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Transplantation Dec 2019Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared... (Review)
Review
Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared to solid organ transplants because of the inherent immune privilege and tolerogenic mechanisms associated with the anterior segment of the eye. However, in a substantial proportion of corneal transplants, the rates of acute rejection and/or graft failure are comparable to or greater than those of the commonly transplanted solid organs. Critically, while registry data and observational studies have helped to identify factors that are associated with increased risk of corneal transplant failure, the extent to which these risk factors operate through enhancing immune-mediated rejection is less clear. In this overview, we summarize a range of important recent clinical and basic insights related to high-risk corneal transplantation, the factors associated with graft failure, and the immunological basis of corneal allograft rejection. We highlight critical research areas from which continued progress is likely to drive improvements in the long-term survival of high-risk corneal transplants. These include further development and clinical testing of predictive risk scores and assays; greater use of multicenter clinical trials to optimize immunosuppressive therapy in high-risk recipients and robust clinical translation of novel, mechanistically-targeted immunomodulatory and regenerative therapies that are emerging from basic science laboratories. We also emphasize the relative lack of knowledge regarding transplant outcomes for infection-related corneal diseases that are common in the developing world and the potential for greater cross-pollination and synergy between corneal and solid organ transplant research communities.
Topics: Allografts; Corneal Diseases; Corneal Transplantation; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Risk Factors
PubMed: 31765363
DOI: 10.1097/TP.0000000000002938 -
Transplantation Dec 2021Transplantation is now performed globally as a routine procedure. However, the increased demand for donor organs and consequent expansion of donor criteria has created... (Review)
Review
Transplantation is now performed globally as a routine procedure. However, the increased demand for donor organs and consequent expansion of donor criteria has created an imperative to maximize the quality of these gains. The goal is to balance preservation of allograft function against patient quality-of-life, despite exposure to long-term immunosuppression. Elimination of immunosuppressive therapy to avoid drug toxicity, with concurrent acceptance of the allograft-so-called operational tolerance-has proven elusive. The lack of recent advances in immunomodulatory drug development, together with advances in immunotherapy in oncology, has prompted interest in cell-based therapies to control the alloimmune response. Extensive experimental work in animals has characterized regulatory immune cell populations that can induce and maintain tolerance, demonstrating that their adoptive transfer can promote donor-specific tolerance. An extension of this large body of work has resulted in protocols for manufacture, as well as early-phase safety and feasibility trials for many regulatory cell types. Despite the excitement generated by early clinical trials in autoimmune diseases and organ transplantation, there is as yet no clinically validated, approved regulatory cell therapy for transplantation. In this review, we summarize recent advances in this field, with a focus on myeloid and mesenchymal cell therapies, including current understanding of the mechanisms of action of regulatory immune cells, and clinical trials in organ transplantation using these cells as therapeutics.
Topics: Animals; Humans; Immune Tolerance; Immunosuppression Therapy; Mesenchymal Stem Cells; Organ Transplantation; Transplantation Tolerance
PubMed: 33756544
DOI: 10.1097/TP.0000000000003765 -
Diagnostics (Basel, Switzerland) Dec 2021Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare....
BACKGROUND
Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare. To close this knowledge gap, this cross-sectional study was initiated to evaluate the extent of solid organ manifestations in newly diagnosed IRD patients, and to present a structured systematic organ screening algorithm.
MATERIALS AND METHODS
The study included 84 patients (63 women, 21 men) with newly diagnosed IRD. None of the patients received any rheumatic therapy. All patients underwent a standardised organ screening programme encompassing a basic screening (including lungs, heart, kidneys, and gastrointestinal tract) and an additional systematic screening (nose and throat, central and peripheral nervous system) on the basis of clinical, laboratory, and immunological findings.
RESULTS
Represented were patients with connective tissue diseases (CTD) (72.6%), small-vessel vasculitis (16.7%), and myositis (10.7%). In total, 39 participants (46.5%) had one or more organ manifestation(s) (one organ, 29.7%; two organs, 10.7%; ≥three organs, 6.0%). The most frequently involved organs were the lungs (34.5%), heart (11.9%), and kidneys (8.3%). Lastly, a diagnostic algorithm for organ manifestation was applied.
CONCLUSION
One-half of the patients presented with a solid organ involvement at initial diagnosis of IRD. Thus, in contrast to what has been described in the literature, organ manifestations were already present in a high proportion of patients at the time of diagnosis of IRD rather than after several years of disease. Therefore, in IRD patients, systematic organ screening is essential for treatment decisions.
PubMed: 35054234
DOI: 10.3390/diagnostics12010067 -
Oxidative Medicine and Cellular... 2015Ischemia-reperfusion (I/R) injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved... (Review)
Review
Ischemia-reperfusion (I/R) injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved situation in clinical practice, especially in the field of solid organ transplantation. Hydrogen sulfide (H2S) is the third gaseous signaling molecule and plays a broad range of physiological and pathophysiological roles in mammals. H2S could protect against I/R injury in many organs and tissues, such as heart, liver, kidney, brain, intestine, stomach, hind-limb, lung, and retina. The goal of this review is to highlight recent findings regarding the role of H2S in I/R injury. In this review, we present the production and metabolism of H2S and further discuss the effect and mechanism of H2S in I/R injury.
Topics: Animals; Humans; Hydrogen Sulfide; Myocardial Reperfusion Injury; Organ Specificity
PubMed: 26064416
DOI: 10.1155/2015/186908 -
World Journal of Nephrology Aug 2014In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances... (Review)
Review
In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances in renal transplant immunology, approximately 40% of recipients will die or lose graft within 10 years. The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve, restore, or replace the renal function. The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney. Due to kidneys peculiar anatomy, extracellular matrix based scaffolds are rational starting point for their regeneration. The perfusion of detergents through the kidney vasculature is an efficient method for delivering decellularizing agents to cells and for removing of cellular material from the tissue. Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems. For an efficient bioengineered kidney, these cells must be attached to the organ and then maturated into the bioractors, which simulates the human body environment. A functional bioengineered kidney is still a big challenge for scientists. In the last ten years we have got many improvements on the field of solid organ regeneration; however, we are still far away from the main target. Currently, regenerative centers worldwide have been striving to find feasible strategies to develop bioengineered kidneys. Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression. The potential of bioengineered organ is to provide a reliable source of organs, which can be refunctionalized and transplanted.
PubMed: 25332894
DOI: 10.5527/wjn.v3.i3.24 -
Journal of Clinical Tuberculosis and... Aug 2016Non-tuberculous mycobacteria are ubiquitous environmental organisms that are now increasingly recognized as important causes of clinical disease in solid organ... (Review)
Review
Non-tuberculous mycobacteria are ubiquitous environmental organisms that are now increasingly recognized as important causes of clinical disease in solid organ transplant recipients. Risk factors of non-tuberculous mycobacteria infection are severe immunologic defects and structural abnormalities. Lung transplant recipients are at higher risk for non-tuberculous mycobacterial disease compared to recipients of other solid organs. The clinical presentation could be skin and soft tissue infection, osteoarticular disease, pleuropulmonary infection, bloodstream (including catheter-associated) infection, lymphadenitis, and disseminated or multi-organ disease. Management of non-tuberculous mycobacteria infection is complex due to the prolonged treatment course with multi-drug regimens that are anticipated to interact with immunosuppressive medications. This review article provides an update on infections due to non-tuberculous mycobacteria after solid organ transplantation, and discusses the epidemiology, risk factors, clinical presentation, and management.
PubMed: 31723683
DOI: 10.1016/j.jctube.2016.04.001 -
Pathogens (Basel, Switzerland) Feb 2024() is a bacterial organism that typically infects the colon, which has had its homeostasis of healthy gut microbiota disrupted by antibiotics or other interventions.... (Review)
Review
() is a bacterial organism that typically infects the colon, which has had its homeostasis of healthy gut microbiota disrupted by antibiotics or other interventions. Patients with kidney transplantation are a group that are susceptible to infection (CDI) and have poorer outcomes with CDI given that they conventionally require long-term immunosuppression to minimize their risk of graft rejection, weakening their responses to infection. Recognizing the risk factors and complex pathophysiological processes that exist between immunosuppression, dysbiosis, and CDI is important when making crucial clinical decisions surrounding the management of this vulnerable patient cohort. Despite the clinical importance of this topic, there are few studies that have evaluated CDI in the context of kidney transplant recipients and other solid organ transplant populations. The current recommendations on CDI management in kidney transplant and solid organ transplant recipients are mostly extrapolated from data relating to CDI management in the general population. We provide a narrative review that discusses the available evidence examining CDI in solid organ transplant recipients, with a particular focus on the kidney transplant recipient, from the epidemiology of CDI, clinical features and implications of CDI, potential risk factors of CDI, and, ultimately, prevention and management strategies for CDI, with the aim of providing areas for future research development in this topic area.
PubMed: 38392878
DOI: 10.3390/pathogens13020140 -
Abdominal Radiology (New York) Jun 2021Infections are the most commonly encountered complications in patients with cancer. The classical signs and symptoms of infections are often not present in this patient... (Review)
Review
Infections are the most commonly encountered complications in patients with cancer. The classical signs and symptoms of infections are often not present in this patient population, which makes the diagnosis more challenging. Host factors play a major role in the development and prognosis of infections in cancer patients; these can be related to the underlying type of malignancy (solid organ versus hematological), tumor burden, anatomic obstruction, altered integrity of barriers (skin or mucosa), treatment-related factors (from chemotherapy, radiation treatment, surgery, interventional procedures, and/or medical device placement) and the degree of immunosuppression. This article reviews common, as well as less common, imaging manifestations of infections and their potential mimics in the abdomen and pelvis in cancer patients and discusses their differentiating features, with the role of imaging in various organs in the abdomen and pelvis taking into consideration relevant clinical background information and the main risk factors.
Topics: Abdomen; Diagnostic Imaging; Humans; Neoplasms; Pelvic Infection; Pelvis
PubMed: 33386914
DOI: 10.1007/s00261-020-02896-7 -
American Journal of Transplantation :... Nov 2017
Topics: Hepacivirus; Hepatitis C; Humans; Organ Transplantation; Tissue Donors; United States
PubMed: 28632974
DOI: 10.1111/ajt.14396 -
World Journal of Transplantation Nov 2021Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate... (Review)
Review
Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate immunity and tissue protective effects. However, some SOT centers are reluctant to administer GCs long-term because of the various related side effects. This review summarizes the advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering "transplantation" and "glucocorticoids". GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients, GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute antibody- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols, to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors, such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells, are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects involving different non-targeted organs/tissues, such as bone, cardiovascular, neuromuscular, skin and gastrointestinal tract, have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.
PubMed: 34868896
DOI: 10.5500/wjt.v11.i11.443