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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 -
Frontiers in Microbiology 2024Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease comprising five stages: fever, hypotension, oliguria, diuresis (polyuria), and convalescence....
INTRODUCTION
Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease comprising five stages: fever, hypotension, oliguria, diuresis (polyuria), and convalescence. Increased vascular permeability, coagulopathy, and renal injury are typical clinical features of HFRS, which has a case fatality rate of 1-15%. Despite this, a comprehensive meta-analyses of the clinical characteristics of patients who died from HFRS is lacking.
METHODS
Eleven Chinese- and English-language research databases were searched, including the China National Knowledge Infrastructure Database, Wanfang Database, SinoMed, VIP Database, PubMed, Embase, Scopus, Cochrane Library, Web of Science, Proquest, and Ovid, up to October 5, 2023. The search focused on clinical features of patients who died from HFRS. The extracted data were analyzed using STATA 14.0.
RESULTS
A total of 37 articles on 140,295 patients with laboratory-confirmed HFRS were included. Categorizing patients into those who died and those who survived, it was found that patients who died were older and more likely to smoke, have hypertension, and have diabetes. Significant differences were also observed in the clinical manifestations of multiple organ dysfunction syndrome, shock, occurrence of overlapping disease courses, cerebral edema, cerebral hemorrhage, toxic encephalopathy, convulsions, arrhythmias, heart failure, dyspnea, acute respiratory distress syndrome, pulmonary infection, liver damage, gastrointestinal bleeding, acute kidney injury, and urine protein levels. Compared to patients who survived, those who died were more likely to demonstrate elevated leukocyte count; decreased platelet count; increased lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase levels; prolonged activated partial thromboplastin time and prothrombin time; and low albumin and chloride levels and were more likely to use continuous renal therapy. Interestingly, patients who died received less dialysis and had shorter average length of hospital stay than those who survived.
CONCLUSION
Older patients and those with histories of smoking, hypertension, diabetes, central nervous system damage, heart damage, liver damage, kidney damage, or multiorgan dysfunction were at a high risk of death. The results can be used to assess patients' clinical presentations and assist with prognostication.https://www.crd.york.ac.uk/prospero/, (CRD42023454553).
PubMed: 38638893
DOI: 10.3389/fmicb.2024.1329683 -
High Blood Pressure & Cardiovascular... Mar 2024Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg...
Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events. Hypertension guidelines proposed a triple combination therapy based on renin angiotensin system blocking agent, a thiazide or thiazide-like diuretic, and a dihydropyridinic calcium-channel blocker, to almost all patients with RHT, who should also receive either a beta-blocker or a mineralocorticoid receptor antagonist, or both, depending on concomitant conditions and contraindications. Several other drugs may be attempted, when elevated BP levels persist in these RHT patients, although their added efficacy in lowering BP levels on top of optimal medical therapy is uncertain. Also, renal denervation has demonstrated to be a valid therapeutic alternative in RHT patients. More recently, novel drug classes and molecules have been tested in phase 2 randomised controlled clinical trials in patients with RHT on top of optimal medical therapy with at least 2-3 antihypertensive drugs. These novel drugs, which are orally administered and are able to antagonize different pathophysiological pathways, are represented by non-steroid mineralocorticorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin receptor antagonists, all of which have proven to reduce seated office and 24-h ambulatory systolic/diastolic BP levels. The main findings of randomized clinical trials performed with these drugs as well as their potential indications for the clinical management of RHT patients are summarised in this systematic review article.
Topics: Humans; Antihypertensive Agents; Blood Pressure; Drug Resistance; Drug Therapy, Combination; Hypertension; Precision Medicine; Treatment Outcome
PubMed: 38616212
DOI: 10.1007/s40292-024-00634-4 -
PloS One 2024Numerous pre-clinical and observational studies have explored the potential effects of fluoride (F) at varying concentrations on diverse systems and organs. While some...
Numerous pre-clinical and observational studies have explored the potential effects of fluoride (F) at varying concentrations on diverse systems and organs. While some have assessed the endocrinological conditions of children and adults, a consensus regarding the interaction between F and the thyroid remains elusive. This systematic review aimed to gather primary evidence on the association between F and changes in the thyroid at optimal and high levels in water supply as stipulated by the World Health Organization. A search strategy, incorporating terms pertinent to the studies, was employed across PubMed, Scopus, Web of Science, Lilacs, and Google Scholar. Following the review of studies, data were extracted and analyzed using the Grading of Recommendations, Assessment, Development, and Evaluations to assess the quality of the evidence. Our results yielded 3,568 studies, of which seven met the inclusion criteria for this review. Five of the seven studies identified an association between high F exposure and thyroid function. In the analysis of methodological quality, every study was found to have major or minor methodological issues and significant risk of bias. The overall confidence in the evidence was deemed low for all outcomes in the seven studies. The evidence compiled in this review suggests a potential association between chronic high levels of F exposure and thyroid damage. Nonetheless, further studies with robust design and high methodological quality are required to provide evidence for policy makers and health care practitioners.
Topics: Child; Adult; Humans; Fluorides; Thyroid Gland
PubMed: 38593166
DOI: 10.1371/journal.pone.0301911 -
World Journal of Transplantation Mar 2024Liver transplantation (LT) is a life-saving intervention for patients with end-stage liver disease. However, the equitable allocation of scarce donor organs remains a...
BACKGROUND
Liver transplantation (LT) is a life-saving intervention for patients with end-stage liver disease. However, the equitable allocation of scarce donor organs remains a formidable challenge. Prognostic tools are pivotal in identifying the most suitable transplant candidates. Traditionally, scoring systems like the model for end-stage liver disease have been instrumental in this process. Nevertheless, the landscape of prognostication is undergoing a transformation with the integration of machine learning (ML) and artificial intelligence models.
AIM
To assess the utility of ML models in prognostication for LT, comparing their per formance and reliability to established traditional scoring systems.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a thorough and standardized literature search using the PubMed/MEDLINE database. Our search imposed no restrictions on publication year, age, or gender. Exclusion criteria encompassed non-English stu dies, review articles, case reports, conference papers, studies with missing data, or those exhibiting evident methodological flaws.
RESULTS
Our search yielded a total of 64 articles, with 23 meeting the inclusion criteria. Among the selected studies, 60.8% originated from the United States and China combined. Only one pediatric study met the criteria. Notably, 91% of the studies were published within the past five years. ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values (ranging from 0.6 to 1) across all studies, surpassing the performance of traditional scoring systems. Random forest exhibited superior predictive capa bilities for 90-d mortality following LT, sepsis, and acute kidney injury (AKI). In contrast, gradient boosting excelled in predicting the risk of graft-versus-host disease, pneumonia, and AKI.
CONCLUSION
This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT, marking a significant evolution in the field of prognostication.
PubMed: 38576762
DOI: 10.5500/wjt.v14.i1.88891 -
Frontiers in Immunology 2024The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple... (Review)
Review
The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple etiologies of these conditions. The number of targeted therapies available on the market is limited, whereas the prevalence of autoimmune conditions in the global population continues to rise. Mathematical modeling of biological systems is an essential tool which may be applied in support of decision-making across R&D drug programs to improve the probability of success in the development of novel medicines. Over the past decades, multiple models of autoimmune diseases have been developed. Models differ in the spectra of quantitative data used in their development and mathematical methods, as well as in the level of "mechanistic granularity" chosen to describe the underlying biology. Yet, all models strive towards the same goal: to quantitatively describe various aspects of the immune response. The aim of this review was to conduct a systematic review and analysis of mathematical models of autoimmune diseases focused on the mechanistic description of the immune system, to consolidate existing quantitative knowledge on autoimmune processes, and to outline potential directions of interest for future model-based analyses. Following a systematic literature review, 38 models describing the onset, progression, and/or the effect of treatment in 13 systemic and organ-specific autoimmune conditions were identified, most models developed for inflammatory bowel disease, multiple sclerosis, and lupus (5 models each). ≥70% of the models were developed as nonlinear systems of ordinary differential equations, others - as partial differential equations, integro-differential equations, Boolean networks, or probabilistic models. Despite covering a relatively wide range of diseases, most models described the same components of the immune system, such as T-cell response, cytokine influence, or the involvement of macrophages in autoimmune processes. All models were thoroughly analyzed with an emphasis on assumptions, limitations, and their potential applications in the development of novel medicines.
Topics: Humans; Autoimmune Diseases; Models, Theoretical; Multiple Sclerosis; Immunity; T-Lymphocytes
PubMed: 38550585
DOI: 10.3389/fimmu.2024.1371620 -
Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487 -
Radiology Case Reports Jun 2024Primary central nervous system post-transplant lymphoproliferative disease (PCNS-PTLD) is a rare subset of post-transplant lymphoproliferative disorder (PTLD) isolated...
Primary central nervous system post-transplant lymphoproliferative disease (PCNS-PTLD) is a rare subset of post-transplant lymphoproliferative disorder (PTLD) isolated to the CNS without nodal or extra-nodal organ involvement [1,2]. PCNS-PTLD occurs primarily in patients following either solid organ transplants or hematopoietic stem cell transplants and tends to be monomorphic DLBCL. The development of PCNS-PTLD is commonly associated with EBV infection [3]. Many intracranial pathologies can resemble the imaging appearance of PCNS-PTLD, including primary CNS lymphoma, glial tumors, metastatic disease, and intracranial abscesses. The purpose of this systematic review is to identify the most common imaging characteristics of PCNS-PTLD. Our review included 97 sources that describe the imaging appearance of PCNS-PTLD. Based on our review, PCNS-PTLD lesions are typically multifocal, ring-enhancing and diffusion-restricting. PCNS-PTLD lesions typically demonstrate focal FDG avidity. Despite advancement in medical imaging, PCNS-PTLD remains a diagnostic challenge due to its rare incidence. Limited data is available on advanced imaging with regards to PTLD, but techniques including DCE-MRI and fMRI demonstrate promising results that may help further delineate PCNS-PTLD.
PubMed: 38515768
DOI: 10.1016/j.radcr.2024.02.030 -
Environment International Mar 2024The World Health Organization is coordinating an international project aimed at systematically reviewing the evidence regarding the association between radiofrequency... (Meta-Analysis)
Meta-Analysis
Effects of radiofrequency electromagnetic field (RF-EMF) exposure on male fertility: A systematic review of experimental studies on non-human mammals and human sperm in vitro.
BACKGROUND
The World Health Organization is coordinating an international project aimed at systematically reviewing the evidence regarding the association between radiofrequency electromagnetic field (RF-EMF) exposure and adverse health effects. Reproductive health outcomes have been identified among the priority topics to be addressed.
OBJECTIVES
To evaluate the effect of RF-EMF exposure on male fertility of experimental mammals and on human sperm exposed in vitro.
METHODS
Three electronic databases (PubMed, Scopus and EMF Portal) were last searched on September 17, 2022. Two independent reviewers screened the studies, which were considered eligible if met the following criteria: 1) Peer-reviewed publications of sham controlled experimental studies, 2) Non-human male mammals exposed at any stage of development or human sperm exposed in vitro, 3) RF-EMF exposure within the frequency range of 100 kHz-300 GHz, including electromagnetic pulses (EMP), 4) one of the following indicators of reproductive system impairment:Two reviewers extracted study characteristics and outcome data. We assessed risk of bias (RoB) using the Office of Health Assessment and Translation (OHAT) guidelines. We categorized studies into 3 levels of overall RoB: low, some or high concern. We pooled study results in a random effects meta-analysis comparing average exposure to no-exposure and in a dose-response meta-analysis using all exposure doses. For experimental animal studies, we conducted subgroup analyses for species, Specific Absorption Rate (SAR) and temperature increase. We grouped studies on human sperm exposed in vitro by the fertility status of sample donors and SAR. We assessed the certainty of the evidence using the GRADE approach after excluding studies that were rated as "high concern" for RoB.
RESULTS
One-hundred and seventeen papers on animal studies and 10 papers on human sperm exposed in vitro were included in this review. Only few studies were rated as "low concern" because most studies were at RoB for exposure and/or outcome assessment. Subgrouping the experimental animal studies by species, SAR, and temperature increase partly accounted for the heterogeneity of individual studies in about one third of the meta-analyses. In no case was it possible to conduct a subgroup analysis of the few human sperm in vitro studies because there were always 1 or more groups including less than 3 studies. Among all the considered endpoints, the meta-analyses of animal studies provided evidence of adverse effects of RF-EMF exposure in all cases but the rate of infertile males and the size of the sired litters. The assessment of certainty according to the GRADE methodology assigned a moderate certainty to the reduction of pregnancy rate and to the evidence of no-effect on litter size, a low certainty to the reduction of sperm count, and a very low certainty to all the other meta-analysis results. Studies on human sperm exposed in vitro indicated a small detrimental effect of RF-EMF exposure on vitality and no-effect on DNA/chromatin alterations. According to GRADE, a very low certainty was attributed to these results. The few studies that used EMP exposure did not show effects on the outcomes. A low to very low certainty was attributed to these results.
DISCUSSION
Many of the studies examined suffered of severe limitations that led to the attribution of uncertainty to the results of the meta-analyses and did not allow to draw firm conclusions on most of the endpoints. Nevertheless, the associations between RF-EMF exposure and decrease of pregnancy rate and sperm count, to which moderate and low certainty were attributed, are not negligible, also in view of the indications that in Western countries human male fertility potential seems to be progressively declining. It was beyond the scope of our systematic review to determine the shape of the dose-response relationship or to identify a minimum effective exposure level. The subgroup and the dose-response fitting analyses did not show a consistent relationship between the exposure levels and the observed effects. Notably, most studies evaluated RF-EMF exposure levels that were higher than the levels to which human populations are typically exposed, and the limits set in international guidelines. For these reasons we cannot provide suggestions to confirm or reconsider current human exposure limits. Considering the outcomes of this systematic review and taking into account the limitations found in several of the studies, we suggest that further investigations with better characterization of exposure and dosimetry including several exposure levels and blinded outcome assessment were conducted.
PROTOCOL REGISTRATION
Protocols for the systematic reviews of animal studies and of human sperm in vitro studies were published in Pacchierotti et al., 2021. The former was also registered in PROSPERO (CRD42021227729 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID = 227729) and the latter in Open Science Framework (OSF Registration DOI https://doi.org/10.17605/OSF.IO/7MUS3).
Topics: Animals; Humans; Male; Electromagnetic Fields; Mammals; Radio Waves; Reproduction; Semen; Infertility, Male
PubMed: 38492496
DOI: 10.1016/j.envint.2024.108509 -
Frontiers in Endocrinology 2024Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations...
BACKGROUND
Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.
METHODS
We systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.
RESULTS
Our study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.
CONCLUSION
Based on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.
Topics: Humans; Hedgehog Proteins; Pituitary Diseases; Pituitary Gland; Hypopituitarism; Mutation; Syndrome
PubMed: 38464967
DOI: 10.3389/fendo.2024.1338781