INTRODUCTION: Methods of multiple sclerosis (MS) treatment are evolving rapidly, with numerous classes of disease-modifying therapies (DMTs). A more aggressive approach to early and effective treatment of MS with a defin...INTRODUCTION: Methods of multiple sclerosis (MS) treatment are evolving rapidly, with numerous classes of disease-modifying therapies (DMTs). A more aggressive approach to early and effective treatment of MS with a defined treatment target increases the chance of achieving a state of no evidence of disease activity (NEDA). Currently, B cell-depleting monoclonal antibodies have been proven as a highly effective strategy for the treatment of relapsing-remitting MS (RRMS). Ofatumumab (OFA), an anti-CD-20 monoclonal antibody, is effective in treatment of RRMS, as it positively affects relapse rates, magnetic resonance imaging (MRI) measures of disease activity, and disability progression. MATERIAL AND METHODS: A retrospective observational study was conducted in six MS clinical centers in Poland, including a cohort of patients with RRMS treated with OFA over a 2-year period. RESULTS: The results of this study showed a statistically significant decrease in the relapse activity of the disease in the course of a year of OFA therapy. The percentage of patients free of relapses increased from 45% before treatment to 88% after 1 year of follow-up. Moreover, the disability assessment index measured by the Expanded Disability Status Scale (EDSS) remained stable after 2 years of follow-up. CONCLUSIONS: In the present study, the high efficacy of OFA therapy in reducing recurrent disease activity, as well as in inhibiting disability progression, with a favorable safety profile, was confirmed. Moreover, it was emphasized that to achieve the best possible inhibition of disease activity and its progression, it is necessary to implement the treatment as soon as possible after the diagnosis.
INTRODUCTION: Cardiovascular disease (CVD) and neoplasms are the two leading causes of death worldwide. Previous research has predominantly addressed these conditions separately or focused on specific regions. We aimed t...INTRODUCTION: Cardiovascular disease (CVD) and neoplasms are the two leading causes of death worldwide. Previous research has predominantly addressed these conditions separately or focused on specific regions. We aimed to characterize the global co-occurrence pattern of CVD and neoplasms from spatial and temporal perspectives and identify corresponding risk factors across different epidemiological contexts. MATERIAL AND METHODS: Using GBD 2021 data, we extracted age-standardized disability-adjusted life year (DALY) rates of CVD and neoplasms and modifiable risk factor exposure from 204 countries and territories (1990-2021). We identified four epidemiological patterns: low-burden, neoplasm-dominant, CVD-dominant, and dual-burden regions. We calculated population attributable fractions (PAF) and integrated machine learning with SHAP values to distinguish intervention priorities. Average annual percentage changes (AAPC) were used to evaluate temporal trends. RESULTS: Each pattern comprised 50-52 countries. Spatial distribution overlapped with socioeconomic development stages and risk factor exposure. Temporal analysis revealed widening global inequality: low-burden regions achieved 3-4% annual reductions while dual-burden regions experienced an increasing burden, creating a 5.8 percentage point gap. High systolic blood pressure was the universal dominant CVD risk factor, accounting for 49.7% of the global burden (49.2-52.4% across patterns). For neoplasms, smoking contributed 18.5% globally but varied dramatically by pattern (10.4-23.4%). Modifiable risk factors' specific combinations greatly influenced global disparities. CONCLUSIONS: The co-occurrence of CVD and neoplasms represents interconnected manifestations of different epidemiological transition stages, with concerning divergence between regions. Interventions targeting hypertension control and tobacco cessation, combined with pattern-specific strategies, can fundamentally reduce the global disease burden.
INTRODUCTION: Observational studies suggest an association between sleep apnea and dementia, but causality and directionality are unclear. This study investigated bidirectional causal relationships between sleep apnea an...INTRODUCTION: Observational studies suggest an association between sleep apnea and dementia, but causality and directionality are unclear. This study investigated bidirectional causal relationships between sleep apnea and various dementia types using two-sample Mendelian randomization (MR). MATERIAL AND METHODS: This study used summary-level data from genome-wide association studies (GWAS). Sleep apnea (including obstructive sleep apnea (OSA) and generalized sleep apnea) exposure data were from a European ancestry study. Dementia (general, Alzheimer's, vascular, etc.) outcome/exposure data were from the Finnish FinnGen consortium. The inverse variance weighted (IVW) method was used as the primary analysis, supplemented by multiple analyses (MR-Egger, weighted median, weighted mode). Robustness was assessed using several sensitivity analyses, including MR-PRESSO, Cochran's Q test, and leave-one-out analysis. RESULTS: Forward analysis, after MR-PRESSO outlier correction, showed that OSA was associated with reduced unspecified dementia risk (IVW, OR = 0.830, 95% CI = 0.700-0.970). Reverse analysis, after outlier removal, indicated that general dementia was associated with reduced OSA risk (IVW, OR = 0.9399, 95% CI = 0.9187-0.9615) and generalized sleep apnea risk (IVW, OR = 0.9141, 95% CI = 0.8863-0.9427). Alzheimer's dementia was also associated with reduced OSA and generalized sleep apnea risk. Sensitivity analyses did not reveal significant horizontal pleiotropy for the main findings, and heterogeneity was generally within acceptable limits. CONCLUSIONS: This MR study revealed complex, bidirectional genetic associations between sleep apnea and dementia subtypes. These findings provide new genetic insights into the complex interplay between sleep apnea and dementia, highlighting subtype-specific associations.
INTRODUCTION: This project intended to develop and validate a diabetes prediction model for high-risk populations based on machine learning algorithms. MATERIAL AND METHODS: A total of 2,355 samples from the National Hea...INTRODUCTION: This project intended to develop and validate a diabetes prediction model for high-risk populations based on machine learning algorithms. MATERIAL AND METHODS: A total of 2,355 samples from the National Health and Nutrition Examination Survey (NHANES) database covering three cycles from 2013 to 2018 were included. The data were divided into training and testing sets in a 7 : 3 ratio. Nineteen risk prediction factors were selected as feature variables, including demographic baseline data, measurement data, medical history, and psychological health. Five machine learning models - decision tree, random forest (RF), multilayer perceptron (MLP), Adaboost, and Extreme Gradient Boosting (XGBoost) - were developed based on the data and variables mentioned above. Model performance was evaluated using accuracy, sensitivity, specificity, the area under curve (AUC) values of receiver operating characteristic (ROC) curves, and Matthews Correlation Coefficient (MCC) scores. Finally, the Shapley feature importance measurement tool was employed to select features in the optimal model. RESULTS: The present work ultimately included 2,355 individuals at high risk of diabetes for analysis, with 260 cases of diabetes and 2,095 cases without diabetes. Among the five machine learning models established in this project., the RF and XGBoost models exhibited better overall performance compared to other models. In the test set, the RF model had an AUC of 0.896, accuracy of 0.784, sensitivity of 0.739, specificity of 0.849, and MCC of 0.418. The XGBoost model had corresponding values of AUC as 0.903, accuracy of 0.815, sensitivity of 0.962, and MCC of 0.443. According to the importance analysis of features in these two optimal models, waist circumference, age, BMI, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), education level, poverty income ratio (PIR), Patient Health Questionnaire (PHQ)-9 score, and race were the top ten key risk factors for diabetes in the high-risk population. CONCLUSIONS: The RF and XGBoost machine learning models demonstrated strong performance in predicting the occurrence of diabetes in high-risk populations. These models can aid in developing more precise intervention measures and personalized treatment plans to effectively reduce the incidence of diabetes and related risks in this population.
Cholesterol is an essential lipid for cellular integrity and metabolic homeostasis; however, dysregulated cholesterol metabolism is increasingly recognized as a key contributor to multiple ocular diseases. Beyond its est...Cholesterol is an essential lipid for cellular integrity and metabolic homeostasis; however, dysregulated cholesterol metabolism is increasingly recognized as a key contributor to multiple ocular diseases. Beyond its established role in cardiovascular pathology, emerging evidence implicates altered lipoprotein balance, impaired cholesterol transport, and lipid-driven inflammation in the pathogenesis of age-related macular degeneration, retinal vascular diseases, cataracts, and glaucoma. This review integrates current knowledge on cholesterol synthesis, transport, and regulation with ocular-specific mechanisms, emphasizing the differential roles of low-density lipoprotein, high-density lipoprotein, and triglyceride-rich lipoproteins. Key molecular pathways, including the mevalonate-SREBP axis, ABCA1/ABCG1-mediated reverse cholesterol transport, VEGF-driven angiogenesis, oxidative stress signaling, and inflammatory cascades, are critically discussed. Clinical and translational implications are highlighted, particularly the potential ocular benefits of lipid-modulating therapies such as statins, fenofibrate, and antioxidant supplementation. Understanding cholesterol as a modifiable determinant of ocular health may enable integrated preventive strategies and guide future therapeutic innovation in vision-threatening diseases.
INTRODUCTION: Respiratory diseases impose a substantial global burden on adolescents and young adults (AYAs, aged 15-39 years), yet this population remains undercharacterized. MATERIAL AND METHODS: Using Global Burden of...INTRODUCTION: Respiratory diseases impose a substantial global burden on adolescents and young adults (AYAs, aged 15-39 years), yet this population remains undercharacterized. MATERIAL AND METHODS: Using Global Burden of Disease 2021 data, we assessed incidence, mortality, DALYs, and attributable risk factors for respiratory diseases among AYAs across 204 countries and territories. Estimates were stratified by age, sex, location, and sociodemographic index (SDI). Temporal trends were evaluated using estimated annual percentage change (EAPC), and associations with development were analyzed via LOESS regression (span = 0.5). RESULTS: In 2021, upper respiratory infections had the highest age-standardized incidence rate (152,791.5/100,000), while tuberculosis caused the highest age-standardized mortality rate (6.8/100,000). Air pollution was the leading risk factor, contributing to 32.76 age-standardized DALYs per 100,000 for chronic obstructive pulmonary disease (COPD) and 62.37 for lower respiratory infections (LRIs). Sex-based disparities were evident: males had higher burdens of pneumoconiosis, LRIs, and tracheal/bronchus/lung cancers, whereas asthma and pulmonary arterial hypertension were more prevalent in females. Regionally, low-SDI areas bore the greatest burden for TB and LRIs, while high-SDI regions had higher rates of URIs and asthma. Smoking was the primary driver of COPD burden specifically in high-income countries. CONCLUSIONS: Respiratory diseases present a heterogeneous global health challenge for AYAs that varies by sex, region, and development status. These findings support targeted strategies: control of infectious disease and air quality improvement in low-SDI regions where TB and LRIs predominate, alongside enhanced asthma management and tobacco control in high-income areas where URIs and smoking-related COPD burden are more prevalent.
INTRODUCTION: Non-alcoholic fatty liver disease, now termed metabolic dysfunction-associated steatotic liver disease (MASLD), represents a significant health burden worldwide. Patients with Cushing's syndrome (CS), a con...INTRODUCTION: Non-alcoholic fatty liver disease, now termed metabolic dysfunction-associated steatotic liver disease (MASLD), represents a significant health burden worldwide. Patients with Cushing's syndrome (CS), a condition characterized by excessive cortisol production, may be at an elevated risk for MASLD due to associated metabolic disturbances. MATERIAL AND METHODS: This study aimed to evaluate the predictive value of the hepatic steatosis index (HSI) in diagnosing MASLD in patients with CS. 101 endogenous CS patients were included, and hepatosteatosis was assessed using ultrasonography. HSI scores were calculated, and associations with clinical and biochemical parameters were analyzed. RESULTS: Hepatosteatosis was observed in 62.4% of CS patients, with all these individuals meeting the criteria for MASLD. The HSI demonstrated hepatosteatosis with high sensitivity (92.1%) and specificity (78.9%) compared to ultrasonography. Factors significantly correlated with hepatosteatosis included higher body mass index, diabetes, hypertension, and hyperlipidemia. There was no correlation with basal morning cortisol, 24-hour urinary free cortisol, low-dose dexamethasone suppression tests, or the etiology of CS. CONCLUSIONS: Our study represents a pioneering effort to explore MASLD in patients with endogenous CS by evaluating the HSI as a diagnostic tool. Using the HSI, we demonstrated high sensitivity and specificity in diagnosing hepatosteatosis, emphasizing its potential as a valuable non-invasive tool in this population. Furthermore, our study fills a significant gap in the literature by being the first to investigate the predictive power of HSI for MASLD diagnosis, specifically in CS patients. Integrating these findings into clinical practice could enhance the early detection and management of MASLD in endogenous CS, ultimately improving patient outcomes.
INTRODUCTION: Membranous nephropathy (MN) is a glomerular autoimmune disease associated with nephrotic syndrome. This study explored the influence of peripheral blood B cell subtypes on MN using Mendelian randomization (...INTRODUCTION: Membranous nephropathy (MN) is a glomerular autoimmune disease associated with nephrotic syndrome. This study explored the influence of peripheral blood B cell subtypes on MN using Mendelian randomization (MR). MATERIAL AND METHODS: Data on single-nucleotide polymorphisms (SNPs) associated with peripheral blood B cells and MN were obtained from a genome-wide association study (GWAS). Analytical methods included instrumental variable weighted (IVW), weighted median, weighted mode methods, and MR-Egger regression. Sensitivity analyses were conducted using MR-Egger, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) for outlier detection, Cochran's Q test for heterogeneity, and leave-one-out analysis to assess the robustness of the findings. RESULTS: Higher levels of IgD+ CD24-B cell absolute count (OR = 0.8285, 95% CI: 0.7317-0.9381, = 0.003), B-cell activating factor receptor (BAFF-R) on IgD+ CD24-B cells (OR 0.9045, 95% CI: 0.8275-0.9886, = 0.0269), BAFF-R on IgD+ CD38dim B cells (OR = 0.9057, 95% CI: 0.8277-0.991, = 0.0311), BAFF-R on IgD- CD27-B cells (OR = 0.9134, 95% CI: 0.8404-0.9928, = 0.0332), CD19 on IgD-CD24-B cells (OR = 0.884, 95% CI: 0.7906-0.9886, = 0.0306), CD24 on switched memory B cells (OR = 0.8927, 95% CI: 0.8133-0.9798, = 0.0169), and CD25 on switched memory B cells (OR = 0.8768, 95% CI: 0.7745-0.9927, = 0.0379) were strongly associated with an decreased risk of membranous nephropathy. Sensitivity analyses were conducted to confirm the stability of the findings. CONCLUSIONS: This MR study supports the possibility of a genetic causal association between peripheral blood B cell subtypes and MN. The results improve our understanding of the immunological basis of MN and may inform the development of personalized medicine.
INTRODUCTION: In patients with chronic obstructive pulmonary disease (COPD), statins may improve lung function and reduce exacerbations. In COPD, growth differentiation factor-15 (GDF-15) has been shown to correlate with...INTRODUCTION: In patients with chronic obstructive pulmonary disease (COPD), statins may improve lung function and reduce exacerbations. In COPD, growth differentiation factor-15 (GDF-15) has been shown to correlate with increasing age, current smoking, and greater comorbidity, and to predict disease outcomes; however, the effect of statins on GDF-15 is not known. MATERIAL AND METHODS: This study was designed as a post-hoc analysis of GDF-15 levels in serum samples obtained from 54 patients with COPD (49 men; 90.7%), who had a 1-second forced expiratory volume (FEV) to forced vital capacity (FVC) ratio < 0.7. Patients assigned (1 : 1) to receive simvastatin (40 mg/day) or to remain without such treatment were followed for 3 months. Lung function and laboratory parameters, including C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-6, and plasminogen activator inhibitor type 1 (PAI-1), were also assessed. RESULTS: Baseline GDF-15 concentrations (median: 907.5 pg/ml, interquartile range: 720-1095 pg/ml) correlated negatively with FEV ( = -0.38, < 0.01) and positively with age ( = 0.32, = 0.017), TNF-α ( = 0.31, = 0.031), and PAI-1 ( = 0.40, < 0.01), but not with lipid profile or other variables. Simvastatin reduced GDF-15 by 23% at 3 months compared to baseline ( < 0.01), independently of changes in lipid variables or inflammatory markers. At both 1 and 3 months, GDF-15 levels in the statin-treated group were 14% and 22% lower compared to the untreated control group (both < 0.05). CONCLUSIONS: Our study suggests that statin treatment can reduce circulating GDF-15 levels associated with COPD severity, which may be an additional benefit of such treatment beyond lipid-lowering or anti-inflammatory effects.
INTRODUCTION: Recently, a relationship between hyperparathyroidism and cardiovascular disorders has been highlighted. The current study aimed to identify a potential relationship between parathyroid hormone (PTH) and val...INTRODUCTION: Recently, a relationship between hyperparathyroidism and cardiovascular disorders has been highlighted. The current study aimed to identify a potential relationship between parathyroid hormone (PTH) and valvular calcification performance. A secondary aim was to evaluate the potential association between PTH concentration and post-procedural outcomes after transcatheter aortic valve implantation (TAVI). MATERIAL AND METHODS: Patients with severe symptomatic aortic stenosis were evaluated for study eligibility. Demographics, clinical data, and blood samples were collected. Pre-procedurally, echocardiography and computed tomography (CT) were performed. Quantitative evaluation of calcific tissue was conducted over the three regions of interest - ascending aorta, aortic and mitral valves - using semiautomated software. RESULTS: The final study group comprised 89 patients (50 females, median (Q1-3) age of 77 (72-82) years. Increased PTH concentration was associated with a higher peak aortic gradient ( = 0.024), but not with mean aortic gradient or mitral annular calcification occurrence. CT analysis revealed an association between increased PTH and mean calcific tissue attenuation in the mitral ( = 0.004) and aortic valves ( < 0.001) and ascending aorta ( < 0.001) but no relationship with calcium volume in the regions of interest. Increased PTH did not differ between patients with and without paravalvular leak or new pacemaker implantation. CONCLUSIONS: Increased PTH concentration is associated with calcific tissue attenuation but not calcium volume, suggesting that PTH may influence the degree of calcium accumulation in degenerated regions. PTH could potentially serve as a biomarker of calcific loading in valvular heart disease. However, PTH concentration does not appear to be associated with the rate of complications following TAVI.
INTRODUCTION: One of the main contributing factors to the growth of atherosclerosis is hyperlipidemia (HLP). is a mitochondrial protein that is essential to mitochondrial function and cellular homeostasis. However, its...INTRODUCTION: One of the main contributing factors to the growth of atherosclerosis is hyperlipidemia (HLP). is a mitochondrial protein that is essential to mitochondrial function and cellular homeostasis. However, its role in hyperlipidemia and atherosclerosis remains underexplored. The aim of the study was to investigate the function of in lipid accumulation, mitochondrial function, and apoptosis in a hyperlipidemia model, and explore its mechanism of action through the HIF-1α pathway. MATERIAL AND METHODS: Bioinformatics analysis of the GSE13985 dataset was performed, and was selected as a hub gene. Free fatty acids were used to treat HepG2 cells to establish a hyperlipidemia model. Lipid buildup was assessed by oil red O (ORO) staining, and cholesterol ester levels, adenosine triphosphate content, and reactive oxygen species (ROS) levels were quantified using kit assays. Western blot (WB), flow cytometry, and CCK-8 were employed to assess protein expression levels, cell viability, and apoptosis. The effects of HIF-1α inhibition were investigated using the HIF-1α inhibitor KC7F2. RESULTS: Overexpression of significantly reduced lipid accumulation, improved cell viability, and alleviated mitochondrial damage in a hyperlipidemia model. Flow cytometry and WB research on apoptosis-related proteins demonstrated that overexpression also reduced ROS production and inhibited apoptosis. In addition, overexpression activated the HIF-1α pathway, further alleviating mitochondrial damage and apoptosis. KC7F2 reversed the protective effect of , indicating that acts through the HIF-1α pathway in the context of hyperlipidemia. CONCLUSIONS: reduces lipid accumulation and apoptosis in a hyperlipidemia model by activating the HIF-1α pathway and may provide a therapeutic strategy for atherosclerosis.
INTRODUCTION: Mental health disorders and constipation are increasingly prevalent health problems worldwide. Previous studies have reported bidirectional associations between depression, anxiety, sleep disorders, and con...INTRODUCTION: Mental health disorders and constipation are increasingly prevalent health problems worldwide. Previous studies have reported bidirectional associations between depression, anxiety, sleep disorders, and constipation. However, observational studies have yielded inconsistent results. MATERIAL AND METHODS: The associations were examined through a two-sample, bidirectional, univariable, and multivariable Mendelian randomization (MR) study. Summary-level data were obtained from the UK Biobank, large consortia, and the FinnGen consortium. The inverse-variance weighted method was applied as the principal analytical approach, and other additional MR methods (maximum likelihood, MR-RAPS, and MR-PRESSO) were used for sensitivity analyses. Multivariable MR analysis was performed to assess the independent effects of selected exposures. RESULTS: The univariable MR analyses indicated that major depression (MD) (OR = 1.28; 95% CI: 1.12-1.46), broad depression (BD) (OR = 3.72; 95% CI: 1.55-8.97), depressed affect (OR = 1.41; 95% CI: 1.13-1.76), and worry (OR = 1.42; 95% CI: 1.13-1.77) were associated with an increased risk of constipation. There was no evidence supporting the causal effects of anxious feelings, sleep duration, and sleeplessness on constipation. The reverse MR analyses found no reverse causal association of constipation with depression, anxiety, and sleep disorders. In multivariable MR, only MD still had a robust causal association with constipation, while the effect of worry was attenuated to null, and the effects of BD and depressed affect were completely reversed. CONCLUSIONS: MD is causally associated with constipation, and worry might also increase the risk of constipation. Future studies are needed to confirm the causality and elucidate the underlying mechanisms.