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Showing papers in "Clinical Transplantation in 2010"


Journal Article
TL;DR: Key benefits of the NTPR are the personal contact between registry staff and participants, the wide range of pregnancy-related variables that are analyzed, and the opportunity for health-care providers to obtain information that helps them care for transplant recipients on a case-by-case basis.
Abstract: The NTPR continues to maintain an ongoing active database as a resource for health professionals counseling recipients regarding pregnancy and for recipients themselves to contact the registry and request information. This includes female transplant recipients as well as male recipients who father pregnancies. Recipients who consent are entered into a database; analyses are ongoing, including long-term follow-up of the recipient, the graft and the offspring. The safety of pregnancy for parent and child remains the goal of the registry. Guidelines for counseling recipients proposed in 1976 remain applicable. Recipients should be in general good health and graft function should be stable and ideally rejection free. Comorbid conditions should be well controlled, especially hypertension and diabetes. While these counseling guidelines were formulated for kidney recipients, they may be extrapolated for other organ recipients. Analyses this year included pregnancy outcomes of recipients on newer agents, MMF and sirolimus. It remains unclear whether these adjunctive therapies should be altered for pregnancy. The balance of immunosuppression and the prevention of rejection need to be weighed against the potential for teratogenicity when counseling these recipients inquiring about pregnancy. Although there are periodic reports of recipients with graft dysfunction, rejection or graft loss possibly related to pregnancy events throughout all the organ groups, whether transplanted as adults or as pediatric patients, the majority of pregnancy outcomes reported to the NTPR appear favorable for parent and newborn. Whether recipients should breastfeed remains controversial. Recent reports in the literature as well as NTPR data appear favorable. This represents the last report from our initial established location at Thomas Jefferson University. In January of this year, the registry moved to Temple University School of Medicine, Department of Surgery, Philadelphia, PA. The NTPR remains committed to investigating outcomes of pregnancies reported by centers or self-referrals nationwide. Some of the active issues for the upcoming year include the potential for teratogenicity with combinations of newer agents, incidence of viral hepatitis, risk assessment for pregnancy in female lung recipients, and long-term maternal and pediatric follow-up.

568 citations


Journal Article
TL;DR: These data indicate increasing use of HCT for persons with blood and bone marrow disorders, and recent trends include increasingUse of alternative donors including HLA-matched unrelated persons and of HLA -matched umbilical cord blood cells, and increasing Use of reduced-intensity pretransplant conditioning regimens.
Abstract: These data indicate increasing use of HCT for persons with blood and bone marrow disorders. Recent trends include increasing use of alternative donors including HLA-matched unrelated persons and of HLA-matched umbilical cord blood cells, increasing use of blood cell rather than bone marrow grafts and increasing use of reduced-intensity pretransplant conditioning regimens. Many of these shifts are driven by logistical considerations like the need for donors in persons without an HLA-identical sibling or expanding access to allotransplants to older patients. In other instances, like the shift from bone marrow to blood cell grafts or from conventional to reduced-intensity pretransplant conditioning regimens few randomized clinical trials have been reported to justify these shifts. More data are needed to critically-assess the impact of these changes.

131 citations


Journal ArticleDOI
TL;DR: Non‐adherence to immunosuppressive medication in renal transplant recipients within the scope of the integrative model of behavioral prediction: a cross‐sectional study.
Abstract: Non-adherence to immunosuppressive medication is strongly associated with poor outcomes. Identifying the factors influencing it is a first step in developing adherence interventions. This study's objective was to investigate the prevalence of self-reported and collaterally-reported non-adherence to immunosuppressives, and, based on the Integrative Model of Behavioral Prediction, to explore the association between non-adherence, intention to adhere, attitudes, norms and self-efficacy.

79 citations


Journal ArticleDOI
TL;DR: The pancreas allograft donor: current status, controversies, and challenges for the future is described.
Abstract: The pancreas allograft is a scarce resource that is currently underutilized. The selection of appropriate deceased donors for pancreas procurement is of paramount importance for minimizing technical failure and optimizing long-term outcomes in pancreas transplantation. Despite the increasing demand for pancreas transplantation, increases in overall organ donation rates and the evolution of criteria that constitute an "acceptable" pancreas donor, the number of deceased donor pancreas transplants being performed in the United States has actually declined in recent years. Although there are many factors that must be considered during evaluation of the potential pancreas allograft donor to minimize morbidity and graft loss, it is evident that there are transplantable organs that are not used. In this review, deceased donor pancreas identification, management, selection, allocation, assessment, preservation, and the problem of pancreas underutilization will be discussed.

79 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examined the dermatologic and mucosal problems associated with mammalian target of rapamycin inhibitor use, and provided personal experiences regarding the management and treatment of these adverse events.
Abstract: Mammalian target of rapamycin inhibitor use is associated with numerous adverse events, including dermatologic and mucosal problems. Awareness of these complications, which clinically manifest across a severity spectrum from minor through severe and may occur at varied time points after initiation of sirolimus therapy, can be useful to clinicians in both managing these events and determining the appropriate intervention(s) for patients. This manuscript examines the dermatologic and mucosal problems associated with mammalian target of rapamycin inhibitor use, reviews the literature, and provides personal experiences regarding the management and treatment of these adverse events.

78 citations


Journal ArticleDOI
TL;DR: Familiarity, ease of access, trust, and awareness of benefits and risks to minimize uncertainty, will all be important for the sustained support of existing treatments.
Abstract: Salles MJC, Sens YAS, Boas LSV, Machado CM. Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs. Clin Transplant 2010: 24: E17–E23. © 2009 John Wiley & Sons A/S. Abstract: Introduction: This study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (MMF). Side effects were investigated. Methods: Sixty-nine patients received one dose of inactivated trivalent influenza vaccine. Antihemagglutinin (HI) antibody response against each strain was measured before and one to six months after vaccination. Results: Geometric mean HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to 13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and 36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively. There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2 protection rates and the seroconversion rate for the H1N1 strain when compared with the use of azathioprine, and subjects transplanted less than 87 months also had inferior antibody response. Adverse events were mild and there were no change on renal function post-vaccination. Conclusion: Renal transplant patients vaccinated against influenza responded with antibody production for influenza A virus strains, but not for influenza B. Use of MMF and shorter time from transplantation decreased the immune response to the vaccine.

74 citations


Journal ArticleDOI
TL;DR: Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes.
Abstract: The purpose of this study was to evaluate risk factors, protective factors, and outcomes associated with Clostridium difficile-associated disease (CDAD) in allogeneic hematopoietic stem-cell transplant (HSCT) recipients. A case-control study was performed with 37 CDAD cases and 67 controls. In the multivariable logistic regression analysis, receipt of a third or fourth generation cephalosporin was associated with increased risk of CDAD (OR = 4.6, 95% CI 1.6-13.1). Receipt of growth factors was associated with decreased risk of CDAD (OR=0.1, 95% CI 0.02-0.3). Cases were more likely to develop a blood stream infection after CDAD than were controls at any point before discharge (p < 0.001). CDAD cases were more likely than controls to develop new onset graft-vs.-host disease (GVHD) (p < 0.001), new onset severe GVHD (p < 0.001), or new onset gut GVHD (p = 0.007) after CDAD/discharge. Severe CDAD was a risk factor for death at 180 d in multivariable Cox proportional hazards regression (HR=2.6, 95% CI 1.1-6.2). CDAD is a significant cause of morbidity and mortality in allogeneic HSCT patients, but modifiable risk factors exist. Further study is needed to determine the best methods of decreasing patients' risk of CDAD.

73 citations


Journal ArticleDOI
TL;DR: Transplantation for Chagas’ disease: an overview of immunosuppression and reactivation in the last two decades and how it has changed since 1990 is described.
Abstract: Over the last 20 yr, the immunosuppression protocols in chagasic heart-transplanted patients have gone through three phases, and we have identified several changes and discoveries about Chagas' disease reactivation, mortality, and neoplasia development. The first phase was especially important because until that time, Chagas' disease was an absolute contraindication for transplantation. The second phase started when an adjustment was made to the immunosuppression protocol, a lower dosage being adopted to avoid adverse effects, especially neoplasias and reactivation episodes. Currently, strategies to change the immunosuppression, especially replacement of mycophenolate mofetil by azathioprine or low doses of mycophenolate in this special situation, have been shown to be effective in reducing Chagas' disease reactivation. Cardiac transplantation for Chagas' disease is a reality. Although patients with Chagas' disease may experience particular complications when undergoing transplantation compared with transplantation for other etiologies, these difficulties are well known, and treatment and preventive strategies are also better established. In other organs and tissues, transplantation in patients with Chagas' disease also has good outcomes. Blood monitoring for parasitemias is mandatory as is the institution of therapy in the case of a reactivation diagnosis. Acute Chagas' disease may occur in patients who received organs from donors with Chagas' disease.

69 citations


Journal ArticleDOI
TL;DR: S Symptomatic lymphoceles after kidney transplantation – multivariate analysis of risk factors and outcome after laparoscopic fenestration.
Abstract: Lymphocele formation is a common complication after kidney transplantation, and laparoscopic surgery has become a widely accepted treatment option. The aim of this retrospective study was to analyze the risk factors of lymphocele development and to assess the treatment outcome after laparoscopic fenestration. We analyzed 426 renal allograft recipients operated between 2002 and 2006 receiving triple immunosuppression with calcineurin inhibitors. The incidence of lymphocele was 9.9%, while 24 (5.6%) patients with symptomatic lymphoceles required laparoscopic surgery. Serum creatinine at diagnosis was significantly higher in patients with lymphoceles treated surgically (3.2 +/- 0.7 vs. 1.7 +/- 0.6 mg/dL; p < 0.001). After successful laparoscopic intervention, creatinine concentrations recovered until discharge and were comparable to other patients (1.6 +/- 0.5 vs. 1.5 +/- 0.5 mg/dL; p = NS). While we observed a significant association of lymphocele formation with diabetes, tacrolimus therapy, and acute rejection in univariate testing, only diabetes remained a significant factor after multivariate analysis. Laparoscopic fenestration proved to be a safe and efficient method without any associated mortality and a low recurrence rate of 8.3% (n = 2). We conclude that diabetes is an independent risk factor for lymphocele development, and laparoscopic fenestration should be the treatment of choice for larger and symptomatic lymphoceles, as it is safe and offers a low recurrence rate.

61 citations


Journal ArticleDOI
TL;DR: A prospective, randomized, multicenter study evaluating early corticosteroid withdrawal with Thymoglobulin in living‐donor kidney transplantation and its effects on survival and quality of life.
Abstract: Woodle ES, Peddi VR, Tomlanovich S, Mulgaonkar S, Kuo PC, for the TRIMS Study Investigators. A prospective, randomized, multicenter study evaluating early corticosteroid withdrawal with Thymoglobulin® in living-donor kidney transplantation. Clin Transplant 2010: 24: 73–83. © 2009 John Wiley & Sons A/S. Abstract: Background: This study compared the safety and efficacy of early corticosteroid withdrawal (ECSWD) with rabbit anti-thymocyte globulin (rATG) induction to chronic corticosteroid therapy (CCST) without antibody induction in primary, living-donor renal transplant recipients. Methods: Eligible subjects were randomized 2:1 to receive either an ECSWD (n = 103) or CCST (n = 48) regimen, with all subjects receiving tacrolimus and mycophenolate mofetil (MMF). Results: Results are reported as ECSWD vs. CCST. No significant differences were observed in the primary composite endpoint of freedom from biopsy-proven acute rejection (BPAR), graft loss, and death at six months (85.4% vs. 85.4%) or 12 months (84.4% vs. 74.4%). At 12 months, no difference was observed in BPAR (13.9% vs. 19.4%); however, ECSWD was associated with lower total cholesterol (159.7 ± 39.2 vs. 196.5 ± 56.7 mg/dL, p = 0.012), and trends toward significance were noted in serum triglycerides (151.9 ± 92.0 vs. 181.4 ± 78.8 mg/dL, p = 0.073) and weight gain (+3.6 ± 9.4 vs. +6.4 ± 9.3 kg, p = 0.069). No differences were observed in serious adverse events or infectious complications, with the exception of a higher incidence of leukopenia with ECSWD. Conclusions: rATG with tacrolimus and MMF therapy may allow early elimination of corticosteroids, is associated with trends toward lower lipid levels, less weight gain, and a safety profile comparable to CCST therapy.

60 citations


Journal ArticleDOI
TL;DR: Serrano MT, Garcia‐Gil A, Arenas J, Ber Y, Cortes L, Valiente C, Araiz JJ: Outcome of liver transplantation using donors older than 60’year of age.
Abstract: Serrano MT, Garcia-Gil A, Arenas J, Ber Y, Cortes L, Valiente C, Araiz JJ. Outcome of liver transplantation using donors older than 60 year of age. Clin Transplant 2010: 24: 543–549. © 2009 John Wiley & Sons A/S. Abstract: The impact of donor age on liver transplantation has been analyzed in several studies with contradictory results. Our aim was to evaluate graft survival and complications in the first year after liver transplantations with livers from older donors. Methods: Prospective analysis of 149 consecutive primary liver transplantations performed between 2000 and 2005. Transplantations were divided into two groups according to donor age: group A, <60 yr old (n = 102); and group B, ≥60 yr old (n = 47). Results: Chronic and acute rejection, vascular complications, and infections were not statistically different between the groups. Anastomotic biliary strictures were similar in the two groups, but non-anastomotic biliary strictures (NABS) were clearly more frequent in the older donor group (17% vs. 4.9%; OR 3.9; p = 0.025). NABS with no arterial complication was diagnosed in 10.6% of cases in group B vs. 1% in group A (OR = 12; p = 0.012). Graft survival in the first year was 86.67% in the younger group of donors and 71.43% in the older group (p < 0.05), but patient survival was not different. Conclusions: The use of grafts from donors ≥60 yr decreased graft survival after liver transplantation and was related to a higher frequency of non-anastomotic biliary strictures.

Journal ArticleDOI
TL;DR: Steatosis of the hepatic graft as a risk factor for post‐transplant biliary complications in mice is found to be a major cause for concern.
Abstract: Baccarani U, Isola M, Adani GL, Avellini C, Lorenzin D, Rossetto A, Curro G, Comuzzi C, Toniutto P, Risaliti A, Soldano F, Bresadola V, De Anna D, Bresadola F. Steatosis of the hepatic graft as a risk factor for post-transplant biliary complications. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01128.x. © 2009 John Wiley & Sons A/S. Abstract: Background: Despite recent advances in organ preservation, immunosuppression, and surgical techniques, the biliary tree is still considered the Achilles’ heel of liver transplantation. The aim of this study is to retrospectively analyze the incidence of biliary complications and identify risk factors that might predispose to the development of biliary problems. Methods: From January 2004 to December 2007, 117 consecutive liver transplantations were retrospectively analyzed for the development of biliary complications by the review of medical records. Patients were divided into group 1 with biliary complications (n = 43) and group 2 without biliary complications (n = 74). Results: The overall biliary complication rate was 36.8% (leakage 6% and stricture 30.8%). Univariate analysis indicated that significant predictors of biliary complications were the time interval between portal and arterial reperfusion (p = 0.037) and macrovacuolar steatosis of the graft > 25% (p = 0.004). Stepwise logistic regression model demonstrated that a macrosteatosis of the graft > 25% (OR = 5.21 CI 95% [1.79–15.15], p = 0.002) was the only independent risk factor predicting biliary complications after liver transplantation. No differences in patient’s and graft’s survival were noted between the two groups. Conclusion: According to our experience, transplanting a liver with > 25% of steatosis is a risk factor for the development of biliary complication.

Journal ArticleDOI
TL;DR: The impact of rituximab‐associated B‐cell defects on West Nile virus meningoencephalitis in solid organ transplant recipients is studied.
Abstract: West Nile virus (WNV) is a flavivirus that has been an important cause of neuroinvasive disease during the late summer and early fall in the United States since 1999. In the immunocompetent population, meningoencephalitis occurs in 1:150 individuals infected with WNV. However, in immunocompromised patients, particularly transplant recipients, the incidence of central nervous system disease has been estimated to be as high as 40%, although these calculations are based on relatively small numbers of cases (1). Multiple case reports describing poor outcome in most, but not all, WNV-infected transplant recipients have been published (2–4), likely due to immunosuppressive agents. These drugs act primarily by inhibiting T-lymphocyte function (5, 6). While mechanisms to block cellular rejection have focused on T-cell pathways, B-cell-mediated transplant rejection has more recently been identified (7). Use of rituximab, a monoclonal antibody directed against the B-cell-specific antigen B1 (CD20) (8, 9) is thought to have antihumoral rejection activity and has been employed as a therapeutic in humoral transplant rejection (7). We report a case of a lung transplant recipient who received two courses of rituximab for acute humoral rejection (capillaritis), followed by a rapidly progressive and fatal WNV meningoencephalitis. Furthermore, she was unable to mount serum WNV IgM or IgG antibody responses against WNV two wk following the onset of her symptoms. The diagnosis of WNV neuroinvasive disease was confirmed by positive WNV polymerase chain reaction identification in the cerebrospinal fluid (CSF). Meningoencephalomyelitis at autopsy was extremely extensive, involving all levels of spinal cord sampled, as well as cerebral subcortical gray matter, cerebellum, brainstem, hippocampi, cerebral white matter, and proximal ventral nerve roots. Our concern is that the use of both T-cell and B-cell immunosuppression may have significantly contributed to her rapid decline, as indicated by the rapidity of her course, lack of WNV antibody production, and the severity of tissue damage on histopathologic examination of the brain and spinal cord tissue.

Journal ArticleDOI
TL;DR: Yanagimachi et al. as mentioned in this paper found that genetic variability in CYP3A5 and ABCB1 genes may be associated with CNI-related neurotoxicity after hematopoietic stem cell transplant.
Abstract: Yanagimachi M, Naruto T, Tanoshima R, Kato H, Yokosuka T, Kajiwara R, Fujii H, Tanaka F, Goto H, Yagihashi T, Kosaki K, Yokota S. Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation. Clin Transplant 2010: 24: 855–861. © 2009 John Wiley & Sons A/S. Abstract: Background: One severe side effect of calcineurin inhibitors (CNIs: such as cyclosporine [CsA] and tacrolimus [FK506]) is neurotoxicity. CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp), encoded by ABCB1 gene. In the present study, we hypothesized that genetic variability in CYP3A5 and ABCB1 genes may be associated with CNI-related neurotoxicity. Methods: The effects of the polymorphisms, such as CYP3A5 A6986G, ABCB1 C1236T, G2677T/A, and C3435T, associated with CNI-related neurotoxicity were evaluated in 63 patients with hematopoietic stem cell transplantation. Results: Of the 63 cases, 15 cases developed CNI-related neurotoxicity. In the CsA patient group (n = 30), age (p = 0.008), hypertension (p = 0.017), renal dysfunction (p < 0.001), ABCB1 C1236T (p < 0.001), and G2677T/A (p = 0.014) were associated with neurotoxicities. The CC genotype at ABCB1 C1236T was associated with it, but not significantly so (p = 0.07), adjusted for age, hypertension, and renal dysfunction. In the FK506 patient group (n = 33), CYP3A5 A6986G (p < 0.001), and ABCB1 C1236T (p = 0.002) were associated with neurotoxicity. At least one A allele at CYP3A5 A6986G (expressor genotype) was strongly associated with it according to logistic regression analysis (p = 0.01; OR, 8.5; 95% CI, 1.4–51.4). Conclusion: The polymorphisms in CYP3A5 and ABCB1 genes were associated with CNI-related neurotoxicity. This outcome is probably because of CYP3A5 or P-gp functions or metabolites of CNIs.

Journal ArticleDOI
TL;DR: Persistent fatigue in liver transplant recipients after a two‐year follow‐up study is found to be a major concern.
Abstract: van Ginneken BTJ, van den Berg-Emons RJG, van der Windt A, Tilanus HW, Metselaar HJ, Stam HJ, Kazemier G. Persistent fatigue in liver transplant recipients: a two-year follow-up study. Clin Transplant 2010: 24: E10–E16. © 2009 John Wiley & Sons A/S. Abstract: Background: Fatigue after liver transplantation (LTx) is a major problem that is associated with lower daily functioning and health-related quality of life (HRQoL). This study aimed to assess changes over time in fatigue following LTx. We also examined daily functioning and HRQoL changes over time and assessed the influence of fatigue and changes in fatigue on daily functioning and HRQoL. We determined whether sleep quality, anxiety, and depression were associated with fatigue. Methods: We identified 70 LTx recipients who had previously participated in a cross-sectional study and reassessed them after two yr to determine changes in level of fatigue, daily functioning, and HRQoL. We also assessed sleep quality, anxiety, and depression after two yr. Results: Level of fatigue and level of daily functioning were unchanged at follow-up. HRQoL domains remained stable or worsened. Fatigue was a significant predictor of daily functioning and all HRQoL domains (p < 0.01). Change in fatigue was a significant predictor of daily functioning and the HRQoL domains of “physical functioning,”“vitality,” and “pain” (p < 0.05). Sleep quality, anxiety, and depression were associated with fatigue severity (r = 0.35 to r = 0.60, p < 0.05). Conclusion: This longitudinal study shows that fatigue is a chronic problem after LTx and that daily functioning and HRQoL do not improve over time. This study supports the need for intervention programs to address fatigue after LTx.

Journal ArticleDOI
TL;DR: In conclusion, acute renal failure early after heart transplantation: risk factors and clinical consequences.
Abstract: Limited information exists about acute renal failure (ARF) early after heart transplantation (HTx). We correlated pre-, per-, and post-operative patient and donor parameters to the risk of developing ARF. We also analyzed the consequences of ARF on kidney function after HTx, risk of later need for chronic dialysis or kidney transplantation, and mortality. In a retrospective study from 1983 to 2007, 145 (25%) of 585 HTx recipients developed ARF, defined as ≥ 26.4 micromol/L or ≥ 50% increase in serum creatinine from pre-operatively to the seventh day post-HTx and/or the need of early post-operative dialysis. Independent risk factors for ARF were intravenous cyclosporine immediately post-operatively (odds ratio [OR] 2.16, 95% CI 1.34-3.50, p = 0.02), donor age (OR 1.02, 95% CI 1.00-1.04, p = 0.02), and pre-operative cardiac output (OR 1.38, 95% CI 1.12-1.71, p = 0.003). The development of ARF was a predictor for short-term survival (≤ 3 months) ranging from 98% for patients who improved their creatinine after HTx vs. 79% for those in need of dialysis (p < 0.001). However, ARF did not predict subsequent end stage renal disease in need of dialysis or renal transplantation. ARF is a common complication post-HTx. As ARF is associated with short-term survival, post-operative strategies of preserving renal function have the potential of reducing mortality. Of avoidable risk factors, the use of intravenous CsA should be discouraged.

Journal ArticleDOI
TL;DR: Agha‐Hosseini F, Jahani M‐A, JahANI M, Mirzaii‐Dizgah I, Ali‐Moghaddam K. In vitro isolation of stem cells derived from human dental pulp.
Abstract: Agha-Hosseini F, Jahani M-A, Jahani M, Mirzaii-Dizgah I, Ali-Moghaddam K. In vitro isolation of stem cells derived from human dental pulp. Clin Transplant 2009: DOI: 10.1111/j.1399-0012.2009.01137.x. © 2009 John Wiley & Sons A/S. Abstract: Stem cells are characterized by the ability to differentiate and to self-renew. Stem cells derived from human dental pulp have been shown to differentiate into osteoblasts serving as a potential source of autologous bone produced in vitro. The purpose of the present study was to isolate mesenchymal stem cells from dental pulp. Dental pulp was gently extracted from 27 intact human permanent third molars of patients aged 18–25. Cow horn forceps were used to isolate intact dental pulp in sterilized condition. The pulps were cultured in a medium containing Dulbecco’s modified Eagle’s medium-low glucose (DMEM)-LG and Amphotericin 1%. The cells were subsequently expanded by passages, two passages were performed before they were stored in liquid nitrogen for further examination. DMEM + fetal bovine serum (FBS) 10% L-Glutamin 0.1% + Trypsin 2.5% + ethylene diamine tetraacetic acid (EDTA) were used for passage. Light microscope and flow cytometry were used to study the cells. The isolated dental pulp cells expressed mesenchymal stem cell markers. The cells were negative for CD34 and CD31 and CD45 but were positive for CD13, CD44, CD90, CD166, and CD105. These results indicate that dental pulp can be use as a source of stem cells that we can isolate and culture.

Journal ArticleDOI
TL;DR: A decade of minimally invasive donation: experience with more than 1200 laparoscopic donor nephrectomies at a single institution at asingle institution is described.
Abstract: Leventhal JR, Paunescu S, Baker TB, Caciedo JC, Skaro A, Kocak B, Gallon L, Friedewald J, Luo X, Kaufman DB, Fryer JP, Abecassis MM. A decade of minimally invasive donation: experience with more than 1200 laparoscopic donor nephrectomies at a single institution. Clin Transplant 2010 DOI: 10.1111/j.1399-0012.2009.01199.x. © 2010 John Wiley & Sons A/S. Abstract: Background: The past decade has seen laparoscopic donor nephrectomy (LDN) transform into a standard of care procedure. Furthermore, LDN has evolved with the introduction of new technologies aimed at increasing efficiency and safety. There are few large, single center experiences detailing the results of LDN, its associated complications, and their management. Methods: We performed a retrospective review of 1200 LDN performed at our center for both pediatric and adult recipients. Results: Mean body mass index of donors was 27.1 (range 17–48). Twenty-six percent of kidneys had multiple renal arteries. Greater than 99% were left LDN. Mean length of stay was 1.37 ± 0.6 d, which decreased to 1.1 ± 0.5 d for the last 475 cases. The overall complication rate was 4.2%. Among those patients, 1.6% of the patients experienced an intraoperative complication, including eight renovascular injuries; 7/8 renovascular injuries led to open conversion. Four conversions were elective; our overall conversion rate was 0.92%; 2.6% had a post-operative complication; 1.2% required readmission for complication management. Three of 1200 patients have required reoperation for prolonged ileus and internal hernia (2), respectively. There have been no cases of donor renal failure or death. Since 2003, we have routinely used hand-assisted LDN (HALDN). There have been no cases of primary non-function. Urologic complications have been uncommon. Conclusions: Our series supports the safety and efficacy of LDN/HALDN.

Journal ArticleDOI
TL;DR: Validation of methodologies for quantifying isolated human islets: an islet cell resources study.
Abstract: Kissler HJ, Niland JC, Olack B, Ricordi C, Hering B J, Naji A, Kandeel F, Oberholzer J, Fernandez L, Contreras J, Stiller T, Sowinski J, Kaufman DB. Validation of methodologies for quantifying isolated human islets: an islet cell resources study. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01052.x. © 2009 John Wiley & Sons A/S. Abstract: Background: Quantification of islet mass is a crucial criterion for defining the quality of the islet product ensuring a potent islet transplant when used as a therapeutic intervention for select patients with type I diabetes. Methods: This multi-center study involved all eight member institutions of the National Institutes of Health-supported Islet Cell Resources Consortium. The study was designed to validate the standard counting procedure for quantifying isolated, dithizone-stained human islets as a reliable methodology by ascertaining the accuracy, repeatability (intra-observer variability), and intermediate precision (inter-observer variability). The secondary aim of the study was to evaluate a new software-assisted digital image analysis method as a supplement for islet quantification. Results: The study demonstrated the accuracy, repeatability and intermediate precision of the standard counting procedure for isolated human islets. This study also demonstrated that software-assisted digital image analysis as a supplemental method for islet quantification was more accurate and consistent than the standard manual counting method. Conclusions: Standard counting procedures for enumerating isolated stained human islets is a valid methodology, but computer-assisted digital image analysis assessment of islet mass has the added benefit of providing a permanent record of the isolated islet product being evaluated that improves quality assurance operations of current good manufacturing practice.

Journal ArticleDOI
TL;DR: Doenecke A, Tsui T‐Y, Zuelke C, Scherer MN, Schnitzbauer AA, Schlitt H‐J, Obed A. Pre‐existent portal vein thrombosis in liver transplantation: influence of pre‐operative disease severity.
Abstract: Doenecke A, Tsui T-Y, Zuelke C, Scherer MN, Schnitzbauer AA, Schlitt H-J, Obed A. Pre-existent portal vein thrombosis in liver transplantation: influence of pre-operative disease severity. Clin Transplant 2010: 24: 48–55. © 2009 John Wiley & Sons A/S. Abstract: Background: Portal vein thrombosis (PVT) is a surgical challenge in liver transplantation (LTx). In contrast to LTx in decompensated liver disease, which are associated with a higher morbidity and mortality, PVT influence on outcome is still under debate. To evaluate this influence at different stages of liver decompensation, we compared the outcome of patients suffering from PVT to patients with patent portal vein within different score ranges. Methods: We included 193 LTx (24 with PVT) in our study, transplanted between 2004 and 2007 at our institution. Patients were divided into four Model of End-Stage Liver Disease (MELD) score groups, and outcome was compared between PVT- and non-PVT patients. Results: In non-decompensated liver disease (MELD 15 (decompensated liver disease) leads to an equal or even better survival in PVT-patients compared with patients without PVT (one-yr survival 91% vs.75%), with an only slightly increased morbidity. Conclusion: Outcome in patients with PVT seems to be dependent on pre-operative disease severity. In contrast to compensated liver disease, no influence of PVT on outcome could be found in decompensated liver disease, and should therefore not be considered as a contraindication in LTx.

Journal ArticleDOI
TL;DR: The effects of classroom education on knowledge and attitudes regarding organ donation in ethnically diverse urban high schools and how these attitudes are shaped in the classroom are studied.
Abstract: School-based health education is a promising approach for improving organ donation rates, but little is known about its efficacy among ethnically diverse youth. The impact of a classroom intervention was examined in a multicultural high school population where students' ethnicities were 45% African American, 30% Asian American, and 33% Caucasian (allowing for multiracial choices). A baseline survey was administered to all health classes within two wk prior to intervention. On the intervention day, classes randomly assigned to the intervention group received an educational session, followed by a second survey; in control classes, the second survey was taken before the educational session. At baseline, non-Caucasian ethnicity and male gender were each associated with lower levels of willingness to donate. Following the intervention, students in the intervention group demonstrated a significant increase in knowledge scores (p < 0.001), as well as positive movement of opinion regarding willingness to donate (p < 0.0001). Most importantly, the positive changes in opinion occurred independently of ethnicity and gender, in spite of these both being negative predictors of opinion at baseline. These results demonstrate that even a single classroom exposure can impact knowledge levels, correct misinformation, and effect opinion change on organ donation among an ethnically diverse adolescent population.

Journal ArticleDOI
TL;DR: Measurement of CD4+ T‐cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation after liver transplants is measured.
Abstract: Recurrence of hepatitis C virus (HCV) can be difficult to distinguish from acute cellular rejection (ACR) following liver transplantation. The Cylex Immune Function Assay (ImmuKnow) provides objective measure of recipient's immune function. The goal is to assess the ability of this assay to distinguish these similar conditions. A retrospective review was performed in 54 recipients with HCV. ImmuKnow assays were measured with allograft biopsies. Levels of adenosine triphosphate (ATP) release from CD4+ T cells (ng/mL) were compared with the following biopsy result classifications: 365 ± 130 with ACR (n = 11), 152 ± 100 with recurrent HCV (n = 26), 240 ± 71 with normal biopsies (n = 12), and 157 ± 130 with overlapping features of ACR and recurrent HCV (n = 5). Recipients with recurrent HCV had lower immune response than those with ACR (p < 0.0001).Using a cutoff level of 220, the sensitivity and specificity for distinguishing two conditions were 88.5% and 90.9%, respectively. When recipients with overlapping features had low immune response, three of four recipients' subsequent biopsies showed recurrent HCV. In conclusion, the ImmuKnow assay can be a sensitive and specific additional test for distinguishing recurrent HCV from ACR and may be useful for predicting which recipients may be most vulnerable to recurrent HCV.

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TL;DR: A single‐center analysis of incidence, reduction in immunosuppression and clinical course in renal transplant recipients in China shows clear trends in polyomavirus BK replication and nephropathy.
Abstract: Huang G, Chen L-Z, Qiu J, Wang C-X, Fei J-G, Deng S-X, Li J, Chen G-D, Zhang L, Fu Q, Zeng W-T, Zhao D-Q. Prospective study of polyomavirus BK replication and nephropathy in renal transplant recipients in China: a single-center analysis of incidence, reduction in immunosuppression and clinical course. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01141.x © 2009 John Wiley & Sons A/S. Abstract: Background: BK virus (BKV)-associated nephropathy (BKVAN) in renal transplant recipients is an important cause of renal transplant dysfunction. Our aim was to determine the kinetics of BKV load within one yr after kidney transplantation under the impact of intensive monitoring and reduction in maintenance immunosuppression, the incidence of BKVAN, and the outcome of BKVAN treatment. Methods: Urine and peripheral blood (PB) were taken from 90 renal transplant recipients for BKV cytological testing and real-time PCR for BKV DNA at one, three, six, nine, and 12 months after transplantation and treatment. Graft biopsies and urinary sediments of recipients with BKVAN were taken to monitor viral particles by conventional transmission electron microscopy (TEM). Results: By one post-transplant year, urinary decoy cells (median, 8/10 HPF), BKV viruria (median, 2.60 × 105 copies/mL), viremia (median, 9.65 × 103 copies/mL), and BKVAN occurred in 42.2%, 45.6%, 22.2%, and 5.6% of patients, respectively. The incidence of BK infection was lower in patients who received cyclosporine A (CsA) (28.9%) compared to tacrolimus (FK506) (57.7%) (p = 0.007). An increased hazard of BK infection was associated with the use of FK506 (HR 2.6, p = 0.009) relative to CsA. After reduction in immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction, or graft loss. BKVAN was diagnosed in five patients (5.6%). The treatment of immunosuppression reduction was effective (i.e., decreased the viral load and number of decoy cells, and improved graft function) in our five patients with BKVAN. Quantitative count of decoy cells (e.g., >10 per 10 HPF) as a marker of viremia and BKVAN had increased positive predictive values of 85.7% and 57.1%, respectively. Conclusions: Choice of FK506 as immunosuppressive agent is an independent risk factor affecting BKV infection. Monitoring and pre-emptive of immunosuppression reduction were associated with resolution of viremia and showed effective in BKVAN recipients at the early stage without acute rejection or graft loss. Quantitative count of urine cytology is a very convenient, useful, and sensitive method for evaluating BKV infection in renal transplant recipients.

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TL;DR: The chances and limitations of non‐invasive tests in the assessment of liver fibrosis in liver transplant patients and their implications for clinical practice are studied.
Abstract: Kamphues C, Lotz K, Rocken C, Berg T, Eurich D, Pratschke J, Neuhaus P, Neumann UP. Chances and limitations of non-invasive tests in the assessment of liver fibrosis in liver transplant patients. Clin Transplant 2009 DOI:10.1111/j.1399-0012.2009.01152.x © 2009 John Wiley & Sons A/S. Abstract: Because fibrosis progression resulting in liver cirrhosis represents the main reason for graft lost in patients after liver transplantation, an early detection of liver fibrosis is crucial. In recent years, several non-invasive tests for the assessment of liver fibrosis have been developed. We prospectively assessed the stage of liver fibrosis of 135 liver transplant patients (94 hepatitis C virus [HCV], 41 alcoholic cirrhosis) using liver biopsy, transient elastography, and serum markers. In the HCV group, the area under the receiver operating characteristic curve (AUROC) for diagnosis of significant fibrosis (F ≥ 2) and cirrhosis (F = 4) was 0.81 (negative predictive value [NPV] = 0.58, positive predictive value [PPV] = 0.9) and 0.87 (NPV = 0.94, PPV = 0.56), respectively. In the alcoholic cirrhosis group, significant fibrosis (F ≥ 2) was diagnosed with an AUROC of 0.83 (NPV = 1.00, PPV = 0.23). In both groups, higher AUROC values were reached in patients with a body mass index of <25 kg/m2, and both serum markers showed no significant correlation to liver fibrosis. The transient elastography is a reliable test for exclusion of liver cirrhosis in HCV transplant and significant liver fibrosis in alcoholic transplant patients. For the diagnosis of significant liver fibrosis in HCV transplant patients, the transient elastography reaches good results but cannot replace liver biopsy. Both serum markers AST-to-platelet ratio index and FIB-4 are not feasible to assess liver fibrosis in liver transplant patients.

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TL;DR: Risk factors and consequences of post‐transplant diabetes mellitus and the impact on survival and quality of life after transplant are studied.
Abstract: Demirci MS, Toz H, Yilmaz F, Ertilav M, Asci G, Ozkahya M, Zeytinoglu A, Nart D, Ok E. Risk factors and consequences of post-transplant diabetes mellitus. Clin Transplant 2010 DOI: 10.1111/j.1399-0012.2010.01247.x. © 2010 John Wiley & Sons A/S. Abstract: Background: The aim of this study is to investigate the clinical course as well as risk factors and prognosis of post-transplant diabetes mellitus (PTDM). Methods: Five hundred fifty-five kidney transplant recipients were retrospectively evaluated. PTDM was defined as fasting blood glucose ≥140 mg/dL on at least two consecutive measurements or requirement of oral antidiabetic drug or insulin. Patients with PTDM were divided into subgroups according to time of onset (early; <90 d vs. late, ≥90 d) and duration of diabetes (transient, <90 d vs. sustained ≥90 d). Results: The frequency of PTDM was 18.3%. In multivariate analysis age (p < 0.001), hepatitis C virus (HCV) infection (p < 0.05) and tacrolimus use (p < 0.001) were independent risk factors. Among 220 HCV+ patients, liver biopsy was performed in 158, the histological grade (3.3 ± 2.8 vs. 4.4 ± 3.1) and stage (0.9 ± 1.1 vs. 1.4 ± 1.2) were significantly more severe in patients with PTDM than in non-diabetics. Incidence of PTDM in patients with severe fibrosis was 46.7%; 19.2% in nil or mild fibrosis (p < 0.05). Patient and graft survival were significantly worse, and cardiovascular events and life-threatening infection episodes were more frequent in PTDM. Half of the patients had early PTDM, while 30.3% of patients with PTDM showed transient nature. Five- and 10-yr death censored graft survival rates were worse in transient subgroup compared with sustained patients with diabetes (log rank 0.025) whereas there was no difference in outcome between early and late subgroups. Conclusions: Age, tacrolimus, and HCV are independent risk factors for PTDM. PTDM has a negative impact on both patient and graft survival, irrespective of the time of onset and duration of diabetes.

Journal ArticleDOI
TL;DR: Magnetic resonance cholangiopancreatography for the accurate diagnosis of biliary complications after liver transplantation: comparison with endoscopic retrogradeCholangiography and percutaneous transhepatic cholANGiography – long‐term follow‐up.
Abstract: Biliary complications after liver transplantation remain a serious cause of morbidity and mortality. Direct invasive cholangiographic techniques, endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC), have procedure-related complications. Magnetic resonance cholangiopancreatography (MRCP) is non-invasive, safe, and accurate. The aim of this study was to evaluate MRCP in detecting biliary complications following liver transplantation and comparing findings with ERCP and PTC. Twenty-seven consecutive liver transplant recipients who presented with clinical and biochemical, ultrasonographic, or histological evidence of biliary complications were evaluated with MRCP. Patients were followed up for a median period of 36 months. The presence of a biliary complication was confirmed in 18 patients (66.6%): anastomotic biliary stricture in 12 (66.6%); diffuse intrahepatic biliary stricture in 5 (27.7%): ischemic (n = 3), recurrence of primary sclerosing cholangitis (n = 2), and choledocholithiasis in one. In nine patients (33.3%), MRCP was normal. Six patients underwent ERCP, and eight PTC. There was a statistically significant correlation between the MRCP and both ERCP and PTC (p = 0.01) findings. The sensitivity and specificity of the MRCP were 94.4% and 88.9%, respectively, and the positive and negative predictive values, 94.4% and 89.9%, respectively. MRCP is an accurate imaging tool for the assessment of biliary complications after liver transplantation. We recommend that MRCP be the diagnostic imaging modality of choice in this setting, reserving direct cholangiography for therapeutic procedures.

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TL;DR: Avelino‐Silva VI, D′Albuquerque LAC, Bonazzi PR, Song ATW, Miraglia JL, de Brito Neves A, Abdala E. Liver transplant from Anti‐HBc‐positive, HBsAg‐negative donor into HBs Ag‐negative recipient: is it safe?
Abstract: Avelino-Silva VI, D′Albuquerque LAC, Bonazzi PR, Song ATW, Miraglia JL, de Brito Neves A, Abdala E. Liver transplant from Anti-HBc-positive, HBsAg-negative donor into HBsAg-negative recipient: is it safe? A systematic review of the literature. Clin Transplant 2010: 24: 735–746. © 2010 John Wiley & Sons A/S. Abstract: Introduction: After liver transplant (LT) from Anti-HBc+/HBsAg− donors into HBsAg− recipients, transmission of hepatitis B virus (HBV) may occur (de novo HBV infection). This study analyzes the incidence of de novo HBV infection in HBsAg− recipients of Anti-HBc+/HBsAg− LT with respect to: (i) the recipients’ HBV serology and (ii) the type of preventive therapy adopted. Methods: A systematic review of the literature using the electronic database Medline. Results: Five hundred and fifty-two LT in 36 articles were selected. Lamivudine, Hepatitis B immune globulin (HBIG), revaccination, and combined therapies were employed in multiple strategies as preventive interventions. Naive recipients had a high risk of de novo HBV infection, with smaller incidences when HBIG and lamivudine were used, either alone or in association. Vaccinated recipients or those with isolated hepatitis B core antibodies (Anti-HBc) and previous HBV infection had lower risks of viral transmission, additionally reduced by any prophylaxis adoption. Discussion: LT from Anti-HBc+/HBsAg− donors into HBsAg− recipients is apparently safe, as long as the recipient is vaccinated or presents an isolated Anti-HBc or previous HBV infection and some prophylaxis is employed. Currently lamivudine seems the best alternative; other nucleoside analogs and revaccination strategies should be considered in future studies. Follow-up and preventive therapies should be maintained for five yr or preferably throughout the recipients’ life span.

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TL;DR: The impact of cytomegalovirus infection ≥1 yr after primary renal transplantation after primary kidney transplantation is studied.
Abstract: Browne BJ, Young J-A, Dunn TB, Matas AJ. The impact of cytomegalovirus infection ≥1 yr after primary renal transplantation. Clin Transplant 2010: 24: 572–579. © 2010 John Wiley & Sons A/S. Abstract: We studied the impact of a first post-transplant cytomegalovirus (CMV) infection greater than one year after primary kidney transplantation. Risk factors for developing late CMV were acute rejection and donor–recipient CMV status. Of those developing late CMV, 35% were donor (D) positive, recipient (R) negative; however, 23% were D+R+, 22% D−R+, and 15% D−R−. Late CMV was associated with significantly decreased patient and graft survival.

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TL;DR: It is necessary to select patients suitable for kidney transplantation on the basis of prior history and once they provide informed consent for the procedure, the risk of adverse events and complications is low.
Abstract: Luan FL, Langewisch E, Ojo A. Metabolic syndrome and new onset diabetes after transplantation in kidney transplant recipients. Clin Transplant 2010: 24: 778–783. © 2009 John Wiley & Sons A/S. Abstract: Background: Metabolic syndrome (MS) and new onset diabetes after transplant (NODAT) are common in kidney transplant patients. We studied the relationship between the two conditions and their impact on metabolic and cardiovascular risk profiles. Methods: All non-diabetic patients transplanted between 1999 and 2005 who were followed up to 2006 were included. MS and NODAT were determined. Kaplan–Meier survival and various regression analyses were performed to determine the clinical correlates for both conditions and their association with various cardiovascular risk factors. Results: Among 591 patients, 314 (53.1%) had MS and 90 (15.2%) developed NODAT. The two conditions were highly associated with each other as 84 patients with NODAT also had MS (14.2%). Elevated body mass index and fasting glucose levels at transplant were risk factors for both conditions, whereas weight gain after transplant was associated only with MS. African American, old age, and hypertension-related ESRD were risk factors for NODAT. Finally, the presence of MS was associated with reduced kidney function and elevated uric acid levels, whereas the presence of NODAT with elevated pulse pressure. Conclusions: MS and NODAT are highly prevalent and significantly associated with impaired metabolic and cardiovascular risk profiles. Early identification of such conditions may facilitate targeted therapeutic intervention.

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TL;DR: Preservation of the donor pancreas for whole Pancreas and islet transplantation and its application in whole and partial replacement patients is described.
Abstract: Whole pancreas and islet cell transplantation are both reliant upon the procurement and preservation of a high quality donor pancreas for a successful outcome. In the climate of a reducing donor pool it is imperative that donor optimization, meticulous surgical retrieval and evidence based methods of preservation are practiced to ensure optimal graft quality. Moreover expanded criteria donors and novel methods of pancreas preservation have the potential to expand the number of usable grafts and increase the availability of these transplant modalities to suitable patients with diabetes. This article provides a review of the current literature surrounding donor management, surgical technique and the various technologies of organ preservation applicable to the donor pancreas.