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.

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.

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.

The impact of deceased versus living donor graft status on kidney transplant outcomes:A Johannesburg single-center 48 years experience of 1685 patients

Background This study is aimed to determine the impact of living donor(LD)versus deceased donor(DD)kidney transplantation on renal graft survival and patient overall survival rates within Johannesburg,South Africa.Materials and methods A retrospective assessment was conducted of all 1685 adult first kidney-alone kidney transplant recipients transplanted between the years 1966 and 2013 in a single center.The patients were divided according to the source of the transplant:LD versus DD.Demographics and post-transplantation follow-up data were determined and tabulated.Graft and overall survival plots were generated.Results Of the recipients enrolled,84.1%were DD recipients and 15.9%were LD recipients.Living donor recipient status was significantly associated with younger age(p≤0.0001),a higher proportion of white,Asian,or mixed race compared to black race(p≤000.1),a higher proportion of urologic etiology of disease(p=0.015),and a lower proportion with hypertension(p≤0.0001)as the cause of end stage kidney disease.Results showed a decreased risk of graft failure(hazard ratio,0.55;95%confidence interval,0.45–0.66)and a decreased risk of death(hazard ratio,0.47;95%confidence interval,0.36–0.61)among LD graft recipients as compared to DD graft recipients.Conclusions In keeping with internationally reported trends,LD recipients continue to have enhanced patient and graft survival outcomes as compared to DD recipients within our local experience.This Johannesburg experience will serve as a foundation for future related studies in this region of the world.

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.

Exocrine drainage in pancreas transplantation:Complications and management

The aim of this minireview is to compare various pancreas transplantation exocrine drainage techniques i.e.,bladder vs enteric.Both techniques have different difficulties and complications.Numerous comparisons have been made in the literature between exocrine drainage techniques throughout the history of pancreas transplantation,detailing complications and their impact on graft and patient survival.Specific emphasis has been made on the early postoperative management of these complications and the related surgical infections and their consequences.In light of the results,a number of bladder-drained pancreas grafts required conversion to enteric drainage.As a result of technical improvements,outcomes of the varied enteric exocrine drainage techniques(duodenojejunostomy,duodenoduodenostomy or gastric drainage)have also been discussed i.e.,assessing specific risks vs benefits.Pancreatic exocrine secretions can be drained to the urinary or intestinal tracts.Until the late 1990s the bladder drainage technique was used in the majority of transplant centers due to ease of monitoring urine amylase and lipase levels for evaluation of possible rejection.Moreover,bladder drainage was associated at that time with fewer surgical complications,which in contrast to enteric drainage,could be managed with conservative therapies.Nowadays,the most commonly used technique for proper driving of exocrine pancreatic secretions is enteric drainage due to the high rate of urological and metabolic complications associated with bladder drainage.Of note,10%to 40%of bladder-drained pancreata eventually required enteric conversion at no detriment to overall graft survival.Various surgical techniques were originally described using the small bowel for enteric anastomosis with Roux-en-Y loop or a direct side-to-side anastomosis.Despite the improvements in surgery,enteric drainage complication rates ranging from 2%-20%have been reported.Treatment depends on the presence of any associated complications and the condition of the patient.Intra-abdominal infection represents a potentially very serious problem.Up to 30%of deep wound infections are associated with an anastomotic leak.They can lead not only to high rates of graft loss,but also to substantial mortality.New modifications of established techniques are being developed,such as gastric or duodenal exocrine drainage.Duodenoduodenostomy is an interesting option,in which the pancreas is placed behind the right colon and is oriented cephalad.The main concern of this technique is the challenge of repairing the native duodenum when allograft pancreatectomy is necessary.Identification and prevention of technical failure remains the main objective for pancreas transplantation surgeons.In conclusion,despite numerous techniques to minimize exocrine pancreatic drainage complications e.g.,leakage and infection,no universal technique has been standardized.A prospective study/registry analysis may resolve this.

Pretransplantation fetal-maternal microchimerism in pediatric liver transplantation from mother

AIM To investigate the rates of pretransplantation fetalmaternal microchimerism(MC) and its effect on rejection in children receiving maternal liver grafts. METHODS DNA or blood samples before liver transplantation(LT) were available in 45 pediatric patients and their mothers. The presence of pretransplantation MC to non-inherited maternal antigens(NIMAs)(NIMA-MC) in the peripheral blood was tested using nested PCRsingle-strand conformation polymorphism analysis for the human leukocyte antigen(HLA)-DRB1 alleles. NIMA-MC was successfully evaluated in 26 of the 45 children. Among these 45 pediatric LT recipients,23 children(51.1%) received transplants from maternal donors and the other 22 from non-maternal donors.RESULTS Among these 26 children,pretransplantation NIMAMC was detected in 23.1%(n = 6),6.1(range,0.8-14) years after birth. Among the children with a maternal donor,the rate of biopsy-proven cellular rejection(BPCR) was 0% in patients with NIMA-MC positivity(0/3) and those with HLA-DR identity with the mother(0/4),but it was 50% in those with NIMA-MC negativity(5/10). Patients with NIMA-MC positivity or HLA-DR identity with the mother showed significantly lower BPCR rate compared with NIMA-MC-negative patients(0% vs 50%,P = 0.04). NIMA-MC-positive patients tended to show lower BPCR rate compared with NIMAMC-negative patients(P = 0.23). CONCLUSION The presence of pretransplantation NIMA-MC or HLADR identity with the mother could be associated with BPCR-free survival in pediatric recipients of LT from maternal donors.

Role of novel biomarkers in kidney transplantation

Clinical application of biomarkers is an integral component of transplant care.Clinicians and scientists alike are in search of better biomarkers than the current serologic(serum creatinine,donor-specific antibodies),urine-derived(urinalysis,urine protein),and histologic ones we now use.The science behind recent biomarker discovery spans across multiple molecular biologic disciplines,including transcriptomics,proteomics,and metabolomics.Innovative methodology and integration of basic and clinical approaches have allowed researchers to unearth molecular phenomena preceding clinical disease.Biomarkers can be classified in several ways.In this review,we have classified them via their origin and outcome:Primarily immunologic,i.e.,representative of immune regulation and dysfunction and non-immunologic,pertaining to delayed graft function,cardiovascular events/mortality,infection,malignancy,posttransplant diabetes,graft,and patient survival.Novel biomarker uses to guide the diagnosis and management of transplant-related outcomes is a promising area of research.However,the use of biomarkers to predict outcomes after kidney transplantation is not well studied.In this review,we summarize the recent studies illustrating biomarker use and transplant outcomes.

Analysis of hepatitis C virus-positive organs in liver transplantation

The authors of this study note that in liver transplantation(LT),the survival rates of hepatitis C virus(HCV)-positive donors and HCV-negative receivers are compa-rable to those of HCV-negative donors and recipients.Direct-acting antiviral(DAA)therapies have nearly 100%effectiveness in treating HCV.Between 2006 and 2016,the percentages of HCV-positive patients on the waiting list and HCVpositive LT recipients fell by 8.2 percent and 7.6 percent,respectively.Records from April 1,2014,in which the donor and receiver were both at least 18 years old and had a positive HCV status,were the only ones eligible for the study.The analysis for this study was restricted to the first transplant recorded for each patient using a data element that documented the number of prior transplants for each recipient,although some recipients appeared multiple times in the data set.HCV-positive recipients or people with fulminant hepatic failure were the main beneficiaries of primary biliary cirrhosis among HCV-positive donors.However,there is still a reticence to use HCV-positive donor organs in HCV recipients due to clinical and ethical considerations.Similar survival rates between HCV-positive donors and recipients and HCV-negative donors and receivers illustrate the efficacy of these DAA regimens.

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.