Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be pre...Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has posed a major public health concern worldwide.Patients with comorbid conditions are at risk of adverse outcomes following COVID-19.Solid organ transplant r...BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has posed a major public health concern worldwide.Patients with comorbid conditions are at risk of adverse outcomes following COVID-19.Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection.It could lead to higher rates of inpatient complications and mortality in this patient population.However,studies on COVID-19 outcomes in liver transplant(LT)recipients have yielded inconsistent findings.AIM To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States.METHODS We conducted a retrospective cohort study using the 2019–2020 National Inpatient Sample database.Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classi-fication of Diseases,Tenth Revision coding system.The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic.Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients.RESULTS A total of 15720 hospitalized LT recipients were included.Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection.In both cohorts,the median admission age was 57 years.The linear trends for LT hospitalizations did not differ significantly before and during the pandemic(P=0.84).The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020.Compared to the pre-pandemic period,a higher association was noted between LT recipients and in-hospital mortality during the pandemic,with an odds ratio(OR)of 1.69[95% confidence interval(CI):1.55-1.84),P<0.001].The frequency of transplant rejections among hospitalized LT recipients increased from 0.2%to 3.6% between January 2019 and December 2020.LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic[OR:1.53(95%CI:1.26-1.85),P<0.001].CONCLUSION The hospitalization rates for LT recipients were comparable before and during the pandemic.Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.展开更多
BACKGROUND Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients(KTRs)and has been established as the treatment of choice for patients with end-stage kidney disea...BACKGROUND Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients(KTRs)and has been established as the treatment of choice for patients with end-stage kidney disease.Health-related quality of life(HRQoL)has become an important outcome measure.It is highly important to develop reliable methods to evaluate HRQoL with disease-specific questionnaires.AIM To translate the disease-specific instrument Kidney Transplant Questionnaire 25(KTQ-25)to the Greek language and perform a cross-cultural adaptation.METHODS The translation and adaptation of the original English version of the KTQ-25 to the Greek language were performed based on the International Quality of Life RESULTS Eighty-four KTRs(59 males;mean age 53.5±10.7 years;mean estimated glomerular filtration rate 47.7±15.1 mL/min/1.73 m2;mean transplant vintage 100.5±83.2 months)completed the Greek version of the KTQ-25 and the 36-item Short-Form Health Survey,and the results were used to evaluate the reliability of the Greek KTQ-25.The Cronbach alpha coefficients for all the KTQ-25 dimensions were satisfactory(physical symptoms=0.639,fatigue=0.856,uncertainty/fear=0.661,appearance=0.593,emotions=0.718,total score=0.708).The statistically significant correlation coefficients among the KTQ-25 dimensions ranged from 0.226 to 0.644.The correlation coeffi-cients of the KTQ-25 dimensions with the SF-36 physical component summary(PCS)ranged from 0.196 to 0.550;the correlation coefficients of the KTQ-25 with the SF-36 mental component summary(MCS)ranged from 0.260 to 0.655;and the correlation coefficients of the KTQ-25 with the total scores with the SF-36 PCS and MCS were 0.455 and 0.613,respectively.CONCLUSION According to the findings,the Greek version of the KTQ-25 is valid and reliable for administration among kidney transplant patients in Greece.展开更多
BACKGROUND Transplant recipients commonly harbor multidrug-resistant organisms(MDROs),as a result of frequent hospital admissions and increased exposure to antimi-crobials and invasive procedures.AIM To investigate th...BACKGROUND Transplant recipients commonly harbor multidrug-resistant organisms(MDROs),as a result of frequent hospital admissions and increased exposure to antimi-crobials and invasive procedures.AIM To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition,as well as the impact of MDRO acquisition on intensive care unit(ICU)and hospital length of stay,and on ICU mortality and 1-year mortality post heart transplantation.METHODS This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period(2013-2022)in a single transplantation center.Data was collected regarding MDROs commonly encountered in critical care.RESULTS Among the 98 transplanted patients(70%male),about a third(32%)acquired or already harbored MDROs upon transplantation(MDRO group),while two thirds did not(MDRO-free group).The prevalent MDROs were Acinetobacter baumannii(14%),Pseudomonas aeruginosa(12%)and Klebsiella pneumoniae(11%).Compared to MDRO-free patients,the MDRO group was characterized by higher body mass index(P=0.002),higher rates of renal failure(P=0.017),primary graft dysfunction(10%vs 4.5%,P=0.001),surgical re-exploration(34%vs 14%,P=0.017),mechanical circulatory support(47%vs 26%P=0.037)and renal replacement therapy(28%vs 9%,P=0.014),as well as longer extracorporeal circulation time(median 210 vs 161 min,P=0.003).The median length of stay was longer in the MDRO group,namely ICU stay was 16 vs 9 d in the MDRO-free group(P=0.001),and hospital stay was 38 vs 28 d(P=0.006),while 1-year mortality was higher(28%vs 7.6%,log-rank-χ2:7.34).CONCLUSION Following heart transplantation,a predominance of Gram-negative MDROs was noted.MDRO acquisition was associated with higher complication rates,prolonged ICU and total hospital stay,and higher post-transplantation mortality.展开更多
BACKGROUND Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart,liver and kidney transplants.However,information on how functional status,before and after tra...BACKGROUND Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart,liver and kidney transplants.However,information on how functional status,before and after transplant impacts post-transplant survival outcomes is lacking.AIM To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States adults.METHODS We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to 2022.The primary outcome was mortality.Using the Karnofsky Performance Status,functional impairment was categorized as severe,moderate and normal.Analyses were conducted using Kaplan-Meier curves and multivariable Cox regression.RESULTS The median age was 41 years,majority(53.4%)were women.Severe impairment was present in 28.3%of recipients.The median survival time was 906.6 days.The median survival time was 1331 and 560 days for patients with normal and severe functional impairment respectively.Recipients with severe impairment had a 56%higher risk of mortality at one year[Hazard ratio(HR)=1.56;95%CI:1.23–1.98;P<0.001]and 58%at five years(HR=1.58;95%CI:1.24–2.00;P<0.001)compared to patients with no functional impairment.Recipients with worse functional status after transplant also had poor survival outcomes.CONCLUSION Pre-and post-transplant recipient functional status is an important prognostic indicator for short-and long-term intestinal transplant outcomes.展开更多
Solid organ transplant recipients face unique challenges in managing their im-munosuppressed status,making vaccination a critical consideration.This review aimed to comprehensively analyze current recommendations,eval...Solid organ transplant recipients face unique challenges in managing their im-munosuppressed status,making vaccination a critical consideration.This review aimed to comprehensively analyze current recommendations,evaluate the effi-cacy of vaccinations in this population,and assess safety concerns.We explored the latest evidence on vaccine types,timing,and potential benefits for transplant patients,highlighting the importance of individualized approaches for routinely used vaccines as well as coronavirus disease 2019 vaccines.By synthesizing avai-lable data,this review underscored the pressing need to optimize vaccination strategies,ensuring that transplant recipients can obtain the full protection against many pathogens while minimizing risks associated with their post-transplant immunosuppression.展开更多
Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.U...Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.展开更多
BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is...BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.展开更多
BACKGROUND Through continuous improvement in transplantation medicine,a wider range of solid organ transplant(SOT)recipients is considered suitable for complex procedures.Despite advances in modern transplantation pra...BACKGROUND Through continuous improvement in transplantation medicine,a wider range of solid organ transplant(SOT)recipients is considered suitable for complex procedures.Despite advances in modern transplantation practice,transpiring invasive fungal infections pose a substantial threat for SOT recipients.To our knowledge,cryptococcal infection confined amidst sole pancreas SOT recipients has not been described to date.Enforcement of a multidisciplinary transplant team approach in the management of pancreas SOT recipients presenting with complex cryptococcal complications is fundamental in improving patient outcomes.CASE SUMMARY We present the case of a female pancreas transplant recipient,with confirmed meningeal cryptococcosis,referred to our institution for further evaluation and treatment from the Regional Center for Infectious Diseases.On admission,the patient was weaned from the protocolized immunosuppression therapy for two consecutive weeks,in addition to tapering systemic corticosteroid remedial treatment.Our novel multidisciplinary transplant team approach embodied exhaustive discussions of possible complex and diverse multiple organ system physiologic and pathologic challenges associated with distinct management strategies in pancreas transplant recipients.Owing to the potentially devastating impact of invasive cryptococcosis in terms of morbidity and mortality,a definitive surgical intervention of pancreas transplant grafectomy was reinforced,as a pathway towards secure access to early meaningful expertise care.The patient was discharged to the Regional Center for Infectious Diseases 2 mo after the admittance further advancing to a clinical improvement.CONCLUSION The precision transplantation approach by tailoring complex medical interventions to individual needs proved indispensable in improving our patient’s outcomes.展开更多
BACKGROUND Given the current organ shortage crisis,split liver transplantation(SLT)has emerged as a promising alternative for select end-stage liver disease patients.AIM To introduce an ex-vivo liver graft splitting a...BACKGROUND Given the current organ shortage crisis,split liver transplantation(SLT)has emerged as a promising alternative for select end-stage liver disease patients.AIM To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT.METHODS A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1,2022,and May 31,2023.The study included 25 SLT cases and 81 whole liver transplantation(WLT)cases.Total ex-vivo liver splitting was employed for SLT graft procurement in three steps.Patient outcomes were determined,including liver function parameters,postoperative complications,and perioperative mortality.Group comparisons for categorical variables were performed using theχ²-test.RESULTS In the study,postoperative complications in the 25 SLT cases included hepatic artery thrombosis(n=1)and pulmonary infections(n=3),with no perioperative mortality.In contrast,among the 81 patients who underwent WLT,complications included perioperative mortality(n=1),postoperative pulmonary infections(n=8),abdominal infection(n=1),hepatic artery thromboses(n=3),portal vein thrombosis(n=1),and intra-abdominal bleeding(n=5).Comparative analysis demonstrated significant differences in alanine aminotransferase(176.0 vs 73.5,P=0.000)and aspartate aminotransferase(AST)(42.0 vs 29.0,P=0.004)at 1 wk postoperatively,and in total bilirubin(11.8 vs 20.8,P=0.003)and AST(41.5 vs 26.0,P=0.014)at 2 wk postoperatively.However,the overall incidence of complications was comparable between the two groups(P>0.05).CONCLUSION Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach,especially under the expertise of an experienced transplant center.The approach developed by our center can serve as a valuable reference for other transplantation centers.展开更多
BACKGROUND Liver transplantation(LT)is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients.There are many indications fo...BACKGROUND Liver transplantation(LT)is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients.There are many indications for LT that vary between countries and settings.The outcome of LT depends on the available facilities and surgical expertise,as well as the types of liver graft donors available.AIM To assess the clinical characteristics of patients from Bahrain who underwent LT overseas,and analyze factors affecting their survival.METHODS In this retrospective cohort study,we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office,Ministry of Health,Kingdom of Bahrain,between 1997 and 2023.Demographic data,LT indication,donor-recipient relationship,overseas LT center,graft type,post-LT medications,and LT complications,were collected.Outcomes measured included the overall and 5-year LT survival rate.Fisher’s exact,Pearsonχ2,and Mann-Whitney U tests were used to compare the pediatric and the adults’group in terms of clinical characteristics,donor-recipient relationship,medication,complications,and outcome.Survival analysis was estimated via the Kaplan-Meier’s method.Univariate and multivariate analyses were used to detect predictors of survival.RESULTS Of the 208 eligible patients,170(81.7%)were sent overseas to undergo LT while 38(18.3%)remained on the waiting list.Of the 170 patients,167(80.3%)underwent LT and were included in the study.The majority of the patients were Bahraini(91.0%),and most were males(57.5%).One-hundred-and-twenty(71.8%)were adults and 47(28.3%)were children.The median age at transplant was 50.0[interquartile range(IQR):14.9–58.4]years.The main indication for pediatric LT was biliary atresia(31.9%),while that of adult LT was hepatitis C-related cirrhosis(35.0%).Six(3.6%)patients required re-transplantation.Most patients received a living-related liver graft(82%).Pediatric patients received more living and related grafts than adults(P=0.038 and P=0.041,respectively),while adult patients received more cadaveric and unrelated grafts.Most patients required long-term immunosuppressive therapy after LT(94.7%),of which tacrolimus was the most prescribed(84.0%),followed by prednisolone(50.7%),which was prescribed more frequently for pediatric patients(P=0.001).Most patients developed complications(62.4%)with infectious episodes being the most common(38.9%),followed by biliary stricture(19.5%).Tonsilitis and sepsis(n=12,8.1%for each)were the most frequent infections.Pediatric patients experienced higher rates of infection,rejection,and early poor graft function than adult patients(P<0.001,P=0.003,and P=0.025,respectively).The median follow-up time was 6.5(IQR:2.6–10.6)years.The overall survival rate was 84.4%,the 5-year survival rate,86.2%,and the mortality rate,15.6%.Younger patients had significantly better odds of survival(P=0.019)and patients who survived had significantly longer follow-up periods(P<0.001).CONCLUSION Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries.Since LT facilities are not available,an overseas LT has offered them great hope.展开更多
BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in che...BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)metformin.During a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related mortality.Statin,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.展开更多
BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal fu...BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal function after LT have not yet been well described.AIM To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant.METHODS This retrospective study included all patients who underwent liver or liverkidney transplant at our institution from January,2011 to December,2021.Patients were classified based on whether they received PGE1.PGE1 was administered post-LT to those with transaminases>1000 U/L in the immediate postoperative period.Demographics,post-LT treatments and/or complications,renal function,and survival were analyzed.Multivariable logistic regression analysis was performed,and a two-tailed P value<0.05 was considered statistically significant.RESULTS A total of 145 patients underwent LT,with 44(30%)receiving PGE1.Baseline patient characteristics were comparable,except the PGE1 group had significantly higher aspartate aminotransferase(AST)(1961.9 U/L±1862.3 U/L vs 878 U/L±741.4 U/L,P=0.000),alanine aminotransferase(1070.6 U/L±895 U/L vs 547.7 U/L±410 U/L,P=0.000),international normalized ratio on post-LT day 1(2±0.74 vs 1.8±0.4,P=0.03),a longer intensive care unit stay(8.1 days±11.8 days vs 3.8 days±4.6 days,P=0.003),more vasopressor use(55.53 hours±111 hours vs 16.33 hours±26.3 hours,P=0.002),and higher immediate postoperative complications(18.6%vs 4.9%,P=0.04).The PGE1 group also had a significantly higher 90-day readmission rate(29.6%vs 13.1%,P=0.02)and lower 1-year liver graft survival(87.5%vs 98.9%,P=0.005).However,30-day readmission(31.6%vs 27.4%,P=0.64),LT complications(hepatic artery thrombosis,biliary complications,rejection of liver graft,cardiomyopathy),1-year patient survival(96.9%vs 97.8%,P=0.77),overall liver graft survival,and overall patient survival were similar between the two groups(95.4%vs 93.9%,P=0.74 and 88.4%vs 86.9%,P=0.81 respectively).Although the PGE1 group had a significantly lower glomerular filtration rate(eGFR)on post-LT day 7(46.3 mL/minute±26.7 mL/minute vs 62.5 mL/minute±34 mL/minute,P=0.009),the eventual need for renal replacement therapy(13.6%vs 5.9%,P=0.09),the number of dialysis sessions(0.91 vs 0.27,P=0.13),and eGFR at 1-month(37.2 mL/minute±35.9 mL/minute vs 42 mL/minute±36.9 mL/minute,P=0.49),6-months(54.8 mL/minute±21.6 mL/minute vs 62 mL/minute±21.4 mL/minute,P=0.09),and 12-months(63.7 mL/minute±20.7 mL/minute vs 62.8 mL/minute±20.3 mL/minute,P=0.85)post-LT were similar to those in the non-PGE1 group.CONCLUSION In patients who received PGE1 for ischemia-reperfusion injury,despite immediate acute renal injury post-LT,the renal function at 1-month,6-months,and 12-months post-LT was similar compared to those without ischemiareperfusion injury.Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.展开更多
Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected.This appro...Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected.This approach is labor-intensive,invasive and costly.In addition,because this approach relies on a rise in serum creatinine above historical baselines,injury to the allograft can be extensive before this rise occurs.In an effort to address this,donor-derived cell-free DNA(dd-cf DNA)is being used with increasing frequency in the clinical setting as a means of diagnosing a rejection of the renal allograft early in the course.This can poten-tially allow for early intervention to minimize not only injury,but the intensity of antirejection therapy needed and the avoidance of side effects.Here,we will review the available methodology for the determination and quantification of dd-cf DNA,the data supporting its use in clinical practice and the limitations of this technology.展开更多
Kidney transplantation(KT),although the best treatment option for eligible patients,entails maintaining and adhering to a life-long treatment regimen of medications,lifestyle changes,self-care,and appointments.Many pa...Kidney transplantation(KT),although the best treatment option for eligible patients,entails maintaining and adhering to a life-long treatment regimen of medications,lifestyle changes,self-care,and appointments.Many patients experience uncertain outcome trajectories increasing their vulnerability and symptom burden and generating complex care needs.Even when transplants are successful,for some patients the adjustment to life post-transplant can be challenging and psychological difficulties,economic challenges and social isola-tion have been reported.About 50%of patients lose their transplant within 10 years and must return to dialysis or pursue another transplant or conservative care.This paper documents the complicated journey patients undertake before and after KT and outlines some initiatives aimed at improving patient-centered care in transplantation.A more cohesive approach to care that borrows its philosophical approach from the established field of supportive oncology may improve patient experiences and outcomes.We propose the"supportive care in transplantation"care model to operationalize a patient-centered approach in transplantation.This model can build on other ongoing initiatives of other scholars and researchers and can help advance patient-centered care through the entire care continuum of kidney transplant recipients and candidates.Multi-dimensionality,multi-disciplinarity and evidence-based approaches are proposed as other key tenets of this care model.We conclude by proposing the potential advantages of this approach to patients and healthcare systems.Core Tip:Kidney transplant recipients and candidates face several uncertainties in their care journey and have several expressed unmet healthcare needs.We recommend a structured and comprehensive approach to transplant care across the entire continuum of a transplant patient’s journey similar to what has been developed in the field of oncology.The supportive care in transplantation model can operationalize patient-centered care and build on the efforts of other researchers in the field.We postulate that such a model would significantly improve care delivery and patients’experiences and outcomes and potentially decrease healthcare utilization and cost.INTRODUCTION Patients with kidney failure benefit from(KT)[1,2],and experience improved survival rates when compared with dialysis[3-6].KT studies,using validated instruments,have also consistently demonstrated that kidney transplant recipients(KTRs)experience better health-related quality of life and several improvements in other disease-specific domains when compared with dialysis[7].In countries where dialysis is out of reach for many,the diagnosis of kidney failure would be futile without KT[8].Thus,increasing KT has been a priority for the nephrology and transplant communities.This priority has been reflected in recent global trends:Of the 79 countries where data were available,the International Society of Nephrology’s Global Kidney Atlas reported that the prevalence of KTRs in 2023 was 279 per million population which represented an increase of 9.4%from the data published four years prior[8].Despite this growth,KT can be a challenging journey for many patients and it is sometimes regarded as a‘cure’,which does not conform with the reality that many patients experience[9-13].KTRs must maintain a life-long treatment regimen of medications,lifestyle changes,self-care and medical appointments[14-17].As poignantly stated by a young female transplant recipient,“I thought everything would change once I got my kidney.I thought I would be healthy again”but after experiencing multiple side effects of immunosuppressive medications and graft loss,she stated,“I am just a different kind of patient now”[18].Indeed,a significant proportion of patients experience graft failure and return to dialysis;it is estimated that over 50%return to dialysis within 10 years of KT[19-23].Patients are often not prepared for this outcome and report several psychosocial and physical ramifications of graft failure[24,25].Overall,high symptom burden,adverse effects of immunosuppressants,risk of graft rejection or failure and mortality,contribute to complex needs,vulnerability and uncertainties for patients,increasing their care needs and treatment burden[26-30].In this paper,we highlight the complex journey that KTRs and candidates undertake that can generate varied outcome trajectories and complex healthcare needs.We highlight the need for a comprehensive patient-centered approach to care and conclude with a proposal for a“supportive care in transplantation”care model.展开更多
In this editorial,we talk about a compelling case focusing on posterior reversible encephalopathy syndrome(PRES)as a complication in patients undergoing liver transplantation and treated with Tacrolimus.Tacrolimus(FK ...In this editorial,we talk about a compelling case focusing on posterior reversible encephalopathy syndrome(PRES)as a complication in patients undergoing liver transplantation and treated with Tacrolimus.Tacrolimus(FK 506),derived from Streptomyces tsukubaensis,is a potent immunosuppressive macrolide.It inhibits Tcell transcription by binding to FK-binding protein,and is able to amplify glucocorticoid and progesterone effects.Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES.PRES presents with various neurological symptoms alongside elevated blood pressure,and is primarily characterized by vasogenic edema on neuroimaging.While computed tomography detects initial lesions,magnetic resonance imaging,especially the Fluid-Attenuated Inversion Recovery sequence,is superior for diagnosing cortical and subcortical edema.Our discussion centers on the incidence of PRES in solid organ transplant recipients,which ranges between 0.5 to 5+ACU-,with varying presentations,from seizures to visual disturbances.The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES.Radiographically evident in the parietal and occipital lobes,PRES underlines the need for heightened vigilance among healthcare providers.This editorial emphasizes the importance of early recognition,accurate diagnosis,and effective management of PRES to optimize outcomes in liver transplant patients.The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks,underlining the necessity for careful monitoring and intervention strategies in this patient population.展开更多
New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Defici...New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells.Thus,the disruption of photoreceptors takes place.However,even in advanced forms of retinal degeneration,a good percentage of the ganglion cells and the inner nuclear layer neurons remain intact.This phenomenon provides evidence for obtaining retinal circuitry through the transplantation of photoreceptors into the subretinal region.The eye is regarded as an optimal organ for cell transplantation because of its immunological privilege and the relatively small number of cells collaborating to carry out visual activities.The eyeball's immunological privilege,characterized by the suppression of delayed-type hypersensitivity responses in ocular tissues,is responsible for the low rate of graft rejection in transplant patients.The main discoveries highlight the capacity of embryonic stem cells(ESCs)and induced pluripotent stem cells to regenerate damaged retinal regions.Recent progress has shown significant enhancements in transplant procedures and results.The research also explores the ethical ramifications linked to the utilization of stem cells,emphasizing the ongoing issue surrounding ESCs.The analysis centers on recent breakthroughs,including the fabrication of three-dimensional retinal organoids and the innovation of scaffolding for cell transportation.Moreover,researchers are currently assessing the possibility of CRISPR and other advanced gene editing technologies to enhance the outcomes of retinal transplantation.The widespread use of universally recognized safe surgical and imaging methods enables retinal transplantation and monitoring of transplanted cell growth toward the correct location.Currently,most therapy approaches are in the first phases of development and necessitate further research,including both pre-clinical and clinical trials,to attain favorable visual results for individuals suffering from retinal degenerative illnesses.展开更多
The number of solid organ transplantations performed annually is increasing and are increasing in the following order:Kidney,liver,heart,lung,pancreas,small bowel,and uterine transplants.However,the outcomes of transp...The number of solid organ transplantations performed annually is increasing and are increasing in the following order:Kidney,liver,heart,lung,pancreas,small bowel,and uterine transplants.However,the outcomes of transplants are impro-ving(organ survival>90%after the 1st year).Therefore,there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen.Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems.The perioperative regulation of immunosuppression,the treatment of accompanying problems of immunosuppression,the administration of cortisol and,above all,the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients.The perioperative assessment and preparation includes evaluation of the patient’s cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis,or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes.Immunosuppression in transplant patients is associated with the use of calci-neurin inhibitors,corticosteroids,and antiproliferation agents.Many times,the clinical picture is atypical,resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality.Multidetector computed tomo-graphy is of utmost importance for early diagnosis and management.Transplant recipients are prone to infections,especially specific infections caused by cytomegalovirus and Clostridium difficile,and they are predisposed to intraop-erative or postoperative complications that require great care and vigilance.It is necessary to follow evidence-based therapeutic protocols.Thus,it is required that the clinician choose the correct therapeutic plan for the patient(conservative,emergency open surgery or minimally invasive surgery,including laparoscopic or even robotic surgery).展开更多
Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric...Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury.Thus,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease.To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,respectively.Using bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting proteins.Interactions between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in vitro.Our data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory effects.Taken together,our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis,and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.展开更多
Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,...Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.展开更多
基金support by European Union's Horizon 2020 Research and Innovation Program under Grant Agreement No.862829,project AVANT-Alternatives to Veterinary ANTimicrobials.
文摘Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has posed a major public health concern worldwide.Patients with comorbid conditions are at risk of adverse outcomes following COVID-19.Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection.It could lead to higher rates of inpatient complications and mortality in this patient population.However,studies on COVID-19 outcomes in liver transplant(LT)recipients have yielded inconsistent findings.AIM To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States.METHODS We conducted a retrospective cohort study using the 2019–2020 National Inpatient Sample database.Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classi-fication of Diseases,Tenth Revision coding system.The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic.Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients.RESULTS A total of 15720 hospitalized LT recipients were included.Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection.In both cohorts,the median admission age was 57 years.The linear trends for LT hospitalizations did not differ significantly before and during the pandemic(P=0.84).The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020.Compared to the pre-pandemic period,a higher association was noted between LT recipients and in-hospital mortality during the pandemic,with an odds ratio(OR)of 1.69[95% confidence interval(CI):1.55-1.84),P<0.001].The frequency of transplant rejections among hospitalized LT recipients increased from 0.2%to 3.6% between January 2019 and December 2020.LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic[OR:1.53(95%CI:1.26-1.85),P<0.001].CONCLUSION The hospitalization rates for LT recipients were comparable before and during the pandemic.Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.
文摘BACKGROUND Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients(KTRs)and has been established as the treatment of choice for patients with end-stage kidney disease.Health-related quality of life(HRQoL)has become an important outcome measure.It is highly important to develop reliable methods to evaluate HRQoL with disease-specific questionnaires.AIM To translate the disease-specific instrument Kidney Transplant Questionnaire 25(KTQ-25)to the Greek language and perform a cross-cultural adaptation.METHODS The translation and adaptation of the original English version of the KTQ-25 to the Greek language were performed based on the International Quality of Life RESULTS Eighty-four KTRs(59 males;mean age 53.5±10.7 years;mean estimated glomerular filtration rate 47.7±15.1 mL/min/1.73 m2;mean transplant vintage 100.5±83.2 months)completed the Greek version of the KTQ-25 and the 36-item Short-Form Health Survey,and the results were used to evaluate the reliability of the Greek KTQ-25.The Cronbach alpha coefficients for all the KTQ-25 dimensions were satisfactory(physical symptoms=0.639,fatigue=0.856,uncertainty/fear=0.661,appearance=0.593,emotions=0.718,total score=0.708).The statistically significant correlation coefficients among the KTQ-25 dimensions ranged from 0.226 to 0.644.The correlation coeffi-cients of the KTQ-25 dimensions with the SF-36 physical component summary(PCS)ranged from 0.196 to 0.550;the correlation coefficients of the KTQ-25 with the SF-36 mental component summary(MCS)ranged from 0.260 to 0.655;and the correlation coefficients of the KTQ-25 with the total scores with the SF-36 PCS and MCS were 0.455 and 0.613,respectively.CONCLUSION According to the findings,the Greek version of the KTQ-25 is valid and reliable for administration among kidney transplant patients in Greece.
文摘BACKGROUND Transplant recipients commonly harbor multidrug-resistant organisms(MDROs),as a result of frequent hospital admissions and increased exposure to antimi-crobials and invasive procedures.AIM To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition,as well as the impact of MDRO acquisition on intensive care unit(ICU)and hospital length of stay,and on ICU mortality and 1-year mortality post heart transplantation.METHODS This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period(2013-2022)in a single transplantation center.Data was collected regarding MDROs commonly encountered in critical care.RESULTS Among the 98 transplanted patients(70%male),about a third(32%)acquired or already harbored MDROs upon transplantation(MDRO group),while two thirds did not(MDRO-free group).The prevalent MDROs were Acinetobacter baumannii(14%),Pseudomonas aeruginosa(12%)and Klebsiella pneumoniae(11%).Compared to MDRO-free patients,the MDRO group was characterized by higher body mass index(P=0.002),higher rates of renal failure(P=0.017),primary graft dysfunction(10%vs 4.5%,P=0.001),surgical re-exploration(34%vs 14%,P=0.017),mechanical circulatory support(47%vs 26%P=0.037)and renal replacement therapy(28%vs 9%,P=0.014),as well as longer extracorporeal circulation time(median 210 vs 161 min,P=0.003).The median length of stay was longer in the MDRO group,namely ICU stay was 16 vs 9 d in the MDRO-free group(P=0.001),and hospital stay was 38 vs 28 d(P=0.006),while 1-year mortality was higher(28%vs 7.6%,log-rank-χ2:7.34).CONCLUSION Following heart transplantation,a predominance of Gram-negative MDROs was noted.MDRO acquisition was associated with higher complication rates,prolonged ICU and total hospital stay,and higher post-transplantation mortality.
文摘BACKGROUND Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart,liver and kidney transplants.However,information on how functional status,before and after transplant impacts post-transplant survival outcomes is lacking.AIM To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States adults.METHODS We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to 2022.The primary outcome was mortality.Using the Karnofsky Performance Status,functional impairment was categorized as severe,moderate and normal.Analyses were conducted using Kaplan-Meier curves and multivariable Cox regression.RESULTS The median age was 41 years,majority(53.4%)were women.Severe impairment was present in 28.3%of recipients.The median survival time was 906.6 days.The median survival time was 1331 and 560 days for patients with normal and severe functional impairment respectively.Recipients with severe impairment had a 56%higher risk of mortality at one year[Hazard ratio(HR)=1.56;95%CI:1.23–1.98;P<0.001]and 58%at five years(HR=1.58;95%CI:1.24–2.00;P<0.001)compared to patients with no functional impairment.Recipients with worse functional status after transplant also had poor survival outcomes.CONCLUSION Pre-and post-transplant recipient functional status is an important prognostic indicator for short-and long-term intestinal transplant outcomes.
基金the European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘Solid organ transplant recipients face unique challenges in managing their im-munosuppressed status,making vaccination a critical consideration.This review aimed to comprehensively analyze current recommendations,evaluate the effi-cacy of vaccinations in this population,and assess safety concerns.We explored the latest evidence on vaccine types,timing,and potential benefits for transplant patients,highlighting the importance of individualized approaches for routinely used vaccines as well as coronavirus disease 2019 vaccines.By synthesizing avai-lable data,this review underscored the pressing need to optimize vaccination strategies,ensuring that transplant recipients can obtain the full protection against many pathogens while minimizing risks associated with their post-transplant immunosuppression.
文摘Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.
文摘BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.
文摘BACKGROUND Through continuous improvement in transplantation medicine,a wider range of solid organ transplant(SOT)recipients is considered suitable for complex procedures.Despite advances in modern transplantation practice,transpiring invasive fungal infections pose a substantial threat for SOT recipients.To our knowledge,cryptococcal infection confined amidst sole pancreas SOT recipients has not been described to date.Enforcement of a multidisciplinary transplant team approach in the management of pancreas SOT recipients presenting with complex cryptococcal complications is fundamental in improving patient outcomes.CASE SUMMARY We present the case of a female pancreas transplant recipient,with confirmed meningeal cryptococcosis,referred to our institution for further evaluation and treatment from the Regional Center for Infectious Diseases.On admission,the patient was weaned from the protocolized immunosuppression therapy for two consecutive weeks,in addition to tapering systemic corticosteroid remedial treatment.Our novel multidisciplinary transplant team approach embodied exhaustive discussions of possible complex and diverse multiple organ system physiologic and pathologic challenges associated with distinct management strategies in pancreas transplant recipients.Owing to the potentially devastating impact of invasive cryptococcosis in terms of morbidity and mortality,a definitive surgical intervention of pancreas transplant grafectomy was reinforced,as a pathway towards secure access to early meaningful expertise care.The patient was discharged to the Regional Center for Infectious Diseases 2 mo after the admittance further advancing to a clinical improvement.CONCLUSION The precision transplantation approach by tailoring complex medical interventions to individual needs proved indispensable in improving our patient’s outcomes.
基金Supported by the Shenzhen Science and Technology Research and Development Fund,No.JCYJ20220530163011026.
文摘BACKGROUND Given the current organ shortage crisis,split liver transplantation(SLT)has emerged as a promising alternative for select end-stage liver disease patients.AIM To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT.METHODS A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1,2022,and May 31,2023.The study included 25 SLT cases and 81 whole liver transplantation(WLT)cases.Total ex-vivo liver splitting was employed for SLT graft procurement in three steps.Patient outcomes were determined,including liver function parameters,postoperative complications,and perioperative mortality.Group comparisons for categorical variables were performed using theχ²-test.RESULTS In the study,postoperative complications in the 25 SLT cases included hepatic artery thrombosis(n=1)and pulmonary infections(n=3),with no perioperative mortality.In contrast,among the 81 patients who underwent WLT,complications included perioperative mortality(n=1),postoperative pulmonary infections(n=8),abdominal infection(n=1),hepatic artery thromboses(n=3),portal vein thrombosis(n=1),and intra-abdominal bleeding(n=5).Comparative analysis demonstrated significant differences in alanine aminotransferase(176.0 vs 73.5,P=0.000)and aspartate aminotransferase(AST)(42.0 vs 29.0,P=0.004)at 1 wk postoperatively,and in total bilirubin(11.8 vs 20.8,P=0.003)and AST(41.5 vs 26.0,P=0.014)at 2 wk postoperatively.However,the overall incidence of complications was comparable between the two groups(P>0.05).CONCLUSION Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach,especially under the expertise of an experienced transplant center.The approach developed by our center can serve as a valuable reference for other transplantation centers.
文摘BACKGROUND Liver transplantation(LT)is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients.There are many indications for LT that vary between countries and settings.The outcome of LT depends on the available facilities and surgical expertise,as well as the types of liver graft donors available.AIM To assess the clinical characteristics of patients from Bahrain who underwent LT overseas,and analyze factors affecting their survival.METHODS In this retrospective cohort study,we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office,Ministry of Health,Kingdom of Bahrain,between 1997 and 2023.Demographic data,LT indication,donor-recipient relationship,overseas LT center,graft type,post-LT medications,and LT complications,were collected.Outcomes measured included the overall and 5-year LT survival rate.Fisher’s exact,Pearsonχ2,and Mann-Whitney U tests were used to compare the pediatric and the adults’group in terms of clinical characteristics,donor-recipient relationship,medication,complications,and outcome.Survival analysis was estimated via the Kaplan-Meier’s method.Univariate and multivariate analyses were used to detect predictors of survival.RESULTS Of the 208 eligible patients,170(81.7%)were sent overseas to undergo LT while 38(18.3%)remained on the waiting list.Of the 170 patients,167(80.3%)underwent LT and were included in the study.The majority of the patients were Bahraini(91.0%),and most were males(57.5%).One-hundred-and-twenty(71.8%)were adults and 47(28.3%)were children.The median age at transplant was 50.0[interquartile range(IQR):14.9–58.4]years.The main indication for pediatric LT was biliary atresia(31.9%),while that of adult LT was hepatitis C-related cirrhosis(35.0%).Six(3.6%)patients required re-transplantation.Most patients received a living-related liver graft(82%).Pediatric patients received more living and related grafts than adults(P=0.038 and P=0.041,respectively),while adult patients received more cadaveric and unrelated grafts.Most patients required long-term immunosuppressive therapy after LT(94.7%),of which tacrolimus was the most prescribed(84.0%),followed by prednisolone(50.7%),which was prescribed more frequently for pediatric patients(P=0.001).Most patients developed complications(62.4%)with infectious episodes being the most common(38.9%),followed by biliary stricture(19.5%).Tonsilitis and sepsis(n=12,8.1%for each)were the most frequent infections.Pediatric patients experienced higher rates of infection,rejection,and early poor graft function than adult patients(P<0.001,P=0.003,and P=0.025,respectively).The median follow-up time was 6.5(IQR:2.6–10.6)years.The overall survival rate was 84.4%,the 5-year survival rate,86.2%,and the mortality rate,15.6%.Younger patients had significantly better odds of survival(P=0.019)and patients who survived had significantly longer follow-up periods(P<0.001).CONCLUSION Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries.Since LT facilities are not available,an overseas LT has offered them great hope.
基金This study was approved by the Austin Health Human Ethics Research Committee(No.HREC/87459/Austin-2022).
文摘BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)metformin.During a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related mortality.Statin,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.
文摘BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal function after LT have not yet been well described.AIM To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant.METHODS This retrospective study included all patients who underwent liver or liverkidney transplant at our institution from January,2011 to December,2021.Patients were classified based on whether they received PGE1.PGE1 was administered post-LT to those with transaminases>1000 U/L in the immediate postoperative period.Demographics,post-LT treatments and/or complications,renal function,and survival were analyzed.Multivariable logistic regression analysis was performed,and a two-tailed P value<0.05 was considered statistically significant.RESULTS A total of 145 patients underwent LT,with 44(30%)receiving PGE1.Baseline patient characteristics were comparable,except the PGE1 group had significantly higher aspartate aminotransferase(AST)(1961.9 U/L±1862.3 U/L vs 878 U/L±741.4 U/L,P=0.000),alanine aminotransferase(1070.6 U/L±895 U/L vs 547.7 U/L±410 U/L,P=0.000),international normalized ratio on post-LT day 1(2±0.74 vs 1.8±0.4,P=0.03),a longer intensive care unit stay(8.1 days±11.8 days vs 3.8 days±4.6 days,P=0.003),more vasopressor use(55.53 hours±111 hours vs 16.33 hours±26.3 hours,P=0.002),and higher immediate postoperative complications(18.6%vs 4.9%,P=0.04).The PGE1 group also had a significantly higher 90-day readmission rate(29.6%vs 13.1%,P=0.02)and lower 1-year liver graft survival(87.5%vs 98.9%,P=0.005).However,30-day readmission(31.6%vs 27.4%,P=0.64),LT complications(hepatic artery thrombosis,biliary complications,rejection of liver graft,cardiomyopathy),1-year patient survival(96.9%vs 97.8%,P=0.77),overall liver graft survival,and overall patient survival were similar between the two groups(95.4%vs 93.9%,P=0.74 and 88.4%vs 86.9%,P=0.81 respectively).Although the PGE1 group had a significantly lower glomerular filtration rate(eGFR)on post-LT day 7(46.3 mL/minute±26.7 mL/minute vs 62.5 mL/minute±34 mL/minute,P=0.009),the eventual need for renal replacement therapy(13.6%vs 5.9%,P=0.09),the number of dialysis sessions(0.91 vs 0.27,P=0.13),and eGFR at 1-month(37.2 mL/minute±35.9 mL/minute vs 42 mL/minute±36.9 mL/minute,P=0.49),6-months(54.8 mL/minute±21.6 mL/minute vs 62 mL/minute±21.4 mL/minute,P=0.09),and 12-months(63.7 mL/minute±20.7 mL/minute vs 62.8 mL/minute±20.3 mL/minute,P=0.85)post-LT were similar to those in the non-PGE1 group.CONCLUSION In patients who received PGE1 for ischemia-reperfusion injury,despite immediate acute renal injury post-LT,the renal function at 1-month,6-months,and 12-months post-LT was similar compared to those without ischemiareperfusion injury.Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.
文摘Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected.This approach is labor-intensive,invasive and costly.In addition,because this approach relies on a rise in serum creatinine above historical baselines,injury to the allograft can be extensive before this rise occurs.In an effort to address this,donor-derived cell-free DNA(dd-cf DNA)is being used with increasing frequency in the clinical setting as a means of diagnosing a rejection of the renal allograft early in the course.This can poten-tially allow for early intervention to minimize not only injury,but the intensity of antirejection therapy needed and the avoidance of side effects.Here,we will review the available methodology for the determination and quantification of dd-cf DNA,the data supporting its use in clinical practice and the limitations of this technology.
文摘Kidney transplantation(KT),although the best treatment option for eligible patients,entails maintaining and adhering to a life-long treatment regimen of medications,lifestyle changes,self-care,and appointments.Many patients experience uncertain outcome trajectories increasing their vulnerability and symptom burden and generating complex care needs.Even when transplants are successful,for some patients the adjustment to life post-transplant can be challenging and psychological difficulties,economic challenges and social isola-tion have been reported.About 50%of patients lose their transplant within 10 years and must return to dialysis or pursue another transplant or conservative care.This paper documents the complicated journey patients undertake before and after KT and outlines some initiatives aimed at improving patient-centered care in transplantation.A more cohesive approach to care that borrows its philosophical approach from the established field of supportive oncology may improve patient experiences and outcomes.We propose the"supportive care in transplantation"care model to operationalize a patient-centered approach in transplantation.This model can build on other ongoing initiatives of other scholars and researchers and can help advance patient-centered care through the entire care continuum of kidney transplant recipients and candidates.Multi-dimensionality,multi-disciplinarity and evidence-based approaches are proposed as other key tenets of this care model.We conclude by proposing the potential advantages of this approach to patients and healthcare systems.Core Tip:Kidney transplant recipients and candidates face several uncertainties in their care journey and have several expressed unmet healthcare needs.We recommend a structured and comprehensive approach to transplant care across the entire continuum of a transplant patient’s journey similar to what has been developed in the field of oncology.The supportive care in transplantation model can operationalize patient-centered care and build on the efforts of other researchers in the field.We postulate that such a model would significantly improve care delivery and patients’experiences and outcomes and potentially decrease healthcare utilization and cost.INTRODUCTION Patients with kidney failure benefit from(KT)[1,2],and experience improved survival rates when compared with dialysis[3-6].KT studies,using validated instruments,have also consistently demonstrated that kidney transplant recipients(KTRs)experience better health-related quality of life and several improvements in other disease-specific domains when compared with dialysis[7].In countries where dialysis is out of reach for many,the diagnosis of kidney failure would be futile without KT[8].Thus,increasing KT has been a priority for the nephrology and transplant communities.This priority has been reflected in recent global trends:Of the 79 countries where data were available,the International Society of Nephrology’s Global Kidney Atlas reported that the prevalence of KTRs in 2023 was 279 per million population which represented an increase of 9.4%from the data published four years prior[8].Despite this growth,KT can be a challenging journey for many patients and it is sometimes regarded as a‘cure’,which does not conform with the reality that many patients experience[9-13].KTRs must maintain a life-long treatment regimen of medications,lifestyle changes,self-care and medical appointments[14-17].As poignantly stated by a young female transplant recipient,“I thought everything would change once I got my kidney.I thought I would be healthy again”but after experiencing multiple side effects of immunosuppressive medications and graft loss,she stated,“I am just a different kind of patient now”[18].Indeed,a significant proportion of patients experience graft failure and return to dialysis;it is estimated that over 50%return to dialysis within 10 years of KT[19-23].Patients are often not prepared for this outcome and report several psychosocial and physical ramifications of graft failure[24,25].Overall,high symptom burden,adverse effects of immunosuppressants,risk of graft rejection or failure and mortality,contribute to complex needs,vulnerability and uncertainties for patients,increasing their care needs and treatment burden[26-30].In this paper,we highlight the complex journey that KTRs and candidates undertake that can generate varied outcome trajectories and complex healthcare needs.We highlight the need for a comprehensive patient-centered approach to care and conclude with a proposal for a“supportive care in transplantation”care model.
文摘In this editorial,we talk about a compelling case focusing on posterior reversible encephalopathy syndrome(PRES)as a complication in patients undergoing liver transplantation and treated with Tacrolimus.Tacrolimus(FK 506),derived from Streptomyces tsukubaensis,is a potent immunosuppressive macrolide.It inhibits Tcell transcription by binding to FK-binding protein,and is able to amplify glucocorticoid and progesterone effects.Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES.PRES presents with various neurological symptoms alongside elevated blood pressure,and is primarily characterized by vasogenic edema on neuroimaging.While computed tomography detects initial lesions,magnetic resonance imaging,especially the Fluid-Attenuated Inversion Recovery sequence,is superior for diagnosing cortical and subcortical edema.Our discussion centers on the incidence of PRES in solid organ transplant recipients,which ranges between 0.5 to 5+ACU-,with varying presentations,from seizures to visual disturbances.The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES.Radiographically evident in the parietal and occipital lobes,PRES underlines the need for heightened vigilance among healthcare providers.This editorial emphasizes the importance of early recognition,accurate diagnosis,and effective management of PRES to optimize outcomes in liver transplant patients.The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks,underlining the necessity for careful monitoring and intervention strategies in this patient population.
文摘New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells.Thus,the disruption of photoreceptors takes place.However,even in advanced forms of retinal degeneration,a good percentage of the ganglion cells and the inner nuclear layer neurons remain intact.This phenomenon provides evidence for obtaining retinal circuitry through the transplantation of photoreceptors into the subretinal region.The eye is regarded as an optimal organ for cell transplantation because of its immunological privilege and the relatively small number of cells collaborating to carry out visual activities.The eyeball's immunological privilege,characterized by the suppression of delayed-type hypersensitivity responses in ocular tissues,is responsible for the low rate of graft rejection in transplant patients.The main discoveries highlight the capacity of embryonic stem cells(ESCs)and induced pluripotent stem cells to regenerate damaged retinal regions.Recent progress has shown significant enhancements in transplant procedures and results.The research also explores the ethical ramifications linked to the utilization of stem cells,emphasizing the ongoing issue surrounding ESCs.The analysis centers on recent breakthroughs,including the fabrication of three-dimensional retinal organoids and the innovation of scaffolding for cell transportation.Moreover,researchers are currently assessing the possibility of CRISPR and other advanced gene editing technologies to enhance the outcomes of retinal transplantation.The widespread use of universally recognized safe surgical and imaging methods enables retinal transplantation and monitoring of transplanted cell growth toward the correct location.Currently,most therapy approaches are in the first phases of development and necessitate further research,including both pre-clinical and clinical trials,to attain favorable visual results for individuals suffering from retinal degenerative illnesses.
文摘The number of solid organ transplantations performed annually is increasing and are increasing in the following order:Kidney,liver,heart,lung,pancreas,small bowel,and uterine transplants.However,the outcomes of transplants are impro-ving(organ survival>90%after the 1st year).Therefore,there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen.Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems.The perioperative regulation of immunosuppression,the treatment of accompanying problems of immunosuppression,the administration of cortisol and,above all,the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients.The perioperative assessment and preparation includes evaluation of the patient’s cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis,or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes.Immunosuppression in transplant patients is associated with the use of calci-neurin inhibitors,corticosteroids,and antiproliferation agents.Many times,the clinical picture is atypical,resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality.Multidetector computed tomo-graphy is of utmost importance for early diagnosis and management.Transplant recipients are prone to infections,especially specific infections caused by cytomegalovirus and Clostridium difficile,and they are predisposed to intraop-erative or postoperative complications that require great care and vigilance.It is necessary to follow evidence-based therapeutic protocols.Thus,it is required that the clinician choose the correct therapeutic plan for the patient(conservative,emergency open surgery or minimally invasive surgery,including laparoscopic or even robotic surgery).
基金supported by the National Natural Science Foundation of China,Nos.82201621(to LS),31930048(to QY)and 81720108016(to QY),and 81971225(to CG)the Key Research and Development Project of Shaanxi Province,No.2022SF-189(to XS)the Tangdu Hospital Supporting Foundation,Nos.2021ZTXM-006(to LS)and 2021JSZH-006(to CG)。
文摘Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury.Thus,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease.To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,respectively.Using bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting proteins.Interactions between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in vitro.Our data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory effects.Taken together,our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis,and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.
文摘Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.
