There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction.
Summary The introduction of living donor liver transplantation (LDLT) has been one of the most remarkable steps in the field of liver transplantation (LT), able to significantly expand the scarce donor pool in countries in which the growing demands of organs are not met by the shortage of available cadaveric grafts. Although the benefits of this procedure are enormous, the physical and psychological sacrifice of the donors is immense, and the expectations for a good outcome for themselves, as well as for the recipients, are high. We report a current overview of the latest trends in live liver donation in its different aspects (i.e. donor's selection, evaluation, operation, morbidity, mortality, ethics and psychology). This review is based on our center's personal experience with almost 200 LDLTs and a detailed analysis of the international literature of the last 7 years about this topic. Knowing in detail how to approach to the different aspects of living liver donation may be helpful in further improve donor's safety and even recipient's outcome.
BackgroundDespite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN) remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression.MethodsWe used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total) of kidney transplant patients with biopsy-documented histology.FindingsGene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild) and 63 (moderate/severe) final candidates as CAN markers with predictive accuracy of 80% (mild) and 92% (moderate/severe). Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN.ConclusionsThis study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.
Cholecystectomy is recommended when medically possible for children with underlying medical diseases. Patients with medical disorders that make them a high surgical risk can be followed clinically, realizing that if urgent surgery is necessary, the morbidity is relatively high. Those children with congenital heart disease and gallstones are at a prohibitively high risk for death after urgent cholecystectomy. For these patients, the risk of an elective cholecystectomy may be acceptable when weighed against the high risk of complications from their gallstones.
Summary To report our experience with 17 children who underwent a liver transplantation (LT) for acute liver failure (ALF). All LT procedures (deceased and living donor) were offered. Since 2003 Molecular Adsorbents Recycling System (MARS®) was proposed as bridging procedure. We monitored the perioperative course and the short‐ and long‐term outcomes. All children developed pretransplant hepatic encephalopathy (mostly grades II and III); six needed ventilator support and three haemodialysis. Median PELD/MELD score was 30. MARS® was used in five children with poor pretransplant prognostic factors: all five survived the LT without sequelae. We performed 13 deceased donor LT (seven whole, five split and onr reduced) and four left lateral LDLT. Postoperative complications were observed in 10 children, requiring re‐operation in seven. Two children developed irreversible neurological disorders. After a median follow up of 45 months, 16 children are still alive. About 1‐ and 5‐year cumulative patient survival rates are 94% with a corresponding graft survival of 88% and 81%, respectively. The combination of experienced paediatric ICU management, the application of new liver support devices, and the capacity to offer both living and deceased donor transplant alternatives in a timely fashion represent the best formula to achieve optimal results in children with ALF.
Purpose of review Inadequate knowledge of the benefits, risks and opportunities for living donation is an important, potentially modifiable barrier to living donor transplantation. We assessed the current state of the evidence regarding strategies to increase knowledge, communication and access to living donor transplantation, as reported in peer-reviewed medical literature. Recent Findings Nineteen studies were reviewed, categorized as programs evaluated in randomized controlled trials (8 studies) and programs supported by observational (non-randomized) studies (11 studies). Content extraction demonstrated that comprehensive education about living donation and living donor transplantation involves multiple learners – the transplant candidate, potential living donors, and social support networks – and requires communicating complex information about the risks and benefits of donation, transplantation and alternative therapies to these different audiences. Transplant centers can help transplant patients learn about living donor transplantation through a variety of formats and modalities, including center-based, home-based and remote technology-based education, outreach to dialysis centers, and social media. Evaluation of these strategies and program themes informed a new Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) public education brochure. Summary Increasing transplant candidate knowledge and comfort in talking about living donation and transplantation can reduce educational barriers to pursuit of living donor transplants. Ongoing efforts are needed to develop, refine and disseminate educational programs to help improve transplant access for more patients in need of organ donors.
As the organ shortage continues to grow, the creation of social media communities by transplant hospitals and the public is rapidly expanding to increase the number of living donors. Social media communities are arranged in myriad ways and without standardization, raising concerns about transplant candidates' and potential donors' autonomy and quality of care. Social media communities magnify and modify extant ethical issues in deceased and living donation related to privacy, confidentiality, professionalism, and informed consent, and increase the potential for undue influence and coercion for potential donors and transplant candidates. Currently, no national ethical guidelines have been developed in the United States regarding the use of social media to foster organ transplantation. We provide an ethical framework to guide transplant stakeholders in using social media for public and patient communication about transplantation and living donation, and offer recommendations for transplant clinical practice and future research.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.