Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
Can proton pump inhibitors increase the risk of sudden unexpected death in Parkinson's disease (SUDPAR)?
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hsa_circ_0004276 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells and exacerbates postmenopausal osteoporosis through interaction with ELAVL1
Objective The aim of this study was to investigate the potential of hsa_circ_0004276 as a diagnostic marker for Postmenopausal Osteoporosis (PMO) and its potential interaction with the RNA-binding protein ELAV-like RNA binding protein-1 (ELAVL1). Methods The circRNA expression profiles obtained from the GSE159121 dataset were used to screen for differentially expressed circRNAs in patients with PMO. hsa_circ_0004276 was further analyzed and validated for its circular structure using a bioinformatics website, actinomycin D, and RNase R assays. Serum samples from 115 PMO patients and 103 healthy controls were collected. RT-qPCR and western blot were applied to assess hsa_circ_0004276 and ELAVL1. The effects of hsa_circ_0004276 and ELAVL1 on osteogenic differentiation of human Bone Marrow Mesenchymal Stem Cells (BMSCs) were investigated by in vitro experiments. Results hsa_circ_0004276 was highly expressed in PMO patients and negatively correlated with low bone mineral density. hsa_circ_0004276 had high specificity and sensitivity for the diagnosis of PMO. hsa_circ_0004276 significantly interacted with ELAVL1. During BMSC osteogenic differentiation, hsa_circ_0004276 knockdown significantly increased calcium deposition and ALP activity, while hsa_circ_0004276 overexpression showed the opposite effect. In addition, ELAVL1 expression was reduced in PMO patients and positively correlated with hsa_circ_0004276. Conclusion hsa_circ_0004276 regulates osteogenic differentiation of BMSCs through its interaction with ELAVL1 in PMO pathogenesis. This finding provides a new perspective for the study of the molecular mechanism of PMO and a theoretical basis for the development of new therapeutic targets.
Analysis of the relationship between antidepressants and seizures based on the food and drug administration's adverse event reporting system database
Background Antidepressants, a cornerstone of depression treatment, are increasingly scrutinized for their safety concerns. The seizure risk of antidepressants has garnered attention. However, the current research on the relationship between antidepressant use and seizures remains unclear, prompting this study to investigate potential associations using data from the FAERS database. Aim This study sought to assess the correlation between seizures and different antidepressants in individuals without pre-existing epilepsy or neurological comorbidities, as well as to explore potential variations in the occurrence of adverse events linked to each specific antidepressant drug. Methods A disproportionality analysis was conducted to identify potential risk indicators within the FAERS database. Signals were detected using both the Reporting Odds Ratio (ROR) via the frequency approach and the Information Component (IC) through the Bayesian approach. Results A total of 15,940,383 FAERS reports from January 1, 2004, to December 31, 2023, were analyzed. 14 antidepressant drugs were associated with seizures, as defined by 41 preferred terms. Conclusion This study identified 14 antidepressant drugs that showed significant associations with seizures. Bupropion had the highest seizure ROR among the antidepressant drugs evaluated in this study.
A randomized controlled trial comparing the efficacy and safety of indobufen versus aspirin in reducing target vessel restenosis after drug-eluting balloon angioplasty in patients with coronary artery disease
Objective This randomized controlled trial aimed to compare the efficacy and safety of indobufen versus aspirin in reducing Target Vessel Restenosis (TVR) after Drug-Eluting Balloon (DEB) angioplasty in patients with Coronary Artery Disease (CAD). Background Despite advancements in Percutaneous Coronary Intervention (PCI) techniques, TVR remains a significant challenge. Antiplatelet therapy is crucial in managing patients post-PCI, and while aspirin is the standard, indobufen may offer a more favorable safety profile by reducing gastrointestinal adverse reactions. Methods The authors conducted a prospective, single-blind, randomized controlled trial involving patients with CAD undergoing PCI with DEB. Patients were randomly allocated to receive either indobufen 100 mg twice daily or aspirin 100 mg daily, both in conjunction with clopidogrel 75 mg daily, for at least 12-months post-procedure. The primary endpoint was TVR assessed by quantitative coronary angiography at 12-months, while secondary endpoints included Major Adverse Cardiovascular Events (MACE), bleeding complications, and patient-reported outcomes. Results A total of 240 patients were evenly distributed between the indobufen and aspirin groups. No significant differences were observed in the rates of TVR (5.83 % vs. 7.50 %, p = 0.603) and MACE (5.00 % vs. 5.83 %, p = 0.776) between the two groups at one-year post-procedure. Importantly, no significant difference in gastrointestinal bleeding rates was observed between the indobufen and aspirin groups (p = 0.156). Conclusion Indobufen demonstrated non-inferior efficacy to aspirin in preventing TVR and MACE after DEB angioplasty in patients with CAD, with comparable safety profiles and no significant difference in gastrointestinal bleeding rates. However, indobufen is relatively more expensive than aspirin. While the present results suggest that indobufen may be a viable alternative to aspirin, particularly in patients at higher risk of gastrointestinal adverse reactions, this conclusion should be interpreted with caution due to the study's limitations, including its single-blind design and relatively small sample size.
Impact of implementing a prioritization process on waiting time for non-scheduled surgeries in a tertiary emergency unit
Objectives To evaluate the impact of implementing a structured prioritization process on surgical waiting times and compliance with time-to-intervention targets for non-elective surgeries in a tertiary academic emergency hospital. Methods This observational retrospective single-center cohort study compared two periods before and after implementing a prioritization system. All non-elective surgeries performed from June to August 2022 (pre-intervention) and from November 2022 to January 2023 (post-intervention) were analyzed. The intervention included urgency classification, a real-time Kanban dashboard, and daily multidisciplinary scheduling meetings. The primary outcome was the median time from surgical indication until surgical procedure. The secondary outcome included adherence to predefined acceptable waiting time windows. Statistical comparisons were performed using Chi-Square, Fisher's exact, or Mann-Whitney U tests. A significance level of p < 0.05 was adopted. Results 1851 surgeries were analyzed (967 pre-implementation and 884 post-implementation). The median waiting time was significantly reduced from 17h20min to 8h52min (p < 0.001). Compliance with acceptable waiting time windows increased from 60.5 % to 77.1 % (OR = 2.205; 95 % CI 1.799-2.701). Conclusions Introducing a structured prioritization strategy significantly reduced waiting times and improved adherence to surgical timelines in a high-complexity emergency environment. The model proved feasible, effective, and well-accepted by multidisciplinary teams. The long-term impact of the implementation of the model could be further addressed in future studies.
Identification of plasminogen activator urokinase receptor-related non-coding RNA and immune prognostic signature for non-small cell lung cancer
Objective To explore the relevant regulation of Plasminogen Activator Urokinase Receptor (PLAUR) by non-coding RNAs (ncRNAs) and the relationship between PLAUR and immune cell infiltration and biomarkers. Methods This is a cross-sectional study. A total of 10 paired primary NSCLC tissues and adjacent noncancerous tissues were collected from Tianjin Medical University General Hospital for RT-qPCR. Clinical data were extracted for RNA sequencing expression data of the PLAUR gene. The authors performed PLAUR’s prognostic value analysis in NSCLC using The Cancer Genome Atlas (TCGA). The authors then identified ncRNAs contributing to PLAUR overexpression by combining analyses of expression, correlation, and survival. Kaplan-Meier curves and log-rank tests were used to evaluate Overall Survival (OS) and Disease-Free Survival (DFS) differences based on PLAUR expression levels. Finally, the relationship between PLAUR and immune cell infiltration, as well as immune cell biomarkers, was analyzed by immune cell infiltration analysis. Results Both the quantitative real-time polymerase chain reaction and the TCGA database results showed significant differences in the expression of PLAUR in NSCLC types. The results showed that patients with a high expression of PLAUR had poorer prognoses, and PLAUR can serve as a prognostic biomarker for patients with NSCLC. The results of studying the regulatory microRNAs (miRNAs) upstream of PLAUR indicated that hsa-miR-340-5p may be the most important regulatory miRNA of PLAUR in NSCLC. Further predictions for upstream long ncRNAs (lncRNAs) in hsa-miR-340-5p indicated that AC008555.6, AC026356.1, TRHDE-AS1, and SNHG14 were the upstream lncRNAs of the has-miR-340-5p/PLAUR axis with the most potential in NSCLC. The expression of PLAUR was significantly correlated with the expression of all immune cells in NSCLC. Conclusion Plasminogen activator urokinase receptor was differently expressed and positively correlated with an unfavorable prognosis in NSCLC. The MIRLET7BHG/hsa-miR-127-3p axis was identified as the most likely upstream ncRNA-related pathway for PLAUR in NSCLC. This study provides insights into the molecular mechanism of action of PLAUR in NSCLC, which may help to develop new drugs to regulate PLAUR expression or its function in tumor development and provide new targets for the treatment of NSCLC.
Plasminogen activator urokinase receptor
Association between fibrinogen-to-albumin ratio and carotid intraplaque neovascularization on AngioPLUS in patients with asymptomatic carotid stenosis
Introduction The importance of the Fibrinogen-to-Albumin Ratio (FAR) as a novel inflammatory and thrombotic biomarker in the development of carotid Intraplaque Neovascularization (IPN) is not well understood. This study aims to investigate the relationship between FAR and carotid IPN characteristics in patients with asymptomatic carotid stenosis. Methods We enrolled patients with carotid plaques for the AngioPLUS examination, and clinical and laboratory indicators were collected. Carotid IPN was evaluated by semi-quantitative visual grading of IPN and Intraplaque Microvascular Flow (IMVF). Binary logistic regression models were performed to determine potential associations between various variables and the presence of high IPN and IMVF. Results In the study, a total of 187 patients were included, with 73 in the high IPN group and 98 in the high IMVF group. The IPN score was positively correlated with the IMVF grade, as indicated by a correlation coefficient of 0.815 (p < 0.001). A FAR value of 7.578 was the optimal cutoff value to differentiate high and low IPN as well as high and low IMVF. After adjusting for various factors, multivariate logistic regression models demonstrated that FAR was a strong predictor of the presence of high IPN and IMVF. Furthermore, a high FAR level was also significantly correlated with the presence of high IPN (OR = 2.81, 95 % CI 1.49‒3.30, p = 0.001) and high IMVF (OR = 2.55, 95 % CI 1.39‒4.68, p = 0.002) when the variable FAR grouping was included in the above models. Conclusion Elevated FAR is closely correlated with the presence of high IPN and IMVF on AngioPLUS and may facilitate plaque vulnerability.
Rising trends on folic acid test requests in a middle-income large academic hospital: A low-value care target for improvement
Objectives To evaluate the trends in serum folate test ordering and their abnormal results. Methods The authors retrieved data from an anonymized laboratory database from a single, large, academic hospital from Brazil. The authors retrieved serum folate test results, the number of repetitions and other laboratory measurements obtained in the same time window, ordering setting and clinic. The authors then evaluated the trends in test ordering, and prevalence of low (< 3 ng/dL) results, and assessed targets for improvement in test ordering. Results From January 1st, 2018, to December 31st, 2022, 181,379 folate tests were ordered from 82,052 patients, with 0.7 % of low results, rising from 33,988 in 2018 to 44,187 in 2022. The outpatient setting was the most frequent (89.5 %). The clinics that most frequently ordered folate tests were Gastroenterology (33 %) and Nephrology (9.8 %). Most patients had more than one test ordered (74.8 %). The 135,787 re-tests were performed in 36,300 patients. Many exams were repeated within three (22,570) or six months (46,881). Only 24,243 repetitions were made more than a year after the prior exam. Conclusions Folate test ordering is an increasing trend in this large academic hospital, suggestive of non-clinical guided test ordering and low-value testing.
The cognitive and motor effects of immersive virtual reality in individuals with neurocognitive disorder: randomized controlled trial protocol
Objective To assess the cognitive and motor effects of an intervention utilizing commercial immersive virtual reality (IVR) games in older adults diagnosed with mild neurocognitive disorder (mild NCD) or mild major neurocognitive disorder and compare these effects with those of a motor-cognitive integrated exercise program. Methods This randomized controlled trial will include volunteers aged 60 years and older diagnosed with mild NCD or mild major NCD. Participants will be randomly assigned to two groups, each undergoing two 45-minute sessions weekly for seven weeks. The Virtual Reality Group (VRG) will engage in six IVR games, while the Exercise Group (EG) will perform integrated motor-cognitive exercises. Outcomes will be measured using the mini-BESTest, Dynamic Gait Index, Box and Block Test, 1-minute sit-to-stand test, Grip Strength Test, Neurocognitive Battery, Word Accentuation Test, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Montreal Cognitive Assessment, and Functional Activities Questionnaire. Sample size calculation indicates 32 participants (16 per group) to achieve 80 % power with α = 0.05, accounting for 20 % attrition. The trial is registered at the Brazilian Clinical Trials Registry (RBR-2kk9vnh). Results It is hypothesized that participants in the VRG will demonstrate greater improvements in cognitive and motor performance compared to the EG.
Expression and clinical significance of MCF2L-AS1 in stomach adenocarcinoma
Background Stomach Adenocarcinoma (STAD) poses a significant burden due to its high prevalence and costly, painful treatments, exerting considerable pressure on individuals. Objectives This study intends to explore novel therapeutic targets to enhance prognosis and alleviate patient stress. Materials and methods Quantitative Real-time Polymerase Chain Reaction was employed to detect MCF2L-AS1 expression in STAD tissues and cell lines. The correlation between this expression and patients' clinical conditions and prognosis was analyzed utilizing the Chi-squared test and Kaplan-Meier method. To investigate the regulatory mechanism of MCF2L-AS1, the Luciferase reporter gene system and transfection experiments were implemented. Cellular behaviors were analyzed through CCK8 and Transwell assays. Results MCF2L-AS1 expression was upregulated in STAD tissues and cells, strongly correlating with TNM stage and lymph node metastases. High MCF2L-AS1 levels were associated with reduced 5-year survival rates compared to the low-expression groups. miR-503-5p, a downstream miRNA, was downregulated in STAD and inversely correlated with MCF2L-AS1. Knockdown of MCF2L-AS1 suppressed miR-503-5p expression, indicating its role as a competitive endogenous RNA. Low miR-503-5p expression reversed the inhibitory effects of MCF2L-AS1 knockdown on STAD cell behaviors. Conclusions The oncogene role of MCF2L-AS1 in STAD is mediated through the negative regulation of miR-503-5p, highlighting its potential as a prognostic marker and therapeutic target.
Neurological adverse events of PD-1/PD-L1 immune checkpoint inhibitors in clinical trials: A meta-analysis
Objective Based on the data in clinical studies, the authors explored the potential link between cancer immunotherapy and Neurological Adverse Events (NAEs), and established a clinical picture. Methods The authors searched PubMed, Embase, Cochrane Library, Web of Science databases, and ClinicalTrials.gov for Randomized Controlled Trials (RCTs) using PD-1/PD-L1 inhibitors for cancer until November 2023. A total of 141 articles were included, covering 12 PD-1/PD-L1 inhibitors and 18 cancer types. Results Finally, 90,079 patients of 141 RCTs met the eligibility criteria. Data showed no significant difference in the incidence of NAEs in patients receiving PD-1/PD-L1 inhibitors compared to the control group (OR = 1.07; 95 % CI 0.95, 1.21; p = 0.25). However, the authors surprisingly found that the incidence of serious NAEs in the PD-1/PD-L1 group was higher than the control group (OR = 1.34; 95 % CI 1.24, 1.44; p < 0.00001), the same with NAEs in atezolizumab subgroup (OR = 1.66; 95 % CI 1.08, 2.56; p = 0.02). It is worth noting that the intra-group heterogeneity of the serious NAEs subgroup was relatively small (I2 = 16 %, p = 0.06). Conclusion The authors first proposed the opinion that the incidence of serious NAEs in immunotherapy patients was significantly higher than in other groups, providing a novel direction for research.
New evidence for the effect of type 2 diabetes and glycemic traits on lung function: a Mendelian randomization and mediation analysis
Background Type 2 Diabetes Mellitus (T2DM) is common worldwide. Patients with T2DM often experience reduced lung function, but the relationship between the two conditions remains uncertain. This study employed Mendelian Randomization (MR) to explore the causal link between T2DM and lung function, and to identify the factors that mediate this relationship. Methods Genome-wide association study data were obtained from public databases. Four glycemic traits were considered exposures, whereas lung function was considered an outcome. Inverse Variance Weighting (IVW) was used to investigate causality, supplemented by MR-Egger and weighted medians methods. Multivariable MR (MVMR) analysis investigated whether T2DM had an independent impact on lung function. Mediation analysis was employed to examine potential mediating impacts. Results IVW revealed that T2DM was associated with decreased forced expiratory volume in 1s (FEV1) (p = 0.012) and Forced Vital Capacity (FVC) (p = 0.004). After adjusting for potential confounders, the effects of T2DM on FEV1 and FVC remained significant. Mediation analysis demonstrated that smoking and Systolic Blood Pressure (SBP) partially mediated the causal relationship between T2DM, and FEV1 and FVC. The proportions mediated by smoking, SBP, and both factors on FEV1 were 0.302, 0.412, and 0.418, respectively, while the proportion mediated by SBP on FVC was 0.594. Conclusions This study validated the causal relationship between T2DM and decreased lung function, with smoking and SBP acting as mediators. This study provides a novel perspective on the occurrence and development mechanisms of reduced lung function as well as potential new targets for metabolic intervention in treatment.
Construction and validation of a predictive model for the efficacy of valproic acid monotherapy in epilepsy based on Lasso-logistic regression
Introduction Valproic acid (VPA) is a broad-spectrum antiepileptic drug; but its therapeutic efficacy varies significantly among individuals. The objective of this study is to identify the specific biomarkers that can predict the efficacy of VPA. Methods The GSE143272 dataset from the Gene Expression Omnibus (GEO) was utilized to identify Differentially Expressed Genes (DEGs) between responders and non-responders to VPA. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify genes related to the non-responder phenotype. Intersection genes were selected to obtain the core genes affecting VPA tolerance. Lasso regression was applied to determine the core genes that influence the VPA effect. Lasso regression was applied to screen these core genes, using their expression values as independent variables and VPA response as the dependent variable in constructing a univariate logistic regression model. Peripheral blood samples from epileptic patients treated solely with VPA were collected according to nano-discharge standard. The expression levels of target genes were determined by qPCR to validate the accuracy of the model. Results 86 genes were closely related to the response phenotype through WGCNA. 13 intersection genes were obtained by intersection with 97 DEGs, which mainly involve mRNA splicing function and transport pathway. Ultimately, 3 genes-NELL2, SNORD3A and mir-1974 were included in the final model. The Area Under Curve (AUC) for this predictive model was found to be 0.70 (95 % CI: 0.70). qPCR analysis revealed a significant difference in the relative expression of the SNORD3A gene between the responder and non-responder groups. Conclusion Epilepsy patients are at an increased risk of developing drug resistance when undergoing VPA monotherapy. The risk prediction model based on Lasso-Logistic regression demonstrates strong predictive capabilities. The SNORD3A gene may serve as a valuable biomarker for predicting the likelihood of VPA resistance.
Recognition and diagnosis of Alzheimer’s Disease using T1-weighted magnetic resonance imaging via integrating CNN and Swin vision transformer
Purpose: Alzheimer’s disease is a debilitating neurological disorder that requires accurate diagnosis for the most effective therapy and care. Methods: This article presents a new vision transformer model specifically created to evaluate magnetic resonance imaging data from the Alzheimer’s Disease Neuroimaging Initiative dataset in order to categorize cases of Alzheimer’s disease. Contrary to models that rely on convolutional neural networks, the vision transformer has the ability to capture large relationships between far-apart pixels in the images. The suggested architecture has shown exceptional outcomes, as its precision has emphasized its capacity to detect and distinguish significant characteristics from MRI scans, hence enabling the precise classification of Alzheimer’s disease subtypes and various stages. The model utilizes both the elements from convolutional neural network and vision transformer models to extract both local and global visual patterns, facilitating the accurate categorization of various Alzheimer’s disease classifications. We specifically focus on the term ’dementia in patients with Alzheimer’s disease’ to describe individuals who have progressed to the dementia stage as a result of AD, distinguishing them from those in earlier stages of the disease. Results: Precise categorization of Alzheimer’s disease has significant therapeutic importance, as it enables timely identification, tailored treatment strategies, disease monitoring, and prognostic assessment. Conclusion: The stated high accuracy indicates that the suggested vision transformer model has the capacity to assist healthcare providers and researchers in generating well-informed and precise evaluations of individuals with Alzheimer’s disease.
Postpartum indicators of stress injury and inflammatory factors in high-risk pregnancies by oxytocin combined with cervical balloon dilators
Objective This work analyzes the effect of the combination of Oxytocin (OXT) combined with cervical balloon dilators on stress injury indicators and inflammatory factors in pregnant women with high-risk pregnancies. Methods Ninety-three pregnant women with high-risk pregnancies from June 2021 to November 2023 were collected and analyzed retrospectively, of which 43 cases were induced by OXT (control group), and 50 cases were induced by OXT combined with cervical balloon dilators (observation group). The differences in blood pressure and Heart Rate (HR) between the two groups were compared, and the pre-and post-treatment oxidative stress indicators Norepinephrine (NE), Adrenaline (AD), and Cortisol (Cor) and the inflammatory factors Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Prostaglandin E2 (PGE2). In addition, postpartum complications were counted in both groups. Results The observation group had higher BP and lower HR than the control group (p < 0.05). After treatment, NE, AD, Cor, TNF-α, IL-1β, IL-6, and PGE2 increased in both groups, but the observation group was lower than the control group (p < 0.05). In addition, there was no difference in the incidence of postpartum complications between the observation group and the control group (p > 0.05). Conclusion OXT combined with cervical balloon dilators can effectively ameliorate oxidative stress injury and reduce inflammatory response in high-risk pregnancy women.
Relationship between Tic disorders and 41 inflammatory factors in circulating blood: a two-sample Mendelian randomization study
Objective To investigate the causal associations between 41 circulating inflammatory factors and Tic Disorders (TD) via the Mendelian Randomization (MR) approach. Methods Single-Nucleotide Polymorphisms (SNPs) related to 41 circulating inflammatory factors were obtained from published Genome-Wide Association Studies (GWASs). The outcome event, TD, was sourced from the FinnGen Biobank database. MR was employed to explore the causal relationship between these inflammatory factors and TD. Causal inference was performed via Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Heterogeneity was assessed by Cochran's Q statistic and the leave-one-out method. Horizontal pleiotropy was examined with MR-Egger regression and MR-PRESSO. SNPs with horizontal pleiotropy were removed via the PhenoScanner database to ensure result reliability. Results MR analysis revealed significant causal associations between three circulating inflammatory factors and TD. Increased levels of Interleukin-17 (IL-17) and macrophage Migration Inhibitory Factor (MIF) were associated with an increased risk of TD (OR = 2.329, 95 % CI [1.069-5.078], p = 0.033; OR = 2.267, 95 % CI [1.097-4.686], p = 0.027), whereas increased levels of Platelet-Derived Growth Factor BB (PDGF-BB) were linked to a reduced incidence of TD (OR = 0.750, 95 % CI [0.387-1.453], p = 0.023). No causal relationships were found for other inflammatory factors. No heterogeneity or horizontal pleiotropy was detected during the study, and the MR statistical power (power > 80 %) confirmed the reliability of these three findings. Conclusion MR analysis revealed causal links between IL-17, MIF, PDGF-BB and TD, suggesting important clinical implications for the development of targeted prevention and treatment strategies for TD.
Comment on “Role of meditation on the essence of self in the psychological profile, quality of life and lifestyle - a comparative study”
H3K18 lactylation in pancreatic cancer: promising yet unproven ‒ a call for validation
Using a computerized database (REDCap) to access the clinical follow-up of patients undergoing bariatric surgery
This study highlights the use of REDCap as an effective tool for the clinical follow-up of bariatric surgery patients. By manually entering data from medical records spanning 2000 to 2020, the study provides insights into REDCap’s capabilities in organizing and analyzing large datasets. Key findings demonstrate its value in monitoring weight changes, biochemical parameters, and adherence to supplementation protocols, contributing to improved patient management and research efficiency. While REDCap’s utility is clear, limitations include the retrospective and single-site nature of the study, which may affect generalizability. Future efforts will focus on expanding data collection and integrating the database into routine clinical workflows.
Exploring the interplay between host genetics and acute and long COVID: A narrative review
Over the past four years, pivotal discoveries have deepened the understanding of the relationship between genetic factors and SARS-CoV-2 infection. Numerous genes associated with severe COVID-19 suggest a potential genetic predisposition, which may help explain why some individuals develop more serious illnesses. Emerging evidence highlights the role of genes involved in pulmonary immunity, such as Forkhead box Protein P4 (FOXP4), whose increased expression in lung tissue has been linked to more severe disease. Other genes - Transmembrane Protease Serine-2 (TMPRSS2), Leucine Zipper Transcription Factor Like-1 (LZTFL1), Solute Carrier family 6 member 20 (SLC6A20), Tyrosine Kinase-2 (TYK2), Angiotensin-Converting Enzyme (ACE), and FYVE and Coiled-Coil Domain-Containing-1 (FYCO1) - have also been implicated in COVID-19 severity. In contrast, certain genetic variants - such as the T-allele of rs12329760 in the TMPRSS2 gene and rs35705950-T in the Mucin-5B (MUC5B) gene - may confer protection against severe disease. Overall, the evidence suggests that genetic factors can influence both susceptibility to and protection from severe COVID-19, although these associations are likely shaped by complex interactions with environmental, behavioral, and other biological factors. This review summarizes current knowledge on genetic determinants linked to COVID-19 outcomes.
Response to commentary on “pembrolizumab in gestational trophoblastic neoplasia: systematic review and meta-analysis with sub-group analysis of potential prognostic factors”
Dear editor, We appreciate the thoughtful commentary by the authors1 regarding our systematic review and meta-analysis on pembrolizumab in Gestational Trophoblastic Neoplasia (GTN).2 Their constructive feedback underscores important methodological considerations that warrant further discussion.
Commentary on “Agreement analysis and associated factors of SARC-F and SARCCalf in screening risk sarcopenia in people living with human immunodeficiency virus
Predicting pancreatic fistulas after pancreatoduodenectomy: development and internal validation of a new preoperative nomogram
Introduction Pancreatic Fistula (PF) is a major complication following Pancreatoduodenectomy (PD), making its prediction crucial for individualized treatment. The aim of this study is to develop a preoperative nomogram to predict PF after PD. Material and methods From January 2009 to January 2018, patients who underwent PD were reviewed. Variables with p < 0.1 from univariate analysis were selected for a multivariate analysis. Variables with p < 0.05 were then included in the nomogram, which was internally validated in a different group of patients. Results 262 patients underwent PD during the period of the study. The risk factors for PF identified in the derivation group were male gender (OR = 2.89), higher BMI (OR = 1.14) and pancreatic duct diameter ≤ 3 mm (OR = 3.52). Preoperative weight loss exceeding 10 % within six months was protective against PF (OR = 0.16). A preoperative nomogram incorporating these four variables was developed and demonstrated good performance in the validation set, with an area under the ROC curve of 0.798. Conclusions male gender, a main pancreatic duct ≤ 3 mm and higher BMI are risk factors for PF, while weight loss is protective. The developed nomogram accurately predicts PF occurrence using these variables.
Risk factors and primary indications for cesarean section in women with gestational diabetes mellitus according to Robson classification
Objective This study aimed to analyze cesarean section rates among women with GDM classified according to the Robson system and to identify independent factors associated with vaginal delivery. Method A retrospective cohort study was conducted with pregnant women receiving care at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, between 2012 and 2020. A total of 1508 pregnant women with GDM were included and divided into two groups based on the mode of delivery. Statistical analyses were performed to assess differences between groups and identify predictive factors for vaginal delivery using Binary logistic regression. Results The overall c-section rate was 65.3 %. Robson group 5 was the most representative, accounting for 39.53 % of all cesarean deliveries, with a single previous uterine scar being the primary indication (40.2 %). Spontaneous labor onset was the strongest independent predictor of vaginal delivery (OR = 8.601, 95 % CI 6.029–12.270), whereas previous cesarean delivery (OR = 0.093, 95 % CI 0.065–0.134), fetal distress (OR = 0.110, 95 % CI 0.071–0.171), and multiple pregnancy (OR = 0.096, 95 % CI 0.036–0.259) significantly reduced this likelihood. Conclusions The high cesarean section rate among women with GDM, particularly in group 5, highlights the importance of previous uterine scar in determining the mode of delivery in this population. Encouraging spontaneous labor onset, provided that maternal and fetal conditions are adequately monitored, may be an effective strategy to reduce unnecessary cesarean sections in pregnancies complicated by GDM.
Optimizing malignancy prediction: A comparative analysis of transfer learning techniques on EBUS images
Background Improving diagnostic accuracy in EBUS image analysis using machine learning is a current challenge. This study aimed to identify the most effective transfer learning model for predicting lymph node malignancy. Methods EBUS images collected between 2020–2023 were retrospectively analyzed. Demographic data, sampled lymph nodes, and pathology results were retrospectively collected from the files. Eight pre-trained CNN models (VGG, ResNet, InceptionNet, Xception, MobileNet, DenseNet, NasNet, EfficientNet) were evaluated. Results The study shows that the VGG19, EfficientNetV2L and DenseNet201 models have the highest performance in malignancy prediction, achieving areas under the curve of 0.96, 0.96 and 0.95 respectively, with consistent training and testing accuracy, indicating successful models without overfitting. In contrast, the ResNet152V2, Xception, and NasNet models show lower performance with areas under the curve of 0.88, 0.85, and 0.84 respectively, indicating overfitting due to discrepancies between training and test data. The MobileNetV2 model, with an area under the curve of 0.50, fails to discriminate between benign and malignant cases, resulting in an accuracy of only 0.51. Conclusions The application of transfer learning to the analysis of EBUS images offers significant potential for improving diagnostic accuracy in thoracic medicine, particularly in lung cancer.
Clinicopathological and prognostic analysis of PIK3CA mutated invasive breast cancer in Chinese women
Objective To explore the relationship between PIK3CA mutations and clinicopathological features and prognosis in breast cancer patients. Methods This retrospective cohort study included 283 patients with invasive breast cancer who underwent surgery from June 2017 to June 2022. PIK3CA exon 9 and 20 mutations were detected using PCR and sequencing. Patients were divided into recurrence (n = 47) and non-recurrence (n = 236) groups based on follow-up data to identify postoperative recurrence factors and build a prediction model. Kaplan-Meier analysis was used to evaluate recurrence rates. Results PIK3CA mutations were identified in 41% of patients, with exon 20 mutations being the most common (62.1%). Mutations correlated with tumor quadrant, histological subtype, clinical stage, perineural invasion, and high NLR (p < 0.05). Recurrence group patients showed higher BMI, multiple tumors, non-luminal types, advanced clinical stage, lymph node metastasis, and higher NLR (p < 0.05). Multivariate analysis identified high BMI, multiple tumors, lymph node metastasis, advanced clinical stage, and perineural invasion as independent recurrence risk factors (p < 0.05). Notably, no significant difference in disease-free survival was observed between PIK3CA mutant and wild-type patients (p > 0.05). Conclusion PIK3CA mutations are associated with specific clinicopathological features but do not significantly impact prognosis in breast cancer patients.
Different prophylactic measures for preventing postoperative deep venous thromboembolism in adenomyosis: a retrospective study
Objective To investigate the incidence of postoperative venous thromboembolism in women with uterine adenomyosis treated using different surgical methods, and to evaluate the associated clinical and laboratory parameters, including thromboembolism assessment after laparoscopic excision of adenomyosis. Methods (1) A retrospective collection of clinical data was conducted for 411 women with uterine adenomyosis and 33 women without adenomyosis who underwent surgical treatment at Hubei Provincial Maternal and Child Healthcare Hospital from March 2020 to December 2022. The clinical data, surgical methods, and preoperative and postoperative coagulation parameters were compared between the two groups. (2) The incidence of venous thromboembolism in women with and without uterine adenomyosis was analyzed. (3) The differences in the incidence of venous thromboembolism among women with uterine adenomyosis who underwent different surgical methods were analyzed, including clinical data and preoperative and postoperative coagulation parameters of women who did not experience venous thromboembolism. (4) The incidence of venous thromboembolism was compared between women receiving mechanical thromboprophylaxis and those receiving a combination of mechanical and pharmacological prophylaxis. Results (1) Comparative analysis of clinical data showed that women with uterine adenomyosis had fewer pregnancies and births, lower hemoglobin levels, and larger uterine volumes compared to women without adenomyosis (p < 0.05). There were no significant differences in preoperative and postoperative coagulation parameters between the two groups (p > 0.05). (2) The preoperative platelet count and postoperative d-dimer levels were higher in women with uterine adenomyosis than in those without adenomyosis (p < 0.05). (3) The incidence of venous thromboembolism was higher in the uterine adenomyosis group (9.78 %) than in the non-adenomyosis group (3.03 %). Among the women with uterine adenomyosis, the incidence of venous thromboembolism after laparoscopic lesion excision (18.46 %) was higher than that after laparoscopic hysterectomy (7.86 %). (4) Compared with the mechanical prophylaxis group, the mechanical plus pharmacological prophylaxis group had a significantly lower incidence of venous thromboembolism [18.52 % (15/81) vs. 7.62 % (25/328)], with a statistically significant difference (p < 0.05). Conclusion The incidence of postoperative venous thromboembolism is relatively high in women with uterine adenomyosis, particularly in those who underwent laparoscopic lesion excision. Even in the absence of typical symptoms and despite thromboprophylaxis, screening for venous thromboembolism should be considered within 7 days postoperatively.
Impact of fiberoptic bronchoscopy with bronchoalveolar lavage on infection control in patients with severe ventilator-associated pneumonia
Objectives To evaluate the impact of Fiberoptic Bronchoscopy (FOB) with Bronchoalveolar Lavage (BAL) on infection control in patients with severe Ventilator-Associated Pneumonia (VAP) and compare it with conventional treatments to provide a reliable basis for clinical therapy. Method This retrospective study included 86 patients with severe VAP who were admitted to the hospital between November 2019 and June 2023. Based on the treatment regimen, the patients were divided into two groups: a control group (conventional lavage and suction therapy, n = 32) and an observation group (FOB with BAL, n = 54). Results The bacterial clearance rate of the observation group was significantly higher than in the control group (87.93 % vs. 70.27 %, p < 0.05). On days 5 and 7 post-treatment, the CPIS scores of the observation group were markedly lower than those of the control group (p < 0.05). After Post-treatment, the observation group demonstrated significantly superior respiratory mechanics (PIP, Cdyn, Raw), blood gas analysis parameters (PaO2, PaO2/FiO2, PaCO2), and pulmonary function indicators (PEF, PEEPi) compared to the control group (p < 0.05). The levels of inflammatory markers in the observation group were notably reduced (p < 0.05). Additionally, the duration of mechanical ventilation, infection control, and length of stay were significantly shorter in the observation group (p < 0.05). There was no significant difference in the incidence of complications between the two groups (p > 0.05). Conclusions FOB with BAL as adjunctive therapy for VAP demonstrated significant advantages in enhancing respiratory mechanics, pulmonary function, blood gas analysis, inflammatory response, and bacterial clearance rate while effectively reducing mechanical ventilation duration and length of stay.
CircHIPK3′s dual role in promoting angiogenesis and inhibiting apoptosis through FASN mRNA stabilization in gallbladder cancer
Objective To investigate the mechanism by which circHIPK3 enhances FASN stability by inhibiting the ubiquitinated degradation of ALYREF on Gallbladder Cancer (GBC). Methods RT-qPCR was performed to detect circHIPK3 in GBC tissues and to analyze the relationship between circHIPK3 and clinicopathological characteristics of GBC patients. CCK-8 and colony formation assays were performed to study the proliferation of GBC cells, flow cytometry to detect apoptosis, tube formation assay to test angiogenesis, and Transwell assay to study migration and invasion. A nude mice implantation assay was conducted. CircHIPK3, FASN and SKP2 were assessed using RT-qPCR and western blot. Ubiquitination assay was performed to detect ALYREF ubiquitination, and RNA pull-down and RIP to investigate the binding relationship between circHIPK3, ALYREF and FASN. Results CircHIPK3 was upregulated in GBC tissues, with elevated expression correlating with TNM stages and lymph node metastasis. CircHIPK3 knockdown suppressed GBC progression by inhibiting proliferation, angiogenesis, migratory and invasive capacity while promoting apoptosis in vitro, paralleled by reduced tumor growth in vivo. CircHIPK3 stabilized ALYREF via inhibiting ubiquitination-mediated degradation. ALYREF knockdown phenocopied the tumor-suppressive effects of circHIPK3 depletion, whereas ALYREF overexpression rescued circHIPK3 knockdown-induced suppression of malignant phenotypes. CircHIPK3 stabilizes FASN mRNA through ALYREF. Overexpressing FASN counteracted the actions of circHIPK3 downregulation on cellular angiogenesis and apoptosis. Conclusion CircHIPK3 enhances FASN stability by inhibiting ALYREF ubiquitination degradation, promoting angiogenesis, and inhibiting apoptosis in GBC. This study positions circHIPK3 as a promising prognostic biomarker and therapeutic target in GBC, with ALYREF and FASN emerging as critical mechanistic nodes within this oncogenic pathway.
Role of meditation on the essence of self in the psychological profile, quality of life and lifestyle – a comparative study
Objectives Meditation has been shown to influence physical and psychological health and well-being, modulating stress response, resilience, emotional regulation, mood, empathy, compassion, and improving quality of life. The authors aim to characterize the psychosocial profile of experienced practitioners of Meditation on the Essence of Self, the Gurusakásha, whose technique is based on visualization and mantra from the Indian tantric tradition. Methods Meditation experts (n = 23) were paired to an age-, gender- and educational level-matched control group (n = 29). Clinical data (presence of baseline diseases, use of medications, habits), stress level (PSS), resilience (CD-RISC), subjective mood states (VAMS), empathy (IRI), quality of life (WHOQOL-BREF), and general lifestyle profile (PEVI) were compared between groups. Results Experienced meditators had lower levels of perceived stress, and better scores on resilience, empathic concern, quality of life, and lifestyle profile suggesting that Meditation on the Essence of Self improves health and well-being. Conclusions These results suggest that experienced meditators on the Essence of Self have higher levels of psychological well-being and quality of life when compared to non-meditators.