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

Treg Therapy in Transplantation: How and When Will We Do It?
Abstract Adoptive therapy with regulatory T cells (Tregs) has shown great promises in many experimental models to induce permanent graft acceptance and tolerance to alloantigens. However, although their tolerogenic therapeutic potential has been demonstrated in clinical hematopoietic stem cell transplantation and partially in patients with early onset type I diabetes, translation into clinical testing for solid organ transplantation is still lacking or only slowly starting. This is in part due to the fact that many questions regarding not only the optimal type of Tregs but also the best-suited clinical trial desig...
Source: Current Transplantation Reports - June 24, 2015 Category: Transplant Surgery Source Type: research

Antibodies to HLA Molecules Mimic Agonistic Stimulation to Trigger Vascular Cell Changes and Induce Allograft Injury
Abstract Human leukocyte antigen (HLA)-induced signaling in endothelial and smooth muscle cells causes dramatic cytoskeletal rearrangement, increased survival, motility, proliferation, adhesion molecule and chemokine expression, and adhesion of leukocytes. These mechanisms are directly related to endothelial activation, neointimal proliferation, and intragraft accumulation of leukocytes during antibody-mediated rejection (AMR) and chronic rejection. Clustering of HLA by ligands in trans, such as in antigen-presenting cells at the immune synapse, triggers physiological functions analogous to HLA antibody-induc...
Source: Current Transplantation Reports - May 24, 2015 Category: Transplant Surgery Source Type: research

Should Both UNOS and CMS Provide Regulatory Oversight in Kidney Transplantation?
Abstract Since publication of the Centers for Medicare and Medicaid Services (CMS) Conditions of Participation Final Rule in 2007, there has been dual regulation of transplant centers by the Organ Procurement and Transplantation Network (OPTN) contractor the United Network for Organ Sharing (UNOS) and CMS. Herein, we summarize the environment leading to the development of the present regulatory framework and identify significant and unintended consequences of the current regulations. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - April 19, 2015 Category: Transplant Surgery Source Type: research

New Tools in Experimental Cellular Therapy for the Treatment of Liver Diseases
Abstract The current standard of care for end stage liver disease is orthotopic liver transplantation (OLT). Through improvement in surgical techniques, immunosuppression, and general medical care, liver transplantation has become an effective treatment over the course of the last half-century. Unfortunately, due to the limited availability of donor organs, there is a finite limit to the number of patients who will benefit from this therapy. This review will discuss current research in experimental cellular therapies for acute, chronic, and metabolic liver failure that may be appropriate when liver transplantation...
Source: Current Transplantation Reports - April 15, 2015 Category: Transplant Surgery Source Type: research

Should Pulsatile Preservation Be the Gold Standard in Kidney Transplantation?
Abstract In recent years, dramatic improvements in kidney transplantation, together with a rising incidence of diseases such as diabetes, have led to an increasing demand for deceased donor kidneys for transplantation. Hence, it has been necessary to expand the kidney donor pool by using organs once considered unsuitable for transplantation. These higher risk kidneys are typically from older donors with additional comorbidities and are more susceptible to injury. Therefore, the transplant community has been focusing efforts in trying to improve the outcomes of these high-risk organs. Preservation by pulsatile mach...
Source: Current Transplantation Reports - April 15, 2015 Category: Transplant Surgery Source Type: research

Diagnosis and Treatment of Pancreas Rejection
Abstract Despite significant improvement in pancreas allograft survival, rejection of the pancreas remains a major clinical problem. In addition to cellular rejection of the pancreas, antibody-mediated rejection of the pancreas is now a well-described entity. The 2011 Banff update established comprehensive guidelines for the diagnosis of acute and chronic AMR. The pancreas biopsy is critical in order to accurately diagnose and treat pancreas rejection. Other modes of monitoring pancreas rejection we feel are neither sensitive nor specific enough. In this review, we examine recent advances in the diagnosis and trea...
Source: Current Transplantation Reports - April 10, 2015 Category: Transplant Surgery Source Type: research

Should the Pancreas be Routinely Included with an Intestinal Graft?
Abstract Intestinal transplant is the only curative solution for children and adults with life-threatening complications of intestinal failure. A dilemma that arises often in real life, typically at the time of organ allocation involving multiple centers, is whether the pancreas can and/or should be procured and transplanted separately from an intestine-containing graft. Evidence appears to support routinely allocating the pancreas along with a composite liver-intestine graft. For all pediatric recipients and recipients of any age requiring foregut replacement, the pancreas would likewise seem fundamental to the g...
Source: Current Transplantation Reports - April 8, 2015 Category: Transplant Surgery Source Type: research

Total Pancreactectomy with Islet Autotransplant Failure: Now What?
Abstract Total pancreatectomy with islet cell autotransplant (TPIAT) is a definitive therapeutic approach to pain management for patients with chronic pancreatitis that is non-responsive to maximum medical management. Total pancreatectomy (TP) results in brittle diabetes unless islet cell autotransplant (IAT) is concomitantly performed. Even with IAT, about 30 % of patients will require long-term basal-bolus insulin therapy due to significant endocrine insufficiency. The focus of this review is on the utility of whole organ pancreas transplantation toward improving quality of life, and decreasing the risk of ...
Source: Current Transplantation Reports - April 7, 2015 Category: Transplant Surgery Source Type: research

Adoptive T Regulatory Cell Therapy for Tolerance Induction
Abstract There is a clear need to develop strategies to induce tolerance without the need of chronic immunosuppression in transplant recipient and in patients with autoimmunity. Adoptive T regulatory cell (Treg) therapy offers the potential of long-lasting protection. However, based on results of clinical trials so far with ex vivo expanded autologous Tregs in type 1 diabetic (T1D) patients, it seems unlikely that single immunotherapy with Treg infusion without immunomodulation regimens that promote stable donor Treg engraftment and persistence would afford truly significant clinical benefit. Combination therapies...
Source: Current Transplantation Reports - April 2, 2015 Category: Transplant Surgery Source Type: research

Pancreas Transplantation for Type 2 Diabetes Mellitus: Who and Why?
Abstract In the past, type 2 diabetes mellitus (T2DM) was a contraindication for simultaneous pancreas-kidney transplantation (SPKT) even though it was generally accepted to be an effective treatment option for selected patients with type 1 DM (T1DM) and advanced chronic kidney disease. However, because there may be tremendous overlap in the clinical presentations of T1DM versus T2DM, the presence of detectable C-peptide is no longer considered reliable in determining DM “type.” Experiences with SPKT in uremic patients with detectable pretransplant C-peptide levels with a type 2 diabetes phenotype (old...
Source: Current Transplantation Reports - April 2, 2015 Category: Transplant Surgery Source Type: research

The Economic Aspects of Pancreas Transplant: Why Is the Organ Acquisition Charge So High?
Abstract Pancreas transplantation in the USA has declined steadily over the past 10 years. Fewer patients are being listed as candidates, and fewer pancreata are being recovered from deceased donors. Of the donors where there is an intent to recover a pancreas for an identified recipient, some are ruled out intraoperatively, and>25 % of pancreas are discarded after recovery. Based on the current Centers for Medicare and Medicaid Services (CMS) cost-finding and reimbursement policies for organ procurement organizations (OPOs), this high level of intended for transplant but untransplanted pancreas ...
Source: Current Transplantation Reports - April 2, 2015 Category: Transplant Surgery Source Type: research

New Steps in the Use of Mesenchymal Stem Cell in Solid Organ Transplantation
Abstract Cell therapy with mesenchymal stem cells stands at the front line of new potential tolerance-inducing therapies in solid organ transplantation. Pre-clinical and in vitro models have shown very potent immunomodulatory effects of MSC, and the first clinical trials hold promising perspectives. On the other hand, new approaches around the therapeutic use of MSC are also under research. In this article, we review recent evidence on MSC immunomodulation and their clinical application. We further discuss and speculate about new lines of research in the field including new applications and alternatives or variati...
Source: Current Transplantation Reports - March 28, 2015 Category: Transplant Surgery Source Type: research

Revamped Rationing of Renal Resources: Kidney Allocation in Search of Utility and Justice for All
Abstract The widening gap between patients in need of a kidney transplant and the finite number of transplantable deceased donor organs resulted in critical review of kidney allocation policy in the USA. The process to reach consensus for change required compromise between arguments for utility and equity. Important amendments to address shortcomings of the old system and projected outcomes of the new system are reviewed. Potential unintended consequences and practical considerations to facilitate implementation of provisions intended to enhance utility and increase access to transplant for population subgroups in...
Source: Current Transplantation Reports - March 28, 2015 Category: Transplant Surgery Source Type: research

The Cost of Transplant Immunosuppressant Therapy: Is This Sustainable?
Abstract A solid organ transplant is a life-saving therapy that engenders the use of immunosuppressive medications for the lifetime of the transplanted organ and its recipient. Conventional therapy includes both induction therapy (a biologic that is infused perioperatively) followed by maintenance therapy. The cost of these medications is a constant concern, and the advent of generics has brought this cost down modestly. For those lacking long-term insurance coverage, this may be a significant out-of-pocket expense that is not affordable. Moreover, transplant centers are managing higher risk transplant recipients ...
Source: Current Transplantation Reports - March 28, 2015 Category: Transplant Surgery Source Type: research

Monocyte-Derived Suppressor Cells in Transplantation
Abstract Myeloid-derived suppressor cells (MDSC) are cells of myeloid origin with enhanced suppressive function. They are negative regulators of the immune responses and comprise a heterogeneous mixture of immunosuppressive cells of monocytic (M-MDSC) and granulocytic (G-MDSC) origin. A more recent nomenclature proposes the term “suppressive monocyte derived cells” (suppressive MCs) to define CSF1/CSF2-dependent mouse suppressor cells that develop from common monocyte progenitors (cMoPs) after birth. Here, we review the literature about monocytic-derived cells with demonstrated suppressor function in v...
Source: Current Transplantation Reports - March 27, 2015 Category: Transplant Surgery Source Type: research

Robotic-assisted Kidney Transplantation: Our Experience and Literature Review
Abstract Kidney transplantation is the preferred treatment for patients with end-stage renal disease. While open surgery remains the gold standard, minimally invasive surgery has recently been introduced for the recipient undergoing kidney transplantation. Our team has employed the robotic surgical system to perform renal transplantation in obese recipients to minimize the risk of surgical site infections, with good results in terms of complications and graft and patient survival. However, others groups have performed kidney transplantation robotically in nonobese patients using different techniques. The da Vinci ...
Source: Current Transplantation Reports - March 26, 2015 Category: Transplant Surgery Source Type: research

Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application
Abstract Dynamic preservation strategies such as hypothermic machine perfusion are increasingly discussed to improve liver graft quality before transplantation. This review summarizes current knowledge of this perfusion technique for liver preservation. We discuss optimization of perfusion conditions and current strategies to assess graft quality during cold perfusion. Next, we provide an overview of possible pathways of protection from ischemia-reperfusion injury. Finally, we report on recent clinical applications of human hypothermic machine liver perfusion. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - February 10, 2015 Category: Transplant Surgery Source Type: research

The Rationale for Incentives for Living Donors: An International Perspective?
Abstract The organ shortage has become a crisis for transplant candidates with end-stage renal disease, and a significant number of them either die while waiting or become too sick to transplant. A consequence, worldwide, has been the development of unregulated markets for donation; these markets have been associated with poor outcomes for both donors and recipients. In contrast, a regulated system of incentives might increase donation rates while also providing a benefit to donors. Criteria for an acceptable system have been proposed: protection of the donor and recipient, regulation, transparency, and oversight....
Source: Current Transplantation Reports - February 7, 2015 Category: Transplant Surgery Source Type: research

Bioreactor Development for Lung Tissue Engineering
Conclusions Significant advances in bioreactors for lung engineering have been made at both the microfluidic and the macroscale. The most advanced are closed systems that incorporate pressure-controlled perfusion and ventilation and are amenable to automation. Ex vivo lung perfusion systems have advanced to clinical trials for lung preservation and reconditioning. The biggest challenges that lie ahead for lung bioengineering can only be overcome by future advances in technology that solve the problems of cell production and tissue incorporation. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - February 5, 2015 Category: Transplant Surgery Source Type: research

Development of Lung Epithelium from Induced Pluripotent Stem Cells
Abstract Considerable progress has been made in the field of in vitro development of alveolar epithelium from induced pluripotent stem cells. Patient specific derived alveolar cells could potentially populate tissue engineered lungs, provide a cell source for drug testing, or function as a model for research into lung diseases. Induced to pluripotency through a variety of techniques, stem cells can be differentiated to alveolar epithelium through exposure to a variety of different culture conditions and growth media. The ultimate success of differentiated cells for translational medicine applications will depend o...
Source: Current Transplantation Reports - January 29, 2015 Category: Transplant Surgery Source Type: research

Evaluation of Kidney Function and Structure in Potential Living Kidney Donors: Implications for the Donor and Recipient
Abstract Kidney transplantation is the best treatment for patients with end-stage renal disease and recipients of living kidney donors fare better than recipients of deceased donors. In view of the shortage of organ supply and the long waiting list, expansion of the living donor pool has been sought. Importantly, donor acceptance criteria must first and foremost be grounded in concerns for donor safety. Recent studies suggesting that live kidney donors may have higher rates of end-stage renal disease in the long term compared with otherwise similar healthy persons highlights the critical importance of pre-donation...
Source: Current Transplantation Reports - January 29, 2015 Category: Transplant Surgery Source Type: research

Infection and Cancer Screening in Potential Living Donors: Best Practices to Protect the Donor and Recipient
Abstract Twenty-one percent of transplants in the US come from live donors. Data show that live-donor transplantation is a safe practice, but is not completely risk free. Malignancy and infection transmission through live organ donation is extremely rare, but can be a devastating event for the recipient, donor and treatment team if it occurs. The donor evaluation is multifactorial, taking into the account the unique medical, social and family history of individual donors, needs of the recipient, and determination of the anatomic and functional suitability of the donor organ, and is further complicated by geographi...
Source: Current Transplantation Reports - January 20, 2015 Category: Transplant Surgery Source Type: research

Effects of Hypercapnia in Lung Tissue Repair and Transplant
Abstract Mammalian cells sense and transduce signals in response to high levels of carbon dioxide. Hypercapnia has a variety of effects on epithelial and immune cells which can be beneficial or detrimental depending on the biologic context. For instance, hypercapnia-mediated suppression of cell proliferation and migration can delay wound repair. Similarly, suppression of macrophages and the inflammatory response during hypercapnia can limit the host’s ability to clear pathogens. However, the suppressive effects of hypercapnia on immunity have potential benefits in the setting of transplantation. Here, we dis...
Source: Current Transplantation Reports - January 20, 2015 Category: Transplant Surgery Source Type: research

Informed Consent of Living Kidney Donors: Pitfalls and Best Practice
Abstract Informed consent is clearly considered the ethical bedrock fundamental to living organ donation, a procedure lacking medical benefits for its participants. Recent guidelines have focused on strengthening content components of living kidney donor informed consent, including Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) policies that prescribe key components, and integration of the Independent Living Donor Advocate (ILDA), as mandated by Centers for Medicare and Medicaid Services (CMS) and the OPTN/UNOS. The European Union member states’ Working Group on ...
Source: Current Transplantation Reports - January 20, 2015 Category: Transplant Surgery Source Type: research

Evaluation of Genetic Renal Diseases in Potential Living Kidney Donors
Abstract Better outcomes for living donor transplantation, together with the shortened waiting time and the increasing gap between supply and demand for kidneys for transplantation, has led to greater pressure on transplant candidates and transplant centers alike to encourage and advocate for living kidney donation as the more timely form of renal replacement therapy. Recent studies report that living kidney donors biologically related to their transplant candidate may be at increased risk of end-stage renal disease (ESRD) and this may reflect the shared inheritance of a disease or risk allele. The possibility of ...
Source: Current Transplantation Reports - January 15, 2015 Category: Transplant Surgery Source Type: research

Breaking the Ice: Early Clinical Results Using Hypothermic Machine Liver Preservation
Abstract Hypothermic machine preservation (HMP) remains investigational in clinical liver transplantation. It is widely used, however, to preserve kidneys for transplantation because it has demonstrated improved results over static cold storage (CS). As with other machine preservations methods, HMP provides continuous circulation of nutrients and metabolic substrates during the ex-vivo period. Over the last few years, several groups worldwide have been actively translating HMP into the clinical arena for liver transplantation. In particular, HMP has been used for livers of varying quality, including those recovere...
Source: Current Transplantation Reports - January 15, 2015 Category: Transplant Surgery Source Type: research

Early Clinical Results Using Normothermic Machine Liver Preservation
Abstract The ongoing shortage of donor organs for liver transplantation results in high mortality rates for those on the waiting list. This has triggered considerable interest in the use of marginal liver grafts to increase the donor pool. Unfortunately, marginal grafts poorly tolerate preservation by cold storage (CS), resulting in an increased risk of liver injury and poor graft function after transplantation. Better preservation techniques are needed to fully utilize marginal grafts and to expand the number of organ donors. Animal studies have demonstrated normothermic ex vivo liver perfusion to be superior to ...
Source: Current Transplantation Reports - January 11, 2015 Category: Transplant Surgery Source Type: research

Preclinical Foundation for Normothermic Machine Liver Preservation
Abstract Liver transplantation is the primary treatment for end-stage liver disease, but demand exceeds supply due to the shortage of available healthy donor grafts. To increase the supply of useable grafts for transplantation, innovative and better preservation methods are needed to enable the use of livers from extended criteria donors. Normothermic machine perfusion (NMP) has been extensively studied in the laboratory and holds great potential for expanding the donor pool. This review summarizes the progress that has been made in NMP over the last two decades, with emphasis on the recent studies preparing the m...
Source: Current Transplantation Reports - January 9, 2015 Category: Transplant Surgery Source Type: research

Impact of Living Kidney Donation on Long-Term Renal and Patient Survival: An Evolving Paradigm
Abstract During the last decades, there have been several studies reporting the outcome after living kidney donation. These studies have not shown any increase in mortality or end-stage renal disease. This is reassuring for potential donors. However, in these studies, kidney donors have been compared with unselected general population controls. In recent studies, kidney donors have been compared with selected healthy controls designed to simulate the donor selection process and improve quantification of the attributable impacts of donation. Also, recent studies describe donor cohorts with a longer follow-up. One o...
Source: Current Transplantation Reports - December 27, 2014 Category: Transplant Surgery Source Type: research

Use of Proliferation Signal Inhibitors in Cardiac Transplantation
Abstract Cardiac transplantation remains the definitive and most highly successful therapy for patients with advanced heart failure who have failed all other therapies. Long-term survival is limited by cardiac allograft vasculopathy, the transplant coronary artery disease, and malignancy. Standard, traditional immunosuppressive agents such as calcineurin inhibitors, anti-proliferative agents, and corticosteroids do little to attenuate cardiac allograft vasculopathy, which, because of its diffuse nature, is usually not amenable to percutaneous or surgical revascularization approaches, and may potentiate the develop...
Source: Current Transplantation Reports - October 12, 2014 Category: Transplant Surgery Source Type: research

Pediatric Liver Transplantation: A Surgical Perspective and New Concepts
Abstract The first successful liver transplantation was carried out in 1967, and the recipient was a pediatric patient. Since then, many challenges have been overcome and, nowadays, 1-year patient survival after liver transplantation is about 90 % in pediatric patient populations. Standardization of surgical technique, development of better immunosuppressive medications, improved understanding of caring for patients with end-stage liver disease, and improvements in anesthesia and intensive care have had a tremendous impact on graft and patient survival. Despite all improvements, challenging issues in pediatri...
Source: Current Transplantation Reports - October 10, 2014 Category: Transplant Surgery Source Type: research

Liver Transplantation for Hepatocellular Carcinoma
Abstract Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is associated with very poor overall survival. Most patients present with advanced-stage disease and are therefore not eligible for curative surgical therapies. In patients who do present with early-stage HCC, liver transplantation (LT) is an optimal curative surgical option, if the patient is eligible for LT. Most HCC develops in the background of chronic liver disease, and LT serves as a treatment for both the cancer and the underlying cirrhosis. Although the initial experience with LT for HCC was associated with a hig...
Source: Current Transplantation Reports - September 25, 2014 Category: Transplant Surgery Source Type: research

Approach to the Sensitized Patient Awaiting Heart Transplantation
Abstract The management of the sensitized patient awaiting heart transplant remains a challenge and an active area of research. The development of solid-phase immunoassays (including the C1q assay) has allowed high-resolution determination of antibodies most likely to be associated with antibody-mediated rejection and adverse outcomes. The precision of these techniques has permitted the adoption of the virtual crossmatch, substantially expanding the donor pool for sensitized patients and reducing wait times to transplant. Desensitization strategies continue to evolve, and the most effective therapies appear to be ...
Source: Current Transplantation Reports - September 20, 2014 Category: Transplant Surgery Source Type: research

Radiology in Transplant
Abstract There have been several advances in liver imaging that have affected liver transplantation, with the adoption of new policies for hepatocellular carcinoma (HCC) and exploration of new imaging techniques for assessment of liver lesions, steatosis, and fibrosis. The implementation of the Organ Procurement and Transplant Network (OPTN) criteria for non-invasive diagnosis of HCC impacted organ allocation, and the proposed LI-RADS (Liver Imaging Reporting and Data System) recommendations should enable standardization of the reporting of liver lesion characteristics. New methods to enhance existing magnetic res...
Source: Current Transplantation Reports - September 19, 2014 Category: Transplant Surgery Source Type: research

Antibody-mediated Rejection in Heart Transplantation
Abstract Heart transplantation is an excellent long-term treatment that confers functionality and longevity in select patients with end-stage heart failure. Yet, allograft rejection continues to pose a significant threat, especially in high-risk recipients and soon after transplantation. Of the two prevailing pathologic types of acute rejection in cardiac allografts, antibody-mediated rejection (AMR) had been variably defined and poorly understood for the past three decades when compared to cellular rejection. As a result, progress in understanding its pathologic and clinical behavior and the ability to find effec...
Source: Current Transplantation Reports - September 13, 2014 Category: Transplant Surgery Source Type: research

Update on Bronchiolitis Obliterans Syndrome in Lung Transplantation
Abstract Lung transplantation has become an important therapeutic option for patients with end-stage organ dysfunction; however, its clinical usefulness has been limited by the relatively early onset of chronic allograft dysfunction and progressive clinical decline. Obliterative bronchiolitis is characterized histologically by luminal fibrosis of the respiratory bronchioles and clinically by bronchiolitis obliterans syndrome (BOS) which is defined by a measured decline in lung function based on forced expiratory volume (FEV1). Since its earliest description, a number of risk factors have been associated with the d...
Source: Current Transplantation Reports - September 12, 2014 Category: Transplant Surgery Source Type: research

Size and Gender Matching in Heart Transplantation – Optimizing Donor Utilization in an Era of Changing Donor and Recipient Characteristics
Abstract Heart transplantation is limited by donor organ availability. Increased use of marginal donor organs, combined with increased recipient complexity, has increased the risk of primary graft failure. These changes in donor and recipient characteristics have led to a renewed focus on modifiable donor–recipient characteristics that have historically been shown to impact on post-transplant outcomes, namely size and gender matching. Recently published analyses of large registries have found that the use of body weight to size donor organs for transplantation fails to predict post-transplant outcomes, where...
Source: Current Transplantation Reports - September 6, 2014 Category: Transplant Surgery Source Type: research

Standardizing MELD Exceptions: Current Challenges and Future Directions
Abstract Since Model for End-Stage Liver Disease (MELD)-based allocation was implemented in 2002, a system of exception points has been in place in order to award increased waitlist priority to those patients whose severity of illness or risk of complications are not captured by the MELD score. These exceptions, categorized as standardized and non-standardized, have been used with increasing frequency over time. Several challenges to the exception point system have emerged, including lack of standardization in the criteria used to approve such exceptions, geographic variability in the use and approval of such exce...
Source: Current Transplantation Reports - September 6, 2014 Category: Transplant Surgery Source Type: research

Primary Graft Dysfunction After Heart Transplantation
Abstract Primary graft dysfunction (PGD) is a life-threatening complication of heart transplantation that presents as left, right, or biventricular dysfunction occurring within the first 24 hours of transplant surgery for which there is no identifiable secondary cause. Myocardial injury caused by acute catecholamine toxicity and the release of multiple proinflammatory mediators in the donor, followed by ischaemia-reperfusion injury sustained during retrieval, have been considered the predominant pathogenetic processes leading to PGD. Donor, recipient, and procedural factors contribute to the development and s...
Source: Current Transplantation Reports - September 4, 2014 Category: Transplant Surgery Source Type: research

Vascularized Composite Allografts: Procurement, Allocation, and Implementation
Abstract Vascularized composite allotransplantation is a continuously evolving area of modern transplant medicine. Recently, vascularized composite allografts (VCAs) have been formally classified as ‘organs’. In this review, key aspects of VCA procurement are discussed, with a special focus on interaction with the procurement of classical solid organs. In addition, options for a matching and allocation system that ensures VCA donor organs are allocated to the best-suited recipients are looked at. Finally, the different steps needed to promote VCA transplantation in society in general and in the medica...
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research

Memory T Cells in Transplantation
Abstract Following infections and other environmental exposures, the resulting primary immune response generates memory T cells that provide long-term protective immunity. Compared to their naïve T cell counterparts, memory T cells possess unique characteristics that endow them with the ability to quickly and robustly respond to foreign antigens. While such memory T cells are beneficial in protecting hosts from recurrent infection, memory cells reactive to donor antigens pose a major barrier to successful transplantation and tolerance induction. Significant progress has been made over the past decade contrib...
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research

Ischemia/Reperfusion Injury and its Consequences on Immunity and Inflammation
Abstract Ischemia/reperfusion injury (IRI), an inherent component of transplantation, affects organ quality and transplant outcomes. Although the complexity of the pathophysiology is recognized, detailed mechanisms remain unclear, and strategies preventing the consequences of IRI have been challenging. Of critical significance appears to be the link between IRI, the initiation of innate immune responses, and the (potential) augmentation of adaptive immunity. An improved understanding of those complex mechanisms and interactions may pave the way for more effective treatment strategies. (Source: Current Transplantation Reports)
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research

Non-Antibody Mediated Roles of B Cells in Allograft Survival
Abstract Antibody production is unquestionably a key effector function of B cells that remains a formidable barrier against long-term graft survival. However, emerging evidence indicates that B cells play a key role in shaping the effector responses by mechanisms that extend beyond their function as antibody producing cells. B cell depletion in transplant recipients has resulted in paradoxical outcomes of increased graft rejection versus improved graft function, implying that B cells function as both enhancers and regulators of the alloimmune response. Based on findings from animal and human studies, we address m...
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research

Evolving Concepts of Skin and Mucosal Biopsy in Facial Vascularized Composite Allotransplantation
Abstract Facial vascularized composite allotransplantation has ushered in a new era in treating complex facial injuries that cannot be reconstructed using traditional techniques. Multiple teams have reported their experiences in monitoring for allograft rejection using skin and mucosal biopsies. The association of biopsy findings and clinical observations are poorly understood and are continuously being redefined. We review the world’s experience in monitoring skin and mucosal histological findings in facial transplantation, review acute rejection, antibody-mediated rejection, chronic rejection, and describ...
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research

Measuring Outcome in Upper-Extremity Transplantation
Abstract Measuring the outcome in upper-extremity transplantation is important to understand the potential of the procedure and to assist the patient and surgeon in decision making. The outcome of replantation varies with the anatomic level and mechanism of amputation; factors which inform the indications for replantation. We review the outcome measures used in upper-extremity transplantation and advocate for a combination of patient-answered outcomes, physical measurements, preference-based measurement, and cost analysis. Since this procedure is not common, and there is significant risk associated with immunosup...
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research

Postoperative Monitoring: Biomarkers and Alloimmune Responses and Their Relevance to Vascularized Composite Allotransplantation
Abstract Vascularized composite allotransplantation (VCA) is an evolving area of transplantation. Postoperative monitoring and immunosuppression strategies draw experience from solid organ transplantation, but VCA provides unique challenges as grafts incorporate histologically heterogenous tissues with differing degrees of antigenicity. In addition, such procedures are often life-improving rather than life-saving; therefore, minimizing the risks of immunosuppression is an important clinical priority. To this end, the identification of biomarkers to monitor the health of the transplanted tissues, assess alloimmune...
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research

Mouse Models of Experimental Vascularized Composite Allotransplantation
Abstract The clinical practice of vascularized composite allotransplantation (VCA) has been limited by the potential side effects of chronic immunosuppression. Studies using rodent models have been useful for dissecting mechanisms underlying immunological events induced by VCA and for developing protocols such as mixed chimerism for tolerance induction. Mouse models of VCA have great advantages over rat and other rodents with regard to dissection of immunologic mechanisms; however, the microsurgical revascularization procedures that are required are much more difficult. Here we review recent advances in surgical ...
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research

Large Animal Models for Vascularized Composite Allotransplantation
Abstract Large animal models have served as the foundation for clinical trials in all solid organ transplantation. Likewise, pre-clinical studies in vascularized composite allotransplantation (VCA) have provided a foundation for initial human applications in VCA. The growth of clinical VCA correspondingly benefits from large animal studies investigating the unique immunobiology, improved immunosuppressive regimens, and the potential induction of immunologic tolerance. VCA studies in large animal models of nonhuman primates, swine, and canines have and continue to build knowledge towards improved clinical outcomes...
Source: Current Transplantation Reports - September 1, 2014 Category: Transplant Surgery Source Type: research