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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 -
Experimental and Clinical... Dec 2021In India, organ donation and transplant activities are managed under the National Organ and Tissue Transplant Organisation, established per the mandate of the...
OBJECTIVES
In India, organ donation and transplant activities are managed under the National Organ and Tissue Transplant Organisation, established per the mandate of the Transplantation of Human Organs and Tissues Act 1994, as stipulated by World Health Organization guidelines.
MATERIALS AND METHODS
The National Organ and Tissue Transplant Organisation reached out to various hospitals and concerned authorities at national, regional, and local levels through E-mails and telephone calls to gather and to analyze 2019 data regarding the World Health Organization-Global Observatory on Donation and Transplantation questionnaire.
RESULTS
In 2019, India had 550 transplant centers registered with state-appropriate authorities and 140 nontransplant organ retrieval centers. Most living donors were kidney donors (8613) or liver donors (1993). Of all solid-organ transplants, most were kidney transplants, followed by liver, heart, lung, and pancreas. There were few heart and pancreas transplants in 2019, with higher percentage of female donors (65.4% and 54.3%, respectively, n = 5633 and 1084). Of transplant procedures, there were more living donor transplants (84%, n = 10 600) than deceased donor transplants (16%, n = 2023). Among all organs, wait lists for kidney transplants were higher than for other organs.
CONCLUSIONS
Reporting on organ donation and transplant of 2019 from the National Organ and Tissue Transplant Organisation, India's national registry, continued in 2020 despite the challenges of COVID-19. India has been submitting organ donation and transplant data at the national level to the Global Observatory on Donation and Transplantation consistently from 2013 to 2019 and is the only country in the World Health Organization South-East Asia Region to have done so, providing information from all states and union territories in India.
Topics: Female; Humans; Living Donors; Male; Organ Transplantation; Tissue Donors; Tissue and Organ Procurement; Treatment Outcome
PubMed: 34763630
DOI: 10.6002/ect.2021.0105 -
Cryobiology Mar 2023Transplantation has substituted dysfunctional organs with healthy organs from donors to significantly lower morbidity and mortality associated with end-stage organ... (Review)
Review
Transplantation has substituted dysfunctional organs with healthy organs from donors to significantly lower morbidity and mortality associated with end-stage organ disease. Since the advent of transplantation, the promise of functional replacement has attracted an exponential mismatch between organ supply and demand. Theoretical proposals to counter the increasing needs have either been to create a source through genetic engineering of porcine donors for xenotransplantation (with more potent immunosuppression protocols) or recreate one's organ in a pig using interspecies blastocyst complementation for exogenic organ transplantation (without immunosuppression). Another promising avenue has been organ banking through cryopreservation for transplantation. Although ice free preservation and acceptable early function following rewarming is critical for success in transplantation, the immunological response that predominantly defines short- and long-term graft survival has failed to captivate attention to date. It is well sorted that thermal and metabolic stress incurred at 4 °C during recovery and reperfusion of organs for clinical transplantation has varying impact on graft survival. Considering the magnitude of cellular imbalance and injury at sub-zero/ultralow temperatures in addition to the chemical toxicity of cryoprotective agents (CPA), it is essential to assess and address the immunological response associated following transplantation to maximize the success of cryopreservation.
Topics: Animals; Swine; Cryopreservation; Kidney; Transplantation, Heterologous; Temperature; Cryoprotective Agents
PubMed: 36640932
DOI: 10.1016/j.cryobiol.2023.01.003 -
Current Opinion in Organ Transplantation Jun 2023Optimizing deceased donor organ utilization is gaining recognition as a topical and important issue, both in the United Kingdom (UK) and globally. This review discusses... (Review)
Review
PURPOSE OF REVIEW
Optimizing deceased donor organ utilization is gaining recognition as a topical and important issue, both in the United Kingdom (UK) and globally. This review discusses pertinent issues in the field of organ utilization, with specific reference to UK data and recent developments within the UK.
RECENT FINDINGS
A multifaceted approach is likely required in order to improve organ utilization. Having a solid evidence-base upon which transplant clinicians and patients on national waiting lists can base decisions regarding organ utilization is imperative in order to bridge gaps in knowledge regarding the optimal use of each donated organ. A better understanding of the risks and benefits of the uses of higher risk organs, along with innovations such as novel machine perfusion technologies, can help clinician decision-making and may ultimately reduce the unnecessary discard of precious deceased donor organs.
SUMMARY
The issues facing the UK with regards to organ utilization are likely to be similar to those in many other developed countries. Discussions around these issues within organ donation and transplantation communities may help facilitate shared learning, lead to improvements in the usage of scarce deceased donor organs, and enable better outcomes for patients waiting for transplants.
Topics: Humans; Tissue and Organ Procurement; Organ Transplantation; Transplants; Perfusion; United Kingdom; Waiting Lists; Tissue Donors
PubMed: 37040628
DOI: 10.1097/MOT.0000000000001071 -
Current Opinion in Organ Transplantation Apr 2020The development and implementation of 'increased risk donor' (IRD) status by the Centers for Disease Control (CDC) was intended to guide patients and providers in... (Review)
Review
PURPOSE OF REVIEW
The development and implementation of 'increased risk donor' (IRD) status by the Centers for Disease Control (CDC) was intended to guide patients and providers in decision making regarding risk of infectious transmission via solid organ transplantation. Several contemporary studies have shown underutilization of these organs. This review summarizes the issues surrounding IRD status as well as recent advances in our understanding of the risks and benefits of increased risk organs and their appropriate utilization.
RECENT FINDINGS
Risk of window-period infection remains exceedingly low, and implementation of nucleic acid testing for HIV and hepatitis C virus (HCV) has resulted in decreasing risk of window-period infection often by an order of magnitude or more. Surgeons remain hesitant to utilize IRD organs. In addition, surgeon assessment of risk by donor behaviour was often discordant with known risks of those behaviours. Studies investigating outcomes of utilization of IRD organs suggest long-term mortality and graft survival is at least equivalent to non-IRD organs. Contemporary results suggest that IRD organs continue to be underutilized, particularly adult kidneys and lungs, with hundreds of wasted organs per year.
SUMMARY
CDC IRD labelling has led to an underutilization of organs for transplantation. The risks associated with acceptance of an IRD organ are inflated by surgeons and patients, and outcomes for patients who undergo transplantation with increased risk organs are similar to or better than those for patients whom accept standard risk organs. The rate of transmission of window-period infection from IRD organs is exceptionally low. The harms regarding the utility of Public Health Service increased risk classification outweigh the benefits for patients in need of transplant.
Topics: Humans; Organ Transplantation; Risk Factors; Tissue Donors
PubMed: 32073497
DOI: 10.1097/MOT.0000000000000735 -
Current Opinion in Organ Transplantation Aug 2019To provide an update on the current landscape of antimicrobial stewardship in solid organ transplant (SOT) recipients. (Review)
Review
PURPOSE OF REVIEW
To provide an update on the current landscape of antimicrobial stewardship in solid organ transplant (SOT) recipients.
RECENT FINDINGS
Constructing personalized antimicrobial prescribing approaches to avoid untoward consequences of antimicrobials while improving outcomes is an emerging and critical aspect of transplant medicine. Stewardship activities encompassing the specialized interests of transplant patients and programs are evolving. New literature evaluating strategies to optimize antimicrobial agent selection, dosing, and duration have been published. Additionally, consensus guidance for certain infectious clinical syndromes is available and should inform institutional clinical practice guidelines. Novel metrics for stewardship-related outcomes in transplantation are desperately needed. Though exciting new molecular diagnostic technologies will likely be pivotal in the care of immunocompromised patients, optimal clinical adaptation and appropriate integration remains unclear. Important studies understanding the behaviors influencing antimicrobial prescribing in organizational transplant cultures are needed to optimize interventions.
SUMMARY
Consequences of antimicrobial use, such as Clostridiodes difficile and infections with multidrug-resistant organisms disproportionately affect SOT recipients and are associated with poor allograft and patient outcomes. Application of ASP interventions tailored to SOT recipients is recommended though further studies are needed to provide guidance for best practice.
Topics: Antimicrobial Stewardship; Humans; Organ Transplantation
PubMed: 31145159
DOI: 10.1097/MOT.0000000000000661 -
Artificial Organs Feb 2022Organ transplantation is the definitive treatment for end-stage solid organ diseases, yet biological and logistical barriers reduce the rate of successful organ... (Review)
Review
Organ transplantation is the definitive treatment for end-stage solid organ diseases, yet biological and logistical barriers reduce the rate of successful organ transplants. As such, there is a need for gene therapy and gene modulation strategies in the organ transplantation setting to prevent rejection, expand the donor pool of available organs, and attenuate ischemia-reperfusion damage. As we are entering an era of "precision medicine," the organ transplant field is becoming equipped with the tools necessary to personalize and optimize organs designed specifically to withstand injurious pathways that occur during transplantation, such that the concept of "designer organs" will be a reality in the near future. In this review, we highlight the recent progress using gene knockout and knock-in strategies used mainly in the context of xenotransplantation. We also discuss advancements in CRISPR-Cas9 gene editing and RNA interference in relation to organ transplantation. Lastly, we discuss the exciting future implications of customized gene therapy in the transplantation setting, and its ability to potentially create a future where organs intended for transplant are personalized to maximize both graft and patient survival.
Topics: Animals; Gene Knock-In Techniques; Gene Knockout Techniques; Genetic Therapy; Graft Rejection; Humans; Organ Preservation; Organ Transplantation; Perfusion; Precision Medicine; RNA Interference; Transplantation, Heterologous
PubMed: 35014719
DOI: 10.1111/aor.14151 -
Radiologic Clinics of North America Sep 2023The availability of effective immunosuppressive medication is primarily responsible for the dramatic improvement in long-term graft survival rates after solid organ... (Review)
Review
The availability of effective immunosuppressive medication is primarily responsible for the dramatic improvement in long-term graft survival rates after solid organ transplantation. The commonly used drugs include monoclonal/polyclonal antibodies, corticosteroids, calcineurin inhibitors (cyclosporine and tacrolimus), antimetabolites, mammalian target of rapamycin, and many novel drugs. Prolonged immunosuppression is accompanied by several well-described potentially life-threatening complications. In addition to drug-related side effects, recipients of solid organs are unavoidably at a higher risk for infections and malignancies. Select infections and malignancies in solid organ transplant patients have distinctive imaging findings, and radiologists play a crucial role in the timely diagnosis and management of these conditions.
Topics: Humans; Immunosuppressive Agents; Organ Transplantation; Immunosuppression Therapy; Neoplasms; Radiologists
PubMed: 37495297
DOI: 10.1016/j.rcl.2023.04.010 -
Transplant Infectious Disease : An... Oct 2022Solid organ transplant (SOT) recipients are challenging populations for antimicrobial stewardship interventions due to a variety of reasons, including immunosuppression,... (Review)
Review
BACKGROUND
Solid organ transplant (SOT) recipients are challenging populations for antimicrobial stewardship interventions due to a variety of reasons, including immunosuppression, consequent risk of opportunistic and donor-derived infections, high rates of infection with multi-drug resistant organisms (MDROs), Clostridioides difficile, and need for prolonged antimicrobial prophylaxis. Despite this, data on stewardship interventions and metrics that address the distinct needs of these patients are limited.
METHODS
We performed a narrative review of the current state of antimicrobial stewardship in SOT recipients, existing interventions and metrics in this population, and considerations for implementation of transplant-specific stewardship programs.
RESULTS
Antimicrobial stewardship metrics are evolving even in the general patient population. Data on metrics applicable to the SOT population are even more limited. Standard process, outcomes, and balancing metrics may not always apply to the SOT population. A successful stewardship program for SOT recipients requires reviewing existing data, applying general stewardship principles, and understanding the nuances of SOT patients.
CONCLUSION
As antimicrobial stewardship interventions are being implemented in SOT recipients; new metrics are needed to assess their impact. In conclusion, SOT patients present a challenging but important opportunity for antimicrobial stewards.
ABBREVIATIONS
SOT, antimicrobial stewardship program, MDRO, Clostridioides difficile infection, Centers for Disease Control and Prevention, Infectious Diseases Society of America, prospective audit and feedback, hematopoietic cell transplant, cytomegalovirus, trimethoprim-sulfamethoxazole, surgical site infections, nucleic acid amplification testing, days of therapy, defined daily dose, and length of stay.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Stewardship; Hematopoietic Stem Cell Transplantation; Humans; Nucleic Acids; Organ Transplantation; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 36254525
DOI: 10.1111/tid.13883 -
Expert Review of Clinical Pharmacology Jan 2020: The introduction of direct-acting antiviral therapy has generated tremendous interest in transplanting organs from HCV-infected donors, an option which has the... (Review)
Review
: The introduction of direct-acting antiviral therapy has generated tremendous interest in transplanting organs from HCV-infected donors, an option which has the potential to lower waiting times for solid organ transplantation (including kidneys). Safe, effective and pangenotypic direct-acting antiviral agents are currently available.: We have identified studies from PubMed, EMBASE, and the Cochrane database to review risks and benefits on solid organ transplantation from HCV-exposed donors in uninfected recipients.: The transmission of HCV with transplantation from anti-HCV positive kidneys without viremia is extremely uncommon whereas recent evidence (five clinical studies, = 94 patients) shows the absence of HCV infection in HCV-naïve recipients who received kidneys from HCV RNA-positive donors and underwent early DAAs. The evidence regarding non-kidney solid organ transplantation from HCV-infected donors is more limited. One report showed the occurrence of dialysis-dependent kidney failure due to glomerulonephritis induced by acute HCV after liver transplant from a NAT-positive donor into an HCV-naïve recipient. Transplantation of kidneys and other solid organs from HCV-viremic donors into uninfected recipients has the potential to become the standard of care resulting in lower waitlist mortality. Further studies are needed urgently to establish clinical practice guidelines on this topic.
Topics: Antiviral Agents; Hepatitis C; Humans; Organ Transplantation; Tissue Donors; Waiting Lists
PubMed: 31786966
DOI: 10.1080/17512433.2020.1697677