The National Health Service(NHS)is a term used to describe the publicly funded healthcare delivery system providing quality healthcare services in the United Kingdom.There are several challenges militating against the...The National Health Service(NHS)is a term used to describe the publicly funded healthcare delivery system providing quality healthcare services in the United Kingdom.There are several challenges militating against the effective laboratory service delivery in the NHS in England.Biomedical scientists work in healthcare to diagnose disease and evaluate the effectiveness of treatment through the analysis of body fluids and tissue samples from patients.They provide the"engine room"of modern medicine with 70%of diagnosis based on the laboratory results generated by them.This review involved the search of literature for information on working condition of biomedical scientist in the NHS in England.Laboratory service delivery in the NHS in England faces numerous daunting challenges;staffing levels in the last few years have become dangerously low,less remunerated,relatively less experienced and predominantly band 5's,multidisciplinary rather than specialty based,associated with working more unsocial hours without adequate recovery time,de-banding of staff,high staff turnaround,profit and cost driven rather than quality.These factors has resulted in burn out,low morale,high sickness absences,increased error rate,poor team spirit,diminished productivity and suboptimal laboratory service delivery.There is the urgent need to retract our steps on unpopular policies to ensure that patient care is not compromised by ensuring adequate staffing level and mix,ensuring adequate remuneralion of laboratory staff,implementing evidenced-based specialty oriented service,determining the root cause/s for the high staff turnover and implementing corrective action,identifying other potential sources of waste in the system rather than pruning the already dangerously low staffing levels and promoting a quality delivery side by side cost effectiveness.展开更多
The release of the Mid Staffordshire hospital report otherwise called the Francis report once again ignited the debate about the issue of abuse of especially vulnerable patients, while navigating the care pathway as i...The release of the Mid Staffordshire hospital report otherwise called the Francis report once again ignited the debate about the issue of abuse of especially vulnerable patients, while navigating the care pathway as inpatients in hospitals;within the National health service (NHS), England. Once more the official reaction from the NHS directorate is more “standards” to monitor failed standards in patient care. Of interest in the official responses so far, are the unheard voices addressing the issue of healthcare and organizational ethics concerns that need revisiting. This article seeks to revisit practice, systems and care issues leading to incidents of the type of the Staffordshire abuses, and the important but yet unheralded place of organizational and care ethics in helping to curb such abuses from re-occurring.展开更多
Objective: To test the feasibility of a fully paperless system, termed “paperlite” in a UK breast screening service. To demonstrate in NHS practice, how workload and workflow could be improved by moving to a paperle...Objective: To test the feasibility of a fully paperless system, termed “paperlite” in a UK breast screening service. To demonstrate in NHS practice, how workload and workflow could be improved by moving to a paperless system and discovering what impact this has upon the complexity within the service. Setting: Warwickshire, Solihull and Coventry Breast Screening Service in the West Midlands of England. Methods: Quality improvement methodologies were employed, including value stream mapping, task analysis and a time-and-motion study. Results: The screening centred screened approximately 50,000 women per year. If they were to implement a paperless system, the administrative workload would decrease. The time saving per batch of screens, which could be achieved by moving to the paperless system ranged from 19 to 56 minutes (mean = 36 minutes). When calculated by batch the mean time saving per woman screened by moving to the paperless system was 42 seconds. This equates to 583 hours of administrative work per year in a centre screening 50,000 women. Conclusions: The paperless system has many benefits compared to the original system in terms of reductions in waste, time and cost. The simplification and standardisation of the process resulted in fewer tasks and interfaces where errors could occur, hence inadvertently improving patient safety. The limitation of the work is the heavy reliance on technology, live interfacing with computer databases and software stability is necessary for a paperless system to be used in NHS practice.展开更多
BACKGROUND Living donor kidney transplantation is the optimal method of long-term renal replacement therapy.Minimally invasive donor nephrectomy techniques,such as robot-assisted(RALDN)and hand-assisted(HALDN)laparosc...BACKGROUND Living donor kidney transplantation is the optimal method of long-term renal replacement therapy.Minimally invasive donor nephrectomy techniques,such as robot-assisted(RALDN)and hand-assisted(HALDN)laparoscopic procedures,are well-established in high-income countries and are being increasingly adopted worldwide.Nevertheless,no studies have reported surgical outcomes of RALDN donor nephrectomy from a United Kingdom center to date.AIM To compare surgical outcomes between RALDN and HALDN laparoscopic donor nephrectomy in a United Kingdom high-volume living kidney donor transplant program.METHODS A case-control matching analysis was performed based on the following parameters:Sex,age,body mass index,procedure laterality,number of renal arteries,and previous abdominal surgeries.Key surgical outcomes,including primary warm ischemia time,operative duration,and post-operative recovery,were evaluated.RESULTS In this cohort of 140 living donors(70 RALDN vs 70 HALDN),donor and recipient outcomes were equivalent across key metrics:Pain scores,overall complication rates,readmissions,reoperations,and creatinine levels at 30 days and 1 year.Recipient long-term renal function did not differ between groups.Operative time for RALDN decreased significantly over the study period,indicating progressive improvement along the learning curve.Although RALDN was associated with a modestly longer mean warm ischaemia time(3.53 minutes vs 2.76 minutes,P<0.001)and extended hospital stay(4.21 days vs 3.17 days,P<0.001),these did not translate into any disadvantage in clinical outcomes.CONCLUSION In this first United Kingdom comparative cohort,RALDN demonstrated excellent safety and efficacy,even in the early phase of our programme,matching the outcomes of the well-established,gold-standard HALDN approach.Moreover,the pronounced learning-curve trajectory suggests considerable potential for further improvements in robotic surgical outcomes as the programme matures.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 tr...Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.展开更多
BACKGROUND Orthopaedic surgical education has traditionally depended on the apprenticeship model of“see one,do one,teach one”.However,reduced operative exposure,stricter work-hour regulations,medicolegal constraints...BACKGROUND Orthopaedic surgical education has traditionally depended on the apprenticeship model of“see one,do one,teach one”.However,reduced operative exposure,stricter work-hour regulations,medicolegal constraints,and patient safety concerns have constrained its practicality.Simulation-based training has become a reliable,safe,and cost-efficient alternative.Dry lab techniques,especially virtual and augmented reality,make up 78%of current dry lab research,whereas wet labs still set the standard for anatomical realism.AIM To evaluate the effectiveness,limitations,and future directions of wet and dry lab simulation in orthopaedic training.METHODS A scoping review was carried out across four databases-PubMed,Cochrane Library,Web of Science,and EBSCOhost-up to 2025.Medical Subject Headings included:"Orthopaedic Education","Wet Lab","Dry Lab","Simulation Training","Virtual Reality",and"Surgical Procedure".Eligible studies focused on orthopaedic or spinal surgical education,employed wet or dry lab techniques,and assessed training effectiveness.Exclusion criteria consisted of non-English publications,abstracts only,non-orthopaedic research,and studies unrelated to simulation.Two reviewers independently screened titles,abstracts,and full texts,resolving discrepancies with a third reviewer.RESULTS From 1851 records,101 studies met inclusion:78 on dry labs,7 on wet labs,4 on both.Virtual reality(VR)simulations were most common,with AI increasingly used for feedback and assessment.Cadaveric training remains the gold standard for accuracy and tactile feedback,while dry labs-especially VR-offer scalability,lower cost(40%-60%savings in five studies),and accessibility for novices.Senior residents prefer wet labs for complex tasks;juniors favour dry labs for basics.Challenges include limited transferability data,lack of standard outcome metrics,and ethical concerns about cadaver use and AI assessment.CONCLUSION Wet and dry labs each have unique strengths in orthopaedic training.A hybrid approach combining both,supported by standardised assessments and outcome studies,is most effective.Future efforts should aim for uniform reporting,integrating new technologies,and policy support for hybrid curricula to enhance skills and patient care.展开更多
Green transplant refers to the realization of the importance of understanding and improving the environmental footprint of transplantation through sustainable practices.This involves assessing the entire transplantati...Green transplant refers to the realization of the importance of understanding and improving the environmental footprint of transplantation through sustainable practices.This involves assessing the entire transplantation process including preoperative evaluation,donation,organ and patient transportation,surgery,postoperative recovery,and follow-up.This is a topic that has not been fully addressed yet,but its importance is being increasingly appreciated in surgery.The aim of this study was to investigate the carbon footprint associated with transplantation and propose sustainable mitigating solutions.A comprehensive review of the existing literature on transplantation was conducted and supplemented with findings from the broader fields of surgical and perioperative care,given the scarcity of available data.The analysis identified the most involved environmental factors and attempted to offer practical solutions based on current sustainability practices.Notably,no study has yet examined the carbon footprint associated with the entire transplantation procedure.Only five studies have attempted to assess the environmental impact of kidney or liver transplants,but they focused,almost explicitly,on specific steps of the process.By employing an extrapolative methodology from the broader surgical field,we determined that the primary contributors to the environmental impact of transplantation are energy,consumables and materials,anesthesia and pharmaceuticals,transportation,and water.This review offers practical solutions utilizing the 5R framework,emphasizing sustainability to ensure transplantation remains clinically and environmentally relevant.展开更多
AIM:To describe the technique and the outcomes of manual Bowman layer and stroma transplant-onlay(BLST-o)for 2 cases of radial keratotomy(RK).METHODS:Two patients with visual fluctuations and corneal irregularity due ...AIM:To describe the technique and the outcomes of manual Bowman layer and stroma transplant-onlay(BLST-o)for 2 cases of radial keratotomy(RK).METHODS:Two patients with visual fluctuations and corneal irregularity due to RK were offered manual BLST-o as an alternative to penetrating keratoplasty(PKP).Visual acuity,refraction,corneal topography,corneal aberrometry,and corneal optical coherence tomography(OCT)pre-and postoperative were analyzed.Histology was obtained for 1 case.RESULTS:Both patients had corneal anatomical and morphological improvement,with elimination of the visual fluctuations.In one case,a subsequent excimer laser treatment improved corneal shape further,thus improving vision.The other case,whereas initially improved,developed epithelial ingrowth following suture removal.The latter was explanted and had a xenogeneic implant.The explanted sample was sent for histology,showing a viable graft of Bowman layer and anterior stroma.CONCLUSION:Manual BLST-o is a potential option for the management of symptoms post RK.These grafts may facilitate subsequent treatments such as laser corrections,and may not preclude from other interventions after explantation.展开更多
Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenv...Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.展开更多
Background Evidence on pre-operative physical activity before hip and knee arthroplasty is limited and heterogeneous.Intervention components and behavior change techniques remain underexplored.This review examined the...Background Evidence on pre-operative physical activity before hip and knee arthroplasty is limited and heterogeneous.Intervention components and behavior change techniques remain underexplored.This review examined the effectiveness of pre-operative physical activity interventions on patient and surgical outcomes in elective hip and knee arthroplasty up to 12 weeks post-surgery.Methods A systematic search of 8 databases up to August 8,2024 identified randomized controlled trials of physical activity interventions before total hip and knee arthroplasty.Quality of evidence was evaluated with Grading of Recommendations,Assessment,Development and Evaluation framework.Random-effects models were used for meta-analyses.The Template for Intervention Description and Replication(TIDieR)was used for detailing the included interventions.Results Forty trials were included.Significant mean differences in favor of the intervention groups were found at pre-and post-surgery in 4 outcomes:health-related quality of life(Knee pre-surgery standardized mean difference(SMD)=−0.5,95%confidence interval(95%CI):−1.0 to−0.1 and Hip and Knee post-surgery SMD=−0.4,95%CI:−0.6 to−0.1),pain(Hip and Knee pre-surgery SMD=−0.4,95%CI:−0.6 to−0.1 and Knee post-surgery SMD=−0.3,95%CI:−0.6 to−0.1),function(Hip and Knee pre-surgery SMD=−0.5,95%CI:−0.8 to−0.2 and Knee post-surgery SMD=−0.6,95%CI:−1.0 to−0.2),and timed-up-and-go(Hip and Knee MD=−1.2 s,95%CI:−2.0 to−0.3 and Hip and Knee MD=−1.3 s,95%CI:−1.7 to−0.8).Half of the interventions reported over 75%of the TIDieR items,while behavior change techniques reporting was limited.Conclusion Pre-operative exercise improves health-related quality of life,pain,and function pre-and post-surgery in elective hip and knee arthroplasty.Standardized reporting is needed for establishing effective intervention components.展开更多
1 Introduction The growing connectivity with mobile internet has significantly enhanced our day-to-day life support through various services and applications with on-demand availability at any time or anywhere.As emer...1 Introduction The growing connectivity with mobile internet has significantly enhanced our day-to-day life support through various services and applications with on-demand availability at any time or anywhere.As emerging technologies with continuous revolutions in the digital transformations,various add-on technologies such as quantum computing,AI,and next-generation networks such as 6G are becoming an integral support to mobile internet systems.The emerging technologies in the next-generation mobile internet bring a lot of new security and privacy challenges.展开更多
Digital twin technology,that creates virtual replicas of physical entities using real-time data and simulation models,has emerged as a transformative innovation across multiple healthcare domains.Its application in ph...Digital twin technology,that creates virtual replicas of physical entities using real-time data and simulation models,has emerged as a transformative innovation across multiple healthcare domains.Its application in physiotherapy and rehabilitation represents a paradigm shift from traditional therapeutic approaches to personalized data-driven interventions that optimize patient outcomes.This narrative review examines the current applications,benefits,challenges,and future prospects of digital twin technology in physiotherapy and rehabilitation,providing a comprehensive analysis of the manner in which this technology is reshaping clinical practice and patient care.A narrative review approach was employed,systematically searching PubMed,IEEE Xplore,Scopus,and Web of Science databases.Studies describing digital twin applications,development methodologies,clinical implementations,and theoretical frameworks in physiotherapy and rehabilitation contexts were included.Digital twin technology demonstrates significant potential in personalizing rehabilitation programs,enabling real-time monitoring of patient progress,predicting treatment outcomes,and facilitating remote therapeutic interventions.Current applications span musculoskeletal rehabilitation,neurological recovery,post surgical care,and sports injury management.Key benefits include enhanced treatment precision,improved patient engagement,reduced healthcare costs,and accelerated recovery times.However,implementation faces challenges including technological complexity,data privacy concerns,interoperability issues,and the need for substantial infrastructure investment.Digital twin technology represents a promising frontier in physiotherapy and rehabilitation,offering unprecedented opportunities for personalized,efficient,and effective patient care.Successful integration requires addressing the current limitations while fostering interdisciplinary collaboration between clinicians,engineers,and data scientists.展开更多
A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiolog...A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.展开更多
Background:Recent evidence suggests continuous bouts of physical activity(PA)are associated with longevity.We hypothesized the risk of mortality would be lower when the most active minutes of the day were in a continu...Background:Recent evidence suggests continuous bouts of physical activity(PA)are associated with longevity.We hypothesized the risk of mortality would be lower when the most active minutes of the day were in a continuous bout.Methods:PA was assessed using accelerometery in UK Biobank participants.The intensity of the most active continuous(MXCONT)and accumulated(MX)X min of the day,and their ratio(MXRATIO=MXCONT/MX),were determined.MXRATIO indicates how the most active minutes of the day are accumulated,ranging from a single continuous bout through to sporadic accumulation spread across the day.Durations(X)considered ranged from 1 to 20 min.The outcome was mortality.Results:In total,94,541 participants(56.5% female)were included.Over a median(interquartile range)follow-up of 6.9(6.3,7.4)years,2649(2.8%)deaths occurred.Intensity moderated the association between how the most active minutes of the day were accumulated and mortality risk,expressed relative to sporadically accumulated moderate PA.If the most active minutes were of moderate intensity,the risk of mortality was halved for continuous compared to sporadic accumulation,irrespective of duration;if the most active minutes were of vigorous intensity,a continuous bout was associated with the lowest risk for durations under 5 min(e.g.,3 min:hazard ratio(HR)=0.27,95% confidence interval(95%CI):0.21-0.34),while sporadic accumulation was associated with the lowest risk for durations beyond 5 min(HR=0.11,95%CI:0.08-0.15 for the most active 20 min).Conclusion:Optimal PA patterns for reducing mortality differ by intensity and duration.For moderate-intensity PA,a lower mortality risk may be optimized by prioritizing continuous PA for up to 20 min.However,for vigorous-intensity PA,multiple short bouts(<5 min)may be optimal.This suggests tailored PA recommendations may enhance longevity benefits.展开更多
Aim:Liver transplantation(LT)offers a potential curative treatment for non-metastatic intrahepatic cholangiocarcinoma(iCCA)in patients with chronic liver disease who are not amenable to liver resection(LR).Recent evid...Aim:Liver transplantation(LT)offers a potential curative treatment for non-metastatic intrahepatic cholangiocarcinoma(iCCA)in patients with chronic liver disease who are not amenable to liver resection(LR).Recent evidence suggests that cirrhotic patients with“very early”iCCA(single tumour,≤2 cm)might benefit the most from LT,with a 5-year survival as high as 73%.In view of these developments,NHS Blood and Transplant’s Liver Advisory Group(LAG)established a Fixed Term Working Group(FTWG)to determine whether iCCA in patients with background cirrhosis should be considered for LT in the United Kingdom.Methods:The FTWG included cholangiocarcinoma/LT patient representatives,experts in cholangiocarcinoma surgery/oncology,LT surgery,hepatology,hepatobiliary radiology,hepatobiliary pathology,nuclear medicine,and representation from various national hepatobiliary/oncology and transplant professional bodies.The objective was to make recommendations on appropriate indications,patient selection criteria,referral criteria,radiological assessment,transplant listing pathways,data management,and overall quality assurance.Results:The FTWG recommended LT for very early iCCA in cirrhotics,who are otherwise not suitable for LR.In this paper,we summarise the selection criteria,patient pathways,referral framework,pre-transplant assessment criteria,outcome measures,and dissemination strategy for implementing this new indication for LT in the UK.Conclusion:The introduction and evaluation of this pilot programme is an important breakthrough for iCCA patients in the UK,marking a significant stride in the field of transplant oncology.The results of this service evaluation will describe the role of LT in iCCA and guide future programmes to optimise patient selection,management,and outcomes.展开更多
Cholangiocarcinoma(CCA)is a highly aggressive and heterogeneous malignancy arising from the epithelial cells of the biliary tract.The limitations of the current methods in the diagnosis of CCA highlight the urgent nee...Cholangiocarcinoma(CCA)is a highly aggressive and heterogeneous malignancy arising from the epithelial cells of the biliary tract.The limitations of the current methods in the diagnosis of CCA highlight the urgent need for new,accurate tools for early cancer detection,better prognostication and patient monitoring.Liquid biopsy(LB)is a modern and non-invasive technique comprising a diverse group of methodologies aiming to detect tumour biomarkers from body fluids.These biomarkers include circulating tumour cells,cell-free DNA,circulating tumour DNA,RNA and extracellular vesicles.The aim of this review is to explore the current and potential future applications of LB in CCA management,with a focus on diagnosis,prognostication and monitoring.We examine both its significant potential and the inevitable limitations associated with this technology.We conclude that LB holds considerable promise,but further research is necessary to fully integrate it into precision oncology for CCA.展开更多
BACKGROUND Kidney and liver transplantation are two sub-specialized medical disciplines,with transplant professionals spending decades in training.While artificial intelligencebased(AI-based)tools could potentially as...BACKGROUND Kidney and liver transplantation are two sub-specialized medical disciplines,with transplant professionals spending decades in training.While artificial intelligencebased(AI-based)tools could potentially assist in everyday clinical practice,comparative assessment of their effectiveness in clinical decision-making remains limited.AIM To compare the use of ChatGPT and GPT-4 as potential tools in AI-assisted clinical practice in these challenging disciplines.METHODS In total,400 different questions tested ChatGPT’s/GPT-4 knowledge and decision-making capacity in various renal and liver transplantation concepts.Specifically,294 multiple-choice questions were derived from open-access sources,63 questions were derived from published open-access case reports,and 43 from unpublished cases of patients treated at our department.The evaluation covered a plethora of topics,including clinical predictors,treatment options,and diagnostic criteria,among others.RESULTS ChatGPT correctly answered 50.3%of the 294 multiple-choice questions,while GPT-4 demonstrated a higher performance,answering 70.7%of questions(P<0.001).Regarding the 63 questions from published cases,ChatGPT achieved an agreement rate of 50.79%and partial agreement of 17.46%,while GPT-4 demonstrated an agreement rate of 80.95%and partial agreement of 9.52%(P=0.01).Regarding the 43 questions from unpublished cases,ChatGPT demonstrated an agreement rate of 53.49%and partial agreement of 23.26%,while GPT-4 demonstrated an agreement rate of 72.09%and partial agreement of 6.98%(P=0.004).When factoring by the nature of the task for all cases,notably,GPT-4 demonstrated outstanding performance,providing a differential diagnosis that included the final diagnosis in 90%of the cases(P=0.008),and successfully predicting the prognosis of the patient in 100%of related questions(P<0.001).CONCLUSION GPT-4 consistently provided more accurate and reliable clinical recommendations with higher percentages of full agreements both in renal and liver transplantation compared with ChatGPT.Our findings support the potential utility of AI models like ChatGPT and GPT-4 in AI-assisted clinical practice as sources of accurate,individualized medical information and facilitating decision-making.The progression and refinement of such AI-based tools could reshape the future of clinical practice,making their early adoption and adaptation by physicians a necessity.展开更多
基金Supported by grant(NEI001)from the management of Nelson Biomedical Limited UK
文摘The National Health Service(NHS)is a term used to describe the publicly funded healthcare delivery system providing quality healthcare services in the United Kingdom.There are several challenges militating against the effective laboratory service delivery in the NHS in England.Biomedical scientists work in healthcare to diagnose disease and evaluate the effectiveness of treatment through the analysis of body fluids and tissue samples from patients.They provide the"engine room"of modern medicine with 70%of diagnosis based on the laboratory results generated by them.This review involved the search of literature for information on working condition of biomedical scientist in the NHS in England.Laboratory service delivery in the NHS in England faces numerous daunting challenges;staffing levels in the last few years have become dangerously low,less remunerated,relatively less experienced and predominantly band 5's,multidisciplinary rather than specialty based,associated with working more unsocial hours without adequate recovery time,de-banding of staff,high staff turnaround,profit and cost driven rather than quality.These factors has resulted in burn out,low morale,high sickness absences,increased error rate,poor team spirit,diminished productivity and suboptimal laboratory service delivery.There is the urgent need to retract our steps on unpopular policies to ensure that patient care is not compromised by ensuring adequate staffing level and mix,ensuring adequate remuneralion of laboratory staff,implementing evidenced-based specialty oriented service,determining the root cause/s for the high staff turnover and implementing corrective action,identifying other potential sources of waste in the system rather than pruning the already dangerously low staffing levels and promoting a quality delivery side by side cost effectiveness.
文摘The release of the Mid Staffordshire hospital report otherwise called the Francis report once again ignited the debate about the issue of abuse of especially vulnerable patients, while navigating the care pathway as inpatients in hospitals;within the National health service (NHS), England. Once more the official reaction from the NHS directorate is more “standards” to monitor failed standards in patient care. Of interest in the official responses so far, are the unheard voices addressing the issue of healthcare and organizational ethics concerns that need revisiting. This article seeks to revisit practice, systems and care issues leading to incidents of the type of the Staffordshire abuses, and the important but yet unheralded place of organizational and care ethics in helping to curb such abuses from re-occurring.
文摘Objective: To test the feasibility of a fully paperless system, termed “paperlite” in a UK breast screening service. To demonstrate in NHS practice, how workload and workflow could be improved by moving to a paperless system and discovering what impact this has upon the complexity within the service. Setting: Warwickshire, Solihull and Coventry Breast Screening Service in the West Midlands of England. Methods: Quality improvement methodologies were employed, including value stream mapping, task analysis and a time-and-motion study. Results: The screening centred screened approximately 50,000 women per year. If they were to implement a paperless system, the administrative workload would decrease. The time saving per batch of screens, which could be achieved by moving to the paperless system ranged from 19 to 56 minutes (mean = 36 minutes). When calculated by batch the mean time saving per woman screened by moving to the paperless system was 42 seconds. This equates to 583 hours of administrative work per year in a centre screening 50,000 women. Conclusions: The paperless system has many benefits compared to the original system in terms of reductions in waste, time and cost. The simplification and standardisation of the process resulted in fewer tasks and interfaces where errors could occur, hence inadvertently improving patient safety. The limitation of the work is the heavy reliance on technology, live interfacing with computer databases and software stability is necessary for a paperless system to be used in NHS practice.
文摘BACKGROUND Living donor kidney transplantation is the optimal method of long-term renal replacement therapy.Minimally invasive donor nephrectomy techniques,such as robot-assisted(RALDN)and hand-assisted(HALDN)laparoscopic procedures,are well-established in high-income countries and are being increasingly adopted worldwide.Nevertheless,no studies have reported surgical outcomes of RALDN donor nephrectomy from a United Kingdom center to date.AIM To compare surgical outcomes between RALDN and HALDN laparoscopic donor nephrectomy in a United Kingdom high-volume living kidney donor transplant program.METHODS A case-control matching analysis was performed based on the following parameters:Sex,age,body mass index,procedure laterality,number of renal arteries,and previous abdominal surgeries.Key surgical outcomes,including primary warm ischemia time,operative duration,and post-operative recovery,were evaluated.RESULTS In this cohort of 140 living donors(70 RALDN vs 70 HALDN),donor and recipient outcomes were equivalent across key metrics:Pain scores,overall complication rates,readmissions,reoperations,and creatinine levels at 30 days and 1 year.Recipient long-term renal function did not differ between groups.Operative time for RALDN decreased significantly over the study period,indicating progressive improvement along the learning curve.Although RALDN was associated with a modestly longer mean warm ischaemia time(3.53 minutes vs 2.76 minutes,P<0.001)and extended hospital stay(4.21 days vs 3.17 days,P<0.001),these did not translate into any disadvantage in clinical outcomes.CONCLUSION In this first United Kingdom comparative cohort,RALDN demonstrated excellent safety and efficacy,even in the early phase of our programme,matching the outcomes of the well-established,gold-standard HALDN approach.Moreover,the pronounced learning-curve trajectory suggests considerable potential for further improvements in robotic surgical outcomes as the programme matures.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
基金the National Institute for Health and Care Research(NHR)Manchester Biomedical Research Centre(BRC)(NIHR203308,NIHR-BRC-1215-20007)Astra-Zeneca(ESR-14-10711)+2 种基金CRUK RadNet(C19941/A27801)TMI and CFF are the recipient of an NIHR Senior Investigator Award(NIHR205054 and NIHR205061)CTH is supported by the NIHR University College London Hospitals NHS Foundation Trust BRC,the City of London CRUK RadNet and the CRUK Lung Cancer Centre of Excellence.
文摘Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.
文摘BACKGROUND Orthopaedic surgical education has traditionally depended on the apprenticeship model of“see one,do one,teach one”.However,reduced operative exposure,stricter work-hour regulations,medicolegal constraints,and patient safety concerns have constrained its practicality.Simulation-based training has become a reliable,safe,and cost-efficient alternative.Dry lab techniques,especially virtual and augmented reality,make up 78%of current dry lab research,whereas wet labs still set the standard for anatomical realism.AIM To evaluate the effectiveness,limitations,and future directions of wet and dry lab simulation in orthopaedic training.METHODS A scoping review was carried out across four databases-PubMed,Cochrane Library,Web of Science,and EBSCOhost-up to 2025.Medical Subject Headings included:"Orthopaedic Education","Wet Lab","Dry Lab","Simulation Training","Virtual Reality",and"Surgical Procedure".Eligible studies focused on orthopaedic or spinal surgical education,employed wet or dry lab techniques,and assessed training effectiveness.Exclusion criteria consisted of non-English publications,abstracts only,non-orthopaedic research,and studies unrelated to simulation.Two reviewers independently screened titles,abstracts,and full texts,resolving discrepancies with a third reviewer.RESULTS From 1851 records,101 studies met inclusion:78 on dry labs,7 on wet labs,4 on both.Virtual reality(VR)simulations were most common,with AI increasingly used for feedback and assessment.Cadaveric training remains the gold standard for accuracy and tactile feedback,while dry labs-especially VR-offer scalability,lower cost(40%-60%savings in five studies),and accessibility for novices.Senior residents prefer wet labs for complex tasks;juniors favour dry labs for basics.Challenges include limited transferability data,lack of standard outcome metrics,and ethical concerns about cadaver use and AI assessment.CONCLUSION Wet and dry labs each have unique strengths in orthopaedic training.A hybrid approach combining both,supported by standardised assessments and outcome studies,is most effective.Future efforts should aim for uniform reporting,integrating new technologies,and policy support for hybrid curricula to enhance skills and patient care.
文摘Green transplant refers to the realization of the importance of understanding and improving the environmental footprint of transplantation through sustainable practices.This involves assessing the entire transplantation process including preoperative evaluation,donation,organ and patient transportation,surgery,postoperative recovery,and follow-up.This is a topic that has not been fully addressed yet,but its importance is being increasingly appreciated in surgery.The aim of this study was to investigate the carbon footprint associated with transplantation and propose sustainable mitigating solutions.A comprehensive review of the existing literature on transplantation was conducted and supplemented with findings from the broader fields of surgical and perioperative care,given the scarcity of available data.The analysis identified the most involved environmental factors and attempted to offer practical solutions based on current sustainability practices.Notably,no study has yet examined the carbon footprint associated with the entire transplantation procedure.Only five studies have attempted to assess the environmental impact of kidney or liver transplants,but they focused,almost explicitly,on specific steps of the process.By employing an extrapolative methodology from the broader surgical field,we determined that the primary contributors to the environmental impact of transplantation are energy,consumables and materials,anesthesia and pharmaceuticals,transportation,and water.This review offers practical solutions utilizing the 5R framework,emphasizing sustainability to ensure transplantation remains clinically and environmentally relevant.
文摘AIM:To describe the technique and the outcomes of manual Bowman layer and stroma transplant-onlay(BLST-o)for 2 cases of radial keratotomy(RK).METHODS:Two patients with visual fluctuations and corneal irregularity due to RK were offered manual BLST-o as an alternative to penetrating keratoplasty(PKP).Visual acuity,refraction,corneal topography,corneal aberrometry,and corneal optical coherence tomography(OCT)pre-and postoperative were analyzed.Histology was obtained for 1 case.RESULTS:Both patients had corneal anatomical and morphological improvement,with elimination of the visual fluctuations.In one case,a subsequent excimer laser treatment improved corneal shape further,thus improving vision.The other case,whereas initially improved,developed epithelial ingrowth following suture removal.The latter was explanted and had a xenogeneic implant.The explanted sample was sent for histology,showing a viable graft of Bowman layer and anterior stroma.CONCLUSION:Manual BLST-o is a potential option for the management of symptoms post RK.These grafts may facilitate subsequent treatments such as laser corrections,and may not preclude from other interventions after explantation.
文摘Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.
文摘Background Evidence on pre-operative physical activity before hip and knee arthroplasty is limited and heterogeneous.Intervention components and behavior change techniques remain underexplored.This review examined the effectiveness of pre-operative physical activity interventions on patient and surgical outcomes in elective hip and knee arthroplasty up to 12 weeks post-surgery.Methods A systematic search of 8 databases up to August 8,2024 identified randomized controlled trials of physical activity interventions before total hip and knee arthroplasty.Quality of evidence was evaluated with Grading of Recommendations,Assessment,Development and Evaluation framework.Random-effects models were used for meta-analyses.The Template for Intervention Description and Replication(TIDieR)was used for detailing the included interventions.Results Forty trials were included.Significant mean differences in favor of the intervention groups were found at pre-and post-surgery in 4 outcomes:health-related quality of life(Knee pre-surgery standardized mean difference(SMD)=−0.5,95%confidence interval(95%CI):−1.0 to−0.1 and Hip and Knee post-surgery SMD=−0.4,95%CI:−0.6 to−0.1),pain(Hip and Knee pre-surgery SMD=−0.4,95%CI:−0.6 to−0.1 and Knee post-surgery SMD=−0.3,95%CI:−0.6 to−0.1),function(Hip and Knee pre-surgery SMD=−0.5,95%CI:−0.8 to−0.2 and Knee post-surgery SMD=−0.6,95%CI:−1.0 to−0.2),and timed-up-and-go(Hip and Knee MD=−1.2 s,95%CI:−2.0 to−0.3 and Hip and Knee MD=−1.3 s,95%CI:−1.7 to−0.8).Half of the interventions reported over 75%of the TIDieR items,while behavior change techniques reporting was limited.Conclusion Pre-operative exercise improves health-related quality of life,pain,and function pre-and post-surgery in elective hip and knee arthroplasty.Standardized reporting is needed for establishing effective intervention components.
文摘1 Introduction The growing connectivity with mobile internet has significantly enhanced our day-to-day life support through various services and applications with on-demand availability at any time or anywhere.As emerging technologies with continuous revolutions in the digital transformations,various add-on technologies such as quantum computing,AI,and next-generation networks such as 6G are becoming an integral support to mobile internet systems.The emerging technologies in the next-generation mobile internet bring a lot of new security and privacy challenges.
文摘Digital twin technology,that creates virtual replicas of physical entities using real-time data and simulation models,has emerged as a transformative innovation across multiple healthcare domains.Its application in physiotherapy and rehabilitation represents a paradigm shift from traditional therapeutic approaches to personalized data-driven interventions that optimize patient outcomes.This narrative review examines the current applications,benefits,challenges,and future prospects of digital twin technology in physiotherapy and rehabilitation,providing a comprehensive analysis of the manner in which this technology is reshaping clinical practice and patient care.A narrative review approach was employed,systematically searching PubMed,IEEE Xplore,Scopus,and Web of Science databases.Studies describing digital twin applications,development methodologies,clinical implementations,and theoretical frameworks in physiotherapy and rehabilitation contexts were included.Digital twin technology demonstrates significant potential in personalizing rehabilitation programs,enabling real-time monitoring of patient progress,predicting treatment outcomes,and facilitating remote therapeutic interventions.Current applications span musculoskeletal rehabilitation,neurological recovery,post surgical care,and sports injury management.Key benefits include enhanced treatment precision,improved patient engagement,reduced healthcare costs,and accelerated recovery times.However,implementation faces challenges including technological complexity,data privacy concerns,interoperability issues,and the need for substantial infrastructure investment.Digital twin technology represents a promising frontier in physiotherapy and rehabilitation,offering unprecedented opportunities for personalized,efficient,and effective patient care.Successful integration requires addressing the current limitations while fostering interdisciplinary collaboration between clinicians,engineers,and data scientists.
基金supported by the National Natural Science Foundation of China,Nos.82171347,82371362the Natural Science Foundation of Hunan Province,No.2022JJ30971the Scientific Research Project of Hunan Provincial Health Commission of China,No.202204040024(all to GX).
文摘A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.
基金funded by UK Research and Innovation(research which commenced between October 1,2020-March 31,2021,Grant ref MC_PC_20029April 1,2021-September 31,2022,Grant ref MC_PC_20058)supported by the National Institute for Health Research(NIHR)Leicester Biomedical Research Centre and NIHR Applied Research CollaborationEast Midlands(ARC-EM)。
文摘Background:Recent evidence suggests continuous bouts of physical activity(PA)are associated with longevity.We hypothesized the risk of mortality would be lower when the most active minutes of the day were in a continuous bout.Methods:PA was assessed using accelerometery in UK Biobank participants.The intensity of the most active continuous(MXCONT)and accumulated(MX)X min of the day,and their ratio(MXRATIO=MXCONT/MX),were determined.MXRATIO indicates how the most active minutes of the day are accumulated,ranging from a single continuous bout through to sporadic accumulation spread across the day.Durations(X)considered ranged from 1 to 20 min.The outcome was mortality.Results:In total,94,541 participants(56.5% female)were included.Over a median(interquartile range)follow-up of 6.9(6.3,7.4)years,2649(2.8%)deaths occurred.Intensity moderated the association between how the most active minutes of the day were accumulated and mortality risk,expressed relative to sporadically accumulated moderate PA.If the most active minutes were of moderate intensity,the risk of mortality was halved for continuous compared to sporadic accumulation,irrespective of duration;if the most active minutes were of vigorous intensity,a continuous bout was associated with the lowest risk for durations under 5 min(e.g.,3 min:hazard ratio(HR)=0.27,95% confidence interval(95%CI):0.21-0.34),while sporadic accumulation was associated with the lowest risk for durations beyond 5 min(HR=0.11,95%CI:0.08-0.15 for the most active 20 min).Conclusion:Optimal PA patterns for reducing mortality differ by intensity and duration.For moderate-intensity PA,a lower mortality risk may be optimized by prioritizing continuous PA for up to 20 min.However,for vigorous-intensity PA,multiple short bouts(<5 min)may be optimal.This suggests tailored PA recommendations may enhance longevity benefits.
文摘Aim:Liver transplantation(LT)offers a potential curative treatment for non-metastatic intrahepatic cholangiocarcinoma(iCCA)in patients with chronic liver disease who are not amenable to liver resection(LR).Recent evidence suggests that cirrhotic patients with“very early”iCCA(single tumour,≤2 cm)might benefit the most from LT,with a 5-year survival as high as 73%.In view of these developments,NHS Blood and Transplant’s Liver Advisory Group(LAG)established a Fixed Term Working Group(FTWG)to determine whether iCCA in patients with background cirrhosis should be considered for LT in the United Kingdom.Methods:The FTWG included cholangiocarcinoma/LT patient representatives,experts in cholangiocarcinoma surgery/oncology,LT surgery,hepatology,hepatobiliary radiology,hepatobiliary pathology,nuclear medicine,and representation from various national hepatobiliary/oncology and transplant professional bodies.The objective was to make recommendations on appropriate indications,patient selection criteria,referral criteria,radiological assessment,transplant listing pathways,data management,and overall quality assurance.Results:The FTWG recommended LT for very early iCCA in cirrhotics,who are otherwise not suitable for LR.In this paper,we summarise the selection criteria,patient pathways,referral framework,pre-transplant assessment criteria,outcome measures,and dissemination strategy for implementing this new indication for LT in the UK.Conclusion:The introduction and evaluation of this pilot programme is an important breakthrough for iCCA patients in the UK,marking a significant stride in the field of transplant oncology.The results of this service evaluation will describe the role of LT in iCCA and guide future programmes to optimise patient selection,management,and outcomes.
文摘Cholangiocarcinoma(CCA)is a highly aggressive and heterogeneous malignancy arising from the epithelial cells of the biliary tract.The limitations of the current methods in the diagnosis of CCA highlight the urgent need for new,accurate tools for early cancer detection,better prognostication and patient monitoring.Liquid biopsy(LB)is a modern and non-invasive technique comprising a diverse group of methodologies aiming to detect tumour biomarkers from body fluids.These biomarkers include circulating tumour cells,cell-free DNA,circulating tumour DNA,RNA and extracellular vesicles.The aim of this review is to explore the current and potential future applications of LB in CCA management,with a focus on diagnosis,prognostication and monitoring.We examine both its significant potential and the inevitable limitations associated with this technology.We conclude that LB holds considerable promise,but further research is necessary to fully integrate it into precision oncology for CCA.
文摘BACKGROUND Kidney and liver transplantation are two sub-specialized medical disciplines,with transplant professionals spending decades in training.While artificial intelligencebased(AI-based)tools could potentially assist in everyday clinical practice,comparative assessment of their effectiveness in clinical decision-making remains limited.AIM To compare the use of ChatGPT and GPT-4 as potential tools in AI-assisted clinical practice in these challenging disciplines.METHODS In total,400 different questions tested ChatGPT’s/GPT-4 knowledge and decision-making capacity in various renal and liver transplantation concepts.Specifically,294 multiple-choice questions were derived from open-access sources,63 questions were derived from published open-access case reports,and 43 from unpublished cases of patients treated at our department.The evaluation covered a plethora of topics,including clinical predictors,treatment options,and diagnostic criteria,among others.RESULTS ChatGPT correctly answered 50.3%of the 294 multiple-choice questions,while GPT-4 demonstrated a higher performance,answering 70.7%of questions(P<0.001).Regarding the 63 questions from published cases,ChatGPT achieved an agreement rate of 50.79%and partial agreement of 17.46%,while GPT-4 demonstrated an agreement rate of 80.95%and partial agreement of 9.52%(P=0.01).Regarding the 43 questions from unpublished cases,ChatGPT demonstrated an agreement rate of 53.49%and partial agreement of 23.26%,while GPT-4 demonstrated an agreement rate of 72.09%and partial agreement of 6.98%(P=0.004).When factoring by the nature of the task for all cases,notably,GPT-4 demonstrated outstanding performance,providing a differential diagnosis that included the final diagnosis in 90%of the cases(P=0.008),and successfully predicting the prognosis of the patient in 100%of related questions(P<0.001).CONCLUSION GPT-4 consistently provided more accurate and reliable clinical recommendations with higher percentages of full agreements both in renal and liver transplantation compared with ChatGPT.Our findings support the potential utility of AI models like ChatGPT and GPT-4 in AI-assisted clinical practice as sources of accurate,individualized medical information and facilitating decision-making.The progression and refinement of such AI-based tools could reshape the future of clinical practice,making their early adoption and adaptation by physicians a necessity.
