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Les derniers abstracts de la revue Transplantation - Current Issue :


    Date de mise en ligne : Jeudi 01 janvier 1970
    Antoine, Corinne; Legendre, Christophe
    Organ Transplantation in France
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Romagnoli, Jacopo; Casanova, Daniel; Papalois, Vassilios
    Transplant Surgery Training in Europe: Board Examinations in Transplant Surgery and the Accreditation of Transplant Centers
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Muller, Elmi
    Research Highlights
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Dean, Wendy K.; Talbot, Simon G.
    Vascularized Composite Allotransplantation at a Crossroad: Adopting Lessons From Technology Innovation to Novel Clinical Applications
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Kurian, Sunil M.; Whisenant, Thomas; Mas, Valeria; Heilman, Raymond; Abecassis, Michael; Salomon, Daniel R.; Moss, Adyr; Kaplan, Bruce
    Biomarker Guidelines for High-Dimensional Genomic Studies in Transplantation: Adding Method to the Madness
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Hall, Isaac E.; Reese, Peter P.
    Shining a Light on the Murky Problem of Discarded Kidneys
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Iltis, Ana S.
    Living Uterus Donors: The Role of Future Research in Addressing Ethical Considerations
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Emond, Jean C.
    Laparoscopic Donor Hepatectomy: A Way Forward?
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Gorantla, Vijay S.; Davis, Michael R.
    Vascularized Composite Allograft Preservation: Ubi Sumus?
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Acuna, Sergio A.; Huang, Johnny W.; Daly, Corinne; Shah, Prakesh S.; Kim, S. Joseph; Baxter, Nancy N.
    Outcomes of Solid Organ Transplant Recipients With Preexisting Malignancies in Remission: A Systematic Review and Meta-Analysis
    imageBackground: Solid organ transplant recipients (SOTR) with a pretransplant malignancy (PTM) are at increased risk for cancer recurrence. However, it is unclear whether differences in survival and incidence of posttransplant de novo malignancies exist between recipients with PTM and those without PTM. We designed a systematic review to synthesize all available evidence assessing these outcomes. Methods: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library to identify studies comparing the following outcomes in SOTR by PTM status: (1) all-cause mortality, (2) cancer-specific mortality, and (3) incidence of posttransplant de novo malignancy. Risk of bias was assessed using the Newcastle-Ottawa Scale. Results: Thirty-two cohort studies were included. Recipients with PTM were at increased risk of all-cause mortality compared to recipients without PTM (pooled hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.27-1.81). Similarly, recipients with PTM were 3 times more likely to die of cancer (pooled HR, 3.13; 95% CI, 2.29-4.27). The pooled HR for developing posttransplant de novo malignancy was also increased (HR, 1.92; 95% CI, 1.52-2.42). The association of all-cause mortality and SOTR with PTM did not vary by transplanted organ. Conclusions: Pretransplant malignancy is associated with increased risk of all cause-mortality, cancer-specific mortality and of developing de novo malignancies after transplantation compared with those without PTM. These results reaffirm the need for careful selection of transplant recipients with PTM. Tailored screening and management strategies should be developed for this group of patients.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Shaw, David; Georgieva, Denie; Haase, Bernadette; Gardiner, Dale; Lewis, Penney; Jansen, Nichon; Wind, Tineke; Samuel, Undine; McDonald, Maryon; Ploeg, Rutger; on behalf of the ELPAT Working Group on Deceased Donation
    Family Over Rules? An Ethical Analysis of Allowing Families to Overrule Donation Intentions
    imageAbstract: Millions of people want to donate their organs after they die for transplantation, and many of them have registered their wish to do so or told their family and friends about their decision. For most of them, however, this wish is unlikely to be fulfilled, as only a small number of deaths (1% in the United Kingdom) occur in circumstances where the opportunity to donate organs is possible. Even for those who do die in the “right” way and have recorded their wishes or live in a jurisdiction with a “presumed consent” system, donation often does not go ahead because of another issue: their families refuse to allow donation to proceed. In some jurisdictions, the rate of “family overrule” is over 10%. In this article, we provide a systematic ethical analysis of the family overrule of donation of solid organs by deceased patients, and examine arguments both in favor of and against allowing relatives to “veto” the potential donor's intentions. First, we provide a brief review of the different consent systems in various European countries, and the ramifications for family overrule. Next, we describe and discuss the arguments in favor of permitting donation intentions to be overruled, and then the arguments against doing so. The “pro” arguments are: overrule minimises family distress and staff stress; families need to cooperate for donation to take place; families might have evidence regarding refusal; and failure to permit overrules could weaken trust in the donation system. The “con” arguments are: overrule violates the patient's wishes; the family is too distressed and will regret the decision; overruling harms other patients; and regulations prohibit overrule. We conclude with a general discussion and recommendations for dealing with families who wish to overrule donation. Overall, overrule should only rarely be permitted.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Snanoudj, Renaud; Timsit, Marc-Olivier; Rabant, Marion; Tinel, Claire; Lazareth, Hélène; Lamhaut, Lionel; Martinez, Frank; Legendre, Christophe
    Dual Kidney Transplantation: Is It Worth It?
    imageAbstract: Use of expanded criteria donor (ECD) kidneys, which are associated with a reduced graft survival rate, has become widely adopted in elderly recipients in an old-to-old allocation system. However, the results are frequently unsatisfactory, and a high proportion of these ECD kidneys are discarded. Dual kidney transplantation (DKT) is an underused way to expand the pool of ECD kidneys and to rapidly transplant elderly patients with satisfactory results because of the transplantation of double the nephronic mass. In this overview, we summarize the results of the main studies on DKT. DKT suffers from a prejudice of heaviness and is considered to be useless by transplant centers that do not perform it. The literature is often biased by the heterogeneity of the criteria leading to a DKT and the common refusal of kidneys that are judged too marginal. In fact, we show that when strictly allocated according to reliable clinical or histological scores, dual and single ECD transplantations yield similar results in terms of patient and graft survival rates despite significant differences in donors' characteristics. DKTs are not associated with a higher proportion of surgical complications, except in some studies showing thrombosis of 1 of the 2 grafts. The benefits of dual transplantation are particularly evident for kidneys coming from most ECDs. There is still a need for more studies to find the best allocation criteria that would permit transplantation to the highest number of patients with similar outcomes in recipients of single and dual ECD kidneys.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Benke, Kálmán; Sayour, Alex Ali; Mátyás, Csaba; Ágg, Bence; Németh, Balázs Tamás; Oláh, Attila; Ruppert, Mihály; Hartyánszky, István; Szabolcs, Zoltán; Radovits, Tamás; Merkely, Béla; Szabó, Gábor
    Heterotopic Abdominal Rat Heart Transplantation as a Model to Investigate Volume Dependency of Myocardial Remodeling
    imageAbstract: Heterotopic abdominal rat heart transplantation has been extensively used to investigate ischemic-reperfusion injury, immunological consequences during heart transplantations and also to study remodeling of the myocardium due to volume unloading. We provide a unique review on the latter and present a summary of the experimental studies on rat heart transplantation to illustrate changes that occur to the myocardium due to volume unloading. We divided the literature based on whether normal or failing rat heart models were used. This analysis may provide a basis to understand the physiological effects of mechanical circulatory support therapy.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Finsterbusch, Michaela; Kitching, A. Richard; Hickey, Michael J.
    Imaging Leukocyte Responses in the Kidney
    imageAbstract: The kidney can be negatively affected by a range of innate and adaptive immune responses, resulting in alterations in the functions of the kidney and, in some cases, progression to renal failure. In many of these responses, infiltration of blood-borne leukocytes into the kidney is central to the response. In addition, a large population of mononuclear phagocytes resident in the kidney can modulate these responses. A great deal of research has investigated both the mechanisms of leukocyte recruitment to the kidney and the actions of immune cells resident within the kidney. Because of the dynamic nature of the processes whereby leukocytes enter sites of inflammation, in vivo imaging has been one of the key approaches used for understanding leukocyte recruitment as it occurs throughout the body, and this is also true for kidney. However, imaging this organ and its complicated microvasculature during different forms of renal pathology presents a unique set of challenges. In this review, we examine the approaches used for intravital imaging of the kidney and summarize the insights gained from these studies regarding the mechanisms of leukocyte entry into the kidney during inflammation and the actions of immune cells within this organ.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Wang, Zheng-Yu; Martens, Gregory R.; Blankenship, Ross L.; Sidner, Richard A.; Li, Ping; Estrada, Jose L.; Tector, Matthew; Tector, A. Joseph
    Eliminating Xenoantigen Expression on Swine RBC
    imageBackground: The rapidly improving tools of genetic engineering may make it possible to overcome the humoral immune barrier that prevents xenotransplantation. We hypothesize that levels of human antibody binding to donor tissues from swine must approximate the antibody binding occurring in allotransplantation. It is uncertain if this is an attainable goal. Here we perform an initial analysis of this issue by comparing human antibody binding to red blood cells (RBC) isolated from knockout swine and to allogeneic or autologous human RBC. Methods: Human sera were incubated with RBC isolated from various genetically engineered swine or from humans. The level of IgG and IgM binding to these cells were compared using either flow cytometry or a novel mass spectrometric assay. Results: Mass spectroscopic quantitation of human antibody binding demonstrated that as few as 3 gene inactivations can reduce the levels human antibody binding to swine RBC that is as low as autologous human RBC. Flow cytometry showed that RBC from 2-gene knockout swine exhibited less human antibody binding than human blood group O allogeneic RBC in 22% of tested sera. Deletion of a third gene from pigs resulted in 30% of human samples having less IgG and IgM RBC xenoreactivity than alloreactivity. Conclusions: Xenoantigenicity of swine RBC can be eliminated via gene disruption. These results suggest that the gene knockout approach may be able reduce antigenicity in other pig tissues to levels that enable the xenotransplantation humoral barrier to be overcome.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Wei, Liang; Kaul, Vandana; Qu, Xiumei; Xiong, Xiaoxing; Lau, Audrey H.; Iwai, Naoharu; Martinez, Olivia M.; Krams, Sheri M.
    Absence of miR-182 Augments Cardiac Allograft Survival
    imageBackground: MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes and are important regulators in immune responses. Previous studies demonstrated that the miRNA, miR-182 was significantly increased during allograft rejection. Further, the transcription factor Forkhead box (FOX) protein 1, (FOXO1) was shown to be a target of miR-182. The aim of this study is to further examine the role of miR-182 in alloimmune responses. Methods: Transplantation of BALB/c cardiac allografts was performed in C57BL/6, miR-182−/−, B6.129S-H2dlAb1-Ea (MHC II− and CD4+ T cell-deficient) and B6.129S2-Tap1tm1Arp (MHC I− and CD8+ T cell-deficient) mice, with or without CTLA-4Ig administration. T cell phenotype, FOXO1 protein levels and graft infiltrating lymphocytes were determined in C57BL/6 or miR-182−/− mice by flow cytometric analysis, Western blot, and immunohistochemistry, respectively. Results: We now show that T cells, mainly CD4+ are the main cellular source of miR-182 during allograft rejection. In the absence of miR-182, CTLA-4Ig treatment significantly increased allograft survival (31.5 days C57BL/6 vs 60 days miR-182−/−; P < 0.01). Further, CTLA4-Ig treatment inhibits miR-182 expression, increases FOXO1 levels, and reduces the percentage of CD4+CD44hi T cells after transplantation. Fewer T cells infiltrate the cardiac allografts, and memory T cells are significantly decreased in allograft recipients deficient in miR-182 with CTLA4-Ig treatment (P < 0.01). Conclusions: Our findings suggest that miR-182 contributes to the T-cell responses to alloantigen especially under costimulation blockade. Therapeutics that target specific miRNAs may prove beneficial in transplantation.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Lollinga, Wouter T.; de Wit, Raymond H.; Rahbar, Afsar; Vasse, Gwenda F.; Davoudi, Belghis; Diepstra, Arjan; Riezebos-Brilman, Annelies; Harmsen, Martin C.; Hillebrands, Jan-Luuk; Söderberg-Naucler, Cecilia; van Son, Willem J.; Smit, Martine J.; Sanders, Jan-Stephan; van den Born, Jacob
    Human Cytomegalovirus-Encoded Receptor US28 Is Expressed in Renal Allografts and Facilitates Viral Spreading In Vitro
    imageBackground: Renal transplantation is the preferred treatment for patients with end-stage renal disease. Human cytomegalovirus (HCMV) activation is associated with decreased renal graft function and survival. Human cytomegalovirus encodes several immune modulatory proteins, including the G protein-coupled receptor US28, which scavenges human chemokines and modulates intracellular signaling. Methods: Our aim was to identify the expression and localization of US28 in renal allograft biopsies by immunohistochemistry and determine its role in viral spreading in vitro. Results: Immunohistochemistry revealed US28 in 31 of 34 renal transplant biopsies from HCMV-seropositive donors. Expression was independent of HCMV viremia or IgG serostatus. US28 was predominantly expressed in the cytoplasm of vascular smooth muscle cells (VSMCs) and tubular epithelial cells, with a median positivity of 20% and 40%, respectively. Also, US28-positive cells were present within arterial neointima. In contrast to US28, HCMV-encoded immediate early antigen was detected in less than 5% of VSMCs, tubular epithelial cells, interstitial endothelium, interstitial inflammatory infiltrates, and glomerular cells. Primary VSMCs were infected with green fluorescent protein–tagged wild type or US28-deficient HCMV. The viral spreading of US28-deficient HCMV, via culture medium or cell-to-cell transmission, was significantly impeded as shown by green fluorescent protein (ie, infected) cell quantification and quantitative real-time polymerase chain reaction. Additionally, the number and size of foci was smaller. Conclusions: In summary, HCMV-encoded US28 was detected in renal allografts from HCMV-positive donors independent of viremia and serostatus. Also, US28 facilitates HCMV spreading in VSMCs in vitro. Because the vasculature is affected in chronic renal transplant dysfunction, US28 may provide a potential target for therapeutic intervention.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Brondani, Leticia A.; Rech, Tatiana H.; Boelter, Gabriela; Bauer, Andrea C.; Leitão, Cristiane B.; Eizirik, Décio L.; Crispim, Daisy
    UCP2 Expression Is Increased in Pancreas From Brain-Dead Donors and Involved in Cytokine-Induced β Cells Apoptosis
    imageBackground: Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in β cell apoptosis, but these findings remain controversial. Methods: We have presently performed a case-control study to assess UCP2 expression in pancreas from BD donors (cases) and subjects who underwent pancreatectomy (controls). We next investigated the role of Ucp2 in cytokine-induced apoptosis of rat insulin-producing INS-1E cells. Results: UCP2 gene expression was higher in pancreas from BD donors compared with controls (1.73 ± 0.93 vs 0.75 ± 0.66; fold change, P < 0.05). Ucp2 knockdown (80% at the protein and messenger RNA levels) reduced by 30% cytokine-induced apoptosis and nitric oxide production in INS-1E cells. This protection was associated with decreased expression of cleaved (activated) caspases 9 and 3, suggesting that Ucp2 knockdown interferes with cytokine triggering of the intrinsic apoptotic pathway. Moreover, both messenger RNA and protein concentrations of the antiapoptotic protein Bcl-2 were increased after Ucp2 knockdown in INS-1E cells. Conclusions: These data suggest that UCP2 has an apoptotic effect in β cells via regulation of the intrinsic pathway of apoptosis.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Nova-Lamperti, Estefania; Chana, Prabhjoat; Mobillo, Paula; Runglall, Manohursingh; Kamra, Yogesh; McGregor, Reuben; Lord, Graham M.; Lechler, Robert I.; Lombardi, Giovanna; Hernandez-Fuentes, Maria P.; The GAMBIT Study
    Increased CD40 Ligation and Reduced BCR Signalling Leads to Higher IL-10 Production in B Cells From Tolerant Kidney Transplant Patients
    imageBackground: An increased percentage of peripheral transitional B cells producing IL-10 has been observed in patients tolerant to kidney allografts. In healthy volunteers, the balance between the CD40 and B-cell receptor (BCR) signalling modulated IL-10 production by B cells, with stimulation via the BCR decreasing CD40-mediated IL-10 production. In this study, we evaluate whether in tolerant kidney transplant patients, the increased IL-10 production by B cells was due to an altered CD40 and/or BCR signalling. Methods: B cells obtained from a new cohort of tolerant renal transplant recipients and those from age- and sex-matched healthy volunteers were activated via CD40 and BCR, either alone or in combination. Results: In tolerant patients, we observed higher percentages of B cells producing IL-10 after CD40 ligation and higher expression of CD40L on activated T cells compared with healthy controls. Furthermore, B cells from tolerant recipients had reduced extracellular signal-regulated kinase signalling after BCR-mediated activation compared with healthy controls. In keeping with this, combining BCR signalling with CD40 ligation did not reduce IL-10 secretion as was observed in healthy control transitional B cells. Conclusions: Altogether, our data suggest that the altered response of B cells in tolerant recipients may contribute to long-term stable graft acceptance.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Rotellar, Fernando; Pardo, Fernando; Benito, Alberto; Zozaya, Gabriel; Martí-Cruchaga, Pablo; Hidalgo, Francisco; Lopez, Luis; Iñarrairaegui, Mercedes; Sangro, Bruno; Herrero, Ignacio
    Totally Laparoscopic Right Hepatectomy for Living Donor Liver Transplantation: Analysis of a Preliminary Experience on 5 Consecutive Cases
    imageBackground: The pure laparoscopic approach in right hepatectomy (LRH) for living donor liver transplantation (LDLT) is a controversial issue. Some authors have reported the procedure to be feasible but surgical outcomes and impact on short and long-term morbidity rates are yet to be determined. The aim of this study is to present the results of a preliminary 5 consecutive cases series of LRH for LDLT and to compare it with a successive cohort of open right hepatectomies (ORH) for LDLT. Methods: From May 2013 to October 2015, 5 consecutive donors underwent LRH for LDLT in our center. The previous last 10 ORH for LDLT were selected for comparison. Special care was taken to include all adverse events. Each patient's complications were graded with the Clavien-Dindo Classification and scored with the Comprehensive Complication Index. Results: All 5 consecutive donors completed a pure laparoscopic procedure. All allografts (open and laparoscopically procured) were successfully transplanted with no primary graft failures. Only 2 Clavien-Dindo Grade-I complications occurred in the LRH donors, while ORH donors had 10 Grade I, 2 Grade II and 1 Grade IIIa complications in the short term (<3 months). In the long term (6–12 months follow-up), LRH donors had a significant lower incidence of complications (Comprehensive Complication Index: 1.74; SD, 3891 vs 15.2 SD; 8.618; P = 0.006). Conclusions: In our experience, LRH for LDLT is a feasible procedure. Further comparative series may support our preliminary findings of reduced incidence and severity of complications as compared with the open approach.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Lai, Quirino; Feys, Estelle; Karam, Vincent; Adam, Rene; Klempnauer, Jurgen; Oliverius, Martin; Mazzaferro, Vincenzo; Pascher, Andreas; Remiszewski, Piotr; Isoniemi, Helena; Pirenne, Jacques; Foss, Aksel; Ericzon, Bo G.; Markovic, Sasa; Lerut, Jan P.; for the European Liver Intestine Transplant Association (ELITA)
    Hepatic Epithelioid Hemangioendothelioma and Adult Liver Transplantation: Proposal for a Prognostic Score Based on the Analysis of the ELTR-ELITA Registry
    imageBackground: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor which has an intermediate aggressive behavior. Although the value of liver transplantation (LT) is well established, its place in the management of HEHE is still unclear. The aim of this study is to confirm, based on a very large patient cohort, the value of LT in the management of HEHE and to identify risk factors for post-LT recurrence. Methods: The outcome of 149 transplant recipients with HEHE recorded in the European Liver Transplant Registry during the period November 1984 to May 2014 was analyzed. Median post-LT follow-up was 7.6 years (interquartile range, 2.8-14.4). Results: Cox regression analysis showed that macrovascular invasion (hazard ratio [HR], 4.8; P < 0.001), pre-LT waiting time of 120 days or less (HR, 2.6; P = 0.01) and hilar lymph node invasion (HR = 2.2; P = 0.03), but not pre-LT extrahepatic disease, were significant risk factors for recurrence. These findings, which were also confirmed in a propensity score analysis, allowed the development of a HEHE-LT score enabling stratification of patients in relation to their risk of tumor recurrence. Patients with a score of 2 or less had a much better 5-year disease-free survival compared to those having a score of 6 or higher (93.9% vs 38.5%; P < 0.001). Conclusions: The analysis of this (largest in the world) HEHE adult liver recipient cohort clearly confirms the value of LT in the treatment of this rare disorder and also permits identification of patients at risk of posttransplant recurrence. Posttransplant follow-up should take the HEHE-LT score into account. Extrahepatic disease localization is reconfirmed not to be a contraindication for LT.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Hamaguchi, Yuhei; Kaido, Toshimi; Okumura, Shinya; Kobayashi, Atsushi; Shirai, Hisaya; Yagi, Shintaro; Kamo, Naoko; Okajima, Hideaki; Uemoto, Shinji
    Impact of Skeletal Muscle Mass Index, Intramuscular Adipose Tissue Content, and Visceral to Subcutaneous Adipose Tissue Area Ratio on Early Mortality of Living Donor Liver Transplantation
    imageBackground: Skeletal muscle depletion has been shown to be an independent risk factor for poor survival in various diseases. However, in surgery, the significance of other body components including visceral and subcutaneous adipose tissue remains unclear. Methods: This retrospective study included 250 adult patients undergoing living donor liver transplantation (LDLT) between January 2008 and April 2015. Using preoperative plain computed tomography imaging at the third lumbar vertebra level, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by the skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral to subcutaneous adipose tissue area ratio (VSR), respectively. The cutoff values of these parameters were determined for men and women separately using the data of 657 healthy donors for LDLT between 2005 and 2016. Impact of these parameters on outcomes after LDLT was analyzed. Results: VSR was significantly correlated with patient age (P = 0.041), neutrophil-lymphocyte ratio (P < 0.001), body mass index (P < 0.001), and SMI (P = 0.001). The overall survival probability was significantly lower in patients with low SMI (P < 0.001), high IMAC (P < 0.001), and high VSR (P < 0.001) than in each respective normal group. On multivariate analysis, low SMI (hazard ratio [HR], 2.367, P = 0.002), high IMAC (HR, 2.096, P = 0.004), and high VSR (HR, 2.213, P = 0.003) were identified as independent risk factors for death after LDLT. Conclusions: Preoperative visceral adiposity, as well as low muscularity, was closely involved with posttransplant mortality.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Stewart, Darren E.; Garcia, Victoria C.; Rosendale, John D.; Klassen, David K.; Carrico, Bob J.
    Diagnosing the Decades-Long Rise in the Deceased Donor Kidney Discard Rate in the United States
    imageBackground: The proportion of deceased donor kidneys recovered for transplant but discarded increased steadily in the United States over 2 decades, from 5.1% in 1988 to 19.2% by 2009. Over 100 000 patients are waiting for a kidney transplant, yet 3159 kidneys were discarded in 2015. Methods: We evaluated trends in donor characteristics, discard reasons, and Organ Procurement Organization–specific discard rates. Multivariable regression and propensity analysis were used to estimate the proportion of the discard rate rise in the 2000s attributable to changes in donor factors and decisions to biopsy and pump kidneys. Results: This study found that at least 80% of the discard rate rise can be explained by the recovery of kidneys from an expanding donor pool and changes in biopsy and pumping practices. However, a residual discard rate increase could not be explained by changes in these factors. From 1987 to 2009, median donor age rose from 26 to 43 years; median Kidney Donor Risk Index increased from 1.1 in 1994 to 1.3 in 2009. Our findings suggest that the increase from 10% to 30% in the proportion of kidneys pumped during the 2000s served as a buffer, keeping the discard rate from rising even higher than it did. Conclusions: The majority of the kidney discard rate rise can be explained by the broadening donor pool. However, the presence of an unexplained, residual increase suggests behavioral factors (eg, increased risk aversion) and/or allocation inefficiencies may have played a role. Reducing risk aversion, improving allocation, and more often pumping less-than-ideal, yet potentially transplantable kidneys, may help reverse the trend.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Lam, Ngan N.; Kim, S. Joseph; Knoll, Gregory A.; McArthur, Eric; Lentine, Krista L.; Naylor, Kyla L.; Li, Alvin H.; Shariff, Salimah Z.; Ribic, Christine M.; Garg, Amit X.
    The Risk of Cardiovascular Disease Is Not Increasing Over Time Despite Aging and Higher Comorbidity Burden of Kidney Transplant Recipients
    imageBackground: Cardiovascular death remains the leading cause of mortality in kidney transplant recipients. Cardiovascular events are associated with significant morbidity. However, current trends in cardiovascular events after kidney transplantation are poorly understood. Methods: We conducted a retrospective study using healthcare databases in Ontario, Canada, to determine whether the incidence of cardiovascular events after kidney transplantation has changed from 1994 to 2009. Our primary endpoint was a 3-year composite outcome of posttransplant death or major cardiovascular event (myocardial infarction, coronary angioplasty, coronary artery bypass graft surgery, stroke). Results: Recipients (n = 4954) were older and had more baseline comorbidity in recent years. A total of 445 recipients (9.0%) died or experienced a major cardiovascular event within 3 years of transplantation. There was no significant change in the incidence of the composite outcome or death-censored cardiovascular events over time (P = 0.41 and 0.92, respectively). After adjusting for age, sex, and comorbidities, the risk of death or major cardiovascular event steadily declined across the years of transplant (2006-2009 adjusted hazard ratio, 0.70; P = 0.009; referent 1994-1997). When recipients were matched on age, sex, and date of cohort entry to members of the general population and to the chronic kidney disease population, the risk was lowest in the general population and highest in the chronic kidney disease population. Conclusion: Despite transplant centers accepting recipients who are older with more comorbidities in recent years, the 3-year cumulative incidence of death or major cardiovascular event has remained stable over time.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Morales, Jose Maria; Serrano, Manuel; Martínez-Flores, Jose Angel; Pérez, Dolores; Castro, Maria José; Sánchez, Elena; García, Florencio; Rodríguez-Antolín, Alfredo; Alonso, Marina; Gutierrez, Eduardo; Morales, Enrique; Praga, Manuel; González, Esther; Andrés, Amado; Paz-Artal, Estela; Martínez, Miguel Angel; Serrano, Antonio
    The Presence of Pretransplant Antiphospholipid Antibodies IgA Anti-β-2-Glycoprotein I as a Predictor of Graft Thrombosis After Renal Transplantation
    imageBackground: Vessel thrombosis is a severe complication after renal transplantation. Antibodies anti-β-2 glycoprotein-I of IgA isotype (IgA-aB2GP1) have been linked to thrombotic events and mortality in hemodialysis patients. Methods: All kidney transplanted patients from 2000 to 2011 (n = 1375) in our hospital were followed up for 2 years, evaluating 3 time periods. Results: At transplantation, 401 patients were positive for IgA-aB2GPI (29.2%, group 1), and the remaining patients were negative (group 2). Graft loss at 6 months posttransplantation was higher in group 1 (18% vs 7.2%; P < 0.001). The most frequent cause of early graft loss was vessel thrombosis, especially in group 1 (12.2% vs 2.6% of patients; P < 0.001). In fact, vessel thrombosis was the most important cause of graft loss in the 3 time periods, irrespective of demographic changes and introduction of transplantation with asystolic donors. Notably, IgA-aB2GP1 was an independent risk factor for graft thrombosis (odds ratio, 5.047; P < 0.001). Furthermore, the presence of IgA-aB2GP1 was associated with early graft loss and delayed graft function. Mortality at 24 months was also higher in group 1. Conclusions: In conclusion, pretransplant IgA-aB2GP1 was the main risk factor for graft thrombosis and early graft loss. Further research should be made on whether anticoagulation in antibody-positive patients could ameliorate this catastrophic complication.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Philogene, Mary Carmelle; Bagnasco, Serena; Kraus, Edward S.; Montgomery, Robert A.; Dragun, Duska; Leffell, Mary S.; Zachary, Andrea A.; Jackson, Annette M.
    Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies
    imageBackground: This is a cross-sectional study designed to evaluate the histologic characteristics of graft injury in the presence of anti-angiotensin II type 1 receptor antibody (AT1R-Ab) and anti-endothelial cell antibody (AECA). Methods: Non-HLA antibody testing was included in the posttransplant evaluation for 70 kidney recipients. Biopsies were performed for cause for 47 patients and as protocol for the remaining 23 patients. Biopsy-proven rejection was defined according to the Banff 2009-2013 criteria. AT1R-Ab was measured on an ELISA platform. Patients were divided into 3 groups based on AT1R-Ab levels (>17, 10-17, and <10 U/ml). AECA was evaluated using an endothelial cell crossmatch (ECXM) in patients whose HLA antibody level was insufficient to cause a positive flow cytometric crossmatch. Results: AT1R-Ab levels were higher in patients diagnosed with antibody mediated rejection compared to those with no rejection (P = 0.004). Glomerulitis (g) and peritubular capillaritis (ptc) scores were independently correlated with increased AT1R-Ab concentrations in the presence or absence of HLA-DSA (P = 0.007 and 0.03 for g scores; p = 0.005 and 0.03 for ptc scores). Patients with a positive ECXM had higher AT1R-Ab levels compared to those with a negative ECXM (P = 0.005). Microcirculation inflammation (MCI = g + ptc score) was higher in patients with a positive ECXM and with AT1R-Ab >17 U/ml, although this did not reach statistical significance (P = 0.07). Conclusions: The data show an association between non-HLA antibodies detected in the ECXM and AT1R ELISA and microvascular injury observed in antibody mediated rejection.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Colombo, Anna Amelia; Marchioni, Enrico; Diamanti, Luca; Di Matteo, Angela Maria; Baldanti, Fausto; Furione, Milena; Cazzola, Mario; Ferretti, Virginia Valeria; Pascutto, Cristiana; Alessandrino, Emilio Paolo
    Neurological Complications Involving the Central Nervous System After Allogeneic Hematopoietic Stem Cell Transplantation During a Period of Evolution in Transplant Modalities: A Cohort Analysis
    imageBackground: Neurological complications (NC) after hematopoietic stem cell transplantation (HSCT) are rare events. The evolution of transplant procedures has resulted in improved survival and has allowed elderly patients or those with comorbidity to receive an HSCT. The risk of NC in these patients has still not been well defined. Therefore, we carried out an observational study to estimate the occurrence and identify the risks associated with NC. Methods: The study cohort included 452 adult-allogeneic HSCT recipients, transplanted from 1997 to 2012. The median follow up was 1.3 year (0-15.7). A myeloablative regimen was used in 307 patients. Two hundred patients were grafted from matched unrelated donor (MUD), of these, 129 (64.5%) received an in vivo T-cell depletion. Results: Out of 452 patients, 30 (6.6%) developed NC. Infections were the most frequent causes of NC (30%). Overall survival decreased in patients developing NC (P < 0.001). Univariate survival regression on the cumulative incidence of NC identified period of transplant, linear trend between 4-year periods (1997-2012) (P < 0.001), MUD (P < 0.001), and recipient's age (P = 0.034) as significant risk factors. In multivariate analysis, period of transplant (P < 0.001) and MUD (P = 0.004) remained significant independent risk factors. Matched unrelated donor recipients showed a 3.8-fold elevated risk of developing NC. Conclusions: Analysis highlights a temporal trend of incidence of NC that progressively increased over time and confirms a strong association between donor type and risk of NC. Our observations suggest that, although relatively uncommon, NC after allo-HSCT, may become more frequent due to the improved overall survival in recent years.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Visentin, Jonathan; Bachelet, Thomas; Borg, Cécile; Franchini, Nicolas; Nong, Thoa; Lee, Jar-How; Couzi, Lionel; Merville, Pierre; Guidicelli, Gwendaline; Taupin, Jean-Luc
    Reassessment of T Lymphocytes Crossmatches Results Prediction With Luminex Class I Single Antigen Flow Beads Assay
    imageBackground: In virtual crossmatch (XM) strategies, a correct anticipation of XM results is required for appropriately allocating organs. We reassessed the ability to predict T lymphocyte flow cytometry and complement dependent cytotoxicity XM results with the mean fluorescence intensity (MFI) in Luminex class I single antigen flow beads (SAFB) assay, after correction of complement interference and exclusion of antidenatured HLA antibodies. Methods: Among 432 XM with T lymphocytes (T-XM), 407 were analyzed after exclusion of antidenatured HLA antibodies. Only ethylenediaminetetraacetic acid-treated serum MFI was considered. Only 1 cellular target HLA antigen for the serum was expressed in 238 cases, 209 and 29 being heterozygous and homozygous for this antigen, respectively. For the remaining 169 cases, at least 2 antigens were recognized. Single antigen flow bead MFI thresholds allowing XM positivity to be predicted were calculated with receiver operating characteristic curves. Results: T-XM results were tightly associated with SAFB MFI values. Anti-HLA-A and anti-HLA-B antibodies behaved similarly. Prediction and sensitivity SAFB MFI thresholds were determined, respectively, assessing the highest sensitivity/specificity ratio and at least 95% sensitivity for predicting T-XM positivity. Both were slightly lower for HLA-B than for HLA-A, whereas anti-HLA-Cw antibodies induced random XM results. Both thresholds were only slightly diminished for homozygous and for multiple HLA targets, considering the immunodominant, but not the sum, of antibodies MFI. Conclusions: Antibodies against HLA-A, -B, or -Cw behave differently. A homozygous HLA target does not trigger a twice higher XM positivity. Multiple antibodies are better evaluated through the immunodominant DSA MFI than through the sum of DSA MFI.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Eskandary, Farsad; Bond, Gregor; Kozakowski, Nicolas; Regele, Heinz; Marinova, Lena; Wahrmann, Markus; Kikic, Željko; Haslacher, Helmuth; Rasoul-Rockenschaub, Susanne; Kaltenecker, Christopher C.; König, Franz; Hidalgo, Luis G.; Oberbauer, Rainer; Halloran, Philip F.; Böhmig, Georg A.
    Diagnostic Contribution of Donor-Specific Antibody Characteristics to Uncover Late Silent Antibody-Mediated Rejection—Results of a Cross-Sectional Screening Study
    imageBackground: Circulating donor-specific antibodies (DSA) detected on bead arrays may not inevitably indicate ongoing antibody-mediated rejection (AMR). Here, we investigated whether detection of complement-fixation, in parallel to IgG mean fluorescence intensity (MFI), allows for improved prediction of AMR. Methods: Our study included 86 DSA+ kidney transplant recipients subjected to protocol biopsy, who were identified upon cross-sectional antibody screening of 741 recipients with stable graft function at 6 months or longer after transplantation. IgG MFI was analyzed after elimination of prozone effect, and complement-fixation was determined using C1q, C4d, or C3d assays. Results: Among DSA+ study patients, 44 recipients (51%) had AMR, 24 of them showing C4d-positive rejection. Although DSA number or HLA class specificity were not different, patients with AMR or C4d + AMR showed significantly higher IgG, C1q, and C3d DSA MFI than nonrejecting or C4d-negative patients, respectively. Overall, the predictive value of DSA characteristics was moderate, whereby the highest accuracy was computed for peak IgG MFI (AMR, 0.73; C4d + AMR, 0.71). Combined analysis of antibody characteristics in multivariate models did not improve AMR prediction. Conclusions: We estimate a 50% prevalence of silent AMR in DSA+ long-term recipients and conclude that assessment of IgG MFI may add predictive accuracy, without an independent diagnostic advantage of detecting complement-fixation.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Ferrari, Paolo; Cantwell, Linda; Ta, Joseph; Woodroffe, Claudia; D'Orsogna, Lloyd; Holdsworth, Rhonda
    Providing Better-Matched Donors for HLA Mismatched Compatible Pairs Through Kidney Paired Donation
    imageBackground: Participation of compatible pairs (CP) in kidney paired donation (KPD) could be attractive to CPs who have a high degree of HLA mismatch, if the CP recipient will gain a better HLA match. Because KPD programs were not designed to help CP, it is important to define allocation metrics that enable CP to receive a better-matched kidney, without disadvantage to incompatible pairs (ICP). Methods: Simulations using 46 ICPs and 11 fully HLA-mismatched CPs were undertaken using the Australian KPD matching algorithm. Allocations were preformed adding 1 CP at a time or all 11 CPs at once, and with and without exclusion of unacceptable antigens selected to give a virtual calculated panel-reactive antibody ranging 70% to 80% to improve HLA matching in CP recipients. Results: On average, most CP recipients could be matched and had a lower eplet mismatch (EpMM) with the matched donor (57 ± 15) than with their own donor (78 ± 19, P < 0.02). However, only recipients who had an EpMM to own donor greater than 65 achieved a significant reduction in the EpMM with the matched donor. The gain in EpMM was larger when CPs were listed with unacceptable antigens. Furthermore, inclusion of 1 CP at a time increased matching in ICP by up to 33%, and inclusion of all 11 CPs at once increased ICP matching by 50%. Conclusions: Compatible pair participation in KPD can increase match rates in ICP and can provide a better immunological profile in CP recipients who have a high EpMM to their own donor when using allocation based on virtual crossmatch.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Garrouste, Cyril; Canaud, Guillaume; Büchler, Mathias; Rivalan, Joseph; Colosio, Charlotte; Martinez, Frank; Aniort, Julien; Dudreuilh, Caroline; Pereira, Bruno; Caillard, Sophie; Philipponnet, Carole; Anglicheau, Dany; Heng, Anne Elisabeth
    Rituximab for Recurrence of Primary Focal Segmental Glomerulosclerosis After Kidney Transplantation: Clinical Outcomes
    imageBackground: Rituximab has shown encouraging results for the treatment of kidney transplantation recipients with focal segmental glomerulosclerosis (FSGS) recurrence. However, the correct, opportune, and safe use of rituximab for this indication remains to be determined. Methods: This multicenter retrospective study reports on 19 new cases aged 35 (15-66) years who developed FSGS recurrence at 12 (1.5-27) days posttransplantation. Initial treatment consisted of plasma exchanges (PE), high doses of calcineurin inhibitors, and steroids. Rituximab was introduced either immediately (N = 6) or after failure of the initial treatment (N = 10) or failed attempted weaning from PE (N = 3). Results: Overall, we observed 9 of 19 complete remissions and 3 of 19 partial remissions. Estimated glomerular filtration rates (Modification of Diet in Renal Disease 4) were significantly higher in the responding patients than in nonresponding patients at month (M)12, M36, and M60. Overall, kidney survival at 5 years was 77.4% (95% range, 41.9-92.7). The 5-year graft survival rates in the responding patients and the nonresponding patients were 100% and 36.5%, respectively (P = 0.01). A further course of rituximab was required for 4 patients as a result of FSGS relapse, with good results. During the first year after renal transplantation, 14 patients developed severe infections (16 bacterial, 4 viral, 1 parasitic). Conclusions: In kidney transplantation recipients with recurrent FSGS, rituximab therapy may be a recommended treatment for cases that have failed either the initial treatment or weaning from PE.


    Date de mise en ligne : Jeudi 01 janvier 1970
    O'Regan, John A.; Prendeville, Susan; McCaughan, Jennifer Anne; Traynor, Carol; O'Brien, Frank J.; Ward, Francis L.; O'Donovan, Denis; Kennedy, Claire; Berzan, Ecaterina; Kinsella, Sinead; Williams, Yvonne; O'Kelly, Patrick; Deady, Sandy; Comber, Harry; Leader, Mary; Conlon, Peter J.
    Posttransplant Lymphoproliferative Disorders in Irish Renal Transplant Recipients: Insights From a National Observational Study
    imageBackground: Posttransplant lymphoproliferative disorders (PTLD) are a common malignancy after renal transplantation with a high incidence of PTLD described in the first posttransplant year. We sought to determine incidence and risk determinants of PTLD in Irish kidney transplant recipients. Methods: Retrospective observational study of 1996 adult first kidney transplant recipients between 1991 and 2010 in the Republic of Ireland. Recipients were cross-referenced with the National Cancer Registry to determine incidence of PTLD. Kaplan-Meier analysis was performed for PTLD-free survival, allograft survival, and patient survival after PTLD. Cox proportional hazards models were used to identify independent risk factors for PTLD in our population. Results: We identified 31 cases of PTLD during the study period. Histological subgroups included: early lesions (n = 1); polymorphic PTLD (n = 1); monomorphic PTLD (n = 27), Hodgkin disease (n = 2). Median time to PTLD diagnosis was 8.3 (range, 1.2-13.9) years. Cumulative incidence (95% CI) of PTLD at 1, 2, 3, 5, 10, and 15 years was 0%, 0.16% (0.05-0.5%), 0.21% (0.08-0.57%), 0.21% (0.08-0.57%), 1.76% (1.15-2.69%), and 3.07% (2.1-4.43%), respectively. Allograft survival after PTLD diagnosis was 94.4% (66.6-99.2%) at 5 years. Patient survival after PTLD diagnosis was 64% at 1 year, 53% at 2 years, 48% at 5 years, and 37% at 10 years. No risk factors for PTLD were identified. Conclusions: We found a paucity of early onset PTLD in our cohort with no cases in the first posttransplant year. Potential contributing factors included a high prevalence of previous Epstein-Barr virus exposure and a relatively low immunological risk profile in our recipient cohort compared with prior studies. Further studies are required to reevaluate the epidemiology of PTLD in the modern era of transplant immunosuppression.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Kvarnström, Niclas; Järvholm, Stina; Johannesson, Liza; Dahm-Kähler, Pernilla; Olausson, Michael; Brännström, Mats
    Live Donors of the Initial Observational Study of Uterus Transplantation—Psychological and Medical Follow-Up Until 1 Year After Surgery in the 9 Cases
    imageBackground: The first prospective observational study of uterus transplantation was initiated in 2013 with live donation to 9 women with absolute uterine factor infertility. We explored the medical complications and psychosocial wellbeing of the donors during the first postoperative year. Methods: Complications were registered and graded according to the Clavien-Dindo (C-D) classification. Symptoms related to the surgery were registered. Data on length of hospital stay, sick leave, socioeconomic parameters, and life events were obtained. Psychological evaluations (Psychological General Well-Being, Dyadic Adjustment Scale, Hospital Anxiety and Depression Scale [HADS], SF-36) questionnaires focusing on quality of life, mood, and relationship, were conducted at inclusion and at 3, 6, and 12 months after uterus donation. Results: One major surgical complication (C-D IIIb) occurred. A ureteric-vaginal fistula developed 2 weeks after uterus procurement. The fistula was surgically repaired. Two self-reported and transient complications (C-D I) were noted (nocturia, meralgia paresthetica). Hospital stays of all donors were 6 days and median sick leave was 56 days (range, 14-132). At inclusion, median scores exceeded the normative values of the Swedish population in Psychological General Well-Being and Dyadic Adjustment Scale. HADS-Anxiety was detected preoperatively in 1 donor. Two donors exceeded 10-point declines in SF-36 summary scores and increased their HADS scores by 6 points during the observation period. All donors returned to their predonation levels of physical health. Conclusions: The results support that it is feasible to retrieve a uterus safely from a live donor. Further studies are needed to better evaluate the method.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Werner, Nicole L.; Alghanem, Fares; Rakestraw, Stephanie L.; Sarver, Dylan C.; Nicely, Bruce; Pietroski, Richard E.; Lange, Paul; Rudich, Steven M.; Mendias, Christopher L.; Rojas-Pena, Alvaro; Magee, John C.; Bartlett, Robert H.; Ozer, Kagan
    Ex Situ Perfusion of Human Limb Allografts for 24 Hours
    imageBackground: Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. Methods: Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL. Results: Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury. Conclusions: Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.