Fortuitous benefits of activity-based rehabilitation in stem cell-based therapy for spinal cord repair: enhancing graft survival

Traumatic injuries to spinal cord elicit diverse signaling pathways leading to unselective and complex pathological outcomes：death of multiple classes of neural cells,formation of cystic cavities and glial scars,disruption of axonal connections,and demyelination of spared axons,all of which can contribute more or less to debilitating functional impairments found in patients with spinal cord injury.

Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival

BACKGROUND The lack of space,as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms,remains controversial.AIM To evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease.METHODS One hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without(kidney transplant alone(KTA)group)and 77 with associated ipsilateral nephrectomy(KTIN group),were retrospectively reviewed.Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival.RESULTS Creation of space for future graft positioning was the main reason(n=74,96.1%)for associated ipsilateral nephrectomy.No significant difference in surgical comorbidity(lymphocele,wound infection,incisional hernia,wound hematoma,urinary infection,need for blood transfusion,hospitalization stay,Dindo Clavien classification and readmission rate)was observed between the two study groups.The incidence of primary nonfunction and delayed graft function was comparable in both groups[0%and 2.6%(P=0.497)and 9.1%and 16.9%(P=0.230),respectively,in the KTA and KTIN group].The 1-and 5-year graft survival were 94.8%and 90.3%,and 100%and 93.8%,respectively,in the KTA and KTIN group(P=0.774).The 1-and 5-year patient survival were 96.1%and 92.9%,and 100%and 100%,respectively,in the KTA and KTIN group(P=0.168).CONCLUSION Simultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short-and long-term graft survival.

Evaluation of corneal graft survival in mice model

AIMTo investigate the characteristics and criterion of graft rejection in mice model.

Evaluation of corneal graft survival in mice model

·AIM: To investigate the characteristics and criterion of graft rejection in mice model. ·METHODS: C57BL/6 or BALB/c mice corneal grafts were grafted onto BALB/c hosts. Each group was divided into two subgroups according to the corneal opacity scores 12d after transplantation. The characteristics of opacity and neovascularization were observed. Mice of the 12 th , 50 th day after transplantation, the grafts biopsy of mice in allogeneic group 1, which opacity score exceed 3, were prepared for histological observation and those restore transparent were endothelial stained. ·RESULTS: There was no difference of corneal opacity score on the 7 th and 12 th day after operation; the histological results had no disparity between syngeneic group and allogeneic group. On the 12 th day after surgery, the turbidity curve was apparent in grafts with opacity score 【2. Mononuclear cells were shown in grafts with opacity score reached 3 in allogeneic group 1. Different rejection performance was observed in tissue sections on the 50 th day after surgery. ·CONCLUSION: Grafts, opacity score exceeds 3 from the 7 th to the 12 th day after operation could not be judged as a rejection. We should pay more attention to the variation of grafts opacity since 12d after corneal transplantation.·

Role of the postoperative cholesterol in early allograft dysfunction and survival after living donor liver transplantation

BACKGROUND:Many studies have confirmed that serum total cholesterol(sTC) concentrations were associated with underlying liver damage and the synthesis capacity of liver.However, the role of postoperative sTC level on evaluating graft function and predicting survival of recipients who underwent liver transplantation has not been discussed.METHODS:Clinical data of 231 living donor liver transplantation recipients from May 2003 to January 2015 were retrospectively collected. Patients were stratified into the low sTC group(sTC <1.42 mmol/L, 57 recipients) and high sTC group(sTC ≥1.42 mmol/L, 174 recipients) according the sTC level on postoperative day 3 based on receiver-operating characteristic curve analysis. The clinical characteristics and postoperative short-and long-term outcomes were compared between the two groups.RESULTS:Recipients with sTC <1.42 mmol/L experienced more severe preoperative disease conditions, a higher incidence of postoperative early allograft dysfunction(38.6% vs 10.3%, P<0.001), 90-day mortality(28.1% vs 10.9%, P=0.002)and severe complications(29.8% vs 17.2%, P=0.041) compared to recipients with sTC ≥1.42 mmol/L. The multivariate analysis demonstrated that sT C <1.42 mmol/L had a 4.08-fold(95% CI:1.83-9.11, P=0.001) and 2.72-fold(95% CI:1.23-6.00,P=0.013) greater risk of developing allograft dysfunction and 90-day mortality, and patients with sTC <1.42 mmol/L had poorer overall recipient and graft survival rates at 1-, 3-, and 5-year than those with sTC ≥1.42 mmol/L(67%, 61% and 61% vs 83%, 71% and 69%, P=0.025; 65%, 59% and 59% vs 81%,68% and 66%, P=0.026, respectively). Cox multivariate anal-ysis showed that sTC <1.42 mmol/L was an independent predicting factor for total recipient survival(HR=2.043; 95% CI:1.173-3.560; P=0.012) and graft survival(HR=1.905; 95% CI:1.115-3.255; P=0.018).CONCLUSIONS:sTC <1.42 mmol/L on postoperative day 3 was an independent risk factor of postoperative early allograft dysfunction, 90-day mortality, recipient and graft survival, which can be used as a marker for predicting postoperative short-and long-term outcomes.

Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study

BACKGROUND Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation.AIM To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients,mainly early allograft dysfunction.METHODS This multicenter retrospective study included brain-dead donors and adult liver graft recipients.Donor-recipient matching was obtained through a crossover list.Clinical and laboratory data were recorded for both donors and recipients.Donor hepatectomy,cold ischemia,and warm ischemia times were recorded.Primary outcome was early allograft dysfunction.Secondary outcomes included need for retransplantation,length of intensive care unit and hospital stay,and patient and graft survival at 12 months.RESULTS From January 2019 to December 2021,a total of 243 patients underwent a liver transplant from a brain-dead donor.Of these,57(25%)developed early allograft dysfunction.The median donor hepatectomy time was 29(23–40)min.Patients with early allograft dysfunction had a median hepatectomy time of 25(22–38)min,whereas those without it had a median time of 30(24–40)min(P=0.126).CONCLUSION Donor hepatectomy time was not associated with early allograft dysfunction,graft survival,or patient survival following liver transplantation.

Predicting outcomes after kidney transplantation: Can Pareto’s rules help us to do so?

Kidney transplantation is the best option for kidney replacement therapy,even considering that most of the times the grafts do not survive as long as their recipients.In the Khalil et al's experience,published in this issue of the Journal,they analyze their second kidney graft survival and describe those significant predictors of early loss.This editorial comments on the results and put in perspective that most of the times,long-term graft survival could be inadvertently jeopardized if the immunosuppressive therapy is reduced or withdrawn for any reason,and that it could happen frequently if the transplant physician intends to innovate with the clinical care without proper evidence-based data.

Porcine vesical acellular matrix graft of tunica albuginea for penile reconstruction

Aim： To characterize the feasibility of the surgical replacement of the penile tunica albuginea （TA） and to evaluate the value of a porcine bladder acellular matrix （BAM） graft. Methods： Acellular matrices were constructed from pigs＇ bladders by cell lysis, and then examined by scanning electron microscopy （SEM）. Expression levels of the mRNA of the vascular endothelial growth factor （VEGF） receptor, fibroblast growth factor （FGF）-1 receptor, neuregulin, and brain-derived neurotrophic factor （BDNF） in the acellular matrix and submucosa of the pigs＇ bladders were determined through the reverse transcription-polymerase chain reaction （PCR）. A 5 mm× 5 mm square was excised from the penile TA of nine rabbits. The defective TA was then covered in porcine BAM. Equal numbers of animals were sacrificed and histochemically examined at 2, 4 and 6 months after implantation. Results： SEM of the BAM showed collagen fibers with many pores. VEGF receptor, FGF-1 receptor and neuregulin mRNA were expressed in the porcine BAM; BDNF mRNA was not detected. Two months after implantation, the graft sites exhibited excellent healing without contracture, and the fusion between the graft and the neighboring normal TA appeared to be well established. There were no significant histological differences between the implanted tunica and the normal control tunica at 6 months after implantation. Conclusion： The porcine BAM graft resulted in a structure which was sufficiently like that of the normal TA. This implantation might be considered applicable to the reconstruction of the TA in conditions such as trauma or Peyronie＇s disease.

Effect of airplane transport of donor livers on post-liver transplantation survival

AIM To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. METHODS A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression.RESULTS One hundred and ninety-three patients received alocal donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase(mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index(mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic time(CIT)(mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation between CIT and transport distance(r2 = 0.29, P < 0.001). Mean follow up was six years and 93 patients had graft failure. Multivariate analysis found only airplane transport retained significance for graft loss(HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver(P = 0.027). CONCLUSION Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.

Role of biliary complications in chronic graft rejection after living donor liver transplantation

Postoperative biliary complications remain a substantial challenge after living donor liver transplantation,especially due to its heterogeneous clinical presentation.

Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation

Tacrolimus(Tac)is currently the most common calcineurin-inhibitor employed in solid organ transplantation.High intra-patient variability(IPV)of Tac(Tac IPV)has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation.Few data are available concerning the impact of high Tac IPV in non-kidney transplants.However,even in kidney transplantation,there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival.This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature.Little is also known about the influence of high Tac IPV in the development of other untoward adverse events,update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney,liver,heart,lung,and pancreas tran-splantation to better evaluate its use in clinical practice.

Diabetes mellitus is not associated with worse short term outcome in patients older than 65 years old post-liver transplantation

BACKGROUND Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation(LT).Hence,more patients with diabetes mellitus(DM)are undergoing LT,especially,above the age of 65.AIM To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of 65.METHODS We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical record.We assessed the impact of DM on short-term outcomes,one-year,post-LT based on the following variables:Survival at one year;acute cellular rejection(ACR)rates;intensive care unit(ICU)and hospital length of stay;and readmissions.RESULTS Total of 148 patients who are 65 year or older underwent LT during the study period.The mean age is 68.5±3.3 years and 67.6%were male.The median Model for End-stage Liver Disease score at time of transplantation was 22(6-39),39%of patients had hepatocellular carcinoma and 77.7%underwent living donor LT.The one-year survival was similar between DM patients and others,91%.ACR occurred in 13.5%of patients(P=0.902).The median ICU stay is 4.5-day P=0.023.The rates of ICU and 90-d readmission were similar(P=0.821)and(P=0.194),respectively.CONCLUSION The short-term outcome of elderly diabetic patients undergoing LT is similar to others.The presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.

Outcome of split liver transplantation vs living donor liver transplantation:A systematic review and meta-analysis

BACKGROUND The outcomes of liver transplantation(LT)from different grafts have been studied individually and in combination,but the reports were conflicting with some researchers finding no difference in both short-term and long-term outcomes between the deceased donor split LT(DD-SLT)and living donor LT(LDLT).AIM To compare the outcomes of DD-SLT and LDLT we performed this systematic review and meta-analysis.METHODS This systematic review was performed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.The following databases were searched for articles comparing outcomes of DD-SLT and LDLT:PubMed;Google Scholar;Embase;Cochrane Central Register of Controlled Trials;the Cochrane Database of Systematic Reviews;and Reference Citation Analysis(https://www.referencecitationanalysis.com/).The search terms used were:“liver transplantation;”“liver transplant;”“split liver transplant;”“living donor liver transplant;”“partial liver transplant;”“partial liver graft;”“ex vivo splitting;”and“in vivo splitting.”RESULTS Ten studies were included for the data synthesis and meta-analysis.There were a total of 4836 patients.The overall survival rate at 1 year,3 years and 5 years was superior in patients that received LDLT compared to DD-SLT.At 1 year,the hazard ratios was 1.44(95%confidence interval:1.16-1.78;P=0.001).The graft survival rate at 3 years and 5 years was superior in the LDLT group(3 year hazard ratio:1.28;95%confidence interval:1.01-1.63;P=0.04).CONCLUSION This meta-analysis showed that LDLT has better graft survival and overall survival when compared to DD-SLT.

Is peri-transplant blood transfusion associated with worse transplant outcomes?A retrospective study

BACKGROUND Blood transfusion is common during the peri-transplantation period.The incidence of immunological reactions to blood transfusion after kidney transplantation and their consequences on graft outcomes have not been extensively studied.AIM To examine the risk of graft rejection and loss in patients who received blood transfusion in the immediate peri-transplantation period.METHODS We conducted a single-center retrospective cohort study of 105 kidney recipients,among them 54 patients received leukodepleted blood transfusion at our center between January 2017 and March 2020.RESULTS This study included 105 kidney recipients,of which 80%kidneys were from living-related donors,14%from living-unrelated donors,and 6%from deceased donors.Living-related donors were mostly first-degree relatives(74.5%),while the rest were second-degree relatives.The patients were divided into transfusion(n=54)and non-transfusion(n=51)groups.The average hemoglobin level at which blood transfusion was commenced was 7.4±0.9 mg/dL.There were no differences between the groups in terms of rejection rates,graft loss,or death.During the study period,there was no significant difference in creatinine level progression between the two groups.Delayed graft function was higher in the transfusion group;however,this finding was not statistically significant.A high number of transfused packed red blood cells was significantly associated with increased creatinine levels at the end of the study.CONCLUSION Leukodepleted blood transfusion was not associated with a higher risk of rejection,graft loss,or death in kidney transplant recipients.

Outcome of Renal Transplantation at Ahmed Gasim Cardiac and Renal Transplant Centre in Sudan-2014

Background: Although not life-saving procedures like liver or heart transplantation, renal transplantation is the preferred treatment for many patients with end-stage renal disease because it improves patients’ quality of life, while other forms of renal replacement therapy (RRT) such as haemodialysis (HDX) shown to regain only 10% of the patient’s renal function [1]. Transplantation releases patients from the dietary and fluid restrictions and the physical constraints imposed by other forms of (RRT), patients become able to return to their normal activities. Patient’s 5-year survival is higher post transplant. Patients and methods: This is Descriptive, retro-prospective, cross sectional analytic and multicentre study done in Ahmed Gasim Cardiac and Renal Transplant Centre including 105 patients. After meeting the Inclusion Criteria and exclusion Criteria, then cases were selected and written in constructed questionnaire. The aim of the study was to evaluate the outcome of renal transplantation in Sudan. Results: 105 cases were used with male predominate and ratio male to female ratio 3:1, the main age of presentation between 31 - 45 years, most of the patients discharge uneventful with good outcome. During one-year follow-up following renal transplantation. Patient survival 95.2 % graft survival 82.4%. Overall morbidity shows 70.5%. Conclusion: this study showed that the one-year patient survival of 95.2%. Actuarial one-year graft survival of 92.4%. Renal transplantation complications can be reduced by meticulous preoperative workup including good cardiovascular assessment, tissue mismatch and BMI good postoperative follow up for early detection of graft rejection and long-term complications and finally patient education.

L-GrAFT_(7) has High Accuracy in Predicting Early Allograft Failure after Liver Transplantation: A Multicenter Cohort Study in China

Background and Aims:Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation.However,consensus of definition of early allograft failure is lacking.Methods:A retrospective,multicenter study was performed to validate the Liver Graft Assessment Following Transplantation(L-GrAFT)risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers.L-GrAFT(L-GrAFT7 and L-GrAFT10)was compared with existing models:the Early Allograft Failure Simplified Estimation(EASE)score,the model of early allograft function(MEAF),and the Early Allograft Dysfunction(EAD)model.Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group.Results:L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival,significantly superior to MEAF[area under the curve(AUC=0.78,p=0.044)]and EAD(AUC=0.78,p=0.006),while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE(AUC=0.84,p>0.05).Furthermore,L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index(DRI)cases(AUC=0.83 vs.MEAF,p=0.007 vs.EAD,p=0.014)and recipients of donors after cardiac death(AUC=0.92 vs.EAD,p<0.001).Through multivariate analysis,pretransplant bilirubin level,units of packed red blood cells,and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group.Conclusions:The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort,indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

Transplantation of human hepatocytes into tolerized genetically immunocompetent rats

AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.

Compared efficacy of preservation solutions on the outcome of liver transplantation:Meta-analysis

AIM To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.METHODS A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31^(st), 2017. The inclusion criteria were comparative, randomized controlled trials(RCTs) for deceased donor liver(DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin(UW) solution or histidinetryptophan-ketoglutarate(HTK), Celsior(CS) and Institut Georges Lopez(IGL-1) solutions. Fifteen RCTs(1830 livers) were included; the primary outcomes were primary non-function(PNF) and one-year posttransplant graft survival(OGS-1). RESULTS All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1(RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1(RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.CONCLUSION Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.

Kidney donation after cardiac death

There is continuing disparity between demand for and supply of kidneys for transplantation. This review describes the current state of kidney donation after cardiac death （DCD） and provides recommendations for a way forward. The conversion rate for potential DCD donors varies from 40%-80%. Compared to con-trolled DCD, uncontrolled DCD is more labour intensive, has a lower conversion rate and a higher discard rate. The super-rapid laparotomy technique involving direct aortic cannulation is preferred over in situ perfusion in controlled DCD donation and is associated with lower kidney discard rates, shorter warm ischaemia times and higher graft survival rates. DCD kidneys showed a 5.73-fold increase in the incidence of delayed graft function （DGF） and a higher primary non function rate compared to donation after brain death kidneys, but the long term graft function is equivalent between the two. The cold ischaemia time is a controllable factor that signifcantly infuences the outcome of allografts, for example, limiting it to 〈 12 h markedly reduces DGF. DCD kidneys from donors 〈 50 function like stan-dard criteria kidneys and should be viewed as such. As the majority of DCD kidneys are from controlled dona-tion, incorporation of uncontrolled donation will expand the donor pool. Efforts to maximise the supply of kid-neys from DCD include： implementing organ recovery from emergency department setting; improving family consent rate; utilising technological developments to optimise organs either prior to recovery from donors or during storage; improving organ allocation to ensure best utility; and improving viability testing to reduce primary non function.

Kidney transplantation from donors with hepatitis C infection

The increasing demand for organ donors to supply the increasing number of patients on kidney waiting lists has led to most transplant centers developing protocols that allow safe utilization from donors with special clinical situations which previously were regarded as contraindications. Deceased donors with previous hepatitis C infection may represent a safe resource to expand the donor pool. When allocated to serology-matched recipients, kidney transplantation from donors with hepatitis C may result in an excellent short-term outcome and a significant reduction of time on the waiting list. Special care must be dedicated to the pre-transplant evaluation of potential candidates, particularly with regard to liver functionality and evidence of liver histological damage, such as cirrhosis, that could be a contraindication to transplantation. Pre-transplant antiviral therapy could be useful to reduce the viral load and to improve the long-term results, which may be affected by the progression of liver disease in the recipients. An accurate selection of both donor and recipient is mandatory to achieve a satisfactory long-term outcome.