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Cells Sep 2023Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its... (Review)
Review
Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its clinical application, including the shortage of organ donations, the quality of donated organs, injury during organ preservation and reperfusion, primary and chronic graft dysfunction, acute and chronic rejection, infection, and carcinogenesis in post-transplantation patients. Acute and chronic inflammation and cell death are two major underlying mechanisms for graft injury. Necroptosis is a type of programmed cell death involved in many diseases and has been studied in the setting of all major solid organ transplants, including the kidney, heart, liver, and lung. It is determined by the underlying donor organ conditions (e.g., age, alcohol consumption, fatty liver, hemorrhage shock, donation after circulatory death, etc.), preservation conditions and reperfusion, and allograft rejection. The specific molecular mechanisms of necroptosis have been uncovered in the organ transplantation setting, and potential targeting drugs have been identified. We hope this review article will promote more clinical research to determine the role of necroptosis and other types of programmed cell death in solid organ transplantation to alleviate the clinical burden of ischemia-reperfusion injury and graft rejection.
PubMed: 37759518
DOI: 10.3390/cells12182296 -
World Journal of Transplantation Sep 2016Diarrhea is a common complication in solid organ transplant (SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria,... (Review)
Review
Diarrhea is a common complication in solid organ transplant (SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria, viruses or parasites. Cryptosporidium usually causes self-limited diarrhea in immunocompetent hosts. Although it is estimated that cryptosporidium is involved in about 12% of cases of infectious diarrhea in developing countries and causes approximately 748000 cases each year in the United States, it is still an under recognized and important cause of infectious diarrhea in SOT recipients. It may run a protracted course with severe diarrhea, fluid and electrolyte depletion and potential for organ failure. Although diagnostic methodologies have improved significantly, allowing for fast and accurate identification of the parasite, treatment of the disease is difficult because antiparasitic drugs have modest activity at best. Current management includes fluid and electrolyte replacement, reduction of immunosuppression and single therapy with Nitazoxanide or combination therapy with Nitazoxanide and other drugs. Future drug and vaccine development may add to the currently poor armamentarium to manage the disease. The current review highlights key epidemiological, diagnostic and management issues in the SOT population.
PubMed: 27683627
DOI: 10.5500/wjt.v6.i3.460 -
Animals : An Open Access Journal From... Jul 2022As an essential component of the skeleton, bone tissue provides solid support for the body and protects vital organs. Bone tissue is a reservoir of calcium, phosphate,... (Review)
Review
As an essential component of the skeleton, bone tissue provides solid support for the body and protects vital organs. Bone tissue is a reservoir of calcium, phosphate, and other ions that can be released or stored in a controlled manner to provide constant concentration in body fluids. Normally, bone development or osteogenesis occurs through two ossification processes (intra-articular and intra-chondral), but the first produces woven bone, which is quickly replaced by stronger lamellar bone. Contrary to commonly held misconceptions, bone is a relatively dynamic organ that undergoes significant turnover compared to other organs in the body. Bone metabolism is a dynamic process that involves simultaneous bone formation and resorption, controlled by numerous factors. Bone metabolism comprises the key actions. Skeletal mass, structure, and quality are accrued and maintained throughout life, and the anabolic and catabolic actions are mostly balanced due to the tight regulation of the activity of osteoblasts and osteoclasts. This activity is also provided by circulating hormones and cytokines. Bone tissue remodeling processes are regulated by various biologically active substances secreted by bone tissue cells, namely RANK, RANKL, MMP-1, MMP-9, or type 1 collagen. Bone-derived factors (BDF) influence bone function and metabolism, and pathophysiological conditions lead to bone dysfunction. This work aims to analyze and evaluate the current literature on various local and systemic factors or immune system interactions that can affect bone metabolism and its impairments.
PubMed: 35953935
DOI: 10.3390/ani12151946 -
ACS Nano Nov 2021Targeted delivery of therapeutics through the use of nanoparticles (NPs) has emerged as a promising method that increases their efficacy and reduces their side effects.... (Review)
Review
Targeted delivery of therapeutics through the use of nanoparticles (NPs) has emerged as a promising method that increases their efficacy and reduces their side effects. NPs can be tailored to localize to selective tissues through conjugation to ligands that bind cell-specific receptors. Although the vast majority of nanodelivery platforms have focused on cancer therapy, efforts have begun to introduce nanotherapeutics to the fields of immunology as well as transplantation. In this review, we provide an overview from a clinician's perspective of current nanotherapeutic strategies to treat solid organ transplants with NPs during the time interval between organ harvest from the donor and placement into the recipient, an innovative technology that can provide major benefits to transplant patients. The use of normothermic machine perfusion (NMP), which is associated with preserving the function of the organ following transplantation, also provides an ideal opportunity for a localized, sustained, and controlled delivery of nanotherapeutics to the organ during this critical time period. Here, we summarize previous endeavors to improve transplantation outcomes by treating the organ with NPs prior to placement in the recipient. Investigations in this burgeoning field of research are promising, but more extensive studies are needed to overcome the physiological challenges to achieving effective nanotherapeutic delivery to transplanted organs discussed in this review.
Topics: Humans; Organ Preservation; Perfusion; Transplants; Organ Transplantation
PubMed: 34714050
DOI: 10.1021/acsnano.1c04707 -
Current Opinion in Organ Transplantation Apr 2020The development and implementation of 'increased risk donor' (IRD) status by the Centers for Disease Control (CDC) was intended to guide patients and providers in... (Review)
Review
PURPOSE OF REVIEW
The development and implementation of 'increased risk donor' (IRD) status by the Centers for Disease Control (CDC) was intended to guide patients and providers in decision making regarding risk of infectious transmission via solid organ transplantation. Several contemporary studies have shown underutilization of these organs. This review summarizes the issues surrounding IRD status as well as recent advances in our understanding of the risks and benefits of increased risk organs and their appropriate utilization.
RECENT FINDINGS
Risk of window-period infection remains exceedingly low, and implementation of nucleic acid testing for HIV and hepatitis C virus (HCV) has resulted in decreasing risk of window-period infection often by an order of magnitude or more. Surgeons remain hesitant to utilize IRD organs. In addition, surgeon assessment of risk by donor behaviour was often discordant with known risks of those behaviours. Studies investigating outcomes of utilization of IRD organs suggest long-term mortality and graft survival is at least equivalent to non-IRD organs. Contemporary results suggest that IRD organs continue to be underutilized, particularly adult kidneys and lungs, with hundreds of wasted organs per year.
SUMMARY
CDC IRD labelling has led to an underutilization of organs for transplantation. The risks associated with acceptance of an IRD organ are inflated by surgeons and patients, and outcomes for patients who undergo transplantation with increased risk organs are similar to or better than those for patients whom accept standard risk organs. The rate of transmission of window-period infection from IRD organs is exceptionally low. The harms regarding the utility of Public Health Service increased risk classification outweigh the benefits for patients in need of transplant.
Topics: Humans; Organ Transplantation; Risk Factors; Tissue Donors
PubMed: 32073497
DOI: 10.1097/MOT.0000000000000735 -
Annals of Translational Medicine Oct 2018Solid organ transplantation (SOT) has emerged from an experimental approach in the 20 century to now being an established and practical definitive treatment option for... (Review)
Review
Solid organ transplantation (SOT) has emerged from an experimental approach in the 20 century to now being an established and practical definitive treatment option for patients with end-organ dysfunction. The evolution of SOT has seen the field progress rapidly over the past few decades with incorporation of a variety of solid organs-liver, kidney, pancreas, heart, and lung-into the donor pool. New advancements in surgical technique have allowed for more efficient and refined multi-organ procurements with minimal complications and decreased ischemic injury events. Additionally, immunosuppression therapy has also seen advancements with the expansion of immunosuppressive protocols to dampen the host immune response and improve short and long-term graft survival. However, the field of SOT faces new barriers, most importantly the expanding demand for SOT that is outpacing the current supply. Allocation protocols have been developed in an attempt to address these concerns. Other avenues for SOT are also being explored to increase the donor pool, including split-liver donor transplants, islet cell implantation for pancreas transplants, and xenotransplantation. The future of SOT is bright with exciting new research being explored to overcome current obstacles.
PubMed: 30498736
DOI: 10.21037/atm.2018.09.68 -
International Journal of Molecular... Mar 2022Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition... (Review)
Review
Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition involving hypoxia, metabolic stress, leukocyte extravasation, cellular death (including apoptosis, necrosis and necroptosis) and an activation of immune response. Although the cycle of sterile inflammation during IRI is consistent among different organs, the underlying mechanisms are poorly understood. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be crucial in the implementation of necroptosis. Moreover, apart from "silent" apoptotic death, necrosis also causes sterile inflammation-necroinflammation, which is triggered by various damage-associated molecular patterns (DAMPs). Those DAMPs activate the innate immune system, causing local and systemic inflammatory responses, which can result in graft failure. In this overview we summarize knowledge on mechanisms of sterile inflammation processes during SOT with special focus on necroptosis and IRI and discuss protective strategies.
Topics: Apoptosis; Humans; Inflammation; Necroptosis; Necrosis; Organ Transplantation; Receptor-Interacting Protein Serine-Threonine Kinases; Reperfusion Injury
PubMed: 35409037
DOI: 10.3390/ijms23073677 -
Gastroenterology & Hepatology Feb 2022Hepatitis C virus (HCV) infection is a common indication for liver transplantation. If the patient's HCV is untreated prior to liver transplant, infection of the...
Hepatitis C virus (HCV) infection is a common indication for liver transplantation. If the patient's HCV is untreated prior to liver transplant, infection of the allograft is nearly universal and can lead to graft failure. The demand for deceased-donor organ transplantation continues to surpass the available supply of donor organs. Waitlist mortality remains an important concern, and several strategies have been enacted to increase organ supply, such as using high-risk donors, including those who are HCV positive. The development of safe and highly effective HCV therapy with direct-acting antiviral agents has revolutionized the management of liver transplant candidates and transplantrecipients. Moreover, thenewer antiviral therapieshave paved the road for use of HCV-viremic organs, effectively expanding the donor pool and changing the landscape of solid organ transplantation. This article reviews the data on HCV treatment prior to and after organ transplantation.
PubMed: 35505819
DOI: No ID Found -
Journal of Fungi (Basel, Switzerland) Jun 2015Histoplasmosis and blastomycosis are geographically restricted dimorphic fungi that cause infection after the conidia produced in the mold phase are inhaled into the... (Review)
Review
Histoplasmosis and blastomycosis are geographically restricted dimorphic fungi that cause infection after the conidia produced in the mold phase are inhaled into the lungs. In the lungs, at 37 °C, these organisms undergo transformation into the yeast phase. In transplant recipients, infection can occur by exposure to the mold in the environment, by reactivation of infection that had occurred previously and had been controlled by the host until immunosuppressive medications were given post-transplantation, and finally by transmission from the donor organ in the case of histoplasmosis. In transplant recipients, disseminated infection is common, and pulmonary infection is more likely to be severe than in a non-immunosuppressed person. Diagnosis has been improved, allowing earlier treatment, with the use of rapid antigen tests performed on serum and urine. Initial treatment, for all but the mildest cases of acute pulmonary histoplasmosis, should be with a lipid formulation of amphotericin B. After clinical improvement has occurred, step-down therapy with itraconazole is recommended for a total of 12 months for most transplant recipients, but some patients will require long-term suppressive therapy to prevent relapse of disease.
PubMed: 29376901
DOI: 10.3390/jof1020094 -
The Chinese Journal of Physiology 2023In traditional Chinese medicine (TCM), the liver is the "general organ" that is responsible for governing/maintaining the free flow of qi over the entire body and... (Review)
Review
In traditional Chinese medicine (TCM), the liver is the "general organ" that is responsible for governing/maintaining the free flow of qi over the entire body and storing blood. According to the classic five elements theory, zang-xiang theory, yin-yang theory, meridians and collaterals theory, and the five-viscera correlation theory, the liver has essential relationships with many extrahepatic organs or tissues, such as the mother-child relationships between the liver and the heart, and the yin-yang and exterior-interior relationships between the liver and the gallbladder. The influences of the liver to the extrahepatic organs or tissues have been well-established when treating the extrahepatic diseases from the perspective of modulating the liver by using the ancient classic prescriptions of TCM and the acupuncture and moxibustion. In modern medicine, as the largest solid organ in the human body, the liver has the typical functions of filtration and storage of blood; metabolism of carbohydrates, fats, proteins, hormones, and foreign chemicals; formation of bile; storage of vitamins and iron; and formation of coagulation factors. The liver also has essential endocrine function, and acts as an immunological organ due to containing the resident immune cells. In the perspective of modern human anatomy, physiology, and pathophysiology, the liver has the organ interactions with the extrahepatic organs or tissues, for example, the gut, pancreas, adipose, skeletal muscle, heart, lung, kidney, brain, spleen, eyes, skin, bone, and sexual organs, through the circulation (including hemodynamics, redox signals, hepatokines, metabolites, and the translocation of microbiota or its products, such as endotoxins), the neural signals, or other forms of pathogenic factors, under normal or diseases status. The organ interactions centered on the liver not only influence the homeostasis of these indicated organs or tissues, but also contribute to the pathogenesis of cardiometabolic diseases (including obesity, type 2 diabetes mellitus, metabolic [dysfunction]-associated fatty liver diseases, and cardio-cerebrovascular diseases), pulmonary diseases, hyperuricemia and gout, chronic kidney disease, and male and female sexual dysfunction. Therefore, based on TCM and modern medicine, the liver has the bidirectional interaction with the extrahepatic organ or tissue, and this established bidirectional interaction system may further interact with another one or more extrahepatic organs/tissues, thus depicting a complex "pan-hepatic network" model. The pan-hepatic network acts as one of the essential mechanisms of homeostasis and the pathogenesis of diseases.
Topics: Male; Female; Humans; Medicine, Chinese Traditional; Diabetes Mellitus, Type 2; Yin-Yang; Liver; Kidney
PubMed: 38149555
DOI: 10.4103/cjop.CJOP-D-22-00131