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Background and Aims HCV is a worldwide cause of chronic liver disease, particularly in Egypt where the most prevalent is genotype 4. HCV-associated cirrhosis is the most common indication for orthotopic liver transplantation (OLT) among adults. HCV infection remains a problem after transplantation, and recurrent hepatic infection is the leading cause of graft failure. Little is known about the long-term effects of direct acting antiviral therapy in patients after liver transplantation. We examined the incidence and severity of liver transplantation rejection in patients treated for HCV, post liver transplantation, with DAAs relative to the incidence and severity of liver transplantation rejection in patients treated for HCV, post liver transplantation, with Interferon based therapy and patients who didn’t receive any treatment for HCV after transplantation. Patients and Methods The study was conducted on 90 patients who had underwent liver transplantation between 2010 and 2017 at Ain Shams Center for Organ Transplantation (ASCOT) with a minimum follow up period of 6 months. Patients were divided into three groups: group I included 16 patients that didn’t receive antiviral treatment after liver transplantation, group II included 20 patients that had received interferon based therapy after liver transplantation and group III included 54 patients that had received direct acting antivirals after liver transplantation. Results Amongst group I, 2 patients (12.5%) developed acute graft rejection while in group II 2 patients (10%) developed chronic graft rejection and in group III 6 patients (11.11%) developed chronic rejection. In group I, all the patients (100%) had developed rejection that was diagnosed within one year of liver transplantation. In group II, 2 patients (100%) developed chronic graft rejection which occurred after one year of liver transplantation, one of them was on treatment with peg interferon and the other had already completed treatment. In group III, 2 patients (40%) had developed chronic rejection within one year of transplantation, while 4 patients (60%) had developed chronic rejection after one year of transplantation. One patient (16.67%) had developed rejection on treatment while 5 patients (83.33%) had developed rejection after the end of treatment. Conclusion It was found that the incidence of chronic rejection was more in patients that had received antiviral treatment after liver transplantation, however no difference was noted between DAAs and peg-interferon. Chronic rejection was found to be more common when treatment was given over one year after liver transplantation (6 cases) as compared to within the 1st year (2 cases). This may be related to the withdrawal of immunosuppression treatment after one year of transplantation and maintenance on monotherapy.

Renal transplantation is the best modality of treatment for end stage renal disease in children when compared to chronic dialysis. The growth, development and quality of life in these children are significantly better after transplantation. There has been a marked increase in the number of children undergoing renal transplantation in the recent years. The short term graft survival rates have increased with improved immunosuppression, but the long term outcome is still poor due to chronic graft rejection and opportunistic infections. In developing countries renal transplantation is not accessible to many children due to economic issues, lack of expertise and the absence of a strong deceased donor program. This article is a brief review of the indications and other aspects of pre-operative evaluation of pediatric renal transplant recipients.

In the current era of rapidly advancing and evolving medicine, a huge emphasis has been placed on the utilization of diagnostic tests and imaging, as well as on following updated guidelines, at the expense of focusing on clinical exams and honing these skills. Poor physical exam skills is a definite risk to patient safety, as they might lead to the misdiagnosis of, sometimes, fatal diseases. In this case, we discuss a case of complicated aortic dissection type A that initially presented to us as a case of worsening chronic graft rejection. Aortic dissection type A was solely uncovered by clinical exam despite unusual presenting symptoms and grossly benign basic labs and initial chest radiograph.

Não recebi financiamento The growth of lung transplantation has been constant throughout the world, and with this, the results presented have been progressively better, both in the short and long term. Despite this reality, some problems of difficult solution limit these programs, such as chronic graft rejection and complications secondary to long-term immunosuppression. The immunosuppressive strategies used in lung transplantation are based on triple schemes, composed of a calcineurin inhibitor, an antimetabolic agent and corticosteroids. A fourth group of immunosuppressants consists of inhibitors of cell proliferation, in particular, mTOR inhibitors. In this sense, this review aimed to compare the immunosuppressive regimen based on a calcineurin inhibitor-associated mTOR inhibitor at reduced dose with the calcineurin inhibitor alone in the chronic rejection of the posttransplant lung graft. In order to do so, we applied the methodological design of systematic review of the literature, through searches in electronic health databases (MEDLINE, Wef of Science, Scopus, Cochrane Central, EMBASE and LILACS) and in secondary manual resources. Six scientific articles composed the corpus of analysis for the qualitative synthesis of the results, which referred to three studies named SHITRIT, NOCTET and 4EVERLUNG. The main outcomes were the safety of substitution therapy for calcineurin inhibitor-based immunosuppressive therapy by the treatment of mTOR inhibitor with low patient mortality as well as maintaining efficacy in controlling events of chronic graft rejection. The relevance of the data that indicated an improvement in the renal function of the patients when submitted to the therapy with inhibitor mTOR in relation to calcineurin inhibitors was unanimously highlighted. The studies present a high reliability index due to the manifestation of low risk of bias in most of the items evaluated for the assertive conduction of a randomized clinical trial, in addition to presenting an important recommendation force for clinical decision making. In this sense, this systematic review guides a weighting in the use of mTOR inhibitors, considering the greater risk of mortality in the first year of treatment associated with this therapy. For patients with renal dysfunction associated with the isolated use of calcineurin inhibitors, this review "recommends" a change in the therapeutic regimen for the insertion of mTOR inhibitors into calcineurin inhibitors at a reduced dose, considering the imminent risk of mortality of lung transplant patients under renal insufficiency. O crescimento do número de transplantes de pulmão tem sido constante no mundo todo, e, com isso, os resultados apresentados têm sido progressivamente melhores, tanto em curto e em longo prazo. Apesar desta realidade, alguns problemas de difícil solução limitam estes programas, como a rejeição crônica do enxerto e as complicações secundárias à imunossupressão de longa duração. As estratégias imunossupressoras utilizadas no transplante de pulmão baseiam-se em esquemas triplos, compostos de um inibidor de calcineurina, um antimetabólico e corticosteroides. Um quarto grupo de imunossupressores constitui-se de inibidores da proliferação celular, em particular, os inibidores de mTOR. Nesse sentido, esta revisão se propôs a comparar o esquema de imunossupressão baseado em inibidor de mTOR associado a inibidor de calcineurina em dose reduzida com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-tranplante de pulmão. Para tanto, aplicou-se o desenho metodológico de revisão sistemática da literatura, por meio de buscas em bases eletrônicas da saúde (MEDLINE, Wef of Science, Scopus, Cochrane Central, EMBASE e LILACS) e em recursos manuais secundários. Seis artigos científicos compuseram o corpus de análise para a síntese qualitativa dos resultados, os quais se referiam a três estudos nominados SHITRIT, NOCTET e 4EVERLUNG. Os desfechos principais apontaram para a segurança da terapêutica de substituição do tratamento imunossupressor baseado em inibidor de calcineurina pelo tratamento baseado em inibidor de mTOR, com baixo índice de mortalidade dos pacientes, assim como da manutenção da eficácia em controlar eventos de rejeição crônica do enxerto. Destacou-se de forma unânime, a relevância dos dados que apontaram melhora na função renal dos pacientes quando submetidos à terapêutica com inibidor mTOR em relação a inibidores de calcineurina. Os estudos apresentam alto índice de confiabilidade pela manifestação de baixo risco de viés na maioria dos itens avaliados para a condução assertiva de um ensaio clínico randomizado, além de apresentarem importante força de recomendação para a tomada de decisão clínica. Nesse sentido, esta revisão sistemática orienta para um ponderamento na utilização de inibidores mTOR, considerando o maior risco de mortalidade do paciente no primeiro ano de tratamento associado a essa terapêutica. Para pacientes que apresentem disfunção renal associada ao uso isolado de inibidores de calcineurina, esta revisão “recomenda” a troca de regime terapêutico para a inserção de inibidores mTOR aos inibidores de calcineurina em dose reduzida, considerando o risco iminente de mortalidade dos pacientes transplantados de pulmão sob insuficiência renal.

Vascularized composite allotransplantation (VCA) has emerged as a useful reconstructive option for patients suffering from major tissue defects and functional deficits. While the technical feasibility has been optimized and more than 130 VCAs have been performed during the last two decades, hurdles such as acute and chronic allograft rejection, graft deterioration, and eventual functional impairment need to be addressed. Recently, chronic graft rejection and progressive failure have been linked to vascular alterations observed in the allografts. Graft vasculopathy (GV) may play a pivotal role in long-term graft deterioration. The understanding of the underlying pathophysiological processes and their initial triggers is of utmost importance in the prevention, attenuation, and therapy of GV. While there are reports on the etiology and development of GV in solid organ transplantation, there are limited data with respect to chronic rejection and GV in the realm of VCA. Nevertheless, recent reports from long-term VCA recipients suggest that GV could truly jeopardize allografts in the follow-up evaluation. Chronic rejection and GV include different entities and might have different pathways in distinct organs. Herein, we reviewed the current literature on vascular changes during both acute and chronic allograft rejection, with a focus on their clinical and translational significance for VCA.

Background. With the increase of primary lung transplantation across major centers worldwide, over the last several years the need of lung retransplant (ReTX) is likely to increase. Therefore, characterization of ReTX patients is prudent and necessary. Our study aimed to investigate and characterize the covariates and outcomes associated with lung ReTX survival in a single large U.S. transplant center. Methods. Demographic, clinical diagnoses, and comorbidities were analyzed. Kaplan-Meier statistics were used to calculate and predict survival for 30 days and up to 3 years. Cox proportional modeling was used to determine the variables associated with mortality. Results. Of included 684 lung transplants performed at the Houston Methodist Hospital between January 2009 and December 2015, 49 were lung ReTX. Median age of primary lung transplant (non-ReTX) and ReTx recipients was 62 and 49 years, respectively. Chronic graft rejection in the form of restrictive chronic lung allograft dysfunction and bronchiolitis obliterans syndrome was the main indications for ReTX. Compared with non-ReTX patients, ReTX patients had higher median lung allocation score (46.2 vs 37.0, respectively) and higher mortality after 6 months posttransplant. ReTX, older age, female sex, hospitalization 15 days or longer, estimated glomerular filtration rate less than 60, 6-minute walk distance less than 400 ft, and donor/recipient height ratio less than 1 were significantly associated with decreased 1-year patient and graft survival. Chronic graft rejection was still the major cause of death in the long-term follow-up recipients. Conclusions. Our findings suggested that lung ReTX recipients have poor long-term survival outcomes. Lung ReTX should only be offered to carefully selected patients.

Transplantation is often the only choice many patients have when suffering from end-stage organ failure. Although the quality of life improves after transplantation, challenges, such as organ shortages, necessary immunosuppression with associated complications, and chronic graft rejection, limit its wide clinical application. Nanotechnology has emerged in the past 2 decades as a field with the potential to satisfy clinical needs in the area of targeted and sustained drug delivery, noninvasive imaging, and tissue engineering. In this article, we provide an overview of popular nanotechnologies and a summary of the current and potential uses of nanotechnology in cell and organ transplantation.

A 43 year-old female, who underwent bilateral lung transplantation for Eisenmenger syndrome 10 years previously, visited our hospital complaining of progressive severe dyspnea. She was diagnosed as having bronchiolitis obliterans syndrome, which was presumably caused by chronic graft rejection following lung transplantation. Due to the aggravated dyspnea despite medical treatment, she required ventilator care and then she underwent lung retransplantation. We report here on a case of lung retransplantation for treating chronic graft rejection following the previous lung transplantation for the first time in Korea.

Objectives: Pneumonia is an important cause of morbidity and mortality in recipients of solid-organ transplant. We aimed to determine risk factors for development of pneumonia and associated deaths in kidney transplant recipients. Materials and Methods: A retrospective review of medical records was performed for all kidney transplant recipients from December 1988, to April 2011. The diagnosis of community-acquired pneumonia was made from symptoms, clinical findings, and chest radiography. The diagnosis of nosocomial pneumonia was made according to published criteria. Laboratory and serologic tests, radiographic findings, cultures of respiratory specimens, and tissue biopsies were reviewed. Results: In 406 kidney transplant recipients, there were 82 patients (20%) who had 111 episodes of pneumonia, including 49 nosocomial episodes of pneumonia (44%). Bacterial infections were the most common cause (34 episodes [31%]). In multivariate analysis, significant risk factors associated with pneumonia episodes were older age, hypertension, cardiac disease, history of acute graft rejection, and not using everolimus/mycophenolate mofetil/prednisolone protocol. There were 28 episodes that resulted in death (25%), including 20 nosocomial episodes (71%). In multivariate analysis, significant risk factors associated with death from pneumonia episodes were antibiotic use in the previous 3 months, high C-reactive protein, and low albumin. Cutoff values for increased risk of death from pneumonia included C-reactive protein > 10 mg/dL and procalcitonin > 8.8 ng/mL. Conclusions: Recipients of kidney transplant may be at risk for pneumonia and associated death. Nosocomial pulmonary infections may be associated with marked morbidity and mortality in kidney transplant recipients.

Since the first studies in immunology, there has been a clear need to understand how, under normal conditions, the immune system tolerates its own antigens and attacks some foreign antigens that it perceives as potentially dangerous and how, in certain circumstances, the loss of tolerance triggers autoimmune diseases. It has been over half a century since Billingham, Brent and Medawar demonstrated, in an experimental model, the mechanisms involved in the development of immunological tolerance. Since then transplant immunologists have intensively investigated the mechanisms involved in maintaining tolerance, in the hope of avoiding the complications of non-specific immunosuppression, as well as the prevention of chronic rejection. An important characteristic was observed by Medawar, who argued that during transplantation an individual's immune system is tolerant to transplanted tissue, maintaining the response to other antigens. Recent studies have shown that loss of tolerance to transplantation is associated with a hyper-response to antigens of the transplanted tissue; a problem that has plagued clinical immunologists, who have focused their efforts on developing accurate measurement systems to enable them to measure how an individual could be tolerant to transplant. Attempts to induce tolerance in the individual are based on understanding the basic mechanisms of tolerance, in which there has been significant progress. This growth in knowledge has been in parallel with a better appreciation of the complexity of immune tolerance. In particular, progress has been made in understanding the essential role of tolerogenic dendritic cells (CDS) and the maintenance of tolerance by regulatory T cells. © 2013 Asociación Colombiana de Reumatología. Published by Elsevier España, S.L. All rights reserved.

Cardiac transplantation displays a well established therapeutic procedure for different end-stage heart diseases. Effective immunosuppressive drugs, progress in operative techniques, modern perioperative intensive care, and application of increasingly potent antibiotics in case of postoperative infections led to an improvement in short term outcome of organ transplantation. Nevertheless, achievements in long term transplant results are rare due to rejection of allografts. Chronic graft rejection is the major cause of late transplant failure.

Ischemia reperfusion injury (IRI) is an inevitable clinical consequence in organ transplantation. It can lead to early graft nonfunction and contribute to acute and chronic graft rejection. Advanced molecular biology has revealed the highly complex nature of this phenomenon and few definitive therapies exist. This paper reviews factors involved in the pathophysiology of IRI and potential ways to attenuate it. In recent years, inhaled nitric oxide, carbon monoxide, and hydrogen sulfide have been increasingly explored as plausible novel medical gases that can attenuate IRI via multiple mechanisms, including microvascular vasorelaxation, reduced inflammation, and mitochondrial modulation. Here, we review recent advances in research utilizing inhaled nitric oxide, carbon monoxide, and hydrogen sulfide in animal and human studies of IRI and postulate on its future applications specific to solid organ transplantation.

Chronic rejection currently limits the long-term efficacy of clinical transplantation. Although B cells have recently been shown to play a pivotal role in the induction of alloimmunity and are being targeted in other transplant contexts, the efficacy of preemptive B cell depletion to modulate alloimmunity or attenuate cardiac allograft vasculopathy (CAV) (classic chronic rejection lesions found in transplanted hearts) in a translational model has not previously been described. We report here that the CD20-specific antibody (alphaCD20) rituximab depleted CD20+ B cells in peripheral blood, secondary lymphoid organs, and the graft in cynomolgus monkey recipients of heterotopic cardiac allografts. Furthermore, CD20+ B cell depletion therapy combined with the calcineurin inhibitor cyclosporine A (CsA) prolonged median primary graft survival relative to treatment with alphaCD20 or CsA alone. In animals treated with both alphaCD20 and CsA that achieved efficient B cell depletion, alloantibody production was substantially inhibited and the CAV severity score was markedly reduced. We conclude therefore that efficient preemptive depletion of CD20+ B cells is effective in a preclinical model to modulate pathogenic alloimmunity and to attenuate chronic rejection when used in conjunction with a conventional clinical immunosuppressant. This study suggests that use of this treatment combination may improve the efficacy of transplantation in the clinic.

Mechanical circulatory support has been used to treat graft failure after heart transplantation, but in patients who needed mechanical circulatory support because of chronic rejection, we have suffered from the treatment because its outcome was catastrophic. Multiple organ failure was often caused by the addition of or increase in immunosuppressive medications, and it is known as a cause of the poor outcomes. The CardioWest total artificial heart was implanted for a case of chronic heart transplant rejection to enable complete withdrawal of immunosuppressive medication. The patient underwent re-heart transplantation, with a good result. This is a new therapeutic technique for chronic graft rejection.

Acute rejection episodes have been cited as a major immunological risk factor for the development of chronic rejection. To examine the influence of a single rejection event on ultimate graft outcome, acutely rejection rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time. Early structural changes (days 3 and 4) were completely reversible, while signs of chronic rejection did become obvious during the long-term follow up. More advanced deteriorated grafts (days 5 and 7) were irreversibly damaged and the rats died shortly after retransplantation. Those results indicate the critical impact of acute rejection episodes on chronic graft rejection. Immediate and aggressive treatment of acute rejection episodes may remove this event as a risk factor for late deteriorating changes.

Four patients underwent liver transplantation in the Cambridge/King's College Hospital programme for malignant primary and secondary apudomas, secreting various peptide hormones and uncontrollable by standard treatment techniques. After transplantation all patients had excellent symptomatic relief and specific peptide hormone levels fell to normal ranges. Two patients remain alive and well after 38 and 22 months, the latter with recurrence of slight tumour-related symptoms and elevation of the specific secretory product. The other two patients died from chronic graft rejection 7 and 8 months after transplantation.