Search Results (11,712)

Prevention of medication-related osteonecrosis of the jaw (MRONJ) associated with low-dose bone-modifying agents (LD-BMAs) remains a clinically relevant challenge, particularly due to the heterogeneity of recommendations and the growing number of patients exposed to these therapies. Unlike high-dose regimens, LD-BMAs are associated with a lower incidence and longer latency of MRONJ, generating uncertainty regarding the optimal timing and scope of dental interventions. This commentary critically compares four major international position papers and consensus documents (AAOMS 2022, SIPMO–SICMF 2020/2024, Chinese Expert Consensus 2024, and SIOT–SIdP 2023) through four pragmatic questions concerning patient stratification, timing of dental assessment, speed of risk reduction, and the role of prescriber-oriented screening tools. The analysis highlights substantial discrepancies among preventive models, particularly regarding whether pre-treatment dental treatments should be mandatory or whether early post-initiation assessment may be acceptable in selected low-risk patients. Full article

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) remains the most frequent and clinically relevant adverse event after ERCP. Although several preventive measures are supported by current evidence, their application in routine practice is often fragmented across the pre-procedural, intra-procedural, and post-procedural phases of care. As a result, patients with evolving risk may not receive timely escalation of prophylaxis or appropriately tailored post-procedural monitoring. This review provides a pragmatic clinical framework for integrating evidence-based PEP prevention with early post-ERCP risk stratification. We summarize baseline risk assessment before ERCP, distinguish routinely applicable preventive measures from strategies reserved for selected high-risk situations, and emphasize the importance of intra-procedural reassessment when procedural events such as difficult cannulation or unintended pancreatic duct manipulation increase risk in real time. We further discuss the role of early symptom assessment and post-procedural amylase/lipase measurement in supporting triage decisions, including selective observation, admission, or same-day discharge in appropriately selected patients. This integrated approach may improve consistency in routine ERCP care while highlighting important limitations related to generalizability, local resources, and implementation. Full article

The cardiovascular risk imposed by chronic kidney disease is significantly enhanced, and carotid atherosclerosis is an early indicator of systemic vascular damage. In this review, we summarize available data relative to primary prevention strategies for carotid atherosclerosis in chronic kidney disease (CKD) with a focus on risk-adapted and stage-specific management. We conducted a narrative review of the literature. A structured literature search was performed in major databases (PubMed, Scopus, Web of Science and Google Scholar), focusing on studies published between 2012 and 2025, including observational studies, randomized controlled trials, and international guideline recommendations. The review focuses on blood pressure management, lipid-lowering therapy, glycemic control, antiplatelet therapy, as well as lifestyle interventions and screening strategies in patients with CKD without a history of cerebrovascular events. CKD-specific processes, such as inflammation, endothelial dysfunction and vascular calcification, may influence the progression of carotid plaques, highlighting the need to improve traditional and non-traditional risk factor management. The focus of prevention continues to emphasize blood pressure (BP) and lipid control as well. At the same time, routine carotid screening and systematically implemented antiplatelet therapy have no known benefit, but the potential for elevated bleeding risk, especially in advanced CKD. Primary prevention should therefore focus on optimal medical treatment, as well as disease-specific strategies according to CKD stage. Additional CKD-specific studies with carotid endpoints are necessary. Full article

Background and Objectives: Cardiac implantable electronic device (CIED) infections remain among the most serious complications of pacemaker, implantable cardioverter-defibrillator, and cardiac resynchronization therapy procedures. They are associated with substantial morbidity, mortality, prolonged hospitalization, system extraction, long-term antimicrobial therapy, and increased healthcare costs. As most infections arise from perioperative contamination or procedure-related complications, prevention has become a major priority in contemporary electrophysiology practice. This review aimed to summarize current evidence on the prevention of CIED infections, with particular emphasis on modifiable risk factors and perioperative preventive measures. Materials and Methods: A focused narrative review was undertaken using targeted searches of PubMed/MEDLINE and Scopus, supplemented by major international guideline and consensus documents, with priority given to contemporary guidelines, randomised trials, meta-analyses, and major observational studies relevant to CIED infection prevention. Results: Prevention of CIED infection requires a structured, multifactorial approach spanning the entire procedural pathway. Key preventive strategies include careful reassessment of device indication, individualized device selection, correction of modifiable risk factors, postponement of elective implantation in the presence of active infection, appropriate perioperative antibiotic prophylaxis, and optimized management of anticoagulant and antiplatelet therapy to minimize pocket hematoma. Additional relevant measures include meticulous skin antisepsis, limitation of temporary invasive devices and unnecessary hardware, appropriate venous access selection, careful generator pocket creation and wound closure, and avoidance of early reintervention whenever feasible. Antibacterial envelopes may reduce major CIED infections in selected high-risk patients, whereas routine escalation of preventive measures without proven benefit is not supported. Conclusions: CIED infection prevention is inherently multifactorial and depends on the consistent application of evidence-based measures before, during, and after device implantation. Rigorous control of modifiable risk factors, prevention of pocket hematoma, appropriate antimicrobial prophylaxis, and meticulous procedural technique remain the cornerstones of effective infection prevention in patients undergoing CIED procedures. Full article

Both diabetes mellitus (DM) and stroke are major global health challenges with high morbidity and mortality. DM is a major risk factor for stroke, contributing to both increased incidence and worse clinical outcomes. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), as well as dual agonists like tirzepatide, have demonstrated significant cardiovascular benefits, raising interest in their potential cerebrovascular effects. This narrative review examines the pathophysiological links between DM and stroke and summarizes recent clinical evidence on the efficacy of GLP-1 RAs and dual GLP-1/GIP receptor agonists (GLP-1/GIP RAs) in stroke prevention and management. Current evidence from large cardiovascular outcome trials supports the role of GLP-1 RAs in reducing major adverse cardiovascular events, including stroke, primarily in the context of primary and secondary prevention. Findings suggest that semaglutide and liraglutide may reduce non-fatal stroke incidence, decrease hospitalizations, and improve neurological outcomes in patients with prior stroke. Comparative analyses of major trials suggest that, although stroke reduction may be a class effect of GLP-1 RAs, meaningful differences exist between individual agents, likely due to variations in pharmacokinetics, receptor affinity, and study populations. Additionally, much of the evidence in acute stroke derives from early-phase or ongoing trials, warranting cautious interpretation. Novel therapies, including orforglipron and retatrutide, as well as combinations like Maridebart cafraglutide and CagriSema, may expand future therapeutic options for individuals at high cerebrovascular risk. GLP-1-based therapies show promising neurovascular effects, but large-scale, long-term studies are needed to define their role in post-stroke management and cerebrovascular risk reduction. Overall, GLP-1 RAs should currently be regarded primarily as agents for long-term vascular risk reduction rather than established therapies for acute stroke. While potential neuroprotective effects are emerging, these require confirmation in adequately powered randomized trials. Future studies should aim to identify the patient subgroups most likely to benefit and to determine whether specific agents confer advantages in acute cerebrovascular contexts. A better understanding of the mechanisms underlying potential neuroprotection will be essential to determine whether these therapies can be effectively integrated into stroke management strategies. Full article

Background: People living with HIV (PLWH) are increasingly reaching older ages due to the success of antiretroviral therapy. However, aging with HIV is associated with increased risk of multimorbidity, neurocognitive impairment, frailty, psychosocial stress, and functional decline. Multidomain geriatric screening framed within an Age-Friendly 4Ms Framework (Mentation, Medication, Mobility, What Matters Most) and consideration of multi-complexity may help identify aging-related vulnerabilities and guide multidisciplinary care with greater impact on patient outcomes. However, real-world implementation of such programs within HIV clinical settings remains limited. Methods: We conducted a retrospective analysis of adults aged ≥50 years enrolled in a multidisciplinary Healthy Aging Program within a large, integrated HIV care system. Multidomain screening assessments included cognitive evaluation (Montreal Cognitive Assessment), mental health screening (PHQ-2, GAD-2), functional assessment (Katz ADL, Lawton IADL), frailty screening (Edmonton Frail Scale), and intrinsic capacity domains using the WHO Integrated Care for Older People (ICOPE) framework. Screening results, referrals, clinical interventions, and cardiometabolic risk management measures were extracted from clinical program databases and electronic medical records. Results: A total of 317 adults aged ≥50 years completed multidomain screening. Participants had well-controlled HIV infection, with viral suppression in 96.2% and a median CD4 count of 660 cells/mm³. Despite this, aging-related vulnerabilities were common. Overall, 78.4% of participants had at least one abnormal screening domain. Cognitive impairment was identified in nearly half of individuals screened, including mild impairment in 39.8% and moderate impairment in 8.7%. Functional limitations were identified in 10.1% of participants, while anxiety symptoms were present in 9.5%. Sensory impairments were common, including vision impairment in 36.5% of participants. Polypharmacy was prevalent, with 33.2% of participants prescribed five or more chronic medications. Screening frequently generated multidisciplinary referrals, including behavioral health services (42.3%), social work support (42.9%), and pharmacist-led cardiometabolic risk review (56.8%). Age-stratified analyses demonstrated similar prevalence of screening abnormalities across age groups, including individuals aged 50–59 years. Modest improvements in cardiometabolic preventive care were observed during follow-up. Statin utilization increased from 65.6% at baseline to 70.0% at 12 months, and LDL cholesterol declined modestly during the observation period. Conclusions: Multidomain screening integrated into routine HIV care identified a high prevalence of aging-related vulnerabilities among PLWH aged ≥50 years despite excellent virologic control. These findings suggest that aging-related risk in HIV is not adequately captured by chronological age alone and support early, universal implementation of multidomain screening within HIV care models. Full article

BK and JC Polyomaviruses (BKPyV and JCPyV) are ubiquitous human pathogens capable of establishing lifelong, asymptomatic persistence in the majority of the global population. While decades of research have focused on their lytic replication cycles and the development of severe diseases, such as polyomavirus-associated nephropathy (PVAN) caused by BKPyV and progressive multifocal leukoencephalopathy (PML) caused by JCPyV, their primary evolutionary strategy is one of persistence rather than pathogenesis. This review shifts the perspective from a replication-centric framework towards an evolutionary persistence model, detailing the multi-layered host and viral determinants that maintain the homeostatic balance. At the cellular level, viral genomes are restricted by chromatinization into minichromosomes and host S-phase licensing. These constraints are reinforced by innate immune sensing and adaptive T-cell and antibody responses that curtail systemic dissemination while permitting periodic, low-level urinary shedding, which is essential for horizontal transmission. In addition to these host barriers, the viruses utilize intrinsic regulatory mechanisms to prevent excessive replication and immune detection, including the stable archetype non-coding control region (NCCR), viral microRNAs that downregulate early gene expression, and the small t antigen (STAg). Finally, we address unresolved questions regarding the full spectrum of cellular reservoirs, the molecular triggers of reactivation, and the ecological factors shaping their transmission routes. Understanding these maintenance mechanisms is crucial for refining clinical interventions and managing the rare, devastating transitions from silent persistence to lytic disease. Full article

Background/Objectives: Anterior open bite (AOB) is a multifactorial malocclusion often associated with dysfunctional orofacial habits, such as tongue thrusting and lip incompetence. Early functional interventions aim to restore muscular balance; however, evidence supporting orofacial exercise therapy as a preventive measure remains limited. This pilot study evaluated the effectiveness of targeted orofacial physical exercises in reducing anterior open bite and improving tongue and lip function in school-aged children. Methods: A controlled clinical trial was conducted following ethical approval (COD-EC-24-0036). A total of 1531 children were screened, of whom 24 presented with AOB; 14 consented to participate. Participants were allocated to a tongue exercise group, a lip exercise group, or a control group receiving verbal advice only. Orofacial exercises focused on tongue posture, swallowing function, and lip seal. Measurements were obtained at baseline and 6 months using intraoral scans and clinical assessments. Treatment adherence was monitored using monthly exercise charts. Data were analyzed using repeated measures ANOVA (α = 0.05). Results: AOB prevalence among screened children was 1.57%. Descriptive analysis showed that both intervention groups demonstrated numerical reductions in anterior open bite over 6 months, whereas minimal changes were observed in the control group. However, no statistically significant differences were detected between groups (p > 0.05). Children with higher cooperation exhibited greater improvement, suggesting adherence may influence treatment response. Conclusions: Orofacial physical exercises demonstrated a trend toward improving anterior open bite and orofacial function; however, changes were not statistically significant. These exercises may serve as supportive early therapeutic management, but larger, adequately powered trials are needed to clarify their therapeutic potential. Full article

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) play essential roles in the brain, influencing neuronal and dendritic growth, as well as neurotransmission. These effects persist throughout life. Numerous studies in animals and humans have demonstrated the beneficial effects of GH therapy on memory and cognitive function, as well as on the restoration of neuronal function following injury. All nerve cells, including neurons, glia, endothelial, epithelial, and perivascular cells, are affected by the actions of GH/IGF-1. IGF-1, in particular, has been associated with cognitive function. The GH-IGF-1 axis increases the proliferation of neuronal progenitor cells and the formation of new neurons, oligodendrocytes, and astrocytes. In this study, we searched databases such as PubMed, Google Scholar, and Embase for human clinical trials evaluating the effect of growth hormone (GH) therapy on dementia, Alzheimer’s disease (AD), post-traumatic brain injury (PTI), and stroke. The following search terms were used: “GH and dementia,” “GH and Alzheimer’s disease,” “GH and TBI,” and “GH and stroke.” Inclusion criteria were all randomized controlled trials and observational studies. Exclusion criteria included the lack of cognitive and memory assessments. We found 28 articles. Most studies show the beneficial effects of GH therapy on memory and recovery of brain function after traumatic injury and stroke; however, consistent data are still lacking. The limited number of clinical trials, the small number of patients, and the lack of data on plasma levels of sex hormones that clearly contribute to brain function are limiting factors. This is the case, for example, with androgens. Other critical factors are dosage and treatment duration. Prolonged administration and supraphysiological doses are more effective in inducing positive clinical changes. Growth hormone (GH) therapy is a very promising intervention for preventing and treating dementia and early-stage Alzheimer’s disease, and it contributes significantly to the recovery of brain function in patients after traumatic injury and stroke. Further studies with more robust methodologies are needed to confirm these results. Full article

Crohn’s disease (CD) is a chronic immune-mediated inflammatory disorder characterized by transmural inflammation and a progressive course that frequently leads to structural complications such as intestinal fibrosis. Fibrostenosing disease represents a major clinical challenge, affecting up to 50% of patients over time and often requiring surgical intervention. Despite advances in anti-inflammatory therapies, no effective treatments currently exist to prevent or reverse established fibrosis. Intestinal fibrosis arises from a dysregulated tissue remodeling process driven by excessive extracellular matrix deposition and persistent activation of mesenchymal cells, particularly fibroblasts and myofibroblasts. This process is orchestrated through complex interactions between immune and non-immune cells and mediated by key signaling pathways, including transforming growth factor beta (TGF-β1) and the TL1A/DR3 axis. Genetic susceptibility, notably variants in NOD2 and other fibrosis-related genes, contributes not only to disease risk but also to phenotype progression. Epigenetic mechanisms, particularly microRNAs such as the miR-29 and miR-200 families, further modulate fibrogenesis and represent promising non-invasive biomarkers. Additionally, intestinal dysbiosis and specific microbial signatures, including reduced short-chain fatty acid-producing bacteria and the presence of adherent-invasive Escherichia coli, play a critical role in promoting fibrotic pathways. Mesenteric adipose tissue, especially creeping fat, also contributes to fibrosis through immune and metabolic signaling. Emerging biomarkers related to collagen metabolism and advances in molecular profiling are improving early detection strategies. Novel therapeutic approaches targeting fibrogenic pathways, including anti-TL1A agents, show promising preliminary results. A deeper understanding of these mechanisms is essential to develop effective antifibrotic therapies and improve long-term outcomes in CD. Full article

Worldwide, breast cancer is the leading cause of death in women. This emphasizes the significance of an accurate breast cancer detection system. This study presents a unified framework for segmentation of breast cancer using multimodal imaging, such as histopathology, MRI, mammogram, and ultrasound. This framework integrates the CNN with Transformer modules and has three core technical innovations. First, features are extracted using an encoder–decoder design. The encoder has Residual Blocks with a base channel of 32, following feature extraction, which are progressively mapped and downsampled into four stages (32 → 64 → 128 → 256) of channels. The spatial channel is reduced using MaxPool2d operations from 256 × 256 to 128 × 128, 64 × 64, 32 × 32, and 16 × 16. After further convolutional refinement, a Transformer encoder is used on the 16 × 16 feature maps in the bottleneck. The Transformer comprises four encoders with multi-head self-attention (eight heads) and a 4.0 MLP ratio, enabling the model to capture local and global contextual dependencies at the lowest resolution. The proposed framework is trained with a learning rate of 1 × 10⁻⁴, up to 50 epochs with early stopping (patience = 12), using a combined Dice and binary cross-entropy loss that balances pixel-wise accuracy and overlap-based learning. Gradient clipping with a maximum norm of 5.0 is used to ensure training stability; ReduceLROnPlateau (factor = 0.5, patience = 5) is used to dynamically adjust the learning rate; and early stopping is used to prevent overfitting. To improve generalization and enhance robustness to data variability, data augmentation techniques such as random horizontal and vertical flips, intensity variations, and small rotations (±15°) are applied. Incremental learning was implemented in this study as a warm-start fine-tuning strategy, where the model was initialized based on learned weights from a previously trained model instead of training from scratch. This is done by loading saved checkpoints of the best-performing model and continuing training on a new dataset. The performance of the proposed framework is evaluated on four publicly available datasets and one local dataset, such as BUS-UCLM, BUSI, BreastDM, TNBC NucleiSegmentation, and BCSD-2024. The impressive results are achieved with Dice scores of 0.974 on ULCM, 0.975 on BUSI, 0.971 on BreastDM, 0.904 on TNBC nuclei segmentation, and 0.982 on BCSD-2024. The proposed model consistently performed better than classical U-Net models. Full article

Background: The aim of this study was to examine the pattern of child-to-parent violence (CPV) across a broad age range, from early adolescence to late emerging adulthood. Specifically, the objectives were to analyze the linear and quadratic relationships between CPV types (psychological, physical, financial, and control/domain behaviors) and age, as well as to examine the interaction of sex within this relationship. Methods: A total of 1959 adolescents (13–17 years) and 1046 young adults (18–25 years) completed, respectively, the adolescent and young adult versions of the Child-to-Parent Violence Questionnaire (CPV-Q). Results: Age was curvilinearly associated with psychological CPV (increasing until approximately age 19 and then decreasing), positively linearly associated with financial CPV (increasing with age), and negatively linearly associated with control/domain behaviors (decreasing with age). No significant association was found between age and physical CPV. Furthermore, boys and girls showed different age-related patterns in some CPV types. Conclusions: These findings suggest that CPV does not disappear after adolescence, and that the pattern is not uniform throughout development nor the same for boys and girls. The results (1) underscore the importance of studying CPV considering developmental stage, sex, and the specific CPV types, and (2) may contribute to facilitate the early detection of CPV, anticipating changes in violence patterns, and guiding prevention strategies tailored to each developmental stage. Full article

Background/Objectives: Intracranial hypotension is a rare and underdiagnosed serious condition characterized by low cerebrospinal fluid (CSF) pressure, often resulting from trauma to the dura mater. While manual therapy is increasingly used for musculoskeletal complaints, it is not without risk and may, in rare cases, result in complications such as dural tears. Although these complications are rare, they require early recognition and appropriate treatment to prevent further morbidity. This case report aims to highlight a rare presentation of multilevel dural defects in temporal association with manual therapy and to demonstrate the efficacy of epidural blood patch (EBP) treatment. Case Presentation: We report a case of a 46-year-old woman without chronic illness who developed worsening orthostatic headaches, weakness, and vomiting after multiple manual therapy sessions. Only after 6 months did the patient undergo magnetic resonance imaging (MRI), which revealed intracranial hypotension due to dural damage in the spinal dura mater at C6–T1 and T8–T10, brain sagging, and an increased risk of subdural hematoma. After excluding other causes of dural defects, EBP was performed under CT guidance at C6–C7 and T8–T9, which resulted in symptom regression. Follow-up MRI was recommended for the patient. Conclusions: This case highlights a rare but clinically significant occurrence of multilevel dural defects and intracranial hypotension in temporal association with manual therapy. This emphasizes the critical role of timely diagnosis using MRI and the clinical effectiveness of EBP as a minimally invasive procedure. Full article

Background and Aims: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of mortality worldwide, with lipid abnormalities playing a central role in disease development. While the causal role of low-density lipoprotein cholesterol (LDL-C) in ASCVD is well-established, the long-term population impact of combined lipid profiles, particularly the HDL-C/LDL-C ratio, remains less clearly quantified. This study aimed to estimate the lifetime burden of cardiovascular outcomes associated with different lipid risk profiles using a patient-level simulation framework. Methods: The authors analyzed projected lifetime ASCVD events across four HDL-C/LDL-C risk strata, ranging from low (≥0.45) to very high (<0.25), using the National Health Model Database of Projected and Estimated Outcomes (NHM-DPEO)—a digital twin of national healthcare systems built from multiple data sources, including national health and demographic statistics and estimates from the relevant literature. The framework is structured as a patient-level simulation model that projects individual health trajectories over a lifetime horizon. Model outputs were assessed for plausibility by comparison with published epidemiological estimates. Results: The NHM simulation revealed a strong, graded relationship between lipid profiles and cardiovascular survival. Life expectancy declined from 80.2 years in the lowest risk group (HDL-C/LDL-C ≥ 0.45) to 63.0 years in the very-high-risk group (HDL-C/LDL-C < 0.25), a reduction of 17.2 years, with 13.7 fewer QALYs. Similarly, participants with LDL-C > 5.0 mmol/L had a life expectancy 13.4 years shorter than those with LDL-C < 3.1 mmol/L. The burden of ASCVD increased exponentially with worsening lipid ratios: MI events rose from 5000 to 73,090 per 100,000 births, with onset in the highest risk group occurring as early as age 20. Ischaemic heart disease followed a similar pattern, showing up to 92% of events attributable to elevated lipid risk. While ischaemic stroke risk displayed a more complex pattern due to earlier MI mortality in high-risk groups, overall cardiovascular mortality and lifetime event burden were dominated by LDL-driven disease. These findings demonstrate that sustained LDL-C reduction and balanced HDL-C/LDL-C ratios confer substantial survival benefits across both sexes and all age groups. Conclusions: This study shows that lipid balance has a decisive influence on cardiovascular survival. Sustained LDL-C reduction and favourable HDL-C/LDL-C ratios markedly extend life expectancy and delay the onset of MI and IHD. The magnitude of this survival benefit highlights the need for early and continuous lipid control as a cornerstone of ASCVD prevention. The NHM quantifies these lifetime effects, offering valuable insights for targeted strategies that improve both longevity and quality of life. Full article

Background and Objectives: Benign prostatic hyperplasia (BPH) is a progressive, androgen-dependent condition driven by dihydrotestosterone (DHT). 5α-reductase inhibitors (5-ARIs), including finasteride and dutasteride, target this pathway and provide disease-modifying effects. Materials and Methods: This narrative review summarizes evidence from randomized trials, meta-analyses, and observational studies evaluating the efficacy, timing, and safety of 5-ARIs in the management of LUTS due to BPH. Results: 5-ARI therapy reduces prostate volume by 18–28% and serum PSA by approximately 50% within 6–12 months. Landmark trials (MTOPS, CombAT) demonstrate significant reductions in acute urinary retention (AUR) and BPH-related surgery (>50% RR reduction). Combination therapy with α-blockers provides superior symptom control and greater prevention of clinical progression, particularly in men with prostate volume ≥ 30–40 mL or PSA ≥ 1.5 ng/mL. Early initiation of combination therapy improves long-term outcomes, while α-blocker withdrawal may be feasible in selected patients. Adverse events are mainly sexual, with emerging data suggesting a possible association with depression. Conclusions: 5-ARIs are central to BPH management, offering sustained clinical benefits and prevention of progression. Optimal outcomes depend on appropriate patient selection, early treatment in high-risk individuals, and individualized long-term strategies. Full article