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,disr...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.展开更多
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 con...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.展开更多
·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 subgro...·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.·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
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,ma...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
Postoperative biliary complications remain a substantial challenge after living donor liver transplantation,especially due to its heterogeneous clinical presentation.
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...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.展开更多
BACKGROUND Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation(LT).Hence,more patients with diabetes mellitus(DM)are undergoing LT,especially,above the...BACKGROUND Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation(LT).Hence,more patients with diabetes mellitus(DM)are undergoing LT,especially,above the age of 65.AIM To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of 65.METHODS We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical record.We assessed the impact of DM on short-term outcomes,one-year,post-LT based on the following variables:Survival at one year;acute cellular rejection(ACR)rates;intensive care unit(ICU)and hospital length of stay;and readmissions.RESULTS Total of 148 patients who are 65 year or older underwent LT during the study period.The mean age is 68.5±3.3 years and 67.6%were male.The median Model for End-stage Liver Disease score at time of transplantation was 22(6-39),39%of patients had hepatocellular carcinoma and 77.7%underwent living donor LT.The one-year survival was similar between DM patients and others,91%.ACR occurred in 13.5%of patients(P=0.902).The median ICU stay is 4.5-day P=0.023.The rates of ICU and 90-d readmission were similar(P=0.821)and(P=0.194),respectively.CONCLUSION The short-term outcome of elderly diabetic patients undergoing LT is similar to others.The presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.展开更多
BACKGROUND The outcomes of liver transplantation(LT)from different grafts have been studied individually and in combination,but the reports were conflicting with some researchers finding no difference in both short-te...BACKGROUND The outcomes of liver transplantation(LT)from different grafts have been studied individually and in combination,but the reports were conflicting with some researchers finding no difference in both short-term and long-term outcomes between the deceased donor split LT(DD-SLT)and living donor LT(LDLT).AIM To compare the outcomes of DD-SLT and LDLT we performed this systematic review and meta-analysis.METHODS This systematic review was performed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.The following databases were searched for articles comparing outcomes of DD-SLT and LDLT:PubMed;Google Scholar;Embase;Cochrane Central Register of Controlled Trials;the Cochrane Database of Systematic Reviews;and Reference Citation Analysis(https://www.referencecitationanalysis.com/).The search terms used were:“liver transplantation;”“liver transplant;”“split liver transplant;”“living donor liver transplant;”“partial liver transplant;”“partial liver graft;”“ex vivo splitting;”and“in vivo splitting.”RESULTS Ten studies were included for the data synthesis and meta-analysis.There were a total of 4836 patients.The overall survival rate at 1 year,3 years and 5 years was superior in patients that received LDLT compared to DD-SLT.At 1 year,the hazard ratios was 1.44(95%confidence interval:1.16-1.78;P=0.001).The graft survival rate at 3 years and 5 years was superior in the LDLT group(3 year hazard ratio:1.28;95%confidence interval:1.01-1.63;P=0.04).CONCLUSION This meta-analysis showed that LDLT has better graft survival and overall survival when compared to DD-SLT.展开更多
BACKGROUND Blood transfusion is common during the peri-transplantation period.The incidence of immunological reactions to blood transfusion after kidney transplantation and their consequences on graft outcomes have no...BACKGROUND Blood transfusion is common during the peri-transplantation period.The incidence of immunological reactions to blood transfusion after kidney transplantation and their consequences on graft outcomes have not been extensively studied.AIM To examine the risk of graft rejection and loss in patients who received blood transfusion in the immediate peri-transplantation period.METHODS We conducted a single-center retrospective cohort study of 105 kidney recipients,among them 54 patients received leukodepleted blood transfusion at our center between January 2017 and March 2020.RESULTS This study included 105 kidney recipients,of which 80%kidneys were from living-related donors,14%from living-unrelated donors,and 6%from deceased donors.Living-related donors were mostly first-degree relatives(74.5%),while the rest were second-degree relatives.The patients were divided into transfusion(n=54)and non-transfusion(n=51)groups.The average hemoglobin level at which blood transfusion was commenced was 7.4±0.9 mg/dL.There were no differences between the groups in terms of rejection rates,graft loss,or death.During the study period,there was no significant difference in creatinine level progression between the two groups.Delayed graft function was higher in the transfusion group;however,this finding was not statistically significant.A high number of transfused packed red blood cells was significantly associated with increased creatinine levels at the end of the study.CONCLUSION Leukodepleted blood transfusion was not associated with a higher risk of rejection,graft loss,or death in kidney transplant recipients.展开更多
Background: Although not life-saving procedures like liver or heart transplantation, renal transplantation is the preferred treatment for many patients with end-stage renal disease because it improves patients’ quali...Background: Although not life-saving procedures like liver or heart transplantation, renal transplantation is the preferred treatment for many patients with end-stage renal disease because it improves patients’ quality of life, while other forms of renal replacement therapy (RRT) such as haemodialysis (HDX) shown to regain only 10% of the patient’s renal function [1]. Transplantation releases patients from the dietary and fluid restrictions and the physical constraints imposed by other forms of (RRT), patients become able to return to their normal activities. Patient’s 5-year survival is higher post transplant. Patients and methods: This is Descriptive, retro-prospective, cross sectional analytic and multicentre study done in Ahmed Gasim Cardiac and Renal Transplant Centre including 105 patients. After meeting the Inclusion Criteria and exclusion Criteria, then cases were selected and written in constructed questionnaire. The aim of the study was to evaluate the outcome of renal transplantation in Sudan. Results: 105 cases were used with male predominate and ratio male to female ratio 3:1, the main age of presentation between 31 - 45 years, most of the patients discharge uneventful with good outcome. During one-year follow-up following renal transplantation. Patient survival 95.2 % graft survival 82.4%. Overall morbidity shows 70.5%. Conclusion: this study showed that the one-year patient survival of 95.2%. Actuarial one-year graft survival of 92.4%. Renal transplantation complications can be reduced by meticulous preoperative workup including good cardiovascular assessment, tissue mismatch and BMI good postoperative follow up for early detection of graft rejection and long-term complications and finally patient education.展开更多
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 Coch...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.展开更多
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 be...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.展开更多
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),...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.展开更多
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.D...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.展开更多
AIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model. ~ METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone,...AIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model. ~ METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subconjunctival injection in mice that underwent high risk penetrating keratoplasty (HRPK). Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3. RESULTS: The two-month graft survival rate for HRPK was 42.86% in sorafenib group, 37.50% in dexamethasone group, 0 in DMSO group, and 0 in PBS group. Sorafenib significantly increased graft survival compared to the DMSO and PBS group (P〈0.05). The sorafenib didn't show significant effect in decreasing neovascularization compared with dexamethsone, DMSO, and PBS group. The sorafenib showed less total lymphangiogenesis than the dexamethasone, DMSO, and PBS group (P=0.011, P〈0.001, P〈0.001, respectively). The sorafenib group showed reduced expression of VEGF-C, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, VEGFR-2 and VEGFR-3 compared with DMSO group and PBS group (all P〈0.05). The sorafenib group didn't show difference in the expression of VEGF-A compared with DMSO, neither withPBS. The sorafenib group showed reduced expression of VEGFR-3 compared with dexamethasone (/〉=-0.051). CONCLUSION: The subconjunctivally administered sorafenib shows significant anti-lymphangiogenic effect, resulting in increased transplant survival in a murine high risk keratoplasty model. We suggest that a close linkage between decreased VEGF-C/VEGFR-2 and -3 signaling and increased corneal graft survival by sorafenib seems to exist.展开更多
AIM: To investigate the anti-(lymph)angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty(PK) model. METHODS: Graft survival, corneal neovascularizatio...AIM: To investigate the anti-(lymph)angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty(PK) model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among itraconazole, amphotericin B, dexamethasone, phosphate buffered saline(PBS) and surgery-only groups following subconjunctival injection in mice that underwent PK and corneal suture. Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction(RT-PCR) was performed to quantify the expression of inflammatory cytokines(TNF-alpha, IL-6) and vascular endothelial growth factor(VEGF)-A, VEGF-C, VEGFR-2, and VEGFR-3.RESULTS: In the suture model, the itraconazole group showed less angiogenesis, less lymphangiogenesis, and less inflammatory infiltration than the PBS group(all P〈0.05). The itraconazole group showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group(all P〈0.05). In PK model, the two-month graft survival rate was 28.57% in itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in amphotericin B group and 0 in surgery-only group. Graft survival in the itraconazole group was higher than that in the amphotericin, PBS and surgery-only group(P=0.057, 0.096, 0.012, respectively). The itraconazole group showed less total angiogenesis and lymphangiogenesis than PBS group(all P〈0.05).CONCLUSION: Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in both a corneal suture model and PK model. Itraconazole has anti-(lymph)-angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal effect and is therefore an alternative treatment option in cases where steroids cannot be used.展开更多
基金supported by a National Research Foundation of Korea grant funded by the Korean Government(NRF-2014R1A1A2056452 to D.H.H.and NRF-2014M3A9B6034224 to BGK)
文摘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.
文摘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.
基金Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province,China(No.2008BS03049 and No.2008BS03035)
文摘·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.·
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.
文摘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.
文摘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.
文摘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.
文摘Postoperative biliary complications remain a substantial challenge after living donor liver transplantation,especially due to its heterogeneous clinical presentation.
文摘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.
文摘BACKGROUND Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation(LT).Hence,more patients with diabetes mellitus(DM)are undergoing LT,especially,above the age of 65.AIM To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of 65.METHODS We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical record.We assessed the impact of DM on short-term outcomes,one-year,post-LT based on the following variables:Survival at one year;acute cellular rejection(ACR)rates;intensive care unit(ICU)and hospital length of stay;and readmissions.RESULTS Total of 148 patients who are 65 year or older underwent LT during the study period.The mean age is 68.5±3.3 years and 67.6%were male.The median Model for End-stage Liver Disease score at time of transplantation was 22(6-39),39%of patients had hepatocellular carcinoma and 77.7%underwent living donor LT.The one-year survival was similar between DM patients and others,91%.ACR occurred in 13.5%of patients(P=0.902).The median ICU stay is 4.5-day P=0.023.The rates of ICU and 90-d readmission were similar(P=0.821)and(P=0.194),respectively.CONCLUSION The short-term outcome of elderly diabetic patients undergoing LT is similar to others.The presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.
文摘BACKGROUND The outcomes of liver transplantation(LT)from different grafts have been studied individually and in combination,but the reports were conflicting with some researchers finding no difference in both short-term and long-term outcomes between the deceased donor split LT(DD-SLT)and living donor LT(LDLT).AIM To compare the outcomes of DD-SLT and LDLT we performed this systematic review and meta-analysis.METHODS This systematic review was performed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.The following databases were searched for articles comparing outcomes of DD-SLT and LDLT:PubMed;Google Scholar;Embase;Cochrane Central Register of Controlled Trials;the Cochrane Database of Systematic Reviews;and Reference Citation Analysis(https://www.referencecitationanalysis.com/).The search terms used were:“liver transplantation;”“liver transplant;”“split liver transplant;”“living donor liver transplant;”“partial liver transplant;”“partial liver graft;”“ex vivo splitting;”and“in vivo splitting.”RESULTS Ten studies were included for the data synthesis and meta-analysis.There were a total of 4836 patients.The overall survival rate at 1 year,3 years and 5 years was superior in patients that received LDLT compared to DD-SLT.At 1 year,the hazard ratios was 1.44(95%confidence interval:1.16-1.78;P=0.001).The graft survival rate at 3 years and 5 years was superior in the LDLT group(3 year hazard ratio:1.28;95%confidence interval:1.01-1.63;P=0.04).CONCLUSION This meta-analysis showed that LDLT has better graft survival and overall survival when compared to DD-SLT.
文摘BACKGROUND Blood transfusion is common during the peri-transplantation period.The incidence of immunological reactions to blood transfusion after kidney transplantation and their consequences on graft outcomes have not been extensively studied.AIM To examine the risk of graft rejection and loss in patients who received blood transfusion in the immediate peri-transplantation period.METHODS We conducted a single-center retrospective cohort study of 105 kidney recipients,among them 54 patients received leukodepleted blood transfusion at our center between January 2017 and March 2020.RESULTS This study included 105 kidney recipients,of which 80%kidneys were from living-related donors,14%from living-unrelated donors,and 6%from deceased donors.Living-related donors were mostly first-degree relatives(74.5%),while the rest were second-degree relatives.The patients were divided into transfusion(n=54)and non-transfusion(n=51)groups.The average hemoglobin level at which blood transfusion was commenced was 7.4±0.9 mg/dL.There were no differences between the groups in terms of rejection rates,graft loss,or death.During the study period,there was no significant difference in creatinine level progression between the two groups.Delayed graft function was higher in the transfusion group;however,this finding was not statistically significant.A high number of transfused packed red blood cells was significantly associated with increased creatinine levels at the end of the study.CONCLUSION Leukodepleted blood transfusion was not associated with a higher risk of rejection,graft loss,or death in kidney transplant recipients.
文摘Background: Although not life-saving procedures like liver or heart transplantation, renal transplantation is the preferred treatment for many patients with end-stage renal disease because it improves patients’ quality of life, while other forms of renal replacement therapy (RRT) such as haemodialysis (HDX) shown to regain only 10% of the patient’s renal function [1]. Transplantation releases patients from the dietary and fluid restrictions and the physical constraints imposed by other forms of (RRT), patients become able to return to their normal activities. Patient’s 5-year survival is higher post transplant. Patients and methods: This is Descriptive, retro-prospective, cross sectional analytic and multicentre study done in Ahmed Gasim Cardiac and Renal Transplant Centre including 105 patients. After meeting the Inclusion Criteria and exclusion Criteria, then cases were selected and written in constructed questionnaire. The aim of the study was to evaluate the outcome of renal transplantation in Sudan. Results: 105 cases were used with male predominate and ratio male to female ratio 3:1, the main age of presentation between 31 - 45 years, most of the patients discharge uneventful with good outcome. During one-year follow-up following renal transplantation. Patient survival 95.2 % graft survival 82.4%. Overall morbidity shows 70.5%. Conclusion: this study showed that the one-year patient survival of 95.2%. Actuarial one-year graft survival of 92.4%. Renal transplantation complications can be reduced by meticulous preoperative workup including good cardiovascular assessment, tissue mismatch and BMI good postoperative follow up for early detection of graft rejection and long-term complications and finally patient education.
基金Supported by grants from the National Research Development and Innovation Office,NKFI K120232Hungarian Science Research Fund,No.GINOP 2.3.2-15-2016-00015 and No.EFOP-3.6.2-16-2017-00006New National Excellence Program of the Ministry of Human Capacities,No.UNKP-17-4
文摘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.
文摘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.
文摘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.
文摘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.
文摘AIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model. ~ METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subconjunctival injection in mice that underwent high risk penetrating keratoplasty (HRPK). Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3. RESULTS: The two-month graft survival rate for HRPK was 42.86% in sorafenib group, 37.50% in dexamethasone group, 0 in DMSO group, and 0 in PBS group. Sorafenib significantly increased graft survival compared to the DMSO and PBS group (P〈0.05). The sorafenib didn't show significant effect in decreasing neovascularization compared with dexamethsone, DMSO, and PBS group. The sorafenib showed less total lymphangiogenesis than the dexamethasone, DMSO, and PBS group (P=0.011, P〈0.001, P〈0.001, respectively). The sorafenib group showed reduced expression of VEGF-C, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, VEGFR-2 and VEGFR-3 compared with DMSO group and PBS group (all P〈0.05). The sorafenib group didn't show difference in the expression of VEGF-A compared with DMSO, neither withPBS. The sorafenib group showed reduced expression of VEGFR-3 compared with dexamethasone (/〉=-0.051). CONCLUSION: The subconjunctivally administered sorafenib shows significant anti-lymphangiogenic effect, resulting in increased transplant survival in a murine high risk keratoplasty model. We suggest that a close linkage between decreased VEGF-C/VEGFR-2 and -3 signaling and increased corneal graft survival by sorafenib seems to exist.
文摘AIM: To investigate the anti-(lymph)angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty(PK) model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among itraconazole, amphotericin B, dexamethasone, phosphate buffered saline(PBS) and surgery-only groups following subconjunctival injection in mice that underwent PK and corneal suture. Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction(RT-PCR) was performed to quantify the expression of inflammatory cytokines(TNF-alpha, IL-6) and vascular endothelial growth factor(VEGF)-A, VEGF-C, VEGFR-2, and VEGFR-3.RESULTS: In the suture model, the itraconazole group showed less angiogenesis, less lymphangiogenesis, and less inflammatory infiltration than the PBS group(all P〈0.05). The itraconazole group showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group(all P〈0.05). In PK model, the two-month graft survival rate was 28.57% in itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in amphotericin B group and 0 in surgery-only group. Graft survival in the itraconazole group was higher than that in the amphotericin, PBS and surgery-only group(P=0.057, 0.096, 0.012, respectively). The itraconazole group showed less total angiogenesis and lymphangiogenesis than PBS group(all P〈0.05).CONCLUSION: Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in both a corneal suture model and PK model. Itraconazole has anti-(lymph)-angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal effect and is therefore an alternative treatment option in cases where steroids cannot be used.