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EBioMedicine May 2024Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols.
METHODS
Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation.
FINDINGS
The systematic review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events).
INTERPRETATION
This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design.
FUNDING
This study was funded in part by Italian Ministry of Health-Current researchIRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.
Topics: Argon; Neuroprotective Agents; Humans; Animals; Administration, Inhalation; Disease Models, Animal; Drug Evaluation, Preclinical
PubMed: 38691938
DOI: 10.1016/j.ebiom.2024.105143 -
World Journal of Gastrointestinal... Apr 2024The quality-adjusted life year (QALY) is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments...
BACKGROUND
The quality-adjusted life year (QALY) is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments and procedures. Surgical waiting lists (SWLs) represent a pressing problem in public healthcare. The QALY measure has rarely been used in the context of surgery. It would be interesting to know how many QALYs are lost by patients on SWLs.
AIM
To investigate the relationship between QALYs and SWLs in a systematic review of the scientific literature.
METHODS
The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. An unlimited search was carried out in PubMed, updated on January 19, 2024. Data on the following variables were investigated and analyzed: Specialty, country of study, procedure under study, scale used to measure QALYs, the use of a theoretical or real-life model, objectives of the study and items measured, the economic value assigned to the QALY in the country in question, and the results and conclusions published.
RESULTS
Forty-eight articles were selected for the study. No data were found regarding QALYs lost on SWLs. The specialties in which QALYs were studied the most in relation to the waiting list were urology and general surgery, with 15 articles each. The country in which the most studies of QALYs were carried out was the United States ( = 21), followed by the United Kingdom ( = 9) and Canada ( = 7). The most studied procedure was organ transplantation ( = 39), including 15 kidney, 14 liver, 5 heart, 4 lung, and 1 intestinal. Arthroplasty ( = 4), cataract surgery ( = 2), bariatric surgery ( = 1), mosaicplasty ( = 1), and septoplasty ( = 1) completed the surgical interventions included. Thirty-nine of the models used were theoretical (the most frequently applied being the Markov model, = 34), and nine were real-life. The survey used to measure quality of life in 11 articles was the European Quality of Life-5 dimensions, but in 32 articles the survey was not specified. The willingness-to-pay per QALY gained ranged from $100000 in the United States to €20000 in Spain.
CONCLUSION
The relationship between QALYs and SWLs has only rarely been studied in the literature. The rate of QALYs lost on SWLs has not been determined. Future research is warranted to address this issue.
PubMed: 38690041
DOI: 10.4240/wjgs.v16.i4.1155 -
Frontiers in Oncology 2024Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with...
Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.
PubMed: 38665946
DOI: 10.3389/fonc.2024.1383730 -
Respiratory Medicine and Research Jun 2024Exertional dyspnoea, a cardinal symptom in interstitial lung disease (ILD), can be objectively measured during a 6-min walk test (6MWT) using the Borg Dyspnoea Score...
BACKGROUND
Exertional dyspnoea, a cardinal symptom in interstitial lung disease (ILD), can be objectively measured during a 6-min walk test (6MWT) using the Borg Dyspnoea Score (BDS). However, the clinical utility of this measurement is unclear. The purpose of this systematic review was to determine the association between 6MWT BDS and prognosis (mortality and lung transplantation), other 6MWT variables and measures of pulmonary function.
METHODS
MEDLINE, EMBASE, Cochrane and SCOPUS databases were used to identify studies reporting an association between post-6MWT BDS and the relevant outcomes in adults with ILD. Language was limited to English. Study quality was assessed using the Quality in Prognosis Study risk of bias tool. A narrative synthesis for each outcome was performed.
RESULTS
Ten full-text studies (n = 518) were included. Four studies had high overall risk of bias. Two studies (n = 127) reported prognosis and both found that higher 6MWT BDS was associated with increased all-cause mortality. However, the certainty of evidence was very low due to study design and likely publication bias. Higher post-6MWT BDS may be associated with shorter, or no effect on 6MWD; and lower pulmonary function. There was insufficient evidence that BDS correlated with 6MWT oxygen saturation.
CONCLUSIONS
Post-6MWT BDS has a potential role as a predictor of all-cause mortality in ILD, 6MWD and lower pulmonary function. Larger studies designed to confirm these relationships and assess the independent association between the 6MWT BDS and clinical outcomes are required.
Topics: Humans; Lung Diseases, Interstitial; Dyspnea; Walk Test; Prognosis; Female; Male; Severity of Illness Index; Middle Aged; Lung Transplantation
PubMed: 38663251
DOI: 10.1016/j.resmer.2024.101103 -
Infectious Diseases and Therapy May 2024Older adults and patients with underlying conditions such as immunocompromised (IC) populations (e.g., due to medical conditions or immunosuppressive medication) are at...
INTRODUCTION
Older adults and patients with underlying conditions such as immunocompromised (IC) populations (e.g., due to medical conditions or immunosuppressive medication) are at increased risk for herpes zoster (HZ). The first HZ recombinant vaccine for IC patients was approved in 2020. Limited evidence exists to inform decision-makers on HZ incidence in high-risk patients in Europe. This systematic literature review (SLR) assessed HZ incidence across 14 high-risk populations in the European Union/European Economic Area, Switzerland, and the United Kingdom.
METHODS
An SLR (Embase, Medline, 2002-2022, observational studies) was performed to identify HZ incidence (i.e., primary outcomes: rate or cumulative; secondary: relative incidence) in type 1 and 2 diabetes mellitus (DM); chronic obstructive pulmonary disease and asthma; depression; rheumatic disorders (RD); multiple sclerosis (MS); inflammatory bowel diseases (IBD); psoriasis; lupus; human immunodeficiency virus (HIV); solid organ transplantation (SOT); solid organ malignancy (SOM); hematologic malignancy (HM); and stem cell transplantation (SCT).
RESULTS
Of 776 unique records screened, 59 studies were included (24 reported incidence rate per 1000 person-years; two, cumulative incidence per 1000 persons; and 33, relative incidence). The highest incidence rates were reported for SOT (12.1-78.8) and SCT (37.2-56.1); HM (2.9-32.0); RD (0.41-21.5); lupus (11.0-16.5); IC mixed population (11.3-15.5); HIV/AIDS (11.8-13.0); chronic respiratory diseases (4.7-11.4); SOM (8.8-11.0); IBD (7.0-10.8); DM (4.3-9.4); depression (7.2-7.6); MS (5.7-6.3); and psoriasis (5.3-6.1). In many high-risk populations, HZ incidence was higher for older age groups, women, and some treatments.
CONCLUSIONS
The HZ incidence rate in Europe increased with age and varied across high-risk populations, with high rates for solid organ and stem cell transplants, cancer, and rheumatoid arthritis. Most studies were retrospective with methodological differences affecting generalizability and comparability. Future studies should stratify data by IC population, age, sex, severity, medication, and study timeframe.
PubMed: 38656653
DOI: 10.1007/s40121-024-00963-w -
Transplant International : Official... 2024The shortage of organs for transplantations is increasing in Europe as well as globally. Many initiatives to the organ shortage, such as opt-out systems for deceased... (Review)
Review
The shortage of organs for transplantations is increasing in Europe as well as globally. Many initiatives to the organ shortage, such as opt-out systems for deceased donation and expanding living donation, have been insufficient to meet the rising demand for organs. In recurrent discussions on how to reduce organ shortage, financial incentives and removal of disincentives, have been proposed to stimulate living organ donation and increase the pool of available donor organs. It is important to understand not only the ethical acceptability of (dis)incentives for organ donation, but also its societal acceptance. In this review, we propose a research agenda to help guide future empirical studies on public preferences in Europe towards the removal of disincentives and introduction of incentives for organ donation. We first present a systematic literature review on public opinions concerning (financial) (dis)incentives for organ donation in European countries. Next, we describe the results of a randomized survey experiment conducted in the United States. This experiment is crucial because it suggests that societal support for incentivizing organ donation depends on the specific features and institutional design of the proposed incentive scheme. We conclude by proposing this experiment's framework as a blueprint for European research on this topic.
Topics: Humans; Public Opinion; Tissue and Organ Procurement; Europe; Motivation; Living Donors; United States; Tissue Donors
PubMed: 38644936
DOI: 10.3389/ti.2024.12483 -
Journal of Cardiothoracic and Vascular... Jul 2024The mismatch between the demand for and supply of organs for transplantation is steadily growing. Various strategies have been incorporated to improve the availability...
OBJECTIVE
The mismatch between the demand for and supply of organs for transplantation is steadily growing. Various strategies have been incorporated to improve the availability of organs, including organ use from patients receiving extracorporeal membrane oxygenation (ECMO) at the time of death. However, there is no systematic evidence of the outcome of grafts from these donors.
DESIGN
Systematic literature review (Scopus and PubMed, up to October 11, 2023).
SETTING
All study designs.
PARTICIPANTS
Organ recipients from patients on ECMO at the time of death.
INTERVENTION
Outcome of organ donation from ECMO donors.
MEASUREMENTS AND MAIN RESULTS
The search yielded 1,692 publications, with 20 studies ultimately included, comprising 147 donors and 360 organ donations. The most frequently donated organs were kidneys (68%, 244/360), followed by liver (24%, 85/360). In total, 98% (292/299) of recipients survived with a preserved graft function (92%, 319/347) until follow-up within a variable period of up to 3 years.
CONCLUSION
Organ transplantation from donors supported with ECMO at the time of death shows high graft and recipient survival. ECMO could be a suitable approach for expanding the donor pool, helping to alleviate the worldwide organ shortage.
Topics: Humans; Extracorporeal Membrane Oxygenation; Tissue and Organ Procurement; Tissue Donors; Organ Transplantation
PubMed: 38643059
DOI: 10.1053/j.jvca.2024.03.020 -
Transplantation Reviews (Orlando, Fla.) Jul 2024Cardiovascular disease, associated risk factors and obesity are prevalent after liver transplant and modifiable through lifestyle changes. Understanding what lifestyle... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Cardiovascular disease, associated risk factors and obesity are prevalent after liver transplant and modifiable through lifestyle changes. Understanding what lifestyle interventions and their respective components are effective is essential for translation to clinical practice. We aimed to investigate the effects of diet and physical activity interventions on weight, body mass index and other cardiovascular disease risk factors in liver transplant recipients, and systematically describe the interventions.
METHODS
We systematically searched Embase, MEDLINE, Psycho Info, CINAHL, Cochrane central register of controlled trials, PeDro, AMED, BNI, Web of Science, OpenGrey, ClinicalTrials.gov and the international clinical trials registry from inception to 31 May 2023. Search results were screened by two independent reviewers: randomised control trials with interventions that targeted diet and physical activity behaviours in liver transplant recipients were considered eligible. Two independent reviewers extracted and synthesised data for study, participant and intervention details and results. We used the Revised Cochrane Risk of Bias Tool for Randomised Trials to assess risk of bias for outcomes and the GRADE approach to rate the quality of the body of evidence. When two or more studies reported findings for an outcome, we pooled data using random-effects meta-analysis.
RESULTS
Six studies were included, reporting three physical activity and three combined diet and physical activity interventions. Participants were 2 months-4 years post-transplant. Interventions lasted 12 weeks-10 months and were delivered remotely and/or in-person, most commonly delivered to individual participants by health care or sports professionals. Five studies described individual tailoring, e.g. exercise intensity. Adherence to interventions ranged from 51% to 94%. No studies reported fidelity. Intervention components were not consistently reported. In meta-analysis, diet and physical activity interventions did not significantly reduce weight or body mass index compared to control groups, however no studies targeted participants with obesity. Diet and physical activity interventions reduced percentage body fat and triglycerides compared to control groups but did not reduce total cholesterol or increase activity. The GRADE quality of evidence was low or very low.
CONCLUSION
Diet and physical activity interventions reduced percentage body fat and triglycerides in liver transplant recipients. Further good quality research is needed to evaluate their effect on other cardiovascular disease risk factors, including weight and BMI. Interventions need to be better described and evaluated to improve evidence base and inform patient care.
Topics: Humans; Liver Transplantation; Exercise; Cardiovascular Diseases; Heart Disease Risk Factors; Transplant Recipients; Diet; Risk Factors
PubMed: 38615497
DOI: 10.1016/j.trre.2024.100852 -
Transplantation Reviews (Orlando, Fla.) Jul 2024Impact of donor smoking history on kidney transplant recipient outcomes is undefined. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Impact of donor smoking history on kidney transplant recipient outcomes is undefined.
METHODS
We systematically searched, critically appraised, and summarized associations between donor smoking and primary outcomes of death-censored and all-cause graft failure (DCGF, ACGF), and secondary outcomes of allograft histology, delayed graft function, serum creatinine, estimated glomerular filtration rate, and mortality. We searched MEDLINE, Embase, and Cochrane Databases from 2000 to 2023. Risk of bias was assessed using Risk of Bias in Non-randomized Studies - of Exposure tool. Quality of evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation Working Group recommendations. We pooled results using inverse variance, random-effects model and reported hazard ratios for time-to-event outcomes or binomial proportions. Statistical heterogeneity was assessed with I statistic.
RESULTS
From 1785 citations, we included 17 studies. Donor smoking was associated with modestly increased DCGF (HR 1.05 (95% CI: 1.01, 1.09); I = 0%; low quality of evidence), predominantly in deceased donors, and ACGF in adjusted analyses (HR 1.12 (95% CI: 1.06, 1.19); I = 20%; very low quality of evidence). Other outcomes could not be pooled meaningfully.
CONCLUSIONS
Kidney donor smoking history was associated with modestly increased risk of death-censored graft failure and all-cause graft failure. This review emphasizes the need for further research, standardized reporting, and thoughtful consideration of donor factors like smoking in clinical decision-making on kidney utilization and allocation.
Topics: Humans; Kidney Transplantation; Graft Survival; Smoking; Graft Rejection; Tissue Donors; Risk Factors; Transplant Recipients
PubMed: 38608414
DOI: 10.1016/j.trre.2024.100854 -
Clinical and Experimental Pediatrics Apr 2024Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to...
Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to pool global data from leading transplant institutions and identify the overall incidence, risk factors, and causative organisms of BSI in pediatric liver transplant recipients. A systematic review of the PubMed and OVID databases was conducted from 2000 to 2022. The initial search yielded 252 unique articles, which were independently reviewed by 2 authors. Articles that reported pediatric-specific data on BSI in isolated liver transplant patients were included, including the incidence of BSI, isolated organisms, and involved risk factors involved. This systematic review was registered with PROSPERO (ID: CRD42023403206). Fourteen articles from the United States, France, Iran, Japan, Korea, South Africa, Thailand, and Turkey were included. A total of 4,812 liver transplants were included in the final analysis. The mean patient age was 25 months (age range, 0-18 years), and 50.9% were male. The overall incidence of BSI was 23.5% (range, 14.7%-55%). The most commonly reported organisms were Staphylococcus epidermidis, Enterococcus, Klebsiella spp., and Escherichia coli. Among the risk factors studied, postoperative biliary complications, a medical history of biliary atresia, and younger age were the risk factors most commonly associated with BSI. Bacterial BSI after pediatric liver transplantation occur at a high incidence, with a unique organism profile notable for a higher percentage of gram-negative organisms. Further studies are required to determine the most appropriate prophylactic and empirical antibiotic management strategies for this population.
PubMed: 38605664
DOI: 10.3345/cep.2023.01466