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
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 Paracetamol overdose(POD)is the most common cause of acute hepatic failure(AHF)in the United Kingdom.Without urgent orthotopic liver transplant(OLT),mortality is high.Psychiatric assessment for transplant i...BACKGROUND Paracetamol overdose(POD)is the most common cause of acute hepatic failure(AHF)in the United Kingdom.Without urgent orthotopic liver transplant(OLT),mortality is high.Psychiatric assessment for transplant is time-pressured and often undertaken by psychiatrists without transplant experience.Assessors may identify absolute psychiatric contraindications(APCIs)precluding transplant in otherwise medically suitable patients.It is unknown how often this occurs.The combination of high but unknown mortality,time pressure,and relative inexperience is likely to provoke anxiety in assessors.This study hypothesised that the proportion of POD patients assessed for OLT who die because psychiatric contraindications preclude transplant would be small but not negligible.AIM To determine the proportion of patients with paracetamol-induced AHF,for whom psychiatric contraindications preclude transplantation,and the consequent mortality.METHODS This is an 18-year single-centre retrospective cohort study based in a national liver transplant centre.524 participants were identified from a departmental database and included if they had AHF from suspected POD and received a psychiatric assessment for OLT.For those who died before discharge,records were reviewed for medical and psychiatric contraindications to transplant,alongside age,sex,and primary psychiatric diagnosis.We calculated the proportion of patients assessed for whom APCIs precluded transplant,resulting in death.RESULTS Among 524 patients undergoing psychiatric assessment for OLT,there were 102 in-episode deaths(19.5%).APCIs were identified in 46 patients who were otherwise medically suitable for transplant and went on to die.This statistic represents 8.8%of the number of persons evaluated and 45%of the number of deaths.Within this subgroup,27(59%)were female,with a mean age of 44.6 years(ranging from 19-72 years).The most common primary psychiatric diagnosis was alcohol dependence syndrome,which accounted for 67%(n=31).CONCLUSION 8.8%of medically suitable patients with AHF following POD died with APCIs to transplant.This indicates a need for ongoing assessor training and support,and(inter)national comparisons of practice.展开更多
BACKGROUND Gastrointestinal tumors are among the most common and deadly cancers globally,with radiotherapy and bevacizumab being key treatment strategies.Radiotherapy uses high-energy radiation to target DNA,reducing ...BACKGROUND Gastrointestinal tumors are among the most common and deadly cancers globally,with radiotherapy and bevacizumab being key treatment strategies.Radiotherapy uses high-energy radiation to target DNA,reducing tumor size and alleviating symptoms.Bevacizumab,a targeted therapy,inhibits angiogenesis and tumor growth,particularly in advanced gastrointestinal cancers.However,both treatments can cause adverse gastrointestinal effects,such as intestinal mucosal damage and perforation.While research on the risk of intestinal perforation has grown,the underlying mechanisms remain underexplored.This study aims to compare the incidence of intestinal perforation and survival rates in patients treated with radiotherapy combined with bevacizumab vs bevacizumab alone.AIM To investigate the effect of radiotherapy on the risk of intestinal perforation in patients with colon cancer treated with bevacizumab.METHODS A total of 70 patients diagnosed with gastrointestinal malignancies admitted to our hospital from January 2023 to December 2024 were selected as research subjects.According to different treatment methods,70 patients were divided into the bevacizumab only group(receiving bevacizumab treatment)and the bevacizumab+radiotherapy group(receiving radiotherapy combined with bevacizumab treatment),with 35 cases in each group.The two groups were compared in terms of clinical efficacy,incidence of intestinal perforation,serum tumor marker levels,overall survival and progression-free survival,levels of angiogenic factors,and adverse reactions.RESULTS Compared with the group treated with bevacizumab alone,the group treated with bevacizumab plus radiotherapy showed significant improvements in effective rate,overall survival,and progression-free survival(P<0.05);the probability of intestinal perforation in the bevacizumab+radiotherapy group was 13.33%,while the probability of intestinal perforation in the bevacizumab group was 0.There was a statistically significant difference in the incidence of intestinal perforation between the two groups(P=0.039).Following treatment,the levels of carbohydrate antigen(CA)125,CA199,and CA153 in patients were significantly reduced(P<0.05).CONCLUSION Radiation therapy may increase the risk of intestinal perforation in colon cancer patients receiving bevacizumab treatment.In clinical applications,the risks of combined use of radiotherapy and bevacizumab should be fully considered and personalized treatment plans should be formulated.展开更多
BACKGROUND The Perceval Sorin S(perceval valve)is a sutureless bioprosthetic designed for use in a high-risk cohort who may not be suitable for transcatheter aortic valve implantation or a conventional surgical aortic...BACKGROUND The Perceval Sorin S(perceval valve)is a sutureless bioprosthetic designed for use in a high-risk cohort who may not be suitable for transcatheter aortic valve implantation or a conventional surgical aortic valve replacement(AVR).AIM To compare five-year post-operative outcomes in a cohort undergoing isolated AVR with the perceval valve to a contemporary cohort undergoing surgical AVR with a sutured bioprosthesis.METHODS This study was a retrospective,cohort study at a single tertiary unit.Between 2017 and 2023,982 suitable patients were identified.174 Perceval valve replacements were matched to 174 sutured valve replacements.Cohort characteristics,intra-operative details,and post-operative outcomes were compared between the two groups.RESULTS Time under the aortic cross-clamp(P<0.001),time on the cardiopulmonary bypass(P<0.001)and total operative time(P<0.001)were significantly reduced in the Perceval group.Patients in the Perceval valve group were at a lower risk of postoperative pneumonia[odds ratio(OR)=0.53(0.29-0.94)]and atrial fibrillation[OR=0.58(0.36-0.93)].After propensity-matching,all-cause mortality did not significantly differ between the two groups in the five-year follow-up period.Larger valve sizes conferred an increased risk of mortality(P=0.020).CONCLUSION Sutureless surgical AVR(SAVR)is a safe and efficient alternative to SAVR with a sutured bioprosthesis,and may confer a reduced risk of post-operative atrial fibrillation.Clinician tendency towards‘oversizing’sutureless aortic valves translates into adverse clinical outcomes.Less time on the cardiopulmonary bypass circuit allows for the treatment of otherwise high-risk patients.展开更多
BACKGROUND Incisional hernia(IH)is a common complication following liver transplantation(LT),contributing to significant morbidity and impaired quality of life.The interplay of transplant-specific factors,patient como...BACKGROUND Incisional hernia(IH)is a common complication following liver transplantation(LT),contributing to significant morbidity and impaired quality of life.The interplay of transplant-specific factors,patient comorbidities,surgical complexity,and immunosuppression presents considerable challenges in hernia repair,often accompanied by substantial risks.AIM To assess the incidence,risk factors,and outcomes of IH repair in LT recipients.METHODS A systematic literature search was conducted across MEDLINE,EMBASE,Scopus,CINAHL,the Cochrane Library,Google Scholar,and PubMed,yielding 493 results.In accordance with PRISMA guidelines,39 studies reporting on IH following LT were included in the final analysis.Studies involving paediatric populations,hernias unrelated to transplant incisions,living liver donors,non-LT,and multiorgan transplants were excluded.Meta-analysis was performed using Cochrane RevMan software.The study has been registered with PROSPERO(CRD420-24563398).RESULTS A review of 39 studies revealed incidence of post-LT IH ranging from 1.7%to upto 42.8%.Pooled analysis showed comparable demographics among groups and post-LT IH incidence was higher in older age recipients[mean difference(MD)=2.39,95%CI:1.15-3.63,P<0.001],male gender(relative risk=1.42,95%CI:1.18-1.72,P<0.001),high body mass index(BMI)(MD=1.06,95%CI:0.82-1.29,P<0.001),Mercedez-Benz incision type[odds ratio(OR)=0.45,95%CI:0.21,0.96,P=0.04],and need for re-laparotomy(OR=2.49,95%CI:1.05-5.93,P=0.04).No significant differences were found in recurrence rates or wound complications between open and laparoscopic IH repairs.CONCLUSION Older recipient age,male gender,high BMI,Mercedes-Benz incision,and re-laparotomy after LT are significant risk factors for IH.In contrast,model for end-stage liver disease score,pre-LT ascites,acute rejection,and mammalian target of rapamycin inhibitor therapy do not appear to influence IH development.While open repair remains the predominant approach post-LT,no significant differences in recurrence or wound complication rates have been observed between open and laparoscopic repairs.However,open repair is associated with a shorter operative time.展开更多
Benign,premalignant or low-grade malignant pancreatic tumors are increasingly diagnosed owing to the widespread uptake of cross-sectional imaging.Surgical excision is a potential treatment option for these tumors.Panc...Benign,premalignant or low-grade malignant pancreatic tumors are increasingly diagnosed owing to the widespread uptake of cross-sectional imaging.Surgical excision is a potential treatment option for these tumors.Pancreatoduodenectomy and distal pancreatectomy are the standard resections for tumors located in the pancreatic head-neck or body-tail,respectively,and not uncommonly sacrifice a significant amount of healthy pancreatic parenchyma.Central pancreatectomy(CP)is a parenchyma-sparing procedure,initially performed by Dagradi and Serio in 1982,in a patient with pancreatic neck insulinoma.Since then,an increasing number of cases are being performed worldwide,either via open or minimally invasive surgical access.Additionally,pancreatic enucleation is reserved for tumors<3 cm,without involvement of the main pancreatic duct.CP remains an alternative approach in selected cases,albeit in the presence of some controversies,such as its use in early pancreatic ductal adenocarcinoma or metastatic deposits to the central aspect of the pancreas from other malignancies.In recent years,clarity is lacking as regards indications for CP,and despite accumulating evidence in favor of limited resections for suitable pancreatic tumors,no evidence-based consensus guidelines are yet available.Nevertheless,it appears that appropriate patient selection is of paramount importance to maximize the advantages of preservation of endocrine and exocrine pancreatic functions as well as to mitigate the risks of higher complication rates.In this comprehensive review,we explore the role of CP in the treatment of lesions located in the neck and proximal body of the pancreas.展开更多
BACKGROUND Diverticular disease of the intestine is a major gastrointestinal cause of mortality in the United States and the world.It is one of the most common gastrointestinal conditions responsible for hospital admi...BACKGROUND Diverticular disease of the intestine is a major gastrointestinal cause of mortality in the United States and the world.It is one of the most common gastrointestinal conditions responsible for hospital admissions.AIM To identify mortality trends of diverticular disease among adults in the United States,examining regional and demographic variations,as these have not been previously studied.These trends are highly beneficial to studying disease burden and vulnerable populations.METHODS Diverticular disease-related mortality data were extracted as age-adjusted mortality rates(AAMRs)from death certificate data of the CDC WONDER database using International Statistical Classification of Diseases and Related Health Problems-10th Revision codes K57.0 to K57.9 from 1999 to 2020 in adults≥45 years of age per 100000 population.These AAMRs were stratified by gender,ethnicity,and demographics and analyzed using Joinpoint regression to determine annual percent changes(APCs)and assess trend changes.RESULTS Between 1999 and 2020,a total of 114044 diverticular disease-related deaths were reported among adults≥45 years of age.Our analysis reports progressive decline in mortality with AAMR decreasing from 6.7 in 1999 to 6.1 in 2003[APC:-2.60;95%confidence interval(CI):-3.79 to-0.33],after which it further declined to 3.6 in 2013(APC:-5.16;95%CI:-7.26 to-4.74),with a minimal decrease to 3.5 in 2020(APC:-0.65;95%CI:-1.87 to 1.51).Women had a higher AAMR(4.8)than men(3.8)throughout the study period.The racial analysis reported the highest overall AAMR in non-Hispanic(NH)Whites(4.7),followed by NH Black or African American(3.9),Hispanic or Latino(3.1),and Asian or Pacific Islander(1.5),with unreliable data for the American Indian or Alaska Native population.States in the top 90th percentile,such as Wyoming and Vermont,had approximately double the AAMRs compared to states in the bottom 10th percentile.The mortality rate also exhibited regional disparities,with an overall AAMR higher in the Midwest and West regions(4.7)compared to the Northeast and South regions(4.2),and higher in nonmetropolitan areas(5.4)compared to metropolitan areas(4.2).CONCLUSION Although the annual mortality of diverticular disease has decreased since 1999,there are certain demographic and regional disparities,with mortality rates higher in women,NH White and NH Black adults,Western regions,and nonmetropolitan areas.Further research is needed to identify factors responsible for these disparities and plan appropriate interventions.展开更多
BACKGROUND In patients with chronic liver disease or hepatic dysfunction with sarcopenia,there is an increased risk of frailty as measured by functional impairment,making frailty a vital predictor of post-transplant m...BACKGROUND In patients with chronic liver disease or hepatic dysfunction with sarcopenia,there is an increased risk of frailty as measured by functional impairment,making frailty a vital predictor of post-transplant mortality.AIM To investigate the effects of frailty on mortality after liver transplantation.METHODS A retrospective review of post-transplant outcomes in liver transplant recipients assessed frailty using Karnofsky Performance Score.Data from the Scientific Registry of Transplant Recipients database for 37427 liver transplant recipients was used.RESULTS Of 82.7%frail patients,42.7%were severely frail and 40%were moderately frail(P<0.001)at the time of transplantation.Compared with non-frail patients,post-transplant mortality in frail patients was significantly higher at 12 months[odds ratio(OR)=1.94,P=0.02].Secondary analysis of the data revealed that liver grafts from donation after circulatory death(DCD)were more likely to be associated with frail patients at transplant(OR=1.86,P<0.001).Furthermore,a donor history of hypertension was associated with a lower likelihood of frailty in the recipient at the time of transplant(OR=0.65,P=0.03).CONCLUSION Recipient frailty is associated with increased mortality at 12 months following liver transplantation,and liver transplants from donors with DCD are associated with increased frailty of the liver transplant recipient.展开更多
BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to expl...BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to explore the mechanistic importance of HDAC10 as a regulator of CRC.AIM To investigate the impact of HDAC10 on tumor growth and its regulation in tumor microenvironment(TME)in CRC,we conducted this study.METHODS The study evaluated HDAC10 expression using immunohistochemistry analyses and assessed its prognostic value in CRC patients.HDAC10 depletion CRC cell lines were generated,and its biological functions were assessed through cell counting kit-8,wound healing,and colony formation assays.Furthermore,gene set variation analysis(GSVA)was employed to explore the potential molecular mechanisms of HDAC10 in CRC.The impact of HDAC10 on TME was subsequently assessed.Finally,the study investigated the influence of HDAC10 on the response to immunotherapy and chemotherapeutic drugs in CRC.RESULTS HDAC10 expression was significantly elevated in CRC and correlated with poor prognosis in patients.Knockdown of HDAC10 reduced colon cancer cell proliferation and migration capabilities.GSVA revealed a strong association between high HDAC10 expression and immune suppression.Additionally,high HDAC10 levels were correlated with a non-inflamed TME.Finally,patients with high HDAC10 expression showed reduced sensitivity to immuno-therapy.CONCLUSION This study revealed the significance of HDAC10 in TME,therapy efficacy,and clinical prognosis in CRC,offering novel insights for therapeutic advancements in CRC.展开更多
Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)im...Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity;(b)inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity.Methods 92,480 UK Biobank participants aged 43-80 years with wrist-worn accelerometer data were included.Average acceleration and intensity gradient were derived as proxies for PA volume and intensity.We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape(GAMLSS)and modeled the effect of adding moderate(walking)or vigorous(running)activity on the combined change in the volume and intensity centiles(change in PA profile).Results In men,volume was lower as age increased while intensity was lower after age 55;in women,both volume and intensity were lower as age increased.Adding 150 min of moderate PA weekly(5×30 min walking)increased the PA profile by 4 percentage points.Defining moderate PA as brisk walking approximately doubled the increase(9 percentage points)while 75 min of vigorous PA weekly(5×15 min running)trebled the increase(13 percentage points).Conclusion These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data.Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile(volume and intensity)than longer duration moderate activity.展开更多
目的观察急性Vogt-小柳-原田综合征(VKH综合征)的相干光断层扫描(OCT)图像特征以及与临床的关联。探讨新型频域OCT在急性VKH综合征结构特征和定量分析中的临床价值。方法回顾分析临床确诊的急性VKH综合征21例(42眼)的OCT检查资料。所有...目的观察急性Vogt-小柳-原田综合征(VKH综合征)的相干光断层扫描(OCT)图像特征以及与临床的关联。探讨新型频域OCT在急性VKH综合征结构特征和定量分析中的临床价值。方法回顾分析临床确诊的急性VKH综合征21例(42眼)的OCT检查资料。所有患者接受最佳矫正视力(BCVA)、直接或间接检眼镜、裂隙灯显微镜+前置镜检查和荧光素眼底血管造影(FFA)检查。5线扫描(5 line Raster)模式下通过中心凹的水平+垂直两条扫描线的分析,对黄斑区视网膜各层结构变化的细微结构进行观察,用软件自带cliaper功能模块手工测量黄斑中心小凹厚度(FT)、神经上皮脱离高度(SRD)、神经上皮厚度(SRT)。在立方体(Cube)扫描模式下,采用软件自带的功能模块对黄斑中心厚度(CFT)、黄斑中心凹体积(V)、平均厚度(AT)进行测量。回顾分析时,重点分析黄斑区视网膜各层结构变化的细微结构,以及OCT图像特征与视力的相互关系。结果所有急性VKH综合征患者均可见后极部浆液性视网膜脱离。FT(r=0.2,P=0.00),SRD(r=0.83,P=0.00),CFT(r=0.81,P=0.000),AT(r=0.59,P=0.0001)和V(r=0.58,P=0.0001)值与初始视力呈负相关。视网膜色素上皮(RPE)上存在膜结构的35眼,平均视力为0.86±0.40logMAR,差于无膜结构的7眼(P=0.0074)。结论频域OCT可对急性VKH综合征特征性的黄斑改变进行定性及定量的观察,具有一定的诊断与鉴别诊断价值。VKH综合征的OCT图像特征性表现为:治疗前的渗出性视网膜脱离,"膜样"、"隔状"结构和RPE皱折,以及激素治疗后的"颗粒样"结构。存在"膜样"结构视力更差,FT和神经上皮脱离高度可能可反映脉络膜炎症的程度和疾病的严重程度。展开更多
Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population.Diabetes-related heart disease occurs in the form of coronary artery disease(CAD)...Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population.Diabetes-related heart disease occurs in the form of coronary artery disease(CAD),cardiac autonomic neuropathy or diabetic cardiomyopathy(DbCM).The prevalence of cardiac failure is high in the diabetic population and DbCM is a common but underestimated cause of heart failure in diabetes.The pathogenesis of diabetic cardiomyopathy is yet to be clearly defined.Hyperglycemia,dyslipidemia and inflammation are thought to play key roles in the generation of reactive oxygen or nitrogen species which are in turn implicated.The myocardial interstitium undergoes alterations resulting in abnormal contractile function noted in DbCM.In the early stages of the disease diastolic dysfunction is the only abnormality,but systolic dysfunction supervenes in the later stages with impaired left ventricular ejection fraction.Transmitral Doppler echocardiography is usually used to assess diastolic dysfunction,but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging are being increasingly used recently for early detection of DbCM.The management of DbCM involves improvement in lifestyle,control of glucose and lipid abnormalities,and treatment of hypertension and CAD,if present.The role of vasoactive drugs and antioxidants is being explored.This review discusses the pathophysiology,diagnostic evaluation and management options of DbCM.展开更多
Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by th...Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multiorgan failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research.展开更多
The use of enteral feeding as part of the management of acute pancreatitis dates back almost two decades.This review describes the indications for and limitations of enteral feeding for the treatment of acute pancreat...The use of enteral feeding as part of the management of acute pancreatitis dates back almost two decades.This review describes the indications for and limitations of enteral feeding for the treatment of acute pancreatitis using up-to-date evidence-based data.A systematic review was carried out to analyse current data on the use of enteral nutrition in the management of acute pancreatitis.Relevant literature was analysed from the viewpoints of enteral vs parenteral feeding,early vs delayed enteral nutrition,nasogastric vs nasojejunal feeding,and early oral diet and immunonutrition,particularly glutamine and probiotic supplementation.Finally,current applicable guidelines and the effects of these guidelines on clinical practice are discussed.The latest meta-analyses suggest that enteral nutrition significantly reduces the mortality rate of severe acute pancreatitis compared to parenteral feeding.To maintain gut barrier function and prevent early bacterial translocation,enteral feeding should be commenced within the first 24 h of hospital admission.Also,the safety of nasogastric feeding,which eases the administration of enteral nutrients in the clinical setting,is likely equal to nasojejunal feeding.Furthermore,an earlylow-fat oral diet is potentially beneficial in patients with mild pancreatitis.Despite the initial encouraging results,the current evidence does not support the use of immunoenhanced nutrients or probiotics in patients with acute pancreatitis.展开更多
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 Paracetamol overdose(POD)is the most common cause of acute hepatic failure(AHF)in the United Kingdom.Without urgent orthotopic liver transplant(OLT),mortality is high.Psychiatric assessment for transplant is time-pressured and often undertaken by psychiatrists without transplant experience.Assessors may identify absolute psychiatric contraindications(APCIs)precluding transplant in otherwise medically suitable patients.It is unknown how often this occurs.The combination of high but unknown mortality,time pressure,and relative inexperience is likely to provoke anxiety in assessors.This study hypothesised that the proportion of POD patients assessed for OLT who die because psychiatric contraindications preclude transplant would be small but not negligible.AIM To determine the proportion of patients with paracetamol-induced AHF,for whom psychiatric contraindications preclude transplantation,and the consequent mortality.METHODS This is an 18-year single-centre retrospective cohort study based in a national liver transplant centre.524 participants were identified from a departmental database and included if they had AHF from suspected POD and received a psychiatric assessment for OLT.For those who died before discharge,records were reviewed for medical and psychiatric contraindications to transplant,alongside age,sex,and primary psychiatric diagnosis.We calculated the proportion of patients assessed for whom APCIs precluded transplant,resulting in death.RESULTS Among 524 patients undergoing psychiatric assessment for OLT,there were 102 in-episode deaths(19.5%).APCIs were identified in 46 patients who were otherwise medically suitable for transplant and went on to die.This statistic represents 8.8%of the number of persons evaluated and 45%of the number of deaths.Within this subgroup,27(59%)were female,with a mean age of 44.6 years(ranging from 19-72 years).The most common primary psychiatric diagnosis was alcohol dependence syndrome,which accounted for 67%(n=31).CONCLUSION 8.8%of medically suitable patients with AHF following POD died with APCIs to transplant.This indicates a need for ongoing assessor training and support,and(inter)national comparisons of practice.
文摘BACKGROUND Gastrointestinal tumors are among the most common and deadly cancers globally,with radiotherapy and bevacizumab being key treatment strategies.Radiotherapy uses high-energy radiation to target DNA,reducing tumor size and alleviating symptoms.Bevacizumab,a targeted therapy,inhibits angiogenesis and tumor growth,particularly in advanced gastrointestinal cancers.However,both treatments can cause adverse gastrointestinal effects,such as intestinal mucosal damage and perforation.While research on the risk of intestinal perforation has grown,the underlying mechanisms remain underexplored.This study aims to compare the incidence of intestinal perforation and survival rates in patients treated with radiotherapy combined with bevacizumab vs bevacizumab alone.AIM To investigate the effect of radiotherapy on the risk of intestinal perforation in patients with colon cancer treated with bevacizumab.METHODS A total of 70 patients diagnosed with gastrointestinal malignancies admitted to our hospital from January 2023 to December 2024 were selected as research subjects.According to different treatment methods,70 patients were divided into the bevacizumab only group(receiving bevacizumab treatment)and the bevacizumab+radiotherapy group(receiving radiotherapy combined with bevacizumab treatment),with 35 cases in each group.The two groups were compared in terms of clinical efficacy,incidence of intestinal perforation,serum tumor marker levels,overall survival and progression-free survival,levels of angiogenic factors,and adverse reactions.RESULTS Compared with the group treated with bevacizumab alone,the group treated with bevacizumab plus radiotherapy showed significant improvements in effective rate,overall survival,and progression-free survival(P<0.05);the probability of intestinal perforation in the bevacizumab+radiotherapy group was 13.33%,while the probability of intestinal perforation in the bevacizumab group was 0.There was a statistically significant difference in the incidence of intestinal perforation between the two groups(P=0.039).Following treatment,the levels of carbohydrate antigen(CA)125,CA199,and CA153 in patients were significantly reduced(P<0.05).CONCLUSION Radiation therapy may increase the risk of intestinal perforation in colon cancer patients receiving bevacizumab treatment.In clinical applications,the risks of combined use of radiotherapy and bevacizumab should be fully considered and personalized treatment plans should be formulated.
文摘BACKGROUND The Perceval Sorin S(perceval valve)is a sutureless bioprosthetic designed for use in a high-risk cohort who may not be suitable for transcatheter aortic valve implantation or a conventional surgical aortic valve replacement(AVR).AIM To compare five-year post-operative outcomes in a cohort undergoing isolated AVR with the perceval valve to a contemporary cohort undergoing surgical AVR with a sutured bioprosthesis.METHODS This study was a retrospective,cohort study at a single tertiary unit.Between 2017 and 2023,982 suitable patients were identified.174 Perceval valve replacements were matched to 174 sutured valve replacements.Cohort characteristics,intra-operative details,and post-operative outcomes were compared between the two groups.RESULTS Time under the aortic cross-clamp(P<0.001),time on the cardiopulmonary bypass(P<0.001)and total operative time(P<0.001)were significantly reduced in the Perceval group.Patients in the Perceval valve group were at a lower risk of postoperative pneumonia[odds ratio(OR)=0.53(0.29-0.94)]and atrial fibrillation[OR=0.58(0.36-0.93)].After propensity-matching,all-cause mortality did not significantly differ between the two groups in the five-year follow-up period.Larger valve sizes conferred an increased risk of mortality(P=0.020).CONCLUSION Sutureless surgical AVR(SAVR)is a safe and efficient alternative to SAVR with a sutured bioprosthesis,and may confer a reduced risk of post-operative atrial fibrillation.Clinician tendency towards‘oversizing’sutureless aortic valves translates into adverse clinical outcomes.Less time on the cardiopulmonary bypass circuit allows for the treatment of otherwise high-risk patients.
文摘BACKGROUND Incisional hernia(IH)is a common complication following liver transplantation(LT),contributing to significant morbidity and impaired quality of life.The interplay of transplant-specific factors,patient comorbidities,surgical complexity,and immunosuppression presents considerable challenges in hernia repair,often accompanied by substantial risks.AIM To assess the incidence,risk factors,and outcomes of IH repair in LT recipients.METHODS A systematic literature search was conducted across MEDLINE,EMBASE,Scopus,CINAHL,the Cochrane Library,Google Scholar,and PubMed,yielding 493 results.In accordance with PRISMA guidelines,39 studies reporting on IH following LT were included in the final analysis.Studies involving paediatric populations,hernias unrelated to transplant incisions,living liver donors,non-LT,and multiorgan transplants were excluded.Meta-analysis was performed using Cochrane RevMan software.The study has been registered with PROSPERO(CRD420-24563398).RESULTS A review of 39 studies revealed incidence of post-LT IH ranging from 1.7%to upto 42.8%.Pooled analysis showed comparable demographics among groups and post-LT IH incidence was higher in older age recipients[mean difference(MD)=2.39,95%CI:1.15-3.63,P<0.001],male gender(relative risk=1.42,95%CI:1.18-1.72,P<0.001),high body mass index(BMI)(MD=1.06,95%CI:0.82-1.29,P<0.001),Mercedez-Benz incision type[odds ratio(OR)=0.45,95%CI:0.21,0.96,P=0.04],and need for re-laparotomy(OR=2.49,95%CI:1.05-5.93,P=0.04).No significant differences were found in recurrence rates or wound complications between open and laparoscopic IH repairs.CONCLUSION Older recipient age,male gender,high BMI,Mercedes-Benz incision,and re-laparotomy after LT are significant risk factors for IH.In contrast,model for end-stage liver disease score,pre-LT ascites,acute rejection,and mammalian target of rapamycin inhibitor therapy do not appear to influence IH development.While open repair remains the predominant approach post-LT,no significant differences in recurrence or wound complication rates have been observed between open and laparoscopic repairs.However,open repair is associated with a shorter operative time.
文摘Benign,premalignant or low-grade malignant pancreatic tumors are increasingly diagnosed owing to the widespread uptake of cross-sectional imaging.Surgical excision is a potential treatment option for these tumors.Pancreatoduodenectomy and distal pancreatectomy are the standard resections for tumors located in the pancreatic head-neck or body-tail,respectively,and not uncommonly sacrifice a significant amount of healthy pancreatic parenchyma.Central pancreatectomy(CP)is a parenchyma-sparing procedure,initially performed by Dagradi and Serio in 1982,in a patient with pancreatic neck insulinoma.Since then,an increasing number of cases are being performed worldwide,either via open or minimally invasive surgical access.Additionally,pancreatic enucleation is reserved for tumors<3 cm,without involvement of the main pancreatic duct.CP remains an alternative approach in selected cases,albeit in the presence of some controversies,such as its use in early pancreatic ductal adenocarcinoma or metastatic deposits to the central aspect of the pancreas from other malignancies.In recent years,clarity is lacking as regards indications for CP,and despite accumulating evidence in favor of limited resections for suitable pancreatic tumors,no evidence-based consensus guidelines are yet available.Nevertheless,it appears that appropriate patient selection is of paramount importance to maximize the advantages of preservation of endocrine and exocrine pancreatic functions as well as to mitigate the risks of higher complication rates.In this comprehensive review,we explore the role of CP in the treatment of lesions located in the neck and proximal body of the pancreas.
文摘BACKGROUND Diverticular disease of the intestine is a major gastrointestinal cause of mortality in the United States and the world.It is one of the most common gastrointestinal conditions responsible for hospital admissions.AIM To identify mortality trends of diverticular disease among adults in the United States,examining regional and demographic variations,as these have not been previously studied.These trends are highly beneficial to studying disease burden and vulnerable populations.METHODS Diverticular disease-related mortality data were extracted as age-adjusted mortality rates(AAMRs)from death certificate data of the CDC WONDER database using International Statistical Classification of Diseases and Related Health Problems-10th Revision codes K57.0 to K57.9 from 1999 to 2020 in adults≥45 years of age per 100000 population.These AAMRs were stratified by gender,ethnicity,and demographics and analyzed using Joinpoint regression to determine annual percent changes(APCs)and assess trend changes.RESULTS Between 1999 and 2020,a total of 114044 diverticular disease-related deaths were reported among adults≥45 years of age.Our analysis reports progressive decline in mortality with AAMR decreasing from 6.7 in 1999 to 6.1 in 2003[APC:-2.60;95%confidence interval(CI):-3.79 to-0.33],after which it further declined to 3.6 in 2013(APC:-5.16;95%CI:-7.26 to-4.74),with a minimal decrease to 3.5 in 2020(APC:-0.65;95%CI:-1.87 to 1.51).Women had a higher AAMR(4.8)than men(3.8)throughout the study period.The racial analysis reported the highest overall AAMR in non-Hispanic(NH)Whites(4.7),followed by NH Black or African American(3.9),Hispanic or Latino(3.1),and Asian or Pacific Islander(1.5),with unreliable data for the American Indian or Alaska Native population.States in the top 90th percentile,such as Wyoming and Vermont,had approximately double the AAMRs compared to states in the bottom 10th percentile.The mortality rate also exhibited regional disparities,with an overall AAMR higher in the Midwest and West regions(4.7)compared to the Northeast and South regions(4.2),and higher in nonmetropolitan areas(5.4)compared to metropolitan areas(4.2).CONCLUSION Although the annual mortality of diverticular disease has decreased since 1999,there are certain demographic and regional disparities,with mortality rates higher in women,NH White and NH Black adults,Western regions,and nonmetropolitan areas.Further research is needed to identify factors responsible for these disparities and plan appropriate interventions.
文摘BACKGROUND In patients with chronic liver disease or hepatic dysfunction with sarcopenia,there is an increased risk of frailty as measured by functional impairment,making frailty a vital predictor of post-transplant mortality.AIM To investigate the effects of frailty on mortality after liver transplantation.METHODS A retrospective review of post-transplant outcomes in liver transplant recipients assessed frailty using Karnofsky Performance Score.Data from the Scientific Registry of Transplant Recipients database for 37427 liver transplant recipients was used.RESULTS Of 82.7%frail patients,42.7%were severely frail and 40%were moderately frail(P<0.001)at the time of transplantation.Compared with non-frail patients,post-transplant mortality in frail patients was significantly higher at 12 months[odds ratio(OR)=1.94,P=0.02].Secondary analysis of the data revealed that liver grafts from donation after circulatory death(DCD)were more likely to be associated with frail patients at transplant(OR=1.86,P<0.001).Furthermore,a donor history of hypertension was associated with a lower likelihood of frailty in the recipient at the time of transplant(OR=0.65,P=0.03).CONCLUSION Recipient frailty is associated with increased mortality at 12 months following liver transplantation,and liver transplants from donors with DCD are associated with increased frailty of the liver transplant recipient.
基金Supported by National Natural Science Foundation of China,No.82403279 and No.82303181.
文摘BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to explore the mechanistic importance of HDAC10 as a regulator of CRC.AIM To investigate the impact of HDAC10 on tumor growth and its regulation in tumor microenvironment(TME)in CRC,we conducted this study.METHODS The study evaluated HDAC10 expression using immunohistochemistry analyses and assessed its prognostic value in CRC patients.HDAC10 depletion CRC cell lines were generated,and its biological functions were assessed through cell counting kit-8,wound healing,and colony formation assays.Furthermore,gene set variation analysis(GSVA)was employed to explore the potential molecular mechanisms of HDAC10 in CRC.The impact of HDAC10 on TME was subsequently assessed.Finally,the study investigated the influence of HDAC10 on the response to immunotherapy and chemotherapeutic drugs in CRC.RESULTS HDAC10 expression was significantly elevated in CRC and correlated with poor prognosis in patients.Knockdown of HDAC10 reduced colon cancer cell proliferation and migration capabilities.GSVA revealed a strong association between high HDAC10 expression and immune suppression.Additionally,high HDAC10 levels were correlated with a non-inflamed TME.Finally,patients with high HDAC10 expression showed reduced sensitivity to immuno-therapy.CONCLUSION This study revealed the significance of HDAC10 in TME,therapy efficacy,and clinical prognosis in CRC,offering novel insights for therapeutic advancements in CRC.
基金supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre and NIHR Applied Research Collaboration East Midlands (ARC EM, (IS-BRC-1215-20010))funded by the National Institute for Health and Care Research Bristol Biomedical Research Centre (IS-BRC-1215-20011)supported by a UKRI research grant (EP/X042464/1)。
文摘Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity;(b)inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity.Methods 92,480 UK Biobank participants aged 43-80 years with wrist-worn accelerometer data were included.Average acceleration and intensity gradient were derived as proxies for PA volume and intensity.We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape(GAMLSS)and modeled the effect of adding moderate(walking)or vigorous(running)activity on the combined change in the volume and intensity centiles(change in PA profile).Results In men,volume was lower as age increased while intensity was lower after age 55;in women,both volume and intensity were lower as age increased.Adding 150 min of moderate PA weekly(5×30 min walking)increased the PA profile by 4 percentage points.Defining moderate PA as brisk walking approximately doubled the increase(9 percentage points)while 75 min of vigorous PA weekly(5×15 min running)trebled the increase(13 percentage points).Conclusion These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data.Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile(volume and intensity)than longer duration moderate activity.
文摘目的观察急性Vogt-小柳-原田综合征(VKH综合征)的相干光断层扫描(OCT)图像特征以及与临床的关联。探讨新型频域OCT在急性VKH综合征结构特征和定量分析中的临床价值。方法回顾分析临床确诊的急性VKH综合征21例(42眼)的OCT检查资料。所有患者接受最佳矫正视力(BCVA)、直接或间接检眼镜、裂隙灯显微镜+前置镜检查和荧光素眼底血管造影(FFA)检查。5线扫描(5 line Raster)模式下通过中心凹的水平+垂直两条扫描线的分析,对黄斑区视网膜各层结构变化的细微结构进行观察,用软件自带cliaper功能模块手工测量黄斑中心小凹厚度(FT)、神经上皮脱离高度(SRD)、神经上皮厚度(SRT)。在立方体(Cube)扫描模式下,采用软件自带的功能模块对黄斑中心厚度(CFT)、黄斑中心凹体积(V)、平均厚度(AT)进行测量。回顾分析时,重点分析黄斑区视网膜各层结构变化的细微结构,以及OCT图像特征与视力的相互关系。结果所有急性VKH综合征患者均可见后极部浆液性视网膜脱离。FT(r=0.2,P=0.00),SRD(r=0.83,P=0.00),CFT(r=0.81,P=0.000),AT(r=0.59,P=0.0001)和V(r=0.58,P=0.0001)值与初始视力呈负相关。视网膜色素上皮(RPE)上存在膜结构的35眼,平均视力为0.86±0.40logMAR,差于无膜结构的7眼(P=0.0074)。结论频域OCT可对急性VKH综合征特征性的黄斑改变进行定性及定量的观察,具有一定的诊断与鉴别诊断价值。VKH综合征的OCT图像特征性表现为:治疗前的渗出性视网膜脱离,"膜样"、"隔状"结构和RPE皱折,以及激素治疗后的"颗粒样"结构。存在"膜样"结构视力更差,FT和神经上皮脱离高度可能可反映脉络膜炎症的程度和疾病的严重程度。
文摘Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population.Diabetes-related heart disease occurs in the form of coronary artery disease(CAD),cardiac autonomic neuropathy or diabetic cardiomyopathy(DbCM).The prevalence of cardiac failure is high in the diabetic population and DbCM is a common but underestimated cause of heart failure in diabetes.The pathogenesis of diabetic cardiomyopathy is yet to be clearly defined.Hyperglycemia,dyslipidemia and inflammation are thought to play key roles in the generation of reactive oxygen or nitrogen species which are in turn implicated.The myocardial interstitium undergoes alterations resulting in abnormal contractile function noted in DbCM.In the early stages of the disease diastolic dysfunction is the only abnormality,but systolic dysfunction supervenes in the later stages with impaired left ventricular ejection fraction.Transmitral Doppler echocardiography is usually used to assess diastolic dysfunction,but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging are being increasingly used recently for early detection of DbCM.The management of DbCM involves improvement in lifestyle,control of glucose and lipid abnormalities,and treatment of hypertension and CAD,if present.The role of vasoactive drugs and antioxidants is being explored.This review discusses the pathophysiology,diagnostic evaluation and management options of DbCM.
文摘Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multiorgan failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research.
文摘The use of enteral feeding as part of the management of acute pancreatitis dates back almost two decades.This review describes the indications for and limitations of enteral feeding for the treatment of acute pancreatitis using up-to-date evidence-based data.A systematic review was carried out to analyse current data on the use of enteral nutrition in the management of acute pancreatitis.Relevant literature was analysed from the viewpoints of enteral vs parenteral feeding,early vs delayed enteral nutrition,nasogastric vs nasojejunal feeding,and early oral diet and immunonutrition,particularly glutamine and probiotic supplementation.Finally,current applicable guidelines and the effects of these guidelines on clinical practice are discussed.The latest meta-analyses suggest that enteral nutrition significantly reduces the mortality rate of severe acute pancreatitis compared to parenteral feeding.To maintain gut barrier function and prevent early bacterial translocation,enteral feeding should be commenced within the first 24 h of hospital admission.Also,the safety of nasogastric feeding,which eases the administration of enteral nutrients in the clinical setting,is likely equal to nasojejunal feeding.Furthermore,an earlylow-fat oral diet is potentially beneficial in patients with mild pancreatitis.Despite the initial encouraging results,the current evidence does not support the use of immunoenhanced nutrients or probiotics in patients with acute pancreatitis.
