associated with surgery. This is an update of a review published in 2011. OBJECTIVES: To assess the benefits and harms of open donor nephrectomy (ODN), laparoscopic donor nephrectomy (LDN), hand-assisted LDN (HALDN) and robotic donor nephrectomy (RDN) as appropriate surgical techniques for live kidney donors. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 31 March 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing LDN with ODN, HALDN, or RDN were included. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Thirteen studies randomising 1280 live kidney donors to ODN, LDN, HALDN, or RDN were included. All studies were assessed as having a low or unclear risk of bias for selection bias. Five studies had a high risk of bias for blinding. Seven studies randomised 815 live kidney donors to LDN or ODN. LDN was associated with reduced analgesia use (high certainty evidence) and shorter hospital stay, a longer procedure and longer warm ischaemia time (moderate certainty evidence). There were no overall differences in blood loss, perioperative complications, or need for operations (low or very low certainty evidence). Three studies randomised 270 live kidney donors to LDN or HALDN. There were no differences between HALDN and LDN for analgesia requirement, hospital stay (high certainty evidence), duration of procedure (moderate certainty evidence), blood loss, perioperative complications, or reoperations (low certainty evidence). The evidence for warm ischaemia time was very uncertain due to high heterogeneity. One study randomised 50 live kidney donors to retroperitoneal ODN or HALDN and reported less pain and analgesia requirements with ODN. It found decreased blood loss and duration of the procedure with HALDN. No differences were found in perioperative complications, reoperations, hospital stay, or primary warm ischaemia time. One study randomised 45 live kidney donors to LDN or RDN and reported a longer warm ischaemia time with RDN but no differences in analgesia requirement, duration of procedure, blood loss, perioperative complications, reoperations, or hospital stay. One study randomised 100 live kidney donors to two variations of LDN and reported no differences in hospital stay, duration of procedure, conversion rates, primary warm ischaemia times, or complications (not meta-analysed). The conversion rates to ODN were 6/587 (1.02%) in LDN, 1/160 (0.63%) in HALDN, and 0/15 in RDN. Graft outcomes were rarely or selectively reported across the studies. There were no differences between LDN and ODN for early graft loss, delayed graft function, acute rejection, ureteric complications, kidney function or one-year graft loss. In a meta-regression analysis between LDN and ODN, moderate certainty evidence on procedure duration changed significantly in favour of LDN over time (yearly reduction = 7.12 min, 95% CI 2.56 to 11.67; P = 0.0022). Differences in very low certainty evidence on perioperative complications also changed significantly in favour of LDN over time (yearly change in LnRR = 0.107, 95% CI 0.022 to 0.192; P = 0.014). Various different combinations of techniques were used in each study, resulting in heterogeneity among the results. AUTHORS' CONCLUSIONS: LDN is associated with less pain compared to ODN and has comparable pain to HALDN and RDN. HALDN is comparable to LDN in all outcomes except warm ischaemia time, which may be associated with a reduction. One study reported kidneys obtained during RDN had greater warm ischaemia times. Complications and occurrences of perioperative events needing further intervention were equivalent between all methods.

Possible Effects of Volcanic Eruptions on the Modern Atmosphere of Venus.

This work reviews possible signatures and potential detectability of present-day volcanically emitted material in the atmosphere of Venus. We first discuss the expected composition of volcanic gases at present time, addressing how this is related to mantle composition and atmospheric pressure. Sulfur dioxide, often used as a marker of volcanic activity in Earth's atmosphere, has been observed since late 1970s to exhibit variability at the Venus' cloud tops at time scales from hours to decades; however, this variability may be associated with solely atmospheric processes. Water vapor is identified as a particularly valuable tracer for volcanic plumes because it can be mapped from orbit at three different tropospheric altitude ranges, and because of its apparent low background variability. We note that volcanic gas plumes could be either enhanced or depleted in water vapor compared to the background atmosphere, depending on magmatic volatile composition. Non-gaseous components of volcanic plumes, such as ash grains and/or cloud aerosol particles, are another investigation target of orbital and in situ measurements. We discuss expectations of in situ and remote measurements of volcanic plumes in the atmosphere with particular focus on the upcoming DAVINCI, EnVision and VERITAS missions, as well as possible future missions.

Neurocognitive functioning among children and young people with Duchenne Muscular Dystrophy: A systematic review and meta-analysis.

Objective: The neurocognitive aspects of DMD have received less attention than the physiological sequalae. This study conducted a systematic review and meta-analysis of available literature on the neurocognitive profile of children and young people with DMD. Method: Five databases (EMBASE, Medline, PsycInfo, Scopus and Web of Science) and the grey literature was searched on 27th January 2023. Eligible articles were available in English and reported neurocognitive outcomes. Neurocognitive domains reported in a comparable way across a minimum of three studies were included. The neurocognitive domains of Full-Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ) and Working memory (WMI) derived from Wechsler scales and receptive vocabulary ability derived from the Peabody Picture Verbal Test (PPVT) were included. A single mean meta-analysis was completed. Results: Relevant data was extracted and presented for 38 eligible studies; 2 of which are from grey literature. Results suggest children with DMD perform around 1SD below non-clinical norms for FSIQ, PIQ, VIQ and WMI. Unlike VIQ, scores derived from the PPVT were within the non-clinical norms. Studies were of moderate - high quality, there was significant heterogeneity and no publication bias. Conclusion: A systematic review of working memory has not previously been completed, it appears that children with DMD perform around 1SD below the mean, like FSIQ, PIQVIQ and WMI. The PPVT is a measure of receptive verbal ability and caution is recommended around the interchangeability of PPVT scores and the wider construct of verbal intelligence.

Contribution of the language network to the comprehension of Python programming code.

Does the perisylvian language network contribute to comprehension of programming languages, like Python? Univariate neuroimaging studies find high responses to code in fronto-parietal executive areas but not in fronto-temporal language areas, suggesting the language network does little. We used multivariate-pattern-analysis to test whether the language network encodes Python functions. Python programmers read functions while undergoing fMRI. A linear SVM decoded for-loops from if-conditionals based on activity in lateral temporal (LT) language cortex. In searchlight analysis, decoding accuracy was higher in LT language cortex than anywhere else. Follow up analysis showed that decoding was not driven by presence of different words across functions, "for" vs "if," but by compositional program properties. Finally, univariate responses to code peaked earlier in LT language-cortex than in the fronto-parietal network. We propose that the language system forms initial "surface meaning" representations of programs, which input to the reasoning network for processing of algorithms.

The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation.

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following donors after circulatory death (DCD) simultaneous pancreas-kidney transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated using a Cox proportional hazards model. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (adjusted hazard ratio HR 0.98, 95% confidence interval 0.68-1.41, P = .901). Increasing asystolic time worsened graft survival (adjusted hazard ratio 2.51, 95% confidence interval 1.16-5.43, P = .020). Restricted cubic spline modeling revealed a nonlinear relationship between asystolic time and graft survival and no relationship between TTD and graft survival. We found no evidence that TTD impacts pancreas graft survival after DCD simultaneous pancreas-kidney transplantation; however, increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimize asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD.

Computer image analysis with artificial intelligence: a practical introduction to convolutional neural networks for medical professionals.

Artificial intelligence tools, particularly convolutional neural networks (CNNs), are transforming healthcare by enhancing predictive, diagnostic, and decision-making capabilities. This review provides an accessible and practical explanation of CNNs for clinicians and highlights their relevance in medical image analysis. CNNs have shown themselves to be exceptionally useful in computer vision, a field that enables machines to 'see' and interpret visual data. Understanding how these models work can help clinicians leverage their full potential, especially as artificial intelligence continues to evolve and integrate into healthcare. CNNs have already demonstrated their efficacy in diverse medical fields, including radiology, histopathology, and medical photography. In radiology, CNNs have been used to automate the assessment of conditions such as pneumonia, pulmonary embolism, and rectal cancer. In histopathology, CNNs have been used to assess and classify colorectal polyps, gastric epithelial tumours, as well as assist in the assessment of multiple malignancies. In medical photography, CNNs have been used to assess retinal diseases and skin conditions, and to detect gastric and colorectal polyps during endoscopic procedures. In surgical laparoscopy, they may provide intraoperative assistance to surgeons, helping interpret surgical anatomy and demonstrate safe dissection zones. The integration of CNNs into medical image analysis promises to enhance diagnostic accuracy, streamline workflow efficiency, and expand access to expert-level image analysis, contributing to the ultimate goal of delivering further improvements in patient and healthcare outcomes.

Volcanic glass from the 1.8 ka Taupo eruption (New Zealand) detected in Antarctic ice at ~ 230 CE.

Chemical anomalies in polar ice core records are frequently linked to volcanism; however, without the presence of (crypto)tephra particles, links to specific eruptions remain speculative. Correlating tephras yields estimates of eruption timing and potential source volcano, offers refinement of ice core chronologies, and provides insights into volcanic impacts. Here, we report on sparse rhyolitic glass shards detected in the Roosevelt Island Climate Evolution (RICE) ice core (West Antarctica), attributed to the 1.8 ka Taupo eruption (New Zealand)-one of the largest and most energetic Holocene eruptions globally. Six shards of a distinctive geochemical composition, identical within analytical uncertainties to proximal Taupo glass, are accompanied by a single shard indistinguishable from glass of the ~25.5 ka Oruanui supereruption, also from Taupo volcano. This double fingerprint uniquely identifies the source volcano and helps link the shards to the climactic phase of the Taupo eruption. The englacial Taupo-derived glass shards coincide with a particle spike and conductivity anomaly at 278.84 m core depth, along with trachytic glass from a local Antarctic eruption of Mt. Melbourne. The assessed age of the sampled ice is 230 ± 19 CE (95% confidence), confirming that the published radiocarbon wiggle-match date of 232 ± 10 CE (2 SD) for the Taupo eruption is robust.

A Pilot Randomised Control Trial Exploring the Feasibility and Acceptability of Delivering a Personalised Modular Psychological Intervention for Anxiety Experienced by Autistic Adults: Personalised Anxiety Treatment-Autism (PAT-A).

Anxiety is commonly experienced by autistic people and impacts on quality of life and social participation. New anxiety interventions are required to effectively meet the needs of autistic people. Personalised Anxiety Treatment-Autism (PAT-A©) is a bespoke, modular approach to treating anxiety in up to 12 sessions. This study explored the feasibility and acceptability of delivering PAT-A© in the UK National Health Service (NHS). A single-blind randomised controlled trial design. Thirty-four autistic adults were recruited via clinical services and randomised to receive either PAT-A© or enhanced treatment as usual (CCSP). Outcome assessments relating to anxiety, quality of life and related constructs were completed at baseline, immediately post intervention; and at 3 and 12 months. Seventy-one percent of the PAT-A© group and 65% of the CCSP met diagnostic threshold for at least three anxiety disorders. Retention was good across both groups, with 82% (N = 14/17) completing the full course of PAT-A© and 71% (N = 12/17) attending both psychoeducational sessions in CCSP. 94% in PAT-A© and 82% in CCSP completed some follow up assessment 3 months post-intervention. Thematic analysis of interview data revealed that many participants valued the personalised approach, developed transferable skills and experienced positive changes to their anxiety. Participants were willing to be recruited and randomised, PAT-A© was feasible to deliver in the NHS and the trial methods and materials were acceptable. Our findings indicate that a fully powered clinical and cost-effectiveness trial of PAT-A© is warranted.

Machine perfusion in liver transplantation.

BACKGROUND: Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box). OBJECTIVES: To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023. SELECTION CRITERIA: We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi-randomised studies to assess treatment harms. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non-function of the graft, 7. early allograft function, 8. non-serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post-transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence. MAIN RESULTS: We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two-group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion. When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I2 = 0%; 4 trials, 482 recipients; low-certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low-certainty evidence due to imprecision and risk of bias). No trials reported quality of life. When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I2 = 0%; 4 trials, 482 recipients; high-certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I2 = 0%; 2 trials, 156 participants; moderate-certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high-certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown. We identified 11 ongoing studies investigating machine perfusion technologies. AUTHORS' CONCLUSIONS: In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.

Fibrin-based haemostatic agents for reducing blood loss in adult liver resection.

BACKGROUND: Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use. OBJECTIVES: To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials. SELECTION CRITERIA: We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables. MAIN RESULTS: We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.

Early versus late removal of urinary catheter after kidney transplantation.

BACKGROUND: The optimal treatment for end-stage kidney disease is kidney transplantation. During the operation, a catheter is introduced into the bladder and remains in place postoperatively to allow the bladder to drain. This decreases tension from the cysto-ureteric anastomosis and promotes healing. Unfortunately, urinary catheters can pose an infection risk to patients as they allow bacteria into the bladder, potentially resulting in a urinary tract infection (UTI). The longer the catheter remains in place, the greater the risk of developing a UTI. There is no consensus approach to the time a catheter should remain in place post-transplant. Furthermore, the different timings of catheter removal are thought to be associated with different incidences of UTI and postoperative complications, such as anastomotic breakdown. OBJECTIVES: This review aimed to compare patients who had their catheter removed < 5 days post-transplant surgery to those patients who had their catheter removed ≥ 5 days following their kidney transplant. Primary outcome measures between the two groups included: the incidence of symptomatic UTIs, the incidence of asymptomatic bacteriuria and the incidence of major urological complications requiring intervention and treatment. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 13 April 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs comparing timing of catheter removal post-transplantation were eligible for inclusion. All donor types were included, and all recipients were included regardless of age, demographics or type of urinary catheter used. DATA COLLECTION AND ANALYSIS: Results from the literature search were screened by two authors to identify if they met our inclusion criteria. We designated removal of a urinary catheter before five days (120 hours) as an 'early removal' and anything later than this as a 'late removal.' The studies were assessed for quality using the risk of bias tool. The primary outcome of interest was the incidence of asymptomatic bacteriuria. Statistical analyses were performed using the random effects model, and results were expressed as relative risk (RR) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Two studies (197 patients) were included in our analysis. One study comprised a full-text article, and the other was a conference abstract with very limited information. The risk of bias in the included studies was generally either high or unclear. It is uncertain whether early versus late removal of the urinary catheter made any difference to the incidence of asymptomatic bacteriuria (RR 0.89, 95% Cl 0.17 to 4.57; participants = 197; I2 = 88%; very low certainty evidence). Data on other outcomes, such as the incidence of UTI and the incidence of major urological complications, were lacking. Furthermore, the follow-up of patients across the studies was short, with no patients being followed beyond one month. AUTHORS' CONCLUSIONS: A high-quality, well-designed RCT is required to compare the effectiveness of early catheter removal versus late catheter removal in patients following a kidney transplant. At the present time, there is insufficient evidence to suggest any difference between early and late catheter removal post-transplant, and the studies investigating this were generally of poor quality.

Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial.

Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69-1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205 .

Donor Liver Blood Tests and Liver Transplant Outcomes: UK Registry Cohort Study.

BACKGROUND: Safely increasing organ utilization is a global priority. Donor serum transaminase levels are often used to decline livers, despite minimal evidence to support such decisions. This study aimed to investigate the impact of donor "liver blood tests" on transplant outcomes. METHODS: This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019); adjusted regressions models were used to assess the effect of donor "liver blood tests" on outcomes. RESULTS: A total of 3299 adult liver transplant recipients were included (2530 following brain stem death, 769 following circulatory death). Peak alanine transaminase (ALT) ranged from 6 to 5927 U/L (median = 45). Donor cause of death significantly predicted donor ALT; 4.2-fold increase in peak ALT with hypoxic brain injury versus intracranial hemorrhage (adjusted P < 0.001). On multivariable analysis, adjusting for a wide range of factors, transaminase level (ALT or aspartate aminotransferase) failed to predict graft survival, primary nonfunction, 90-d graft loss, or mortality. This held true in all examined subgroups, that is, steatotic grafts, donation following circulatory death, hypoxic brain injury donors, and donors, in which ALT was still rising at the time of retrieval. Even grafts from donors with extremely deranged ALT (>1000 U/L) displayed excellent posttransplant outcomes. In contrast, donor peak alkaline phosphatase was a significant predictor of graft loss (adjusted hazard ratio = 1.808; 1.016-3.216; P = 0.044). CONCLUSIONS: Donor transaminases do not predict posttransplant outcomes. When other factors are favorable, livers from donors with raised transaminases can be accepted and transplanted with confidence. Such knowledge should improve organ utilization decision-making and prevent future unnecessary organ discard. This provides a safe, simple, and immediate option to expand the donor pool.

Non-Invasive Vagus Nerve Stimulation Improves Brain Lesion Volume and Neurobehavioral Outcomes in a Rat Model of Traumatic Brain Injury.

Abstract Traumatic brain injury (TBI) continues to be a major cause of death and disability worldwide. This study assessed the effectiveness of non-invasive vagus nerve stimulation (nVNS) in reducing brain lesion volume and improving neurobehavioral performance in a rat model of TBI. Animals were randomized into three experimental groups: (1) TBI with sham stimulation treatment (Control), (2) TBI treated with five lower doses (2-min) nVNS, and (3) TBI treated with five higher doses (2 × 2-min) nVNS. We used the gammaCore nVNS device to deliver stimulations. Magnetic resonance imaging studies were performed 1 and 7 days post-injury to confirm lesion volume. We observed smaller brain lesion volume in the lower dose nVNS group compared with the control group on days 1 and 7. The lesion volume for the higher dose nVNS group was significantly smaller than either the lower dose nVNS or the control groups on days 1 and 7 post-injury. The apparent diffusion coefficient differences between the ipsilateral and contralateral hemispheres on day 1 were significantly smaller for the higher dose (2 × 2 min) nVNS group than for the control group. Voxel-based morphometry analysis revealed an increase in the ipsilateral cortical volume in the control group caused by tissue deformation and swelling. On day 1, these abnormal volume changes were 13% and 55% smaller in the lower dose and higher dose nVNS groups, respectively, compared with the control group. By day 7, nVNS dampened cortical volume loss by 35% and 89% in the lower dose and higher dose nVNS groups, respectively, compared with the control group. Rotarod, beam walking, and anxiety performances were significantly improved in the higher-dose nVNS group on day 1 compared with the control group. The anxiety indices were also improved on day 7 post-injury compared with the control and the lower-dose nVNS groups. In conclusion, the higher dose nVNS (five 2 × 2-min stimulations) reduced brain lesion volume to a level that further refined the role of nVNS therapy for the acute treatment of TBI. Should nVNS prove effective in additional pre-clinical TBI models and later in clinical settings, it would have an enormous impact on the clinical practice of TBI in both civilian and military settings, as it can easily be adopted into routine clinical practice.

Adapted suicide safety plans to address self-harm, suicidal ideation, and suicide behaviours in autistic adults: protocol for a pilot randomised controlled trial.

BACKGROUND: Suicide prevention is a national priority for the UK government. Autistic people are at greater risk of experiencing self-harm and suicidal thoughts and behaviours than the general population. Safety plans are widely used in suicide prevention but have not yet been designed with and for autistic people. We developed the first safety plan specifically targeting suicidality in autistic adults: the Autism Adapted Safety Plan (AASP). It consists of a prioritised list of hierarchical steps that can be used prior to or during a crisis to mitigate risk of self-harm and suicidal behaviour. This is a pilot study that aims to assess the feasibility and acceptability of the AASPs and the research processes, including the response rates, potential barriers and reach of AASPs, methods of recruitment, what comprises usual care, and economic evaluation methods/tools. METHODS: This is an external pilot randomised controlled trial of a suicide prevention tool aimed at mitigating the risk of self-harm and suicidal behaviour in autistic adults: AASPs. Participants will be assessed at baseline and followed up 1 month and 6 months later. Assessments include questions about self-harm, suicidality, service use, and their experience of the AASP/taking part in the study. Autistic adults who have a clinical autism diagnosis and self-reported history of self-harm, suicidal thoughts, or suicidal behaviours within the last 6 months will be invited to take part in the study. Informed consent will be obtained. Participants will be recruited via community and third sector services (including community settings, autism charities, and mental health charities). They may also "self-refer" into the study through social media recruitment and word of mouth. Ninety participants will be randomised to either develop an AASP or receive their usual care in a 1:1 ratio. DISCUSSION: The present study will provide an evaluation of the suitability of the processes that would be undertaken in a larger definitive study, including recruitment, randomisation, methods, questionnaires, outcome measures, treatment, and follow-up assessments. TRIAL REGISTRATION: ISRCTN70594445, Protocol v4: 8/2/22.

Co-design of an NHS primary care health check for autistic adults.

LAY ABSTRACT: Autistic people are on average more likely to experience poor health than people who are not autistic. Health checks have been shown to improve access to effective healthcare. This study investigated people's views about a primary care health check for autistic adults. We held discussion groups and interviewed autistic adults, adults with intellectual disabilities, supporters and health professionals. People wanted the health check to look at a person's physical and mental health, and how they were doing socially. They thought people should be able to share information about their needs and the reasonable adjustments they would like before the health check. They wanted healthcare services to change the way they communicate with autistic people, such as being able to book appointments online rather than by telephone. They wanted a choice in how the health check was completed, with video call or email offered as well as face-to-face appointments. People thought further training of primary care staff on autism was needed, to increase awareness of the diversity of experiences of autistic people and ways in which difficulties, such as pain, may present differently to non-autistic people. Clinicians raised questions about whether mental health and social care services could meet the additional needs that might be identified through the health check. We used this information to design an NHS primary care health check for autistic people in collaboration with autistic people, supporters and health professionals.

Consensus statements on optimal adult post-autism diagnosis support and services: Delphi process following a UK survey of autistic adults, relatives and clinicians.

LAY ABSTRACT: Research has identified types of support helpful to autistic people, for example, physical and mental health interventions, psycho-education, peer support, developing positive identities and affiliation with social groups. However, accessing suitable post-autism diagnosis support and services is extremely difficult. We asked autistic adults, relatives and clinicians about their experiences of receiving and delivering post-autism diagnosis support/services. In Stage 1, 343 autistic adults and 45 relatives completed a survey. They answered questions about their experiences of UK autism post-diagnosis support/services for adults within 12 months after receiving a diagnosis. Thirty-five clinicians completed a similar survey. Just over half of adults and relatives said there was a follow-up appointment or discussion about support after diagnosis. Fewer than 40% received any support/services in 12 months after diagnosis. We used information from the surveys to create 11 statements describing characteristics of appropriate adult post-autism diagnosis support/services. In Stage 2, we asked clinicians for their views on the statements - they agreed with all of them. For example, those adults are offered an additional follow-up meeting after diagnosis and have access to mental and physical health services. We shared results with autistic adults, relatives and clinicians at two events. Some autistic adults, relatives and clinicians were positive about post-autism diagnosis support/services. However, they described many areas for improvement. The study findings can be used to define, develop and improve the types of adult post-diagnosis support services.