Showing papers in "Clinical Transplantation in 2013"

2013 report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and bone marrow disorders.

Abstract: Data reported herein indicate increasing use of hematopoietic cell transplants for persons with blood and bone marrow disorders. Recent trends include increasing use of alternative donors including human leukocyte antigen (HLA)-matched unrelated persons and 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 such as the need for donors in persons without an HLA-identical sibling or expanding use of allotransplants to older persons. Many changes in transplant practices are not supported by results of large randomized trials. More data are needed to critically-assess the impact of these changes.

Lung transplant outcomes in cystic fibrosis patients with pre-operative Mycobacterium abscessus respiratory infections.

Abstract: Background Mycobacterium abscessus in cystic fibrosis (CF) patients is considered a contraindication to lung transplantation. We examine the post-transplant outcomes of CF patients with M. abscessus pre-transplant. Methods CF patients transplanted at the University of North Carolina from 1992 to 2012 were retrospectively examined. Patients with at least one respiratory sample positive for M. abscessus prior to transplantation were included. Data collected included age, FEV1, body mass index (BMI), systemic steroid use, diabetes mellitus, ventilatory assistance, co-existent CF pathogens, imaging, post-transplant complications, and survival. Results (n = 13) At transplant, mean age was 24.6 yr, mean BMI was 18.1 kg/m2, six had 3+ positive smears for M. abscessus, and three were ventilator dependent. All met American Thoracic Society microbiological criteria for disease pre-transplant. Three patients developed M. abscessus-related complications, with clearance of the organism following treatment. Survival post-transplant shows 77% alive at one yr, 64% at three yr, and 50% at five yr; none died of M. abscessus. The survival data showed no statistically significant difference (p = 0.8) compared with a contemporaneously transplanted population of CF patients without M. abscessus (n = 154). Conclusion Lung transplantation, with favorable survival, is possible in CF patients with M. abscessus. Even if M. abscessus recurs, local control and clearance is possible.

Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis.

Abstract: Experimental studies suggest that the regenerating liver provides a "fertile field" for the growth of hepatocellular carcinoma (HCC). However, clinical studies report conflicting results comparing living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) for HCC. Thus, disease-free survival (DFS) and overall survival (OS) were compared after LDLT and DDLT for HCC in a systematic review and meta-analysis. Twelve studies satisfied eligibility criteria for DFS, including 633 LDLT and 1232 DDLT. Twelve studies satisfied eligibility criteria for OS, including 637 LDLT and 1050 DDLT. Altogether, there were 16 unique studies; 1, 2, and 13 of these were rated as high, medium, and low quality, respectively. Studies were heterogeneous, non-randomized, and mostly retrospective. The combined hazard ratio was 1.59 (95% confidence interval [CI]: 1.02-2.49; I(2) = 50.07%) for DFS after LDLT vs. DDLT for HCC, and 0.97 (95% CI: 0.73-1.27; I(2) = 5.68%) for OS. This analysis provides evidence of lower DFS after LDLT compared with DDLT for HCC. Improved study design and reporting is required in future research to ascribe the observed difference in DFS to study bias or biological risk specifically associated with LDLT.

Fungal infections after liver transplantation: outcomes and risk factors revisited in the MELD era.

Abstract: Antifungal prophylaxis is recommended in high-risk patients, but risk criteria remain unclear and the predictive value of Model of End-Stage Liver Disease (MELD) score is unknown. In a retrospective, single-center analysis of 667 liver transplants, potential risk factors for fungal infection were assessed, including MELD score. Antifungal prophylaxis was administered in 198 patients (29.4%). During follow-up (mean 43.6 ± 29.6 months), 263 patients (39.4%) developed ≥ 1 episode of fungal infection, and 187 (28.0%) patients developed a probable or proven invasive fungal infection requiring systemic antifungal treatment. Patients receiving antifungal prophylaxis had a lower incidence of fungal infection (29.8% vs. 43.5% without prophylaxis, p < 0.001) and invasive fungal infection (17.7% vs. 32.4%, p < 0.001). One-yr patient survival was 91%, 85% and 69%, respectively, in patients with no fungal infection, fungal colonization and treated invasive fungal infection (p < 0.001); graft survival was 88%, 85% and 66% (p < 0.001). Multivariate analysis indicated that MELD score of 20-30 or ≥ 30 was associated with a 2.0-fold or 4.3-fold increase in relative risk of fungal infection, respectively, and a 2.1-fold or 3.1-fold increase in relative risk of invasive fungal infection. In conclusion, liver transplant patients with a MELD score ≥ 20, and particularly patients with a score ≥ 30, are candidates for antifungal prophylaxis.

Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study.

Abstract: Background Stem cell–based therapy has received attention as a possible alternative to organ transplantation. The aim of this study was to assess the safety and efficacy of autologous transplantation of bone marrow (BM)–derived stromal cells in post-HCV liver cirrhosis patients. Methodology 10 × 106 of isolated human bone marrow (HBM)-stromal cells in 10 mL normal saline were injected in the spleen of 20 patients with end-stage liver cirrhosis guided by the ultrasonography, and then patients were followed up on monthly basis for six months. Results A statistically significant decrease was detected in the total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) (p-value<0.01), prothrombin time (PT), and international normalized ratio (INR) levels (p-value<0.05), while a statistically significant increase in the albumin and PC (p-value<0.05) after follow-up. Conclusion This study suggested the safety, feasibility, and efficacy of the intrasplenic injection of autologous BM stromal cells in improving liver function in Egyptian patients with cirrhosis.

Vascularized composite tissue allotransplantation--state of the art.

Abstract: Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including – but not limited to – trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques. Although the risks of lifelong immunosuppression continue to be an important factor when evaluating the benefits of VCA, reported short- and long-term outcomes have been excellent, thus far. Acute rejections are common in the early post-operative period, and immunosuppression-related side effects have been manageable. A multidisciplinary approach to the management of VCA has proven successful. Reports of long-term graft losses have been rare, while several factors may play a role in the pathophysiology of chronic graft deterioration in VCA. Alternative approaches to immunosuppression such as cellular therapies and immunomodulation hold promise, although their role is so far not defined. Experimental protocols for VCA are currently being explored. Moving forward, it will be exciting to see whether VCA-specific aspects of allorecognition and immune responses will be able to help facilitate tolerance induction.

The role of diet and physical activity in post‐transplant weight gain after renal transplantation

Abstract: BACKGROUND: Long-term survival of renal transplant recipients (RTR) has not improved over the past 20 yr. The question rises to what extent lifestyle factors play a role in post-transplant weight gain and its associated risks after transplantation. METHODS: Twenty-six RTR were measured for body weight, body composition, blood lipids, renal function, dietary intake, and physical activity at six wk, and three, six, and 12 months after transplantation. RESULTS: Weight gain ranged between -2.4 kg and 19.5 kg and was largely due to increase in body fat. RTR who remained body fat stable, showed more daily physical activity (p = 0.014), tended to consume less energy from drinks and dairy (p = 0.054), consumed less mono- and disaccharides (sugars) (p = 0.021) and ate more vegetables (p = 0.043) compared with those who gained body fat. Gain in body fat was strongly related to total cholesterol (r = 0.46, p = 0.017) and triglyceride (r = 0.511, p = 0.011) at one yr after transplantation. CONCLUSIONS: Gain in adiposity after renal transplantation is related to lifestyle factors such as high consumption of energy-rich drinks, high intake of mono- and disaccharides and low daily physical activity. RCTs are needed to investigate potential benefits of lifestyle intervention on long-term morbidity and mortality.

Outcome and development of symptoms after orthotopic liver transplantation for Wilson disease.

Abstract: Background Wilson disease (WD) is an autosomal recessive copper storage disease resulting in hepatic and neurologic dysfunction. Liver transplantation is an effective treatment for fulminant cases for patients with chronic liver disease. Reports on the outcome of neuropsychiatric symptoms after orthotopic liver transplantation (OLT) are limited. Aim To assess the course of neuropsychiatric and hepatic symptoms after liver transplantation for Wilson disease Methods Nineteen patients with Wilson disease received liver transplantation and were followed prospectively from 2005 to 2010 for the development of hepatic, neurological and psychiatric symptoms. Results Eight patients (all female) were transplanted for acute liver failure and eleven patients for chronic liver failure. Patient survival rates one and five yr after transplantation were 78% and 65%, respectively. Of the surviving patients, hepatic symptom scores improved in all patients and neurological symptom scores improved in all but one patient after OLT compared to the time of initial diagnosis and compared to pre-OLT status. Psychiatric symptoms showed moderate improvements. Conclusion Survival after OLT for Wilson disease with end-stage liver disease is excellent. Overall, neuropsychiatric symptoms improved after transplantation, substantiating arguments for widening of the indication for liver transplantation in symptomatic neurologic Wilson disease patients with stable liver function.

Everolimus leads to a lower risk of BKV viremia than mycophenolic acid in de novo renal transplantation patients: a single-center experience.

Abstract: Background There are limited published data concerning the effects of different immunosuppressive regimens on the development of polyomavirus (BKV) viremia. We examined the risk of developing BKV viremia in kidney transplant recipients receiving everolimus (EVR) or mycophenolic acid (MPA) as maintenance therapy. Methods We observationally analyzed 296 patients who underwent renal transplantation at our center between 2005 and 2010: 58 were treated with EVR and low-dose cyclosporine (LD-CyA) (group 1) and 238 with MPA and standard-dose CyA (group 2). All of the patients received induction therapy with basiliximab and maintenance steroids. BKV viremia (a whole-blood viral load of >850 copies/mL) was measured by means of real-time polymerase chain reaction at least once a month during a 12-month follow-up period. Results BKV viremia was detected in 57 patients (19%), five (9%) in group 1 and 52 (22%) in group 2. Kaplan–Meier analyses showed that freedom from BKV viremia was significantly more frequent in group 1. The mean time of onset of BKV viremia was about four months after transplantation in both groups. The median viral load was greater in group 2 (12.5 ± 6.1 vs. 2.5 ± 1.8 × 104 copies/mL; p = 0.01). After the onset of BKV viremia, graft function significantly declined in group 2: 11 patients developed polyomavirus-associated nephropathy (PVAN) and four presumptive PVAN; nine experienced an acute rejection after the discontinuation of MPA, and 11 (21%) lost their graft. There was no graft loss in group 1. Conclusion These findings suggest that in comparison with MPA and Cya, an EVR and LD-CyA regimen lowers the risk of BKV viremia after kidney transplantation and favorably alters outcomes.

Epstein-Barr virus reactivation in allogeneic stem cell transplantation is highly related to cytomegalovirus reactivation.

Abstract: Monitoring of Epstein-Barr virus (EBV) load and pre-emptive rituximab is an appropriate approach to prevent post-transplant lymphoproliferative disease (PTLD) occurring after hematopoietic stem cell transplantation (HSCT). This pre-emptive approach, based on EBV-DNA monitoring through a quantitative polymerase chain reaction, was applied to 101 consecutive patients who underwent allo HSCT at our Institute (median age 50). A single infusion of rituximab was administered to 11 of 16 patients who were at high risk for progression to PTLD, defined as a DNA value >10 000 copies/mL. All patients cleared EBV DNAemia, without any recurrences. Main factors significantly associated with high risk for PTLD were as follows: (i) unrelated vs. sibling (26% vs. 7%; p = 0.011); (ii) T-cell depletion (29% vs. 6%; p = 0.001); (iii) graft versus host disease (GVHD; 30% vs. 7%; p = 0.002); and (iv) cytomegalovirus (CMV) reactivation (29% vs. 4%; p = 0.001). Multivariate analysis showed that CMV reactivation was the only independent variable associated with EBV reactivation. We conclude that: (i) a single infusion of rituximab is able to prevent the risk of progression into EBV-related PTLD; and (ii) CMV reactivation is strongly associated with EBV reactivation; therefore, an intensive EBV monitoring strategy could be advisable only in case of CMV reactivation.

Standardizing skin biopsy sampling to assess rejection in vascularized composite allotransplantation.

Abstract: Over 70 hands and 20 faces have been transplanted during the past 13 yr, which have shown good to excellent functional and esthetic outcomes. However, (skin) rejection episodes complicate the post-operative courses of hand and face transplant recipients and are still a major obstacle to overcome after reconstructive allotransplantation. This article summarizes all relevant information on the skin component and rejection of a vascularized composite allograft. As more and more centers plan to implement a vascularized composite allotransplantation (VCA) program, we further develop guidelines and recommendations on collection and processing of skin biopsies from hand and face allograft recipients. This will help to standardize post-operative monitoring, avoid pitfalls for those new in the field and facilitate comparison of data on VCA between centers.

The use of eculizumab in renal transplantation.

Abstract: The complement system plays a vital role in mediating disease processes within renal allografts. Eculizumab is a humanized monoclonal antibody that targets complement protein C5, inhibiting cleavage into C5a and C5b, and therefore preventing formation of the membrane attack complex (MAC). It has been used primarily within renal transplantation to treat atypical hemolytic-uremic syndrome (aHUS) and antibody-mediated rejection (AMR) post-transplant, and also as prophylaxis in transplants at high risk for these conditions. Eculizumab appears to be effective in protecting renal allografts when post-transplant aHUS or AMR occur, although the published cases report relatively short follow-up. It is unclear how long treatment should continue (a particularly important issue given the expense of the drug), or whether eculizumab contributes to the development of accommodation in humans. When used for prophylaxis, eculizumab also appears to be effective. Some highly sensitized patients have developed either acute AMR or features of chronic AMR despite administration of the drug - this suggests that complement activation is not the only mechanism responsible for AMR. All patients should receive vaccination against Neisseria meningitidis prior to receiving eculizumab. Clinical trials, predominantly in antibody-incompatible renal transplantation, are ongoing to determine the optimal use of C5 inhibition.

Attitudes of Islamic religious officials toward organ transplant and donation.

Abstract: Uskun E, Ozturk M. Attitudes of Islamic religious officials toward organ transplant and donation. Abstract: Background: The decision to donate organs is an essential step in the process prior to transplantation. Religious leaders play an important role in decision-making in Islamic countries. The aim of this study is to reveal the attitudes of Islamic religious officials toward organ donation and transplantation. Methods: The study group for this cross-sectional research consisted of 165 religious people. A questionnaire was provided to the study group, asking about socio-demographic features, behaviors, and attitudes toward organ donation. Results: Most of the religious leaders who responded (71.5%) believe that donation is appropriate according to Islamic beliefs. Only 51.5% of those surveyed indicated a willingness to donate, however. Only three of the officials had donor cards. More than half (57.6%) declared that people had asked them for advice and opinions on organ donation. Among the religious officials, 32.7% said that they do not have enough knowledge about organ donation. Conclusion: The findings indicate that consultation with a religious leader on organ donation is an important source of information for the community, providing an opportunity to improve the current organ donation rates. This study indicates that education, especially directed toward religious leaders, to improve organ and tissue donation and transplantation would help to improve those rates.

A high antithymocyte globulin dose increases the risk of relapse after reduced intensity conditioning HSCT with unrelated donors

Abstract: The study included 110 consecutive patients with hematological malignancies receiving fludarabine-based reduced intensity conditioning (RIC) and hematopoietic stem cell transplantation (HSCT) from matched unrelated donors. The median age was 55 yr (range 11-68) and all but 15 patients received peripheral blood stem cell grafts. Antithymocyte globulin (ATG) (Thymoglobulin, Genzyme) at a total dose of 6 mg/kg (n = 66) or 8 mg/kg (n = 44) was given to all patients according to protocol. The ATG dose did not affect time-to-neutrophil or platelet engraftment. The incidences of acute GVHD grades II-IV were 34% and 18% (p = 0.11) and of chronic GVHD were 40% and 26% (p = 0.46) in patients receiving 6 and 8 mg/kg of ATG, respectively. The five-yr relapse-free survival (RFS) was 61% and 36% (p = 0.14) in patients, given low and high ATG dose, respectively. In patients given low-dose ATG, the incidence of relapse was lower compared to those given high-dose ATG, 19% vs. 41% (p = 0.04). In multivariate analysis, age >50 yr (p < 0.001), absence of acute (p < 0.001) and chronic GVHD (p = 0.001) were correlated to relapse, and low-dose ATG was associated with improved RFS (p < 0.05). A high dose (8 mg/kg) of ATG in RIC HSCT with unrelated donors increased the risk for relapse and reduced the RFS.

Difference in quality of life, fatigue and societal participation between living and deceased donor kidney transplant recipients

Abstract: Purpose of this study was to assess whether living (LD) and deceased donor (DD) kidney transplant recipients differ in health-related quality of life (HRQoL), fatigue and societal participation, depending on time since transplantation and after adjustment for clinical and demographic variables. A questionnaire study was performed among 309 LD and 226 DD recipients (response rate 74% and 61%) transplanted between 1997 and 2009. After adjustment for age, sex, and education, LD recipients transplanted less than or equal to five yr ago experienced better HRQoL than DD recipients on the domains' role limitations due to physical problems, general health perception, and on the physical component summary score (all p < 0.05) and a better societal participation (all subscales, p < 0.05). No differences were found in the mental health domains. The LD recipients also had better renal clearance than DD recipients (62.1 vs. 55.9 mL/min, p = 0.01). After additional adjustment for renal clearance, the differences in HRQoL and societal participation between LD and DD recipients remained. No differences were found in recipients transplanted more than five yr ago. We conclude that LD recipients on average have better HRQoL and societal participation than DD recipients, in the first years after transplantation.

Impaired exercise capacity after lung transplantation is related to delayed recovery of muscle strength.

Abstract: Lung transplant recipients report reduced exercise capacity despite satisfactory graft function We analysed changes in lung function, six-min walk distance (6MWD), and quadriceps strength in the first 26-wk post-transplant and examined what factors predict 6MWD recovery All lung transplant recipients at a single institution between June 2007 and January 2011 were considered for inclusion Lung function, 6MWD, and quadriceps strength corrected for body weight (QS%) were recorded pre- and two-, six-, 13-, and 26-wk post-transplant Fifty recipients, of mean (± SD) age 42 (± 13) yr, were studied Mean FEV1 % and 6MWD improved from 264% to 889% and from 397 to 549 m at 26 wk, respectively (both p < 0001) QS% declined in the first two wk but had improved to above pre-transplant levels by 26 wk (p = 0027) On multivariate analysis (n = 35), lower pre-transplant exercise capacity and greater recovery in muscle strength explained most of the improvement in exercise capacity Delayed recovery of exercise capacity after lung transplantation is unrelated to delay in improvement in graft function, but occurs secondary to the slow recovery of muscle strength Our findings show that additional controlled trials are needed to better understand the influence of exercise rehabilitation on improvement in exercise capacity post-transplantation

Long-term outcome in patients treated with combined heart and liver transplantation for familial amyloidotic cardiomyopathy.

Abstract: Background The amyloidogenic transthyretin (ATTR) mutation Leu111Met causes a primarily cardiac amyloidosis: Familial amyloidotic cardiomyopathy (FAC). Combined heart–liver transplantation (CHLTx) is the preferred treatment for patients with heart failure due to familial amyloidosis, but information on outcome of patients with Leu111Met mutation is limited. The aim of this study was to evaluate the long-term outcome of CHLTx in patients with FAC. Methods and materials Between 1998 and 2009, CHLTx was performed in 7 FAC patients (four men). Six patients underwent simultaneous transplantation. All patients suffered from severe cardiomyopathy. Results Mean recipient age at transplantation was 48.3 ± 4.2 yr. Mean follow-up was 55 months. No peroperative mortality occured. Two patients died within the first year (infection, multi-organ failure) of transplantation. Cumulative survival at 4.5 yr was 71%. No significant liver rejections occurred. One patient experienced an episode of cardiac rejection requiring treatment (H2R). For the surviving five patients, most recent left ventricular ejection fraction was 0.61 ± 0.02, and plasma creatinine was 129 ± 47 μM. None developed significant allograft vasculopathy or neuropathy after transplantation. No recurrence of cardiac amyloid was found. Conclusions CHLTx in selected patients with FAC due to Leu111Met mutation offers acceptable long-term survival, almost comparable with isolated cardiac transplantation. Allograft rejection was rare.

Managing renal transplant ischemia reperfusion injury: novel therapies in the pipeline.

Abstract: Ischemia reperfusion injury (IRI) is an early, non-specific inflammatory response that follows perfusion of warm blood into a cold asanguinous organ following transplantation. The occurrence of IRI may have a pivotal impact on acute and long-term renal allograft function. Initially, IRI contributes to delayed graft function (DGF), a term typically defined as the need for dialysis within one wk after renal transplantation. DGF frequently leads to prolonged hospital stay, increased healthcare costs, and potentially worse prognosis. Strategies to prevent IRI have so far been fairly limited, poorly defined, inadequately studied, and mostly anecdotal. The purpose of this review is to summarize the existing and novel therapies, which may mitigate IRI in renal transplantation. Agents currently in the pipeline include: Diannexin, which reduces endothelial cell injury by shielding phosphatidylserine; YSPSL, which mimics the binding portion of P-selectin glycoprotein ligand-1 to competitively inhibit translocation of P-selectin and recruitment of polymorphonuclear leukocytes to the surface of endothelial cells; and I5NP, a synthetic small interfering ribonucleic acid that results in the inhibition of p53 expression. These agents represent an exciting frontier in transplant pharmacotherapy; they are in various phases of investigation and may have broader benefits in reducing complications of DGF.

Safe use of highly steatotic livers by utilizing a donor/recipient clinical algorithm

Abstract: The aim of this study was to assess the long-term safety and clinical outcomes associated with the utilization of highly steatotic donor livers utilizing a specific donor/recipient matching algorithm. This was a prospective, observational, single-center, 10-yr follow-up study. Highly steatotic livers were utilized according to a donor/recipient algorithm that guided the surgeon to use highly steatotic donor organs judiciously in low-risk recipients. This study initially compared fat assessment based on frozen-section Ehrlich's hematoxylin and eosin (H&E) to reperfusion biopsy fat assessment and demonstrated that H&E is an insensitive analysis to determine degree of steatosis. Patients were divided into three groups based on donor steatosis (group 1: 60% steatosis), and clinical outcomes were assessed. One hundred and sixteen patients were included in the analysis. Patients that received severely steatotic livers (>60% fat) showed increased reperfusion liver injury and delayed return of liver function in the early postoperative period, demonstrated by biochemical markers. However, there were no differences in primary non-function, postoperative complications, length of stay, and patient and graft survival. Using rigorous donor/recipient matching through a detailed algorithm, these data demonstrate that normal liver allograft outcomes are not superior to those in highly steatotic grafts.

Incidence of donor-specific antibodies in kidney transplant patients following conversion to an everolimus-based calcineurin inhibitor-free regimen

Abstract: Scarce data exist regarding the incidence of donor-specific antibodies (DSAs) in kidney transplant patients receiving everolimus-based immunosuppression without calcineurin inhibitors (CNIs). The aim of this retrospective case-control study was to compare the incidence of de novo DSAs in patients converted to an everolimus-based regimen without CNIs with that seen in patients maintained on CNIs. Sixty-one DSA-free kidney transplant patients who had been converted to an everolimus-based regimen (everolimus group) were compared to 61 other patients maintained on CNIs-based regimen (control group). Patients were matched according to age, gender, induction therapy, date of transplantation, and being DSA-free at baseline. At last follow-up, the incidence of DSAs was 9.8% in the everolimus group and 5% in the control group (p = ns). In the everolimus group, the increased incidence of DSAs between baseline and last follow-up was statistically significant. Antibody-mediated rejection occurred in 6.5% in the everolimus group and 0% in the CNIs group. The incidence of DSAs is numerically increased in kidney transplant patients treated with an everolimus-based without CNIs. A study including a larger number of patients is required to determine whether a CNI-free everolimus-based immunosuppression significantly increases DSAs formation.

Incidence and risk factors for new-onset diabetes in living-donor liver transplant recipients

Abstract: With the increased number of long-term survivors after liver transplantation, new-onset diabetes after transplantation (NODAT) is becoming more significant in patient follow-up. However, the incidence of new-onset diabetes after living-donor liver transplantation (LDLT) has not been well elucidated. The aim of this study was to evaluate the incidence and risk factors for NODAT in adult LDLT recipients at a single center in Japan. A retrospective study was performed on 161 adult patients without diabetes who had been followed up for ≥three months after LDLT. NODAT was defined according to the 2003 American Diabetes Association/World Health Organization guidelines. The recipient-, donor-, operation-, and immunosuppression-associated risk factors for NODAT were assessed. Overall, the incidence of NODAT was 13.7% (22/161) with a mean follow-up of 49.8 months. In a multivariate analysis, the identified risk factors for NODAT were donor liver-to-spleen (L-S) ratio (hazard ratio [HR] = 0.022, 95% confidence interval [CI] = 0.001-0.500, p = 0.017), and steroid pulse therapy for acute rejection (HR = 3.320, 95% CI = 1.365-8.075, p = 0.008). In conclusion, donor L-S ratio and steroid pulse therapy for acute rejection were independent predictors for NODAT in LDLT recipients. These findings can help in screening for NODAT and applying early interventions.

The factors that influence attitudes toward organ donation for transplantation among UK university students of Indian and Pakistani descent.

Abstract: Background The shortage of organs donated for transplantation is particularly severe among ethnic minorities. Previous work has often studied ethnic minorities in broad groups, failing to differentiate by age or country of education. We investigated the younger generation of UK-educated ethnically Indian and Pakistani students to determine their attitudes toward organ donation. Methods We conducted nine focus groups and eight semi-structured interviews. Participants were divided by ethnicity, gender, and medical/non-medical background. Interview transcripts were analyzed by thematic analysis. Results Six key factors influencing attitudes toward organ donation were found: religion, awareness of the importance of donation, impact of medical education, culture-specific factors, treatment of donors and their organs, and influence of family. The attitude of Islam to donation was highly relevant to Pakistani participants, more than other factors; for Indians, all six factors were similarly relevant. We found that medical education specifically had an important effect on shaping attitudes toward donation. Cultural changes suggested the younger generation may differ from their elders as they adopt British culture. Awareness of donation was universally low. Conclusions Indian and Pakistani students are hesitant to donate organs because of multiple factors, which if addressed in a culturally relevant manner could substantially improve donation rates.

De novo malignancies in renal transplant recipients: experience at a single center with 1882 transplant patients over 39 yr

Abstract: Purpose Cancers complicating organ allografts are a major cause of morbidity and mortality after renal transplantation. Different registries have described an overall three to eightfold increase in cancer risk compared with the general population. This retrospective study investigated the incidence and outcome of de novo malignancies following kidney transplantation in a single German kidney transplantation center. Materials and Methods Between 1966 and 2005, 1882 patients underwent kidney transplantation at the Erlangen–Nuremberg kidney transplantation center. The incidence and types of post-transplant malignancies were retrospectively analyzed according to the patients' records and the database of the local cancer registry. Results We identified 257 malignancies in 231 patients, an overall incidence of 13.7%. The mean follow-up time was 9.9 yr (range, 0.4–25.5 yr). The observed incidence data corresponded to a 12.1-fold increase in the overall risk of developing a malignant nonskin tumor compared with the nontransplanted population. Urinary tract malignancies represented the most frequent malignancies among the nonskin tumors (32.1%), followed by gastrointestinal tract (30.7%) and gynecological (14%) cancers. When we considered the duration from renal transplantation to tumor detection and tumor-specific survival, there was no difference between patients treated with or without a cyclosporine A-based regimen. Conclusions In our study, the overall risk of developing a post-transplant nonskin malignancy was 12.1-fold higher compared with the age-matched general population. Development of solid organ malignancies is one of the most frequent causes of morbidity and mortality in renal transplant recipients; thus, close tumor screening in patients after kidney transplantations is warranted.

Safety and efficacy of sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation

Abstract: Introduction Recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) carries a poor prognosis. The aim of our study was to assess the safety and efficacy of sorafenib in patients with recurrent HCC following LT. Methods A prospectively maintained LT database was retrospectively analyzed for patients with recurrent HCC following LT between 2001 and 2011–34 patients. Patients were divided into two groups based on whether they were prescribed sorafenib (n = 17) or not prescribed sorafenib (n = 17). The primary endpoint was overall survival. Results There were no significant differences between the two groups analyzed. Seventeen patients were on sorafenib for recurrent HCC, with a mean daily dose of ~444 mg. Mean duration of treatment was ~10 months. Side effects included: thrombocytopenia, diarrhea, rising transaminases, fatigue, hand–foot skin reaction, and nausea. Survival in the sorafenib vs. non-sorafenib group was greater at three-, six-, nine-, and 12-month intervals and overall survival. Conclusion Sorafenib can be well tolerated and safe in patients with recurrent HCC following LT and may be associated with a modest survival benefit. To our knowledge, this is the largest single-center retrospective analysis of patients prescribed sorafenib for recurrent HCC after LT.

Current concepts and systematic review of vascularized composite allotransplantation of the abdominal wall.

Abstract: Introduction Abdominal wall vascularized composite allotransplantation (AW-VCA) is a rarely utilized technique for large composite abdominal wall defects. The goal of this article is to systematically review the literature and current concepts of AW-VCA, outline the challenges ahead, and provide an outlook for the future. Methods Systematic review of the literature was performed using MEDLINE, EMBASE, and PubMed to identify relevant articles discussing results of AW-VCA. Cadaver and animal studies were excluded from the systematic review, but selectively included in the discussion. Results The resultant five papers report their results on AW-VCA(Transplantation, 85, 2008, 1607; Am J Transplant, 7, 2007, 1304; Transplant Proc, 41, 2009, 521; Transplant Proc, 36, 2004, 1561; Lancet, 361, 2003, 2173). These papers represent the result of two study groups in which a total of 18 AW-VCA were performed in 17 patients. Two different operative approaches were used. Overall flap/graft survival was 88%. No mortality related to the transplant was reported. One cadaver study and two animal models were identified and separately presented (Transplant Proc, 43, 2011, 1701; Transplantation, 90, 2010, 1590; Journal of Surgical Research, 162, 2010, 314). Conclusion Literature review reports AW-VCA is technically feasible with low morbidity and mortality. Functional outcomes are not reported and minimally considered. With advancements in vascularized composite allotransplantation research and decreasing toxicity of immunosuppression therapies and immunomodulatory regimens, AW-VCA can be applied in circumstances beyond conjunction with visceral transplantation.

Identifying potential kidney donors using social networking web sites

Abstract: Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation They allow for wide dissemination of information and discussion and could lessen anxiety associated with a face-to-face request for donation However, sparse data exist on the use of social media for this purpose We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2-69); 88% were US residents Other posted information included the individual's photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%) Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live-donor kidney transplant Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic Facebook is already being used to identify potential kidney donors Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation

Simultaneous pancreas kidney transplants in diabetic patients with end‐stage renal disease: the 20‐yr experience

Abstract: Introduction We are reporting the results over a 20 yr period of simultaneous pancreas-kidney transplants in patients with end-stage renal disease and diabetes mellitus. The outcomes of the transplants, performed between 1989 and 2008, are stratified by pretransplant c-peptide value. Methods One hundred and seventy-three patients with end-stage renal disease due to diabetes, and were stratified according to undetectable c-peptide (x 0.8 ng/mL) levels. Results Patients with detectable c-peptide (x > 0.8 ng/mL) were the oldest at diabetes diagnosis (24.2 vs. 15.4 yr, p 0.8 ng/mL) had better graft survival than those with an undetectable c-peptide level (x < 0.8 ng/mL), p = 0.064; while those with undetectable levels, had better patient survival than those with detectable c-peptide levels (p = 0.019). Conclusion Despite the differences between groups by BMI, age of onset of insulin use, and age at transplant, there was a difference in patient but not graft survival within the 20 yr follow-up period.

Pre-existing diabetes significantly increases the risk of graft failure and mortality following renal transplantation.

Abstract: The aim of this study was to examine the impact of pre-existing diabetes mellitus (DM) on acute rejection, graft loss, and mortality following kidney transplant and whether glycemic control or cardiovascular disease (CVD) risk control with medications influenced outcomes. This was a cohort study of 1002 renal transplants conducted between 2000 and 2008. Patients were included if they received a kidney transplant within the allotted time and were at least 18 yr of age. Cox regression was used to assess acute rejection, graft failure, or death controlling for relevant sociodemographic, clinical, and post-transplant variables. Five-yr patient survival (83% vs. 93%, p < 0.001) and graft survival (74% vs. 79%, p = 0.005) were significantly lower in patients with pre-existing DM. Sequential Cox regression models demonstrated that pre-existing DM was consistently associated with a higher risk of death (HR 2.3-3.0, p < 0.01) and graft failure (HR 1.5-1.8, p < 0.04) in all models except after adjusting for CVD medication use (HR 1.9, p = 0.174 and HR 1.5, p = 0.210, respectively). These data suggest pre-existing DM is a significant risk factor for graft failure and death following renal transplantation and aggressive CVD risk reduction with medications may be an important strategy to reduce mortality and graft failure.

De novo malignancy post-liver transplantation: a single center, population controlled study.

Abstract: Background With the growing numbers of liver transplant recipients, it is increasingly important to understand the risks of de novo malignancy after liver transplantation.

Individualization of tacrolimus dosage basing on cytochrome P450 3A5 polymorphism--a prospective, randomized, controlled study.

Abstract: We investigated how cytochrome P450 (CYP) 3A5 polymorphism affects pharmacokinetics of tacrolimus and its interaction with diltiazem in Chinese kidney transplant recipients. Sixty-two CYP3A5 expressers and 58 non-expressers were, respectively, randomized to receive diltiazem supplement or not. Their pharmacokinetic profiles were acquired on 14th day, sixth month, and 18th month post-transplant and compared among groups. A dosing equation was fit based on above data with CYP3A5 genotype and diltiazem co-administration as variables. Then, necessary initial doses with or without diltiazem were calculated and used in 11 CYP3A5 expressers, respectively, when another 11 expressers received routine doses as control. Trough concentration was measured on the third-day post-transplant and patients failed to reach target range were presented in percentage. These two parameters were compared among three groups. Patients were followed up until June 2010, kidney function, biopsy-proved acute rejection, and other adverse events were monitored. Results showed that CYP3A5 expressers needed more tacrolimus to reach therapeutic concentration window and were more susceptible to diltiazem-induced concentration increase than CYP3A5 non-expressers. CYP3A5 polymorphism-guided dosing equation helped to determine appropriate initial doses of tacrolimus in individuals. In conclusion, CYP3A5 polymorphism profoundly influences pharmacokinetics of tacrolimus and helps to individualize tacrolimus dose.