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European Journal of Clinical... Jun 2020Tocilizumab, a monoclonal antibody directed against the IL-6 receptor, might block detrimental effects of IL-6 on transplantation. IL-6 plays a considerable role in... (Review)
Review
PURPOSE
Tocilizumab, a monoclonal antibody directed against the IL-6 receptor, might block detrimental effects of IL-6 on transplantation. IL-6 plays a considerable role in cytokine storm after stem cell transplantation as well as graft versus host disease, and it has also been shown to be involved in solid organ allograft rejection; therefore, tocilizumab is expected to promote graft survival. Nonetheless, due to the small number of studies and disparate methods of drug administration and outcome evaluation, for which types of transplantation, at which stages, and to what extent tocilizumab could be applied remains to be defined.
METHODS
The Pubmed, SCOPUS and Google Scholar search engines were used to collect data. The keywords were determined by Pubmed MeSH. No time limitation was set and all types of articles were allowed. RESULTS: According to the potential of Tocilozumab in controlling both cellular and humoral immunity it could be considered as a promising agent in tolerance induction; however, blocking IL-6 signaling might result in augmented infection rate in recipients.
CONCLUSION
The need for providing effective and safe immunosuppressive agents to protect transplanted cells and organs against allo-reactivity urges the collection and discussion of all available findings about inhibition of determining immune components including cytokines; herein, we have summarized the clinical consequences of blocking IL-6 by tocilizumab in stem cell and solid organ transplantations.
Topics: Antibodies, Monoclonal, Humanized; Graft Rejection; Graft Survival; Graft vs Host Disease; Humans; Immunosuppressive Agents; Organ Transplantation; Receptors, Interleukin-6
PubMed: 32266480
DOI: 10.1007/s00228-020-02864-6 -
Mechanisms of Ageing and Development Dec 2021Older organs provide a substantial unrealized potential with the capacity to close the gap between demand and supply in organ transplantation. The potential of... (Review)
Review
Older organs provide a substantial unrealized potential with the capacity to close the gap between demand and supply in organ transplantation. The potential of senolytics in improving age-related conditions has been shown in various experimental studies and early clinical trials. Those encouraging data may also be of relevance for transplantation. As age-differences between donor and recipients are not uncommon, aging may be accelerated in recipients when transplanting older organs; young organs may, at least in theory, have the potential to 'rejuvenate' old recipients. Here, we review the relevance of senescent cells and the effects of senolytics on organ quality, alloimmune responses and outcomes in solid organ transplantation. This article is part of the Special Issue - Senolytics - Edited by Joao Passos and Diana Jurk.
Topics: Aging, Premature; Cellular Senescence; Humans; Organ Transplantation; Senotherapeutics; Tissue Survival
PubMed: 34606875
DOI: 10.1016/j.mad.2021.111582 -
Current Opinion in Infectious Diseases Aug 2022This review summarizes the impact of coronavirus disease 2019 (COVID-19) on solid organ transplantation and the most recent data pertinent to disease course and outcomes... (Review)
Review
PURPOSE OF REVIEW
This review summarizes the impact of coronavirus disease 2019 (COVID-19) on solid organ transplantation and the most recent data pertinent to disease course and outcomes in this patient population.
RECENT FINDINGS
The COVID-19 pandemic negatively impacted solid organ transplantation with decreased transplant rates in 2020 but improved in 2021, albeit not entirely to prepandemic levels. Mortality rates of COVID-19 in this patient population continued to be higher, although have improved with more available therapeutic options and vaccination. Immunosuppressed patients were found to require additional vaccine doses given blunted response and continue to be more vulnerable to the infection. Data on immunosuppression alteration when patients have COVID-19 are not available and is an area of ongoing research. Significant interaction with the metabolism of immunosuppression limits the use of some of the new antiviral therapies in patients with organ transplants. Finally, many logistical challenges continue to face the transplantation discipline, especially with pretransplant vaccine hesitancy, however acceptance of organs from donor who had COVID-19 recent infection or died from the infection is increasing.
SUMMARY
Immunosuppressed solid organ transplant recipients continue to be vulnerable to COVID-19 infection with a blunted response to the available vaccines and will likely remain more susceptible to infection.
Topics: COVID-19; Humans; Organ Transplantation; Pandemics; SARS-CoV-2; Transplant Recipients
PubMed: 35849518
DOI: 10.1097/QCO.0000000000000852 -
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 -
Gastroenterology Clinics of North... Dec 2019"The intestinal transplantation is reserved for patients with life-threatening complications of permanent intestinal failure or underlying gastrointestinal disease. The... (Review)
Review
"The intestinal transplantation is reserved for patients with life-threatening complications of permanent intestinal failure or underlying gastrointestinal disease. The choice of the allograft for a particular patient depends on several factors and the presence of concurrent organ failure, and availability of the donor organs, and specialized care. Combined liver and intestinal transplant allows for patients who have parenteral nutrition-associated liver disease a possibility of improved quality of life and nutrition as well as survival. Intestinal transplantation has made giant strides over the past few decades to the present era where current graft survivals are comparable with other solid organ transplants."
Topics: Abdominal Wall; Allografts; Humans; Intestines; Liver Transplantation; Malabsorption Syndromes; Parenteral Nutrition; Pseudomyxoma Peritonei; Quality of Life; Viscera
PubMed: 31668184
DOI: 10.1016/j.gtc.2019.08.010 -
Transplantation Sep 2019Single-cell RNA sequencing (scRNA-seq) allows the measurement of transcriptomes from individual cells providing new insights into complex biological systems. scRNA-seq... (Review)
Review
Single-cell RNA sequencing (scRNA-seq) allows the measurement of transcriptomes from individual cells providing new insights into complex biological systems. scRNA-seq has enabled the identification of rare cell types, new cell states, and intercellular communication networks that may be masked by traditional bulk transcriptional profiling. Researchers are increasingly using scRNA-seq to comprehensively characterize complex organs in health and disease. The diversity of immune cell types, some present at low frequency, in a transplanted organ undergoing rejection makes scRNA-seq ideally suited to characterize transplant pathologies because it can quantify subtle transcriptional differences between rare cell types. In this review, we discuss single-cell sequencing methods and their application in transplantation to date, current challenges, and future directions. We believe that the remarkably rapid pace of technological development in this field makes it likely that single-cell technologies such as scRNA-seq will have an impact on clinical transplantation within a decade.
Topics: Animals; Gene Expression Regulation; Gene Regulatory Networks; Humans; Organ Transplantation; Predictive Value of Tests; RNA-Seq; Risk Factors; Signal Transduction; Single-Cell Analysis; Transcriptome; Treatment Outcome
PubMed: 30946217
DOI: 10.1097/TP.0000000000002725 -
Transplantation Aug 2021There are a variety of definitions and criteria used in clinical practice to define frailty. In the absence of a gold-standard definition, frailty has been operationally... (Review)
Review
There are a variety of definitions and criteria used in clinical practice to define frailty. In the absence of a gold-standard definition, frailty has been operationally defined as meeting 3 out of 5 phenotypic criteria indicating compromised function: low grip strength, low energy, slowed walking speed, low physical activity, and unintentional weight loss. Frailty is a common problem in solid organ transplant candidates who are in the process of being listed for a transplant, as well as after transplantation. Patients with diabetes or chronic kidney disease (CKD) are known to be at increased risk of being frail. As pancreas transplantation is exclusively performed among patients with diabetes and the majority of them also have CKD, pancreas transplant candidates and recipients are at high risk of being frail. Sarcopenia, fatigue, low walking speed, low physical activity, and unintentional weight loss, which are some of the phenotypes of frailty, are very prevalent in this population. In various solid organs, frail patients are less likely to be listed or transplanted and have high waitlist mortality. Even after a transplant, they have increased risk of prolonged hospitalization, readmission, and delayed graft function. Given the negative impact of frailty on solid organ transplants, we believe that frailty would have a similar or even worse impact on pancreas transplantation. Due to the paucity of data specifically among pancreas transplant recipients, here we include frailty data from patients with CKD, diabetes, and various solid organ transplant recipients.
Topics: Body Mass Index; Exercise; Fatigue; Frailty; Humans; Pancreas Transplantation; Renal Insufficiency, Chronic; Sarcopenia; Walking Speed
PubMed: 33606487
DOI: 10.1097/TP.0000000000003586 -
Transplantation Reviews (Orlando, Fla.) Dec 2022Pigs, or Sus scrofa domestica, are commonly used animal models in translational transplantation research due to their anatomical, physiological, and immunological... (Review)
Review
Pigs, or Sus scrofa domestica, are commonly used animal models in translational transplantation research due to their anatomical, physiological, and immunological similarities to humans. In solid organ transplantation studies, immunosuppressive medications may be administered to pigs to prevent rejection. We provide an overview of the immunosuppressive regimens used in allogeneic solid organ transplantation in pigs, including heart, lung, kidney, bowel and cotransplanted organs and focus on the use of tacrolimus, mycophenolate mofetil, and corticosteroids.
Topics: Animals; Swine; Humans; Immunosuppressive Agents; Tacrolimus; Mycophenolic Acid; Organ Transplantation; Transplantation, Homologous
PubMed: 36054957
DOI: 10.1016/j.trre.2022.100725 -
Handbook of Experimental Pharmacology 2022Corticosteroids have been utilized as mainstay pharmacological intervention for successful organ transplantation since the beginning. Several challenges exist in...
Corticosteroids have been utilized as mainstay pharmacological intervention for successful organ transplantation since the beginning. Several challenges exist in establishing a balance between achieving a tolerant atmosphere in the host immune system while minimizing the long-term impact of steroids on the body. Corticosteroids are used early in all solid organ transplantation but there is wide variability across various organs and centers in the duration of use and protocols of planned steroid wean. The adverse event profile of steroids is exhaustive and across many organ systems.
Topics: Adrenal Cortex Hormones; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Steroids
PubMed: 35156139
DOI: 10.1007/164_2021_567 -
Infectious Disease Clinics of North... Nov 2023The authors summarize recent updates in the prevention and management of cytomegalovirus (CMV) in solid organ transplant (SOT) recipients with a focus on CMV... (Review)
Review
The authors summarize recent updates in the prevention and management of cytomegalovirus (CMV) in solid organ transplant (SOT) recipients with a focus on CMV seronegative recipients of organs from seropositive donors (CMV D+/R-) who are at highest risk of CMV infection and disease. They discuss advantages of preemptive therapy for CMV disease prevention in CMV D+/R- liver transplant recipients, letermovir for CMV prophylaxis, and updates in the development of monoclonal antibodies and vaccines as immune-based preventative strategies. They review the roles of maribavir and virus-specific T cells for management of resistant or refractory CMV infection in SOT recipients.
PubMed: 37989636
DOI: 10.1016/j.idc.2023.10.001