-
The Journal of Surgical Research Dec 2023Heart transplantation is the treatment of choice for end-stage heart failure. There is a mismatch between the number of donor hearts available and the number of patients... (Review)
Review
INTRODUCTION
Heart transplantation is the treatment of choice for end-stage heart failure. There is a mismatch between the number of donor hearts available and the number of patients awaiting transplantation. Expanding the donor pool is critically important. The use of hearts donated following circulatory death is one approach to increasing the number of available donor hearts.
MATERIALS AND METHODS
A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines utilizing Pubmed/MEDLINE and Embase. Articles including adult human studies and preclinical animal studies of heart transplantation following donation after circulatory death were included. Studies of pediatric populations or including organs other than heart were excluded.
RESULTS
Clinical experience and preclinical studies are reviewed. Clinical experience with direct procurement, normothermic regional perfusion, and machine perfusion are included. Preclinical studies addressing organ function assessment and enhancement of performance of marginal organs through preischemic, procurement, preservation, and reperfusion maneuvers are included. Articles addressing the ethical considerations of thoracic transplantation following circulatory death are also reviewed.
CONCLUSIONS
Heart transplantation utilizing organs procured following circulatory death is a promising method to increase the donor pool and offer life-saving transplantation to patients on the waitlist living with end-stage heart failure. There is robust ongoing preclinical and clinical research to optimize this technique and improve organ yield. There are also ongoing ethical considerations that must be addressed by consensus before wide adoption of this approach.
PubMed: 37657140
DOI: 10.1016/j.jss.2023.07.050 -
Frontiers in Medicine 2022Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage...
INTRODUCTION
Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.
METHODS
A systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.
RESULTS
We report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).
CONCLUSION
The results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.
PubMed: 35833101
DOI: 10.3389/fmed.2022.930071 -
Frontiers in Medicine 2021Many putative uremic toxins-like indoxyl sulfate, p-cresol sulfate, kynurenic acid, uric acid, and CMPF-are organic anions. Both inter-organ and inter-organismal...
Many putative uremic toxins-like indoxyl sulfate, p-cresol sulfate, kynurenic acid, uric acid, and CMPF-are organic anions. Both inter-organ and inter-organismal communication are involved. For example, the gut microbiome is the main source of indole, which, after modification by liver drug metabolizing enzymes (DMEs), becomes indoxyl sulfate. Various organic anion transporters (organic anion transporters, OATs; organic anion-transporting polypeptides, OATPs; multidrug resistance-associated proteins, MRPs, and other ABC transporters like ABCG2)-often termed "drug transporters"-mediate movement of uremic toxins through cells and organs. In the kidney proximal tubule, critical roles for OAT1 and OAT3 in regulating levels of protein-bound uremic toxins have been established using knock-out mice. OATs are important in maintaining residual tubular function in chronic kidney disease (CKD); as CKD progresses, intestinal transporters like ABCG2, which extrude urate and other organic anions into the gut lumen, seem to help restore homeostasis. Uremic toxins like indoxyl sulfate also regulate signaling and metabolism, potentially affecting gene expression in extra-renal tissues as well as the kidney. Focusing on the history and evolving story of indoxyl sulfate, we discuss how uremic toxins appear to be part of an extensive "remote sensing and signaling" network-involving so-called drug transporters and drug metabolizing enzymes which modulate metabolism and signaling. This systems biology view of uremic toxins is leading to a new appreciation of uremia as partly due to disordered remote sensing and signaling mechanisms-resulting from, and causing, aberrant inter-organ (e.g., gut-liver- kidney-CNS) and inter-organismal (e.g., gut microbiome-host) communication.
PubMed: 33937275
DOI: 10.3389/fmed.2021.592602 -
SAGE Open Medicine 2023Multifocal fibrosclerosis is a rare disorder causing progressive fibrosis of multiple organ systems. Existing data on the disease show that there are multiple... (Review)
Review
OBJECTIVES
Multifocal fibrosclerosis is a rare disorder causing progressive fibrosis of multiple organ systems. Existing data on the disease show that there are multiple manifestations of the disease, with different outcomes. However, quantitative data are scarce, prompting the need for our investigation.
METHOD
A comprehensive systematic review was performed from inception to November 16, 2022, with the restriction of English language, not including review articles. Article screening and extraction was performed independently, and shortlisted articles were assessed for bias. Analysis was performed using SPSS Version 25 (IBM® SPSS® Statistics; Chicago, IL, USA). Data were presented as frequencies and percentages, with a confidence interval of 95%.
RESULT
This review included 134 patients, with 78 (58.2%) males. Mean age was 53.6 years and included two pediatric patients. The most common comorbidity was diabetes (9.7%). Prevalent presenting symptoms included pain (47.8%) and swelling (35.1%). A mean of 2.51 organs or anatomical sites was affected, retroperitoneum (64.2%) being most affected. The pancreas (30.0%) and digestive system (47.0%) were the organs/organ systems most affected. Patients had favorable outcomes in 79.1% of cases, 87.3% had no relapse, and 91.8% of patients survived the condition.
CONCLUSION
The findings in this study provide a quantitative measurement of the demographics, presentations, organ manifestations, and outcomes of multifocal fibrosclerosis. We found the disease to be prevalent in males in Japan or the United States, with the abdomen and its organs being commonly involved.
PubMed: 37275844
DOI: 10.1177/20503121231178046 -
International Journal of Gynaecology... Nov 2022Primary vaginal cancer is a rare gynecologic malignancy. Few cases describing the concurrence of a vaginal tumor with advanced genital prolapse are reported in the... (Review)
Review
BACKGROUND
Primary vaginal cancer is a rare gynecologic malignancy. Few cases describing the concurrence of a vaginal tumor with advanced genital prolapse are reported in the literature and there is no consensus on optimal treatment.
OBJECTIVES
To investigate available evidence on presentation, treatment, and outcomes of these concurrent conditions.
SEARCH STRATEGY
We performed a systematic search of literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by "pelvic organ prolapse", "genital prolapse", and "vaginal cancer", "vaginal carcinoma".
SELECTION CRITERIA
No article type restrictions were applied.
DATA COLLECTION AND ANALYSIS
Twenty-one studies (case reports and two small case series) were incorporated into the review process, for a total of 27 patients.
MAIN RESULTS
Management usually involved surgery or primary external beam radiation therapy. External beam radiation therapy was reported to be highly associated with the development of vesicovaginal fistula. A surgical approach was the treatment of choice in most cases. Exclusive interstitial brachytherapy was rarely performed.
CONCLUSION
A multidisciplinary approach considering risks and benefits is of the utmost importance to provide counseling and tailor treatment strategy in these complex cases.
Topics: Female; Gynecologic Surgical Procedures; Humans; Pelvic Organ Prolapse; Vaginal Neoplasms
PubMed: 35167139
DOI: 10.1002/ijgo.14137 -
Diagnostics (Basel, Switzerland) Jan 2022The microbiome is vital for the proper function of the gastrointestinal tract (GIT) and the maintenance of overall wellbeing. Gut ischemia may lead to disruption of the... (Review)
Review
The microbiome is vital for the proper function of the gastrointestinal tract (GIT) and the maintenance of overall wellbeing. Gut ischemia may lead to disruption of the intestinal mucosal barrier, resulting in bacterial translocation. In this systematic review, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines, we constructed a search query using the PICOT (Patient, Intervention, Comparison, Outcome, Time) framework. Eligible studies reported in PubMed, up to April 2021 were selected, from which, 57 publications' data were included. According to these, escape of intraluminal potentially harmful factors into the systemic circulation and their transmission to distant organs and tissues, in utero, at birth, or immediately after, can be caused by reduced blood oxygenation. Various factors are involved in this situation. The GIT is a target organ, with high sensitivity to ischemia-hypoxia, and even short periods of ischemia may cause significant local tissue damage. Fetal hypoxia and perinatal asphyxia reduce bowel motility, especially in preterm neonates. Despite the fact that microbiome arouse the interest of scientists in recent decades, the pathophysiologic patterns which mediate in perinatal hypoxia/asphyxia conditions and gut function have not yet been well understood.
PubMed: 35054381
DOI: 10.3390/diagnostics12010214 -
Transplantation Reviews (Orlando, Fla.) Jul 2021Efforts to ameliorate the organ shortage have predominantly focused on improving processes and interventions at multiple levels in the organ donation process, but no... (Review)
Review
BACKGROUND
Efforts to ameliorate the organ shortage have predominantly focused on improving processes and interventions at multiple levels in the organ donation process, but no comprehensive review of hospital-level features contributing to organ donation exists. We undertook a systematic review of the literature to better understand current knowledge and knowledge gaps about hospital-level metrics and interventions associated with successful organ donation.
METHODS
We searched six electronic databases (PubMed, Embase, CINAHL, Web of Science, Health Business Elite, and Google scholar) and conference abstracts for articles on hospital-level features associated with the final outcome of organ donation (PROSPERO CRD42020187080). Editorials, letters to the editor, and reviews without original data were excluded. Our main outcomes were conversion rate, donation rate, number of organs recovered, number of donors, and authorization rate.
RESULTS
Our search yielded 2177 studies, and after a thorough assessment, 72 articles were included in this systematic review. Studies were thematically categorized into 1) Hospital-level interventions associated with metrics of organ donation; these included patient- and family-centric measures (i.e. standardized interviews, collaborative requesting and decoupling, and dedicated in-house coordinators), and donor management goals that significantly increased conversion rates by up to 64%; 2) Hospital-level multi-stage programs/policies; which increased authorization rates between 30 and 50%; and 3) Hospital characteristics and qualities; being an academic center, trauma center and larger hospital correlated with higher authorization and conversion rates. Most studies had considerable risk of bias and were of low quality.
CONCLUSIONS
There is a lack of well-designed studies on hospital-level metrics and interventions associated with organ donation. The use of thoughtful, patient- and family-centric approaches to authorization generally is associated with more organ donors. Future work can build on what is known about the hospital role in organ donation to improve the entire organ donation process.
Topics: Benchmarking; Hospitals; Humans; Organ Transplantation; Tissue Donors; Tissue and Organ Procurement
PubMed: 33744820
DOI: 10.1016/j.trre.2021.100613 -
The Cochrane Database of Systematic... Jan 2017Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU), despite advances in the treatment of patients with severe sepsis and septic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU), despite advances in the treatment of patients with severe sepsis and septic shock, including early recognition, appropriate treatment with antibiotics and support of organs that may have been affected by the illness. High-volume haemofiltration (HVHF) is a blood purification technique that may improve outcomes in severe sepsis or septic shock. The technique of HVHF has evolved from renal replacement therapies used in the ICU to treat critically ill patients with acute kidney injury (AKI). This review was first published in 2013 and was updated in 2016.
OBJECTIVES
To investigate whether HVHF improves outcomes in critically ill adults admitted to the intensive care unit with severe sepsis or septic shock. The primary outcome of this systematic review is patient mortality; secondary outcomes include duration of stay, severity of organ dysfunction and adverse events.
SEARCH METHODS
For this updated version, we extended searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), Web of Science and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to 31 December 2015. The original search was performed in 2011. We also searched trials registers.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration versus standard or usual dialysis therapy, as well as RCTs and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration versus no similar dialysis therapy. These studies involved adults treated in critical care units.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data and assessed trial quality. We sought additional information from trialists as required.
MAIN RESULTS
We included four randomized trials involving 200 participants. Owing to small numbers of studies and participants, it was not possible to combine data for all outcomes. Two trials reported 28-day mortality, and one trial reported hospital mortality; in the third trial, the number of deaths stated did not match the quoted mortality rates. The pooled risk ratio (95% confidence interval) for 28-day mortality associated with HVHF was 0.89 (0.60 to 1.32, two trials, 146 participants, low-quality evidence). One study (137 participants, low-quality evidence) reported length of stay in the ICU. Two trials (170 participants, low-quality evidence) reported organ dysfunction, but we could not pool results owing to reporting differences. Three studies (189 participants, low-quality evidence) reported on haemodynamic changes, but we could not pool results owing to reporting differences. Investigators reported no adverse events. Overall, the included studies had low risk of bias.
AUTHORS' CONCLUSIONS
Investigators reported no adverse effects of HVHF (low-quality evidence). The results of this meta-analysis show that very few studies have been conducted to investigate the use of HVHF in critically ill patients with severe sepsis or septic shock (four studies, 201 participants, low-quality evidence). Researchers should consider additional randomized controlled trials that are large and multi-centred and have clinically relevant outcome measures. The cost-effectiveness of HVHF should also be studied. .
Topics: Adult; Critical Illness; Hemodiafiltration; Hemofiltration; Hospital Mortality; Humans; Intensive Care Units; Organ Dysfunction Scores; Randomized Controlled Trials as Topic; Sepsis; Shock, Septic; Time Factors
PubMed: 28141912
DOI: 10.1002/14651858.CD008075.pub3 -
Sensors (Basel, Switzerland) May 2021Three-dimensional (3D) in vitro models, such as organ-on-a-chip platforms, are an emerging and effective technology that allows the replication of the function of... (Review)
Review
Three-dimensional (3D) in vitro models, such as organ-on-a-chip platforms, are an emerging and effective technology that allows the replication of the function of tissues and organs, bridging the gap amid the conventional models based on planar cell cultures or animals and the complex human system. Hence, they have been increasingly used for biomedical research, such as drug discovery and personalized healthcare. A promising strategy for their fabrication is 3D printing, a layer-by-layer fabrication process that allows the construction of complex 3D structures. In contrast, 3D bioprinting, an evolving biofabrication method, focuses on the accurate deposition of hydrogel bioinks loaded with cells to construct tissue-engineered structures. The purpose of the present work is to conduct a systematic review (SR) of the published literature, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, providing a source of information on the evolution of organ-on-a-chip platforms obtained resorting to 3D printing and bioprinting techniques. In the literature search, PubMed, Scopus, and ScienceDirect databases were used, and two authors independently performed the search, study selection, and data extraction. The goal of this SR is to highlight the importance and advantages of using 3D printing techniques in obtaining organ-on-a-chip platforms, and also to identify potential gaps and future perspectives in this research field. Additionally, challenges in integrating sensors in organs-on-chip platforms are briefly investigated and discussed.
Topics: Animals; Bioprinting; Humans; Hydrogels; Lab-On-A-Chip Devices; Printing, Three-Dimensional; Tissue Engineering
PubMed: 34068811
DOI: 10.3390/s21093304 -
Revista Da Associacao Medica Brasileira... Mar 2020Melatonin has anti-inflammatory and antioxidant properties that can influence tissue growth and apoptosis. This aspect may influence the success of organ...
OBJECTIVE
Melatonin has anti-inflammatory and antioxidant properties that can influence tissue growth and apoptosis. This aspect may influence the success of organ transplantation. To evaluate the relationship between melatonin and organ transplantation.
METHODS
A systematic review was performed in PubMed databases using the search terms: "melatonin physiology" or "melatonin therapy" and "transplant pharmacology" or "transplant physiology" or "transplant therapy" or "Transplant therapy". Experiments on the organs of the reproductive system were not included. After analysis, five articles were selected after reading the title and abstract of 50 manuscripts. The works were divided into two aspects: a) analysis of the influence of the organ transplantation procedure on melatonin production; b) action of melatonin on organ transplantation.
RESULTS
The cardiac transplantation surgical procedure, immunosuppression, and graft did not influence melatonin secretion in rodents, but there was a significant reduction of melatonin in the renal transplantation procedure in patients with renal insufficiency. Melatonin administration in experimental models decreased rejection and improved transplant success.
CONCLUSION
Studies show that melatonin can reduce organ and species dependence, and the use of melatonin decreases graft rejection.
Topics: Animals; Antioxidants; Graft Rejection; Graft Survival; Heart Transplantation; Humans; Immunosuppression Therapy; Kidney Transplantation; Melatonin; Organ Transplantation; Rats
PubMed: 32520157
DOI: 10.1590/1806-9282.66.3.353