Search

Extracorporeal membrane oxygenation (ECMO) has emerged as an alternative treatment to conventional ventilation maneuvers in the nontransplantation literature to support acute respiratory distress syndrome. However, the role of ECMO in transplant is unclear, and few case reports have described using ECMO pretransplant. We discuss the successful use of veno-arteriovenous ECMO as a bridge therapy to deceased donor liver transplant (LT) in acute respiratory distress syndrome. Because the incidence of severe pulmonary complications resulting in acute respiratory distress syndrome with multiorgan failure is rare before LT, determining the usefulness of ECMO is challenging. However, in acute but reversible respiratory failure and cardiovascular failure, veno-arteriovenous ECMO provides a useful therapeutic option as a bridge for patients awaiting LT and should be considered if available even in multiorgan failure., Competing Interests: DISCLOSURE All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Gemigliptin is a potent, selective dipeptidyl peptidase (DPP)-4 inhibitor that does not require any dosage adjustment based on renal function. It is also known to have no apparent interaction with commonly used drugs. In the present study, we aimed to evaluate the glucose-lowering efficacy and safety of gemigliptin in post-transplant patients with type 2 diabetes mellitus (T2D)., Methods: A total of 84 patients who were prescribed gemigliptin for more than 180 days after transplantation were analyzed retrospectively. Six-month changes in blood glucose and glycated hemoglobin (HbA1c) levels were checked to assess glycemic efficacy. Safety was evaluated by examining its influence on immunosuppressive treatment, as determined by the blood trough level and dosage of calcineurin inhibitors, as well as changes in parameters related to liver and renal function., Results: Six months of gemigliptin treatment significantly lowered blood glucose level (HbA1c: 8.16 ± 1.69 to 7.44 ± 1.26%; P < .001). There were no significant changes in blood trough levels of immunosuppressants, including tacrolimus, cyclosporine, and sirolimus. The dosage of immunosuppressants was also stable. In addition, there were no significant changes in the levels of liver enzymes and renal function during 6 months of treatment., Conclusion: Gemigliptin robustly lowered blood glucose levels without exerting any significant effect on immunosuppressive treatment, renal function, and liver enzymes in post-transplant patients with T2D., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In clinical islet transplantation, hepatic ischemia and insufficient neovascularization of transplanted islets are barriers to islet survival and function. However, hepatocytes have a potency to protect themselves against ischemia. We hypothesized that ischemia/reperfusion preconditioning (IRP) of hepatocytes might beneficially affect islet cells in a coculture system. Primary islets were cocultured with primary hepatocytes, and hepatocyte IRP was conducted by subjecting cells to hypoxic conditions for single 15-minute/30-minute hypoxia, or 2 tandem 15-minute/30-minute hypoxic treatments (hypoxic-normoxic-hypoxic). We show that gene expression levels of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), transforming growth factor-α (TGF-α), and TGF-β1 in hepatocytes were increased by IRP. IRP hepatocytes secreted hepatocyte growth factor and insulin-like growth factor-1. Coculture of islets with IRP hepatocytes enhanced islet insulin secretion in glucose challenge test and expression of the survival-related gene Bcl-2 and the regenerating gene-1α (Reg-1α). Islets cocultured with the 30-minute double-IRP hepatocytes displayed significantly higher viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase dUTP nick end labeling stain compared with that of islets subjected to 30 minutes of hypoxia. These results suggest that islet coculture with IRP hepatocytes can improve islet survival and insulin secretion., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Carbapenemase-producing Enterobacteriaceae (CPE) can lead to life-threatening outcomes with rapid spread of the carbapenemase gene in solid organ transplantation (SOT) recipients because of limitations of available antibiotics. We examined the characteristics and importance of CPE acquisition in SOT recipients with large numbers of CPE isolates., Methods: Between November 2015 and October 2016, 584 CPE isolates were found in 37 recipients and verified by carbapenemase gene multiplex polymerase chain reaction (PCR). One hundred recipients with at least 2 negative results in carbapenemase PCR for stool surveillance and no CPE isolates in clinical samples were retrospectively included., Results: Most CPE isolates were Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (546, 93.5%). The most frequent transplantation organ was lung (43.3%), and the most common sample with CPE isolates other than stool was respiratory tract (22.6%). The median time between SOT and first CPE acquisition was 7 days. All-cause mortality was significantly higher in recipients with CPE than in those without CPE (24.3% vs 10.0%; P = .03). In multivariate regression analysis, stool colonization of vancomycin-resistant Enterococci and/or Clostridium difficile during 30 days before SOT (odds ratio [OR], 3.28; 95% CI, 1.24-8.68; P = .02), lung transplantation (OR, 4.50; 95% CI, 1.19-17.03; P = .03), and intensive care unit stay ≥2 weeks (OR, 6.21; 95% CI, 1.72-22.45; P = .005) were associated with acquisition of CPE., Conclusions: Early posttransplantation CPE acquisition may affect the clinical outcome of SOT recipients. Careful screening for CPE during the early posttransplantation period would be meaningful in recipients with risk factors., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The Milan criteria are widely accepted for indicating liver transplantation in patients with hepatocellular carcinoma (HCC). However, a 7% to 20% possibility of HCC recurrence remains, even among patients who fulfill the Milan criteria., Methods: We retrospectively reviewed 88 patients with HCC who underwent liver transplantation at Pusan National University Yangsan Hospital between May 2010 and December 2014. The risk factors for HCC recurrence were analyzed, and the overall survival and disease-free survival rates were calculated based on each risk factor., Results: Seventeen patients (19.3%) experienced HCC recurrence. Multivariate analyses revealed that the independent risk factors for HCC recurrence were protein induced by vitamin K absence or antagonist II (PIVKA-II) levels of >200 mAU/mL, levels of >200 for alpha-fetoprotein (ng/mL) or PIVKA-II (mAU/mL), and microvascular invasion. Therefore, we defined the A-P 200 criteria as simultaneously exhibiting alpha-fetoprotein levels of ≤200 ng/mL and PIVKA-II levels of ≤200 mAU/mL. The 3-year overall survival rates among patients who fulfilled or exceeded the A-P 200 criteria were 89.2% and 80.0%, respectively (P = .79). The 3-year disease-free survival rates among patients who fulfilled or exceeded the A-P 200 criteria were 89.9% and 43.1%, respectively (P < .001). We also applied the A-P 200 criteria to patient data from another major center and observed similar results., Conclusion: These findings confirm that the A-P 200 criteria can be used to predict recurrence after liver transplantation among patients with HCC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Donor organ quality from deceased donors affects graft survival after kidney transplantation. This study was performed to identify clinico-histological factors that affect early graft outcome, using time-zero biopsies of deceased donors., Methods: Between December 2006 and July 2011, 135 recipients of deceased donor kidneys were included, and data concerning donor and recipient-related clinical characteristics and histological findings of time-zero biopsies categorized by use of the Banff 07 scoring system were included in the analysis. Mean donor age was 44.3 ± 12.3 years. Mean terminal serum creatinine level and cold ischemic time were 1.50 ± 0.96 mg/dL and 349 ± 166 minutes. Mean follow-up time after transplantation was 37 ± 16 months, and all recipients were followed for at least 1 year., Results: Global glomerulosclerosis (38.5%), tubular atrophy (37.8%), arteriolar hyaline thickening (25.9%), interstitial fibrosis (23%), vascular fibrous intimal thickening (21.5%), and interstitial inflammation (20%) were the major pathologic findings of time-zero biopsies. The majority of pathologic scores were of mild degree. Among histological findings, arteriolar hyaline thickening and interstitial fibrosis were only significantly associated with early post-transplant renal function in multivariate analyses., Conclusions: Considerations of clinico-histological findings were found to be valuable for predicting early graft outcome after deceased donor kidney transplantation., (Copyright © 2016. Published by Elsevier Inc.)

Background: Thalidomide (TM) is known to have anti-cancer and anti-inflammatory properties; however, its mechanism on T cells is still unclear. We previously showed the immune modulatory effect of TM on T cells and its therapeutic effect on lupus nephritis models. Here we examined the changes in the expression of tumor necrosis factor receptor superfamilies (TNFRSFs), including OX40, 4-1BB, and glucocorticoid-induced TNFR-related protein (GITR) in T cell subsets by TM treatments., Methods: Splenic naïve T cells (Tnaives) from C57BL/6 mice were sort-purified and cultured for CD4(+) T cell proliferation and regulatory T cells (Tregs) conversion with TM treatments. All samples were analyzed by flow cytometry after stained with anti-mouse CD4, Foxp3, OX40, 4-1BB, or GITR antibodies., Results: Expressions of OX40, 4-1BB, and GITR on CD4(+) T cells showed a decreasing tendency by TM treatments. Especially, downregulation of these molecules on CD4(+)CFSE(low) T cells was significant in TM treatment groups. On the condition of Treg conversion, OX40 was downregulated significantly. In contrast, the expression of GITR was increased, and that of 4-1BB had shown no particular change under the condition of Treg., Conclusion: Considering these results, TM may have an immune modulatory role through the T cell subset-specific change of OX40, 4-1BB, and GITR expression. Further study is required to elucidate the effect of thalidomide on T cells., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The mechanism of podocyte injury observed with the use of rapamycin (RPM) remains unclear. The conversion from calcineurin inhibitors (CNIs) to RPM in kidney transplant recipients has been associated with a higher incidence of proteinuria and renal injury. In this study, we performed proteomic analyses to investigate the alteration of protein expression in mouse podocytes treated with RPM in comparison with CNI/RPM combination., Methods: Immortalized mouse podocytes were treated with 20 nmol/L RPM or 20 nmol/L RPM + 1 μg/mL cyclosporine. Podocyte proteins were separated by 2-dimensional polyacrylamide gel electrophoresis (2DE) and identified by matrix-assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry and peptide fingerprinting. Selected proteins were analyzed by means of Western blot assay., Results: We identified 36 differently expressed proteins after isolated RPM or CNI/RPM combination treatment in cultured mouse podocytes. There are 3 distinct patterns of protein expression: (1) potentiated down- or upregulation of proteins by CNI/RPM treatment compared with isolated RPM treatment (n = 4); (2) partial offset of down-regulation by CNI/RPM in comparison with RPM treatment (n = 25); (3) no difference in down-regulation between RPM and CNI/RPM treatment (n = 5). We found a significant interplay between RPM and CNI on the expression of the selected proteins in mouse podocytes. This might explain the higher incidence of proteinuria by CNI/RPM combination in clinical settings., Conclusions: Further study is required to elucidate the target protein associated with RPM-induced podocyte injury., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Because of the development of various desensitization strategies, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has become a feasible option for patients with end-stage liver disease. However, there has been no united desensitization protocol for ABOi LDLT. We analyzed the outcomes after establishment of simplified protocol without splenectomy, intravenous immunoglobulin, and local infusion therapy., Methods: We analyzed 19 ABOi LDLT cases that had been performed between January 2012 and December 2013, without splenectomy and local infusion. We used a single dose of rituximab (375 mg/m(2)) 10 days before transplantation and several series of plasma exchange according to the recipients' iso-agglutinin titer-to-target titer ratio of 1:32., Results: Nineteen recipients received ABOi LTs from living donors. The mean initial immunoglobulin (Ig) M and IgG anti-ABO titers were 76.63 ± 78.81 (range, 8∼256) and 162.53 ± 464.1 (0∼2048). We performed preoperative plasma exchange to 16 recipients (mean number of sessions, 3.58; range, 1-10). After surgery, 9 patients received plasma exchange (mean, 1.84; range 1∼14). One death occurred as the result of pneumonia (5.3%). There were 4 cases of acute rejections (21.1%), and all of them were treated successfully with steroid pulse or thymoglobulin. Antibody-mediated rejection and graft failure did not occur. Six cases of postoperative complications (31.6%) occurred, including 3 cases of infections. There were 2 cases of biliary anastomotic stricture (10.5%) and 1 case of portal vein stenosis (5.3%)., Conclusions: ABOi LDLT with the use of simplified protocol can be safely performed without increased risk of antibody-mediated rejection and other complications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Mycophenolic acid (MPA)-induced beta cell toxicity limits islet graft survival. However, the signal transduction mechanisms underlying MPA-induced β-cell toxicity have not been fully elucidated. Previously, we showed that MPA-induced pancreatic β-cell apoptosis proceeds via RhoGDI-α down-regulation linked to Rac1 activation. In the present study, we investigated factors affecting RhoGDI-α during MPA-induced β-cell apoptosis. The presence of RhoGDI-α-related protein was determined with the use of yeast 2-hybrid (Y2H) analysis. Y2H screening of RhoGDI-α was performed in yeast PBN204 strain containing 3 reporters (URA3, lacZ, and ADE2) under the control of different GAL promoters. INS-1E cells (an insulin-secreting pancreatic β-cell line) were treated with MPA for 12, 24, and 36 hours. Eighty-three real positives were obtained by Y2H analysis, and of these, arginine N-methyltransferase 3 (PRMT3) protein interacted with RhoGDI-α in INS-1E cells. PRMT3 gene expressions and its protein levels were significantly decreased during MPA-induced apoptosis. In summary, PRMT3 and RhoGDI-α were found to interact in INS-1E cells. Furthermore, MPA was found to regulate this interaction in INS-1E cells by down-regulating the gene expression of PRMT3. These findings suggest that control of the interaction between PRMT3 and RhoGDI-α could be used to prevent MPA-induced β-cell death., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Living kidney donation has become an important source for renal transplantation. Thus, renal function after donation is an important issue. In this study, we examined histological abnormalities in implantation biopsy specimens from living kidney donors and analyzed the renal function of the remaining kidney., Methods: Using the 2007 Banff classification system, we analyzed 121 kidneys from living donors who underwent implantation biopsies (IBs) between 2010 and 2011. Donor characteristics, intraoperative factors, and perioperative renal functions, such as serum creatinine and glomerular filtration rate (GFR), were evaluated. Univariate and multivariate regression analyses were performed to identify the factors related to each histological abnormality and postoperative 1-year donor renal function., Results: Most histological abnormalities in healthy living donors were scored as 1 on the Banff scale. Univariate and multivariate analyses revealed that donor age was the only preoperative factor related to tubular atrophy (odds ratio [OR] = 1.104; P = .012) and glomerular sclerosis (OR = 1.050; P = .019). Intraoperative factors were not related to histological parameters. And histological abnormalities did not affect postoperative 1-year renal function. In contrast, donor age, preoperative GFR, and estimated blood loss were significantly related to 1-year postoperative GFR., Conclusion: Most histological abnormalities in healthy living donors were minor. The incidence of abnormalities correlated with donor age. However, postoperative renal functions in living donors were not affected by histological abnormalities. Larger-scale investigations with long-term follow-up analysis will be needed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Liver stiffness measurements (LSMs) using transient elastography (TE) provide a noninvasive means to assess liver fibrosis that correlate with hepatic cholestasis. However, few studies have examined the correlation of TE to obtain LSMs with perioperative clinical and laboratory parameters in living donor liver transplantation (LDLT)., Patients and Methods: We retrospectively reviewed forty-eight subjects who underwent LDLT between November 2010 and October 2012. All donors and recipients underwent TE, abdominal computed tomography (CT), and biochemical tests within 1 month before and at 1 week after transplantation. Using a cut-off LSM of 7.5 kPa, which we arbitrarily assigned to be indicative of significant fibrosis, we divided our study population into ≤7.5 kPa (group L; n = 15, 31.3%) versus >7.5 kPa; (group H; n = 33, 68.8%)., Results: Pretransplantation serum total bilirubin, international normalized ratio, and Model for End-stage Liver Disease scores of recipients were significantly higher in group H than group L. Regarding the pretransplantation donor characteristics, the graft-recipient weight ratio was significantly smaller among those in group H (P = .039). In addition, the post-transplantation 1-week serum total bilirubin level was significantly higher in group H (2.3 mg/dL versus 1.2 mg/dL, P = .015), although neither biliary complications norhepatic congestion was identified by abdominal CT. Among the 1-week post-transplantation laboratory findings, only total bilirubin positively correlated with LSM (P = .044)., Conclusions: This pilot study suggested that a high LSM after LDLT suggests intrahepatic cholestasis and portal hypercirculation in the graft, irrespective of liver fibrosis, outflow obstruction, or biliary obstruction., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: In contrast with deceased donor transplantation, the clinical significance of pathologic findings in time-zero biopsies after living donor kidney transplantation are rarely reported, due to the expectation that histologic findings and renal function are normal. The aim of this study was to identify subclinical pathologic findings in living donors and examine the effect on early graft renal function., Methods: Between December 2006 and July 2011, 146 living-donor kidney transplant recipients were enrolled in this study. We retrospectively analyzed donor and recipient-related clinical parameters, and post-transplant 6 months and 1 year estimated glomerular filtration rate (eGFR) as early graft renal function. Time-zero biopsies were evaluated using the 2007 Banff criteria., Results: Most abnormal histologic findings were of mild degree as determined by Banff scores. Global glomerulosclerosis (GS, 35.6%), tubular atrophy (CT, 36.3%), interstitial fibrosis (CI, 20.5%), vascular fibrous intimal thickening (CV, 4.1%), arteriolar hyaline thickening (AH, 14.4%), interstitial inflammation (I, 3.4%) were pathologic findings in time-zero biopsies. The univariate analysis revealed that donor age and gender were significantly associated with eGFR at post-transplant 6 months and at 1 year (P < .05). Furthermore, GS and CT were significantly associated with early graft renal function (P < .05). However, multivariate linear regression analysis showed only donor age was significantly associated with early graft renal function (P = .001)., Conclusion: A mild degree of subclinical, pathologic findings on time-zero biopsy did not affect early graft renal function in living-donor kidney transplantation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: This study was undertaken to investigate risk factors of mortality in patients with fulminant hepatic failure (FHF)., Methods: Fifty-three patients with FHF treated from January 2006 to April 2011 were allocated to a spontaneous survival group (group 1), a death without liver transplantation (LT) group (group 2), and an LT group (group 3). To analyze risk factors associated with mortality in FHF, we excluded group 3 patients. Clinical features, Model for End-Stage Liver Disease (MELD) scores, and King's College Hospital criteria at the time of hepatic encephalopathy in group 2 were compared with those of group 1., Results: The causes of FHF were acute viral infection (n = 29, hepatitis A:B, 28:1), drugs (n = 18; including 4 acetaminophen and 14 herbal medication), autoimmune (n = 4), and miscellaneous (n = 2). Of the 53 patients, 19 were allocated to group 1, 18 to group 2, and 16 to group 3. According to univariate analysis, risk factors for mortality in group 2 were acute renal failure requiring renal replacement therapy and a MELD score ≥30 at the time of hepatic encephalopathy. However, by multivariate analysis, a MELD score ≥30 was the only independent risk factor for mortality in group 2 (P = .042; hazard ratio, 4.500)., Conclusions: A MELD score ≥30 was found to be the only independent risk factor of mortality in FHF patients without LT. Therefore, the findings of this study suggest that these patients may need emergent LT for survival., (Copyright © 2013. Published by Elsevier Inc.)

Background: Laparoscopic fenestration (LF) and percutaneous catheter drainage (PCD) are widely accepted treatments for symptomatic lymphoceles. The aim of this study was to review the results and compare the outcomes of LF with those of PCD., Patients and Methods: Among 1363 patients who underwent kidney transplantation at our institute between 1999 and 2011, 35 (2.5%) developed symptomatic lymphoceles. Among them, 7 were treated by LF after PCD; 10, LF only, and 18 PCD only. The patients were divided into 2 groups based upon the treatment method: LF (n = 17) and PCD-only groups (n = 18)., Results: No intergroup differences in age, gender, diabetes prevalence, retransplant rate, delayed graft function, or serum creatinine was observed at 7 days after the treatment. However, acute rejection episodes and sirolimus use were more frequent among the LF group (P = .028). Furthermore, median drainage on the first day was significantly greater in the LF versus PCD group. After catheter insertion, the PCD group showed a significant decrease in drainage on the following day, but no decrease was observed in the LF group., Conclusions: LF is a safe treatment for symptomatic lymphocele. LF should be held in reserve for treatment failures after PCD. LF seems to be a more reasonable first-line treatment for symptomatic lymphoceles in patients at high risk for graft dysfunction., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The present study compared the efficacy and safety of mizoribine (MZR) with mycophenolate mofetil (MMF) in kidney transplantation. This multicenter, randomized clinical trial. Employed doses of study drug tailored to the immunosuppressive need. The primary efficacy outcome was the incidence of biopsy-proven acute rejection episodes (BPAR). The safety of the study drug was assessed using the incidences of adverse events, drug discontinuations, and abnormal laboratory results. The 7 (6.4%) BPARs above grade II were observed in the MZR group noninferior to the 2 (1.8%) in the MMF group (95% confidence interval, -0.007-0.097 > noninferiority limit [-0.2]). BPAR was significantly decreased in the MZR group after the dose change (17/41 [41.4%] vs 8/69 [11.6%]; P < .0001) and the incidence of BPAR was similar between the MZR and MMF groups after the dose change (P = .592). The uric acid level was significantly elevated in the MZR group (P = .002). In conclusion, the efficacy and safety of MZR were similar and statistically noninferior to MMF in combination therapy with tacrolimus., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Few studies have evaluated the long-term effects of kidney donation on the donors themselves. This study investigated postoperative renal function stabilization in kidney donors after living-donor transplantation to determine the optimal follow-up period., Methods: Between March 2006 and July 2010, 203 patients in our hospital underwent live donor nephrectomy. Renal function recovery patterns were analyzed by calculating the postoperative rate of change of their Modification of Diet in Renal Disease study equation estimating glomerular filtration rate (MDRD-GFR) versus their preoperative level (%MDRD). We divided normal (n = 121) versus chronic kidney disease subjects (CKD; MDRD-GFR < 60 mL/min/1.73 m(2) at 6 months postoperatively, n = 82) for 1 year follow-up to compare time to renal function stabilization using the repeated measured data method., Results: When all donors were considered together at 1 month after transplantation, MDRD-GFRs were significantly increased compared with earlier follow-up times (for postoperative days 1, 4, and 7), P values were < .001, .006, and .002, respectively). Among all donors, there was no significant difference between MDRD-GFRs at 1 versus 3, 6, and 12 months posttransplantation (P < .05 in all three comparisons), indicating renal function stabilization. Importantly the %MDRD was significantly higher among the normal than the CKD group at postoperative months 1, 3, and 6 (P < .05 for all comparisons), although after 12 months there was no significant difference between the groups (69.06 ± 9.28% versus 70.14 ± 8.38%, P = .442)., Conclusion: After live donor kidney transplantation, renal function began to stabilize at 1 month postoperatively. Poor renal functional recovery and CKD later were predicted by inferior stabilization at 1 month postnephrectomy. These data suggested that even patients with normal GFRs should be followed beyond 1 year postoperatively to determine their ultimate renal functional outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Encapsulation of transplanted cells within an immunoisolating membrane may provide a new strategy for protecting these cells from recipient immune responses without the use of immunosuppressive drugs. We have previously reported a novel concept of immunoisolation and immunodelusion using recipient cells instead of traditional artificial materials. We developed a chondrocyte sheeting immunodelusive immunoisolated bioartificial pancreas (CSI-BAP) that would enable transplantation of cells across allogeneic and xenogeneic barriers without the cells being recognized as donor cells and without the need for immunosuppression. Recently, we have constructed hybrid cellular spheroids (HCSs) containing cells from two different cell lines (RIN-5F, an insulin-secreting cell line, and Hep-G2, a hepatocellular carcinoma cell line) to enhance the function and biocompatibility of the HCSs. These HCSs were then encapsulated with multiple layers of chondrocyte sheets obtained from the auricular cartilage of Sprague-Dawley (SD) rats. The in vitro ability of the CSI-BAP to secrete insulin was tested before transplantation. Histological evaluation of CSI-BAP chondrocyte microencapsulated immunoisolated islet morphology and viability of allogeneic or xenogeneic cell lines was performed 100 days after the CSI-BAP was transplanted into SD rats. Morphological evaluations revealed good viability of the islets and progression of islet encapsulation. In vitro insulin secretion from the CSI-BAP was well maintained. Additionally, insulin and albumin secretion from the CSI-BAP was confirmed by in vivo immunohistochemical examination. Moreover, the cell lines transplanted into the subcutaneous space in the form of HCSs within the chondrocyte sheets showed good viability of more than 100 days and sustained insulin and albumin secreting ability., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Improving human islet transplantation is often limited by the shortage of donors and the side effects of immunosuppressive agents. If immunoisolation is properly used, it can overcome these obstacles. Because artificial materials are adopted in this technique, however, there are still multiple issues with biocompatibility and foreign body reactions. We developed a chondrocyte microencapsulated immunoisolated islet (CMI-islet) that allows living cells to act as the immunoisolating material. To manufacture CMI-islets for xenotransplantation, isolated rat pancreatic islets were placed on low cell-binding culture dishes. Subsequently, expanded canine auricular cartiage primary cells were seeded on these dishes at a high density and maintained in a suspended state via a shaking culture system. Morphological evaluations showed good islet viability and a clear progression of the islet- encapsulation events. When the cells were challenged with glucose, they were able to secrete sufficient insulin according to glucose concentrations. The CMI-islets responded better to the glucose challenge than did nude pancreatic islets and created better glucose-insulin feedback regulation. Moreover, insulin secretion into the culture medium was confirmed over a period of 100 days, showing the survival and secretory capacity of the CMI-islet cells. By microencapsulating pancreatic islets with recipient ear cartilage cells, long-term insulin secretion can be maintained and the response to glucose challenges improved. This new immunodelusion technology differs from other immunoisolation techniques in that the donor tissue is enclosed with the recipient's tissue, thus allowing the transplanted cells to be recognized as recipient cells. This microencapsulation method may lead to developing viable xenotransplantation techniques that do not use immunosuppressive drugs., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Although Islet cell isolation and culture have been well developed, there has been little progress to prolong transplanted islet survival. Hepatic ischemia and insufficient neovascularization of islets are considered to be the barriers to long-term survival, Hepatocytes that survive ischemic injury have been reported to protect themeslves and regenerate using the IL-6 interleukin 6 and STAT3 pathways., Materials and Methods: The hepatocellular carcinoma (Hep-G2) cell line preconditioned for 0, 2, 4, 6, and 24 hours in a hypoxic chamber, was cocultured with rat insulin-secreting celline (RIN-5F) cells. We measured cell viabilities, insulin secretion, and p-STAT3, IL-6, and NF-κB levels., Results: Cocultured Hep-G2 and RIN-5F cells aggregated to form spheroids. Viabilities of Hep-G2 cells were no different after various ischemic preconditioning times, but insulin secretion increased in a time-dependent fashion with preconditioning. Western blotting showed p-STAT3, NF-κB, and IL-6 levels to increase with preconditioning time., Conclusion: The IL-6/STAT3 pathway of Hep-G2 cells after ischemic injury showed beneficial effects on insulin secretion of RIN-5f cells cocultured with themselves., (Copyright © 2012 Elsevier Inc. All rights reserved.)

During islet transplantation into the portal vein of the liver, the islet cells are expected to have complex interactions with hepatocytes. However, the mechanism underlying this interaction is not yet understood. Hence, we developed cellular complexes containing a mixture of human hepatocellular carcinoma cell line (Hep-G2) and rat insulin-secreting cell line (RIN-5F) by using a co-culture model and studied the function and morphology of the resultant hybrid cellular spheroids (HCSs). The RIN-5F and Hep-G2 cells were suspension cultured and, within 5 days of culture, the two types of cells aggregated to yield spheroids. The functionality of the thus formed HCSs was evaluated by measuring the levels of insulin and albumin in the culture supernatant. The HCSs retained their insulin- and albumin-secreting ability and their morphology, as revealed by immunohistological staining. The insulin and albumin levels secreted by the HCSs were considerably higher than those secreted by spheroids of single-cell origin. Generally, obtaining complexes from more than two types of cells is difficult. However, we were able to generate HCSs. We believe that this culture method could have various applications such as studying the in vitro cell-cell interactions and developing new cell transplantation models., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Mycophenolic acid (MPA) is an immunosuppressive agent that is widely used in clinical therapy, including pancreas and islet transplantation. Previously, we showed that MPA induces significant apoptosis of insulin-secreting cells by downregulating RhoGDI-α and increasing JNK expression. In this study, we investigated Rac1 directly associated with RhoGDI-α during MPA-induced apoptosis in INS-1E cells (an insulin-secreting cell line). Cells were treated with MPA for 24 and 36 hours. Immunoprecipitation was used to examine physical interactions between RhoGDI-α and Rac1. Activation and immunoprecipitation assays showed expressions of Rac1 and RhoGDI-α to be directly correlated. Rac1 binding to RhoGDI-α decreased after MPA treatment, and Rac1 was induced and subsequently activated by MPA. We concluded that this novel RhoGDI-α/Rac1/JNK pathway induced apoptosis of transplanted islet cells after MPA treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Transplant glomerulopathy (TG) a morphological feature of chronic active antibody-mediated rejection, is associated with donor-specific antibody, peritubular capillary deposition of C4d, and multilayering of peritubular capillary basement membranes. To evaluate the significance of accompanying nonimmunologic injuries in TG, we retrospectively reviewed 2839 renal allograft cases at our institute among which TG was diagnosed in 81 patients (2.9%). Among TG cases, 48 samples showed accompanying diseases such as chronic calcineurin inhibitor toxicity, hepatitis viral infection, posttransplant diabetes, and glomerulonephritis. Comparing the pure form of TG with TG-mixed diseases, there was no difference in patient demography, serum creatinine values, and proteinuria. Among histological parameters, severe hyalinosis was more frequently observed among the TG plus other diseases group. The two groups did not show significant difference in graft survival (P = .216)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The role of lymphocyte cross-matches (LCM) remains controversial in the liver transplant field. The aim of this study was to correlate the risk for acute rejection episodes and graft survival in liver transplantation with pretransplant LCM results., Patients and Methods: We enrolled 184 adult liver transplantation patients, excluding pediatric and second grafts. The 129 living donor and 55 deceased donor liver transplantations were divided into 2 groups: LCM (+); (n=20) and LCM (-); (n=164)., Results: There were no differences in the demographic features, such as gender and recipient age, original disease, Model for End-Stage Liver Disease score, donor type, number of human leukocyte antigen mismatches, and cold ischemia times. There were no hyperacute rejection episodes in the LCM (+) group. Also, posttransplant complications such as acute rejection episode, biliary complication, or hepatic artery thrombosis were not different. Acute rejection episodes occurred in 5.0% of the LCM (+) group and 15.2% of the LCM (-) group (P=.317). Bile duct complications after transplantation arose in 20.0% of the LCM (+) group and in 32.9% of the LCM (-) group (P=.312). The 2 groups showed no difference in graft survival rate analyzed by the Kaplan-Meier method according to LCM results., Conclusion: Pretransplant LCM results were not associated with overall graft survival or acute rejection episodes in this study., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Recently, the impact of human leukocyte antigen (HLA) mismatch (MM) on graft outcome has diminished since the introduction of potent immunosuppressive agents, whereas previous reports support the notion that greater numbers of HLA matches are beneficial. This study was undertaken to evaluate outcomes after five or six HLA-mismatched living donor kidney transplantations (LDKT)., Methods: The authors retrospectively reviewed graft function after 2687 LDKTs performed between June 1984 and February 2010. A database of 1364 living related and 1063 living-unrelated donor (LURD) kidney transplantations was used for this study. LURD kidney transplantations were classified into three groups; (1) zero to one HLA MM (n = 158); (2) two to four HLA MM (n = 851); and (3) five to six MM (n = 54). An acute rejection episode was diagnosed based on clinical deterioration of graft function or biopsy findings. Graft survival was calculated using the Kaplan-Meier method., Results: Graft survivals in the zero to one HLA MM, two to four HLA MM, five to six HLA MM, and one-haplo MM LDKT were not significantly different. The rates of acute rejection episodes within 1 year after transplantation were similar irrespective of the HLA MM; (1) zero to one HLA MM (37.3%), (2) two to four HLA MM (35.3%), (3) five to six HLA MM (33.3%; P = .832)., Conclusions: Survival of five or six HLA-mismatched LDKTs was comparable to that of one-haplo MM and relatively well-matched LDKT. The study showed that the presence of five or six HLA MM was not a risk factor for graft survival after LDKT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Sirolimus is a potent immunosuppressive agent used with increasing frequency in kidney transplantation. However, sirolimus can increase the rate of unexplained interstitial pneumonitis. The aim of this study was to evaluate the clinical characteristics of sirolimus-induced pneumonitis and the therapeutic results in renal transplant recipients., Patients and Methods: Seventy-two patients received sirolimus, conversion or de novo regimen, at our center between January 2007 and April 2011. Twelve of the 72 patients (16.7%) developed interstitial pneumonitis. The patients were divided into three groups according to the following indications of sirolimus use: de novo, early conversion, and late conversion groups., Results: The mean duration of follow-up was 11.0 ± 11.5 months. The mean blood level of sirolimus measured by microparticulate enzyme immunoassay was 16.5 ± 7.4 ng/mL at the time of diagnosis. The mean time from the start of sirolimus to pneumonitis onset was 14.7 ± 8.0 months. The clinical presentation included fever, cough, dyspnea, general weakness, and periorbital edema. In most cases, radiological imaging tests revealed bilateral lower-lobe involvement. Bronchoalveolar lavage was performed in three patients and two patients showed lymphocytic alveolitis. Sirolimus was discontinued or reduced for the treatment of pneumonitis. All cases of pneumonitis were resolved within 2 to 4 weeks., Conclusion: Sirolimus blood level should be monitored tightly and early intervention is important when sirolimus-induced pneumonitis is suspected., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: This study examined the current state of information on renal replacement therapy and the educational demands of kidney transplant recipients., Methods: The study was conducted through a survey. The questionnaire of this study was developed by researchers and was completed by 72 kidney recipients., Results: The recipients were most frequently informed of hemodialysis (87.5%), followed by kidney transplantation (69.4%) or peritoneal dialysis (48.6%) as a modality of renal replacement therapy at the time of diagnosis of chronic renal failure. Information about kidney transplantation was provided when they were diagnosed with end-stage renal disease (ESRD; 33.3%) or right after initiation of dialysis (15.3%) or a few years thereafter (9.7%). They were informed about kidney transplantation mostly by transplantation surgeons (mean degree score = 3.1 ± 1.3; range, 1-4), followed in order by transplant coordinators, nephrologists, family members, other patients, artificial kidney unit nurses, and mass media or internet. Regarding the influence of the information on their decision to receive a transplant, the mean score was 3.2 ± 1.2 (range, 1-5). Also, kidney transplantation was evaluated as the best renal replacement therapy for work, pregnancy/delivery, traveling, and diet., Conclusion: Patients diagnosed with ESRD are not fully informed of transplantation as a primary optimal renal replacement therapy for their quality of life., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Proper maintenance of immunosuppression is required to achieve long-term graft survival. The aim of this study was to evaluate the effect of change or modulation of an immunosuppressive regimen (IR) on graft survival during the posttransplant period in patients undergoing kidney transplantation. A total of 1164 patients who underwent kidney transplantation between January 1997 and December 2008 at Yonsei University Health System were enrolled. All patients initially received calcineurin inhibitor (CNI)-based double or triple IR (DIR and TIR, respectively). The causes of IR changes or modulation were reviewed retrospectively. Graft survival rate was compared according to types of maintenance immunosuppression (DIR versus TIR). Initially, DIR and TIR were adopted in 201 (17.3%) and 963 (82.7%) recipients, respectively. In 77 DIR recipients (38.8%) and 271 TIR recipients (28.1%), IRs were changed. Among recipients of an initial DIR, the most frequent reasons for IR change were acute rejection (50%) within 6 months of transplantation and chronic allograft dysfunction (70%) after 6 months. In TIR recipients, the reasons for IR change included drug toxicity or drug-related side effects (34.3%) within 6 months of transplantation and complications related to overimmunosuppression (39.3%) after 6 months. The group in which the IR was changed from the initial DIR to the later TIR had a statistically superior graft survival rate compared to the group that did not have a change in the initial DIR (P = .032). In contrast, TIR recipients without change had better graft survival rate than recipients with initial TIR change to later DIR (P < .001). Change or modulation of immunosuppression from initial DIR to later TIR could affect long-term graft survival., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: There have been many efforts to find methods to increase insulin production by islets or modified cells. Commercially available established cell lines can be a good source of artificial islets. We manufactured sphere-shaped cell clusters composed of insulin-secreting cells from the commercially available RIN-5F cell line., Methods: To generate artificial islets with insulin-secretion functions, we used the RIN-5F cell line. When cells cultured in RPMI-1640 medium containing 10% fetal bovine serum reached near confluency, they were trypsinized for suspension culture at high density, using a horizontal shaker. The cells were maintained for 5 days under 5% CO(2) with humidification. Next, the media from the RIN cell spheroid culture was collected over 5 consecutive days to test for insulin secretion., Results: Spheroids of artificial islets exhibited an oval shape with an approximate size of 94.13 ± 20.41 μm on day 5 during the shaking culture. Abnormal outgrowth of spheroids was not observed. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells were not detected among the overall spheroids, including the core position. Insulin secretion, measured by enzyme-linked immunosorbent assay, was well maintained in the culture media over 5 days after spheroid formation., Conclusion: This result suggested that a culture method with shaking can be applied to commercially available established cell lines to generate artificial islets, which might be used for a bioartificial pancreas., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Biliary complications remain a major cause of morbidity after liver transplantation, especially in living donor liver transplantation (LDLT). Maintaining adequate blood supply to the bile duct is important for the prevention of biliary complications. The objective of this study was to analyze the effects of different techniques for bile duct anastomosis on posttransplantation biliary complications. From August 2005 to August 2008, 121 liver transplantations were performed at our center. Among the total 121 liver transplant recipients, 68 patients underwent a LDLT using a right lobe graft and were enrolled in this study. We used classic dissection for the first 38 recipients and the hilar plate looping technique for the next 30 patients. The hilar plate looping technique involves the looping of the complete hilar plate and Glissonian sheath around the hepatic duct after full dissection of the right hepatic artery and portal vein. Biliary complications were defined as bilomas or strictures that developed within 6 months after transplantation and required surgical or radiological intervention. There were no significant demographic differences between the 2 groups. The incidence of complications was 15 (39.5%) for classic dissection and 3 (18.8%) for hilar plate looping. Furthermore, there were no biliary strictures in the hilar plate looping group, and there was a significant difference in the complication rate between the 2 groups (P = .011). In conclusion, the hilar plate looping technique during LDLT significantly reduces recipient biliary complications., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: We compared the results of 2 immunoassay systems (affinity column-mediated immunoassay [ACMIA] and microparticle enzyme immunoassay [MEIA]), regarding hematologic and biochemical values at 2 weeks after liver transplantation., Methods: We obtained 256 blood samples from 35 patients, at 2 weeks after liver transplantation, excluding those from patients who were treated with interacting medications or renal replacement therapy. We also excluded the early mortality cases within 2 weeks of liver transplantation. A Dimension RxL HM with the tacrolimus Flex reagent cartilage was used for the ACMIA and the IMx tacrolimus II for the MEIA method., Results: The tacrolimus concentrations measured by the ACMIA method correlated closely with those measured by the MEIA method (r = 0.953). However, the weighted concordance correlation coefficient for the repeated-measurement design was 0.74 (95% confidence interval, 0.66-0.85). The discrepancies in the tacrolimus level between the 2 methods was large among samples with low tacrolimus concentrations especially <5 ng/mL. When the difference ratio of the 2 methods ([ACMIA - MEIA]/ACMIA) was analyzed with a linear mixed-effects model to identify significant laboratory findings, there were no significant differences based on hematocrit, renal function, or hepatic function. However, the serum potassium level correlated with the difference ratio of the 2 methods (estimated slope, 10.173; P = .02)., Conclusions: Both the ACMIA and the MEIA methods are precise; however, the ACMIA method has the advantage of fewer pretreatment procedures. In the early liver transplant period, however, there was a difference between the serum tacrolimus concentrations measured by the 2 methods, especially at a low drug concentrations., (Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.)

Right hepatectomy with the middle hepatic vein (MHV) affects venous return and function of the remaining liver. We compared the remnant liver volume in the donors of resection with or without the MHV on the remnant liver volume regeneration. Living donors who had undergone right hepatectomy without MHV (RH group; n = 36) and those with MHV (ERH group; n = 19) were reviewed. Volume regeneration of segments I-III, segment IV, and total remnant liver volume was assessed at postoperative day (POD) 7 and 30 using a computed tomography-based volumetry program. According to the measured volume data, we calculated the liver remnant volume and the rate of liver remnant volume increase. The regeneration rate of segment IV was significantly low in the ERH group compared with that in the RH group at POD 7 and POD 30 (160% vs 141%; P = .018 and 189% vs 154%; P = .007). In contrast, the regeneration rate of the total remnant liver volume was not significantly different between the 2 groups (173% vs 175%; P = .758 and 199% vs 198%; P = .880). In conclusion, extended right hepatectomy can be safely performed with careful preoperative evaluation without significant impairment of remnant liver regeneration., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This study compared open and video-assisted minilaparotomy surgery in live kidney donors for quality of life (QoL), pain, cosmesis, and recovery. Between January 2003 and March 2006, we reviewed data from 205 patients who underwent live-donor nephrectomy: 116 by video-assisted minilaparotomy and 89 by open surgery. Pain and satisfaction were evaluated using scales from 1 to 10, and QoL, with the 36-item Short Form questionnaire. Hospital stay was significantly shorter among the video-assisted (5.1 +/- 1.6 days) than the open group (6.9 +/- 1.3 days; P < .01). Time to resumption of walking without difficulty and normal activity was significantly shorter among the video-assisted than the open group (P<.01). The video-assisted group showed better QoL scores in 6 of 8 QoL categories, including physical role (P < .01), bodily pain (P < .01), general health (P < .01), vitality (P < .01), emotional health (P < .01), and mental health (P < .01). Patients in the video-assisted group (score, 7.3 +/- 2.4) were more satisfied with the cosmetic outcome than those in the open group (score, 5.1 +/- 3.0; P < .01). In conclusion, donors who underwent nephrectomy via video-assisted minilaparotomy showed better outcomes regarding pain, convalescence, cosmesis, and QoL than those who underwent open surgery.

Donor scarcity is a major obstacle for clinical islet transplantation. Hence, the effective use of the limited number of available islets is necessary for successful islet transplantation. We have developed a new technology that could produce pseudo-islets. Morphologic and functional evaluation was performed to test the feasibility of using these cells for transplantation. A 3-step procedure known as disaggregation-expansion-reaggregation (DER) was employed for pseudo-islet preparation. Islets isolated from 200 to 250-g male Lewis rats by collagenase digestion were separated into single cells by trypsinization. These pancreatic endocrine cells (PECs) were expanded by serial passages in culture before being aggregated at a high cell-density in a suspended state. After DER, cells were morphologically analyzed over time, and gene expression evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). Through expansion by passage for 2 weeks in continuous cultures, approximately 1 million PECs were recovered after aggregation. By phase-contrast microscopy, they presented with spherical shapes and similar sizes compared with naïve islets (50-800 microm). RT-PCR results indicated expression of insulin, glucagon, and pancreatic and duodenal homeobox gene 1, which were observed in primary isolated islets as well. The insulin secretion capacity of pseudo-islets was confirmed by enzyme-linked immunosorbent assay. In conclusion, PECs treated with DER showed potential to serve as a cell source for pseudo-islet generation after in vitro cellular expansion. These cells were both morphologically and genetically similar to naïve islets. Our new technique could be a potential method to overcome the scarcity of donor islets in the near future., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: Reactive oxygen species are believed to be responsible for organ injury after reperfusion. We evaluated serial changes in lipid peroxide (LPO) as an oxidative stress marker after kidney transplantation and investigated its effects on graft function., Methods: Fifty-nine kidney transplant recipients were enrolled between September 2006 and March 2009. The control group consisted of kidney donors (n=40). Serum LPO concentrations were measured by a thiobarbituric acid reaction. The serum creatinine concentration and estimated glomerular filtration rate (eGFR) were used to evaluate graft function. Blood samples were obtained preoperatively, on postoperative day (POD) 5, and at 1 year posttransplantation. The median concentration of LPO on POD 5 was used as a cut-off., Results: The mean preoperative LPO concentration was greater than the control group. The mean LPO concentration on POD 5 was increased compared with the preoperative level. However, the mean LPO concentration at 1 year was significantly decreased compared with the preoperative day, but greater than the control group. On POD 5, the mean serum creatinine concentration in the low LPO group was lower than that in the high LPO group. The mean eGFR in the low LPO group was significantly higher than that in the high LPO group. There was no difference in mean serum creatinine concentrations and eGFR at 1 year between the groups., Conclusion: Oxidative stress showed a significant impact on graft function in the immediate posttransplant period., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

In islet transplantation, encapsulation of immunoisolated islets may provide a way to protect the graft from immune attacks with no immunosuppression. To develop an immunodelusive immunoisolated bioartificial pancreas (BAP), chondrocyte sheets were prepared by cell sheet engineering. We made an immunoisolated BAP encapsulated with rodent-derived chondrocyte sheets and then evaluated its function. Sprague-Dawley rats were used as the source of auricular cartilage and chondrocytes were maintained and expanded by passages. Lewis rats were prepared for islet isolation. A 3-dimensional chondrocyte sheeting immunodelusive immunoisolated BAP (CSI-BAP) was created by multi-layering and unifying the chondrocyte sheets. Subsequently, islets were embedded between each multi-layer sheet. To evaluate the function of the CSI-BAP, a glucose challenge test was performed and secretion of insulin in the culture medium was measured by an enzyme-linked immunosorbent assay. When observed by phase-contrast microscopy, the CSI-BAP maintained close connections between chondrocyte sheets. Islets in the CSI-BAP maintained viability at day 10 and showed good insulin secretion, as revealed by a prompt reaction to increased concentrations of glucose at days 5 and 10. In long-term culture, the CSI-BAP maintained its ability to secrete insulin for 8 weeks. This BAP technology could be an important tool for successful islet transplantation without immunosuppressive drugs., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Inhibition of T-cell activation is the most efficient way to prevent transplant rejection. Protein kinase C (PKC) is an important signaling enzyme in the activation and regulation of T lymphocytes. AEB-071 (AEB) is a low-molecular-weight compound that blocks early T-cell activation via selective inhibition of PKC, a mechanism that differs from that of the calcineurin inhibitors. The present study sought to compare the effects of AEB versus tacrolimus (Tac) to prevent acute rejection in rats that had undergone heterotopic heart transplantation. We investigated the Brown Norway-Lewis rat strain combination for cardiac graft survival over 30 days after transplantation using varying doses of oral AEB and Tac monotherapy. Grafts were monitored by daily palpation; cessation of palpable ventricular contraction was considered to be rejection. Apart from necropsy, we performed histologic examinations of cardiac graft at 7 days after transplantation. In untreated recipients, allograft mean survival times (MST) was 6.83+/-0.41 days. AEB at 15, 30, or 60 mg/kg versus Tac at 1.2 mg/kg significantly prolonged graft survival to a MST of 12.33+/-1.21, 16.67+/-1.21, and 19.33+/-3.83, versus 17.00+/-6.90 days, respectively. Histologic assessment at 7 days after transplantation showed that high-dose AEB significantly decreased the histologic rejection score, indicative of decreased inflammatory cell infiltration into the graft. These results suggested that the administration of AEB (medium or high-dose), a PKC inhibitor, mitigated acute rejection and displayed significantly longer MST, similar to high-dose Tac after heterotopic heart transplantation in the rat., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Invasive pulmonary aspergillosis (IPA) is a serious and lethal complication among organ transplant recipients. This report described the clinical manifestations and treatment of IPA over a 28-year period. From January 1979 to December 2007, 3215 organ transplant patients (2954 kidney and 261 liver recipients) were enrolled in the study. Nine patients developed IPA (7 kidney and 2 liver recipients), yielding an incidence of 0.003% (9/3215). Five IPA patients (55.6%) were diagnosed by transbronchial lung biopsy or autopsy, and 3 (33.3%) by sputum culture study. One patient was diagnosed through clinical manifestations and observations of IPA characteristics on chest X ray. We used amphotericin B (n = 4; 44.4%), voriconazole (n = 2; 22.2%), or fluconazole (n = 1; 11.1%) as the primary antifungal agents, but 2 patients could not receive antifungal agents due to rapid disease progression and sequential mortality. This study showed a high mortality rate among IPA patients (55.6%; 5/9). Only patients who received early antifungal agent thereby after a prompt diagnosis recovered from IPA. This survival advantage warrants careful monitoring for invasive fungal infections after organ transplantation with immediate administration of antifungal agents or surgical intervention.