Search Results (10,111)

Background/Objectives: Iron-deficiency anemia (IDA) is a common extraintestinal complication of inflammatory bowel disease (IBD). Among high-dose intravenous (IV) iron options, ferric carboxymaltose (FCM) carries a higher risk of treatment-emergent hypophosphatemia than ferric derisomaltose (FDI), with potential clinical consequences. Slovenia’s healthcare setting, characterized by very low IV iron infusion tariffs and recent pricing in which FCM is substantially less expensive than FDI, warrants a setting-specific cost effectiveness evaluation. Methods: We integrated two methodological components: (i) a payer-perspective cost-effectiveness analysis using a patient-level microsimulation model with (ii) an umbrella review of systematic reviews and a targeted search of expert consensus statements on IV-iron-associated hypophosphatemia. Results: In the base case, FDI required fewer infusions than FCM (11.1 vs. 14.2 over 10 years) but generated only €95 in IV iron administration savings due to low tariffs, while drug procurement was €1166 higher with FDI than FCM. When incorporating the clinical impact of hypophosphatemia, incremental quality-adjusted life years (QALYs) were 0.136, yielding an incremental cost-effectiveness ratio (ICER) of €6590/QALY. The umbrella review consistently showed higher hypophosphatemia incidence with FCM (up to 92%) compared with other IV iron formulations (<10%), with recent recommendations emphasizing phosphate monitoring and risk mitigation through alternative formulations. Conclusions: Despite Slovenia’s low IV iron infusion tariffs and lower FCM price, FDI remained cost-effective in this model, largely due to its more favorable hypophosphatemia profile within the model. These findings suggest that hypophosphatemia risk should be considered when selecting IV iron therapy in routine IBD care. Full article

Background/Objectives: Stereotactic Body Radiation Therapy (SBRT) is increasingly used for localized prostate cancer (PCa), but evidence supporting its use in high-risk PCa (HRPC) remains limited. Standard management continues to favor conventional or moderately hypofractionated radiotherapy combined with long-course androgen deprivation therapy (ADT). This systematic review aimed to synthesize current data on SBRT biochemical outcomes, toxicity, and technical aspects in localized HRPC. Methods: A systematic PubMed search was conducted on 1 May 2024, following PRISMA 2020 guidelines (PROSPERO ID CRD420251235649). Studies reporting biochemical control (BC) for HRPC treated definitively with SBRT, with or without ADT, were included. Studies not meeting these criteria or including ≤10 HRPC patients were excluded. Risk of bias was assessed through qualitative appraisal of study methodology. Substantial heterogeneity across study design, SBRT schedules, cohort composition, and ADT integration precluded a meta-analysis; data were synthesized descriptively. Results: Thirty studies contributed biochemical control data after prostate SBRT for 1354 patients meeting inclusion criteria. SBRT was delivered using diverse platforms and dose-fractionation schemes, frequently in combination with ADT. Across studies, BC was generally favorable, though follow-up duration varied widely. Toxicity profiles were acceptable, with most reports describing predominantly grade 1–2 events and low rates of severe toxicity. Marked variability was observed in target volume definition, focal-boost strategies, urethra-sparing techniques, and the use of rectal spacers. Conclusions: Although current evidence is heterogeneous and largely derived from non-randomized studies, BC and toxicity outcomes are consistently promising, supporting SBRT as a potentially effective strategy for localized HRPC. Randomized prospective trials are needed to confirm these findings and refine optimal SBRT regimens and the role of ADT. This review received no funding. Full article

Background/Objectives: Prediction models are implemented frequently, yet, compared with other study designs, their incorporation of clinical measurements (CMs; i.e., vital signs and laboratory results) is rather underdeveloped. The purpose is to describe methods used and illustrate clinical utility in parameters systematically derived from CMs; as a case study, we use the risk of all-cause mortality following coronavirus disease 2019 (COVID-19) as the basis for prognosis. Methods: We identified cases through the Department of Veterans Affairs COVID-19 Shared Data Resource, utilizing data from the first visit until 14 days before testing positive. Thirteen parameters were derived from each of the 11 CMs, capturing departures from normality considering variability and time. The 143 candidate predictors were used to generate the main logistic regression model. The area under the receiver operating characteristic curve (AUROC) analysis was performed to assess discrimination between those who lived and died for subset and main regressions; for comparison, this was performed for an age-only model and the Charlson Comorbidity and Elixhauser Indices. Results: There were 329,491 patients. The main model’s AUROC (0.785 ± 0.002) was similar to the age-only model (0.783 ± 0.002; p > 0.05) and significantly greater than the comorbidity indices’ (range: 0.675 ± 0.002 to 0.729 ± 0.002; p < 0.001 each). Conclusions: The study found several parameters were significant determinants of mortality following COVID-19, highlighting the importance of a systematic approach for multivariate modeling to obtain informative insights into underlying pathophysiology. The main model outperforms common comorbidity indices as a summary metric for pre-existing conditions in this case study. If validated, this approach could revolutionize the way CMs are handled in multivariate models. Full article

Background: Preterm birth is a significant risk factor for neurodevelopmental delays, but the appropriate use and timing of age correction for developmental assessment remain debated. Objective: This study investigated psychomotor development in preterm children at two years of age, with the aim of clarifying whether age correction remains necessary at this stage, particularly across different gestational age groups. Methods: A total of 161 preterm infants were assessed at a mean chronological age of 25.4 months (mean corrected age: 23.3 months) and compared with two control groups of typically developing children matched for gender and either corrected age (Control–Corr, N = 88) or chronological age (Control–Chron, N = 87). The preterm group was further stratified by gestational age: extremely preterm (<28 weeks), very preterm (28–31 weeks), and moderate-to-late preterm (32–36 weeks). Cognitive, Language (Receptive, Expressive), and Motor (fine, gross) scales of Bayley-III were analysed using t-tests and MANOVAs. Results: Using corrected age, preterm children showed a selective profile, with deficits in Receptive Language, borderline mean score in Gross Motor, and preserved performance in Cognitive, Expressive Communication, and Fine Motor. When compared with controls of the same age, significant differences emerged in the Cognitive, Language, and Gross Motor, but not Fine Motor, domains. In contrast, scoring by chronological age produced a generalised delay, with preterm children performing significantly worse than chronological-age controls across all domains. Subgroup analyses further showed that extremely preterm children already displayed marked Language vulnerabilities at corrected age, which became more severe with chronological scoring and extended to other domains. Very preterm children also fell into the deficit range in Cognitive, Language, and Gross Motor scales/subscales when chronological age was applied, whereas moderate-to-late preterm children performed comparatively better. Conclusions: Developmental assessment using corrected age remains essential at least until 24 months, especially for extremely and very preterm children, to avoid substantial overestimation of developmental difficulties. Chronological scoring, while helpful to highlight persistent vulnerabilities, may inflate delay classification if used too early. Tailoring correction strategies by gestational age and developmental domain could provide a more accurate and clinically meaningful representation of preterm children’s developmental trajectories. Full article

Cellular senescence is a stress-induced cell-cycle arrest that constrains expansion of ultraviolet-damaged keratinocytes yet can remodel the microenvironment. This systematic review evaluated histological and genetic or epigenetic senescence markers in actinic keratosis (AK), cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). PubMed, Scopus, and Web of Science were searched (January 2005–May 2025); 34 human studies were included. AK showed an early senescent signature with frequent cyclin-dependent kinase inhibitor p21 (p21CIP1) expression (82.1%) and DNA damage signaling, including phosphorylated histone H2AX (gamma-H2AX) positivity (77%). In invasive cSCC, p21^CIP1 fell to 43.9% and tumor suppressor p53 immunoreactivity often declined, whereas cyclin-dependent kinase inhibitor p16 (p16INK4a) commonly accumulated without arrest, including cytoplasmic staining at invasion fronts. Reported escape pathways involved c-Jun N-terminal kinase 2 activity and long noncoding RNA PVT1–dependent repression of p21. Telomerase reverse transcriptase (TERT) promoter mutations were prevalent in cSCC (about 50%) and BCC (up to 78%) but uncommon in AK, consistent with late telomerase activation. Study heterogeneity, variable antibody scoring, and limited assessment of senescence-associated beta-galactosidase and secretory mediators restricted cross-study comparability. Standardized, spatially resolved profiling may refine risk stratification and support senescence-targeted prevention and therapy in keratinocyte cancers. Full article

Backgrounds/Objectives: Adolescent soccer players are exposed to elevated injury risk due to rapid musculoskeletal development and high physical demands. Neuromuscular training (NMT) and speed–agility–quickness (SAQ) training are widely used to enhance performance and reduce injury risk in youth athletes. While both approaches are effective, comparative evidence regarding their modality-specific performance adaptations remains limited. Furthermore, few studies have discussed how such performance data may inform evidence-based or data-driven training selection in youth sports contexts. Methods: Thirty-six male youth soccer players with at least three years of playing experience, affiliated with Team A in Gyeonggi-do and Team B in Chungcheongbuk-do, participated in the study (NMTG, n = 21; SAQG, n = 15). Participants completed either an NMT or SAQ training program for eight weeks. To objectively assess exercise performance, pre- and post-tests were conducted measuring dynamic balance, vertical jump, zigzag run, and carioca. Results: Findings revealed a significant main effect of time for lower limb power (p < 0.05), but no significant group × time interaction, indicating that both NMTG and SAQG improved significantly over the 8-week period. Conversely, significant interaction effects were found for agility (p < 0.001), with SAQG demonstrating superior enhancements compared to NMTG. Dynamic balance showed no significant time effect or interaction. Conclusions: While NMTG and SAQG are equally effective for enhancing lower limb power, SAQG provides modality-specific advantages for agility in youth soccer players. These results emphasize time-dependent adaptations for power and the distinct benefits of SAQG for multi-directional speed. These adaptation profiles offer a data-driven framework for optimizing training selection in youth athletes. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) shows marked molecular and histopathological heterogeneity. Among the alterations most strongly associated with clinical outcome are mutations in TP53 and CTNNB1, as well as the presence of microvascular invasion (MVI). Although these factors are well established as prognostic indicators, how their molecular effects relate to tumor morphology remains unclear. In this work, we studied transcriptomic changes linked to TP53 and CTNNB1 mutational status and to MVI, and examined whether these changes are reflected in routine histology. Methods: RNA sequencing data from HCC samples annotated for mutations and vascular invasion were analyzed using differential expression analysis combined with machine learning-based feature selection to characterize the underlying transcriptional programs. In parallel, we trained a weakly supervised multitask deep learning model on hematoxylin and eosin-stained whole-slide images using slide-level labels only, without spatial annotations, to assess whether these features could be inferred from global histological patterns. Results: Distinct gene expression profiles were observed for TP53-mutated, CTNNB1-mutated, and MVI-positive tumors, involving pathways related to proliferation, metabolism, and invasion. Image-based models were able to capture morphological patterns associated with these states, achieving above-random discrimination with variable performance across tasks. Conclusions: Taken together, these results support the existence of coherent biological programs underlying key risk determinants in HCC and indicate that their phenotypic effects are, at least in part, detectable in routine histopathology. This provides a rationale for integrative morpho-molecular approaches to risk assessment in HCC. Full article

Objective: Heart failure (HF) remains a major global health challenge. We evaluated ten-year trends in clinical profiles, diagnostic/therapeutic management, and outcomes in patients hospitalized for de novo acute heart failure (AHF). Methods: We compared two multicenter cohorts of patients admitted to Internal Medicine departments in Spain for a first episode of HF (excluding acutely decompensated chronic HF): a retrospective cohort (CH-2005; n = 600) and a prospective cohort (CH-2015; n = 180). We assessed clinical characteristics, adherence to guideline-recommended diagnostic testing, discharge treatment, and 12-month outcomes (HF readmissions and all-cause mortality). Results: The patients in CH-2015 showed a markedly higher comorbidity burden (Charlson Comorbidity Index > 2: 90.0% vs. 12.8%, p < 0.001) and higher chronic kidney disease prevalence (17.8% vs. 11.8%, p = 0.01), while mean age was similar (75.0 vs. 73.6 years, p = 0.16). Diagnostic adherence improved with higher echocardiography use (92.2% vs. 66.5%, p < 0.001). Discharge beta-blocker prescriptions increased (50.6% vs. 31.3%, p < 0.001). HF readmissions were higher in CH-2015 at 1 month (35.6% vs. 7.3%, p < 0.001) and 12 months (49.4% vs. 21.2%, p < 0.001). One-year mortality was higher in CH-2015 (22.5% vs. 16.3%, p = 0.07). In the multivariable analyses, the between-cohort difference in mortality was not significant, whereas the higher readmission risk in CH-2015 persisted. Conclusions: Over a decade, de novo AHF admissions shifted toward a more complex, multimorbid phenotype. Despite improved diagnostic testing and small advances in evidence-based therapy, the readmission burden increased, highlighting the need for integrated, post-discharge management strategies in older multimorbid populations. Full article

Background: Cardiac rehabilitation (CR) is a key component of secondary prevention after acute coronary events, coronary and valve interventions, and device implantation, yet participation and long-term adherence remain suboptimal. Digital technologies offer the potential to extend CR beyond the centre-based model and to support more flexible, patient-centred care. Methods: This narrative “review on a systematic backbone” synthesizes original clinical studies published between 2005 and 2025 that evaluated the use of digital technologies as an integral part of CR in adults after myocardial infarction, revascularization, valve procedures or implantation of cardiac devices. Interventions were grouped into four categories: mobile health (mHealth) and tele-rehabilitation, virtual reality (VR) and exergaming, virtual education platforms, and other multi-component digital CR solutions. Only original studies with clinical, functional, or patient-reported outcomes were included. Results: Twenty-one studies on the categories mentioned above met the eligibility criteria. mHealth-enabled home-based or hybrid CR programs consistently achieved improvements in functional capacity and physical activity that were broadly comparable to centre-based CR, with generally high adherence. VR and exergaming interventions were feasible and safe, produced at least similar functional gains, and showed more consistent benefits as far as anxiety levels and engagement levels. Virtual education platforms delivered knowledge and produced behaviour change similar to traditional education and, in some studies, supported better control of blood pressure and lipids. Comprehensive digital CR platforms improved risk-factor profiles and quality of life to a degree comparable with face-to-face CR. Conclusions: Digital technologies can credibly support core objectives of CR in high-risk patients and expand access, but must be implemented as a complement to, rather than a replacement for, multidisciplinary, patient-centred rehabilitation. Full article

The OHI demonstrated moderate internal consistency and consistent associations with oral health-related quality of life and cardiovascular risk indicators. Objective: The primary objective was to propose and internally assess an Oral Health Index (OHI) which integrates multiple clinically assessed oral health variables. The secondary objective was to investigate its association with oral health-related quality of life (OHRQoL) and common clinical cardiovascular risk (CVR) factors. Material and Methods: This observational study included 191 participants. Seven parameters (tooth loss, periodontal disease, endodontic involvement, residual roots, extractions due to periodontitis, inflammatory oral mucosal diseases, and dental maintenance and rehabilitation status) were combined using Z-scores to compute the OHI, with higher scores indicating poorer oral health. CVR factors included age/sex thresholds, education level, BMI, smoking status, diabetes, hypertension, pulse pressure, and lung function. OHRQoL was assessed using the Oral Health Impact Profile. Results: Higher OHI scores were associated with poor oral health-related quality of life. Participants with cardiovascular risk factors had significantly higher OHI scores. The analysis demonstrated that the OHI was directly associated with worse oral health-related quality of life and a greater cardiovascular risk burden, independent of age, sex, and comorbidities. Conclusions: This study proposed and internally assessed the Oral Health Index, designed to integrate multiple clinical parameters into a single standardized measure of oral health. The OHI demonstrated moderate internal consistency and showed consistent associations with poorer oral health conditions, reduced oral health-related quality of life, and a greater cardiovascular risk burden. Full article

Background/Objectives: Health Promotion Centres (HPCs) in Slovenia represent a European best practice for integrated prevention and health promotion. This study explores the feasibility of adapting the Slovenian HPC model to Bergamo Province, Lombardy, considering local population needs and health system characteristics. Methods: We conducted a qualitative feasibility and policy analysis based primarily on documentary review, complemented by a webinar, a study visit to Slovenia, and expert consultations (conducted in two group discussions) with professionals from ATS (Agenzia Tutela della Salute) Bergamo and local ASST (Azienda Socio-Sanitaria Territoriale) providers. Data were analysed using the PIET-T framework (Population–Intervention–Environment–Transfer). Results: Eight key elements define the Slovenian model: (1) governance and stewardship; (2) structural financing; (3) standardized service portfolio; (4) systematic preventive referrals; (5) integration with primary care and screening; (6) multidisciplinary teams with codified training; (7) community outreach and equity orientation; and (8) information systems and reporting. While Bergamo shares similar demographic and epidemiological profiles, differences in behavioral risk factors, project-based financing, fragmented initiatives, and limited digital integration necessitate adaptation. The comparative assessment highlighted key areas requiring contextual adaptation, including financing mechanisms, organisational coordination, workforce capacity, digital interoperability, and approaches to equity. Conclusions: The Slovenian HPC experience demonstrates the potential of integrated, community-based health promotion. Its adaptation to Lombardy appears feasible if core components are preserved and tailored to local governance, population, and health system conditions. These organisational features may be particularly relevant for time-dependent conditions, such as acute cardiovascular and cerebrovascular events, by potentially supporting more timely risk-factor management and coordination across diagnostic and emergency pathways. Rather than a blueprint for reform, this experience offers useful insights to reinforce prevention and health promotion within the ongoing territorial care reform in Lombardy. Full article

Rapid industrialization and urbanization have drawn increasing attention to the problem of agricultural potentially toxic element (PTE) pollution. Identifying priority control sources and elements through risk-based quantification of farmland PTE pollution sources is pivotal for effective soil pollution prevention and control. By investigating agriculture fields in Pengzhou, China, the pollution sources of soil PTEs (Cr, Cu, Ni, Zn, Pb, Cd, Hg, and As) were identified and quantified by a positive matrix factorization (PMF) receptor model, and their ecological and human health risks were quantitatively assessed by combining risk exposure with source profiles. The results revealed that point percentages of soil Zn, Cr, Ni, Cu, and Cd concentrations exceeding their corresponding environmental risk screening values were 0.98%, 2.94%, 16.67%, 5.88%, and 80.39%, respectively. The soil PTEs originated from atmospheric deposition, industrial emission, farming activities, and natural sources, which accounted for 22.73%, 39.94%, 24.43%, and 12.90%, respectively. Ecological and human health risk assessments showed that Cd contributed the most to ecological risk, whereas Cr posed the greatest human health exposure risk. Source-oriented risk assessment indicated that agricultural activities predominantly contributed to ecological risk, while industrial emissions primarily affected human health. These findings indicated that the source contributing most to soil PTE concentrations may not necessarily pose the greatest risk. Overall, agricultural and industrial sources, along with Cd and Cr, were identified as priority targets for control. Policies promoting scientific use of fertilizers and pesticides in the agricultural sector, along with technological upgrades and emission controls in the industrial sector, should be implemented to mitigate exposure risks and promote sustainable soil health. Full article

Background: Type 2 diabetes (T2D) increases cardiovascular disease (CVD) risk and predisposes individuals to heart failure with preserved ejection fraction. Metabolic dysfunction-associated steatotic liver disease (MASLD), prevalent in T2D, may worsen cardiac remodelling and haemodynamics. This secondary analysis of the DIASTOLIC trial examined the relationship of liver fat to cardiac remodelling in T2D at baseline and after a 12-week intervention or standard care. Methods: Adults with obesity and T2D and matched controls underwent hepatic MRI, cardiac MRI, echocardiography, and adipokine profiling as part of the DIASTOLIC study (NCT02590822). Participants with T2D were randomised to supervised exercise, a low-calorie meal-replacement plan (MRP), or routine care for 12 weeks. A baseline case–control and then pre- and post-analyses in those with T2D were performed. Associations between changes in liver fat and cardiovascular measures were assessed using correlation and adjusted generalised linear models. Results: At baseline, 81 T2D and 35 healthy controls were compared, and 76 subjects with T2D completed the trial. Participants with T2D had ~4× higher hepatic fat and adverse haemodynamics. The MRP arm achieved the greatest reductions in BMI, blood pressure, dysglycaemia, insulin resistance, and hepatic fat (−8.9%), with favourable adipokine changes. Overall, hepatic fat loss was associated with reductions in cardiac index and stroke volume and with additional reductions in end-diastolic volume in the MRP arm, independent of BMI. Conclusions: In T2D, hepatic fat is strongly linked to pathological haemodynamic profiles. Intensive caloric restriction achieves substantial hepatic fat loss and normalisation of hyperdynamic cardiovascular physiology independent of weight loss, identifying hepatic steatosis as a potential therapeutic target for early cardiovascular risk reduction. Full article

Objective: This study aimed to evaluate the association between mitral annular calcification (MAC) and ventricular tachycardia (VT) in patients with reduced and mildly reduced ejection fraction and to identify independent predictors of VT. Materials and Methods: A total of 143 patients with heart failure and left ventricular ejection fraction (LVEF) under 50% were included in this retrospective cross-sectional study. Patients were classified into two groups according to the presence of VT. Clinical, biochemical, and echocardiographic variables were compared between groups. Independent predictors of VT were identified using multivariable logistic regression analysis. Results: MAC was significantly more prevalent in the VT group compared with controls (43.6% vs. 17.4%, p < 0.001) and was the strongest independent predictor of VT (OR: 2.74; 95% CI: 1.13–6.65; p = 0.026). Higher inflammatory activity, lower serum albumin levels, increased left atrial volume, renal dysfunction, and elevated diastolic filling pressures were also associated with VT. Conclusion: MAC is a strong and independent predictor of ventricular tachycardia in patients with reduced and mildly reduced ejection fraction. Incorporating MAC into the overall arrhythmic risk profile alongside inflammatory, metabolic, and structural parameters may improve risk stratification in this population. Full article

Background: Mammary ductal hyperplasia represents a spectrum of benign proliferative breast lesions, some of which pose elevated risks for malignant transformation into ductal carcinoma in situ and invasive breast cancer. This narrative review explores why only specific types, particularly those with atypia, exhibit higher progression potential, synthesizing epidemiologic, histopathologic, molecular, and environmental insights. Methods: We reviewed key literature from databases, including PubMed, focusing on classification, risk stratification, genetic/epigenetic mechanisms, tumor microenvironment dynamics, and modifiable factors influencing progression. Results: Benign breast lesions are categorized into non-proliferative, proliferative without atypia, and proliferative with atypia, such as atypical ductal hyperplasia and atypical lobular hyperplasia. Atypia represents a morphologic continuum toward low-grade ductal carcinoma in situ, driven by genetic alterations, epigenetic reprogramming, and changes in the tumor microenvironment, including stromal remodeling, immune infiltration, hypoxia-induced angiogenesis, and extracellular matrix degradation. Dietary factors, such as high-fat intake and obesity, exacerbate progression through inflammation, insulin resistance, and adipokine imbalance, while environmental toxins, including endocrine disruptors, pesticides, and ionizing radiation, amplify genomic instability. Conclusions: Understanding differential risks and mechanisms underscores the need for stratified surveillance, biomarker-driven interventions, and lifestyle modifications to mitigate progression. Future research should prioritize molecular profiling for personalized prevention in high-risk hyperplasia. Full article