Mechanisms and Strategies for Tolerance in Liver Transplantation
AbstractAlthough there has been improvement in immunosuppressive therapy in preventing acute rejection following liver transplantation, there is less progress in reducing morbidity and mortality related to immunosuppression. In particular, the use of the current maintenance agents is associated with high rates of chronic kidney disease and metabolic and neoplastic complications. The search for improved treatment algorithms includes trial and error dose minimization or even complete withdrawal; most of which have been attempted with variable success rates. These strategies would be potentially more successful if more were k...
Source: Current Transplantation Reports - September 30, 2016 Category: Transplant Surgery Source Type: research

Face Transplantation: Medical Considerations
AbstractFace transplantation has been performed in 37 patients worldwide. To provide excellent outcomes, it is important to understand the medical considerations that are present in every aspect of this procedure. Pre-operative medical considerations are largely related to patient selection, intra-operative considerations are related to anesthesia, and post-operative considerations include complications and treatment of adverse effects of immunosuppression. This paper will discuss each area in more detail. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - September 30, 2016 Category: Transplant Surgery Source Type: research

How Do We Determine Futility for Patients in Need of Liver Transplantation?
AbstractFutility remains poorly defined in healthcare and entails a large portion of healthcare spending. With limited resources, the field of liver transplantation attempts to minimize cases of futility but struggles to balance the difficulty to provide a life-saving procedure to an increasingly sick patient population as seen with rising Model-for-End-Stage-Liver Disease (MELD) scores. This paper aims to explore the historical context of organ allocation, utilize the medical ethical principles for organ allocation, and review the literature on how to improve transplant outcomes and reduce ‘futile’ cases. In a...
Source: Current Transplantation Reports - September 30, 2016 Category: Transplant Surgery Source Type: research

Vascularized Composite Allotransplantation: Medical Complications
The objective of this review is to summarize the collective knowledge regarding the risks and complications in vascularized composite tissue allotransplantation (VCA), focusing on upper extremity and facial transplantation. The field of VCA has entered its second decade with an increasing experience in both the impressive good outcomes, as well as defining challenges, risks, and experienced poor results. The limited and selective publishing of negative outcomes in this relatively new field makes it difficult to conclusively evaluate outcomes of graft and patient survival and morbidities. Therefore, published data, conferen...
Source: Current Transplantation Reports - August 15, 2016 Category: Transplant Surgery Source Type: research

Update on Chronic Lung Allograft Dysfunction
AbstractChronic lung allograft dysfunction (CLAD) encompasses a range of pathologies that cause a transplanted lung to not achieve or maintain normal function. CLAD manifests as airflow restriction and/or obstruction and is predominantly a result of chronic rejection. Three distinct phenotypes of chronic rejection are now recognized: bronchiolitis obliterans, neutrophilic reversible allograft dysfunction, and restrictive allograft syndrome. Recent investigations have revealed that each phenotype has a unique pathology and histopathological findings, suggesting that treatment regimens should be tailored to the underlying et...
Source: Current Transplantation Reports - August 2, 2016 Category: Transplant Surgery Source Type: research

Is It Time to Use De Novo mTOR Inhibitors Posttransplant?
Abstract The use of mTOR inhibitors evokes debate in transplantation. Numerous clinical trials have explored the role of the mTOR inhibitors sirolimus and everolimus in kidney transplantation, but the results have been mixed; they have not shown a clear benefit over the current regimens. However, many of these trials were impacted by the difficulties and uncertainties in managing side effects and the dosing of the mTOR inhibitors. Being aware of the effective treatments available for these side effects, understanding the pathophysiology of the mTOR pathway allows patients to remain on therapy. Successful side effect manag...
Source: Current Transplantation Reports - July 29, 2016 Category: Transplant Surgery Source Type: research

Does Delayed Graft Function Still Herald a Poorer Outcome in Kidney Transplantation?
Abstract Delayed graft function (DGF), or post-operative acute kidney injury leading to the need for dialysis within the first week after kidney transplantation, most commonly occurs in the setting of donor kidney recovery and the ischemia–reperfusion injury associated with the transplantation process. Despite advances in immunosuppressive regimens and medical management of kidney transplant recipients, the short- and long-term sequelae of DGF continue to be important determinants of kidney allograft prognosis. In this review, we will highlight the following areas as it relates to DGF: definition, pathophysi...
Source: Current Transplantation Reports - June 28, 2016 Category: Transplant Surgery Source Type: research

Potential of Tolerogenic Dendritic Cells in Transplantation
Abstract Dendritic cells (DC) are the most important subset of antigen presenting cells (APC) that are able to polarize the immune response to pro-inflammatory or anti-inflammatory response. This duality places DC in the axis between tolerance and immunogenicity. The regulation of polarization is the key point in autoimmune diseases and organ transplantation. In order to manipulate this duality, DC have been generated ex vivo with a tolerogenic or immunogenic profile since several years. During the last decade, cell therapy using tolerogenic DC (TolDC) has been shown to be safe and effective both in autoimmune dis...
Source: Current Transplantation Reports - June 15, 2016 Category: Transplant Surgery Source Type: research

Autologous Cells for Kidney Bioengineering
Abstract Worldwide, increasing numbers of patients are developing end-stage renal disease, and at present, the only treatment options are dialysis or kidney transplantation. Dialysis is associated with increased morbidity and mortality, poor life quality and high economic costs. Transplantation is by far the better option, but there are insufficient numbers of donor kidneys available. Therefore, there is an urgent need to explore alternative approaches. In this review, we discuss how this problem could potentially be addressed by using autologous cells and appropriate scaffolds to develop ‘bioengineered&rsqu...
Source: Current Transplantation Reports - June 9, 2016 Category: Transplant Surgery Source Type: research

Lung Transplant Rejection and Surveillance in 2016: Newer Options
Abstract Lung allograft rejection is a major risk factor for the development of chronic lung allograft dysfunction. It is a significant cause of morbidity and mortality, and limits survival post lung transplantation, which is lower than any other solid organ transplant. The invasive nature of current methods of diagnosis which consists of histological diagnosis via transbronchial biopsy and the lack of sensitivity of clinical surveillance warrants the search for novel less invasive and more accurate methods of diagnosis. This review aims to highlight recent changes to current methods of surveillance and diagnosis ...
Source: Current Transplantation Reports - June 7, 2016 Category: Transplant Surgery Source Type: research

Cardiac Allograft Vasculopathy: What We Know in 2016
Abstract Cardiac allograft vasculopathy (CAV) is an immune and nonimmune-mediated process in which heart transplantation patients develop neointimal proliferative hyperplasia of the coronary arteries, typically starting distally and resulting in diffuse luminal narrowing. Risk factors include traditional coronary risk factors often resulting from side effects of immunosuppressive drugs, infection by cytomegalovirus and rejection, particularly antibody-mediated. Despite the advent of effective immunosuppression, CAV remains the primary cause of long-term mortality for heart transplant recipients. Patients undergo r...
Source: Current Transplantation Reports - June 4, 2016 Category: Transplant Surgery Source Type: research

Early Results Using Donation After Circulatory Death (DCD) Donor Hearts
Abstract Donation after circulatory death (DCD) has contributed significantly to kidney, lung and liver transplant activities over the last decade. With an ever increasing demand for cardiac transplantation and worsening shortages of donor hearts, there has been growing interests in transplanting hearts from DCD donors. This was initially made possible by co-locating the donor and recipient to ensure the shortest possible ischaemic time for the DCD heart. More recently, reconditioning and distant procurement of arrested DCD hearts has been achieved by using machine perfusion. Early outcomes have been very encourag...
Source: Current Transplantation Reports - June 2, 2016 Category: Transplant Surgery Source Type: research

The “Unusual Suspects” in Allograft Rejection: Will T Regulatory Cell Therapy Arrest Them?
Abstract Several trials with adoptively transferred T regulatory cells (TRegs) have shown to be safe and—in some instances—to be effective in patients with hematological malignancies after allogeneic hematopoietic stem cell transplantation (to prevent graft-versus-host disease), with type 1 diabetes (to preserve residual beta cell function), and with refractory Crohn’s disease (to control the disease). In solid organ transplantation, TReg-cell therapy trials with TReg-supportive immunosuppression are currently being undertaken to control the well-documented T effector cells responsible for allogr...
Source: Current Transplantation Reports - June 2, 2016 Category: Transplant Surgery Source Type: research

Islet Cell Transplantion: Update on Current Clinical Trials
Abstract In the last 15 years, clinical islet transplantation has made the leap from experimental procedure to standard of care for a highly selective group of patients. Due to a risk/benefit calculation involving the required systemic immunosuppression, the procedure is only considered in patients with type 1 diabetes, complicated by severe hypoglycemia or end stage renal disease. In this review, we summarize current outcomes of the procedure and take a look at ongoing and future improvements and refinements of beta cell therapy. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - May 17, 2016 Category: Transplant Surgery Source Type: research

Impact of Pancreas Transplant on Diabetic Complications: Retinoparhy, Gastroparesis and Automatic Dysregulation
Conclusion Proof of the beneficial effects on diabetic complications requires detailed long-term follow-up to clarify and validate many of the small studies performed with regard to the various comorbidities associated with diabetes. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - April 12, 2016 Category: Transplant Surgery Source Type: research

Post-transplant Lymphoproliferative Disorder (PTLD): Infection, Cancer?
Abstract Post-transplant lymphoproliferative disorder encompasses a broad spectrum of lymphoid disorders that occur in immune-suppressed patients following solid or hematopoietic stem cell transplantation. The Epstein-Barr virus (EBV) is an oncogenic virus capable of transforming B lymphocytes and is associated with the pathogenesis of multiple benign and malignant lymphoproliferative disorders, including PTLD. This review outlines current knowledge of EBV pathogenesis, its role in B cell immortalization, transformation, and as an etiologic agent in lymphoproliferative disorders in immune-suppressed patients follo...
Source: Current Transplantation Reports - April 8, 2016 Category: Transplant Surgery Source Type: research

What Did We Really Learn From the Collaborative? Is It In Our Best Interest to Use “Every Organ Every Time” in Kidney Transplantation?
This article is based on currently available data and reviews the circumstances that led to the formation of the ODBC and its short- and long-term impact on kidney transplantation. We question whether this is the right direction for the current situation and discuss whether there might be other potential avenues to pursue in bridging this divide. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - April 4, 2016 Category: Transplant Surgery Source Type: research

Living Donation Mitigates Poorer Outcomes in Marginal Recipients
Abstract Increasing the number of kidney transplantations results in the trend toward the utilization of marginal but acceptable kidneys for deceased donor renal transplantations (DDRT). At the same time, the acceptance of recipients with high medical, surgical, immunological, or psychosocial risks of poor transplant outcomes as we refer to here as “marginal recipients” has been increasing. The combination of both a low quality donor kidney and marginal kidney transplant recipient leads to unfavorable outcomes during the peri- and post-transplant periods. Since some of the risk factors are non-modifiab...
Source: Current Transplantation Reports - March 9, 2016 Category: Transplant Surgery Source Type: research

Pancreas Transplant After the New Allocation System? What Is the Impact on Access and Utilization?
Abstract A new pancreas allocation system was implemented in October 2014 which, amongst other features, mandated local allocation of the kidney with pancreas allocation, created a single list for simultaneous pancreas and kidney transplant (SPK) as well as isolated pancreas transplant candidates, and defined minimum qualifying criteria for an SPK candidate to accrue waiting time. This manuscript will describe the new allocation policy in detail and present initial data from the first 6 months after implementation of both the new pancreas as well as the new kidney allocation policies. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - March 9, 2016 Category: Transplant Surgery Source Type: research

Immunosuppression in Pancreas Transplantation: What Has Changed in 20 Years?
Abstract Pancreas transplantation offers a functional cure for many patients suffering from diabetes mellitus. Although the outcomes of pancreas transplants were originally plagued with high rates of acute cellular rejection, innovations in immunosuppression regimens over the last two decades have helped steadily improve the graft survival of pancreas transplants. This review surveys the latest trends in immunosuppressive management for pancreas transplant recipients, discussing the controversies and weighing the evidence supporting induction therapy, steroid avoidance/withdrawal, mTOR inhibitors, and new regimens...
Source: Current Transplantation Reports - March 5, 2016 Category: Transplant Surgery Source Type: research

Liver Allograft Allocation and Distribution: Toward a More Equitable System
Abstract The liver allocation system in the USA has undergone an evolution during the last 25 years from one largely based on waiting time to one based on disease severity. Utilizing the Model for End-stage Liver Disease (MELD) score resulted in objectively ordering the waitlisted candidates in a “sickest first” manner. However, the geographic boundaries that define the 58 donor service areas, which define the area of distribution of organ donors, as well as the MELD exception policies (particularly related to hepatocellular carcinoma) have created inequity in the organ allocation system such that...
Source: Current Transplantation Reports - February 26, 2016 Category: Transplant Surgery Source Type: research

Vascularized Composite Tissue Allografts (VCA): the Policy Side
Abstract In July 2013, the Secretary of Health amended the National Organ Transplant Act of 1986 to designate vascularized composite tissue allografts (VCAs) as organs. The definition of a VCA as an organ required that all nine criteria published in the Final Rule were fulfilled. VCAs meeting the definition of an organ would henceforth come under the oversight of the Organ Procurement Transplant Network (OPTN) and were required to develop and be in compliance with policies and bylaws as for traditional organ transplantation. The implementation date for the Final Rule modification was July 3, 2014. The OPTN and the...
Source: Current Transplantation Reports - February 26, 2016 Category: Transplant Surgery Source Type: research

3D Printing of Organs for Transplantation: Where Are We and Where Are We Heading?
Abstract In the field of transplantation, the demand for organs continues to increase and has far outpaced the supply. This ever-growing unmet need for organs calls for innovative solutions in order to save more lives. The development of new technologies in the field of biomedical engineering might be able to provide some solutions. With the advent of 3D bioprinting, the potential development of tissues or organ grafts from autologous cells might be within the reach in the near future. Based on the technology and platform used for regular 3D printing, 3D bioprinters have the ability to create biologically function...
Source: Current Transplantation Reports - February 22, 2016 Category: Transplant Surgery Source Type: research

Glomerular Function and Structure in Living Donors: Lessons from Single Nephron Studies
We describe the ‘remnant kidney’ model of kidney disease and the reasons why such progressive kidney disease very rarely ensues in healthy humans following uninephrectomy. We also review some of the methods used to determine glomerular number and size and outline their associations. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - February 11, 2016 Category: Transplant Surgery Source Type: research

Addressing the ESRD Risks of the Young Living Kidney Donor: Putting “Normal for Now” into Practice
Abstract Individuals who are free of traditional clinical risk factors for kidney diseases at the time of living kidney donation have been thought to be at low risk of end-stage renal disease (ESRD) after donor nephrectomy. However, the reassuring low rates of ESRD in available donor follow-up studies have captured only the risks of very rapidly progressing kidney diseases that begin during the study interval, not the higher risks of diabetic ESRD and other slowly evolving diseases that are far more common over a lifetime. The natural histories and age-related characteristics of renal diseases in the general popul...
Source: Current Transplantation Reports - February 1, 2016 Category: Transplant Surgery Source Type: research

Changing the Kidney Allocation System: a 20-Year History
Abstract The development of the current kidney allocation policy took almost a decade to complete and required compromise on many levels. The history of this process provides an excellent case study of how public policy is made. The final product of this process is a policy that balances utility and equity and establishes priorities for the allocation of a scarce national resource—deceased donor kidneys. While it may be imperfect, it is a dramatic improvement from the prior system and provides a framework for further revisions in the future. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - January 30, 2016 Category: Transplant Surgery Source Type: research

Update on 2015 OPTN/UNOS Strategic Plan: Allocation of Effort and Distribution of Manpower
Abstract The process by which the United Network for Organ Sharing (UNOS) allocates its effort is central to the pursuit of its mission. UNOS serves to support the field of solid organ and vascularized composite allograft transplantation and donation, and its many members, as well as to meet the requirements in its role as the contractor for the Organ Procurement and Transplantation Network (OPTN). As the responsibilities of UNOS have increased markedly over the past three decades, the role of strategic planning has become increasingly critical in providing direction to the organization. Over the course of the pas...
Source: Current Transplantation Reports - January 30, 2016 Category: Transplant Surgery Source Type: research

Use of 3D Printing for Medical Education Models in Transplantation Medicine: a Critical Review
This article presents a critical-realist review of the medical literature evaluating different ways 3D printing has been used to produce training models for medical education, with a special emphasis on transplantation medicine. From the 68 articles identified by this review, three themes emerged: (a) 3D printing of patient-specific models for preoperative planning, (b) printing training devices for direct use in simulation-based medical education, and (c) printing molds for simulation models that are then used to cast non-printable materials such as soft tissues. Only two reports were identified that described the use of ...
Source: Current Transplantation Reports - January 27, 2016 Category: Transplant Surgery Source Type: research

Educating Prospective Kidney Transplant Recipients and Living Donors about Living Donation: Practical and Theoretical Recommendations for Increasing Living Donation Rates
Abstract A promising strategy for increasing living donor kidney transplant (LDKT) rates is improving education about living donation for both prospective kidney transplant recipients and living donors to help overcome the proven knowledge, psychological, and socioeconomic barriers to LDKT. A recent Consensus Conference on Best Practices in Live Kidney Donation recommended that comprehensive LDKT education be made available to patients at all stages of chronic kidney disease (CKD). However, in considering how to implement this recommendation across different healthcare learning environments, the current lack of av...
Source: Current Transplantation Reports - January 26, 2016 Category: Transplant Surgery Source Type: research

Changing the US Public Health Service Guideline for Reducing Viral Transmission Through Organ Transplantation
This article will attempt to review the revision process of the US PHS Guideline and make suggestions for next steps in further refining the guideline. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - January 26, 2016 Category: Transplant Surgery Source Type: research

The OPTN/UNOS Policy Development Cycle: Challenges and Opportunities
Abstract The policies governing organ procurement and transplantation in the USA are developed and implemented by the Organ Procurement and Transplantation Network (OPTN) which was established by the National Organ and Transplant Act in 1984. The OPTN, operated by the United Network for Organ Sharing (UNOS), develops and revises policies through an iterative, evidence-based, consensus-driven process involving input from OPTN/UNOS committees and regions, the donation and transplant community, and the general public. Nonetheless, circumstances have arisen where the OPTN/UNOS Board of Directors has acted prior to pub...
Source: Current Transplantation Reports - January 26, 2016 Category: Transplant Surgery Source Type: research

Living Kidney Donor Criteria Based on Blood Pressure, Body Mass Index, and Glucose: Age-Stratified Decision-Making in the Absence of Hard Data
Abstract Kidney transplantation is the preferred choice for many patients with end-stage renal disease. Long waiting times for deceased donor kidneys and declining health on dialysis remain major barriers. It is within this paradigm that optimal timing of kidney transplantation requires the availability of a living donor. Historically, potential donors were most often young and in excellent health by standards of the time. Accepted values of blood pressure and glucose have become more restrictive in recent decades. Living kidney donation has appeared generally safe but nonetheless carries some surgical and potenti...
Source: Current Transplantation Reports - January 23, 2016 Category: Transplant Surgery Source Type: research

3D Printing for Liver Tissue Engineering: Current Approaches and Future Challenges
Abstract Recent developments in 3D printing have greatly accelerated progress in the field of liver tissue engineering by enabling the fabrication of more tissue-mimetic structures capable of restoring function. A variety of 3D printing and additive manufacturing techniques ranging from stereolithography to direct ink writing have shown great promise in liver tissue engineering and the study of cellular interactions. Despite these advances, however, there is significant room for improvement. Furthermore, because of the enormous capabilities of 3D printing, methods to analyze complex heterogeneous tissues in vitro ...
Source: Current Transplantation Reports - January 22, 2016 Category: Transplant Surgery Source Type: research

A Role for 3D Printing in Kidney-on-a-Chip Platforms
Abstract The advancement of “kidney-on-a-chip” platforms—submillimeter-scale fluidic systems designed to recapitulate renal functions in vitro—directly impacts a wide range of biomedical fields, including drug screening, cell and tissue engineering, toxicity testing, and disease modeling. To fabricate kidney-on-a-chip technologies, researchers have primarily adapted traditional micromachining techniques that are rooted in the integrated circuit industry; hence the term “chip.” A significant challenge, however, is that such methods are inherently monolithic, which limits one&rsqu...
Source: Current Transplantation Reports - January 20, 2016 Category: Transplant Surgery Source Type: research

Considerations for Living Kidney Donation Among Women of Childbearing Age: Evidence from Recent Studies
Abstract Each year, approximately 16,000 women become living kidney donors worldwide, donating a kidney to a spouse, family member, or friend. A common concern of women with childbearing potential is whether donation will affect future pregnancy outcomes. The first studies to examine pregnancy outcomes after living kidney donation were mostly reassuring; however, the two largest reported an increased risk of gestational hypertension and preeclampsia in groups of women with pregnancies after donation compared with groups of women with pregnancies before donation. A concern for donation-related risk was recently con...
Source: Current Transplantation Reports - January 16, 2016 Category: Transplant Surgery Source Type: research

Cardiac Donor Selection and Management
Abstract Heart transplantation remains the gold standard treatment for patients with end-stage heart failure. In the USA, the number of available donors has remained stable despite the steadily increasing need for organs. Optimal donor selection and management are critical to deriving the greatest benefit from this limited resource. Methods to expand the donor pool without compromising long-term outcomes for heart recipients are needed. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - October 20, 2015 Category: Transplant Surgery Source Type: research

Normothermic Ex Vivo Lung Perfusion in Clinical Lung Transplantation
Abstract Normothermic ex vivo lung perfusion is a novel strategy of donor lung preservation that preserves the metabolic activity of the organ. There are therefore opportunities for further lung evaluation and therapeutic intervention during the ex vivo stage. We review our clinical experience with this technique and offer perspectives for future development. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - October 10, 2015 Category: Transplant Surgery Source Type: research

The Importance of Prehabilitation in Liver Transplantation
Abstract Over 15,000 patients are listed for liver transplantation across the USA while only 6500 transplants are performed each year. Given the realities of this profound organ shortage, optimal patient preparation is important to assure good outcomes. In recent years, frailty and sarcopenia have emerged as important predictors of post-transplant mortality. Potentially, these risk factors may be remediable with preoperative preparation. Efforts to improve disease management and physical conditioning could not only optimize patients for liver transplantation but could also improve outcomes among those who do not u...
Source: Current Transplantation Reports - October 10, 2015 Category: Transplant Surgery Source Type: research

Update on Immune Monitoring in Heart Transplantation
Abstract We summarize the results of the most important research of the past decade on the post-transplant monitoring of heart transplant patients by gene expression profiling and the quantification of immunoactivity, donor-derived cell-free DNA and rejection-related microRNAs. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - October 9, 2015 Category: Transplant Surgery Source Type: research

Simultaneous Liver—Kidney Transplantation
Abstract In 2014, simultaneous liver kidney transplants (SLK) accounted for 8.2 % of all liver transplants performed in the USA. Prior to introduction of the model of end stage liver disease (MELD) system, SLK accounted for 2.5 % in 2001 and only 1.7 % in 1990. Transplant centers have struggled to balance the moral and ethical aspects of SLK in the setting of organ scarcity with an algorithm that best qualifies patients for such treatment options. Few centers have even ventured into DCD territory for SLK. Advancement in immunosuppression protocols and treatment of HCV and HIV have impacted SLK over ...
Source: Current Transplantation Reports - October 6, 2015 Category: Transplant Surgery Source Type: research

Utilization of Machine Perfusion and Nanotechnology for Liver Transplantation
Abstract Over the past four decades, advances in the technology supporting solid organ transplantation have been remarkable. Transplantation is now entering a new era where multidisciplinary approaches, including the use of bioengineering, are being utilized in the pursuit of perfection for the field. In this review article, we will introduce and recap two broad categories that are on the verge of revolutionizing the utilization of donor organs and delivery of immunosuppression, metabolic additives, and gene therapies. Machine perfusion techniques and nanotechnology are areas of significant interest in the transpl...
Source: Current Transplantation Reports - October 6, 2015 Category: Transplant Surgery Source Type: research

Current Treatment Strategies in Pulmonary Hypertension Associated with Left Heart Disease
Abstract Pulmonary hypertension (PH) is a common complication of left heart disease (LHD) and is associated with impaired functional capacity and decreased survival. Recent guidelines have proposed a new classification system for PH-LHD that is based on the diastolic pulmonary gradient. Despite a sound physiologic basis, subsequent studies have not found a significant correlation between the diastolic pulmonary gradient and meaningful outcomes. Treatment of PH-LHD focuses on optimizing the left heart disease. The use of medications for the treatment of combined post- and pre-capillary PH in left heart disease is c...
Source: Current Transplantation Reports - October 5, 2015 Category: Transplant Surgery Source Type: research

Antibody-Mediated Rejection in Lung Transplantation
Abstract There has been increasing awareness of antibody-mediated rejection (AMR) as an important cause of graft failure after lung transplantation in recent years. However, the diagnostic criteria for pulmonary AMR are not well defined. All four tenets of AMR in kidney and heart transplantation, graft dysfunction, complement component deposition, circulating donor-specific antibodies (DSA), and histopathologic changes consistent with AMR are infrequently present in lung transplantation. Nonetheless, the lung transplant community has made important progress recognizing cases of AMR and developing a definition. How...
Source: Current Transplantation Reports - September 30, 2015 Category: Transplant Surgery Source Type: research

Autoimmune Reactivity in Graft Injury: Player or Bystander?
Abstract Organ transplantation is the only viable treatment for several end-stage organ failures. However, chronic rejection prevents long-term graft survival. Traditionally, this rejection was attributed to the development of alloimmunity in transplant patients. However, recent evidence suggests that autoimmunity plays a larger role in chronic rejection of certain organ transplants, than alloimmunity. In this review, we will focus on the history of autoimmunity in solid organ transplantation and look at the collagen type V, Kα1 tubulin, vimentin, cardiac myosin, and heat shock proteins as classical examples...
Source: Current Transplantation Reports - July 7, 2015 Category: Transplant Surgery Source Type: research

Vascularized Composite Allotransplantation: Military Interest for Wounded Service Members
This article is an articulation of the ideals, goals, unknowns, challenges, and risks facing the DoD in the context of this investment. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - July 7, 2015 Category: Transplant Surgery Source Type: research

The Impact of Regulated Cell Death Pathways on Alloimmune Responses and Graft Injury
Abstract Transplantation is invariably associated with organ injury following donor organ procurement. Death of cells can negatively impact organ function if sufficient numbers of parenchymal cells are eliminated and not replaced as part of remodelling. Additionally by the release of contents, the death of cells can alter immune responses that are related to ischemia-reperfusion injury and alloimmune rejection. There is increasing awareness of the link between innate and adaptive immunity, and the profound influence inflammation has on organ function, tolerance induction, rejection responses and perhaps survival. ...
Source: Current Transplantation Reports - July 3, 2015 Category: Transplant Surgery Source Type: research

Immunological Challenges in Vascularised Composite Allotransplantation
Abstract Vascularised composite allotransplantation (VCA) is a new field in transplantation aiming to improve disabled patients’ quality of life. Two tissues appear to play an important role in the immune response: the skin, which is highly immunogenic and the main target of T-lymphocyte-mediated acute rejection, and the vessels, which are targeted by the humoral arm of recipient’s immune response, which lead to chronic rejection, as in solid organ transplantation. In preclinical models, transplantation of bone marrow is associated with mixed chimerism inducing and maintaining tolerance to allogeneic V...
Source: Current Transplantation Reports - July 1, 2015 Category: Transplant Surgery Source Type: research

Abdominal Wall Transplantation
Abstract Abdominal wall vascularized composite allotransplantation (AW-VCA) is a relatively young field within transplantation with 21 reported cases to date in the last decade. All AW-VCAs have been performed on patients undergoing either simultaneous multivisceral transplantation (MVT) or intestinal transplantation (IT). The two approaches to AW-VCA described are macrovascular and microvascular approaches. While at the time that this review is written, only three institutions have performed this procedure; their outcomes have shown low allograft loss. In addition, acute rejection of the abdominal wall graft was ...
Source: Current Transplantation Reports - June 30, 2015 Category: Transplant Surgery Source Type: research

Preclinical Models in Vascularized Composite Allotransplantation
Abstract Vascularized composite allotransplantation (VCA) has the potential to reconstruct any non-visceral tissue defect, using like for like tissue, delivering optimal form and function. Over 150 VCA transplants have been performed worldwide; however, this treatment remains experimental. Things systematically tried in the clinic should follow thorough science and tested in a model that allows predicting as possible the safety of the procedure. This is generally the function of animal experimentation. Advantages of preclinical models include greater control of bias, of subject numbers and of variables compared to...
Source: Current Transplantation Reports - June 28, 2015 Category: Transplant Surgery Source Type: research

Mechanisms of Renal Graft Chronic Injury and Progression to Interstitial Fibrosis
Abstract Following transplantation, the kidney is exposed to many different injuries which result in inflammation, overproduction of extracellular matrix, interstitial fibrosis and progressive loss of renal function. To date, treatment options for patients with progressive graft dysfunction are very limited. The development of new therapies requires a better understanding of the pathogenesis of transplant interstitial fibrosis and specific biomarkers to identify patients with progressive transplant fibrosis and monitor response to new therapies. Here, we review our current understanding of how and why extracellula...
Source: Current Transplantation Reports - June 26, 2015 Category: Transplant Surgery Source Type: research