Search Results (19,761)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

African swine fever (ASF) needs to be controlled, and prevention of the spread of African swine fever virus (ASFV) is dependent on enhanced surveillance and early disease detection. Commercial swine operations, especially in North America, Europe, and Asia, are characterized by comparatively large numbers of pigs, and sampling individual pigs, which represents the main strategy for current ASF surveillance, can be both costly and labor intensive. A study performed in Ghana was designed to estimate the diagnostic sensitivity of pen-based aggregate oral fluid testing for ASFV in infected pigs in a pen of 30 animals and to evaluate its utility as a tool to support surveillance of ASF in the US. This study was performed in three phases: (i) virus (Ghana ASFV24) amplification in a target host species to generate the challenge inoculum; (ii) titration of the inoculum (10% spleen homogenate) in target host species to determine the minimum dose inducing acute ASF in pigs with survival up to 5–6 days post-inoculation (dpi); and (iii) the main study, involving 186 pigs, consisting of 6 replicates of 30 pigs per pen and one seeder pig inoculated with wildtype ASFV (highly virulent genotype II) per pen. Daily sampling of aggregate oral fluids, uncoagulated blood, oropharyngeal swabs, fecal and water nipple swabs, and recording of rectal temperatures and clinical observations was carried out. The seeder pigs were each inoculated intramuscularly with 0.5 mL of the 10% spleen homogenate, which induced the desired clinical course of ASF in the pigs, with survival of up to 6 dpi. ASFV DNA was detected in the seeder pigs as early as 1 dpi and 2 dpi in the blood and oropharyngeal swabs, respectively. Transmission of ASFV from the seeder pigs to the contact pig population was detected via positive amplification of ASFV DNA in aggregate oral fluid samples at 3 days post-contact (dpc) in 4 out of 6 pens, and in all 6 pens, at 4 dpc. Testing of oropharyngeal swabs and blood samples from individual pigs revealed a variable number of ASFV-positive pigs between 3 and 5 dpc, with detection of 100% positivity between 6 and 18 dpc, the study endpoint. These findings demonstrate the potential utility of aggregate oral fluid sampling for sensitive and early detection of ASFV incursion into naïve swine herds. It also demonstrates that testing of environmental samples from the premises could further enhance overall ASF early detection and surveillance strategies. Full article

Background/Objectives: Hemodialysis catheter-related bloodstream infection (HD-CRBSIs) is a main cause of morbidity in hemodialysis. New preventive strategies have emerged, such as using lock solutions with antiseptic or antibiotic capacity. In this study, the antimicrobial effect was analyzed in vitro and with a catheter model of lock solutions of gentamicin (LSG), gentamicin/heparin (LSG/H), and gentamicin/citrate (LSG/C) in clinical and ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The formation, minimum inhibitory concentration, and minimum inhibitory concentration of the biofilm and minimum biofilm eradication concentration of the lock solutions were determined. Additionally, colony-forming unit assays were performed to evaluate the antimicrobial efficacy of the lock solutions in a hemodialysis catheter inoculation model. Results: The minimum inhibitory concentration (MIC) of planktonic cells of both P. aeruginosa and S. aureus for LSG/H and LSG/C was 4 µg/mL. In the minimum biofilm inhibitory concentration (MBIC) tests, the LSG/H was less effective than LSG/C, requiring higher concentrations for inhibition, contrary to the minimum biofilm eradication concentration (MBEC), where LSG/H was more effective. All lock solutions eradicated P. aeruginosa biofilms in the HD catheter model under standard conditions. Nevertheless, under modified conditions, the lock solutions were not as effective versus ATCC and clinical strains of S. aureus. Conclusions: Our analysis shows that the lock solutions studied managed to eradicate intraluminal mature P. aeruginosa in non-tunneled HD catheters under standard conditions. Biofilm inhibition and eradication were observed at low gentamicin concentrations, which could optimize the gentamicin concentration in lock solutions used in HD catheters. Full article

Background: Optimal timing for surgery following acute rotator cuff tears remains unclear. This study examines how the timing of arthroscopic rotator cuff repair (RCR) affects retear rates and functional outcomes. Methods: This PROSPERO-registered review (CRD42024528249) followed PRISMA guidelines and included randomized trials, and cohort, studies on adults with imaging-confirmed full-thickness rotator cuff tears. Studies lacking timing data or key outcomes were excluded. Risk of bias was assessed using ROBINS-I. Meta-analysis of retear rates was performed comparing surgical timing. Qualitative analysis was conducted classifying results as early-beneficial, delayed-detrimental, or neutral. Results: Our review included 13 studies and 871 patients with an average age of 57.9. Meta-analysis of eight studies comparing retear rates between early and delayed RCR demonstrated a significant benefit associated with early intervention risk ratio 0.60 (95% CI: 0.38–0.96). Functional outcomes also favored early intervention with four studies demonstrating significantly greater postoperative functional improvements in the early intervention group. Conclusions: Early arthroscopic RCR decreased the rate of retear and improved functional outcomes. No study found early intervention to be detrimental or delayed intervention to be superior. These findings support consideration of early repair when clinically appropriate. Future studies should determine more finite timing guidelines. Full article

In the original randomised Dietary Intervention to Stop Coronary Atherosclerosis (DISCO-CT) trial, a 12-month Dietary Approaches to Stop Hypertension (DASH) project led by dietitians improved cardiovascular and metabolic risk factors and reduced platelet chemokine levels in patients with coronary artery disease (CAD). It is unclear whether these benefits are sustained. Objective: To determine whether the metabolic, inflammatory, and clinical benefits achieved during the DISCO-CT trial are sustained six years after the structured intervention ended. Methods: Ninety-seven adults with non-obstructive CAD confirmed in coronary computed tomography angiography were randomly assigned to receive optimal medical therapy (control group, n = 41) or the same therapy combined with intensive DASH counselling (DASH group, n = 43). After 301 ± 22 weeks, 84 individuals (87%) who had given consent underwent reassessment of body composition, meal frequency assessment, and biochemical testing (lipids, hs-CRP, CXCL4, RANTES and homocysteine). Major adverse cardiovascular events (MACE) were assessed. Results: During the intervention, the DASH group lost an average of 3.6 ± 4.2 kg and reduced their total body fat by an average of 4.2 ± 4.8 kg, compared to an average loss of 1.1 ± 2.9 kg and a reduction in total body fat of 0.3 ± 4.1 kg in the control group (both p < 0.01). Six years later, most of the lost body weight and fat tissue had been regained, and there was a sharp increase in visceral fat area in both groups (p < 0.0001). CXCL4 decreased by 4.3 ± 3.0 ng/mL during the intervention and remained lower than baseline values; in contrast, in the control group, it initially increased and then decreased (p < 0.001 between groups). LDL cholesterol and hs-CRP levels returned to baseline in both groups but remained below baseline in the DASH group. There was one case of MACE in the DASH group, compared with four cases (including one fatal myocardial infarction) in the control group (p = 0.575). Overall adherence to the DASH project increased by 26 points during counselling and then decreased by only four points, remaining higher than in the control group. Conclusions: A one-year DASH project supported by a physician and dietitian resulted in long-term suppression of the proatherogenic chemokine CXCL4 and fewer MACE over six years, despite a decline in adherence and loss of most anthropometric and lipid benefits. It appears that sustained systemic reinforcement of behaviours is necessary to maintain the benefits of lifestyle intervention in CAD. Full article

Background/Objectives: Fat and inflammation confound current magnetic resonance imaging (MRI) methods for assessing fibrosis in liver disease. Sodium or amide proton transfer-weighted MRI methods may be more specific for assessing liver fibrosis. The purpose of this study was to determine the feasibility of sodium and amide proton transfer-weighted MRI in individuals with liver disease and to determine if either method correlated with clinical markers of fibrosis. Methods: T₁ and T₂ relaxation maps, proton density fat fraction maps, liver shear stiffness maps, amide proton transfer-weighted (APTw) images, and sodium images were acquired at 3T. Image data were extracted from regions of interest placed in the liver. ANOVA tests were run with disease status, age, and body mass index as independent factors; significance was set to p < 0.05. Post-hoc t-tests were run when the ANOVA showed significance. Results: A total of 36 participants were enrolled, 34 of whom were included in the final APTw analysis and 24 in the sodium analysis. Estimated liver tissue sodium concentration differentiated participants with liver disease from those without, whereas amide proton transfer-weighted MRI did not. Estimated liver tissue sodium concentration negatively correlated with the Fibrosis-4 score, but amide proton transfer-weighted MRI did not correlate with any clinical marker of disease. Conclusions: Amide proton-weighted imaging was not different between groups. Estimated liver tissue sodium concentrations did differ between groups but did not provide additional information over conventional methods. Full article

Background and Objectives: Effective myocardial protection is essential for successful cardiac surgery outcomes, especially in complex and prolonged procedures. To this end, Del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solutions are widely used; however, their comparative efficacy in adult surgeries with prolonged aortic cross-clamp (ACC) times remains unclear. This study aimed to compare the efficacy and safety of DN and HTK for myocardial protection during prolonged ACC times in adult cardiac surgery and to define clinically relevant thresholds. Materials and Methods: This retrospective study included a total of 320 adult patients who underwent cardiac surgery under cardiopulmonary bypass (CPB) with an aortic cross-clamp time ≥ 90 min. Data were collected from the medical records of elective adult cardiac surgery cases performed at a single center between 2019 and 2025. Patients were categorized into two groups based on the type of cardioplegia received: Del Nido (n = 160) and HTK (n = 160). The groups were compared using 1:1 propensity score matching. Clinical and biochemical outcomes—including troponin I (TnI), CK-MB, lactate levels, incidence of low cardiac output syndrome (LCOS), and need for mechanical circulatory support—were analyzed between the two cardioplegia groups. Subgroup analyses were performed according to ACC duration (90–120, 120–150, 150–180 and >180 min). The predictive threshold of ACC duration for each complication was determined by ROC analysis, followed by the analysis of independent predictors of each endpoint by multivariate logistic regression. Results: Intraoperative cardioplegia volume and transfusion requirements were lower in the DN group (p < 0.05). HTK was associated with lower TnI levels and less intra-aortic balloon pump (IABP) requirement at ACC times exceeding 180 min. Markers of myocardial injury were lower in patients with an ACC duration of 120–150 min in favor of HTK. The propensity for ventricular fibrillation after ACC was significantly lower in the DN group. Significantly lower postoperative sodium levels were observed in the HTK group. Prolonged ACC duration was an independent risk factor for LCOS (odds ratio [OR]: 1.023, p < 0.001), VIS > 15 (OR, 1.015; p < 0.001), IABP requirement (OR: 1.020, p = 0.002), and early mortality (OR: 1.016, p = 0.048). Postoperative ejection fraction (EF), troponin I, and CK-MB levels were associated with the development of LCOS and a VIS > 15. Furthermore, according to ROC analysis, HTK cardioplegia was able to tolerate ACC for up to a longer duration in terms of certain complications, suggesting a higher physiological tolerance to ischemia. Conclusions: ACC duration is a strong predictor of major adverse outcomes in adult cardiac surgeries. Although DN cardioplegia is effective and economically advantageous for shorter procedures, HTK may provide superior myocardial protection in operations with long ACC duration. This study supports the need to individualize cardioplegia choice according to ACC duration. Further prospective studies are needed to establish standard dosing protocols and to optimize cardioplegia selection according to surgical duration and complexity. Full article

Objectives: Diabetes Mellitus involves demanding challenges that interfere with family functioning and routines. In turn, family and social context impacts individual glycemic control. This study aims to identify this recursive interplay, the mutual influences of family systems and diabetes management. Design: Data was collected through a cross-sectional design comparing patients, aged 22–55, with and without metabolic control. Methods: Participants filled out a set of self-report measures of sociodemographic, clinical and family systems assessment. Patients (91) were also invited to describe their perception about disease management interference regarding family functioning. We first examined the extent to which family variables grouped dataset to determine if there were similarities and dissimilarities that fit with our initial diabetic groups’ classification. Results: Cluster analysis results identify a two-cluster solution validating initial classification of two groups of patients: 49 with metabolic control (MC) and 42 without metabolic control (NoMC). Independent sample tests suggested statistically significant differences between groups in family subscales- family difficulties and family communication (p < 0.05). Binary logistic regression shed light on predictors of explained variance to no metabolic control, in four models: Sociodemographic, Clinical data, SCORE-15/Congruence Scale and Eating Behavior. Furthermore, groups differ on family support, level and sources of family conflict caused by diabetes management issues. Considering only patients who co-habit with a partner for more than one year (N = 44), NoMC patients score lower on marital functioning in all categories (p < 0.05). Discussion: Family-Chronic illness interaction plays a significant role in a patient’s adherence to treatment. This study highlights the Standards of Medical Care for Diabetes, considering caregivers and family members on diabetes care. Full article

Background/Objectives: Artificial Intelligence (AI) is increasingly being applied in otolaryngology, including cochlear implants (CIs). This study evaluates the accuracy and completeness of ChatGPT-4 and Microsoft Copilot in determining the appropriate implantation side based on audiological and radiological data, as well as the presence of tinnitus. Methods: Data from 22 CI patients (11 males, 11 females; 12 right-sided, 10 left-sided implants) were used to query both AI models. Each patient’s audiometric thresholds, hearing aid benefit, tinnitus presence, and radiological findings were provided. The AI-generated responses were compared to the clinician-chosen sides. Accuracy and completeness were scored by two independent reviewers. Results: ChatGPT had a 50% concordance rate for right-side implantation and a 70% concordance rate for left-side implantation, while Microsoft Copilot achieved 75% and 90%, respectively. Chi-square tests showed significant associations between AI-suggested and clinician-chosen sides for both AI (p < 0.05). ChatGPT outperformed Microsoft Copilot in identifying radiological alterations (60% vs. 40%) and tinnitus presence (77.8% vs. 66.7%). Cronbach’s alpha was >0.70 only for ChatGPT accuracy, indicating better agreement between reviewers. Conclusions: Both AI models showed significant alignment with clinician decisions. Microsoft Copilot was more accurate in implantation side selection, while ChatGPT better recognized radiological alterations and tinnitus. These results highlight AI’s potential as a clinical decision support tool in CI candidacy, although further research is needed to refine its application in complex cases. Full article

Background/Objectives: Chronological age (CA) is commonly used in clinical decision-making, yet it may not accurately reflect biological aging. Recent advances in artificial intelligence (AI) allow estimation of electrocardiogram (ECG)-derived heart age, which may serve as a non-invasive biomarker for physiological aging. This study aimed to develop and validate a deep learning model to predict ECG-heart age in individuals with no structural heart disease. Methods: We trained a convolutional neural network (DenseNet-121) using 12-lead ECGs from 292,484 individuals (mean age: 51.4 ± 13.8 years; 42.3% male) without significant cardiac disease. Exclusion criteria included missing age data, age <18 or >90 years, and structural abnormalities. CA was used as the target variable. Model performance was evaluated using the coefficient of determination (R²), Pearson correlation coefficient (PCC), mean absolute error (MAE), and root mean square error (RMSE). External validation was conducted using 1191 independent ECGs. Results: The model demonstrated strong predictive performance (R² = 0.783, PCC = 0.885, MAE = 5.023 years, RMSE = 6.389 years). ECG-heart age tended to be overestimated in younger adults (≤30 years) and underestimated in older adults (≥70 years). External validation showed consistent performance (R² = 0.703, PCC = 0.846, MAE = 5.582 years, RMSE = 7.316 years). Conclusions: The proposed AI-based model accurately estimates ECG-heart age in individuals with structurally normal hearts. ECG-derived heart age may serve as a reliable biomarker of biological aging and support future risk stratification strategies. Full article

Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT₃), free thyroxine (fT₄), total triiodothyronine (tT₃), total thyroxine (tT₄) and reverse triiodothyronine (rT₃). We additionally calculated the total activity of peripheral deiodinases (G_D) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral G_D activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article

Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was to investigate the differences in the content of cytokines and oxidative stress markers in patients with gastric adenocarcinoma associated with H. pylori infection depending on the stage. The study included 281 patients with gastric cancer. At stage I of the disease—75 people, stage II—70 people, stage III—69 people, and stage IV of the disease—67 people. The levels of TNF-α, IL-2, IL-8, IFNγ, TNF-β, IL-17A, IL-6, IL-10, and IL-4 in the blood serum of patients and healthy individuals were determined by enzyme immunoassay and plasma oxidative stress scores (MDA, SOD, CAT, GST, GPO, CP). The present study revealed that H. pylori-infected gastric adenocarcinoma at different stages is associated with different plasma levels of cytokines, lipid peroxidation products, and antioxidant defense factors. Further studies are needed to evaluate the effectiveness of therapeutic strategies combining cytokine regulation and oxidative stress to improve clinical outcomes in gastric cancer. Full article

The management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remains a topic of active debate. Although neoadjuvant therapy (NAT) has shown clinical benefits in BR-PDAC, especially in increasing resectability and achieving higher rates of margin-negative (R0) resections, its role in R-PDAC is less clearly defined. Additionally, the role of immunotherapy in PDAC is still being explored, with ongoing trials investigating new combinations to overcome the tumor’s immune-resistant microenvironment. This article provides a comprehensive narrative review of the current evidence comparing NAT with upfront surgery in pancreatic cancer management, focusing on randomized controlled trials and meta-analyses that assess outcomes in R-PDAC and BR-PDAC. The review aims to determine whether NAT offers a significant survival advantage over traditional post-operative strategies and to clarify which clinical scenarios may benefit most from NAT. The literature was identified through a systematic search of PubMed, Scopus, and Google Scholar databases up to March 2025. Article selection adhered to the PRISMA guidelines. Our review of existing evidence supports NAT as the standard of care for BR-PDAC. Meanwhile, management of R-PDAC should be tailored individually, guided by risk stratification that considers both clinical parameters and molecular features. Immunotherapy and targeted therapies are still in early research phases, and their further integration as NAT remains controversial. Full article

Background/Objectives: The quality of clinical studies is largely determined by the bioanalytical methods used for testing study samples. Rigorous assay validation following defined criteria, for example, the European Medicines Agency guideline for bioanalytical method validation, is a prerequisite for such assays. Alpha1-antitrypsin (AAT) measurement, i.e., the specific measurement of AAT protein and its associated elastase-inhibitory activity, is an integral part of assay panels for clinical studies addressing AAT deficiency. Specifically, AAT must be measured in the matrix of citrated human plasma as well as in diluted solutions with high salt concentrations obtained through bronchoalveolar lavage (BAL). Sensitive and selective measurement methods are required, as BAL has a low level of AAT. Methods: We present the validation data obtained for three AAT measurement methods. Two of them, nephelometry and the enzyme-linked immunosorbent assay, which clearly differ in their sensitivity, provide AAT protein concentrations. The third is the highly sensitive, newly developed elastase complex formation immunosorbent assay that specifically measures the inhibitory activity of AAT against its pivotal target, protease neutrophil elastase. Using samples with relevant AAT concentrations, we addressed the assays’ characteristics: accuracy, precision, linearity, selectivity, specificity, limit of quantification and short-term analyte stability Results: Overall, the three methods demonstrated low total errors, a combined measure reflecting accuracy and precision, even at low analyte concentrations of less than 0.5 µg/mL; adequate linearity over the required assay range; and acceptable selectivity and specificity. Furthermore, the short-time stability of the analyte was also demonstrated. Conclusions: All three AAT measurement methods met the acceptance criteria defined by the guidelines on bioanalytical assay validation, qualifying these methods for clinical sample analysis. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article