Showing papers in "Transplantation in 2018"
TL;DR: This review shall provide a complete and simple illustrated reference guide of the Banff Classification of Kidney Allograft Pathology based on all publications including the 2017 update, intended as a concise desktop reference for pathologists and clinicians.
Abstract: The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplants. Since its initial conception in 1991 for renal transplants, it has undergone review every 2 years, with attendant updated publications. The rapid expansion of knowledge in the field has led to numerous revisions of the classification. The resultant dispersal of relevant content makes it difficult for novices and experienced pathologists to faithfully apply the classification in routine diagnostic work and in clinical trials. This review shall provide a complete and simple illustrated reference guide of the Banff Classification of Kidney Allograft Pathology based on all publications including the 2017 update. It is intended as a concise desktop reference for pathologists and clinicians, providing definitions, Banff Lesion Scores and Banff Diagnostic Categories. An online website reference guide hosted by the Banff Foundation for Allograft Pathology (www.banfffoundation.org) is being developed, which will be updated with future refinement of the Banff Classification from 2019 onward.
422 citations
University of Chicago1, Northwestern University2, Mayo Clinic3, University of Cambridge4, Indiana University – Purdue University Indianapolis5, University of Utah6, University of Padua7, Hospital of the University of Pennsylvania8, Baylor University Medical Center9, University of California, San Francisco10, Primary Children's Hospital11, University of Colorado Denver12
TL;DR: The consensus findings and recommendations of the ILTS Consensus guidelines on immunosuppression in liver transplant recipients are presented in this article.
Abstract: Effective immunosupression management is central to achieving optimal outcomes in liver transplant recipients. Current immunosuppression regimens and agents are highly effective in minimizing graft loss due to acute and chronic rejection but can also produce a substantial array of toxicities. The utilization of immunosuppression varies widely, contributing to the wide disparities in posttransplant outcomes reported between transplant centers. The International Liver Transplantation Society (ILTS) convened a consensus conference, comprised of a global panel of expert hepatologists, transplant surgeons, nephrologists, and pharmacologists to review the literature and experience pertaining to immunosuppression management to develop guidelines on key aspects of immunosuppression. The consensus findings and recommendations of the ILTS Consensus guidelines on immunosuppression in liver transplant recipients are presented in this article.
152 citations
TL;DR: Newer studies evaluating rituximab showed little or no difference to early graft survival, and the efficacy of bortezomib and complement inhibitors for the treatment of AMR remains unclear.
Abstract: BackgroundCurrent treatments for antibody-mediated rejection (AMR) in kidney transplantation are based on low-quality data from a small number of controlled trials. Novel agents targeting B cells, plasma cells, and the complement system have featured in recent studies of AMR.MethodsWe conducted a sy
115 citations
TL;DR: Differences in height and MELD exception points explained most of the sex-based disparity in LT, while MELD score underestimated disease severity in women by up to 2.4 points andMELD Na exacerbated this disparity.
Abstract: BackgroundSex-based disparities in liver transplantation (LT) are incompletely understood. We assessed the role of height, Model for End-Stage Liver Disease (MELD), MELD-Na, and exception points in the disparate access to LT.MethodsAdults waitlisted for LT at Organ Procurement and Transplantation Ne
91 citations
TL;DR: Frailty and markers of inflammation were associated with increased waitlist mortality risk, but only markers ofinflammation significantly improved ESRD risk prediction.
Abstract: BackgroundAmong community-dwelling older adults, frailty is associated with heightened markers of inflammation and subsequent mortality. Although frailty is common among end-stage renal disease (ESRD) patients, the role of frailty and markers of inflammation in this population remains unclear. We qu
89 citations
Pennsylvania State University1, University of Duisburg-Essen2, Mayo Clinic3, Cleveland Clinic4, University of Miami5, Cairo University6, Yeshiva University7, University of Texas Health Science Center at Houston8, University of California, Los Angeles9, Columbia University10, University of Tennessee Health Science Center11
TL;DR: Current coagulation management for patients undergoing liver transplantation, Pharmacologic treatment and prevention of coagulopathy, management of patients receiving antiplatelet medications, and the role of transesophageal echocardiography for early detection and management of thromboses are presented.
Abstract: We review contemporary coagulation management for patients undergoing liver transplantation. A better understanding of the complex physiologic changes that occur in patients with end-stage liver disease has resulted in significant advances in anesthetic and coagulation management. A group of internationally recognized experts have critically evaluated current approaches for coagulopathy detection and management. Strategies for blood component and factor replacement have been evaluated and recommended therapies proposed. Pharmacologic treatment and prevention of coagulopathy, management of patients receiving antiplatelet medications, and the role of transesophageal echocardiography for early detection and management of thromboses are presented.
75 citations
TL;DR: Pure laparoscopic donor right hepatectomy is both feasible and safe when performed at a center experienced in adult living donor liver transplantation, and performance of about 60 PLDRHs over 1 year is sufficient to standardize the procedure.
Abstract: BackgroundThe pure laparoscopic approach to donor hepatectomy is being taken more often. However, few centers perform pure laparoscopic donor right hepatectomy (PLDRH) because it requires a high level of surgical skill. Studies reporting initial outcomes of PLDRH may prompt further implementation of
74 citations
TL;DR: Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late chronic kidney disease and to propose guidelines for the prevention and treatment of postliver transplantation AKI.
Abstract: Since the implementation of the Model of End-stage Liver Disease score-based allocation system, the number of transplant candidates with impaired renal function has increased. The aims of this review are to present new insights in the definitions and predisposing factors that result in acute kidney injury (AKI), and to propose guidelines for the prevention and treatment of postliver transplantation (LT) AKI. This review is based on both systematic review of relevant literature and expert opinion. Pretransplant AKI is associated with posttransplant morbidity, including prolonged post-LT AKI which then predisposes to posttransplant chronic kidney disease. Prevention of posttransplant AKI is essential in the improvement of long-term outcomes. Accurate assessment of baseline kidney function at evaluation is necessary, taking into account that serum creatinine overestimates glomerular filtration rate. New diagnostic criteria for AKI have been integrated with traditional approaches in patients with cirrhosis to potentially identify AKI earlier and improve outcomes. Delayed introduction or complete elimination of calcineurin inhibitors during the first weeks post-LT in patients with early posttransplant AKI may improve glomerular filtration rate in high risk patients but with higher rates of rejection and more adverse events. Biomarkers may in the future provide diagnostic information such as etiology of AKI, and prognostic information on renal recovery post-LT, and potentially impact the decision for simultaneous liver-kidney transplantation. Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late chronic kidney disease.
73 citations
TL;DR: HLSC-EV treatment was feasible and effectively reduced liver injury during hypoxic NMP, and livers were able to maintain homeostasis and produce bile.
Abstract: BACKGROUND The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). METHODS We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. RESULTS During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). CONCLUSIONS HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.
73 citations
TL;DR: The epidemiology and risk factors for SSIs in SOT are described, and potential approaches to the selection, dosing, and duration of perioperative antibiotic prophylaxis for each of these clinical situations are provided.
Abstract: Antibiotic prophylaxis in the perioperative period is the standard of care for nearly all surgical procedures and routinely prescribed during solid organ transplantation (SOT). The primary goal of perioperative antibiotic prophylaxis is to minimize postoperative surgical site infections (SSIs). SSIs are a significant issue in SOT. Depending on the organ transplanted, SSIs occur in 3% to 53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. SOT recipients are also at increased risk of developing SSIs with antimicrobial-resistant organisms. In this article, we describe the epidemiology and risk factors for SSIs in SOT and examine the available literature to guide the use of different regimens for perioperative antibiotic prophylaxis for each organ. We have further addressed specific situations that are unique to each organ transplant type, such as the use of extracorporeal membrane oxygenation in thoracic organ transplantation, as well as an approach to perioperative antibiotic prophylaxis in the setting of recipient and/or donor infection before transplantation. We provide potential approaches to the selection, dosing, and duration of perioperative antibiotic prophylaxis for each of these clinical situations.
68 citations
TL;DR: HLA molecular mismatch represents a precise method of alloimmune risk assessment for renal transplant patients and is likely to be driven by familiarity and ease of use as highly correlated results are produced by each method.
Abstract: BACKGROUND Antibody-mediated rejection is a major cause of premature graft loss in kidney transplantation. Multiple scoring systems are available to assess the HLA mismatch between donors and recipients at the molecular level; however, their correlation with the development of de novo donor-specific antibody (dnDSA) has not been compared in recipients on active immunosuppression. METHODS HLA-DRβ1/3/4/5/DQα1β1 molecular mismatch was determined using eplet analysis, amino acid mismatch, and electrostatic mismatch for 596 renal transplant recipients and correlated with HLA-DR/DQ dnDSA development. The molecular mismatch scores were evaluated in multivariate models of posttransplant dnDSA-free survival. RESULTS Eplet mismatch correlated with amino acid mismatch and electrostatic mismatch (R = 0.85-0.96). HLA-DR dnDSA-free survival correlated with HLA-DR eplet mismatch (hazards ratio [HR], 2.50 per 10 eplets mismatched; P < 0.0001), amino acid mismatch (HR, 1.49 per 10 amino acids mismatched; P < 0.0001), and electrostatic mismatch (HR, 1.23 per 10 units mismatched; P < 0.0001). HLA-DQ dnDSA-free survival correlated with HLA-DQ eplet mismatch (HR, 1.98 per 10 eplets mismatched; P < 0.0001), amino acid mismatch (HR, 1.24 per 10 amino acids mismatched; P < 0.0001), and electrostatic mismatch (HR, 1.14 per 10 units mismatched; P < 0.0001). All 3 methods were significant multivariate correlates of dnDSA development after adjustment for recipient age, baseline immunosuppression, and nonadherence. CONCLUSIONS HLA molecular mismatch represents a precise method of alloimmune risk assessment for renal transplant patients. The method used to determine the molecular mismatch is likely to be driven by familiarity and ease of use as highly correlated results are produced by each method.
University of Pennsylvania1, University of California, San Francisco2, Leiden University3, Charité4, University of Miami5, University of Minnesota6, University of Geneva7, King's College London8, University of Oxford9, University of Melbourne10, Vrije Universiteit Brussel11, Mayo Clinic12, JDRF13, University of Zurich14, Dresden University of Technology15, Harvard University16, University of Wisconsin-Madison17, Lille University of Science and Technology18, University of Alberta19, Newcastle University20
TL;DR: There was consensus that &bgr;-cell replacement therapy could be considered as a treatment for cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia.
Abstract: β-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplantation Association held a workshop to develop consensus for an International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplant Association Statement on the definition of function and failure of current and future forms of β-cell replacement therapy. There was consensus that β-cell replacement therapy could be considered as a treatment for β-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA1c) and the occurrence of severe hypoglycemia. Optimal β-cell graft function is defined by near-normal glycemic control (HbA1c ≤6.5% [48 mmol/mol]) without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good β-cell graft function requires HbA1c less than 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal β-cell graft function is defined by failure to achieve HbA1c less than 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed β-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good function are considered successful clinical outcomes.
TL;DR: In the past 5 years, several studies correlated the IgG subclass pattern with occurrence of antibody-mediated rejection and allograft outcomes, but a clear picture has not emerged yet because of differences of the used Igg subclass assay, the time point of analyses, and the definition of outcomes.
Abstract: Immunoglobulin G (IgG) is the dominant immunoglobulin and can be divided into 4 distinct subclasses. The evolution of IgG subclass switches is regulated by interaction with T cells and follows a 1-way direction (IgG3 → IgG1 → IgG2 → IgG4). Based on their structure, the 4 IgG subclasses can initiate different effector function such as complement activation, recruitment of various cells by Fc receptors, and agonistic signaling. Using current assays for HLA antibody detection as a template and replacing the generic reporter antibody with IgG subclass-specific reporter antibodies, it is possible to investigate the IgG subclasses of HLA antibodies. There are 15 different IgG subclass compositions possible. Based on the capability to activate the complement system and the class switch direction, 3 arbitrary patterns can be defined (ie, only complement-binding subclasses [IgG3 and/or IgG1], expansion to noncomplement-binding subclasses [IgG3 and/or IgG1 plus IgG2 and/or IgG4], and switch to noncomplement-binding subclasses [IgG2 and/or IgG4]). The latter group accounts for less than 5%, whereas the former 2 groups have a similar prevalence close to 50%. In the past 5 years, several studies correlated the IgG subclass pattern with occurrence of antibody-mediated rejection and allograft outcomes. Because of differences of the used IgG subclass assay, the time point of analyses, and the definition of outcomes, a clear picture has not emerged yet. Future needs are standardization of the assay, a more detailed knowledge of the initiated effector functions, and more well-designed clinical studies also looking at changes of the IgG subclass pattern over time.
TL;DR: Lee et al. as discussed by the authors evaluated the impact of recipient's age on liver transplantation outcome between January 2007 and May 2016 covered by the Korean National Health Insurance system (n = 9415).
Abstract: BackgroundThe feasibility of liver transplantation (LT) in elderly recipients remains a topic of debate.MethodsThis cohort study evaluated the impact of recipient's age on LT outcome between January 2007 and May 2016 covered by the Korean National Health Insurance system (n = 9415). Multilevel regre
University of Wisconsin-Madison1, Harvard University2, JDRF3, University of Toronto4, University of Illinois at Chicago5, Vrije Universiteit Brussel6, Beth Israel Deaconess Medical Center7, Memorial Sloan Kettering Cancer Center8, Columbia University9, Broad Institute10, University of Cambridge11, University of Sydney12, University of California, San Francisco13, Leiden University Medical Center14, University of Miami15, University of Pennsylvania16, Wake Forest University17, Massachusetts Institute of Technology18, University of Massachusetts Medical School19, University of Minnesota20, Geneva College21
TL;DR: Current technology, recent significant breakthroughs, unmet needs and roadblocks to stem cell-derived beta cell therapies, with the aim of spurring future preclinical collaborative investigations and progress toward the clinical application of stem cell -derived beta cells are highlighted.
Abstract: Beta cell replacement has the potential to restore euglycemia in patients with insulin-dependent diabetes. Although great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association in collaboration with the Harvard Stem Cell Institute, the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells. The following summary highlights current technology, recent significant breakthroughs, unmet needs and roadblocks to stem cell-derived beta cell therapies, with the aim of spurring future preclinical collaborative investigations and progress toward the clinical application of stem cell-derived beta cells.
TL;DR: Adult SOT recipients face a prolonged risk of late PTLD, whereas risk of early PTLD may have declined in recent years.
Abstract: BackgroundPosttransplant lymphoproliferative disorders (PTLD) are a complication of solid organ transplantation (SOT) associated with Epstein-Barr virus (EBV).MethodsWe analyzed the incidence of and risk factors for PTLD among adult SOT recipients at our center over 30 years (1984-2013). We also com
TL;DR: The evidence relating to the diagnosis and management of persistent hepatitis E in solid organ transplant recipients and the methods of prevention of HEV infection are reviewed.
Abstract: The incidence and prevalence of hepatitis E virus (HEV) infection has increased in many developed countries over the last decade, predominantly due to infection with genotype 3 (G3) HEV. Infection with HEV G3 is important in transplant recipients because it can persist in immunosuppressed in
TL;DR: HMP resulted in remarkably lower rates of DGF in renal grafts that were transplanted after a short CIT, and CIT remained an independent risk factor for DGF for machine perfused kidneys recovered from donation after brain death donors.
Abstract: BackgroundHypothermic machine perfusion (HMP) of deceased donor kidneys is associated with better outcome when compared to static cold storage (CS). Nevertheless, there is little evidence whether kidneys with short cold ischemia time (CIT) also benefit from HMP and whether HMP can safely extend CIT.
TL;DR: Transplantation of declined livers can achieve comparable outcomes to primary liver low-risk graft offers and with appropriate recipient selection, more lives could be saved.
Abstract: BACKGROUND In the United Kingdom, up to 20% of liver graft offers are not used for transplantation, and the reasons for graft refusal are multifactorial and not consistent among transplant units. METHODS Liver grafts previously declined by other transplant centers in the United Kingdom but transplanted in our unit in Birmingham between 2011 and 2015 were analyzed. According to the indicated reason for previous declines, liver grafts were categorized into 3 refusal groups: "quality," "logistics," and "other reasons." Results were compared with a matched, low-risk cohort of livers primarily accepted and transplanted at our center. RESULTS During the study period, 206 livers (donation after brain death: n = 141 (68.4%); donation after circulatory arrest: n = 65 (31.6%) were transplanted, which were previously discarded by a median of 4 other UK centers. The majority of declines were donor quality (n = 102; 49.5%), refusals followed by logistics (n = 45; 21.8%), and other reasons (n = 59; 28.6%). Transplantation from both graft types (donation after brain death and donation after circulatory arrest) and all 3 refusal groups achieved equally good outcomes with an overall low complication rate. The incidence of primary nonfunction (2.4% vs 1.7%; P = 0.5483), in-hospital mortality (6.3% vs 4.1%; P = 0.2293) and 3-year graft (82.5% vs 84.1%; P = 0.6872) and patient (85.4% vs 87.6%; P = 0.8623) survival was comparable between livers previously declined and livers primarily accepted and transplanted at our center. CONCLUSIONS Transplantation of declined livers can achieve comparable outcomes to primary liver low-risk graft offers. Previous refusal should not be taken as a barrier to use the graft, and with appropriate recipient selection, more lives could be saved.
TL;DR: The present study demonstrates that acceptable graft and patient survival can be achieved with the usage of DCD LT with donor age ≥50 years and optimizing recipient selection criteria and minimizing CIT may further improve outcomes.
Abstract: BackgroundAs the population in the United States continues to age, an increase in the number of potential donation after circulatory death (DCD) donors with advanced chronological age can be expected. The aim of this study was to analyze a multi-institutional experience in liver transplantation usin
TL;DR: Standardization and more widespread adoption of routine posttransplant DSA monitoring may permit timely diagnosis and understanding of the natural course of type 2 and chronic AMR.
Abstract: Despite major advances in understanding the pathophysiology of antibody-mediated rejection (AMR); prevention, diagnosis and treatment remain unmet medical needs. It appears that early T cell-mediated rejection, de novo donor-specific antibody (dnDSA) formation and AMR result from patient or physician initiated suboptimal immunosuppression, and represent landmarks in an ongoing process rather than separate events. On April 12 and 13, 2017, the Food and Drug Administration sponsored a public workshop on AMR in kidney transplantation to discuss new advances, importance of immunosuppressive medication nonadherence in dnDSA formation, associations between AMR, cellular rejection, changes in glomerular filtration rate, and challenges of clinical trial design for the prevention and treatment of AMR. Key messages from the workshop are included in this summary. Distinction between type 1 (due to preexisting DSA) and type 2 (due to dnDSA) phenotypes of AMR needs to be considered in patient management and clinical trial design. Standardization and more widespread adoption of routine posttransplant DSA monitoring may permit timely diagnosis and understanding of the natural course of type 2 and chronic AMR. Clinical trial design, especially as related to type 2 and chronic AMR, has specific challenges, including the high prevalence of nonadherence in the population at risk, indolent nature of the process until the appearance of graft dysfunction, and the absence of accepted surrogate endpoints. Other challenges include sample size and study duration, which could be mitigated by enrichment strategies.
TL;DR: After LT, outcomes are similar between NASH and non-NASH etiologies for HCC, and the hypothesis that patients with more advanced HCC tumors in the context of NASH may have more favorable outcomes after LT has been generated, but requires further study.
Abstract: Background Liver transplant (LT) for nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) is not well characterized in the literature. The aim of the study was to examine characteristics and outcomes of patients who had LT for NASH-HCC (NASH) versus HCC from other liver diseases (non-NASH). Methods Using a 2-center retrospective design, all patients from 2004 to 2014 that received LT for HCC were analyzed. Subgroup analysis stratified patients according to Milan criteria. Results Nine hundred twenty-nine patients were transplanted for HCC. Sixty (6.5%) of 929 had HCC in the context of NASH. There were no significant differences between groups for pretransplant or explant tumor characteristics. The actuarial 1-, 3- and 5-year overall survival was 98%, 96%, and 80% in NASH versus 95%, 84%, and 78% in non-NASH (P = 0.1). No differences in tumor recurrence were observed in patients within and beyond Milan in the NASH group. Multivariate Cox regression demonstrated NASH status to be a protective factor for recurrence among patients with tumors beyond Milan (hazard ratio, 0.21; 95% confidence interval, 0.05-0.86; P = 0.029). Conclusion After LT, outcomes are similar between NASH and non-NASH etiologies for HCC. The hypothesis that patients with more advanced HCC tumors in the context of NASH may have more favorable outcomes after LT has been generated, but requires further study.
TL;DR: To promote wider application of MSC in renal transplantation, it is of importance to determine efficacy, to increase the understanding of the mechanism of action, and to develop tools to identify eligible patients.
Abstract: Improvement of long-term outcome of kidney transplantation has reached its limits due to consequences of efficient, but nonspecific immunosuppressive drugs. Mesenchymal stromal cells (MSC) have been proposed as an alternative strategy for more refined therapy. The interest in MSCs comes from their anti-inflammatory properties on the one hand and their propensity to ameliorate tissue damage and mediate repair on the other hand. First clinical trials have demonstrated that administration of MSCs in kidney transplant recipients is safe and feasible, and follow-up studies have been initiated with the desired clinical efficacy to reduce ischemia-reperfusion injury, to prevent/reverse acute transplant rejection, and to improve long-term transplant survival with minimization of immunosuppression. To further promote wider application of MSC in renal transplantation, it is of importance to determine efficacy, to increase the understanding of the mechanism of action, and to develop tools to identify eligible patients. In addition, we should overcome challenges particularly at the transition of early phase I studies to more advanced stages of clinical development. In this review, latest insights, first clinical experiences, and future challenges of MSC in solid organ transplantation are discussed.
TL;DR: The most current data is summarized to highlight the role of mTORis in the management of viral infections after solid organ transplant and their toxicity profile must be balanced with their potential antiviral effects in combination with patient-specific factors.
Abstract: Viruses are the leading cause of infections after solid organ transplant. The antiviral properties of mammalian target of rapamycin inhibitors (mTORis) have been ascribed to a variety of mechanisms and historical data have supported their use over other immunosuppressants for a myriad of viruses. Herein, we summarize the most current data to highlight the role of mTORis in the management of viral infections after solid organ transplant. The mTORis play a clear role in the management of cytomegalovirus, and have data supporting their potential use for BK virus and human herpesvirus 8-related Kaposi sarcoma. No data definitively supports mTORis for use in Epstein-Barr virus-mediated posttransplant lymphoproliferative disorder or hepatitis C virus viral replication. Although theoretically an advantageous therapy for hepatitis C virus-related liver allograft fibrosis and human immunodeficiency virus, mTORi use specifically for these indications is less attractive with modern treatments currently available. Data surrounding mTORi efficacy in preventing rejection, and their toxicity profile must be balanced with their potential antiviral effects in combination with patient-specific factors.
Universidade Federal de Minas Gerais1, University of São Paulo2, University of Miami3, Carlos III Health Institute4, University of Córdoba (Spain)5, Aarhus University6, Federal University of São Paulo7, Harvard University8, University of Liverpool9, Liverpool School of Tropical Medicine10, Federal University of Rio de Janeiro11, Autonomous University of Barcelona12, State University of Campinas13, University of Lausanne14, Ondokuz Mayıs University15, Icahn School of Medicine at Mount Sinai16, Complutense University of Madrid17
TL;DR: The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America.
Abstract: The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.
TL;DR: Chronic C disease is a zoonotic protozoan infection caused by Trypanosoma cruzi and naturally transmitted by domestic and sylvatic blood-sucking triatomine bugs, known as “kissing bugs.”
Abstract: C disease (ChD) is a zoonotic protozoan infection caused by Trypanosoma cruzi and naturally transmitted by domestic and sylvatic blood-sucking triatomine bugs, known as “kissing bugs.” In the human host, trypomastigotes circulate in the blood stream,whereas intracellular amastigotes appear in tissues, especially muscle (heart) and ganglion cells. T. cruzi may be alternatively transmitted to humans congenitally, orally, or via transfusion and organ transplantation. Acute infection from vectorial transmission in endemic areas is mostly asymptomatic with high parasitemia, which generally becomes controlled in immunocompetent hosts after a few months. Without treatment, the infection proceeds to the chronic phase, characterized by low-level parasitemia and poor response to treatment. Although most chronically infected patients do not develop clinical symptoms (a period of clinical latency called indeterminate form), approximately 30% progress to irreversible cardiac, gastrointestinal, and/or more rarely, peripheral nervous system disease characterized by the involvement of the autonomic nervous system and neuritis or the central nervous system. Heart disease is characterized by increasing arrhythmias or heart failure; sudden death is a characteristic of chronic ChD occurring in about 40%of patients with orwithout congestive heart failure. The digestive tract is affected in about 15% to 20%of chronic ChDpatients who develop alteration ofmotility, secretion and absorption in the digestive tract, followed
TL;DR: A high CV of TAC concentrations was found to be predictive of Tac-related toxicity and poorer survival and was identified as risk factors for presenting a high CV.
Abstract: BACKGROUND Tacrolimus (TAC) is the cornerstone of immunosuppressive regimen in liver transplantation (LT). Its pharmacokinetics is characterized by a high interpatient and intrapatient variability (IPV) leading to an unpredictable dose-response relationship. The aim of our study was to evaluate the impact of TAC IPV (IPV) on graft and patient outcomes after LT. METHODS We retrospectively analyzed 812 LT recipients treated with TAC. The IPV of TAC concentrations was estimated by calculating the coefficient of variation (CV) of whole blood trough concentrations. Patients were categorized in 2 groups: low IPV (CV < 40%) and high IPV (CV ≥ 40%). RESULTS There were significantly more neurologic complications (31.2% vs 16.6%, P < 0.001), cardiovascular complications (19.7% vs 9.7%, P < 0.001), and acute renal failure requiring dialysis (8.5% vs 2.2%, P < 0.001) in the high CV group than in the low CV group. Moreover, graft survival was significantly poorer in the high CV group (hazard ratio, 1.42; 95% confidence interval, 1.04-1.95; P = 0.03). A pretransplantation elevated Model for End-Stage Liver Disease score (P < 0.001) and Child-Pugh grade (P < 0.001) were identified as risk factors for presenting a high CV. CONCLUSIONS A high CV of TAC concentrations was found to be predictive of TAC-related toxicity and poorer survival.
TL;DR: Describing of a role for CD8 Treg cells in tolerance in both solid organ transplantation and graft-versus-host disease and their potential for clinical trials is described.
Abstract: Although cluster of differentiation (CD)8 regulatory T (Treg) cells have been in the last 20 years more studied since evidences of their role in tolerance as been demonstrated in transplantation, autoimmune diseases and cancer, their characteristics are still controversial. In this review, we will focus on recent advances on CD8 Treg cells and description of a role for CD8 Treg cells in tolerance in both solid organ transplantation and graft-versus-host disease and their potential for clinical trials.
TL;DR: Data evaluating HLA antibody strength is compared using the conventional IgG-mean fluorescence intensity approach with serial dilution studies (titration) and of C1q binding (C1q-meanfluorescence intensity).
Abstract: HLA antibodies, and specifically donor-specific-HLA antibodies, play a key role in transplant-related diagnostics and decision-making. It is now clear that the simple differentiation between absence and presence of HLA donor-specific antibodies does not provide sufficient granularity in all clinical circumstances. It addition, knowledge of HLA antibody strength has potential utility at different stages of recipient evaluation along the transplant timeline from initial pretransplant evaluation, evaluation of a specific potential donor, and posttransplant monitoring for de novo donor-specific antibodies. Here we compare data evaluating HLA antibody strength using the conventional IgG-mean fluorescence intensity approach with serial dilution studies (titration) and of C1q binding (C1q-mean fluorescence intensity). The added value of titration studies along the 3 milestones of the transplant cycle is emphasized.
TL;DR: The use of laparoscopic donor nephrectomy and developments within the UK Living Kidney Sharing Schemes to maximize the effectiveness of paired/pooled donation and nondirected altruistic donors are studied.
Abstract: • Stable living donation rate representing approximately one third of total kidney transplantation. • Near universal use of laparoscopic donor nephrectomy. • 17% reduction in transplant waiting list largely driven by increased deceased circulatory death donation, the use of extended criteria donors, and developments within the UK Living Kidney Sharing Schemes to maximize the effectiveness of paired/pooled donation and nondirected altruistic donors.