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Frontiers in Immunology 2021The complexity of transplant medicine pushes the boundaries of innate, human reasoning. From networks of immune modulators to dynamic pharmacokinetics to variable... (Review)
Review
The complexity of transplant medicine pushes the boundaries of innate, human reasoning. From networks of immune modulators to dynamic pharmacokinetics to variable postoperative graft survival to equitable allocation of scarce organs, machine learning promises to inform clinical decision making by deciphering prodigious amounts of available data. This paper reviews current research describing how algorithms have the potential to augment clinical practice in solid organ transplantation. We provide a general introduction to different machine learning techniques, describing their strengths, limitations, and barriers to clinical implementation. We summarize emerging evidence that recent advances that allow machine learning algorithms to predict acute post-surgical and long-term outcomes, classify biopsy and radiographic data, augment pharmacologic decision making, and accurately represent the complexity of host immune response. Yet, many of these applications exist in pre-clinical form only, supported primarily by evidence of single-center, retrospective studies. Prospective investigation of these technologies has the potential to unlock the potential of machine learning to augment solid organ transplantation clinical care and health care delivery systems.
Topics: Clinical Decision-Making; Data Mining; Decision Support Techniques; Diagnosis, Computer-Assisted; Graft Survival; Humans; Machine Learning; Organ Transplantation; Postoperative Complications; Predictive Value of Tests; Risk Assessment; Risk Factors; Therapy, Computer-Assisted; Time Factors; Treatment Outcome
PubMed: 34603324
DOI: 10.3389/fimmu.2021.739728 -
Diagnostic and Interventional Imaging 2015In multiple injuries, features of bleeding from solid organs mostly involve the liver, spleen and kidneys and may be treated by embolization. The indications and... (Review)
Review
In multiple injuries, features of bleeding from solid organs mostly involve the liver, spleen and kidneys and may be treated by embolization. The indications and techniques for embolization vary between organs and depend on the pathophysiology of the injuries, type of vascularization (anastomotic or terminal) and type of embolization (curative or preventative). Interventional radiologists should have a full understanding of these indications and techniques and management algorithms should be produced within each facility in order to define the respective place of the different treatment options.
Topics: Acute Kidney Injury; Angiography; Cooperative Behavior; Embolization, Therapeutic; Emergency Medical Services; Endovascular Procedures; Hemorrhage; Humans; Interdisciplinary Communication; Liver; Multiple Trauma; Splenic Rupture; Syndrome
PubMed: 26206744
DOI: 10.1016/j.diii.2015.06.004 -
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 -
Blood Advances Mar 2018Sickle-cell disease (SCD) leads to recurrent vaso-occlusive crises, chronic end-organ damage, and resultant physical, psychological, and social disabilities. Although... (Review)
Review
Sickle-cell disease (SCD) leads to recurrent vaso-occlusive crises, chronic end-organ damage, and resultant physical, psychological, and social disabilities. Although hematopoietic stem-cell transplantation (HSCT) is potentially curative for SCD, this procedure is associated with well-recognized morbidity and mortality and thus is ideally offered only to patients at high risk of significant complications. However, it is difficult to identify patients at high risk before significant complications have occurred, and once patients experience significant organ damage, they are considered poor candidates for HSCT. In turn, patients who have experienced long-term organ toxicity from SCD such as renal or liver failure may be candidates for solid-organ transplantation (SOT); however, the transplanted organs are at risk of damage by the original disease. Thus, dual HSCT and organ transplantation could simultaneously replace the failing organ and eliminate the underlying disease process. Advances in HSCT conditioning such as reduced-intensity regimens and alternative donor selection may expand both the feasibility of and potential donor pool for transplantation. This review summarizes the current state of HSCT and organ transplantation in SCD and discusses future directions and the clinical feasibility of dual HSCT/SOT.
Topics: Anemia, Sickle Cell; Hematopoietic Stem Cell Transplantation; Humans; Organ Transplantation; Tissue Donors
PubMed: 29535106
DOI: 10.1182/bloodadvances.2017012500 -
Vaccines Aug 2022Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event... (Review)
Review
BACKGROUND
Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ.
OBJECTIVES
To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection.
METHODS
For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction.
RESULTS
One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male ( = 51, 53.1%) and were of White (Caucasian) ( = 51, 53.7%) and Hispanic ( = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech ( = 31), Moderna ( = 14), Oxford Uni-AstraZeneca ( = 10) and Sinovac-CoronaVac ( = 1)]. The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2-17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5-21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy [graft success ( = 70, 85.4%), graft failure ( = 12, 14.6%), survived ( = 90, 95.7%) and died ( = 4, 4.3%)].
CONCLUSION
The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks.
PubMed: 36016180
DOI: 10.3390/vaccines10081289 -
JAC-antimicrobial Resistance Feb 2024Solid organ transplant (SOT) recipients are at risk of bloodstream infections (BSIs) with MDR organisms (MDROs).
BACKGROUND
Solid organ transplant (SOT) recipients are at risk of bloodstream infections (BSIs) with MDR organisms (MDROs).
OBJECTIVES
To describe the epidemiology of BSI in the year after several types of SOT, as well as the prevalence of MDRO infections in this population.
METHODS
We conducted a single-centre, retrospective study of kidney, liver, heart, and multi-organ transplantation patients. We examined BSIs ≤1 year from SOT and classified MDRO phenotypes for , enterococci, Enterobacterales, and spp. We compared BSI characteristics between SOT types and determined risk factors for 90 day mortality.
RESULTS
We included 2293 patients [1251 (54.6%) kidney, 663 (28.9%) liver, 219 (9.6%) heart and 160 (7.0%) multi-organ transplant]. Overall, 8.5% of patients developed a BSI. BSIs were most common after multi-organ (23.1%) and liver (11.3%) transplantation ( < 0.001). Among 196 patients with BSI, 323 unique isolates were recovered, 147 (45.5%) of which were MDROs. MDROs were most common after liver transplant (53.4%). The most frequent MDROs were VRE (69.8% of enterococci) and ESBL-producing and carbapenem-resistant Enterobacterales (29.2% and 27.2% of Enterobacterales, respectively). Mortality after BSI was 9.7%; VRE was independently associated with mortality (adjusted OR 6.0, 95% CI 1.7-21.3).
CONCLUSIONS
BSI incidence after SOT was 8.5%, with a high proportion of MDROs (45.5%), especially after liver transplantation. These data, in conjunction with local antimicrobial resistance patterns and prescribing practices, may help guide empirical antimicrobial selection and stewardship practices after SOT.
PubMed: 38213312
DOI: 10.1093/jacamr/dlad158 -
Seminars in Nephrology Jul 2022Despite the effectiveness of solid organ transplantation, progress to close the gap between donor organs and demand remains slow. An organ shortage increases the waiting... (Review)
Review
Despite the effectiveness of solid organ transplantation, progress to close the gap between donor organs and demand remains slow. An organ shortage increases the waiting time for transplant and involves significant costs including patient morbidity and mortality. Against the background of a low deceased organ donation rate, this article discusses the option of introducing incentives and removing disincentives to deceased organ donation. Perspectives from ethics, general public opinion, and the health care profession are examined to ensure a comprehensive appraisal and illustrate different facets of opinion on this complex area. Special cultural and psychosocial considerations in Asia, including the family based consent model, are discussed.
Topics: Humans; Tissue Donors; Motivation; Tissue and Organ Procurement; Organ Transplantation; Attitude
PubMed: 36577641
DOI: 10.1016/j.semnephrol.2022.07.002 -
Biomedicine & Pharmacotherapy =... Aug 2022Fibrosis can occur in various organs, leading to structural destruction, dysfunction, and even organ failure. Hence, organ fibrosis is being actively researched... (Review)
Review
Fibrosis can occur in various organs, leading to structural destruction, dysfunction, and even organ failure. Hence, organ fibrosis is being actively researched worldwide. Glucagon-like peptide-1 (GLP-1), a naturally occurring hormone, binds to a G-protein-coupled receptor widely distributed in the pancreas, kidney, lung, heart, gastrointestinal tract, and other organs. Synthetic GLP-1 analogs can be used as GLP-1 receptor agonists (GLP-1RAs) for treating diabetes mellitus. In recent years, GLP-1RAs have also been found to exert anti-inflammatory, antioxidant, and cardiovascular protective effects. GLP-1RAs have also been shown to inhibit fibrosis of solid organs, such as the lung, heart, liver, and kidney. In this review, we discuss the advancements in research on the role of GLP-1RAs in the fibrosis of the heart, lung, liver, kidney, and other organs to obtain new clues for treating organ fibrosis.
Topics: Diabetes Mellitus, Type 2; Fibrosis; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents
PubMed: 35691154
DOI: 10.1016/j.biopha.2022.113236 -
Hepatobiliary Surgery and Nutrition Feb 2019Human leukocyte antigen (HLA) compatibility is very important for successful transplantation of solid organs. In this paper, we focused on the humoral arm of immunity in... (Review)
Review
Human leukocyte antigen (HLA) compatibility is very important for successful transplantation of solid organs. In this paper, we focused on the humoral arm of immunity in the clinical setting of organ transplantation: how HLA antibodies develop, how they can be detected, and what they can do to injure organ transplants. Specifically, we explore the technical perspectives of detecting donor-specific antibodies (DSA) in HLA laboratories, and use real-life clinical cases to explain the principles. Currently there are many tools in our HLA antibody detection toolbox: conventional cytotoxicity cross match, flow cross match, and solid phase assays using beads conjugated with single or multiple HLA antigens. Single antigen bead (SAB) assay is the most sensitive tool available for detecting HLA antibodies and assessing the immunological risk for organ transplant. However, there are intrinsic limitations to solid-phase assays and they are prone to both false negativity and importantly, false positivity. Denatured antigens on single antigen beads might be the most prominent source of false positive reactivity, and may have been underestimated by many HLA experts. No single assay is perfect and therefore multiple methods, including the less sensitive assays, should be employed to determine the clinical relevance of detected HLA antibodies. Thoughtful process, including knowledge of HLA systems, cross reactivity, epitopes, and the patient's clinical history should be employed to correctly interpret data. The clinical team should work closely with HLA laboratories to ensure accurate interpretation of information and optimal management of patients before and after organ transplantation.
PubMed: 30881964
DOI: 10.21037/hbsn.2019.01.01 -
Frontiers in Immunology 2022Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension,... (Review)
Review
Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension, various congenital diseases, idiopathic diseases, traumas, and other end-organ failure. While organ transplants have been monumental in treatment for these conditions, the ten year survival and long-term outcome for these patients is poor. After receiving the transplant, patients receive a multi-drug regimen of immunosuppressants. These drugs include cyclosporine, mTOR inhibitors, corticosteroids, and antibodies. Polyclonal antibodies, which inhibit the recipient's B lymphocytes, and antibodies targeting host cytokine inhibitors which prevent activation of B cells by T cells. Use of these drugs suppresses the immune system and increases the risk of opportunistic pathogen infections, tumors, and further damage to the transplanted organs and vasculature. Many regulatory mechanisms are present in organs to prevent the development of autoimmune disease, and Tregs are central to these mechanisms. Tregs secrete suppressive cytokines such as IL-10, TGF-B, and IL-35 to suppress T cells. Additionally, Tregs can bind to target cells to induce cell cycle arrest and apoptosis and can inhibit induction of IL-2 mRNA in target T cells. Tregs also interact with CTLA-4 and CD80/CD86 on antigen presenting cells (APCs) to prevent their binding to CD28 present on T cells. Due to their various immunosuppressive capabilities, Tregs are being examined as a possible treatment for patients that receive organ transplants to minimize rejection and prevent the negative outcomes. Several studies in which participants were given Tregs after undergoing organ transplantations were reviewed to determine the efficacy and safety of using Tregs in solid organ transplantation to prevent adverse outcomes.
Topics: Autoimmune Diseases; Clinical Studies as Topic; Graft Rejection; Humans; Immunosuppression Therapy; Organ Transplantation; T-Lymphocytes, Regulatory
PubMed: 35185868
DOI: 10.3389/fimmu.2022.746889