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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 -
Current Opinion in Organ Transplantation Feb 2022Solid organ transplantation (SOT) has become a widely accepted therapy for end-stage disease across the spectrum of thoracic and abdominal organs. With contemporary... (Review)
Review
PURPOSE OF REVIEW
Solid organ transplantation (SOT) has become a widely accepted therapy for end-stage disease across the spectrum of thoracic and abdominal organs. With contemporary advances in medical and surgical therapies in transplantation, candidates for SOT are increasingly older with a larger burden of comorbidities, including cardiovascular disease (CVD). CVD, in particular, is a leading cause of morbidity and mortality in SOT candidates with end-stage disease of noncardiac organs [1].
RECENT FINDINGS
Identification of coronary artery disease (CAD), heart failure, and valvular disease are important in noncardiac SOT to ensure both appropriate peri-transplant management and equitable organ allocation. Although the American College of Cardiology (ACC) and the American Heart Association (AHA) have published guidelines and recommendations for the perioperative cardiovascular evaluation of patients undergoing noncardiac surgery, the implications of both symptomatic and asymptomatic CVD differ in patients with end-stage organ failure being considered for SOT when compared to the general population.
SUMMARY
Herein, we review the epidemiology, diagnosis, and evidence for the management of CVD in kidney and liver transplantation, combining current guidelines from the 2012 ACC/AHA scientific statement on cardiac disease evaluation in SOT with more contemporary evidenced-based algorithms.
Topics: American Heart Association; Cardiovascular Diseases; Coronary Artery Disease; Humans; Organ Transplantation; Risk Factors; United States
PubMed: 34939961
DOI: 10.1097/MOT.0000000000000942 -
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 -
Nephron 2017Following transplantation (TX) of both renal and non-renal organs, a large proportion of patients have renal dysfunction. There are multiple causes for this. Chronic... (Review)
Review
Following transplantation (TX) of both renal and non-renal organs, a large proportion of patients have renal dysfunction. There are multiple causes for this. Chronic nephrotoxicity and high doses of calcineurin inhibitors are important factors. Preoperative and perioperative factors like hypertension, hypotension, drugs and infections may play a causative role as well. Organ-specific causes include hepatorenal syndrome, cirrhosis, low cardiac function, low respiratory function and diabetes developed both before and after TX. It is important to be able to perform precise and valid measurements or estimates of renal function in these patients, in order to accurately and safely dose immunosuppressive medication and perform and adjust the treatment and prophylaxis of renal dysfunction. This is a short overview and discussion of relevant studies and possible caveats of estimated glomerular filtration rate methods for use in renal and non-renal TX.
Topics: Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Transplantation; Organ Transplantation
PubMed: 27388425
DOI: 10.1159/000447673 -
Frontiers in Surgery 2017Abdominopelvic trauma (APT) remains a leading cause of morbidity and mortality in the 15- to 44-year-old age group in the Western World. It can be life-threatening as... (Review)
Review
Abdominopelvic trauma (APT) remains a leading cause of morbidity and mortality in the 15- to 44-year-old age group in the Western World. It can be life-threatening as abdominopelvic organs, specifically those in the retroperitoneal space, can bleed profusely. APT is divided into blunt and penetrating types. While surgery is notably considered as a definitive solution for bleeding control, it is not always the optimum treatment for the stabilization of a polytrauma patient. Over the past decades, there has been a shift toward more sophisticated strategies, such as non-operative management of abdominopelvic vascular trauma for haemodynamically stable patients. Angiographic embolization for bleeding control following blunt and/or penetrating intra- and retroperitoneal injuries has proven to be safe and effective. Embolization can achieve hemostasis and salvage organs without the morbidity of surgery, and the development and refinement of embolization techniques has widened the indications for non-operative treatment in solid organ injury. Moreover, advances in computed tomography provided more efficient scanning times with improved image quality. While surgery is still usually recommended for patients with penetrating injuries, non-operative management can be effectively used as well as an alternative treatment. We review indications, technical considerations, efficacy, and complication rates of angiographic embolization in APT.
PubMed: 28824919
DOI: 10.3389/fsurg.2017.00043 -
JAMA Network Open Oct 2019Presumed consent, or an opt-out organ transplant policy, has been adopted by many countries worldwide to increase organ donation. The implication of such a policy for...
IMPORTANCE
Presumed consent, or an opt-out organ transplant policy, has been adopted by many countries worldwide to increase organ donation. The implication of such a policy for transplants in the United States is uncertain, however.
OBJECTIVE
To simulate the potential implications of a presumed consent policy in the United States.
DESIGN, SETTING, AND PARTICIPANTS
In a decision analytical model, a simulation model was developed using cohort data from January 1, 2004, to December 31, 2014, in the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files. All US patients (n = 524 359) who were on the waiting list for at least 1 solid organ and all deceased organ donors during the study period were included in the analyses. All data and statistical analyses were performed from January 30, 2019, to July 31, 2019.
MAIN OUTCOMES AND MEASURES
Increase in the organs available for donation and life-years gained associated with a 5%, 15%, or 25% increase in deceased donors, based on the published changes from a presumed consent policy.
RESULTS
This study considered 524 359 unique candidates (aged ≥18 years; 320 908 [61.2%] male) for a solid organ transplant from January 1, 2004, to December 31, 2014. With a base case scenario of a 5% presumed consent-associated increase in donors, the removals (owing to death or illness) from the waiting list for all organs would have an associated 3.2% to 10.4% mean reduction, depending on the random or ideal allocation of new organs to patients on the waiting list. Sensitivity analyses showed that waiting list removals could be decreased up to 52%; however, this reduction was not enough to completely eliminate waiting list removals during the study period. The biggest estimated increases in annual life-years gained associated with a presumed consent policy were in kidney transplant candidates (95% CIs by deceased donor increase: 5% increase, 3440-3466 years; 15% increase, 10 321-10 399 years; 25% increase, 17 201-17 332 years) and liver transplant candidates (95% CIs by deceased donor increase: 5% increase, 898-905 years; 15% increase, 2693-2714 years; 25% increase, 4448-4523 years). Adoption of a presumed consent policy could result in a 4295-year (95% CI, 4277-4313 years) to 11 387-year (95% CI, 11 339-11 435 years) increase in life-years, accounting for the survival advantages associated with a transplant.
CONCLUSIONS AND RELEVANCE
In this study, presumed consent was estimated to be associated with modest but important improvement in the number of organ transplants and increases in life-years gained for patients awaiting an organ transplant. Further consideration and even debate about the ethical and public policy implications of a presumed consent policy are warranted.
Topics: Computer Simulation; Female; Health Policy; Humans; Male; Organ Transplantation; Presumed Consent; Tissue Donors; Tissue and Organ Procurement; United States; Waiting Lists
PubMed: 31577360
DOI: 10.1001/jamanetworkopen.2019.12431 -
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 -
American Journal of Transplantation :... May 2010The organ shortage is widely acknowledged as the most critical factor hindering the full realization of success for solid organ transplantation. Innovation in the areas... (Review)
Review
The organ shortage is widely acknowledged as the most critical factor hindering the full realization of success for solid organ transplantation. Innovation in the areas of donor management and organ preservation offers the most realistic hope to improve both the quality and size of the current organ supply. Although the basic science dissecting the complex processes of brain death and ischemia/reperfusion injury is replete with exciting discoveries, the clinical science investigating donor management and organ preservation is sparse in contrast. This review will survey the current landscape of trials to mitigate organ injury through interventions administered to donors in vivo or organs ex vivo. Consideration will then be given to the scientific, logistical and ethical obstacles that impede the transformation of laboratory breakthroughs into innovative treatments that simultaneously improve organ quality and supply.
Topics: Brain Death; Humans; Organ Preservation; Reperfusion Injury; Tissue Donors
PubMed: 20420628
DOI: 10.1111/j.1600-6143.2010.03100.x -
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