Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipien...Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.展开更多
Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical...Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.展开更多
Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripher...Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.展开更多
BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for ...BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results.AIM To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results.METHODS This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of Transplantation and Radiology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from August 2022 to February 2023.All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this study.SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility.RESULTS The mean age of all patients was 35.32±11.08 years.Among these,126(81.8%)were males and 28(18.2%)were females.The mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 m2.Kidney allograft biopsy results showed chronic changes in 55(37.66%)biopsies.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage.It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.展开更多
BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise cr...BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.展开更多
BACKGROUND Fibrous dysplasia is a congenital disorder in which normal bone is replaced by fibro-osseous tissue or irregular trabeculae of woven bone intermixed with mature collagenous tissue.A single or multiple bones...BACKGROUND Fibrous dysplasia is a congenital disorder in which normal bone is replaced by fibro-osseous tissue or irregular trabeculae of woven bone intermixed with mature collagenous tissue.A single or multiple bones are affected.This rare bone disorder has three clinical patterns including monostotic,polyostotic,and that associated with McCune-Albright syndrome.Most studies report primary fibrous dysplasia.However,a few cases of recurrent monostotic fibular fibrous dysplasia have been reported.Here,we report a therapeutic strategy for recurrent fibular fibrous dysplasia.CASE SUMMARY A 4-year-old boy was admitted for persistent pain in the left lower limb and abnormal gait over the previous 9 mo.He had no history of present or past illness.Preoperative imaging data showed erosion-like changes with bone expansion of the left middle and lower fibular segment.Tumor tissue in the fibular bone marrow cavity was removed by curettage,and rapid intraoperative pathological examination suggested fibular fibrous dysplasia.An allograft was implanted into the fibular medullary cavity.However,he was readmitted with clinical symptoms including persistent pain,abnormal gait,and local swelling at the age of 6 years.He was diagnosed with recurrent fibular fibrous dysplasia based on the second medical examination.He underwent fibular bone tumor radical resection and longus fibular allograft transplantation combined with fibular bone locking plate and screws.Good host bone to allogenic bone graft fusion was observed by the physician on postoperative regular follow-up.CONCLUSION Radical resection of fibrous dysplasia and longus fibula allograft combined with internal fixation for reconstruction are suitable for the treatment of recurrent monostotic fibular fibrous dysplasia.展开更多
The second half of the previous century witnessed a tremendous rise in the number of clinical kidney transplants worldwide.This activity was,however,accompanied by many issues and challenges.An accurate diagnosis and ...The second half of the previous century witnessed a tremendous rise in the number of clinical kidney transplants worldwide.This activity was,however,accompanied by many issues and challenges.An accurate diagnosis and appropriate management of causes of graft dysfunction were and still are,a big challenge.Kidney allograft biopsy played a vital role in addressing the above challenge.However,its interpretation was not standardized for many years until,in 1991,the Banff process was started to fill this void.Thereafter,regular Banff meetings took place every 2 years for the past 30 years.Marked changes have taken place in the interpretation of kidney allograft biopsies,diagnosis,and classification of rejection and other non-rejection pathologies from the original Banff 93 classification.This review attempts to summarize those changes for increasing the awareness and understanding of kidney allograft pathology through the eyes of the Banff process.It will interest the transplant surgeons,physicians,pathologists,and allied professionals associated with the care of kidney transplant patients.展开更多
Renal transplantation is the treatment of choice for end stage kidney disease.However,despite all the efforts to expand the donor pool,the shortage of donors is increasing and as a consequence,there has been a signifi...Renal transplantation is the treatment of choice for end stage kidney disease.However,despite all the efforts to expand the donor pool,the shortage of donors is increasing and as a consequence,there has been a significant increase in the number of patients on transplant waiting lists globally.Societies worldwide have employed different methods to address this,each with specific ethical concerns surrounding them.Over three decades ago,a governmentally regulated program of kidney transplantation from living unrelated donors was introduced in Iran and since practiced which has been the subject of hot debate in the literature.Nevertheless,despite all these extensive discussions and publications,several key aspects of the program have still not been properly elucidated and addressed.In this article,the author aims to illuminate some dark corners related to this issue that have largely escaped the notice of ethicists.展开更多
Currently,the most feasible and widely practiced option for patients with endstage organ failure is the transplantation of part of or whole organs,either from deceased or living donors.However,organ shortage has posed...Currently,the most feasible and widely practiced option for patients with endstage organ failure is the transplantation of part of or whole organs,either from deceased or living donors.However,organ shortage has posed and is still posing a big challenge in this field.Newer options being explored are xenografts and engineered/bioengineered tissues/organs.Already small steps have been taken in this direction and sooner or later,these will become a norm in this field.However,these developments will pose different challenges for the diagnosis and management of problems as compared with traditional allografts.The approach to pathologic diagnosis of dysfunction in these settings will likely be significantly different.Thus,there is a need to increase awareness and prepare transplant diagnosticians to meet this future challenge in the field of xenotransplantation/regenerative medicine.This review will focus on the current status of transplant pathology and how it will be changed in the future with the emerging scenario of routine xenotransplantation.展开更多
BACKGROUND Exosomes are 30-150 nm nanovesicles with sophisticated nucleic acids cargo,actively secreted by all cells within human body,and found in abundance in all body fluids,including urine.These extracellular vesi...BACKGROUND Exosomes are 30-150 nm nanovesicles with sophisticated nucleic acids cargo,actively secreted by all cells within human body,and found in abundance in all body fluids,including urine.These extracellular vesicles have tremendous potential for next generation diagnostics,theoretically enabling noninvasive assessment of organ and tissue function via liquid biopsy analysis.AIM Recently,feasibility of an exosomal molecular test was demonstrated for postorgan transplant monitoring:Analysis of urine-derived exosomal mRNA cargo allowed early detection of kidney allograft rejection.Here,we further studied urine-derived exosomes and their mRNA content as a highly promising diagnostic modality.This included stability studies of urine samples and exosomal mRNA upon transportation from the point of collection to a centralized testing facility,short-term storage of urine at different conditions upon receipt till the point molecular assay is performed,and effects of various potentially interfering substances on the downstream quantitative polymerase chain reaction(qPCR)assay.METHODS The urine specimens were stored at various conditions and pre-processed in different ways.Next,samples were passed through the columns to capture all extracellular vesicles,the vesicles were lysed to release their content and the exosomal RNA was purified on the mini-columns,reverse transcription was performed,next pre-amplification,followed by a qPCR analysis for a panel of RESULTS To ensure exosomal RNA integrity,the harvested urine specimens should be shipped refrigerated,by overnight delivery.Urine can next be stored at the test site for up to 1 wk at 4°C,and long term should be frozen at-80°C.Urine specimens must be centrifuge at low G-force to deplete cells and debris,to ensure consistent top results in downstream molecular assays.All commonly used medications(tacrolimus,cyclosporin A,mycophenolic acid,everolimus,sirolimus,ascomycin,teriflunomide)were tested and confirmed that they do not cause assay interference.CONCLUSION mRNA from urine-derived exosomes was shown to be stable across a broad range of conditions and produced accurate results when analyzed via qPCR assay for detection of kidney allograft rejection.We identified the most optimal conditions for every step of the process,ensuring pre-analytical sample integrity and robust qPCR results.展开更多
Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment ...Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes:Bronchiolitis obliterans syndrome and restrictive allograft syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In this review,we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome,which have been elucidated from clinicopathological observations and animal experiments worldwide.展开更多
One of the most important functions of skins is to protect our bodies from microbes or pollutant sources. Skins containing physical substances serve as a physical barrier which protects our bodies from pathogens. A he...One of the most important functions of skins is to protect our bodies from microbes or pollutant sources. Skins containing physical substances serve as a physical barrier which protects our bodies from pathogens. A healthy skin contains a variety of antibacterial substances such as defensin, cathelicidin and psoriasin. However deep and wide burns cause the skin to lose its original functions, so our skins are exposed to various danger factors. For the burn patients, human alloskin graft serves as a very important temporary biological wound dressing. It protects the wound before autograft procedure, forms revascularization and granulation tissues and protects the wound from an invasion of microbes. This study was conducted with the aim to analyze the antimicrobial effect of cryopreserved allograft (CPA) and glycerol-preserved allograft (GPA) which was a type of allograft widely used for burn patients, and measure the difference in comparison with the fresh skin before processing it. The most common contaminants found in burn patients such as S. aureus, P. aeruginosa, C. albicans and E. coli, were used for experiment. The antimicrobial effect against S. aureus and E. coli was observed in fresh skin and some CPA. In some clinical cases, infection is frequently observed in the wounds treated with allograft, indicating the allograft completely block every kind of microbes. To prevent the infection, it is required to use antibiotics and manage wounds thoroughly.展开更多
Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues.Tissues like bone,skin,amniotic membrane and soft tissues obtained from human donor can be used for repa...Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues.Tissues like bone,skin,amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body.Allograft tissues from human donor provide an excellent alternative to autografts.However,major concern with the use of allografts is the risk of infectious disease transmission.Therefore,tissue allografts should be sterilized to make them safe for clinical use.Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues.This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts.展开更多
BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation...BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation after brain death(DBD) and donation after cardiac death(DCD) allograft recipients.METHODS:We reviewed our prospectively entered database for all DBD(n=377) and DCD(n=38) liver transplantations between January 1,2006 and October 30,2011.The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups.RESULTS:EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients,but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD(11.5%) compared with those without EAD(16.7%)(P=0.664) or in the rate of death in recipients with EAD(3.8%) compared with those without EAD(8.3%)(P=0.565).The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7(P=0.022).CONCLUSIONS:The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts.On initial assessment,it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts,however a study with a larger sample size of DCD allografts is needed to confirm these findings.The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure.An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.展开更多
Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation...Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging. Three days later, 1 mL ganglioside solution （1 g/L） was sub- cutaneously iniected into the right hind leg of rabbits. Compared with non-injected rats, muscle wet weight ratio was increased at 2-12 weeks after modeling. The quantity of myelinated fibers in regenerated sciatic nerve, myelin thickness and fiber diameter were elevated at 4-12 weeks after modeling. Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks, while conduction latencies were decreased at 12 weeks. Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopre- served peripheral nerve allografts.展开更多
BACKGROUND Early allograft dysfunction(EAD)after liver transplantation(LT)is an important cause of morbidity and mortality.To ensure adequate graft function,a critical hepatocellular mass is required in addition to an...BACKGROUND Early allograft dysfunction(EAD)after liver transplantation(LT)is an important cause of morbidity and mortality.To ensure adequate graft function,a critical hepatocellular mass is required in addition to an appropriate blood supply.We hypothesized that intraoperative measurement of portal venous and hepatic arterial flow may serve as a predictor in the diagnosis of EAD.AIM To study whether hepatic flow is an independent predictor of EAD following LT.METHODS This is an observational cohort study in a single institution.Hepatic arterial blood flow and portal venous blood flow were measured intraoperatively by transit flow.EAD was defined using the Olthoff criteria.Univariate and multivariate analyses were used to determine the intraoperative predictors of EAD.Survival analysis and prognostic factor analysis were performed using the Kaplan-Meier and Cox regression models.RESULTS A total of 195 liver transplant procedures were performed between January 2008 and December 2014 in 188 patients.A total of 54(27.7%)patients developed EAD.The median follow-up was 39 mo.Portal venous flow,hepatic arterial flow(HAF)and total hepatic arterial flow were associated with EAD in both the univariate and multivariate analyses.HAF is an independent prognostic factor for 30-d patient mortality.CONCLUSION Intraoperative measurement of blood flow after reperfusion appears to be a predictor of EAD;Moreover,HAF should be considered a predictor of 30-d patient mortality.展开更多
The pathophysiology of LaPeyronie＇s disease （PD） is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been valida...The pathophysiology of LaPeyronie＇s disease （PD） is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excisionwith subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat＇s tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograff, and both collagen-Ⅱ- and osteocalcin-positive cells were also noted. Tunica albuginea （TA） allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.展开更多
Acellular nerve ailograft preserves the basilar membrane tube and extracellular matrix, which promotes selective regeneration of neural defects via bridging. In the present study, a Sprague Dawley rat sciatic nerve wa...Acellular nerve ailograft preserves the basilar membrane tube and extracellular matrix, which promotes selective regeneration of neural defects via bridging. In the present study, a Sprague Dawley rat sciatic nerve was utilized to prepare acellular nerve allografts through the use of the chemical extraction method. Subsequently, the allograft was transplanted into a 10-mm sciatic nerve defect in Wistar rats, while autologous nerve grafts from Wistar rats served as controls. Compared with autologous nerve grafts, the acellular nerve allografts induced a greater number of degenerated nerve fibers from sural nerves, as well as a reduced misconnect rate in motor fibers, fewer acetylcholine esterase-positive sural nerves, and a greater number of carbonic anhydrase-positive sensory nerve fibers. Results demonstrated that the acellular nerve allograft exhibited significant neural selective regeneration in the process of bridging nerve defects.展开更多
The overall incidence of osteochondral defect in the general population is estimated to be 15 to 30 per100000 people.These lesions can become symptomatic causing pain,swelling and decreased function of the knee,and ma...The overall incidence of osteochondral defect in the general population is estimated to be 15 to 30 per100000 people.These lesions can become symptomatic causing pain,swelling and decreased function of the knee,and may eventually progress to osteoarthritis.In the young and active population,partial or total knee arthroplasty(TKA)is rarely the treatment of choice due to risk of early failure.Osteochondral allograft transplantation has been demonstrated to be a safe and effective treatment of large osteochondral and chondral defects of the knee in appropriately selected patients.The treatment reduces pain,improves function and is a viable limb salvage procedure for patients,especially young and active patients for whom TKA is not recommended.Either large dowels generated with commercially available equipment or free hand shell allografts can be implanted in more posterior lesions.Current recommendations for fresh allografts stored at4C advise implantation within 21-28 d of procurement for optimum chondrocyte viability,following screening and testing protocols.Higher rates of successful allograft transplantation are observed in younger patients,unipolar lesions,normal or corrected malalignment,and defects that are treated within 12 mo of symptom onset.Patients with bipolar lesions,uncorrectable malalignment,advanced osteoarthritis,and those over40 tend to have less favourable outcomes.展开更多
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 ...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.展开更多
基金supported by grants from the National Nat-ural Science Foundation of China (81570587 and 81700557)the Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (2013A061401007 and 2017B030314018)+3 种基金Guangdong Provincial Natural Science Funds for Major Basic Science Culture Project (2015A030308010)Science and Technology Program of Guangzhou (201704020150)the Natural Science Foundations of Guangdong province (2016A030310141 and 2020A1515010091)Young Teachers Training Project of Sun Yat-sen University (K0401068) and the Guangdong Science and Technology Innovation Strategy (pdjh2022b0010 and pdjh2023a0002)。
文摘Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.
基金supported by the National Natural Science Foundation of China(82200725)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202002)+4 种基金the Fundamental Research Funds for the Central Universities(226-2023-00114,226-2022-00226,and 226-2023-00059)the Key Program of National Natural Science Foundation of China(81930016)the Key Research and Development Program of China(2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(92159202)the Ningbo Top Medical and Health Research Program(2022030309).
文摘Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.
基金supported by grants from the Lone Star Paralysis Foundation,NIH R01NS081063Department of Defense award W81XWH-19-2-0054 to GDB+2 种基金supported by University of Wyoming Startup funds,Department of Defense grant W81XWH-17-1-0402the University of Wyoming Sensory Biology COBRE under National Institutes of Health(NIH)award number 5P20GM121310-02the National Institute of General Medical Sciences of the NIH under award number P20GM103432 to JSB。
文摘Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.
文摘BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results.AIM To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results.METHODS This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of Transplantation and Radiology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from August 2022 to February 2023.All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this study.SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility.RESULTS The mean age of all patients was 35.32±11.08 years.Among these,126(81.8%)were males and 28(18.2%)were females.The mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 m2.Kidney allograft biopsy results showed chronic changes in 55(37.66%)biopsies.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage.It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.
文摘BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.
基金The Scientific and Technological Innovation Platform of Huaihua,China,No.2022F2701The Science and Technology Planning Project of Huaihua,China,No.2021R3117.
文摘BACKGROUND Fibrous dysplasia is a congenital disorder in which normal bone is replaced by fibro-osseous tissue or irregular trabeculae of woven bone intermixed with mature collagenous tissue.A single or multiple bones are affected.This rare bone disorder has three clinical patterns including monostotic,polyostotic,and that associated with McCune-Albright syndrome.Most studies report primary fibrous dysplasia.However,a few cases of recurrent monostotic fibular fibrous dysplasia have been reported.Here,we report a therapeutic strategy for recurrent fibular fibrous dysplasia.CASE SUMMARY A 4-year-old boy was admitted for persistent pain in the left lower limb and abnormal gait over the previous 9 mo.He had no history of present or past illness.Preoperative imaging data showed erosion-like changes with bone expansion of the left middle and lower fibular segment.Tumor tissue in the fibular bone marrow cavity was removed by curettage,and rapid intraoperative pathological examination suggested fibular fibrous dysplasia.An allograft was implanted into the fibular medullary cavity.However,he was readmitted with clinical symptoms including persistent pain,abnormal gait,and local swelling at the age of 6 years.He was diagnosed with recurrent fibular fibrous dysplasia based on the second medical examination.He underwent fibular bone tumor radical resection and longus fibular allograft transplantation combined with fibular bone locking plate and screws.Good host bone to allogenic bone graft fusion was observed by the physician on postoperative regular follow-up.CONCLUSION Radical resection of fibrous dysplasia and longus fibula allograft combined with internal fixation for reconstruction are suitable for the treatment of recurrent monostotic fibular fibrous dysplasia.
文摘The second half of the previous century witnessed a tremendous rise in the number of clinical kidney transplants worldwide.This activity was,however,accompanied by many issues and challenges.An accurate diagnosis and appropriate management of causes of graft dysfunction were and still are,a big challenge.Kidney allograft biopsy played a vital role in addressing the above challenge.However,its interpretation was not standardized for many years until,in 1991,the Banff process was started to fill this void.Thereafter,regular Banff meetings took place every 2 years for the past 30 years.Marked changes have taken place in the interpretation of kidney allograft biopsies,diagnosis,and classification of rejection and other non-rejection pathologies from the original Banff 93 classification.This review attempts to summarize those changes for increasing the awareness and understanding of kidney allograft pathology through the eyes of the Banff process.It will interest the transplant surgeons,physicians,pathologists,and allied professionals associated with the care of kidney transplant patients.
文摘Renal transplantation is the treatment of choice for end stage kidney disease.However,despite all the efforts to expand the donor pool,the shortage of donors is increasing and as a consequence,there has been a significant increase in the number of patients on transplant waiting lists globally.Societies worldwide have employed different methods to address this,each with specific ethical concerns surrounding them.Over three decades ago,a governmentally regulated program of kidney transplantation from living unrelated donors was introduced in Iran and since practiced which has been the subject of hot debate in the literature.Nevertheless,despite all these extensive discussions and publications,several key aspects of the program have still not been properly elucidated and addressed.In this article,the author aims to illuminate some dark corners related to this issue that have largely escaped the notice of ethicists.
文摘Currently,the most feasible and widely practiced option for patients with endstage organ failure is the transplantation of part of or whole organs,either from deceased or living donors.However,organ shortage has posed and is still posing a big challenge in this field.Newer options being explored are xenografts and engineered/bioengineered tissues/organs.Already small steps have been taken in this direction and sooner or later,these will become a norm in this field.However,these developments will pose different challenges for the diagnosis and management of problems as compared with traditional allografts.The approach to pathologic diagnosis of dysfunction in these settings will likely be significantly different.Thus,there is a need to increase awareness and prepare transplant diagnosticians to meet this future challenge in the field of xenotransplantation/regenerative medicine.This review will focus on the current status of transplant pathology and how it will be changed in the future with the emerging scenario of routine xenotransplantation.
文摘BACKGROUND Exosomes are 30-150 nm nanovesicles with sophisticated nucleic acids cargo,actively secreted by all cells within human body,and found in abundance in all body fluids,including urine.These extracellular vesicles have tremendous potential for next generation diagnostics,theoretically enabling noninvasive assessment of organ and tissue function via liquid biopsy analysis.AIM Recently,feasibility of an exosomal molecular test was demonstrated for postorgan transplant monitoring:Analysis of urine-derived exosomal mRNA cargo allowed early detection of kidney allograft rejection.Here,we further studied urine-derived exosomes and their mRNA content as a highly promising diagnostic modality.This included stability studies of urine samples and exosomal mRNA upon transportation from the point of collection to a centralized testing facility,short-term storage of urine at different conditions upon receipt till the point molecular assay is performed,and effects of various potentially interfering substances on the downstream quantitative polymerase chain reaction(qPCR)assay.METHODS The urine specimens were stored at various conditions and pre-processed in different ways.Next,samples were passed through the columns to capture all extracellular vesicles,the vesicles were lysed to release their content and the exosomal RNA was purified on the mini-columns,reverse transcription was performed,next pre-amplification,followed by a qPCR analysis for a panel of RESULTS To ensure exosomal RNA integrity,the harvested urine specimens should be shipped refrigerated,by overnight delivery.Urine can next be stored at the test site for up to 1 wk at 4°C,and long term should be frozen at-80°C.Urine specimens must be centrifuge at low G-force to deplete cells and debris,to ensure consistent top results in downstream molecular assays.All commonly used medications(tacrolimus,cyclosporin A,mycophenolic acid,everolimus,sirolimus,ascomycin,teriflunomide)were tested and confirmed that they do not cause assay interference.CONCLUSION mRNA from urine-derived exosomes was shown to be stable across a broad range of conditions and produced accurate results when analyzed via qPCR assay for detection of kidney allograft rejection.We identified the most optimal conditions for every step of the process,ensuring pre-analytical sample integrity and robust qPCR results.
文摘Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes:Bronchiolitis obliterans syndrome and restrictive allograft syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In this review,we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome,which have been elucidated from clinicopathological observations and animal experiments worldwide.
文摘One of the most important functions of skins is to protect our bodies from microbes or pollutant sources. Skins containing physical substances serve as a physical barrier which protects our bodies from pathogens. A healthy skin contains a variety of antibacterial substances such as defensin, cathelicidin and psoriasin. However deep and wide burns cause the skin to lose its original functions, so our skins are exposed to various danger factors. For the burn patients, human alloskin graft serves as a very important temporary biological wound dressing. It protects the wound before autograft procedure, forms revascularization and granulation tissues and protects the wound from an invasion of microbes. This study was conducted with the aim to analyze the antimicrobial effect of cryopreserved allograft (CPA) and glycerol-preserved allograft (GPA) which was a type of allograft widely used for burn patients, and measure the difference in comparison with the fresh skin before processing it. The most common contaminants found in burn patients such as S. aureus, P. aeruginosa, C. albicans and E. coli, were used for experiment. The antimicrobial effect against S. aureus and E. coli was observed in fresh skin and some CPA. In some clinical cases, infection is frequently observed in the wounds treated with allograft, indicating the allograft completely block every kind of microbes. To prevent the infection, it is required to use antibiotics and manage wounds thoroughly.
文摘Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues.Tissues like bone,skin,amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body.Allograft tissues from human donor provide an excellent alternative to autografts.However,major concern with the use of allografts is the risk of infectious disease transmission.Therefore,tissue allografts should be sterilized to make them safe for clinical use.Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues.This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts.
文摘BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation after brain death(DBD) and donation after cardiac death(DCD) allograft recipients.METHODS:We reviewed our prospectively entered database for all DBD(n=377) and DCD(n=38) liver transplantations between January 1,2006 and October 30,2011.The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups.RESULTS:EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients,but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD(11.5%) compared with those without EAD(16.7%)(P=0.664) or in the rate of death in recipients with EAD(3.8%) compared with those without EAD(8.3%)(P=0.565).The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7(P=0.022).CONCLUSIONS:The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts.On initial assessment,it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts,however a study with a larger sample size of DCD allografts is needed to confirm these findings.The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure.An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.
文摘Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging. Three days later, 1 mL ganglioside solution （1 g/L） was sub- cutaneously iniected into the right hind leg of rabbits. Compared with non-injected rats, muscle wet weight ratio was increased at 2-12 weeks after modeling. The quantity of myelinated fibers in regenerated sciatic nerve, myelin thickness and fiber diameter were elevated at 4-12 weeks after modeling. Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks, while conduction latencies were decreased at 12 weeks. Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopre- served peripheral nerve allografts.
文摘BACKGROUND Early allograft dysfunction(EAD)after liver transplantation(LT)is an important cause of morbidity and mortality.To ensure adequate graft function,a critical hepatocellular mass is required in addition to an appropriate blood supply.We hypothesized that intraoperative measurement of portal venous and hepatic arterial flow may serve as a predictor in the diagnosis of EAD.AIM To study whether hepatic flow is an independent predictor of EAD following LT.METHODS This is an observational cohort study in a single institution.Hepatic arterial blood flow and portal venous blood flow were measured intraoperatively by transit flow.EAD was defined using the Olthoff criteria.Univariate and multivariate analyses were used to determine the intraoperative predictors of EAD.Survival analysis and prognostic factor analysis were performed using the Kaplan-Meier and Cox regression models.RESULTS A total of 195 liver transplant procedures were performed between January 2008 and December 2014 in 188 patients.A total of 54(27.7%)patients developed EAD.The median follow-up was 39 mo.Portal venous flow,hepatic arterial flow(HAF)and total hepatic arterial flow were associated with EAD in both the univariate and multivariate analyses.HAF is an independent prognostic factor for 30-d patient mortality.CONCLUSION Intraoperative measurement of blood flow after reperfusion appears to be a predictor of EAD;Moreover,HAF should be considered a predictor of 30-d patient mortality.
文摘The pathophysiology of LaPeyronie＇s disease （PD） is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excisionwith subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat＇s tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograff, and both collagen-Ⅱ- and osteocalcin-positive cells were also noted. Tunica albuginea （TA） allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.
文摘Acellular nerve ailograft preserves the basilar membrane tube and extracellular matrix, which promotes selective regeneration of neural defects via bridging. In the present study, a Sprague Dawley rat sciatic nerve was utilized to prepare acellular nerve allografts through the use of the chemical extraction method. Subsequently, the allograft was transplanted into a 10-mm sciatic nerve defect in Wistar rats, while autologous nerve grafts from Wistar rats served as controls. Compared with autologous nerve grafts, the acellular nerve allografts induced a greater number of degenerated nerve fibers from sural nerves, as well as a reduced misconnect rate in motor fibers, fewer acetylcholine esterase-positive sural nerves, and a greater number of carbonic anhydrase-positive sensory nerve fibers. Results demonstrated that the acellular nerve allograft exhibited significant neural selective regeneration in the process of bridging nerve defects.
文摘The overall incidence of osteochondral defect in the general population is estimated to be 15 to 30 per100000 people.These lesions can become symptomatic causing pain,swelling and decreased function of the knee,and may eventually progress to osteoarthritis.In the young and active population,partial or total knee arthroplasty(TKA)is rarely the treatment of choice due to risk of early failure.Osteochondral allograft transplantation has been demonstrated to be a safe and effective treatment of large osteochondral and chondral defects of the knee in appropriately selected patients.The treatment reduces pain,improves function and is a viable limb salvage procedure for patients,especially young and active patients for whom TKA is not recommended.Either large dowels generated with commercially available equipment or free hand shell allografts can be implanted in more posterior lesions.Current recommendations for fresh allografts stored at4C advise implantation within 21-28 d of procurement for optimum chondrocyte viability,following screening and testing protocols.Higher rates of successful allograft transplantation are observed in younger patients,unipolar lesions,normal or corrected malalignment,and defects that are treated within 12 mo of symptom onset.Patients with bipolar lesions,uncorrectable malalignment,advanced osteoarthritis,and those over40 tend to have less favourable outcomes.
基金supported by grants from the National Science and Technology Major Project of China(2012ZX10002-016 and 2012ZX10002-017)
文摘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.
