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Organogenesis 2018The transplantation of living cells, tissues or organs from one species to another is termed xenotransplantation. The history of xenotransplantation is as old as...
The transplantation of living cells, tissues or organs from one species to another is termed xenotransplantation. The history of xenotransplantation is as old as allogeneic transplantation itself. Early attempts were made at a time when the immunologic basis of organ rejection were poorly understood. The advent of potent immunosuppressive medications along with the parallel advances in the field of genetic engineering has provided a fresh perspective on the role of xenotransplantation as a means to alleviate the disparity between the number of candidates on the waitlist and the available organs. As the science behind xenotransplantation advances, the transplantation community must take it upon themselves to educate the community at large regarding both the benefits and potential risks of this promising field.
PubMed: 30252598
DOI: 10.1080/15476278.2018.1517508 -
Annals of the American Thoracic Society Feb 2015Achromobacteria are ubiquitous environmental organisms that may also become opportunistic pathogens in certain conditions, such as cystic fibrosis, hematologic and solid... (Review)
Review
Achromobacteria are ubiquitous environmental organisms that may also become opportunistic pathogens in certain conditions, such as cystic fibrosis, hematologic and solid organ malignancies, renal failure, and certain immune deficiencies. Some members of this genus, such as xylosoxidans, cause primarily nosocomially acquired infections affecting multiple organ systems, including the respiratory tract, urinary tract, and, less commonly, the cardiovascular and central nervous systems. Despite an increasing number of published case reports and literature reviews suggesting a global increase in achromobacterial disease, most clinicians remain uncertain of the organism's significance when clinically isolated. Moreover, effective treatment can be challenging due to the organism's inherent and acquired multidrug resistance patterns. We reviewed all published cases to date of non-cystic fibrosis achromobacterial lung infections to better understand the organism's pathogenic potential and drug susceptibilities. We found that the majority of these cases were community acquired, typically presenting as pneumonias (88%), and were most frequent in individuals with hematologic and solid organ malignancies. Our findings also suggest that achromobacterial lung infections are difficult to treat, but respond well to extended-spectrum penicillins and cephalosporins, such as ticarcillin, piperacillin, and cefoperazone.
Topics: Achromobacter; Age Factors; Anti-Bacterial Agents; Bronchiectasis; Cefoperazone; Cephalosporins; Community-Acquired Infections; Comorbidity; Drug Resistance, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Neoplasms; Penicillins; Piperacillin; Pneumonia, Bacterial; Respiratory Tract Infections; Risk Factors; Sex Factors; Ticarcillin; Virulence Factors
PubMed: 25706494
DOI: 10.1513/AnnalsATS.201406-288FR -
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 -
Annals of Medicine and Surgery (2012) Apr 2018The establishment of bio-banks together with high throughput technologies, such as genomics, transcriptomics and proteomics has opened new frontiers in biomarker... (Review)
Review
The establishment of bio-banks together with high throughput technologies, such as genomics, transcriptomics and proteomics has opened new frontiers in biomarker discovery and the development of systems biology approaches to identifying key pathways that could be exploited to improve outcomes of solid organ transplantation. One of the major challenges in organ donation has been the lack of access to large scale well characterised material to facilitate projects that aim to characterise injury to donor organs and identify biomarkers. This may have hampered research in the field of organ donation by not allowing researchers to materials of high quality and lower pre-analytical variability. We describe in this manuscript the need for bio-banks in organ donation, research opportunities and the particular challenges in establishing such an initiative.
PubMed: 29744049
DOI: 10.1016/j.amsu.2018.02.007 -
Current Opinion in Infectious Diseases Jun 2022Hyperammonemia syndrome is an increasingly recognized and often fatal condition that occurs in immunosuppressed individuals, most commonly lung transplant recipients.... (Review)
Review
PURPOSE OF REVIEW
Hyperammonemia syndrome is an increasingly recognized and often fatal condition that occurs in immunosuppressed individuals, most commonly lung transplant recipients. Growing evidence suggests hyperammonemia syndrome is associated with systemic infections caused by urease-producing organisms, namely Ureaplasma spp., an organism unable to grow with routine culturing techniques. This review will summarize the epidemiology and clinical manifestations of hyperammonemia syndrome, as well as diagnostic and management strategies once hyperammonemia syndrome is suspected.
RECENT FINDINGS
Hyperammonemia syndrome is being described in increasing frequency in the solid organ transplant population. Morbidity and mortality, even with treatment, is high once hyperammonemia syndrome occurs. Surveillance studies indicate the prevalence of lung donor colonization with Ureaplasma spp. is high, suggesting screening and treatment may be of benefit. Antibiotic resistance is common, and rapid diagnostics can facilitate appropriate antimicrobial therapy in the peri-transplant period.
SUMMARY
Hyperammonemia syndrome is most commonly seen in lung transplant recipients and has a high mortality rate once it occurs. Screening for Ureaplasma spp. should be considered in all lung transplant donors.
Topics: Humans; Hyperammonemia; Immunocompromised Host; Syndrome; Transplant Recipients; Ureaplasma; Ureaplasma Infections
PubMed: 35665721
DOI: 10.1097/QCO.0000000000000828 -
Cells, Tissues, Organs 2022Bioengineering a solid organ for organ replacement is a growing endeavor in regenerative medicine. Our approach - recellularization of a decellularized cadaveric organ... (Review)
Review
Bioengineering a solid organ for organ replacement is a growing endeavor in regenerative medicine. Our approach - recellularization of a decellularized cadaveric organ scaffold with human cells - is currently the most promising approach to building a complex solid vascularized organ to be utilized in vivo, which remains the major unmet need and a key challenge. The 2008 publication of perfusion-based decellularization and partial recellularization of a rat heart revolutionized the tissue engineering field by showing that it was feasible to rebuild an organ using a decellularized extracellular matrix scaffold. Toward the goal of clinical translation of bioengineered tissues and organs, there is increasing recognition of the underlying need to better integrate basic science domains and industry. From the perspective of a research group focusing on whole heart engineering, we discuss the current approaches and advances in whole organ engineering research as they relate to this multidisciplinary field's 3 major pillars: organ scaffolds, large numbers of cells, and biomimetic bioreactor systems. The success of whole organ engineering will require optimization of protocols to produce biologically-active scaffolds for multiple organ systems, and further technological innovation both to produce the massive quantities of high-quality cells needed for recellularization and to engineer a bioreactor with physiologic stimuli to recapitulate organ function. Also discussed are the challenges to building an implantable vascularized solid organ.
Topics: Animals; Extracellular Matrix; Humans; Perfusion; Rats; Regenerative Medicine; Tissue Engineering; Tissue Scaffolds
PubMed: 33640893
DOI: 10.1159/000511382 -
Journal of the Pediatric Infectious... Feb 2024The microbial communities that inhabit our bodies have been increasingly linked to host physiology and pathophysiology. This microbiome, through its role in colonization... (Review)
Review
The microbial communities that inhabit our bodies have been increasingly linked to host physiology and pathophysiology. This microbiome, through its role in colonization resistance, influences the risk of infections after transplantation, including those caused by multidrug-resistant organisms. In addition, through both direct interactions with the host immune system and via the production of metabolites that impact local and systemic immunity, the microbiome plays an important role in the establishment of immune tolerance after transplantation, and conversely, in the development of graft-versus-host disease and graft rejection. This review offers a comprehensive overview of the evidence for the role of the microbiome in hematopoietic cell and solid organ transplant complications, drivers of microbiome shift during transplantation, and the potential of microbiome-based therapies to improve pediatric transplantation outcomes.
Topics: Humans; Child; Gastrointestinal Microbiome; Hematopoietic Stem Cell Transplantation; Microbiota; Organ Transplantation; Graft vs Host Disease
PubMed: 38417089
DOI: 10.1093/jpids/piad062 -
Acta Haematologica 2020Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding... (Review)
Review
Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding intermediaries, which are deposited in target tissues causing progressive organ damage. In all forms of amyloidosis, vital organs may fail; depending on the specific amyloidosis type, this may occur rapidly or progress slowly. Beyond therapies to reduce the precursor protein (chemotherapy for light chain [AL] amyloidosis, anti-inflammatory therapy in serum A amyloid-osis [AA], and antisense RNA therapy in transthyretin amyloidosis [ATTR]), organ transplantation may also be a means to reduce amyloidogenic protein, e.g., in types of amyloid-osis in which the variant precursor is produced by the liver. Heart transplantation is a life-saving approach to the treatment of patients with advanced cardiac amyloidosis; however, amyloidosis may still be considered a contraindication to the procedure despite data supporting improved outcomes, similar to patients with other indications. Kidney transplantation is associated with particularly favorable outcomes in patients with amyloidosis, especially if the precursor protein has been eliminated. Overall, outcomes of solid organ transplantation are improving, but more data are needed to refine the selection criteria and the timing for organ transplantation, which should be performed in highly experienced centers involving multidisciplinary teams with close patient follow-up to detect amyloid recurrence.
Topics: Amyloidosis; Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Organ Transplantation; Treatment Outcome
PubMed: 32535598
DOI: 10.1159/000508262