Search Results (35,664)

Background/Objectives: Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) that often requires long-term parenteral nutrition (PN). Extended PN results in severe complications and reduced quality of life (QoL). This study aimed to evaluate the QoL utility weights associated with PN duration using vignettes. Methods: We developed detailed scenarios and descriptions to represent eight hypothetical health states, reflecting variations in PN frequency in both pediatric and adult patients. A cross-sectional survey was conducted among 359 Korean adults (aged 19–59 years) from the general population, assigned to evaluate adult (n = 179) or pediatric (n = 180) vignette groups. Health utility was measured using the EuroQol 5-Dimension (EQ-5D), visual analog scale (VAS), and time trade-off (TTO) methods. Multivariable regression analysis using a mixed-effects model was employed to manage repeated measures and control for sociodemographic variables. Results: Utility scores measured using the EQ-5D, VAS, and TTO were negatively correlated with increasing PN days in both adult and pediatric patients with SBS-IF. The highest mean utility values were “0 days on PN” (adults: EQ-5D 0.808, VAS 0.689, TTO 0.874; pediatric: EQ-5D 0.804, VAS 0.680, TTO 0.883), while the lowest were “7 days on PN” (adults: EQ-5D 0.117, VAS 0.180, TTO 0.272; pediatric: EQ-5D 0.070, VAS 0.178, TTO 0.291). These trends remained significant after covariate adjustment (p < 0.001). Conclusions: The study revealed a steady decline in utility values with an increasing number of PN days. These findings highlight the importance of enhancing the QoL in patients with SBS-IF by supporting intestinal adaptation and reducing PN dependency. Full article

Teacher wellbeing is a matter of social justice since burnout syndrome disproportionately affects those working in under-resourced and diverse educational contexts by limiting their ability to foster inclusive and equitable learning. To this situation, art museums respond as pedagogical spaces for wellbeing while contributing to socially just and sustainable arts education. School teachers are offered new opportunities for ongoing professional development tailored to their well-being needs, such as burnout prevention. A two-round international Delphi study with experts from universities, schools, museums, and arts-and-wellbeing organizations (n = 26 1st round, n = 17 2nd round)—rather than focusing on teachers’ personal accounts—develops consensus on a pedagogical framework for art-based programs designed to prevent teacher burnout and enhance wellbeing. The findings identify nine pedagogical guidelines highlighting participatory approaches—audience, objectives, content, methodology, scheduling, facilitators, activities, evaluation, and program adherence. By positioning art museums as democratic, inclusive, and relational spaces, the framework advances the role of the arts in addressing systemic challenges in education, such as supporting teachers’ wellbeing. This research contributes to the international debate on socially just arts education by demonstrating how teacher wellbeing can be fostered through innovative, evidence-based museum practices aligned with SDG 4. Full article

Background: Diabetic foot syndrome is a common complication of diabetes mellitus, and its incidence is increasing due to increasing rates of overweight and an aging population. Negative pressure wound therapy has been shown to improve wound healing. This study aimed to analyze the efficacy of this therapy compared with conventional treatments in patients with diabetic foot ulcers. Methods: A systematic search was conducted in the following databases: PubMed, SCOPUS, CINAHL, and the Cochrane Library, and the methodological quality was assessed using the Rob2 scale. This meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: A total of 11 clinical trials involving 1117 subjects. The primary outcome was efficacy, which was measured by the complete healing rate, wound size, time to granulation tissue formation, adverse effects, amputations, hospital stay, and cost. This study demonstrated that this therapy improves healing (OR= −10.39, 95% CI [−14.22, −6.57]) and reduces wound size (OR = −4.11, 95% CI [−7.83, −0.39]) while potentially lowering overall costs. Conclusions: Limitations include heterogeneity and different variables measured in studies. Additionally, there were differences among the trials due to the lack of blinding. Although no significant differences were found in amputations or infections, this therapy reduces pain and decreases the use of antibiotics and analgesics. Its use requires individual and expert assessment to maximize its benefits. Full article

Background: Wolf–Hirschhorn syndrome (WHS) is a rare contiguous gene deletion disorder associated with a high incidence of early-onset epilepsy. Despite the clinical relevance of seizures in this population, few large-scale studies have provided detailed data on epilepsy phenotypes and treatment outcomes. Methods: We analyzed a cohort of 140 individuals with WHS from Spain and Latin America. Using validated caregiver-reported questionnaires, we collected detailed information on seizure types, antiseizure medications (ASM) use, and associated comorbidities. Statistical comparisons were made to identify correlations between epilepsy severity, deletion size, and functional outcomes. Results: Epilepsy was observed in 92% of patients, typically beginning before 12 months of age. Multiple seizure types were common, particularly generalized tonic–clonic and atypical absence seizures. Status epilepticus occurred in 58% of cases, with a high proportion requiring multiple ASMs. Valproic acid and levetiracetam were the most commonly used treatments. Patients with more severe epilepsy tended to have larger deletions (>9 Mb) and poorer developmental outcomes. ASM discontinuation was significantly associated with older age at evaluation, supporting improved seizure control over time. Conclusions: Epilepsy in WHS is frequent, often severe in early childhood, and associated with neurodevelopmental impairment and increased treatment burden. While some patients show improvement with age, early aggressive management using appropriate ASMs may be critical to improve neurological prognosis. Advances in diagnosis, early intervention, and targeted therapies offer hope for improved long-term outcomes in this vulnerable population. Full article

Hepatorenal syndrome (HRS) is a high-mortality, potentially reversible form of kidney failure that arises from a tight hemodynamic–inflammatory coupling in cirrhosis. Contemporary redefinitions prioritize creatinine kinetics over static thresholds and recognize non-acute kidney injury (AKI) functional phenotypes, enabling earlier recognition but heightening the need for precise etiologic triage. This narrative synthesis integrates current concepts across pathophysiology, diagnosis and management. Portal hypertension, bacterial translocation and inflammatory mediators amplify splanchnic vasodilation and effective arterial underfilling. Compensatory neurohumoral activation precipitates renal vasoconstriction, intrarenal microcirculatory dysfunction and sodium–water retention. The pivotal diagnostic fork remains HRS–AKI versus acute tubular necrosis. A pragmatic, tiered strategy, structured volume assessment, filtration markers and a parsimonious tubular-injury panel offer actionable discrimination, whereas fractional excretion indices serve as adjuncts only. Initial therapy should be bundled and time-sensitive: remove nephrotoxins, treat infection and initiate albumin plus a vasoconstrictor. The transplant strategy should default to isolated liver transplantation unless end-stage renal disease is established. Future priorities include validated biomarker cut-offs, ultrasound-guided volume algorithms and pathway-based trials to reduce diagnostic delay and improve survival. Full article

Background: The application of large language model (LLM) in surgical decision-making is rapidly expanding, yet its potential in hand and peripheral nerve surgery remains largely unexplored. This study assessed the diagnostic and therapeutic performance of a large language model (ChatGPT-4o) in scenarios characterized by multiple valid management strategies and absent expert consensus. Methods: Three representative cases—thumb carpometacarpal (CMC I) arthritis, scaphoid nonunion, and carpal tunnel syndrome (CTS)—were developed to reflect frequent conditions in hand surgery with competing but accepted treatment options. Each case was submitted to ChatGPT-4o using a standardized prompt. LLM-generated responses were evaluated by 52 participants (34 board-certified hand surgeons and 18 residents) across diagnostic accuracy, clinical relevance, and completeness. Readability indices, including Flesch–Kincaid Grade Level, were analyzed to assess appropriateness for a medical audience. Results: ChatGPT-4o demonstrated coherent but limited diagnostic accuracy (mean 2.9 ± 1.2 SD), moderate clinical relevance (3.5 ± 1.0 SD), and slightly higher completeness (3.4 ± 1.1 SD). Performance was strongest in the standardized scenario (carpal tunnel syndrome, CTS) and weakest in individualized reasoning (CMC I arthritis). No significant differences were observed between experts and residents (p > 0.05). In higher-level reasoning, ChatGPT-4o performed best in CTS and weakest in CMC I arthritis. Readability confirmed professional-level language (mean Flesch–Kincaid Grade Level: 16.4). Conclusions: ChatGPT-4o shows promise as a supportive tool for diagnostic reasoning and surgical education, particularly where standardized frameworks exist. Its limitations in ambiguous scenarios highlight the ongoing need for expert oversight. Future large language model development should emphasize specialty-specific training and context-aware reasoning to enhance their role in surgical decision support. Full article

Trauma is a major cause of morbidity and mortality in dogs and cats. While prognostic tools are well-established in human medicine, few guidelines exist in veterinary trauma care. The Animal Trauma Triage (ATT) score and modified Glasgow Coma Scale (mGCS) are used to assess illness severity, but their clinical utility in veterinary patients remains undervalued. This study aimed to evaluate the prognostic value of ATT and mGCS scores and their association with organ dysfunction and survival in polytraumatized veterinary patients. We hypothesized that multi-organ failure (MOF) is more prevalent in non-survivors and correlates with higher ATT and lower mGCS scores. A prospective observational study was conducted for 30 patients (20 dogs and 10 cats) admitted to two veterinary hospitals. Clinical data, trauma scores, and outcomes were collected and analyzed. The overall survival rate was 83.3%; blunt trauma accounted for 80% of cases. Non-survivors (n = 5) had higher respiratory rates at admission (p = 0.01). The ATT score accurately predicted all fatalities, while the mGCS score showed limited prognostic value. MOF was the leading cause of death in 60% of non-survivors. ATT appears to be a more reliable tool for outcome prediction, enabling improved triage, resource allocation, and early intervention in veterinary trauma cases. Full article

Background: Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare autosomal dominant disorder characterized by persistently elevated serum ferritin and early-onset bilateral cataracts in the absence of systemic iron overload. It is caused by pathogenic variants in the iron-responsive element (IRE) of the FTL gene, leading to dysregulated L-ferritin synthesis. Methods: We evaluated a 12-year-old Czech girl with markedly elevated serum ferritin identified incidentally during workup for abdominal pain. Clinical assessment included biochemical, radiological, ophthalmological, and genetic testing of the proband and available family members. Results: Magnetic resonance imaging excluded systemic iron overload, while ophthalmological evaluation revealed bilateral cataracts. Family history indicated multiple affected relatives across three generations. Genetic testing confirmed a heterozygous FTL c.-168G>C variant. Additional screening for common HFE variants revealed heterozygous H63D in several family members, with no impact on ferritin or hepcidin levels. Beyond this case, we provide a comprehensive review of HHCS, including molecular mechanisms, an updated overview of reported FTL mutations, and ophthalmological features that distinguish HHCS cataracts from other congenital cataracts. Conclusions: This report underscores the translational relevance of combining molecular diagnostics, clinical evaluation, and family screening to improve recognition and management of HHCS, and to prevent misdiagnosis and unnecessary iron-depletion therapy. Full article

Mitochondrial dysfunction contributes to female reproductive endocrine disorders and is frequently associated with multisystem symptoms. Insulin resistance (IR) is a common metabolic disorder strongly linked to polycystic ovary syndrome (PCOS), while premature ovarian insufficiency (POI) also impairs fertility. Mitochondrial DNA (mtDNA) deletions and the stress-responsive cytokine growth differentiation factor 15 (GDF-15) have recently emerged as complementary biomarkers of mitochondrial impairment. In this retrospective observational study, we examined reproductive hormones, plasma GDF-15, mtDNA deletions, and clinical symptoms in insulin-resistant women, including those with PCOS or POI. Eighty-one patients were divided into three subgroups: IR-only (n = 49), IR-PCOS (n = 19), and IR-POI (n = 13). IR was defined based on elevated insulin levels during oral glucose tolerance testing (>10 mU/L at 0 min, >50 mU/L at 60 min, >30 mU/L at 120 min) according to national gynecological endocrinology guidelines, acknowledging that IR is not universally accepted as a distinct clinical entity. POI was defined as reduced ovarian reserve before age 40 with anti-Müllerian hormone (AMH) <1.0 ng/mL. Clinical symptoms were assessed using a questionnaire, medical record, and physical examination. MtDNA deletions were detected by long-range PCR, and GDF-15 was measured by ELISA. Free thyroxine (T4) emerged as an independent predictor of GDF-15, suggesting that thyroid function modulates mitochondrial stress signaling in insulin-resistant women. MtDNA deletions and/or elevated GDF-15 correlated with endocrine, gastrointestinal, and neuropsychiatric symptoms, and reduced AMH/FSH ratios indicated impaired ovarian function. Cross-sectional analysis further revealed lower AMH and AMH/FSH ratios in older women with mtDNA deletions, consistent with a trend toward accelerated reproductive aging. Overall, these findings support the role of GDF-15 and mtDNA deletions as complementary biomarkers of mitonuclear stress, with potential relevance for both systemic and reproductive health. Full article

Background: Metabolic syndrome (MetS) is a significant global health burden and a known risk factor of cardiovascular disease and diabetes. Growing evidence also links MetS to cancer development, likely via chronic inflammation, insulin resistance, and hormone disruption. However, its association with laryngeal cancer remains largely unclear and underexplored. Methods: For this review, we thoroughly searched PubMed/MEDLINE, Scopus, and Web of Science for observational studies investigating associations of MetS with laryngeal or head and neck cancers (HNCs) until 1 August 2025. Five large population-based studies were found to meet inclusion criteria, and risk of bias was assessed using the Joanna Briggs Institute checklist (JBI). Results: Three Korean cohort studies consistently found that MetS increased the risk of laryngeal cancer (HR 1.13–1.32), independent of smoking and alcohol use. Hypertension and hyperglycemia were the most consistent components associated with increased risk, and chronic MetS conferred the highest hazard. In contrast, analyses from the UK Biobank (HNC) and SEER-Medicare (HNSCC) cohorts showed null and inverse associations, respectively. Additional findings included dose–response effects with increasing MetS components, U-shaped associations for HDL-C and waist circumference and increased risk associated with elevated C-reactive protein. Conclusions: Current evidence suggests a possible association between MetS and risk of laryngeal cancer, although the direction and strength of effect vary across populations. Findings from Korean cohorts provide consistent signals of increased risk, whereas Western datasets have not replicated this pattern. Overall, the certainty of evidence is low to moderate, warranting cautious interpretation and further validation in diverse populations before inferring causality. Full article

Introduction: Clinical variability within families harbouring disease-causing genetic variants hampers clinical care and risk stratification. We studied a multigenerational family presenting with sinus bradycardia and long QT syndrome type 2 (LQTS2). The family harboured a pathogenic variant in KCNH2, which co-segregated with the observed LQTS2. We studied the genetic cause of the high occurrence of sinus bradycardia in this family. Methods: Clinical data was collected, including heart rate, QT-interval, symptoms, and echocardiographic parameters. QTc was calculated using the Bazett and the Fridericia formula. Sanger sequencing of HCN4 was performed, followed by segregation analysis of the identified variant with sinus bradycardia. The biophysiological consequences of two variants, KCNH2-p.L69P (c.206T>C) and HCN4-p.R666W (c.1996C>T), were assessed by patch-clamp experiments. Therefore, a heterologous model was generated by transfection of HEK293A or CHO-k1 cells, respectively. Results: Sanger sequencing of HCN4 identified HCN4-p.R666W (c.1996C>T), which has a stronger segregation with the observed sinus bradycardia than KCNH2-p.L69P. Patch-clamp experiments revealed that KCNH2-p.L69P and HCN4-p.R666W lead to a decrease in the corresponding current densities, which explains the LQTS and sinus bradycardia observed in the patients. Carriers of both genetic variants have a more severe LQTS2 phenotype, reflected in longer QT and higher incidence of syncope. Conclusions: We identified two (likely) pathogenic variants, KCNH2-p.L69P and HCN4-p.R666W, co-segregating with LQTS2 and sinus bradycardia, respectively. Patients carrying both variants showed a more severe phenotype. These findings highlight the importance of additional genetic testing when discordant features are present, thereby enabling more accurate diagnosis, risk prediction, and management. Full article

Background: High-throughput metabolomics studies have promoted the discovery of candidate biomarkers linked to atherosclerosis (AS). This narrative systematic review summarises metabolomics studies conducted in (1) individuals with subclinical AS (assessed by imaging techniques such as carotid intimal media thickness, IMT, and coronary artery calcium, CAC), (2) patients with established atherosclerotic plaques, and (3) individuals with AS risk factors. Methods: The systematic search was conducted in the PubMed database according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were as follows: (i) publication date between 2009 and 2024; (ii) identification of potential biomarkers for AS in subjects with a diagnosis of AS or with one or more traits characteristic of the disease (i.e., CAC or IMT); (iii) identification of potential AS biomarkers in subjects with atherogenic clinical conditions (i.e., Down’s syndrome, DS, polycystic ovarian syndrome, PCOS, and systemic lupus erythematosus, SLE); (iv) metabolomic studies; and (iv) studies in human samples. Exclusion criteria comprised the following: (i) studies on lipid metabolic diseases unrelated to AS, (ii) “omics” results not derived from metabolomics, (iii) reviews and studies in animal models or cell cultures, and (iv) systematic reviews and meta-analyses. Of 90 eligible studies screened, 24 met the inclusion criteria. Results: Across subclinical and overt AS, consistent disturbances were observed in amino acid, lipid, and carbohydrate metabolism. Altered profiles included branched-chain amino acids (BCAAs), aromatic amino acids (AACs) and derivatives (e.g., kynurenine–tryptophan pathway), bile acids (BAs), androgenic steroids, short-chain fatty acids (FAs)/ketone intermediates (e.g., acetate, 3-hydroxybutyrate, 3-HB), and Krebs cycle intermediates (e.g., citrate). Several metabolites (e.g., glutamine, lactate, 3-HB, phosphatidylcholines, PCs/lysophosphatidylcholines, lyso-PCs) showed reproducible associations with vascular phenotypes (IMT/CAC) and/or clinical AS. Conclusions: The identification of low-weight metabolites altered in both subclinical and overt AS suggests their potential as candidate biomarkers for early AS diagnosis. Given the steady increase in deaths from cardiovascular disease, a manifestation of advanced AS, this finding could have significant clinical relevance. Full article

Background: Dexmedetomidine (Dex) is a well-known a2-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic effects that has been used principally as adjuvant sedation in the ICU. The enhanced clinical experience of Dex’s use and its physiological effects encourage its application beyond the initial indications. Aim: The purpose of this review is to summarize the current knowledge of Dex’s recently expanded applications in critically ill intensive care unit (ICU) adult patients. Methods: It is a narrative review that critically examines studies published since 2015 and referring to Dex’s use in ICU patients. Results: Despite the preliminary applications and the weak existing recommendation, the unique arousable sedation, in combination with mild opioid-spare analgesic effects, has been confirmed to effectively improve ICU outcomes. Moreover, the anxiolytic and sympatholytic actions have proved to sufficiently enhance sleep quality and prevent and treat ICU delirium and post-ICU syndrome, especially among elderly patients. Recently, increasing evidence advocates for promising neuro-, renal-, and cardio-protective and anti-inflammatory effects of Dex, which are attributed to autophagy and apoptosis inhibition and sympatholytic and ischemia/reperfusion (I/R) injury-protective effects. Conclusions: Beyond sedation, Dex seems to present promising neuroprotective, anti-inflammatory, and immunomodulating effects. Full article

Introduction: Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with both venous and arterial thrombosis, most notably ischemic stroke. Patients face a high risk of recurrence, and yet optimal strategies for secondary prevention remain uncertain. Methods: We conducted a narrative review of the literature on secondary prevention of ischemic stroke in APS. We performed a comprehensive literature search of PubMed for English-language articles on secondary stroke prevention in APS. Studies were included if they were original human research (e.g., randomized trials, cohort, or case–control studies) or relevant reviews addressing APS-related stroke prevention. Results: Vitamin K antagonists (VKAs) remain the standard of care for high-risk patients with arterial events. Several randomized controlled trials demonstrated higher recurrence rates, particularly of stroke, among APS patients treated with direct oral anticoagulants (DOACs). The optimal target INR remains debated; pooled analyses suggest no clear advantage of high-intensity anticoagulation (INR 3–4) over standard-intensity (INR 2–3), but individualized adjustment is warranted in select cases. In patients with recurrence despite adequate anticoagulation, adding an antiplatelet agent may be beneficial, although supporting evidence is limited. Adjunctive statin therapy shows promise in reducing endothelial dysfunction and prothrombotic markers, with observational data suggesting a possible protective effect, although randomized evidence is lacking. In addition, patent foramen ovale (PFO) closure has been proposed in selected APS patients with paradoxical embolisms, particularly when combined with anticoagulation. Non-pharmacological strategies, including structured lifestyle modification and rigorous vascular risk-factor management, are strongly recommended, as traditional cardiovascular risk factors synergistically increase recurrence risk. Conclusions: Secondary prevention of ischemic stroke in APS requires an individualized approach. VKAs remain first-line, with consideration of antiplatelet add-on, statins, lifestyle interventions, and PFO closure in appropriate settings. Future well-designed clinical trials are needed to refine INR targets, validate combination strategies, and clarify the role of adjunctive therapies in this complex patient population. Full article

Zika virus (ZIKV) was first identified in Africa in the mid-20th century and circulated for decades with limited and often unnoticed human cases. This situation changed with the emergence of the Asian lineage, responsible for large outbreaks in the Pacific and the Americas and for severe complications such as Guillain–Barré syndrome and Congenital Zika Syndrome (CZS). In contrast, the African lineage, although frequently more efficient in replication, cytopathogenicity, and mosquito transmission in experimental systems, has not been linked to comparable epidemics or congenital disease clusters. This review summarizes current knowledge on the differences between African and Asian lineages at the molecular, cellular, and epidemiological levels. It highlights how genetic variation interacts with host immunity, ecological factors, and human activity to shape epidemic potential. Understanding these interactions is essential for anticipating future outbreaks and for improving strategies to mitigate the impact of emerging arboviruses. Full article