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The Science of the Total Environment Dec 2023Plastic pollution has become a significant global problem over the years, leading to the continuous decomposition and accumulation of micro/nanoplastics (MNPLs) in the... (Review)
Review
Plastic pollution has become a significant global problem over the years, leading to the continuous decomposition and accumulation of micro/nanoplastics (MNPLs) in the environment. As a result, human exposure to these MNPLs is inevitable. The liver, in particular, is highly susceptible to potential MNPL toxicity. In this study, we systematically reviewed the current literature on MNPLs-induced hepatotoxicity and collected data on toxic events occurring at different biological levels. Then, to better understand the cause-mechanism causality, we developed an Adverse Outcome Pathway (AOP) framework for MNPLs-induced hepatotoxicity. The AOP framework provided insights into the mechanism of MNPL-induced hepatotoxicity and highlighted potential health risks such as liver dysfunction and inflammation, metabolism disorders and liver fibrosis. Moreover, we discussed the potential application of emerging toxicological models in the hepatotoxicity study. Liver organoids and liver-on-chips, which can simulate the structure and function of the liver in vitro, offer a promising alternative platform for toxicity testing and risk assessment. We proposed combining the AOP framework with these emerging toxicological models to improve our understanding of the hepatotoxic effects of MNPLs. Overall, this study performed a preliminary exploration of novel toxicological methodologies to assess the hepatotoxicity of MNPLs, providing a deeper understanding of environmental toxicology.
Topics: Humans; Adverse Outcome Pathways; Microplastics; Drug-Related Side Effects and Adverse Reactions; Chemical and Drug Induced Liver Injury
PubMed: 37517720
DOI: 10.1016/j.scitotenv.2023.165659 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
Antioxidants (Basel, Switzerland) Jul 2023Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver... (Review)
Review
Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver inflammation, which are critical for the development of alcoholic liver disease (ALD). Autophagy is a regulated dynamic process that sequesters damaged and excess cytoplasmic organelles for lysosomal degradation and may counteract the harmful effects of ROS-induced oxidative stress. These effects include hepatotoxicity, mitochondrial damage, steatosis, endoplasmic reticulum stress, inflammation, and iron overload. In liver diseases, particularly ALD, macroautophagy has been implicated as a protective mechanism in hepatocytes, although it does not appear to play the same role in stellate cells. Beyond the liver, autophagy may also mitigate the harmful effects of alcohol on other organs, thereby providing an additional layer of protection against ALD. This protective potential is further supported by studies showing that drugs that interact with autophagy, such as rapamycin, can prevent ALD development in animal models. This systematic review presents a comprehensive analysis of the literature, focusing on the role of autophagy in oxidative stress regulation, its involvement in organ-organ crosstalk relevant to ALD, and the potential of autophagy-targeting therapeutic strategies.
PubMed: 37507963
DOI: 10.3390/antiox12071425 -
Frontiers in Molecular Biosciences 2023Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the... (Review)
Review
Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.
PubMed: 37614441
DOI: 10.3389/fmolb.2023.1215039 -
Frontiers in Neurology 2023Fabry disease (FD) is an X-chromosome-linked disorder characterized by a reduced or complete absence of the enzyme α-galactosidase, resulting in the accumulation of...
BACKGROUND
Fabry disease (FD) is an X-chromosome-linked disorder characterized by a reduced or complete absence of the enzyme α-galactosidase, resulting in the accumulation of lysosomal globotriaosylceramide. Despite the presence of these deposits in multiple organs, the problem of sleep disorders within this population has very rarely been documented.
OBJECTIVE
This study aimed to investigate the types and prevalence of sleep disorders among patients with FD.
METHODS
Screening of the following medical databases using key terms was performed on 10 February 2023: PubMed, Scopus, and Embase. A total of 136 records were identified. The quality assessment of the studies was conducted by using tools from the National Institutes of Health (NIH) and critical appraisal tools from the Joanna Briggs Institute (JBI).
RESULTS
The study included nine studies on sleep disorders in patients with FD. The overall quality of the majority of these studies was assessed as either poor or fair. Among 330 patients, there was a slightly higher representation of female patients (56%). Sleep problems manifested 4-5 years after the onset of FD and sometimes even after 10-11 years. Genotypes of disease associated with sleep problems were rarely described. Within the FD population, the most commonly reported conditions were excessive daytime sleepiness (EDS) as well as obstructive and central sleep apnea (OSA, CSA). However, EDS occurred more frequently in FD patients, while the prevalence of OSA and CSA was within the ranges observed in the general population. The studies included indicated a lack of association between organ impairment by primary disease and EDS and OSA. The effectiveness of enzyme replacement therapy (ERT) in treating sleep disorders was not demonstrated.
CONCLUSION
The findings of this report revealed the presence of many sleep-related disorders within the FD population. However, very few studies on this subject are available, and their limited results make it difficult to truly assess the real extent of the prevalence of sleep disturbances among these individuals. There is a need to conduct further studies on this topic, involving a larger group of patients. It is important to note that there are no guidelines available for the treatment of sleep disorders in patients with FD.
PubMed: 37869133
DOI: 10.3389/fneur.2023.1217618 -
Transplant Infectious Disease : An... Aug 2023Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a...
Epidemiology, management, and burden of cytomegalovirus in solid organ transplant recipients in selected countries outside of Europe and North America: A systematic review.
BACKGROUND
Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a systematic review was conducted to describe the epidemiology, management, and burden of CMV post-SOT in selected countries outside of Europe and North America.
METHODS
MEDLINE, Embase, and Cochrane databases were searched for observational studies in SOT recipients across 15 countries in the regions of Asia, Pacific, and Latin America (search period: January 1, 2011 to September 17, 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatment patterns and guidelines, refractory and/or resistant CMV, patient-reported outcomes, and economic burden.
RESULTS
Of 2708 studies identified, 49 were eligible (n = 43/49; 87.8% in adults; n = 34/49, 69.4% in kidney recipients). Across studies, selection of CMV preventive strategy was based on CMV serostatus. Overall, rates of CMV infection (within 1 year) and CMV disease post-SOT were respectively, 10.3%-63.2% (9 studies) and 0%-19.0% (17 studies). Recurrence occurred in 35.4%-41.0% cases (3 studies) and up to 5.3% recipients died of CMV-associated causes (11 studies). Conventional treatments for CMV infection/disease included ganciclovir (GCV) or valganciclovir. Up to 4.4% patients were resistant to treatment (3 studies); no studies reported on refractory CMV. Treatment-related adverse events with GCV included neutropenia (2%-29%), anemia (13%-48%), leukopenia (11%-37%), and thrombocytopenia (13%-24%). Data on economic burden were scarce.
CONCLUSION
Outside of North America and Europe, rates of CMV infection/disease post-SOT are highly variable and CMV recurrence is frequent. CMV resistance and treatment-associated adverse events, including myelosuppression, highlight unmet needs with conventional therapy.
Topics: Adult; Humans; Cytomegalovirus; Cytomegalovirus Infections; Europe; North America; Ganciclovir; Organ Transplantation; Leukopenia
PubMed: 37254966
DOI: 10.1111/tid.14070 -
Non-coding RNA Jul 2023MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been... (Review)
Review
MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been shown to function in the genetic pathways that control many biological processes and have been implicated in roles in human disease. First identified as an aging-associated gene in , miR-71, a miRNA, has a demonstrated capability of regulating processes in numerous different invertebrates, including platyhelminths, mollusks, and insects. In these organisms, miR-71 has been shown to affect a diverse range of pathways, including aging, development, and immune response. However, the exact mechanisms by which miR-71 regulates these pathways are not completely understood. In this paper, we review the identified functions of miR-71 across multiple organisms, including identified gene targets, pathways, and the conditions which affect regulatory action. Additionally, the degree of conservation of miR-71 in the evaluated organisms and the conservation of their predicted binding sites in target 3' UTRs was measured. These studies may provide an insight on the patterns, interactions, and conditions in which miR-71 is able to exert genotypic and phenotypic influence.
PubMed: 37624033
DOI: 10.3390/ncrna9040041 -
Neurosurgical Review Sep 2023Endoscopic transsphenoidal surgery is a novel surgical technique requiring specific training. Different models and simulators have been recently suggested for it, but no... (Review)
Review
Endoscopic transsphenoidal surgery is a novel surgical technique requiring specific training. Different models and simulators have been recently suggested for it, but no systematic review is available. To provide a systematic and critical literature review and up-to-date description of the training models or simulators dedicated to endoscopic transsphenoidal surgery. A search was performed on PubMed and Scopus databases for articles published until February 2023; Google was also searched to document commercially available. For each model, the following features were recorded: training performed, tumor/arachnoid reproduction, assessment and validation, and cost. Of the 1199 retrieved articles, 101 were included in the final analysis. The described models can be subdivided into 5 major categories: (1) enhanced cadaveric heads; (2) animal models; (3) training artificial solutions, with increasing complexity (from "box-trainers" to multi-material, ct-based models); (4) training simulators, based on virtual or augmented reality; (5) Pre-operative planning models and simulators. Each available training model has specific advantages and limitations. Costs are high for cadaver-based solutions and vary significantly for the other solutions. Cheaper solutions seem useful only for the first stages of training. Most models do not provide a simulation of the sellar tumor, and a realistic simulation of the suprasellar arachnoid. Most artificial models do not provide a realistic and cost-efficient simulation of the most delicate and relatively common phase of surgery, i.e., tumor removal with arachnoid preservation; current research should optimize this to train future neurosurgical generations efficiently and safely.
Topics: Humans; Animals; Endoscopy; Cadaver; Computer Simulation; Databases, Factual; Skull Base Neoplasms
PubMed: 37725193
DOI: 10.1007/s10143-023-02149-3 -
Blood Reviews Jan 2024Chronic graft-versus-host-disease (cGvHD) remains the leading cause of morbidity among transplant recipients. The efficacy of second-line treatments varies widely based... (Review)
Review
Chronic graft-versus-host-disease (cGvHD) remains the leading cause of morbidity among transplant recipients. The efficacy of second-line treatments varies widely based on many factors, including wide differences in the organ overall response-rate response and in the current era where multiple agents are approved, and optimal sequencing of drugs based on organ ORR is unknown. We aimed to evaluate outcomes based on ORRs to the most common agents for the treatment of steroid-refractory/steroid-dependent cGvHD by conducting a systematic literature review. A total of 387 studies were evaluated for the ORRs of 12 cGvHD treatments. The highest skin ORR was observed to be 77% though some agents had an acceptable ORR. Most agents had an ocular response ranging from 17 to 50% Some agents resulted in a GI ORR of ≥88%. Rituximab showed the best response for musculoskeletal-GvHD. In the case of lung-GvHD (bronchiolitis obliterans syndrome [BOS]), negligible response was observed in patients treated with various agents. No clinically meaningful responses to treatments were reported for genital-GvHD. Most GvHD trials are focused on the ORR and partial response rates (PRR). The evidence for optimal agents for each organ is limited, and therefore, our study results are striking for differences in organ-ORR yields for a clinically meaningful difference. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD could result in favorable outcomes.
Topics: Humans; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Rituximab; Steroids; Chronic Disease
PubMed: 38087715
DOI: 10.1016/j.blre.2023.101142 -
Spine Aug 2023Systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
STUDY DESIGN
Systematic review and meta-analysis.
OBJECTIVE
To determine a pooled incidence rate for deep surgical site infection (SSI) and compare available evidence for deep SSI management among instrumented spinal fusions.
SUMMARY OF BACKGROUND DATA
Deep SSI is a common complication of instrumented spinal surgery associated with patient morbidity, poorer long-term outcomes, and higher health care costs.
MATERIALS AND METHODS
We systematically searched Medline and Embase and included studies with an adult patient population undergoing posterior instrumented spinal fusion of the thoracic, lumbar, or sacral spine, with a reported outcome of deep SSI. The primary outcome was the incidence of deep SSI. Secondary outcomes included persistent deep SSI after initial debridement, mean number of debridements, and microbiology. The subsequent meta-analysis combined outcomes for surgical site infection using a random-effects model and quantified heterogeneity using the χ 2 test and the I2 statistic. In addition, a qualitative analysis of management strategies was reported.
RESULTS
Of 9087 potentially eligible studies, we included 54 studies (37 comparative and 17 noncomparative). The pooled SSI incidence rate was 1.5% (95% CI, 1.1%-1.9%) based on 209,347 index procedures. Up to 25% of patients (95% CI, 16.8%-35.3%), had a persistent infection. These patients require an average of 1.4 (range: 0.8-1.9) additional debridements. Infecting organisms were commonly gram-positive, and among them, staphylococcus aureus was the most frequent (46%). Qualitative analysis suggests implant retention, especially for early deep SSI management. Evidence was limited for other management strategies.
CONCLUSIONS
The pooled incidence rate of deep SSI post-thoracolumbar spinal surgery is 1.5%. The rate of recurrence and repeat debridement is at least 12%, up to 25%. Persistent infection is a significant risk, highlighting the need for standardized treatment protocols. Our review further demonstrates heterogeneity in management strategies. Large-scale prospective studies are needed to develop better evidence around deep SSI incidence and management in the instrumented thoracolumbar adult spinal fusion population.
Topics: Adult; Humans; Surgical Wound Infection; Incidence; Persistent Infection; Spine; Staphylococcal Infections; Spinal Fusion; Retrospective Studies
PubMed: 37163651
DOI: 10.1097/BRS.0000000000004713