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Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. Finally, antibody mediated rejection due to donor specific antibodies strongly affects allograft survival. Many drugs have been tested in the last decades, but very few have come to clinical use. The most recent one is CTLA4-Ig (belatacept), a costimulation blockade molecule that targets the second signal of T cell activation and is associated with a better long term kidney function than calcineurin inhibitors, despite an increased risk of acute cellular rejection. The research of new maintenance long-term immunosuppressive agents focuses on costimulation blockade. Agents inhibiting CD40-CD40 ligand interaction may enable a good control of both T cells and B cells responses. Anti-CD28 antibodies may promote regulatory T cells. Agents targeting this costimulation pathways are currently evaluated in clinical trials. Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Criteria for selection of FFP blood type has not been clearly established and use of group AB plasma is preferred by numerous transplantation protocols., Aims: This study assesses the safety and efficacy of alternative group A or B plasma in ABO incompatible solid organ transplantation., Materials & Methods: Alternative use of group A or B plasma (incompatible plasma) was inevitable during the shortage of group AB plasma. Experience from select number of patients during the period of extreme group AB plasma shortage is described., Results: The result of alternative use of group A or B plasma was within expectation, showing effective reduction of isoagglutinin titers for pre-operative desensitization and efficacy for treatment of post-operative patients. No immediate hemolytic transfusion reaction was reported., Discussion: While validation in a larger cohort of patients is necessary, our limited experience have shown satisfactory clinical outcomes without adverse events., Conclusions: Use of incompatible group A or B plasma is a viable option when group AB plasma is limited., (© 2021 Wiley Periodicals LLC.)

In this article, we address a missing data problem that occurs in transplant survival studies. Recipients of organ transplants are followed up from transplantation and their survival times recorded, together with various explanatory variables. Due to differences in data collection procedures in different centers or over time, a particular explanatory variable (or set of variables) may only be recorded for certain recipients, which results in this variable being missing for a substantial number of records in the data. The variable may also turn out to be an important predictor of survival and so it is important to handle this missing-by-design problem appropriately. Consensus in the literature is to handle this problem with complete case analysis, as the missing data are assumed to arise under an appropriate missing at random mechanism that gives consistent estimates here. Specifically, the missing values can reasonably be assumed not to be related to the survival time. In this article, we investigate the potential for multiple imputation to handle this problem in a relevant study on survival after kidney transplantation, and show that it comprehensively outperforms complete case analysis on a range of measures. This is a particularly important finding in the medical context as imputing large amounts of missing data is often viewed with scepticism., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The spleen is a large lymphoid organ located in the abdomen that filters blood and regulates the immune system. The extent of mobilization of splenic immune cells to peripheral tissues in health and disease, however, remains poorly understood. This is due, in large part, to a lack of in vivo, spleen-specific lineage tagging strategies. Here, we describe a detailed practical protocol of spleen transplantation and its evaluation for long-term graft survival. Unlike implantation of splenic morsels in the great omentum, our approach uses arterial and venous anastomoses which rapidly restores blood flow and facilitates long-term survival of the graft. The use of congenic mouse strains permits the use of immunofluorescence and flow cytometry-based methodologies to unambiguously track the migration of spleen-derived cells to peripheral tissues.

Donation after circulatory death (DCD) has become an accepted practice in many countries and remains a focus of intense interest in the transplant community. The present study is aimed at providing a description of the current situation of DCD in European countries. Specific questionnaires were developed to compile information on DCD practices, activities and post-transplant outcomes. Thirty-five countries completed the survey. DCD is practiced in 18 countries: eight have both controlled DCD (cDCD) and uncontrolled DCD (uDCD) programs, 4 only cDCD and 6 only uDCD. All these countries have legally binding and/or nonbinding texts to regulate the practice of DCD. The no-touch period ranges from 5 to 30 min. There are variations in ante and post mortem interventions used for the practice of cDCD. During 2008-2016, the highest DCD activity was described in the United Kingdom, Spain, Russia, the Netherlands, Belgium and France. Data on post-transplant outcomes of patients who receive DCD donor kidneys show better results with grafts obtained from cDCD versus uDCD donors. In conclusion, DCD is becoming increasingly accepted and performed in Europe, importantly contributing to the number of organs available and providing acceptable post-transplantation outcomes., (© 2019 Steunstichting ESOT.)

Background: The ideal donor in intestinal transplantation (ITX) is generally considered to be 50% to 70% of recipient body weight. This may be due to concerns for "small for size" syndrome as seen in liver transplantation. We report our experience using smaller donors (donor-recipient weight ratio [DRWR], < 50%) in ITX recipients., Methods: We studied a group of ITX recipients with DRWR of 50% or less to unmatched controls who received intestinal allografts with DRWR greater than 50%. We examined patient and graft survival and enteral autonomy from parenteral nutrition as surrogate markers for safety of using smaller donors and ease of abdominal wall closure between groups to determine the value., Results: There was no difference in overall patient and graft survival, time to enteral autonomy from parenteral nutrition, and weight gain after ITX over time between groups. The need for complicated abdominal closure techniques was significantly more frequent in the control group than in the study group (34.6% vs 6.9%, P = 0.01). Secondary abdominal closure occurred more frequently in the control group (15.4% vs 0%, P = 0.014). Wound revisions also occurred more frequently in the control group (15.4% vs 0%, P = 0.028)., Conclusions: Our data suggest that ITX using smaller donors (DRWR ≤ 50%) seems to be an acceptable practice without adverse impact on surgical complications, nutritional autonomy, and patient and graft survival. Abdominal wall closure seems easier in recipients of smaller donors and "small for size" syndrome as described in liver transplantation does not occur with intestinal allografts.

AMR is a risk factor for graft failure after SBTx. We studied impact of DSAs and AMR in 22 children transplanted between 2008 and 2012 (11 isolated SBTx, 10 liver inclusive Tx, and one modified multivisceral Tx). Three patients never developed DSA, but DSAs were found in seven in the pre-Tx period and de novo post-Tx in 19 children. Pathology revealed cellular rejection (15/19), with vascular changes and C4d+. Patients were treated with IV immunoglobulins, plasmapheresis, and steroids. Rescue therapy included antithymocyte globulins, rituximab, eculizumab, and bortezomib. Pathology and graft function normalized in 13 patients, graft loss occurred in two, and death in seven. At the end of the follow-up, 15 children were alive (68%), 13 with functioning graft (59%). Prognosis factors for poor outcome after Tx were the presence of symptoms at AMR suspicion (P +.033). DSAs were often found following SBTx, mostly de novo. Resistant ACR or severe AMR is still difficult to differentiate, with a high need for immunosuppression in both. DSAs may precede development of severe disease and pathology features on the graft: relationship and correlation need to be better investigated with larger groups before and after Tx., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Our aim was to describe our achievements in pediatric intestinal transplantation (ITx) and define areas for improvement. After a period (1987-1990) of nine isolated small bowel transplants (SBTx) where only one patient survived with her graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45 liver-small bowel, four multivisceral (three with kidneys), and one modified multivisceral. Indications were short bowel syndrome (36), motility disorders (30), congenital enteropathies (34), and others (1). Induction treatment was introduced in 2000. Patient/graft survival with a liver-containing graft or SBTx was, respectively, 60/41% and 46/11% at 18 years. Recently, graft survival at 5/10 years was 44% and 31% for liver-containing graft and 57% and 44% for SBTx. Late graft loss occurred in 13 patients, and 7 of 10 retransplanted patients died. The main causes of death and graft loss were sepsis and rejection. Among the 55 currently living patients, 21 had a liver-containing graft, 19 a SBTx (17 after induction), and 15 were on parenteral nutrition. ITx remains a difficult procedure, and retransplantation even more so. Over the long term, graft loss was due to rejection, over-immunosuppression was not a significant problem. Multicenter studies on immunosuppression and microbiota are urgently needed., (© 2016 Steunstichting ESOT.)

Solid-organ transplant recipients are at increased risk of developing de novo malignancies compared with the general population, and malignancies become a major limitation in achieving optimal outcomes. The prevention and the management of posttransplant malignancies must be considered as a main goal in our transplant programs. For these patients, immunosuppression plays a major role in oncogenesis by both impairement of immunosurveillance, enhancement of chronic viral infection, and by direct prooncogenic effects. It is essential to manage the recipient with a long-term adapted screening program beginning before transplantation to use a prophylaxis to decrease infection-related cancer, to propose a viral monitoring, and to modulate the immunosuppression toward lower doses especially for calcineurin inhibitors. Indeed, strategies to induce tolerance or to allow a dramatic reduction of the immunosuppression burden are the more promising approaches for the reduction of the posttransplant malignancies.

Scientific presentations at the 26th International Congress of The Transplantation Society held in Hong Kong from August 18 to 23, 2016, highlighted accomplishments, challenges and opportunities in contemporary clinical organ transplantation. With nearly 1600 original abstract submissions, this review summarizes notable presentations in addressing a diversity of issues including deceased and living organ donation, improving allograft survival and unmet clinical needs in organ transplantation.

Complement is a major contributor to inflammation and graft injury. This system is especially important in ischemia-reperfusion injury/delayed graft function as well as in acute and chronic antibody-mediated rejection (AMR). The latter is increasingly recognized as a major cause of late graft loss, for which we have few effective therapies. C1 inhibitor (C1-INH) regulates several pathways which contribute to both acute and chronic graft injuries. However, C1-INH spares the alternative pathway and the membrane attack complex (C5-9) so innate antibacterial defenses remain intact. Plasma-derived C1-INH has been used to treat hereditary angioedema for more than 30 years with excellent safety. Studies with C1-INH in transplant recipients are limited, but have not revealed any unique toxicity or serious adverse events attributed to the protein. Extensive data from animal and ex vivo models suggest that C1-INH ameliorates ischemia-reperfusion injury. Initial clinical studies suggest this effect may allow transplantation of donor organs which are now discarded because the risk of primary graft dysfunction is considered too great. Although the incidence of severe early AMR is declining, accumulating evidence strongly suggests that complement is an important mediator of chronic AMR, a major cause of late graft loss. Thus, C1-INH may also be helpful in preserving function of established grafts. Early clinical studies in transplantation suggest significant beneficial effects of C1-INH with minimal toxicity. Recent results encourage continued investigation of this already-available therapeutic agent.

Overlooked for decades, the humoral alloimmune response is increasingly recognized as a leading cause of graft loss after transplantation. However, improvement in the diagnosis of antibody-mediated rejection has not yet translated into better outcomes for transplanted patients. After an update on B cell physiology and antibody generation, the 2015 Beaune Seminar in Transplant Research challenged the conventional view of antibody-mediated rejection pathophysiology and discussed the latest promising therapeutic approaches.

Vaccination is an effective strategy to decrease infections in transplant recipients. Children after intestinal transplantation carry a high risk of infection due to increased immunosuppression. In a series of 22 children after intestinal transplantation, we studied the vaccination schedules and the antibodies against vaccine-preventable diseases before transplantation, and at one and five yr after transplantation. We reviewed whether the vaccination schedules were complete, and we analysed the factors that may influence serological immunity and the incidence of disease in patients with deficient immunity. All patients completed the recommended vaccination schedules for DTaP-IPV and HBV. After transplantation, the negative antibodies against vaccine-preventable diseases were mostly related to an antirejection therapy: for DTaP-IPV: four of four patients with no antibody had been treated for rejection, for HBV: two of five, HAV: three of four, MMR: three of seven, and VZV: three of four. A post-transplantation varicella infection was followed by acute rejection, with probability for a relationship between both events. We observed 50% of varicella cases in unvaccinated children, highlighting the importance of pretransplant vaccination. Waning immunogenicity mediated by antibodies against vaccine-preventable disease after transplantation indicated a need for boosters. The recommendations should be regularly enforced, as the reliance on routine immunizations schedules is not adequate in immunocompromised patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Developments in transplantation have progressed dramatically over the past century. Current research is underway to optimize immune modulation, genetically engineering animals for xenografting, and breakthroughs are occurring in regenerative medicine. However, pioneering live-donor transplantation has transformed transplantation in the organ shortage, and these contribute an increased proportion of transplanted organs. Live-donor transplantation is associated with better long-term outcomes, and techniques to recover organs have become less invasive. We set out to examine the evolution of transplantation from its historic beginnings to the developments that make it successful today.

In response to recommendations from a recent consensus conference and from the Committee of Presidents of Statistical Societies, the Scientific Registry of Transplant Recipients explored the use of Bayesian hierarchical, mixed-effects models in assessing transplant program performance in the United States. Identification of underperforming centers based on 1-year patient and graft survival using a Bayesian approach was compared with current observed-to-expected methods. Fewer small-volume programs (<10 transplants per 2.5-year period) were identified as underperforming with the Bayesian method than with the current method, and more mid-volume programs (10-249 transplants per 2.5-year period) were identified. Simulation studies identified optimal Bayesian-based flagging thresholds that maximize true positives while holding false positive flagging rates to approximately 5% regardless of program volume. Compared against previous program surveillance actions from the Organ Procurement and Transplantation Network Membership and Professional Standards Committee, the Bayesian method would have reduced the number of false positive program identifications by 50% for kidney, 35% for liver, 43% for heart and 57% for lung programs, while preserving true positives for, respectively, 96%, 71%, 58% and 83% of programs identified by the current method. We conclude that Bayesian methods to identify underperformance improve identification of programs that need review while minimizing false flags., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Based on recommendations from a recent consensus conference and a report commissioned by the Centers for Medicare & Medicaid Services to the Committee of Presidents of Statistical Societies, the Scientific Registry of Transplant Recipients (SRTR) plans to adopt Bayesian methods for assessing transplant program performance. Current methods for calculating program-specific reports (PSRs) often generate implausible point estimates of program performance, wide confidence intervals and underpowered conventional statistical tests. Although technically correct, these methods produce statistical summaries that are prone to misinterpretation. The Bayesian approach assumes that performance of most programs is about average and few programs perform much better or much worse than average; thus, strong evidence is required to conclude that performance is extremely good or poor. In Bayesian statistics, inference is performed via a posterior probability distribution, which reflects both the available data and prior beliefs about what model parameter values are most likely. In the PSRs, the posterior distribution of a program-specific hazard ratio will show whether a program is likely to be performing better or worse than average. Bayesian-derived PSRs will be available for preview by programs on the private SRTR website in mid-2014 and will likely replace current methods for public reporting in early 2015., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In Switzerland, organ procurement is well organized at the national-level but transplant outcomes have not been systematically monitored so far. Therefore, a novel project, the Swiss Transplant Cohort Study (STCS), was established. The STCS is a prospective multicentre study, designed as a dynamic cohort, which enrolls all solid organ recipients at the national level. The features of the STCS are a flexible patient-case system that allows capturing all transplant scenarios and collection of patient-specific and allograft-specific data. Beyond comprehensive clinical data, specific focus is directed at psychosocial and behavioral factors, infectious disease development, and bio-banking. Between May 2008 and end of 2011, the six Swiss transplant centers recruited 1,677 patients involving 1,721 transplantations, and a total of 1,800 organs implanted in 15 different transplantation scenarios. 10 % of all patients underwent re-transplantation and 3% had a second transplantation, either in the past or during follow-up. 34% of all kidney allografts originated from living donation. Until the end of 2011 we observed 4,385 infection episodes in our patient population. The STCS showed operative capabilities to collect high-quality data and to adequately reflect the complexity of the post-transplantation process. The STCS represents a promising novel project for comparative effectiveness research in transplantation medicine.

CKD is a frequent long-term complication after SBTx. CNIs are a well-known factor, but probably not the only cause. We assessed the incidence, risk factors, and severity of CKD in 27 children with SBTx (15 combined liver/SBTx) and prednisone/TAC-based maintenance immunosuppression. Median follow-up was seven yr (3-21). A renal biopsy was performed in 14 patients, 1-18 yr post-SBTx. A reduced GFR was observed in 17 children (63%) during the follow-up with none requiring dialysis. CNI toxicity was observed in 11/14 biopsies, as early as two yr post-transplant, and could occur with a normal mGFR. The dose of TAC was reduced by 50% in 13 patients with CKD and/or significant kidney histological lesions, and six were also given MMF. This led to a significant improvement in renal function: mGFR normalized in eight patients and improved or stabilized in five. No rejection occurred. At last follow-up, 37% had CKD stage 2 and 15% had CKD stage 3. In conclusion, CKD is frequent in children after SBTx and probably multifactorial. Less nephrotoxic immunosuppressive protocols may improve mGFR and should be further considered. The kidney histology helps in designing personalized immunosuppression strategies for patients., (© 2012 John Wiley & Sons A/S.)

Initial poor graft function (IPGF) is a major factor influencing the clinical outcome after liver transplantation (LT), but there is no reliable method to assess and predict graft dysfunction. To help clinicians determine prognosis in the early postoperative period, individual parameters and complex scoring systems have been suggested, but most of them are inaccurate because of the multifactorial nature of transplantation courses. Therefore, the aim of our study was to retrospectively evaluate predictive criteria for retransplantation. Forty-two patients were enrolled in this study: 18 who experienced primary non-function (PNF) and 24 with delayed graft function (DGF). All of the patients were treated with the Molecular Adsorbent Recirculating System (MARS). They were into 3 subgroups: patients who survived without LT (n = 20; 47.7%); patients who underwent LT (n = 16; 37%), and patients who died before transplantation (n = 6; 14%). Stepwise multivariable logistic regression analysis was performed with the intent to find the risk factors for LT or death after MARS treatment (second analysis). Receiver operating characteristic (ROC) curves were performed on significant variables in the logistic regression model with the intent to individually predict variables for LT or death. After a stepwise multivariable logistic regression analysis enrolling all of the previously reported features only 2 variables, tumor necrosis factor (TFN)-α and Glasgow coma score (GCS) score, were statistically significant. TNF-α was an unique independent risk factor for retransplantation or death after MARS treatment (odds ratio [OR] 1.235; P = .013). Conversely, GCS score was protective against retransplantation or death (OR 0.150; P = .003). Starting from these assumptions, a predictive model was created using these 2 variables. On ROC analysis, the combined score showed an area under the curve greater than that of the 2 variables considered separately. Validating these results with a larger number of patients, we considered these 2 factors as subjective parameters to determine outcomes and the difference between PNF and DGF., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Prior studies have presented contradictory results after analyzing associations between donor and recipient sex on survival after heart transplantation and causes of death such as acute rejection (AR) and cardiac allograft vasculopathy (CAV). We used the International Society for Heart and Lung Transplantation (ISHLT) Registry, the largest repository of heart transplant outcomes worldwide, to comprehensively address these questions., Method: We studied 60,584 adult recipients of heart transplants performed between 1990 and 2008. Outcomes of interest were overall survival, death-censored allograft survival, AR, and CAV, which were studied using regression models. To assess whether donor/recipient sex mismatch affected outcomes, the experience of male recipients with female vs male donors was compared with that of female recipients with female vs male donors through inclusion of an interaction term between donor and recipient sex., Results: Significant differences were observed between male and female recipients in overall survival and death-censored allograft survival for female vs male donors. Male recipients of female allografts had a 10% increase in adjusted mortality relative to male recipients of male allografts, whereas female recipients of female allografts had a 10% decrease in adjusted mortality relative to female recipients of male allografts (p < 0.0001). Findings were similar for death-censored allograft survival. Differences in the effect of donor sex on AR or CAV between male and female recipients were not significant., Conclusions: Analysis of the ISHLT data set has demonstrated a strong association between donor/recipient sex mismatch and reduced survival after heart transplantation., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Both donor and recipient race impact outcomes after liver transplantation (LT), especially for hepatitis C virus (HCV). The interaction and simultaneous impact of both on patient survival is not clearly defined. The purpose of this study was to examine the impact of donor and recipient race on recipient and graft survival after HCV-related LT using the United Network for Organ Sharing database., Methods: A total of 16,053 recipients (75.5% white, 9.3% black, and 15.2% Hispanic) who underwent primary LT for HCV between 1998 and 2008 were included. Cox regression models were used to assess the association between recipient/donor race and patient survival., Results: A significant interaction between donor and recipient race was noted (P=0.01). Black recipients with white donors had a higher risk of patient mortality (adjusted hazard ratio, 1.66; 95% confidence interval, 1.47-1.87) compared with that of white recipients with white donors. In contrast, the pairing of Hispanic recipients with black donors was associated with a lower risk of recipient mortality compared with that of white recipients with white donors (adjusted hazard ratio, 0.64; 95% confidence interval, 0.46-0.87). Similar results were noted for graft failure., Conclusion: In conclusion, the impact of donor and recipient race on patient survival varies substantially by the matching of recipient/donor race.

The majority of transplant centers around the world face an ethical debate whether to retransplant a young non-adherent patient. Non-adherence to lifelong immunosuppressants presents a significant risk for graft loss, yet rates remain consistently high. Despite a number of these patients presenting for retransplantation, there is little evidence to guide professionals in their decision-making. This paper aims to provide such guidance, by systematically reviewing the existing outcome data for retransplantation in patients who are known to be non-adherent to their immunosuppressants. This review searched for original papers that addressed retransplantation of a solid organ and included quantitative data on adherence or graft function. Only one original research paper was found to meet the inclusion criteria. This paper is reviewed, and details of the protocol to determine eligibility for retransplantation are summarized. The findings are discussed within the ethical context that transplant professionals work within, and the arguments for and against retransplantation are considered. The need for effective integration of adherence management into routine practice is highlighted, with an emphasis on reliable measurement of adherence throughout the patient's life. Examples of good practice are discussed, favoring prevention over cure., (© 2012 John Wiley & Sons A/S.)

Introduction: We investigated the outcomes of adult liver transplants, according to their donor-recipient cytomegalovirus (CMV) serology., Materials and Methods: We included in the study all adult primary liver transplants, from January 1, 2002, to December 31, 2005. Follow-up was until December 31, 2007. According to the donor-recipient CMV serology, patients were divided into positive-negative (PN), positive-positive, negative-negative, and negative-positive groups, and all received CMV prophylaxis for 4 months posttransplantation. Hepatitis C patients received conventional immunosuppression, whereas all other patients received either conventional treatment or alemtuzumab (Campath-1H) induction., Results: We studied 438 adult liver transplants. Comparisons were made between high-risk group patients (PN) versus all others: 5-year patient survival was 74.31% vs. 78.8%, (P=NS) and graft survival 63.87% vs. 74.77%, (P=0.042). Five-year freedom from rejection was 42.84% vs. 51.95% (P=0.036). CMV infection (n=3) or disease (n=27) was observed in 30 patients (PN [n=23], positive-positive [n=6], and negative-positive [n=1]). Incidence of CMV infection was 9.8% overall and 34.84% and 2.5%, respectively, for the PN group versus all others (P=0.0000). Patients who received Campath-1H induction did not have an increased incidence of CMV infections compared with those who received conventional immunosuppression., Conclusions: In our center, in adult liver transplantation, CMV donor-recipient PN serology is associated with rejection, graft survival, and CMV infection but is not correlated with patient survival, Epstein-Barr virus (EBV) occurrence, or viral hepatitis recurrence. The introduction of more potent induction immunosuppression did not accentuate these negative outcomes.

Hand transplantation now represents a therapeutic alternative for amputees. Arm transplantation poses a serious challenge regarding many respects of the reconstructive procedure. To the end of 2010, only seven such procedures had been performed in four patients. The goal of this article was to present the preliminary results of an arm transplant in a 30-year-old male patient at 14 months. The patient sustained an amputation at the elbow-joint level as a 2-year-old child. The procedure was performed in October 2010. His postoperative course was complicated by one rejection episode (BANFF grade II), and a de novo cytomegalovirus infection. At this early stage, the patient is doing well regaining function. He can flex at the elbow joint, move his fingers, and experience protective sensitivity reaching the palm. The patient is satisfied with his transplantation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Troponin I is often obtained during the evaluation of a potential transplant donor heart. It is not clear whether elevations in donor troponin I levels predict adverse outcomes and should thus preclude acceptance of a donor heart. This study examined whether troponin I levels from donors accepted for pediatric heart transplantation predicted graft failure., Methods: Deidentified data on heart transplants performed in recipients aged < 21 years between April 2007 and April 2009 was provided by the Organ Procurement and Transplantation Network. Donor troponin I level and recipient outcomes, including survival without retransplantation (graft survival), were examined for statistical correlation., Results: Overall graft survival in 839 heart transplants was 81% at 2 years. At least 1 troponin I level was recorded in 657 donors before transplant, with a median value of 0.1 ng/ml (range, 0-50 ng/ml). Troponin I level and graft status were not correlated (p = 0.74). A receiver operating characteristic curve showed no association between troponin I and graft status (area under the curve, 0.51; p = 0.98). Graft survival did not differ significantly (p = 0.60) among quartiles of troponin I levels (<0.04, 0.04-<0.1, 0.1-<0.35, ≥ 0.35 ng/ml). A troponin I level ≥ 1 ng/ml was found in 74 transplanted donor hearts; graft survival was not associated with troponin I ≥ 1 (80%) vs < 1 (80%) at 2 years (p = 0.93). Troponin I values were not associated with post-transplant hospital length of stay (r = -0.06; p = 0.10)., Conclusions: In donor hearts accepted for pediatric heart transplantation, troponin I elevation before procurement is not associated with increased graft failure. The significance of elevated troponin I levels, which occurs in many heart donors, remains unclear and should therefore be considered in the context of other clinical information., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Kidney transplantation in the elderly is complicated by comorbidities and a higher incidence of death. The Eurotransplant Senior Program (ESP) has been established to allocate kidneys from older donors to the increasing number of older recipients. In this retrospective, single center data analysis, we compare the outcome of recipients older than 70 years with younger recipients transplanted under the ESP protocol., Methods: Between 1999 and 2009, a total of 83 kidneys were transplanted under the ESP protocol in Innsbruck and 19 of the recipients were older than 70 years (mean, 72.7 years). Cold ischemia time was kept short in both groups by giving preference to regional donor organs., Results: Patient survival at 1 and 5 years were 95% and 67% in the 70+ group and 94.4% and 82.6% in the 70- group. Graft survival was 95% and 52% at 1 and 5 years in the 70+ group and 94.4% and 79.0% in the 70- group. When censored for death, graft survival at year 1 and 5 were 100% and 82% in the 70+ group and 98.1% and 92.7% in the 70- group. The delayed graft function rate was high in both groups (36.8% and 41.1%, respectively). Morbidities were largely related to hemodynamic, oncologic, and infectious events. Cardiac failure was the major cause of death., Conclusion: Relatively good results can be achieved with renal transplantation in patients older than 70 years under careful pretransplant evaluation and postoperative management of comorbidities.

The prevalence of obesity in dialysis patients is increasing, and as a result, more obese dialysis patients are being evaluated for kidney transplant. Despite several limitations associated with the use of body mass index (BMI), BMI is commonly used to define obesity, with many transplant centers using BMI of 30-35 kg/m(2) as a limit for transplant eligibility. This limit evolved from the belief that obese patients have more complications and shorter transplant and patient survival than ideal-weight patients. Data for obesity and posttransplant complications are conflicting, with the exception of increased risk of postoperative wound complications, and there are no large trials showing a benefit of weight loss before transplant on subsequent patient or transplant survival. In our opinion, patient death and transplant failure rates in patients with BMI of 30-35 kg/m(2) are low enough that these individuals should not be excluded from transplant. Weight gain posttransplant is relatively common, and although sustained weight loss through conservative intervention is difficult to achieve, prevention of weight gain is a more feasible goal that should be addressed routinely. Although obesity is a complex and often multifactorial clinical condition that includes nonmodifiable factors, obese individuals often are viewed as being solely responsible for their obesity. Accordingly, in addition to encouragement of lifestyle modification, available pharmacologic and surgical options should be reviewed in appropriate patients. After pharmacologic and/or surgical interventions, close monitoring of immunosuppressive medications is necessary because of variability in drug absorption.

The problem of graft size is one of the critical factors limiting the expansion of adult-to-adult living donor liver transplantation (LDLT). We compared the outcome of LDLT recipients who received grafts with a graft-to-recipient weight ratio (GRWR) < 0.8% or a GRWR > or = 0.8%, and we analyzed the risk factors affecting graft survival after small-for-size grafts (SFSGs) were used. Between June 1997 and April 2008, 427 patients underwent LDLT with right lobe grafts at the Department of Surgery of Samsung Medical Center. Recipients were divided into 2 groups: group A with a GRWR < 0.8% (n = 35) and group B with a GRWR > or = 0.8% (n = 392). We retrospectively evaluated the recipient factors, donor factors, and operative factors through the medical records. Small-for-size dysfunction (SFSD) occurred in 2 of 35 patients (5.7%) in group A and in 14 of 392 patients (3.6%) in group B (P = 0.368). Graft survival rates at 1, 3, and 5 years were not different between the 2 groups (87.8%, 83.4%, and 74.1% versus 90.7%, 84.5%, and 79.4%, P = 0.852). However, when we analyzed risk factors within group A, donor age and middle hepatic vein tributary drainage were significant risk factors for graft survival according to univariate analysis (P = 0.042 and P = 0.038, respectively). Donor age was the only significant risk factor for poor graft survival according to multivariate analysis. The graft survival rates of recipients without SFSD tended to be higher than those of recipients with SFSD (85.3% versus 50.0%, P = 0.074). The graft survival rates of recipients with grafts from donors < 44 years old were significantly higher than those of recipients with grafts from donors > or = 44 years old (92.2% versus 53.6%, P = 0.005). In conclusion, an SFSG (GRWR < 0.8%) can be used safely in adult-to-adult right lobe LDLT when a recipient is receiving the graft from a donor younger than 44 years.

Endoplasmic reticulum (ER) stress is a situation caused by the accumulation of unfolded proteins in the endoplasmic reticulum, triggering an evolutionary conserved adaptive response termed the unfolded protein response. When adaptation fails, excessive and prolonged ER stress triggers cell suicide. Important roles for ER-initiated cell death pathways have been recognized for several diseases, including diabetes, hypoxia, ischemia/reperfusion injury, neurodegenerative and heart diseases. The implication of the ER stress is not well recognized in solid organ transplantation, but increasing evidence suggests its implication in mediating allograft injury. The purpose of this review is to summarize the mechanisms of ER stress and to discuss its implication during tissue injury in solid organ transplantation. The possible implications of the ER stress in the modifications of cell functional properties and phenotypic changes are also discussed beyond the scope of adaptation and cell death. Increasing the understanding of the cellular and molecular mechanisms of acute and chronic allograft damages could lead to the development of new biomarkers and to the discovery of new therapeutic strategies to prevent the initiation of graft dysfunction or to promote the tissue regeneration after injury.

Established in 1989 in Brussels as an international nonprofit association, the European Homograft Bank (EHB) has been collaborating closely with the transplant coordination of the different centers in Belgium and other European countries. Donor selection is made after discussion of exclusion criteria with the transplant coordinator of the procurement center. EHB collaborates with 15 Belgian, 11 German, 10 French, 10 Swiss, 3 Italian, 3 Dutch, and some other procurement and/or implantation centers. Donor ages range from newborn to 65 years. Tissue preparation, morphologic evaluation, and functional testing are performed under Class A laminar flow. After decontamination in a cocktail of 3 antibiotics (lincomycin, vancomycin, and polymixin B) during 20-48 hours, the tissues cryopreserved with liquid nitrogen to -100 degrees C are stored in vapors of liquid nitrogen below -150 degrees C for a maximum of 5 years. Systematic virologic examination of donor blood is performed for HIV, HTLV, hepatitis B/C, and syphilis, as well as for enteroviruses, Q fever, malaria, and West Nile virus by indication. Bacteriologic examination for anaerobic and aerobic contamination is performed at the different steps of processing. Histologic examination for malignant disease and infection is performed systematically. Indications for implantation are discussed with the requesting surgeon. Transport to the implantation center is carried out safely in a dry shipper at -150 degrees C or in dry ice at -76 degrees C. The EHB received 4,511 hearts and 1,169 batches of arteries from January 1989 to December 2008. The 5,133 heart valves (1,974 aortic, 3,106 pulmonary, and 53 mitral) and 2,066 arterial segments have been prepared and stored; 4,600 cryopreserved valvular (2,717 pulmonary, 1,835 aortic, and 48 mitral) and 1,937 arterial allografts have been distributed for implantation in various European Cardiovascular Centers. EHB is not always able to meet the increased demand for heart valves and arterial allografts. Collaboration between the EHB and the Transplant Coordination is satisfactory. Donor selection criteria are discussed with the transplant coordinator; whereas, implantation indication, with the implanting surgeon. Because the EHB is not always able to meet demands for the cryopreserved valves and arterial segments, there is a need to increase number of procurements. Cardiovascular surgeons need to play more active roles in the resolution of this problem.

Since the earliest days of transplantation, immunobiologists have sought means to prevent recognition and rejection of foreign tissue. The goal of these strategies is the retention of recipient immune function while selectively avoiding graft injury. Although considerable theoretical and technical problems remain, an analogous problem and solution already exists in nature. Here, we discuss the mechanisms by which organisms preclude or control autotoxicity, and for each, consider the corollaries between prevention of autotoxicity and graft rejection. Further study of these controls, including structural and conditional tolerance and accommodation, will offer insight into new therapies for allo- and xenotransplantation.

Proteinuria is highly prevalent after kidney transplant, occurring in up to 45% of patients, depending on the definition. In addition to glomerulonephritis, proteinuria in kidney transplant recipients is associated commonly with such transplant-specific diagnoses on biopsy as allograft nephropathy, transplant glomerulopathy, and acute rejection. Proteinuria is associated with decreased patient and allograft survival, as well as an increased risk of cardiovascular events. In proteinuric chronic kidney disease in the nontransplant setting, randomized trials have confirmed that blockade of the renin-angiotensin system is associated with improved clinical outcomes. In proteinuric transplant recipients, treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker can decrease proteinuria, but there is no evidence from randomized trials that this strategy improves patient or graft survival. This review focuses on the measurement, prevalence, pathological findings, prognostic significance, and evidence-based management of proteinuria in kidney transplant recipients.

Donor cause of death (DCOD) has been described to influence allograft survival. Whether this effect is independent of other donor characteristics and whether it is similar across different solid organ allografts is not known. The aim of our study was to determine the impact of DCOD on organ utilization and on transplantation outcomes-graft rejection, function, and survival. The registry data were provided by the United Network for Organ Sharing/Organ Procurement and Transplantation Network. Stroke, head trauma, and anoxia were the cause of brain death in 97% of the more than 86,000 donors whose data were recorded between 1989 and 2008. In univariate analysis, stroke DCOD was associated with worse graft survival across all organs. After adjustment in a multivariable analysis, modest differences persisted in survival of heart, kidney, and liver allografts. DCOD also appeared to affect the incidence of allograft rejection. Anoxia DCOD was associated with significantly less rejection relative to donor death caused by head trauma and stroke. In summary, this multi-institutional study confirms that DCOD is a modest predictor of survival and rejection of solid organ allografts of different types.

Preservation of ovarian functions in woman with premature ovarian failure remains an issue in reproductive medicine. Hormone replacement therapy for maintaining endocrine functions, and cryopreservation of embryos or oocytes for those who wish pregnancy, are some of the choices. However, ovarian transplantation is a more physiological alternative, although problems related to ovarian ischemia have been reported. Herein, we investigated the viability of autologous transplantation of the ovarian tissue into the rat peritoneum, without vascular reanastomosis. Twenty animals in the study group had both ovaries excised, and each ovary was dissected into two halves. A half of an ovary was autotransplanted to the peritoneal surface, closely located to the left epigastric vessels. This simple procedure does not require surgical vascular reanastomosis while it maintains appropriate follicular growth and therefore should be further considered as an alternative for women undergoing oophorectomy, not only to maintain endocrine functions but also for fertility preservation.

Introduction: Blockade of the CD40-CD154 costimulatory pathway can prolong allograft survival, but does not prevent the development of transplant arteriosclerosis in several models. In this study, we investigated the mechanisms of CD40-CD154-independent transplant arteriosclerosis in major histocompatibility complex (MHC)-class I-mismatched aortic allografts., Methods: MHC class I-mismatched CBK (H2k+Kb) donor aortas were transplanted into CBA (H2k) recipients who can only recognize the graft through CD8+ T cells and CD4+ T cells responding to the class I MHC mismatch through the indirect pathway of allorecognition. Recipients were treated with anti-CD154 antibody (MR1) alone or in combination with anti-CD8 (YTS169) or anti-interleukin (IL)-4 (11B11) antibodies. Grafts were analyzed by histology on days 30 and 60 and for intragraft mRNA expression on day 14 after transplantation., Results: Repeated treatment with anti-CD154 alone or in combination with anti-CD8 antibody did not prevent intimal proliferation compared with untreated controls (65%+/-6%, 62%+/-9%, and 71%+/-7% luminal occlusion, respectively, 60 days after transplantation). In both treatment groups, the expression of IL-4, IL-5, and eotaxin was increased compared with control grafts, and an eosinophilic infiltration was observed. Neutralizing IL-4 in combination with CD40-CD154 blockade and CD8+ T-cell depletion abrogated transplant arteriosclerosis (9%+/-4% luminal occlusion 60 days after transplantation)., Conclusion: Prolonged treatment with anti-CD154 was not able to prevent the development of transplant arteriosclerosis in MHC class I-mismatched aortic allografts, in the presence or absence of CD8+ T cells. This CD40-CD154 pathway resistant transplant arteriosclerosis was mediated by IL-4, because neutralizing IL-4 in addition to CD40-CD154 costimulation blockade and CD8+ T-cell depletion prevented its development.

The transplantation program in Bulgaria started in 1968 with renal transplantations to a child and adult woman. In 1986 the first heart transplantation was performed. To date a total of 10 heart transplants have been performed, including one combined heart/lung. A liver transplantation program was launched in 2005 with a total number of 16 transplantations-7 from living donors and 9 from deceased donors. The highest transplantation activity is registered in the field of renal transplantation. During the period 1980-2006, 462 Bulgarian recipients of kidney were transplanted in Bulgaria. The ratio between transplantations from deceased and living related donors is approximately 1:0.9. Annual transplantation activity varies among the years from 1 to 12 renal transplantations p.m.p./per year. The 1- (80.7% vs. 63.1%), 5- (57.86% vs. 39.0%) and 10-year (42.65% vs. 23.62%) graft survival rates are higher for recipients of living donor kidneys compared to those of deceased donor. In 1983 a National kidney waiting list was established. Currently the number of the registered patients eligible for renal transplantation is 885. The proportion of sensitized patients in the waiting list is 20.45% and 4.34% of them are hyperimmunized. Recently HLAMatchmaker program has been implemented not only for sensitized patients but also for those with rare alleles and haplotypes. Post-transplant immunological monitoring showed a strong association between alloantibody presence and delayed graft function (Chi-square=10.73, P<0.001), acute rejection (Chi-square=14.504, P<0.001), chronic rejection (Chi-square=12.84, P<0.001) and graft loss (Chi-square=20.283, P<0.001). Based on the experience in our transplant center a strategy for improvement of long-term renal graft survival was developed and implemented.

Transplant centers juggle at least three objectives important to success: transplant volume, outcomes and costs. Improving one frequently occurs at the expense of the others. It may be difficult to have a high-volume program with excellent outcomes and low costs. There are some programs that can do well in all these areas, but even they might be able to improve one of the outcome measures if they would compromise on the one of the others (i.e. a transplant center with good outcomes might be able to achieve even better outcomes if it restricted the patients it was willing to transplant or used only the best organs). It is up to transplant surgeons and physicians to balance all these objectives.

Aim: To investigate the safety of adult-to-adult living donor liver transplantation (A-A LDLT) in both donors and recipients., Methods: From January 2002 to July 2006, 50 cases of A-A LDLT were performed at West China Hospital, Sichuan University, consisting of 47 cases using right lobe graft without middle hepatic vein (MHV), and 3 cases using dual grafts (one case using two left lobe, 2 using one right lobe and one left lobe). The most common diagnoses were hepatitis B liver cirrosis, 30 (60%) cases; and hepatocellular carcinoma, 15 (30%) cases in adult recipients. Among them, 10 cases had the model of end-stage liver disease (MELD) with a score of more than 25. Donor screening consisted of reconstruction of the hepatic blood vessels and biliary system with 3-dimension computed tomography and volumetry of whole liver and right liver volume. Various improved surgical techniques were adopted in the procedures for both donors and recipients., Results: Forty-nine right lobes and 3 left lobes (2 left lobe grafts for 1 recipient, 1 left lobe graft for 1 recipient who had received right lobe graft donated by relative living donor) were obtained from 52 living donors. The 49 right lobe grafts, without MHV, weighed 400 g-850 g (media 550 g), and the ratio of graft volume to recipient standard liver volume (GV/SLV) ranged from 31.74% to 71.68% (mean 45.35%). All donors' remnant liver volume was over 35% of the whole liver volume. There was no donor mortality. With a follow-up of 2-52 mo (media 9 mo), among 50 adult recipients, complications occurred in 13 (26%) cases and 4 (8%) died postoperatively within 3 mo. Their 1-year actual survival rate was 92%., Conclusion: When preoperative CT volumetry shows volume of remnant liver is more than 35%, the ratio of right lobe graft to recipients standard liver volume exceeding 40%, A-A LDLT using right lobe graft without MHV should be a very safe procedure for both donors and recipients, otherwise dual grafts liver transplantation should be considered.