European review for medical and pharmacological sciences最新文献

Objective: Antithrombin (AT) has anti-inflammatory and anti-coagulant properties, but its role in COVID-19 and the rate of deficiency is unknown. We hypothesize that AT3 deficiency is common in COVID-19, and supplementing AT3 will impact COVID-19 coagulopathy.

Patients and methods: This is a prospective randomized control trial. Patients with plasma AT3<100% were randomized to either standard of care (SOC) or SOC+AT3 q48hr weight-based for a goal of 120% for up to 5 doses. An additional reference group with AT3>100% received SOC.

Results: 531 subjects were assessed for eligibility; 324 did not meet inclusion criteria, 151 did not consent, 6 withdrew consent, and 50 subjects completed the study. Enrollment AT3 (M±SD) was 91±13%.  AT3 levels were <100% in 38 (76%) and <80% in 11 (22%) patients. SOC+AT3, SOC only, and AT3>100% had a disseminated intravascular coagulation (DIC) score change (M±SD) of 0.4±1.5, -0.13±1.85 and 0±1.54, respectively, (p=0.63). Hospital length of stay was 11.7 [6-14], 6 [4.5-10], 8.5 [6-21] respectively, (p=0.176). Mortality occurred in 2 (11%), 3 (15%), and 3 (25%) patients, respectively (p=0.56). There was one bleeding event in a subject with AT3>100%, and no bleeding events were observed with exogenous AT3. There were no observed drug-related adverse events. Subjects received a median dose of 1,825.5 IU (IQR 794).

Conclusions: COVID-19 is associated with relative AT3 deficiency (22% of this cohort). No bleeding complications or drug-related adverse events with exogenous AT3 were observed. There were no significant differences in length of stay or mortality. Further studies should evaluate higher doses of exogenous AT3 and focus on higher-risk groups.

Clinicaltrials: gov: NCT04899232.

Objective: Burden of disease studies evaluate the direct impact of disease in terms of morbidity and premature mortality over a given time horizon. The objective of this study was to estimate the burden of COVID-19 in Luxembourg during the first three years of the pandemic, with a particular focus on methodologies applied to two areas of high uncertainty: post-acute consequences (PAC) of COVID-19 and the disparity of associated pathologies to COVID-19 deaths compared to other causes of deaths.

Materials and methods: Epidemiological monitoring data on screening, hospital admission, and mortality associated with COVID-19 were used to estimate disability-adjusted life years (DALYs). Years of Life lost due to premature death (YLL) estimates have been adjusted for the impact of comorbidity profiles from cause-of-death data using the Charlson Comorbidity Index (CCI). In the absence of a PAC-specific disability weight, a symptom-based approach using data from a national cohort study was applied and compared with alternative weights used in the literature. A one-by-one sensitivity analysis was performed to evaluate the uncertainty associated with each model parameter.

Results: The total burden of COVID-19, including PAC, over three years, was estimated at 17,801 DALYs, combining 14,903 YLLs and 2,898 YLDs (Years of Healthy Life lived with Disability). Comorbidity adjustment led to an average reduction of 9% in YLL estimates. Alternative choices for PAC led to an up to 3-fold increase in YLD compared to our base case estimates. Prevalence, disability weight, and duration of PAC were the most influential parameters identified in the sensitivity analysis.

Conclusions: The COVID-19 pandemic has produced a significant burden on the resident population in Luxembourg. Adjusting for comorbidities is an important step in assessing the burden of COVID-19. The uncertainty associated with PAC parameters has highlighted the need for further research to standardize the definition of the prevalence, duration, and severity of this condition. The suggested symptom-based approach presents a flexible option until PAC-specific disability weights are derived in the future.

Objective: Pesticide use is disseminated worldwide. It plays a major role in expanding agribusiness and poses a serious threat to the health of the population through various forms of exposure (nutritional, occupational, environmental). In this review, we summarize and evaluate the scientific evidence available on toxicity and pesticides in humans.

Materials and methods: We researched the databases of PubMed and Embase by combining a few search terms. Only studies on human beings of both sexes over 18 years of age were included, evaluating the toxicity of pesticides in human beings from 2010 to 2023. This systematic review was performed according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE). The protocol was registered in the International Prospective Register for Systematic Reviews (PROSPERO) with the number CRD42023408863 in April of 2023. The search strategy used to search for articles in PubMed was (("Pesticides"[Mesh]) AND "toxicity" [Subtitle]) NOT "Animals"[Mesh]).

Results: The electronic search produced 247 potentially relevant articles based on the search in the databases (PubMed/MEDLINE=187 and EMBASE=82). After the removal of the duplicates, 241 articles were identified. Additional research (until January 15, 2024) identified 2 studies. Fifteen articles were selected for review of the full text, and 9 articles were included.

Conclusions: This review identified that there is no gold standard or single biomarker for exposure to agricultural pesticides that can determine their toxicity, and it is indicated that tests and associated methods, as available, should be used for a careful anamnesis. It is also strongly suggested that damage to deoxyribonucleic acid (DNA) appears as an alternative for an early biomarker of alterations of agricultural pesticides in the human body.

Objective: Cervical cancer is known as one of the most common malignant tumors in the female population. It can be prevented by early detection and treatment of cervical intraepithelial neoplasia (CIN), which is a recognized precursor. Large Loop Excision of the Transformation Zone (LLETZ) has been widely applied with ideal therapeutic effects. However, 2-25% of patients with HSIL who are treated with LLETZ have been reported to have persistent/recurrent disease. Data about risk stratification and possible influencing factors for recurrence after treatment for CIN are present in the literature, but robust evidence is still lacking. We analyzed data from a well-defined and homogeneous cohort of patients treated for CIN in an Italian referral center for HPV disease to identify significant risk factors that could influence persistent/recurrent disease after treatment.

Patients and methods: We retrospectively collected and reviewed data from 255 patients treated for the first time for CIN in our University Hospital from January 2015 to December 2017 by LLETZ. Demographic data, smoking habits, colposcopy, pre-treatment and follow-up HPV testing, pre-treatment cytology, histology, and treatment histology were collected and analyzed, as well as data about follow-up visits up to date (5 years of maximum follow-up). A multiple logistic regression model was therefore developed to identify the factors that are more predictive of relapse. CIN relapse was recorded when applicable as the main outcome.

Results: As previously underlined by other studies in literature, our results confirmed that HPV positivity after treatment, end margin positivity, higher grading of the lesion at the margin, and smoking habit are significant risk factors for recurrence after treatment for CIN.

Conclusions: With a more and more tailored approach, a validated predictive tool based on the identified significant risk factors could be of great help in the improvement of guidelines and the follow-up of treated patients.

Objective: Chronic rhinosinusitis (CRS) has traditionally been classified phenotypically according to the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. However, the phenotypic dichotomy does not represent the complexity of the disease. Current research thus focuses on identifying underlying inflammatory mechanisms and distinguishing different endotypes. The objectives of this study were 1) to identify maximally predictive non-invasive biomarkers from nasal mucus, 2) to apply machine learning algorithms to use mucus-derived biomarkers to classify phenotype, and 3) to determine the feature importance of each mucus biomarker to phenotypes.

Patients and methods: This is an IRB-approved study of 103 CRS patients (37 CRSsNP, 66 CRSwNP). Nasal mucus was collected using merocele sponges after a 3-week steroid washout period. The nasal mucus was then examined for twelve cytokines/inflammatory protein biomarkers, including interferon (IFN)-γ, interleukin (IL)-4, -5, -17A, -22, immunoglobulin (Ig) E, cystatin-SA (CST-2), eosinophilic cationic protein (ECP), matrix metalloproteinase-9 (MMP-9), pappalysin-A (PAPP-A), periostin, and serpin E1. Protein concentrations were determined by ELISAs and Luminex assays. For phenotype classification, different artificial intelligence algorithms in increasing complexity, including t-distributed stochastic neighbor embedding (t-SNE), Adaboost, and XGBoost, were applied to the data from the biomarker analysis.

Results: TThe analysis showed that IL-5 is a non-invasive marker to distinguish between the two phenotypic clusters. This was true for immune cell-derived proteins, and all proteins were analyzed conjointly. Periostin and CST-2 showed the highest feature importance for the epithelial- and tissue-derived proteins. The combination of IL-5, IgE, IL-17, and periostin showed the highest accuracy for prediction.

Conclusions: Nasal mucus can predict phenotypes similar to tissue, with IL-5 as the main trigger for clustering. Periostin and CST-2 may be part of important targetable pathways. Future efforts will be directed at determining how these markers may be used to guide therapeutic choices and individualize treatment.

The article "Performance improvement in sport through vitamin D - a narrative review" by K. Weiss, A. Devrim-Lanpir, Z. Jastrzębski, P.T. Nikolaidis, L. Hill, B. Knechtle, published Eur Rev Med Pharmacol Sci 2022; 26 (21): 7756-7770-DOI: 10.26355/eurrev_202211_30124-PMID: 36394723 has been retracted by the Editor in Chief. This decision follows concerns of potential plagiarism with the following article "Plausible ergogenic effects of vitamin D on athletic performance and recovery", raised by third parties, prompting the journal to conduct an investigation. The investigation determined that, although the original manuscript was cited in the references (ref. 23), the paraphrasing was excessively similar to the original text, constituting plagiarism. The authors were notified of the investigation but were unable to provide a satisfactory explanation to address these concerns. Consequently, the Editor in Chief has decided to retract the article. The authors have been informed about this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/30124.

Objective: Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality worldwide. This study aims to comprehensively evaluate the prognostic factors influencing survival in patients diagnosed with HCC.

Patients and methods: This is a cross-sectional study aimed at identifying prognostic factors in HCC using Cox regression and Kaplan-Meier analysis. A cohort of 364 predominantly male HCC patients with a mean age of 61.6 ± 10.9 years was analyzed.

Results: Significant risk factors for mortality included HCV infection, alcoholism, elevated alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA) II levels, and a Child-Pugh score of 8. HCV-positive patients had a hazard ratio (HR) of 2.25. Average survival time was 32.99 ± 31.64 months, with 1, 2, and 3-year survival rates of 73.6%, 44.5%, and 31.3%, respectively. Patients with PIVKA-II levels ≤ 125 mAU/mL had a significantly higher 50% chance of surviving 42 months. Patients with the Barcelona clinic liver cancer (BCLC) stage B1 displayed a higher survival rate, except at the 24-month time point, with BCLC A and B1 groups showing survival rates exceeding 80% in the first year.

Conclusions: The findings provide valuable insights into the prognostic implications and risk stratification in HCC, facilitating personalized treatment decisions and potentially improving patient outcomes.

Objective: The study evaluated the lack of neurological improvement and the factors influencing it in patients with acute ischemic stroke (AIS) without major arterial occlusion.

Patients and methods: A cross-sectional study was conducted on patients diagnosed with acute ischemic stroke without significant occlusion of major arteries, with imaging evidence from 3-tesla magnetic resonance imaging (MRI) scans at the S.I.S Hospital in Can Tho, Vietnam, from 2019 to 2023. Eligible patients received treatment with low-dose alteplase (a single dose of 0.6 mg/kg).

Results: Among the 268 patients included in the study, a significant improvement in neurological function was observed in 195 patients (72.8%) [modified Rankin Scale (mRS): 0-1 points], while 73 patients (27.2%) demonstrated little or no improvement after 3 months of treatment. There were no recorded fatalities during the study period. Female patients accounted for 35.8% of the total sample. The average age of the participants was 62.9 years. The multivariate regression analysis identified several predictive factors associated with the risk of lack of improvement after 3 months, including advanced age, higher National Institute of Health Stroke Scale (NIHSS) scores, elevated blood glycemia levels (mmol/L), and elevated high-sensitive (hs) troponin I levels (ng/mL) (p < 0.05). Glycemia and hs troponin I levels were identified as biomarkers for predicting outcomes after ischemic stroke. No evidence was found linking sex, a history of chronic illness, and a lack of improvement.

Conclusions: Predicting prognostic factors for lack of neurological improvement will assist neurologists in developing personalized treatment plans for patients, reducing complications, and promoting patient recovery.

Objective: Monoamine oxidase (MAO) inhibitors reduce inflammation in a number of in vitro and in vivo models. This finding led to the development of a novel MAO-B selective inhibitor (RG0216) designed to reduce blood-brain barrier penetration. To elucidate RG0216's regulatory role in inflammation-relevant signaling pathways, we employed a transcriptome analytic approach to identify genes that are differentially regulated by RG0216 and then globally identified which inflammation-relevant biological signaling pathways were altered by this drug.

Material and methods: Primary human gingival keratinocyte (HGK) cells were treated with RG0216, and RNA was extracted (4 h). RNAseq transcriptome analysis was utilized to identify differentially expressed genes (DEGs), while Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify significantly enriched biological pathways. Relevant genes associated with these pathways and RG0216 regulation of Porphyromonnas gingivalis lipopolysaccharide (PgLPS)-induced cytokine/chemokine expression were evaluated using the real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) approach.

Results: RG0216 significantly altered the expression of 50 DEGs in HGK cells. Using GO and KEGG analytic approaches, these genes were associated with the biological pathways relevant to mitogen-activated protein kinase (MAPK) and MAPK phosphatases. These phosphatases are part of the 10-member catalytically active dual-specificity phosphatase (DUSP) family. RG0216 induced the expression of DUSP10, reduced the expression of DUSP4 and DUSP6, and decreased IL-6 and IL-8 expression in control and PgLPS-stimulated cultures.

Conclusions: In HGK cells, a novel MAO-B inhibitor (RG0216) significantly altered DUSP4, DUSP6, and DUSP10 expression. DUSPs play a regulatory role in MAPK activity and, therefore, can alter cellular inflammatory responses. We found that RG0216 inhibited IL-6 and IL-8 expression. Further studies are planned to examine RG0216's regulatory role in DUSP expression and its impact on the regulation of cytokine/chemokine expression.

Objective: The detrimental effects of cigarette smoking on overall health are well-documented, with nicotine and carbon monoxide contributing to peripheral vasoconstriction and impaired oxygen delivery to tissues. This study reviews the impact of smoking on wound and bone healing, specifically in foot and ankle surgery, given its significant role as a modifiable risk factor for complications in orthopedic procedures.

Materials and methods: A systematic literature review was conducted in May 2024 following PRISMA guidelines. An electronic search of PubMed was performed using keywords related to smoking and wound complications in foot and ankle surgery. Inclusion criteria were studies published in English from 1993 to May 2024 focusing on orthopedic procedures. After screening 28 studies, six relevant articles were selected, comprising literature reviews, retrospective studies, and comparative series.

Results: The review highlights that smoking, including smokeless tobacco, significantly increases the risk of complications in foot and ankle surgeries. Smokers show markedly higher rates of non-union, wound infections, and delayed bone healing compared to non-smokers. For instance, smokers exhibit a 14.8% wound infection rate and higher rates of malunion and non-union, with 14.5% vs. 6.7% in non-smokers. Elective procedures such as total ankle replacement (TAR) also show worse outcomes for smokers, including increased infection rates and poorer functional scores. Conversely, smoking's impact on amputation procedures is less pronounced, although complications remain significant in patients with comorbid conditions.

Conclusions: This review underscores the severe impact of smoking on surgical outcomes in foot and ankle procedures. Smoking cessation before surgery has demonstrated substantial benefits, including reduced infection rates and improved healing. Preoperative counseling and smoking cessation programs are crucial for optimizing patient outcomes, and a multidisciplinary approach should be considered to enhance therapeutic strategies. Future studies should focus on refining smoking cessation guidelines and exploring new tobacco alternatives.