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Frontiers in Endocrinology 2023Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain...
INTRODUCTION
Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM.
METHODS
We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models.
RESULTS
In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes.
CONCLUSION
The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.
Topics: Adult; Humans; Female; Middle Aged; Male; Cohort Studies; Immunosuppressive Agents; Immunosuppression Therapy; Antilymphocyte Serum; Diabetes Mellitus
PubMed: 37929038
DOI: 10.3389/fendo.2023.1248940 -
Clinical and Experimental Immunology Aug 2017
Topics: Animals; Humans; Immunosuppression Therapy; Immunotherapy, Adoptive; T-Lymphocytes, Regulatory; Transplantation Chimera; Transplantation Immunology; Transplantation Tolerance
PubMed: 28703287
DOI: 10.1111/cei.12994 -
Polish Archives of Internal Medicine Feb 2022
Topics: COVID-19; Humans; Immunosuppression Therapy; Organ Transplantation; Pandemics; SARS-CoV-2
PubMed: 35226438
DOI: 10.20452/pamw.16212 -
Journal of the American College of... Jun 2019
Topics: Heart Transplantation; Humans; Immunosuppression Therapy; Incidence; Neoplasms; Sirolimus
PubMed: 31146813
DOI: 10.1016/j.jacc.2019.03.472 -
Advanced Science (Weinheim,... Oct 2021The deficiency of antigen-specific T cells and the induction of various treatment-induced immunosuppressions still limits the clinical benefit of cancer immunotherapy....
The deficiency of antigen-specific T cells and the induction of various treatment-induced immunosuppressions still limits the clinical benefit of cancer immunotherapy. Although the chemo-immunotherapy adjuvanted with Toll-like receptor 7/8 agonist (TLR 7/8a) induces immunogenic cell death (ICD) and in situ vaccination effect, indoleamine 2,3-dioxygenase (IDO) is also significantly increased in the tumor microenvironment (TME) and tumor-draining lymph node (TDLN), which offsets the activated antitumor immunity. To address the treatment-induced immunosuppression, an assemblable immune modulating suspension (AIMS) containing ICD inducer (paclitaxel) and supra-adjuvant (immune booster; R848 as a TLR 7/8a, immunosuppression reliever; epacadostat as an IDO inhibitor) is suggested and shows that it increases cytotoxic T lymphocytes and relieves the IDO-related immunosuppression (TGF-β, IL-10, myeloid-derived suppressor cells, and regulatory T cells) in both TME and TDLN, by the formation of in situ depot in tumor bed as well as by the efficient migration into TDLN. Local administration of AIMS increases T cell infiltration in both local and distant tumors and significantly inhibits the metastasis of tumors to the lung. Reverting treatment-induced secondary immunosuppression and reshaping "cold tumor" into "hot tumor" by AIMS also increases the response rate of immune checkpoint blockade therapy, which promises a new nanotheranostic strategy in cancer immunotherapy.
Topics: Animals; Breast Neoplasms; Disease Models, Animal; Immunosuppression Therapy; Immunotherapy; Nanomedicine
PubMed: 34363349
DOI: 10.1002/advs.202102043 -
Frontiers in Immunology 2023Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there... (Review)
Review
Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there are a lot of research endeavors focusing on induction of transplantation tolerance, to relieve the burden derived from long-term immunosuppressant uptake. The mesenchymal stromal cells (MSCs) have been demonstrated with potent immunomodulatory capacities and applied as promising cellular therapeutics to promote allograft survival and induce tolerance. As a rich source of adult MSCs, adipose tissue provides additional advantages of easy accessibility and good safety profile. In recent years, the stromal vascular fraction (SVF) isolated from adipose tissues following enzymatic or mechanical processing without culture and expansion has demonstrated immunomodulatory and proangiogenic properties. Furthermore, the secretome of AD-MSCs has been utilized in transplantation field as a potential "cell-free" therapeutics. This article reviews recent studies that employ these adipose-derived therapeutics, including AD-MSCs, SVF, and secretome, in various aspects of organ and tissue allotransplantation. Most reports validate their efficacies in prolonging allograft survival. Specifically, the SVF and secretome have performed well for graft preservation and pretreatment, potentially through their proangiogenic and antioxidative capacities. In contrast, AD-MSCs were suitable for peri-transplantation immunosuppression. The proper combination of AD-MSCs, lymphodepletion and conventional immunosuppressants could consistently induce donor-specific tolerance to vascularized composite allotransplants (VCA). For each type of transplantation, optimizing the choice of therapeutics, timing, dose, and frequency of administration may be required. Future progress in the application of adipose-derived therapeutics to induce transplantation tolerance will be further benefited by continued research into their mechanisms of action and the development of standardized protocols for isolation methodologies, cell culture, and efficacy evaluation.
Topics: Humans; Adult; Transplantation Tolerance; Cells, Cultured; Mesenchymal Stem Cells; Adipose Tissue; Immunosuppression Therapy; Immunosuppressive Agents
PubMed: 37187733
DOI: 10.3389/fimmu.2023.1111813 -
Transplant International : Official... Aug 2011Overall, more than 60 hand/forearm/arm transplantations and 16 face transplantations have been performed in the past 12 years. In the European experience summarized... (Review)
Review
Overall, more than 60 hand/forearm/arm transplantations and 16 face transplantations have been performed in the past 12 years. In the European experience summarized here, three grafts have been lost in response to a vascular thrombosis (n = 1), rejection and incompliance with immunosuppression (n = 1) and death (n = 1). The overall functional and esthetic outcome is very satisfactory, but serious side effects and complications related to immunosuppression are challenges hindering progress in this field. The high levels of immunosuppression, skin rejection, nerve regeneration, donor legislation and the acceptance level need to be addressed to promote growth of this promising new field in transplantation and reconstructive surgery.
Topics: Arm; Europe; Facial Transplantation; Female; Graft Rejection; Hand Transplantation; Humans; Immunosuppression Therapy; Male; Thrombosis; Transplantation Immunology; Transplantation, Homologous; Treatment Outcome
PubMed: 21554424
DOI: 10.1111/j.1432-2277.2011.01261.x -
Cell Communication and Signaling : CCS May 2020Efferocytosis is a physiologic phagocytic clearance of apoptotic cells, which modulates inflammatory responses and the immune environment and subsequently facilitates... (Review)
Review
Efferocytosis is a physiologic phagocytic clearance of apoptotic cells, which modulates inflammatory responses and the immune environment and subsequently facilitates immune escape of cancer cells, thus promoting tumor development and progression. Efferocytosis is an equilibrium formed by perfect coordination among "find-me", "eat-me" and "don't-eat-me" signals. These signaling pathways not only affect the proliferation, invasion, metastasis, and angiogenesis of tumor cells but also regulate adaptive responses and drug resistance to antitumor therapies. Therefore, efferocytosis-related molecules and pathways are potential targets for antitumor therapy. Besides, supplementing conventional chemotherapy, radiotherapy and other immunotherapies with efferocytosis-targeted therapy could enhance the therapeutic efficacy, reduce off-target toxicity, and promote patient outcome. Video abstract.
Topics: Animals; Apoptosis; Disease Progression; Humans; Immunosuppression Therapy; Inflammation; Neoplasms; Phagocytosis; Regulated Cell Death; Tumor Escape
PubMed: 32370748
DOI: 10.1186/s12964-020-00542-9 -
Die Anaesthesiologie Nov 2023Organ transplant patients who must undergo nontransplant surgical interventions can be challenging for the anesthesiologists in charge. On the one hand, it is important... (Review)
Review
Organ transplant patients who must undergo nontransplant surgical interventions can be challenging for the anesthesiologists in charge. On the one hand, it is important to carefully monitor the graft function in the perioperative period with respect to the occurrence of a possible rejection reaction. On the other hand, the ongoing immunosuppression may have to be adapted to the perioperative requirements in terms of the active substance and the route of administration, the resulting increased risk of infection and possible side effects (e.g., myelosuppression, nephrotoxicity and impairment of wound healing) must be included in the perioperative treatment concept. Furthermore, possible persistent comorbidities of the underlying disease and physiological peculiarities as a result of the organ transplantation must be taken into account. Support can be obtained from the expertise of the respective transplantation center.
Topics: Humans; Organ Transplantation; Anesthesia; Immunosuppression Therapy
PubMed: 37874343
DOI: 10.1007/s00101-023-01332-x -
Transplant Infectious Disease : An... Aug 2021"Outcomes of COVID-19 in solid organ transplant (SOT) recipients: a matched cohort study" by Pereira et al found similar 28 day mortality among hospitalized SOT...
"Outcomes of COVID-19 in solid organ transplant (SOT) recipients: a matched cohort study" by Pereira et al found similar 28 day mortality among hospitalized SOT recipients and comorbidity matched controls, shedding light on the relationship between immunosuppression and Covid-19 outcomes.
Topics: COVID-19; Cohort Studies; Humans; Immunosuppression Therapy; Organ Transplantation; SARS-CoV-2; Transplant Recipients
PubMed: 34325492
DOI: 10.1111/tid.13650