Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipid...Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipids and electrolytes,have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts.This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.Methods The present study consecutively collected 306 patients who underwent their first single kidney transplantation(KT)from adult deceased donors in our center from January 1,2018 to December 31,2019.The correlation between postoperative outcomes[DGF and abnormal serum creatinine(SCr)after 6 and 12 months]and risk factors of donors,including gender,age,body mass index(BMI),past histories,serum lipid biomarkers[cholesterol,triglyceride,high-density lipoprotein(HDL)and low-density lipoprotein(DL)],and serum electrolytes(calcium and sodium)were analyzed and evaluated.Results(1)Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level(≥2 mg/dL)at 6 and 12 months after KT(P<0.05);(2)The donor’s BMI was significantly correlated with the incidence rate of DGF after KT(P<0.05);(3)For serum lipids,merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT[P<0.05,OR(95%CI):0.425(0.202–0.97)];(4)The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT[P<0.05,OR(95%CI):0.184(0.045–0.747)and P<0.05,OR(95%CI):0.114(0.014–0.948),respectively].Conclusion The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT,in addition to the donor’s age,BMI and pre-existing hypertension.展开更多
Objective We aimed to identify new,more accurate risk factors of liver transplantation for liver cancer through using the Surveillance,Epidemiology,and End Results(SEER)database.Methods Using the SEER database,we iden...Objective We aimed to identify new,more accurate risk factors of liver transplantation for liver cancer through using the Surveillance,Epidemiology,and End Results(SEER)database.Methods Using the SEER database,we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma(HCC)and subsequent liver transplantation between 2010 and 2017.Overall survival(OS)was estimated using Kaplan-Meier plotter.Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease[presented as adjusted hazard ratios(HR)with 95%CIs].Results Totally,1530 eligible patients were included in the analysis.There were significant differences in ethnicity(P=0.04),cancer stage(P<0.001),vascular invasion(P<0.001)and gall bladder involvement(P<0.001)between the groups that survived,died due to cancer,or died due to other causes.In the Cox regression model,there were no significant differences in OS at 5 years with different operative strategies(autotransplantation versus allotransplantation),nor at survival at 1 year with neoadjuvant radiotherapy.However,neoadjuvant radiotherapy did appear to improve survival at both 3 years(HR:0.540,95%CI:0.326–0.896,P=0.017)and 5 years(HR:0.338,95%CI:0.153–0.747,P=0.007)from diagnosis.Conclusion This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC.These criteria can be used to inform patient selection and consent in this setting.Preoperative radiotherapy may improve long-term survival post-transplantation.展开更多
Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asia...Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian,especially in Chinese.To update the genotypes of PH1 in the Chinese population,we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center,five of whom had delayed diagnosis and failed in kidney transplantation.Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT.Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations.Furthermore,a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees.To the best of ourknowledge,2 novel variants of A GXT,p.Gly41 Trp and p.Leu33Met,were first reported.Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT)at a protein level.The systematic review revealed significant population heterogeneity in PH1.In conclusion,new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore,a genotype-phenotype correlation is found in PH1.展开更多
Background:Long-term survival after liver transplantation(LT)for hepatocellular carcinoma(HCC)patients remains poor because of tumor recurrence.To improve the prognosis of HCC patients after LT,we aimed to identify di...Background:Long-term survival after liver transplantation(LT)for hepatocellular carcinoma(HCC)patients remains poor because of tumor recurrence.To improve the prognosis of HCC patients after LT,we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center.Methods:In total,data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis.The patients were divided into the following three groups:Group 1,within the Milan and Hangzhou criteria(n=51);Group 2,beyond the Milan but within the Hangzhou criteria(n=36);and Group 3,beyond the Milan and Hangzhou criteria(n=112).Survival probabilities for the three groups were calculated using multivariate Cox regression analysis.The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis.Results:Child-Pugh stage C and hepatitis B virus(HBV)infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria.The overall survival rates of the 199 patients showed statistically significant differences among the three groups(P<0.001).Moreover,no significant difference was noted in the survival rate between Group 1 and Group 2(P>0.05).Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria(OR=0.478;95%CI:0.308–0.741;P=0.001).Conclusions:Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT.The Hangzhou criteria were effective and analogous compared with the Milan criteria.Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.展开更多
Objective:This study investigated the composition of pathogenic microorganisms,clinical features,and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor(DD)kid...Objective:This study investigated the composition of pathogenic microorganisms,clinical features,and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor(DD)kidneys.Methods:We retrospectively studied the clinical data of the DD kidney transplant recipients with donor-associated infection at Tongji Hospital,Wuhan,China from January 1,2015 to December 31,2018,related recipients and corresponding donors.We collected the entire results of pathogenic microorganisms cultured from these related ruptured kidneys and then analyzed their distribution and differences.Results:A total of 1440 kidney transplants from DD were performed in our center.The total incidence of infective artery rupture in kidney transplants was about 0.76%(11/1440),and the annual incidence ranged from 0.25%to 1.03%.The microbial culture results revealed that 11 recipients suffered from infective artery rupture and 3 recipients who accepted the kidney from same donor had the donor-associated pathogens,including 9 fungal strains(28.1%)and 23 bacterial strains(71.9%).There were 4 recipients infected with multi-drug-resistant Staphylococcus and Klebsiella pneumoniae from the above 11 recipients,of which,10 recipients underwent graft loss,and one died of septic shock.The microbial cultures of the remaining 3 recipients who received appropriate anti-infective regimens turned negative eventually,and the patients were discharged successfully without significant complications.Conclusion:Renal recipients with infections derived from DDs were at high risk of artery rupture,graft loss,or even death.Appropriate anti-infective treatment is essential to reduce the incidence of artery rupture and mortality.展开更多
AIM To analyze retrospectively a 5-year experience of human hepatocyte isolation from resected liver tissues with benign disease.METHODS We established a method of modified four-step retrograde perfusion to isolate pr...AIM To analyze retrospectively a 5-year experience of human hepatocyte isolation from resected liver tissues with benign disease.METHODS We established a method of modified four-step retrograde perfusion to isolate primary human hepatocytes. Samples were collected from the resected livers of patients with intrahepatic duct calculi(n = 7) and liver hemangioma(n = 17). Only the samples weighing ≥ 15 g were considered suitable for hepatocyte isolation. By using the standard trypan blue exclusion technique, hepatocyte viability and yield were immediately determined after isolation.RESULTS Twenty-four liver specimens, weighing 15-42 g, were immediately taken from the margin of the removed samples and transferred to the laboratory for hepatocyte isolation. Warm ischemia time was 5-35 min and cold ischemia time was 15-45 min. For the 7 samples of intrahepatic duct calculi, the method resulted in a hepatocyte yield of 3.49 ± 2.31 × 10~6 hepatocytes/g liver, with 76.4% ± 10.7% viability. The 17 samples of liver hemangioma had significantly higher yield of cells(5.4 ± 1.71 × 10~6 cells/g vs 3.49 ± 2.31 × 10~6 cells/g, P < 0.05) than the samples of intrahepatic duct calculi. However, there seems to be no clear difference in cell viability(80.3% ± 9.67% vs 76.4% ± 10.7%, P > 0.05). We obtained a cell yield of 5.31 ± 1.87 × 10~6 hepatocytes/g liver when the samples weighed > 20 g. However, for the tissues weighing ≤ 20 g, a reduction in yield was found(3.08 ± 1.86 × 10~6 cells/g vs 5.31 ± 1.87 × 10~6 cells/g, P < 0.05).CONCLUSION Benign diseased livers are valuable sources for largenumber hepatocyte isolation. Our study represents the largest number of primary human hepatocytes isolated from resected specimens from patients with benign liver disease. We evaluated the effect of donor liver characteristics on cell isolation, and we found that samples of liver hemangioma can provide better results than intrahepatic duct calculi, in terms of cell yield. Furthermore, the size of the tissues can affect the outcome of hepatocyte isolation.展开更多
Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipie...Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.展开更多
基金The study was supported by the Innovation Team Fund Project of Hubei Province(No.WJ2021C001)the Key Research and Development Plan of Hubei Province(No.2022BCA015).
文摘Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipids and electrolytes,have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts.This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.Methods The present study consecutively collected 306 patients who underwent their first single kidney transplantation(KT)from adult deceased donors in our center from January 1,2018 to December 31,2019.The correlation between postoperative outcomes[DGF and abnormal serum creatinine(SCr)after 6 and 12 months]and risk factors of donors,including gender,age,body mass index(BMI),past histories,serum lipid biomarkers[cholesterol,triglyceride,high-density lipoprotein(HDL)and low-density lipoprotein(DL)],and serum electrolytes(calcium and sodium)were analyzed and evaluated.Results(1)Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level(≥2 mg/dL)at 6 and 12 months after KT(P<0.05);(2)The donor’s BMI was significantly correlated with the incidence rate of DGF after KT(P<0.05);(3)For serum lipids,merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT[P<0.05,OR(95%CI):0.425(0.202–0.97)];(4)The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT[P<0.05,OR(95%CI):0.184(0.045–0.747)and P<0.05,OR(95%CI):0.114(0.014–0.948),respectively].Conclusion The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT,in addition to the donor’s age,BMI and pre-existing hypertension.
基金supported by funds from the National Natural Science Foundation of China(No.82000602)the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province(No.CXPJJH11900001-2019330)Innovation Team Project of Health Commission of Hubei Province(No.WJ2021C001).
文摘Objective We aimed to identify new,more accurate risk factors of liver transplantation for liver cancer through using the Surveillance,Epidemiology,and End Results(SEER)database.Methods Using the SEER database,we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma(HCC)and subsequent liver transplantation between 2010 and 2017.Overall survival(OS)was estimated using Kaplan-Meier plotter.Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease[presented as adjusted hazard ratios(HR)with 95%CIs].Results Totally,1530 eligible patients were included in the analysis.There were significant differences in ethnicity(P=0.04),cancer stage(P<0.001),vascular invasion(P<0.001)and gall bladder involvement(P<0.001)between the groups that survived,died due to cancer,or died due to other causes.In the Cox regression model,there were no significant differences in OS at 5 years with different operative strategies(autotransplantation versus allotransplantation),nor at survival at 1 year with neoadjuvant radiotherapy.However,neoadjuvant radiotherapy did appear to improve survival at both 3 years(HR:0.540,95%CI:0.326–0.896,P=0.017)and 5 years(HR:0.338,95%CI:0.153–0.747,P=0.007)from diagnosis.Conclusion This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC.These criteria can be used to inform patient selection and consent in this setting.Preoperative radiotherapy may improve long-term survival post-transplantation.
基金This work was supported by the grants from the Special Project of Ministry of Health (No.201302009)and the National Natural Science Foundation of China (No. 81700300).
文摘Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian,especially in Chinese.To update the genotypes of PH1 in the Chinese population,we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center,five of whom had delayed diagnosis and failed in kidney transplantation.Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT.Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations.Furthermore,a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees.To the best of ourknowledge,2 novel variants of A GXT,p.Gly41 Trp and p.Leu33Met,were first reported.Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT)at a protein level.The systematic review revealed significant population heterogeneity in PH1.In conclusion,new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore,a genotype-phenotype correlation is found in PH1.
基金grants from the National Natural Science Foundation of China(No.81770652)Science and Technology Foundation of Hubei Province(No.2017ACA096 and WJ2017Z011).
文摘Background:Long-term survival after liver transplantation(LT)for hepatocellular carcinoma(HCC)patients remains poor because of tumor recurrence.To improve the prognosis of HCC patients after LT,we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center.Methods:In total,data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis.The patients were divided into the following three groups:Group 1,within the Milan and Hangzhou criteria(n=51);Group 2,beyond the Milan but within the Hangzhou criteria(n=36);and Group 3,beyond the Milan and Hangzhou criteria(n=112).Survival probabilities for the three groups were calculated using multivariate Cox regression analysis.The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis.Results:Child-Pugh stage C and hepatitis B virus(HBV)infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria.The overall survival rates of the 199 patients showed statistically significant differences among the three groups(P<0.001).Moreover,no significant difference was noted in the survival rate between Group 1 and Group 2(P>0.05).Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria(OR=0.478;95%CI:0.308–0.741;P=0.001).Conclusions:Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT.The Hangzhou criteria were effective and analogous compared with the Milan criteria.Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.
基金supported by the Natural,Science Foundation of China(No.8187351l and No.81471587).
文摘Objective:This study investigated the composition of pathogenic microorganisms,clinical features,and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor(DD)kidneys.Methods:We retrospectively studied the clinical data of the DD kidney transplant recipients with donor-associated infection at Tongji Hospital,Wuhan,China from January 1,2015 to December 31,2018,related recipients and corresponding donors.We collected the entire results of pathogenic microorganisms cultured from these related ruptured kidneys and then analyzed their distribution and differences.Results:A total of 1440 kidney transplants from DD were performed in our center.The total incidence of infective artery rupture in kidney transplants was about 0.76%(11/1440),and the annual incidence ranged from 0.25%to 1.03%.The microbial culture results revealed that 11 recipients suffered from infective artery rupture and 3 recipients who accepted the kidney from same donor had the donor-associated pathogens,including 9 fungal strains(28.1%)and 23 bacterial strains(71.9%).There were 4 recipients infected with multi-drug-resistant Staphylococcus and Klebsiella pneumoniae from the above 11 recipients,of which,10 recipients underwent graft loss,and one died of septic shock.The microbial cultures of the remaining 3 recipients who received appropriate anti-infective regimens turned negative eventually,and the patients were discharged successfully without significant complications.Conclusion:Renal recipients with infections derived from DDs were at high risk of artery rupture,graft loss,or even death.Appropriate anti-infective treatment is essential to reduce the incidence of artery rupture and mortality.
基金Supported by the Major Scientific and Technological Project of Shandong Province,China,No.201221019 and No.2014GSF118178the Cisco Clinical Oncology Research Fund and Bayer Schering Cancer Research Fund,No.Y-B2012-011
文摘AIM To analyze retrospectively a 5-year experience of human hepatocyte isolation from resected liver tissues with benign disease.METHODS We established a method of modified four-step retrograde perfusion to isolate primary human hepatocytes. Samples were collected from the resected livers of patients with intrahepatic duct calculi(n = 7) and liver hemangioma(n = 17). Only the samples weighing ≥ 15 g were considered suitable for hepatocyte isolation. By using the standard trypan blue exclusion technique, hepatocyte viability and yield were immediately determined after isolation.RESULTS Twenty-four liver specimens, weighing 15-42 g, were immediately taken from the margin of the removed samples and transferred to the laboratory for hepatocyte isolation. Warm ischemia time was 5-35 min and cold ischemia time was 15-45 min. For the 7 samples of intrahepatic duct calculi, the method resulted in a hepatocyte yield of 3.49 ± 2.31 × 10~6 hepatocytes/g liver, with 76.4% ± 10.7% viability. The 17 samples of liver hemangioma had significantly higher yield of cells(5.4 ± 1.71 × 10~6 cells/g vs 3.49 ± 2.31 × 10~6 cells/g, P < 0.05) than the samples of intrahepatic duct calculi. However, there seems to be no clear difference in cell viability(80.3% ± 9.67% vs 76.4% ± 10.7%, P > 0.05). We obtained a cell yield of 5.31 ± 1.87 × 10~6 hepatocytes/g liver when the samples weighed > 20 g. However, for the tissues weighing ≤ 20 g, a reduction in yield was found(3.08 ± 1.86 × 10~6 cells/g vs 5.31 ± 1.87 × 10~6 cells/g, P < 0.05).CONCLUSION Benign diseased livers are valuable sources for largenumber hepatocyte isolation. Our study represents the largest number of primary human hepatocytes isolated from resected specimens from patients with benign liver disease. We evaluated the effect of donor liver characteristics on cell isolation, and we found that samples of liver hemangioma can provide better results than intrahepatic duct calculi, in terms of cell yield. Furthermore, the size of the tissues can affect the outcome of hepatocyte isolation.
基金supported by grants from the National S&T Major Project (2017ZX10203205)Key Program,National Natural Science Foundation of China (81930016)Zhejiang Provincial Natural Science Foundation of China (LY21H160026)。
文摘Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.
