1.Efficacy of individualized donor-specific antibody removal therapy after kidney transplantation at a single center
Xiaolong ZHU ; Jiazhao FU ; Hanlan LU ; Wenyu ZHAO ; Mingxing SUI ; Li ZENG ; Youhua ZHU ; Lei ZHANG
Chinese Journal of Organ Transplantation 2024;45(9):628-635
Objective:To evaluate the efficacy of individualized removal therapeutic regimen for donor-specific antibodies (DSA) and examine its related influencing factors.Method:From January 2016 to January 2021, 34 recipients of kidney transplant (KT) underwent regular DSA testing and the results were positive. DSA removal therapy based upon rituximab (RTX) plus intravenous immune globulin (IVIG) was offered. Correlation between DSA negative conversion rate and DSA types, time from start of treatment to transplantation, HLA loci targeted by DSA and DSA mean fluorescent intensity (MFI) were analyzed retrospectively. Changes of immunedominant DSA (iDSA) and serum creatinine in individuals with de novo DSA (dnDSA) before and after treatment were also examined.Results:At Month 3 post-treatment, antibodies turned negative in 17/34(50.0%) patients and DSA became negative in 19/34(55.9%) at the last follow-up. Then we identified 78 DSA from all patients. No significant difference existed in negative conversion rate of pfDSA and dnDSA at Month 3 post-treatment [62.9%(39/62) vs 37.5%(6/16)] and at the last follow-up [4.2%(46/62) vs 56.3%(9/16)]( P=0.067, 0.219). For pfDSA, negative conversion rate of pfDSA with different MFIs after 3-month treatment varied significantly [negative conversion rate of weak positive DSA was 78.6%(33/42) and positive and above DSA 30%(6/20), P<0.001]. It was an independent related factor of whether or not pfDSA could turn negative (48.6%, 95% CI: 22.3%-66.8%, P=0.001). At the last follow-up, negative conversion rate of pfDSA differed markedly at different timepoints from start of treatment to transplantation [treated within 30 days post-operation was 79.2%(42/53) and over 30 days post-operation was 44.4%(4/9), P=0.042] and among different DSA MFI [88.1%(37/42) of weakly positive DSA and 45%(9/20) of positive and above DSA, P<0.001] and they were independent related factors for negative conversion of pfDSA (34.8%, 95% CI: 3.2%-61.8%, P=0.008; 43.1%, 95% CI: 18.5%-63.4%, P=0.001). Mean decline rate in iDSA was 66.67% at Month 3 post-treatment and 77.90% at the last follow-up. The difference was statistically significant ( P=0.035). Serum level of creatinine of 9 patients with dnDSA was (110.2±26.9) μmol/L pre-treatment, (178.8±90.5) μmol/L during treatment, (153.9±72.8) μmol/L at Month 3 post-treatment and (213.6±185.8) μmol/L at the last follow-up. Serum creatinine rose during treatment ( t=-2.794, P=0.023), declined at Month 3 post-treatment ( t=3.430, P=0.009) and spiked again at the last follow-up ( P=0.028). Conclusion:After DSA removal therapy based upon RTX plus IVIG, negative conversion rate of pfDSA is correlated with its MFI and time from start of treatment to transplantation. There is no significant rebound in DSA MFI and graft function of dnDSA patients improves immediately after treatment.
2.Analysis of risk factors related to acute rejection after pediatric kidney transplantation
Wenyu ZHAO ; Jiazhao FU ; Yuhong LI ; Mingxing SUI ; Rui CHEN ; Hanlan LU ; Youhua ZHU ; Li ZENG ; Lei ZHANG
Chinese Journal of Organ Transplantation 2023;44(2):87-93
Objective:To explore the risk factors related to acute rejection (AR) after pediatric kidney transplantation (KT).Methods:Retrospective analysis was performed for 189 pediatric KT recipients from September 2011 to August 2022.They were divided into two groups of AR (n=33) and non-AR (n=156).Univariate and multivariate Logistic regression analyses were performed for identifying potential risk factors of AR.And the effects of AR on graft function and survival were also examined.Results:During follow-ups, a total of 33(17.5%) patients developed AR with a 1-year cumulative incidence of AR of 16.9%(32/189).Univariate analysis revealed that median time on dialysis was longer in AR group than that in non-AR group (19 vs. 11 months, P=0.034).Median age of donors (12 vs. 24 months, P=0.033), median weight of donors (9.5 vs. 12 kg, P=0.025) and median donor/recipient body weight ratio (0.36 vs. 0.50, P=0.005) were lower in AR group than those in non-AR group.And the proportion of subtherapeutic tacrolimus (TAC) trough level was higher in AR group than that in non-AR group (45.5% vs. 21.2%, P=0.004).Multivariate regression analysis indicated that subtherapeutic TAC trough level was an independent risk factor for AR ( OR=2.977, 95% CI: 1.314-6.743, P=0.009).At the last follow-up, serum creatinine and eGFR were (78.4±24.3) vs. (74.6±24.7) μmol/L and (85.3±26.3) vs. (89.5±24.2) ml·min -1·1.73 m -2 in AR and non-AR groups respectively.There were no significant differences.1/5-year patient survival rate was both 97% in AR group and both 99.4% in non-AR group; 1/5-year graft survival rate both 90.9% in AR group and was 98.1% and 97.4% in non-AR group.No significant inter-group differences existed in patient and graft survival. Conclusions:Although an occurrence of early AR does not negatively impact graft outcomes, the incidence of AR remains high after pediatric KT.Therefore prompt diagnosis and treatment of AR should be strengthened.
3.Failure mode and long-term survival after neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma
Ruiqi WANG ; Lin WANG ; Xiao HU ; Honglian MA ; Guoqin QIU ; Zhun WANG ; Xiaojiang SUN ; Yongling JI ; Xiaojing LAI ; Wei FENG ; Liming SHENG ; Yuezhen WANG ; Xia ZHOU ; Youhua JIANG ; Changchun WANG ; Qiang ZHAO ; Xun YANG ; Jinshi LIU ; Jian ZENG ; Haitao JIANG ; Pu LI ; Xianghui DU ; Qixun CHEN ; Yujin XU
Chinese Journal of Radiation Oncology 2023;32(4):301-306
Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.
4.Renal graft artery stenosis associated with pediatric kidney
Jiazhao FU ; Wenyu ZHAO ; Mingxing SUI ; Hanlan LU ; Yanxin SONG ; Youhua ZHU ; Li ZENG ; Lei ZHANG
Chinese Journal of Organ Transplantation 2022;43(1):14-19
Objective:To retrospectively summarize the clinical experiences of managing renal artery stenosis after donor kidney transplantation in children.Methods:From January 2018 to October 2021, 114 pediatric kidney transplants(donor/recipient aged <18 years)were performed.According to the findings of color Doppler ultrasonography, they were divided into two groups of normal( n=80)and rapid flow( n=34). Rapid flow group were assigned into symptomatic( n=13)and asymptomatic( n=21)sub-groups based upon clinical features of hypertension and renal instability. Results:Among them, there were 65 males and 49 females.A significant inter-gender difference existed in the proportion of higher arterial flow rate of transplanted kidney(38.5% and 18.4%, P=0.02). No significant difference existed in age or body weight of transplant recipients among all groups( P>0.05). The mean age(10.4 months)and body weight(9 kg)of donors were significantly lower in symptomatic group than those in normal group(65.3 months, 21 kg)and asymptomatic group(64.4 months, 21.2 kg). The mean velocity of symptomatic group was significantly higher than that of asymptomatic group(363.5 vs 228.8 cm/s)( P<0.001). In symptomatic group, 6 cases received medications and their clinical manifestations were completely relieved.Among 7 patients invasively treated, one percutaneous transluminal angioplasty(PTA)was offer once( n=2), twice( n=2)and triple( n=1)with clinical relief and stable renal function.One case of bleeding at puncture site during PTA had treatment failure with a gradual loss of graft function.One ineffective case of PTA was subsequently placed with an endovascular stent.However, repeated stent dilation failed due to restenosis.After surgical exploration, vascular stent removal and transplantation of renal artery clipping, clinical symptoms were relieved. Conclusions:Male recipient, low body weight or young donor may be risk factors for transplant renal artery stenosis(TRAS)during pediatric donor renal transplantation.A higher flow rate of transplanted renal artery on ultrasonography could not confirm the diagnosis of TRAS.Greater arterial flow and associated clinical manifestations often hint at a strong possibility of TRAS, requiring drug or invasive treatment interventions.If PTA efficacy is not satisfactory, multiple treatments should be performed.Nevertheless, stenting should be avoided as far as possible to prevent in-stent restenosis.
5.Post-transplantation lymphoproliferative disorders of kidney in children: two cases report and literature review
Fang LIN ; Qian SHEN ; Hong XU ; Lihong TAN ; Jing CHEN ; Xiaoyan FANG ; Yihui ZHAI ; Jia RAO ; Li ZENG ; Lei ZHANG ; Youhua ZHU
Chinese Journal of Nephrology 2021;37(3):183-190
Objective:To report two cases of post-transplantation lymphoproliferative disorders (PTLD) after kidney transplantation in children and review the literature, and to improve clinicians' understanding of PTLD in children.Methods:The clinical data of two children with PTLD admitted to the Children's Hospital of Fudan University were collected and analyzed. The PTLD-related literature of PubMed, Embase, Web of Science, Scopus, Cochrane Library, Wanfang, CNKI, Weipu Database and China Biomedical Literature Service System from the establishment of the database to January 2020 were collected for literature review. Multivariate logistic regression analysis method was used to analyze the influencing factors of prognostic in children with PTLD.Results:Both of the patients had negative Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) before transplantation and anti-thymocyte immunoglobulin (ATG) were induced during transplantation. PTLD in case 1 and case 2 was diagnosed at 3 and 12 months after transplantation, respectively, with positive EBV and CMV serological reaction. The pathological diagnosis was monomorphic PTLD in case 1 and the case 2 was clinically considered as non-hodgkin lymphoma. They all received thrapies of immunosuppressive reduction combined with anti-CD20 monoclonal antibody and chemotherapy. PTLD was relieved and graft function was normal in 2 cases, while case 1 died two and half years after transplantation due to intracranial fungal infection. According to the analysis of 56 children (including 2 cases in this study) with PTLD from the literature review, the median time of PTLD from transplantation was 41.8 months. The initial involved organs were digestive tract [17 cases (30.4%)], respiratory system [8 cases (14.3%)], nervous system [7 cases (12.5%)] and pharyngeal lymph ring [7 cases (12.5%)], respectively. The main pathologic type of PTLD was monomorphic [34 cases (60.8%)]. Fifty-six cases were all positive in EBV serological reaction when PTLD was diagnosed. The treatment included immunosuppressive reduction combined with anti-CD20 monoclonal antibody and chemotherapy. Forty-eight cases of PTLD were relieved, while 8 cases lost graft function. Eleven cases died, including 3 cases due to infection and the other 8 cases due to PTLD. Multivariate logistic regression showed that monomorphic PTLD was a risk factor of death for PTLD children ( OR=21.616, 95% CI 1.007-464.107, P=0.049). Conclusions:PTLD in children with kidney transplantation is mostly associated with EBV infection, and the clinical manifestations are diverse. Monomorphic PTLD has a poor prognosis and high mortality.
6.Clinical analysis of 147 cases of pediatric kidney transplantation with kidney donation after death of minors
Rui CHEN ; Wenyu ZHAO ; Xiaogang GAO ; Mingxing SUI ; Hanlan LU ; Lei ZHANG ; Youhua ZHU ; Li ZENG
Chinese Journal of Organ Transplantation 2020;41(1):15-19
Objective:To explore the feasibility and efficacy of kidney transplantation with pediatric donors to pediatric recipients (PTP) according to the quality control parameters of kidney transplantation in China.Methods:From September 2011 to September 2019, the clinical data were reviewed for 147 children undergoing kidney transplantation. The general status of donors and recipients, survival rate and complications of transplantation were analyzed.The median age was 130(21-270) month and the median weight 26.0(8.5-71.5) kg. The median age of 120 donors was 12 month (4 day-180 month) and the median weight 9.3(2.5-50.0) kg.Results:After a follow-up period of 10 days to 9 years, the cumulative survival rates of patients and grafts were 97.3% and 88.8%. The cumulative survival rates of patients and grafts were 95.7% and 60.9% in en bloc kidney transplant recipients versus 96.8% and 94.2% in single kidney transplant recipients. The major complications of en bloc kidney transplantation were graft thrombosis (47.8%) and ureteral complications (17.4%). Single kidney transplantation was characterized by delayed graft function recovery (DGF, 18.6%) and acute rejection reaction (10.5%). Two cases died from donor-derived infection after transplantation, one from cytomegalovirus infection and one from epileptic seizure.Conclusions:PTP kidney transplantation is effective. Organ matching and optimal operative mode selection are essential. Preventing postoperative thrombosis for avoiding an early graft loss has remained a high priority during PTP kidney transplantation.
7.Application of high-throughput second-generation gene sequencing in the diagnosis of pulmonary infection after organ transplantation
Hanlan LU ; Mingxing SUI ; Wenyu ZHAO ; Rui CHEN ; Jiazhao FU ; Li ZENG ; Youhua ZHU ; Lei ZHANG
Chinese Journal of Organ Transplantation 2020;41(7):388-392
Objective:To explore the application of high-throughput second-generation gene sequencing technology based upon metagenomics in the diagnosis of pulmonary infection after organ transplantation.Methods:From June 2016 to January 2020, clinical records were retrospectively reviewed for 34 renal and liver transplant recipients hospitalized for pulmonary infection. From June 2016 to December 2018, they were assigned as group A (n=20) of traditional pathogen detections. From January 2019 to January 2020, 14 cases in group B were sequenced by high-throughput second-generation technology. The detection rate, sensitivity and specificity, the return time of detection results, the average length of stay and the mortality of 28 days between two groups were analyzed.Results:No significant inter-group difference existed in clinical data (age, gender, antibody induction method, immunosuppressant use, etc.). As compared with group A, the positive detection rate of etiology and the the sensitivity were higher in group B and the differences in specificity were statistically insignificant. The return time of test results in group B was significantly shorter than that in group A. And the difference was statistically significant. The average hospitalization stay and 28-day mortality of group B were lower than those of group A. And the differences were statistically significant.Conclusions:High-throughput second-generation gene sequencing technology can improve the detection rate of pulmonary infection after organ transplantation. Providing a " precise and accurate" direction for disease treatment, it is a useful supplement to traditional diagnostic methods.
8.Clinical risk stratification ofde novo DSA after kidney transplantation based upon eplet mismatch
Mingxing SUI ; Liping MA ; Rui CHEN ; Wenyu ZHAO ; Hanlan LU ; Xiaolong ZHU ; Li ZENG ; Youhua ZHU ; Lei ZHANG
Chinese Journal of Organ Transplantation 2019;40(8):452-456
Objective To compare HLA loci versus eplet match in predicting de novo DSA after renal transplantation and establish a risk stratification scheme based upon eplet mismatch for predicting the risk of de novo DSA .Methods A retrospective analysis of HLA serological versus and eplet mismatch was performed for 141 pairs of donors and recipients .And the predictive power of de novo DSA was evaluated by the follow-up results .Based upon eplet mismatch ,a preliminary scheme of risk stratification was established and experimentally verified .Results No significant difference existed in HLA serological mismatch between de novo DSA and DSA negative groups (10 .40 vs 8 .94 ,P=0 .1224) while there was a significant difference in eplet mismatch (100 .60 vs 70 .37 , P< 0 .0001 ) . The risk stratification scheme based upon HLA serological mismatch could not differentiate de novo DSA-free rates between low/medium/high-risk groups (100% vs 94 .74% vs 90 .41% , P=0 .4485 , P=0 .4506 , P=0 .2060 ) .Instead the novel scheme based upon eplet mismatch revealed significant difference in the prevalence of de novo DSA between low /medium/high-risk groups (100% vs 91 .04% vs 66 .67% ,P=0 .0001 ,P=0 .0001 ,P<0 .0001) .Conclusions As a better tool of predicting de novo DSA ,Eplet match is vital for the risk stratification scheme of de novo DSA .
9.Impact of the electroacupuncture treatment in Jiao's scalp acupuncture balance area combined with rehabilitation on the walking ability of patients with stroke
Min ZHU ; Jiamei CHU ; Youhua ZENG
China Modern Doctor 2019;57(10):139-142
Objective To investigate the impact of the electroacupuncture treatment in Jiao's scalp acupuncture balance area on the walking ability of patients with stroke. Methods The stroke patients who met the inclusion criteria were randomly divided into the control group (ordinary acupuncture group) and the treatment group (Jiao's scalp group). The two groups were scored before treatment, after 1 course of treatment and 2 courses of treatment, by using Fugl-Meyer lower limb score, Berg balance score and Holden walking grading. Results After 1 course of treatment, the Fugl-Meyer, Berg, and Holden walking grading of the two groups were higher than those before treatment (P<0.01). The Fugl-Meyer, Berg, and Holden walking grading of the treatment group were better than those of the control group, and the difference was significant (P<0.01). The Fugl-Meyer, Berg, Holden walking grading of the two groups after treatment for 2 courses were significantly higher than those before treatment and after 1 course of treatment (P<0.01). There was no difference between the two groups (P>0.05). Conclusion Electroacupuncture treatment of Jiao's scalp balance area can effectively improve the balance of stroke patients, increase the ability of lower limbs to improve walking function, reduce the risk of falls.
10.Non-alcoholic fatty liver disease of liver stagnation and spleen deficiency pattern treated with acupoint embedding therapy: a randomized controlled trial.
Zhen HUANG ; Shuanglin SONG ; Keping TAN ; Jiamei CHU ; Xiaoying ZHU ; Youhua ZENG
Chinese Acupuncture & Moxibustion 2016;36(2):119-123
OBJECTIVETo compare the difference between the acupoint embedding therapy and polyene phosphatidylcholine capsules in the clinical efficacy on non-alcoholic fatty liver disease (NAFLD) of liver stagnation and spleen deficiency pattern.
METHODSThe multi-center clinical trial was adopted and 180 cases of NAFLD of liver stagnation and spleen deficiency pattern were randomized into an embedding therapy group and a western medication group, 90 cases in each one. On the basis of general treatment such as diet control and proper physical exercise, in the embedding therapy group, the acupoint embedding therapy was applied to Ganshu (BL 18), Tai-chong (LR 3), Fenglong (ST 40), Zusanli (ST 36) and Sanyinjiao (SP 6), once every 7 days; in the western medication group, polyene phosphatidylcholine capsules (essentiale) were prescribed, 228 mg/capsule, 2 capsules each time, three times a day. In 6 months of treatment, TCM syndrome score, liver enzymology, blood lipid and abdomen B-ultrasound examination were observed and compared before and after treatment between the two groups.
RESULTS(1) For TCM syndrome score, the total score in the embedding therapy group was lower significantly than that in the western medication group (P<0. 05); (2) For liver enzymology and blood lipid, the levels of serum alanine transarninase (ALT), serum glutamic oxalacetic transaminase (AST), total cholesterol (TC) and triacylglycerol (TG) in the embedding therapy group were reduced significantly as compared with those in the western medication group (all P<0. 05); (3) For abdomen B-ultrasound examination, the fatty liver degree in the embedding therapy group was relieved significantly as compared with that in the western medication group (P< 0. 05); (4) For clinical efficacy, the total effective rate was 89. 8%o (79/88) in the embedding therapy group, higher significantly than 76. 7% (69/90) in the western medication group(P<0. 05).
CONCLUSIONThe acupoint embedding therapy achieves the definite efficacy on NAFLD of liver stagnation and spleen deficiency pattern, better than polyene phosphatidylcholine capsules.
Acupuncture Points ; Acupuncture Therapy ; Adult ; Catgut ; utilization ; Female ; Humans ; Liver ; physiopathology ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; physiopathology ; therapy ; Spleen ; physiopathology ; Treatment Outcome ; Young Adult

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