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
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
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
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
Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression an...Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.展开更多
Fluctuating voltage levels in power grids necessitate automatic voltage regulators(AVRs)to ensure stability.This study examined the modeling and control of AVR in hydroelectric power plants using model predictive cont...Fluctuating voltage levels in power grids necessitate automatic voltage regulators(AVRs)to ensure stability.This study examined the modeling and control of AVR in hydroelectric power plants using model predictive control(MPC),which utilizes an extensive mathe-matical model of the voltage regulation system to optimize the control actions over a defined prediction horizon.This predictive feature enables MPC to minimize voltage deviations while accounting for operational constraints,thereby improving stability and performance under dynamic conditions.Thefindings were compared with those derived from an optimal proportional integral derivative(PID)con-troller designed using the artificial bee colony(ABC)algorithm.Although the ABC-PID method adjusts the PID parameters based on historical data,it may be difficult to adapt to real-time changes in system dynamics under constraints.Comprehensive simulations assessed both frameworks,emphasizing performance metrics such as disturbance rejection,response to load changes,and resilience to uncertainties.The results show that both MPC and ABC-PID methods effectively achieved accurate voltage regulation;however,MPC excelled in controlling overshoot and settling time—recording 0.0%and 0.25 s,respectively.This demonstrates greater robustness compared to conventional control methods that optimize PID parameters based on performance criteria derived from actual system behavior,which exhibited settling times and overshoots exceeding 0.41 s and 5.0%,respectively.The controllers were implemented using MATLAB/Simulink software,indicating a significant advancement for power plant engineers pursuing state-of-the-art automatic voltage regulations.展开更多
Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to spe...Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to specific mutations affecting insulin synthesis,secretion and glucose regulation.Common traits across MODY subtypes include early-onset diabetes,a family history of autosomal dominant diabetes,lack of features of insulin resistance,and absent islet cell autoimmunity.Many cases are misdiagnosed as type 1 and type 2 diabetes mellitus.Biomarkers and scoring systems can help identify candidates for genetic testing.GCK-MODY,a common subtype,manifests as mild hyperglycemia and doesn’t require treatment except during pregnancy.In contrast,mutations in HNF4A,HNF1A,and HNF1B genes lead to progressive beta-cell failure and similar risks of complications as type 2 diabetes mellitus.Neonatal diabetes mellitus(NDM)is a rare form of monogenic diabetes that usually presents within the first six months.Half of the cases are lifelong,while others experience transient remission.Permanent NDM is most commonly due to activating mutations in genes encoding the adenosine triphosphate-sensitive potassium channel(KCNJ11 or ABCC8)and can be transitioned to sulfonylurea after confirmation of diagnosis.Thus,in many cases,monogenic diabetes offers an opportunity to provide precision treatment.The scope has broadened with next-generation sequencing(NGS)technologies,replacing older methods like Sanger sequencing.NGS can be for targeted gene panels,whole-exome sequencing(WES),or whole-genome sequencing.Targeted gene panels offer specific information efficiently,while WES provides comprehensive data but comes with bioinformatic challenges.The surge in testing has also led to an increase in variants of unknown significance(VUS).Deciding whether VUS is disease-causing or benign can be challenging.Computational models,functional studies,and clinical knowledge help to determine pathogenicity.Advances in genetic testing technologies offer hope for improved diagnosis and personalized treatment but also raise concerns about interpretation and ethics.展开更多
Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical r...Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical research and,until recently,a series of disappointing clinical trials,no specific disease mod-ifying pharmacological treatment has yet been approved for this condition.Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery.Although digestive enzyme activation is the hallmark of AP,a critical mechanism that initiates AP is intracellular calcium(Ca2+)overload in pancreatic parenchymal cells,which triggers mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and impairs autophagic flux.These processes are piv-otal to the disease and present a range of drug targets,associated with the inflammatory responses that drive local and systemic inflammation in AP.Progress in translation has now been made,targeting the ORAI channel with the inhibitor zegocractin(Auxora)to reduce pancreatic injury and inflammatory re-sponses in human AP.Herein we evaluated potential drug targets for the early treatment of AP,focused on intra-acinar mechanisms of injury central to the onset and severity of AP.Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.展开更多
Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially me...Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially mesenchymal stem cells(MSCs),has surfaced as a viable approach for tissue regeneration and immunological regulation in DED.Preclinical and early clinical investigations indicate that MSCs can improve lacrimal gland functionality,diminish inflammation,and facilitate corneal regeneration.Nonetheless,obstacles persist in enhancing MSC viability,determining the optimal MSC source,and guaranteeing sustained therapeutic effectiveness.Additional extensive randomized clinical trials are required to confirm the efficacy of MSC-based therapies for severe DED.展开更多
Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,im...Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.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.
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.
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.
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Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.
文摘Fluctuating voltage levels in power grids necessitate automatic voltage regulators(AVRs)to ensure stability.This study examined the modeling and control of AVR in hydroelectric power plants using model predictive control(MPC),which utilizes an extensive mathe-matical model of the voltage regulation system to optimize the control actions over a defined prediction horizon.This predictive feature enables MPC to minimize voltage deviations while accounting for operational constraints,thereby improving stability and performance under dynamic conditions.Thefindings were compared with those derived from an optimal proportional integral derivative(PID)con-troller designed using the artificial bee colony(ABC)algorithm.Although the ABC-PID method adjusts the PID parameters based on historical data,it may be difficult to adapt to real-time changes in system dynamics under constraints.Comprehensive simulations assessed both frameworks,emphasizing performance metrics such as disturbance rejection,response to load changes,and resilience to uncertainties.The results show that both MPC and ABC-PID methods effectively achieved accurate voltage regulation;however,MPC excelled in controlling overshoot and settling time—recording 0.0%and 0.25 s,respectively.This demonstrates greater robustness compared to conventional control methods that optimize PID parameters based on performance criteria derived from actual system behavior,which exhibited settling times and overshoots exceeding 0.41 s and 5.0%,respectively.The controllers were implemented using MATLAB/Simulink software,indicating a significant advancement for power plant engineers pursuing state-of-the-art automatic voltage regulations.
文摘Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to specific mutations affecting insulin synthesis,secretion and glucose regulation.Common traits across MODY subtypes include early-onset diabetes,a family history of autosomal dominant diabetes,lack of features of insulin resistance,and absent islet cell autoimmunity.Many cases are misdiagnosed as type 1 and type 2 diabetes mellitus.Biomarkers and scoring systems can help identify candidates for genetic testing.GCK-MODY,a common subtype,manifests as mild hyperglycemia and doesn’t require treatment except during pregnancy.In contrast,mutations in HNF4A,HNF1A,and HNF1B genes lead to progressive beta-cell failure and similar risks of complications as type 2 diabetes mellitus.Neonatal diabetes mellitus(NDM)is a rare form of monogenic diabetes that usually presents within the first six months.Half of the cases are lifelong,while others experience transient remission.Permanent NDM is most commonly due to activating mutations in genes encoding the adenosine triphosphate-sensitive potassium channel(KCNJ11 or ABCC8)and can be transitioned to sulfonylurea after confirmation of diagnosis.Thus,in many cases,monogenic diabetes offers an opportunity to provide precision treatment.The scope has broadened with next-generation sequencing(NGS)technologies,replacing older methods like Sanger sequencing.NGS can be for targeted gene panels,whole-exome sequencing(WES),or whole-genome sequencing.Targeted gene panels offer specific information efficiently,while WES provides comprehensive data but comes with bioinformatic challenges.The surge in testing has also led to an increase in variants of unknown significance(VUS).Deciding whether VUS is disease-causing or benign can be challenging.Computational models,functional studies,and clinical knowledge help to determine pathogenicity.Advances in genetic testing technologies offer hope for improved diagnosis and personalized treatment but also raise concerns about interpretation and ethics.
基金supported by grants from the National Nat-ural Science Foundation of China(82122010 and 82070659)the National High Level Hospital Clinical Research Funding(2022-PUMCH-E-003)+1 种基金the CAMS Innovation Fund for Medical Science(2022-I2M-1-004)an NIHR Senior Investigator Award。
文摘Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical research and,until recently,a series of disappointing clinical trials,no specific disease mod-ifying pharmacological treatment has yet been approved for this condition.Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery.Although digestive enzyme activation is the hallmark of AP,a critical mechanism that initiates AP is intracellular calcium(Ca2+)overload in pancreatic parenchymal cells,which triggers mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and impairs autophagic flux.These processes are piv-otal to the disease and present a range of drug targets,associated with the inflammatory responses that drive local and systemic inflammation in AP.Progress in translation has now been made,targeting the ORAI channel with the inhibitor zegocractin(Auxora)to reduce pancreatic injury and inflammatory re-sponses in human AP.Herein we evaluated potential drug targets for the early treatment of AP,focused on intra-acinar mechanisms of injury central to the onset and severity of AP.Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.
文摘Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially mesenchymal stem cells(MSCs),has surfaced as a viable approach for tissue regeneration and immunological regulation in DED.Preclinical and early clinical investigations indicate that MSCs can improve lacrimal gland functionality,diminish inflammation,and facilitate corneal regeneration.Nonetheless,obstacles persist in enhancing MSC viability,determining the optimal MSC source,and guaranteeing sustained therapeutic effectiveness.Additional extensive randomized clinical trials are required to confirm the efficacy of MSC-based therapies for severe DED.
文摘Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.
