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Journal of Thrombosis and Haemostasis :... Jun 2015There has been extraordinary progress over the last half-century in the field of medical transplantation in which tissue, organs, or body parts from one human are placed... (Review)
Review
There has been extraordinary progress over the last half-century in the field of medical transplantation in which tissue, organs, or body parts from one human are placed into another. Solid organ transplants have allowed thousands of children with otherwise devastating inherited or acquired disorders to survive. Depending upon the clinical situation, there are many specific peri-transplant issues that must be carefully addressed to optimize outcomes. Although surgical, immunologic, and infectious concerns are usually in the forefront, important aspects regarding hemostasis frequently arise. The number of solid organs that can be successfully transplanted in children has expanded over the last decades and includes kidney, liver, heart, lung, intestine, pancreas, and thymus. Bleeding complications may occur in the setting of organ failure prior to transplantation, during the surgical procedure, or in the post-transplant setting, and can results in significant morbidity. This report will focus on preventing and managing non-surgical-related bleeding complications in children undergoing liver, heart, kidney transplantation, in whom there are often unique aspects of coagulation to be considered.
Topics: Adolescent; Age Factors; Blood Coagulation; Blood Coagulation Disorders; Child; Child, Preschool; Coagulants; Heart Transplantation; Hemorrhage; Humans; Infant; Kidney Transplantation; Liver Transplantation; Risk Factors; Treatment Outcome
PubMed: 26149048
DOI: 10.1111/jth.12913 -
Virulence Apr 2016Solid-organ transplantation (SOT) has become the preferred strategy to treat a number of end-stage organ disease, because a continuous improvement in survival and... (Review)
Review
Solid-organ transplantation (SOT) has become the preferred strategy to treat a number of end-stage organ disease, because a continuous improvement in survival and quality of life. While preventive strategies has decreased the risk for classical opportunistic infections (such as viral, fungal and parasite infections), bacterial infections, and particularly bloodstream infections (BSIs) remain the most common and life-threatening complications in SOT recipients. The source of BSI after transplant depends on the type of transplantation, being urinary tract infection, pneumonia, and intraabdominal infections the most common infections occurring after kidney, lung and liver transplantation, respectively. The risk for candidemia is higher in abdominal-organ than in thoracic-organ transplantation. Currently, the increasing prevalence of multi-drug resistant (MDR) Gram-negative pathogens, such as extended-spectrum betalactamase-producing Enterobacteriaciae and carbapenem-resistant Klebsiella pneumoniae, is causing particular concerns in SOT recipients, a population which presents several risk factors for developing infections due to MDR organisms. The application of strict preventive policies to reduce the incidence of post transplant BSIs and to control the spread of MDR organisms, including the implementation of specific stewardship programs to avoid the overuse of antibiotics and antifungal drugs, are essential steps to reduce the impact of post transplant infections on allograft and patient outcomes.
Topics: Anti-Bacterial Agents; Bacteremia; Candidemia; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Humans; Klebsiella pneumoniae; Opportunistic Infections; Organ Transplantation; Pneumonia; Postoperative Complications; Quality of Life; Risk Factors; Urinary Tract Infections
PubMed: 26766415
DOI: 10.1080/21505594.2016.1139279 -
Korean Journal of Transplantation Dec 2023Due to a critical organ shortage, pig organs are being explored for use in transplantation. Differences between species, particularly in cell surface glycans, can... (Review)
Review
Due to a critical organ shortage, pig organs are being explored for use in transplantation. Differences between species, particularly in cell surface glycans, can trigger elevated immune responses in xenotransplantation. To mitigate the risk of hyperacute rejection, genetically modified pigs have been developed that lack certain glycans and express human complement inhibitors. Nevertheless, organs from these pigs may still provoke stronger inflammatory and innate immune reactions than allotransplants. Dysregulation of coagulation and persistent inflammation remain obstacles in the transplantation of pig organs into primates. Regulatory macrophages (Mregs), known for their anti-inflammatory properties, could offer a potential solution. Mregs secrete interleukin 10 and transforming growth factor beta, thereby suppressing immune responses and promoting the development of regulatory T cells. These Mregs are typically induced via the stimulation of monocytes or macrophages with macrophage colony-stimulating factor and interferon gamma, and they conspicuously express the stable marker dehydrogenase/reductase 9. Consequently, understanding the precise mechanisms governing Mreg generation, stability, and immunomodulation could pave the way for the therapeutic use of Mregs generated . This approach has the potential to reduce the required dosages and durations of anti-inflammatory and immunosuppressive medications in preclinical and clinical settings.
PubMed: 38115165
DOI: 10.4285/kjt.23.0055 -
Transplantation Reviews (Orlando, Fla.) Oct 2016Solid organ transplantation provides lifesaving therapy for patients with end stage organ disease. In order for the transplanted organ to survive, the recipient must... (Review)
Review
Solid organ transplantation provides lifesaving therapy for patients with end stage organ disease. In order for the transplanted organ to survive, the recipient must take a lifelong cocktail of immunosuppressive medications that increase the risk for infections, malignancies and drug toxicities. Data from many animal studies have shown that recipients can be made tolerant of their transplanted organ by infusing stem cells, particularly hematopoietic stem cells, prior to the transplant. The animal data have been translated into humans and now several clinical trials have demonstrated that infusion of hematopoietic stem cells, along with specialized conditioning regimens, can permit solid organ allograft survival without immunosuppressive medications. This important therapeutic advance has been made possible by understanding the immunologic mechanisms by which stem cells modify the host immune system, although it must be cautioned that the conditioning regimens are often severe and associated with significant morbidity. This review discusses the role of hematopoietic stem cells in solid organ transplantation, provides an understanding of how these stem cells modify the host immune system and describes how newer information about adaptive and innate immunity might lead to improvements in the use of hematopoietic stem cells to induce tolerance to transplanted organs.
Topics: Animals; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immune Tolerance; Immunity, Innate; Organ Transplantation; Transplantation, Homologous
PubMed: 27553809
DOI: 10.1016/j.trre.2016.07.005 -
Journal of Hepatology Oct 2022The COVID-19 pandemic has significantly changed organ donation and transplantation worldwide. Since the beginning of the pandemic, the uncertainty regarding the... (Review)
Review
The COVID-19 pandemic has significantly changed organ donation and transplantation worldwide. Since the beginning of the pandemic, the uncertainty regarding the potential route of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created tremendous pressures on transplantation communities, and international organisations have advised against using organs from deceased donors who have tested positive for SARS-CoV-2. The possibility of SARS-CoV-2 transmission through organ donation has only been reported for lung transplantation; hence, based on current experience, transplantation of non-lung organs from donors with active SARS-CoV-2 infection has been considered possible and safe, at least over short-term follow-up. As the evolving outbreak of SARS-CoV-2 continues, alongside the presence of vaccines and new treatment options, clinicians should consider transplanting organs from deceased donors with active SARS-CoV-2 infection to recipients with limited opportunities for transplantation and those with specific natural or vaccine-induced immunity. This article proffers an expert opinion on the use of organs from deceased donors with resolved or active SARS-CoV-2 infection in the absence of more definitive data and standardised acceptance patterns.
Topics: COVID-19; Humans; Organ Transplantation; Pandemics; SARS-CoV-2; Tissue Donors; Tissue and Organ Procurement
PubMed: 35798131
DOI: 10.1016/j.jhep.2022.06.021 -
Chemical Reviews Oct 2020The field of tissue engineering has advanced over the past decade, but the largest impact on human health should be achieved with the transition of engineered solid... (Review)
Review
The field of tissue engineering has advanced over the past decade, but the largest impact on human health should be achieved with the transition of engineered solid organs to the clinic. The number of patients suffering from solid organ disease continues to increase, with over 100 000 patients on the U.S. national waitlist and approximately 730 000 deaths in the United States resulting from end-stage organ disease annually. While flat, tubular, and hollow nontubular engineered organs have already been implanted in patients, in vitro formation of a fully functional solid organ at a translatable scale has not yet been achieved. Thus, one major goal is to bioengineer complex, solid organs for transplantation, composed of patient-specific cells. Among the myriad of approaches attempted to engineer solid organs, 3D bioprinting offers unmatched potential. This review highlights the structural complexity which must be engineered at nano-, micro-, and mesostructural scales to enable organ function. We showcase key advances in bioprinting solid organs with complex vascular networks and functioning microstructures, advances in biomaterials science that have enabled this progress, the regulatory hurdles the field has yet to overcome, and cutting edge technologies that bring us closer to the promise of engineered solid organs.
Topics: Bioprinting; Humans; Printing, Three-Dimensional; Tissue Engineering
PubMed: 32885956
DOI: 10.1021/acs.chemrev.0c00145 -
The Cochrane Database of Systematic... Sep 2022Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and... (Review)
Review
BACKGROUND
Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and post-transplant recovery, immunosuppressive medications are often accompanied by a high prevalence of gastrointestinal (GI) symptoms and side effects. Apart from GI side effects, long-term exposure to immunosuppressive medications has seen an increase in drug-related morbidities such as diabetes mellitus, hyperlipidaemia, hypertension, and malignancy. Non-adherence to immunosuppression can lead to an increased risk of graft failure. Recent research has indicated that any microbial imbalances (otherwise known as gut dysbiosis or leaky gut) may be associated with cardiometabolic diseases in the long term. Current evidence suggests a link between the gut microbiome and the production of putative uraemic toxins, increased gut permeability, and transmural movement of bacteria and endotoxins and inflammation. Early observational and intervention studies have been investigating food-intake patterns, various synbiotic interventions (antibiotics, prebiotics, or probiotics), and faecal transplants to measure their effects on microbiota in treating cardiometabolic diseases. It is believed high doses of synbiotics, prebiotics and probiotics are able to modify and improve dysbiosis of gut micro-organisms by altering the population of the micro-organisms. With the right balance in the gut flora, a primary benefit is believed to be the suppression of pathogens through immunostimulation and gut barrier enhancement (less permeability of the gut).
OBJECTIVES
To assess the benefits and harms of synbiotics, prebiotics, and probiotics for recipients of solid organ transplantation.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register up to 9 March 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials measuring and reporting the effects of synbiotics, prebiotics, or probiotics, in any combination and any formulation given to solid organ transplant recipients (any age and setting). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.
DATA COLLECTION AND ANALYSIS
Data extraction was independently carried out by two authors using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Five studies (250 participants) were included in this review. Study participants were adults with a kidney (one study) or liver (four studies) transplant. One study compared a synbiotic to placebo, two studies compared a probiotic to placebo, and two studies compared a synbiotic to a prebiotic. Overall, the quality of the evidence is poor. Most studies were judged to have unclear (or high) risk of bias across most domains. Of the available evidence, meta-analyses undertaken were of limited data from small studies. Across all comparisons, GRADE evaluations for all outcomes were judged to be very low certainty evidence. Very low certainty evidence implies that we are very uncertain about results (not estimable due to lack of data or poor quality). Synbiotics had uncertain effects on the change in microbiota composition (total plasma p-cresol), faecal characteristics, adverse events, kidney function or albumin concentration (1 study, 34 participants) compared to placebo. Probiotics had uncertain effects on GI side effects, infection rates immediately post-transplant, liver function, blood pressure, change in fatty liver, and lipids (1 study, 30 participants) compared to placebo. Synbiotics had uncertain effects on graft health (acute liver rejection) (2 studies, 129 participants: RR 0.73, 95% CI 0.43 to 1.25; 2 studies, 129 participants; I² = 0%), the use of immunosuppression, infection (2 studies, 129 participants: RR 0.18, 95% CI 0.03 to 1.17; I² = 66%), GI function (time to first bowel movement), adverse events (2 studies, 129 participants: RR 0.79, 95% CI 0.40 to 1.59; I² = 20%), serious adverse events (2 studies, 129 participants: RR 1.49, 95% CI 0.42 to 5.36; I² = 81%), death (2 studies, 129 participants), and organ function measures (2 studies; 129 participants) compared to prebiotics.
AUTHORS' CONCLUSIONS
This review highlights the severe lack of high-quality RCTs testing the efficacy of synbiotics, prebiotics or probiotics in solid organ transplant recipients. We have identified significant gaps in the evidence. Despite GI symptoms and postoperative infection being the most common reasons for high antibiotic use in this patient population, along with increased morbidity and the growing antimicrobial resistance, we found very few studies that adequately tested these as alternative treatments. There is currently no evidence to support or refute the use of synbiotics, prebiotics, or probiotics in solid organ transplant recipients, and findings should be viewed with caution. We have identified an area of significant uncertainty about the efficacy of synbiotics, prebiotics, or probiotics in solid organ transplant recipients. Future research in this field requires adequately powered RCTs comparing synbiotics, prebiotics, and probiotics separately and with placebo measuring a standard set of core transplant outcomes. Six studies are currently ongoing (822 proposed participants); therefore, it is possible that findings may change with their inclusion in future updates.
Topics: Adult; Albumins; Anti-Bacterial Agents; Cardiovascular Diseases; Dysbiosis; Endotoxins; Humans; Lipids; Organ Transplantation; Prebiotics; Probiotics; Synbiotics
PubMed: 36126902
DOI: 10.1002/14651858.CD014804.pub2 -
International Journal of Molecular... Dec 2022The gastrointestinal and genitourinary tracts share several similarities. Primarily, these tissues are composed of hollow structures lined by an epithelium through which... (Review)
Review
The gastrointestinal and genitourinary tracts share several similarities. Primarily, these tissues are composed of hollow structures lined by an epithelium through which materials need to flow with the help of peristalsis brought by muscle contraction. In the case of the gastrointestinal tract, solid or liquid food must circulate to be digested and absorbed and the waste products eliminated. In the case of the urinary tract, the urine produced by the kidneys must flow to the bladder, where it is stored until its elimination from the body. Finally, in the case of the vagina, it must allow the evacuation of blood during menstruation, accommodate the male sexual organ during coitus, and is the natural way to birth a child. The present review describes the anatomy, pathologies, and treatments of such organs, emphasizing tissue engineering strategies.
Topics: Child; Female; Male; Humans; Tissue Engineering; Urinary Tract; Urinary Bladder; Gastrointestinal Tract; Vagina
PubMed: 36613452
DOI: 10.3390/ijms24010009 -
Transplant International : Official... Jun 2019Organ preservation and re-conditioning using machine perfusion technologies continue to generate promising results in terms of viability assessment, organ utilization... (Review)
Review
Organ preservation and re-conditioning using machine perfusion technologies continue to generate promising results in terms of viability assessment, organ utilization and improved initial graft function. Here, we summarize the latest findings and study the results of ex-vivo/ex-situ hypothermic (HMP) and normothermic machine perfusion (NMP) in the area of abdominal organ transplantation (kidney, liver, pancreas and intestine). We also consider the potential role of normothermic regional perfusion (NRP) to re-condition donors after circulatory death organs before retrieval. The findings from clinical studies reported to date suggest that machine perfusion will offer real benefits when compared with conventional cold preservation. Several randomized trials are expected to report their findings within the next 2 years which may shed light on the relative merits of different perfusion methods and could indicate which perfusion parameters may be most useful to predict organ quality and viability. Further work is needed to identify composite endpoints that are relevant for transplanted organs that have undergone machine preservation. Multi-centre trials to compare and analyse the combinations of NRP followed by HMP and/or NMP, either directly after organ retrieval using transportable devices or when back-to-base, are needed. The potential applications of machine preservation technology beyond the field of solid organ transplantation are also considered.
Topics: Animals; Graft Survival; Humans; Intestines; Kidney; Kidney Transplantation; Liver; Liver Transplantation; Organ Preservation; Pancreas; Pancreas Transplantation; Perfusion; Tissue Donors
PubMed: 30980772
DOI: 10.1111/tri.13441 -
American Journal of Transplantation :... Sep 2022The COVID-19 pandemic has influenced organ transplantation decision making. Opinions regarding the utilization of coronavirus disease-2019 (COVID-19) donors are mixed....
The COVID-19 pandemic has influenced organ transplantation decision making. Opinions regarding the utilization of coronavirus disease-2019 (COVID-19) donors are mixed. We hypothesize that COVID-19 infection of deceased solid organ transplant donors does not affect recipient survival. All deceased solid organ transplant donors with COVID-19 testing results from March 15, 2020 to September 30, 2021 were identified in the OPTN database. Donors were matched to recipients and stratified by the COVID-19 test result. Outcomes were assessed between groups. COVID-19 test results were available for 17 694 donors; 150 were positive. A total of 269 organs were transplanted from these donors, including 187 kidneys, 57 livers, 18 hearts, 5 kidney-pancreases, and 2 lungs. The median time from COVID-19 testing to organ recovery was 4 days for positive and 3 days for negative donors. Of these, there were 8 graft failures (3.0%) and 5 deaths (1.9%). Survival of patients receiving grafts from COVID-19-positive donors is equivalent to those receiving grafts from COVID-19-negative donors (30-day patient survival = 99.2% COVID-19 positive; 98.6% COVID-19 negative). Solid organ transplantation using deceased donors with positive COVID-19 results does not negatively affect early patient survival, though little information regarding donor COVID-19 organ involvement is known. While transplantation is feasible, more information regarding COVID-19-positive donor selection is needed.
Topics: COVID-19; COVID-19 Testing; Graft Survival; Humans; Organ Transplantation; Pandemics; Tissue Donors; Tissue and Organ Procurement
PubMed: 35822320
DOI: 10.1111/ajt.17145