Background Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. Objective To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. Design A prospective multicentre observational cohort study (the ‘SONAR’ study). Setting Seventeen haemodialysis centres in the UK. Participants Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Intervention Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Main outcome measures Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. Results A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas’ non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset ( n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Conclusions Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. Trial Registration This trial is registered as ISRCTN36033877 and ISRCTN17399438. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment ; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

Introduction:We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.Methods:Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.Results:Of 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9-77.3]; elbow, 66.7% [48.9-84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan's findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data.Conclusion:Early ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation.

The liver performs important functions that are essential for life. If the liver fails, patients will die unless they receive a new liver from a donor (transplant). Unfortunately, there are not enough livers for everyone and some patients die while waiting for a suitable organ. This article describes a novel technique that allows resuscitation and testing of a potential donor liver so that more patients can safely receive a transplant.

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.

In 2019, the Ewamian Aboriginal Corporation, together with archaeologists and community rangers, set out to challenge the idea that the Undara lava tubes of Far North Queensland, Australia were places Aboriginal people avoided in the past. Our initial motivation was for Ewamian cultural values to be included in park planning, alongside the natural values. Over 12 months, a team of archaeologists and community rangers conducted surveys in Undara Volcanic National Park and carried out a small test pit excavation at Darcy Cave. So far, we have surveyed 15 tubes, 12 containing cultural material, and found evidence of at least 1000 years of human occupation. Our research demonstrates the value and challenges of Indigenous archaeologies in an under-investigated part of northern Australia.

deceased been utilised to the potential and up the ever-increasing for The main limitation of this approach is the extra warm ischemic injury, which is not experienced in donation after brainstem death (DBD), and which impacts on rates of early allograft dysfunction, primary non-function (PNF), ischemic cholangiopathy and failure.

During the past 5 decades, liver transplantation has moved from its pioneering days where success was measured in days to a point where it is viewed as a routine part of medical care. Despite this progress, there are still significant unmet needs and outstanding questions that need addressing in clinical trials to improve outcomes for patients. The traditional endpoint for trials in liver transplantation has been 1-year patient survival, but with rates now approaching 95%, this endpoint now poses a number of significant financial and logistical barriers to conducting trials because of the large numbers of participants required to demonstrate only an incremental improvement. Here, we suggest the following solutions to this challenge: adoption of validated surrogate endpoints; bigger and better collaborative multiarm, multiphase studies; recognition by funders and institutions that work on larger collaborative research projects is potentially more important than smaller, self-led bodies of work; ringfenced areas of research within trial frameworks where individuals can take a lead; and fair funding structures using both industry and public sector money across national and international borders.

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Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes. The probe is placed on the surface of the liver and emits red and near infrared light from the tip of the device and measures the amount of backscatter of light from liver tissue via two photodiodes. Measurement of optical backscatter (Mantel-Cox P < 0.0001) and histopathological scoring of macrovesicular steatosis (Mantel-Cox P = 0.046) were predictive of 5-year graft survival. Recipients with early allograft dysfunction defined according to both Olthoff (P = 0.0067) and MEAF score (P = 0.0097) had significantly higher backscatter levels from the donor organ. Backscatter was predictive of graft loss (AUC 0.75, P = 0.0045). This study demonstrates the feasibility of real-time measurement of optical backscatter in donor livers. Early results indicate readings correlate with steatosis and may give insight to graft outcomes such as early allograft dysfunction and graft loss.

The rotator cuff has an important role in the stability and function of the glenohumeral joint. It is a complex anatomic structure commonly affected by injury such as tendinopathy and cuff tears. The rotator cuff helps to provide a stabilising effect to the shoulder joint by compressing the humeral head against the glenoid cavity via the concavity compression mechanism. To appreciate the function of the cuff it is imperative to understand the normal biomechanics of the cuff as well as the mechanisms involved in the pathogenesis of cuff disease. The shoulder joint offers a wide range of motion due to the variety of rotational moments the cuff muscles are able to provide. In order for the joint to remain stable, the cuff creates a force couple around the glenohumeral joint with coordinated activation of adjacent muscles, which work together to contain the otherwise intrinsically unstable glenohumeral joint and prevent proximal migration of the humerus. Once this muscular balance is lost, increased translations or subluxation of the humeral head may result, leading to changes in the magnitude and direction of the joint reaction forces at the glenohumeral joint. These mechanical changes may then result in a number of clinical presentations of shoulder dysfunction, disease and pain. This narrative review aims to highlight the importance of functional rotator cuff biomechanics whilst assessing the kinetics and kinematics of the shoulder joint, as well as exploring the various factors involved in cuff disease.

BACKGROUND:Passive-dynamic ankle-foot orthosis (PD-AFO) bending stiffness, which assists plantar flexor function, can be prescribed to improve poststroke gait. However, outcomes with PD-AFOs are variable likely because of improper personalization. We implemented a prescription model that objectively personalizes PD-AFO bending stiffness based on each individual's level of plantar flexor weakness (quantitatively prescribed PD-AFO).OBJECTIVES:To evaluate whether a quantitatively prescribed PD-AFO improves peak paretic plantar flexion moment compared with the original AFO for individuals after stroke and to examine the immediate effects of wearing a quantitatively prescribed PD-AFO.STUDY DESIGN:This is a repeated-measures study.METHODS:PD-AFO bending stiffness was personalized for 10 individuals after stroke through the previously developed prescription model. Participants underwent an instrumented gait analysis while wearing their original AFO and the quantitatively prescribed PD-AFO.RESULTS:Participants' peak paretic plantar flexion moment significantly increased while wearing the quantitatively prescribed PD-AFO compared with the original AFO. In addition, participants showed different levels of improvements in a series of other key biomechanical and walking performance parameters with PD-AFO use. Some participants showed improvements in all parameters, whereas others showed moderate to no improvements.CONCLUSIONS:Quantitatively prescribed PD-AFO bending stiffness resulted in inconsistent improvements in biomechanical and walking performance parameters, which warrants further investigation. Future work should investigate whether more consistent benefits are seen with faster walking speeds and longer-term PD-AFO use. In addition, future work should conduct larger-scale studies that aim to understand and optimize orthosis-patient matching for all AFO designs/characteristics.

Simultaneous pancreas and kidney transplantation is the optimum treatment for patients with type 1 diabetes and renal failure, providing survival benefit over deceased donor kidney transplant alone. Here the authors demonstrate that utilization of donation after circulatory death pancreases is a safe approach to expanding the donor pool with equivalent results to donation after brainstem death transplantation. They also demonstrate that pancreas transplantation after normothermic regional perfusion is feasible, but it will require ongoing prospective study to ensure that the benefits seen for liver transplantation do not come at the expense of pancreas transplant outcomes.