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Seminars in Pediatric Surgery Jun 2022The international practice of transplant in the pediatric population is heterogenous. Global trends in pediatric transplant activity are increasing, with diffusion of...
The international practice of transplant in the pediatric population is heterogenous. Global trends in pediatric transplant activity are increasing, with diffusion of transplant activities into developing and emerging economies. There have been impacts of the COVID-19 pandemic which have in the earlier part of the pandemic caused a decrease in the number of transplants. While deceased donor programs are well established in advanced economies, emerging and developing countries rely heavily on live donor programs. Prioritization of organs for children exists in different forms throughout the world. Pediatric transplantation as a sub-specialty is young but growing around the world with a need to train surgeons and physicians in this discipline. Outreach efforts with multi-national and multi-institutional partnerships have enabled resource poor countries to establish new transplant programs for children. Further international collaboration, good quality data collection and audit, prospective research and ongoing mentorship and education are needed to further improve outcomes of all children receiving solid organ transplants.
Topics: COVID-19; Child; Humans; Internationality; Living Donors; Pandemics; Prospective Studies
PubMed: 35725047
DOI: 10.1016/j.sempedsurg.2022.151192 -
Current Opinion in Organ Transplantation Aug 2019Carbapenem-resistant enterobacteriaceae (CRE) are a critical healthcare threat. Infections caused by CRE disproportionately affect transplant patients. Retrospective... (Review)
Review
PURPOSE OF REVIEW
Carbapenem-resistant enterobacteriaceae (CRE) are a critical healthcare threat. Infections caused by CRE disproportionately affect transplant patients. Retrospective case studies suggest that up to 10% of transplant recipients develop a CRE infection. The current literature is reviewed with a particular focus on transplant-specific implications.
RECENT FINDINGS
There are specific risks inherent to transplant recipients that result in an elevated risk for CRE carriage and subsequent infection. Additionally, the manifestations of these infections are dependent on the specific transplant type. The optimal treatment of CRE infections in transplant recipients has not been defined.
SUMMARY
A reduction in the regional community CRE burden can lead to a secondary reduction in their occurrence within vulnerable transplant populations. Therefore, core principles of antibiotic stewardship and infection control within all levels of the healthcare system remains the most effective strategy for addressing the current health crisis. Simultaneously, an integrated approach to risk stratification and an approach to treatment is postulated for management of CRE infection within the solid-organ transplant population.
Topics: Bacterial Proteins; Enterobacteriaceae Infections; Humans; Organ Transplantation; beta-Lactamases
PubMed: 31169529
DOI: 10.1097/MOT.0000000000000664 -
Experimental and Clinical... Aug 2022With the introduction of effective screening strategies, cancers are being diagnosed at earlier stages and cumulative survival rates of patients with cancer are... (Review)
Review
With the introduction of effective screening strategies, cancers are being diagnosed at earlier stages and cumulative survival rates of patients with cancer are increasing. On the other hand, the number of people who would benefit from a solid-organ transplant is also increasing. Continued organ shortages have resulted in evaluations of further potential donors, including patients with cancer. The literature related to donor- derived malignancy transmission is mostly limited to case reports, data registry series, and retrospective studies. According to data from the literature, organs from deceased and living donors with some types of current or past cancers may be safely used for transplant. The risk of cancer transmission must be balanced against the risk of a patient dying or becoming clinically worse during the period of waiting for a transplant on a case-by-case basis. Current transplant protocols are only allowed for patients with central nervous system tumors in Turkey and most other countries. However, some other patients with a history of cancer can be acceptable as organ donors. This review has summarized data from the literature.
Topics: Central Nervous System Neoplasms; Humans; Living Donors; Organ Transplantation; Retrospective Studies; Tissue Donors; Tissue and Organ Procurement; Treatment Outcome
PubMed: 36018022
DOI: 10.6002/ect.DonorSymp.2022.L30 -
International Journal of Molecular... Mar 2022Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition... (Review)
Review
Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition involving hypoxia, metabolic stress, leukocyte extravasation, cellular death (including apoptosis, necrosis and necroptosis) and an activation of immune response. Although the cycle of sterile inflammation during IRI is consistent among different organs, the underlying mechanisms are poorly understood. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be crucial in the implementation of necroptosis. Moreover, apart from "silent" apoptotic death, necrosis also causes sterile inflammation-necroinflammation, which is triggered by various damage-associated molecular patterns (DAMPs). Those DAMPs activate the innate immune system, causing local and systemic inflammatory responses, which can result in graft failure. In this overview we summarize knowledge on mechanisms of sterile inflammation processes during SOT with special focus on necroptosis and IRI and discuss protective strategies.
Topics: Apoptosis; Humans; Inflammation; Necroptosis; Necrosis; Organ Transplantation; Receptor-Interacting Protein Serine-Threonine Kinases; Reperfusion Injury
PubMed: 35409037
DOI: 10.3390/ijms23073677 -
Current Opinion in Infectious Diseases Aug 2019Adenoviruses are an important cause of morbidity and mortality of solid organ transplant patients and remain a clinical challenge with regard to diagnosis and treatment.... (Review)
Review
PURPOSE OF REVIEW
Adenoviruses are an important cause of morbidity and mortality of solid organ transplant patients and remain a clinical challenge with regard to diagnosis and treatment. In this review, we provide an approach to identification and classification of adenovirus infection and disease, highlight risk factors, and outline management options for adenovirus disease in solid organ transplant patients.
RECENT FINDINGS
Additional clinical data and pathologic findings of adenovirus disease in different organs and transplant recipients are known. Unlike hematopoietic cell transplant recipients, adenovirus blood PCR surveillance and preemptive therapy is not supported in solid organ transplantation. Strategies for management of adenovirus disease continue to evolve with newer antivirals, such as brincidofovir and adjunctive immunotherapies, but more studies are needed to support their use.
SUMMARY
Distinguishing between adenovirus infection and disease is an important aspect in adenovirus management as treatment is warranted only in symptomatic solid organ transplant patients. Supportive care and decreasing immunosuppression remain the mainstays of management. Cidofovir remains the antiviral of choice for severe or disseminated disease. Given its significant nephrotoxic effect, administration of probenecid and isotonic saline precidofovir and postcidofovir infusion is recommended.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Antiviral Agents; DNA, Viral; Diagnosis, Differential; Disease Management; Disease Susceptibility; Humans; Immunocompromised Host; Organ Transplantation; Polymerase Chain Reaction; Public Health Surveillance; Risk Factors; Transplant Recipients; Treatment Outcome
PubMed: 31116132
DOI: 10.1097/QCO.0000000000000558 -
Experimental and Clinical... Sep 2022Awareness regarding organ donation has been steadily growing in the Arab world yet is still far from the current demand. A thorough analysis of population behavior... (Observational Study)
Observational Study
OBJECTIVES
Awareness regarding organ donation has been steadily growing in the Arab world yet is still far from the current demand. A thorough analysis of population behavior toward organ donation can improve organ transplant education. Therefore, we designed this study to assess the knowledge, attitude, donation desires, and views on organ donation among adults in Arab countries.
MATERIALS AND METHODS
An observational cross- sectional study approach was used by assessing 1004 adult survey respondents from 22 Arab countries through the snowball sampling technique via social media platforms and emails. A fact sheet was used to collect demographic information, which was followed by a predesigned questionnaire to assess the attitude and willingness of participants toward solid-organ donation.
RESULTS
Results showed that only 17.0% of respondents had willingness to donate in the future, and only 2.0% respondents were already organ donors or registered as organ donors. Respondents indicated that the most acceptable organs to be donated after death were kidneys (57.8%), followed by liver (45.1%) and heart (42.3%). Regarding the type of surgery for living donation, 48.1% of the respondents had no surgery type preference, whereas 12.9% would only agree to laparoscopic intervention. A significant difference (P < .001) was noted among respondents with transplant experience and without experience regarding organ donation willingness. In terms of paired exchange and list exchange donation, 18.0% indicated that they would refuse to donate, 23.0% would accept, and 19.0% would accept if no alternative was available.
CONCLUSIONS
This study highlighted the psychology of the Arab world and factors influencing decisions toward solid-organ donation and transplant. The biggest factor for unwillingness to donate organs was posttransplant health-related risks; almost 50% of respondents were afraid of health complications. A need for awareness and education regarding the importance of organ donation and transplant emerged as common themes in this study.
Topics: Adult; Arab World; Health Knowledge, Attitudes, Practice; Humans; Living Donors; Organ Transplantation; Surveys and Questionnaires; Tissue Donors; Tissue and Organ Procurement; Treatment Outcome
PubMed: 36169103
DOI: 10.6002/ect.2022.0010 -
Transplant Immunology Aug 2023Biological aging is the accumulation of cellular and molecular damage within an individual over time. The biological age of a donor organ is known to influence clinical... (Review)
Review
INTRODUCTION
Biological aging is the accumulation of cellular and molecular damage within an individual over time. The biological age of a donor organ is known to influence clinical outcomes of solid organ transplantation, including delayed graft function and frequency of rejection episodes. While much research has focused on the biological age of donor organs, the recipient's biological age may also influence transplantation outcomes. The aim of this scoping review was to identify and provide an overview of the existing evidence regarding biological aging in solid organ transplant recipients and the impact on patient outcomes post-transplant.
METHODS
Literature searches were carried out on PubMed, Web of Science, Google Scholar, Embase and TRIP using the phrases 'solid organ transplant', 'cell senescence', 'cell aging' and 'outcomes', using boolean 'and/or' phrases and MeSH terms. Duplicates were removed and abstracts were reviewed by two independent reviewers. Full papers were then screened for inclusion by two reviewers. Data extraction was carried out using a standardised proforma agreed on prior to starting.
RESULTS
32 studies, including data on a total of 7760 patients, were identified for inclusion in this review; 23 relating to kidney transplant recipients, three to liver transplant, five to lung transplant and one to heart transplantation. A wide range of biomarkers of biological aging have been assessed in kidney transplant recipients, whereas studies of liver, lung and heart transplant have predominantly assessed recipient telomere length. The most robust associations with clinical outcomes are observed in kidney transplant recipients, possibly influenced by the larger number of studies and the use of a wider range of biomarkers of biological aging. In kidney transplant recipients reduced thymic function and accumulation of terminally differentiated T cell populations was associated with reduced risk of acute rejection but increased risk of infection and mortality.
CONCLUSION
Studies to date on biological aging in transplant recipients have been heavily biased to kidney transplant recipients. The results from these studies suggest recipient biological age can influence clinical outcomes and future research is needed to prioritise robust biomarkers of biological aging in transplant recipients.
Topics: Humans; Organ Transplantation; Heart Transplantation; Liver Transplantation; Lung Transplantation; Transplant Recipients; Aging; Graft Rejection
PubMed: 37182719
DOI: 10.1016/j.trim.2023.101851 -
The Chinese Journal of Physiology 2023In traditional Chinese medicine (TCM), the liver is the "general organ" that is responsible for governing/maintaining the free flow of qi over the entire body and... (Review)
Review
In traditional Chinese medicine (TCM), the liver is the "general organ" that is responsible for governing/maintaining the free flow of qi over the entire body and storing blood. According to the classic five elements theory, zang-xiang theory, yin-yang theory, meridians and collaterals theory, and the five-viscera correlation theory, the liver has essential relationships with many extrahepatic organs or tissues, such as the mother-child relationships between the liver and the heart, and the yin-yang and exterior-interior relationships between the liver and the gallbladder. The influences of the liver to the extrahepatic organs or tissues have been well-established when treating the extrahepatic diseases from the perspective of modulating the liver by using the ancient classic prescriptions of TCM and the acupuncture and moxibustion. In modern medicine, as the largest solid organ in the human body, the liver has the typical functions of filtration and storage of blood; metabolism of carbohydrates, fats, proteins, hormones, and foreign chemicals; formation of bile; storage of vitamins and iron; and formation of coagulation factors. The liver also has essential endocrine function, and acts as an immunological organ due to containing the resident immune cells. In the perspective of modern human anatomy, physiology, and pathophysiology, the liver has the organ interactions with the extrahepatic organs or tissues, for example, the gut, pancreas, adipose, skeletal muscle, heart, lung, kidney, brain, spleen, eyes, skin, bone, and sexual organs, through the circulation (including hemodynamics, redox signals, hepatokines, metabolites, and the translocation of microbiota or its products, such as endotoxins), the neural signals, or other forms of pathogenic factors, under normal or diseases status. The organ interactions centered on the liver not only influence the homeostasis of these indicated organs or tissues, but also contribute to the pathogenesis of cardiometabolic diseases (including obesity, type 2 diabetes mellitus, metabolic [dysfunction]-associated fatty liver diseases, and cardio-cerebrovascular diseases), pulmonary diseases, hyperuricemia and gout, chronic kidney disease, and male and female sexual dysfunction. Therefore, based on TCM and modern medicine, the liver has the bidirectional interaction with the extrahepatic organ or tissue, and this established bidirectional interaction system may further interact with another one or more extrahepatic organs/tissues, thus depicting a complex "pan-hepatic network" model. The pan-hepatic network acts as one of the essential mechanisms of homeostasis and the pathogenesis of diseases.
Topics: Male; Female; Humans; Medicine, Chinese Traditional; Diabetes Mellitus, Type 2; Yin-Yang; Liver; Kidney
PubMed: 38149555
DOI: 10.4103/cjop.CJOP-D-22-00131 -
Frontiers in Immunology 2020Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored... (Review)
Review
Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.
Topics: Animals; Humans; Immunosuppression Therapy; Mesenchymal Stem Cell Transplantation; Organ Transplantation; Transplantation Tolerance
PubMed: 33643298
DOI: 10.3389/fimmu.2020.618243 -
Trends in Molecular Medicine Jun 2021Advances in allogeneic transplantation of solid organs and tissues depend on our understanding of mechanisms that mediate the prevention of graft rejection. For the past... (Review)
Review
Advances in allogeneic transplantation of solid organs and tissues depend on our understanding of mechanisms that mediate the prevention of graft rejection. For the past decades, clinical practice has established guidelines to prevent allograft rejection, which mostly rely on the intake of nontargeted immunosuppressants as the gold standard. However, such lifelong regimens have been reported to trigger severe morbidities and commonly fail in preventing late allograft loss. In this review, the biology of allogeneic rejection and self-tolerance is analyzed, as well as the mechanisms of cellular-based therapeutics driving suppression and/or tolerance. Bioinspired engineering strategies that take advantage of cells, biomaterials, or combinations thereof to prevent allograft rejection are addressed, as well as biological mechanisms that drive their efficacy.
Topics: Animals; Graft Rejection; Graft Survival; Hematopoietic Stem Cell Transplantation; Humans; Organ Transplantation; Transplantation Tolerance; Transplantation, Homologous
PubMed: 33865718
DOI: 10.1016/j.molmed.2021.03.005