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BioMed Research International 2014INTRODUCTION; Face transplantation (FT) is an innovative achievement of modern reconstructive surgery and is on the verge of becoming a common surgical opportunity. This... (Review)
Review
UNLABELLED
INTRODUCTION; Face transplantation (FT) is an innovative achievement of modern reconstructive surgery and is on the verge of becoming a common surgical opportunity. This review article was compiled to provide an update on this surgical field, especially regarding clinical outcomes, benefits, and complications implied.
METHODS
We performed an extensive research on all English-language Medline articles, case reports, and reviews published online until September 15, 2013. Used search terms were "face transplantation," "face transplant," "facial transplantation," "facial transplant," "face allograft," and "facial allograft."
RESULTS
To date 27 FTs have been performed worldwide. 19 of these cases have been published in the Medline database. Long-term follow-up reports of FT cases are rare. Three deaths associated with the procedure have occurred to date. The clinical outcomes of FT are satisfying. Reinnervation of sensation has been faster than motor recovery. Extensive functional improvements have been observed. Due to strict immunosuppression protocols, no case of hyperacute or chronic rejection and no graft-versus-host disease have occurred to date.
CONCLUSIONS
As studies on long-term outcomes are missing, particularly regarding immunosuppression-related complications, FT will stay experimental for the next years. Nevertheless, for a small group of patients, FT already is a feasible reconstructive option.
Topics: Allografts; Facial Transplantation; Humans; Immunosuppression Therapy; MEDLINE
PubMed: 25009821
DOI: 10.1155/2014/907272 -
Xenotransplantation Nov 2018The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution... (Review)
Review
The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosuppressive therapy. If one could safely and effectively exploit neonatal tolerance for successful xenotransplantation of the heart, the challenge of severe cardiac failure in the newborn infant might be met. We discuss the need, the potential for applying neonatal tolerance in the setting of xenotransplantation and the possibility that other approaches to this problem might emerge.
Topics: Animals; Graft Rejection; Heart Defects, Congenital; Heart Failure; Heart Transplantation; Humans; Immunosuppression Therapy; Infant, Newborn; Transplantation, Heterologous
PubMed: 30537350
DOI: 10.1111/xen.12479 -
World Journal of Gastroenterology Aug 2017Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism underlying this disease is yet to be fully understood, old and newer generation treatments can only target selected pathways of this complex inflammatory process. This narrative review aims to provide an update on the most recent advances in treatment of paediatric IBD. A MEDLINE search was conducted using "paediatric inflammatory bowel disease", "paediatric Crohn's disease", "paediatric ulcerative colitis", "treatment", "therapy", "immunosuppressant", "biologic", "monitoring" and "biomarkers" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2014 and 2016 were selected. Studies referring to earlier periods were also considered in case the data was relevant to our scope. Major advances have been achieved in monitoring the individual metabolism, toxicity and response to relevant medications in IBD including thiopurines and biologics. New biologics acting on novel mechanisms such as selective interference with lymphocyte trafficking are emerging treatment options. Current research is investing in the development of reliable prognostic biomarkers, aiming to move towards personalised treatments targeted to individual patients.
Topics: Age Factors; Biological Products; Biosimilar Pharmaceuticals; Child; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Diet Therapy; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Treatment Outcome
PubMed: 28852307
DOI: 10.3748/wjg.v23.i30.5469 -
Journal For Immunotherapy of Cancer Oct 2021Tumors accumulate metabolites that deactivate infiltrating immune cells and polarize them toward anti-inflammatory phenotypes. We provide a comprehensive review of the... (Review)
Review
Tumors accumulate metabolites that deactivate infiltrating immune cells and polarize them toward anti-inflammatory phenotypes. We provide a comprehensive review of the complex networks orchestrated by several of the most potent immunosuppressive metabolites, highlighting the impact of adenosine, kynurenines, prostaglandin E2, and norepinephrine and epinephrine, while discussing completed and ongoing clinical efforts to curtail their impact. Retrospective analyses of clinical data have elucidated that their activity is negatively associated with prognosis in diverse cancer indications, though there is a current paucity of approved therapies that disrupt their synthesis or downstream signaling axes. We hypothesize that prior lukewarm results may be attributed to redundancies in each metabolites' synthesis or signaling pathway and highlight routes for how therapeutic development and patient stratification might proceed in the future.
Topics: Humans; Immune Evasion; Immunosuppression Therapy; Immunotherapy; Neoplasms
PubMed: 34667078
DOI: 10.1136/jitc-2021-003013 -
Current Opinion in Organ Transplantation Oct 2018The long-term adverse effects of immunosuppressive treatment, the high rate of acute rejection and the development of chronic rejection are the main factors preventing a... (Review)
Review
PURPOSE OF REVIEW
The long-term adverse effects of immunosuppressive treatment, the high rate of acute rejection and the development of chronic rejection are the main factors preventing a wider clinical application of vascularized composite allotransplantation (VCA). Targeted immunosuppression using innovative drug delivery systems (DDS) may help to overcome these hurdles, increasing therapeutic efficacy while reducing systemic toxicity. This review provides a summary of the recently developed strategies for targeted delivery of immunosuppressive drugs in VCA.
RECENT FINDINGS
Currently, several innovative strategies for targeted immunosuppression have been designed based on the anatomy and function of the target organ. Site-specific DDS have been developed both for directly accessible organs (i.e. skin, eye and lung) and internal organs (i.e. lymph nodes, liver, nervous system, etc.). In preclinical models, DDS designed for sustained, 'on demand,' or 'on cue' drug release has been shown to promote VCA survival while reducing systemic toxicity. These findings suggest that targeted delivery could increase patient compliance and potentially decrease toxicity in VCA recipients.
SUMMARY
Targeted immunosuppression in VCA represents a promising approach for improving patient compliance and graft survival while reducing off-target toxicity, intensity and frequency of acute rejection episodes and risk of chronic rejection. VIDEO ABSTRACT.
Topics: Drug Delivery Systems; Humans; Immunosuppression Therapy; Vascularized Composite Allotransplantation
PubMed: 30074507
DOI: 10.1097/MOT.0000000000000564 -
Texas Heart Institute Journal Feb 2019
Review
Topics: Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Organ Transplantation
PubMed: 30833848
DOI: 10.14503/THIJ-18-6746 -
Current Opinion in Organ Transplantation Aug 2020The current tools to proactively guide and individualize immunosuppression in solid organ transplantation are limited. Despite continued improvements in posttransplant...
PURPOSE OF REVIEW
The current tools to proactively guide and individualize immunosuppression in solid organ transplantation are limited. Despite continued improvements in posttransplant outcomes, the adverse effects of over-immunosuppression or under-immunosuppression are common. The present review is intended to highlight recent advances in individualized immunosuppression.
RECENT FINDINGS
There has been a great focus on genomic information to predict drug dose requirements, specifically on single nucleotide polymorphisms of CYP3A5 and ABCB1. Furthermore, biomarker studies have developed ways to better predict clinical outcomes, such as graft rejection.
SUMMARY
The integration of advanced computing tools, such as artificial neural networks and machine learning, with genome sequencing has led to intriguing findings on individual or group-specific dosing requirements. Rapid computing allows for processing of data and discovering otherwise undetected clinical patterns. Genetic polymorphisms of CYP3A5 and ABCB1 have yielded results to suggest varying dose requirements correlated with race and sex. Newly proposed biomarkers offer precise and noninvasive ways to monitor patient's status. Cell-free DNA quantitation is increasingly explored as an indicator of allograft injury and rejection, which can help avoid unneeded biopsies and more frequently monitor graft function.
Topics: ATP Binding Cassette Transporter, Subfamily B; Cytochrome P-450 CYP3A; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Organ Transplantation; Polymorphism, Single Nucleotide; Precision Medicine; Transplantation, Homologous
PubMed: 32520785
DOI: 10.1097/MOT.0000000000000771 -
The Journal of Surgical Research Mar 2021This study explores the use of induction therapy in orthotopic heart transplantation as it relates to preoperative renal function and evaluates the impact of its...
BACKGROUND
This study explores the use of induction therapy in orthotopic heart transplantation as it relates to preoperative renal function and evaluates the impact of its utilization on post-transplant outcomes.
METHODS
We conducted a retrospective analysis using the United Network for Organ Sharing database from 2000 to 2018 evaluating the initiation of de novo dialysis after transplantation. We examined the relationship between induction immunosuppression and pre-transplant estimated glomerular filtration rate with post-transplant outcomes, accounting for inter-center variability through a mixed-effects logistic regression model.
RESULTS
In total, 16,201 patients were included with a median age of 57 y (interquartile range 47, 63); 26% were women (n = 4222) and 28% (n = 4552) had a history of diabetes mellitus. The median estimated glomerular filtration rate (eGFR) was 67.5 mL/min (interquartile range 53.1, 86.7); 51.2% (n = 3068) of the recipients with eGFR < 60 received induction therapy compared to 42.5% (n = 4336) within the eGFR ≥ 60 group (P < 0.001). Adjusted multivariable analysis found that induction therapy was associated with de novo dialysis (odds ratio 1.25, 95% confidence interval 1.10-1.43, P < 0.001), with the most significant effect on patients with eGFR ≥ 60. Although significant, there was a weak correlation between center-level induction utilization and mean eGFR (r = -0.2, P < 0.001).
CONCLUSION
In this analysis, the use of induction immunosuppression in orthotopic heart transplantation varied widely between centers and did not correlate strongly with pre-transplant eGFR. In addition, its utilization did not mitigate the risk of renal replacement therapy after transplantation and in fact was associated with increased risk even after adjusting for confounders most notably in patients with eGFR ≥ 60.
Topics: Adult; Aged; Confounding Factors, Epidemiologic; Female; Glomerular Filtration Rate; Graft Rejection; Heart Failure; Heart Transplantation; Humans; Immunosuppression Therapy; Male; Middle Aged; Postoperative Complications; Practice Guidelines as Topic; Practice Patterns, Physicians'; Preoperative Period; Renal Dialysis; Renal Insufficiency; Retrospective Studies; Risk Factors; Young Adult
PubMed: 33278793
DOI: 10.1016/j.jss.2020.11.021 -
Journal of Cellular and Molecular... Aug 2013Allogeneic hematopoietic stem cell transplantation (HSCT) has been widely used for the treatment of hematologic malignant and non-malignant hematologic diseases and... (Review)
Review
Allogeneic hematopoietic stem cell transplantation (HSCT) has been widely used for the treatment of hematologic malignant and non-malignant hematologic diseases and other diseases. However, acute graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic transplantation. Acute GVHD may occur in 30% of transplant recipients, which is a syndrome of erythematous skin eruption, cholestatic liver disease and intestinal dysfunction, resulting from the activation of donor T lymphocytes by host antigen-presenting cells, resulting in an immune-mediated inflammatory response. Recent scientific advances in the understanding of the pathogenesis involved in the development of acute GVHD and clinical investigation have provided more effective therapeutic strategies for acute GVHD. This review focuses on major scientific and clinical advances in the treatment of acute GVHD.
Topics: Acute Disease; Graft vs Host Disease; Humans; Immunosuppression Therapy
PubMed: 23802653
DOI: 10.1111/jcmm.12093 -
Transplant International : Official... Mar 2009Neurologic complications are common after solid organ transplantation and are associated with significant morbidity. Approximately one-third of transplant recipients... (Review)
Review
Neurologic complications are common after solid organ transplantation and are associated with significant morbidity. Approximately one-third of transplant recipients experiences neurologic alterations with incidence ranging from 10% to 59%. The complications can be divided into such of those common to all types of transplant and others of those specific to transplanted organ. The most common complication seen with all types of transplanted organ is neurotoxicity attributable to immunosuppressive drugs, followed by seizures, opportunistic central nervous system (CNS) infections, cardiovascular events, encephalopathy and de novo CNS neoplasms. Amongst immunosuppressants, calcineurin inhibitors are the main drugs involved in neurotoxicity, leading to complications which ranges from mild symptoms, such as tremors and paresthesia to severe symptoms, such as disabling pain syndrome and leukoencephalopathy. Neurologic complications of liver transplantation are more common than that of other solid organ transplants (13-47%); encephalopathy is the most common CNS complication, followed by seizures; however, central pontine myelinolysis can appear in 1-8% of the patients leading to permanent disabilities or death. In kidney transplanted patients, stroke is the most common neurologic complication, whereas cerebral infarction and bleeding are more typical after heart transplantation. Metabolic, electrolyte and infectious anomalies represent common risk factors; however, identification of specific causes and early diagnosis are still difficult, because of patient's poor clinical status and concomitant systemic and metabolic disorders, which may obscure symptoms.
Topics: Central Nervous System Diseases; Humans; Immunosuppression Therapy; Incidence; Postoperative Complications; Risk Factors; Transplants
PubMed: 19076332
DOI: 10.1111/j.1432-2277.2008.00780.x