Abstract Introduction Prader-Willi syndrome (PWS) is a complex genetic disorder characterized by a constellation of phenotypic features and hypothalamic dysfunction, including multiple endocrine abnormalities, short stature, and severe hyperphagia associated with satiety center dysfunction that leads to morbid obesity. Hormone deficiencies diagnosed and managed in childhood necessitate lifelong continuation and monitoring into adulthood. Material and Methods This retrospective observational study included 14 young adult patients with Prader-Willi syndrome (aged 18-30 years) who received GLP-1 receptor agonist therapy (semaglutide; n = 10) or dual GLP-1/GIP receptor agonist therapy (tirzepatide; n = 4) over 12 months. Semaglutide treatment was initiated at a dose of 0.25 mg once weekly and gradually escalated every 4 weeks up to a maximum dose of 1.7 mg/week, whereas tirzepatide treatment was started at 2.5 mg/week and maintained at 5 mg/week (without dose escalation due to economic constraints). None had type 2 diabetes mellitus. Body weight, BMI, and body fat percentage were evaluated in all patients, while fasting glucose, insulin, lipid profile, glycated hemoglobin, and hormone levels were measured and statistically analyzed with between-group comparisons. Results The mean age in the tirzepatide-treated group was 21.25 years (±SD 4.7; range 18-28 years), whereas in the semaglutide-treated group it was 23.9 years (±SD 3.03; range 20-30 years). Mean baseline BMI in the tirzepatide group was 40.68 kg/m2 (±SD 0.98; range 39.47-41.86) compared to 42.3 kg/m2 (±SD 9.49; range 27.2-54.68) in the semaglutide group. After 12 months of treatment, no significant between-group differences were observed in ΔBMI (P = .945; mean ΔBMI −2.59 in the tirzepatide group vs −2.66 in the semaglutide group), potentially attributable to the small sample size in the tirzepatide cohort and the low doses administered (due to economic constraints). Both treatment groups demonstrated improvements in metabolic control, including reductions in HbA1c, fasting glucose, and lipid profile parameters. Caregivers reported better appetite regulation, with decreased active food-seeking behavior—particularly at night. No serious adverse effects were reported. Conclusions The main aim of PWS clinical management in adulthood is prevention of obesity and its comorbidities, treatment of hormonal disorders and mental health stabilization. GLP1 receptor agonist (semaglutide) and dual GLP-1/GIP receptor agonist (tirzepatide) therapy appears safe in PWS patients and may have potential benefits for weight, metabolic and appetite control. Further research and long-term clinical studies are essential to confirm these benefits and refine therapeutic strategies.
Background Colorectal cancer (CRC) resection imposes profound physiological stress, often leading to acute catabolism, immunosuppression, and a drastic decline in functional capacity. While Enhanced Recovery After Surgery (ERAS) protocols have revolutionized intra- and postoperative care, multimodal prehabilitation capitalizes on the preoperative window. By integrating physical therapy, targeted nutritional support, psychological interventions, and medical optimization, this approach aims to maximize the patient's physiological and psychological reserves prior to surgical trauma. Aim To evaluate the efficacy of multimodal prehabilitation in mitigating postoperative complications in CRC patients and to assess the physiological foundations and methodological challenges present in current literature. Materials and methods: This narrative review was conducted using articles sourced from PubMed by keywords: colorectal cancer, colorectal surgery, multimodal prehabilitation, postoperative complications, ERAS. We examined randomized clinical trials, observational studies, meta-analyses published between 2021-2026. Due to the narrative nature of this review, study selection was based on thematic relevance rather than strict methodological criteria. Results: The majority of studies included in this review demonstrated that multimodal prehabilitation significantly reduces the incidence of postoperative complications in patients undergoing colorectal cancer (CRC) resection. Conclusions: Multimodal prehabilitation proactively optimizes functional and immunological reserves, reducing the incidence of postoperative complications. However, considerable methodological heterogeneity persists across trials regarding intervention duration, adherence to FITT principles, and evaluation metrics. Future high-quality research must standardize protocols and assessment tools to facilitate the routine integration of prehabilitation into perioperative care.
Obesity-related adipose tissue dysfunction leads to a chronic inflammatory state affecting distant organs and tissues. This metabolic inflammation has a detrimental impact on the expression of genes related to glucose metabolism, leading to systemic insulin resistance, which also affects the central nervous system and contributes to cognitive decline. Adipose tissue-derived microRNAs (miRNAs) have been implicated in this phenomenon. This study aimed to investigate whether the expression of genes critical for both insulin action and neuronal metabolism (APP, SOCS3, PTPN1, PTPN2) is altered in the adipose tissue of patients with obesity due to miRNA interference, predisposing them directly to the development of insulin resistance and metabolic inflammation, while indirectly leading to a decline in cognitive function. The expression of mRNAs of the above-mentioned genes, selected adipokines (interleukins 1β, 6, 8, 15, tumor necrosis factor-alpha, resistin, adiponectin) and miRNAs was measured by real-time PCR in adipose tissue of 75 patients with obesity, 19 patients who successfully reduced body mass after metabolic surgery and 25 normal weight subjects, stratified by insulin sensitivity and diabetic status. The results were correlated with patients’ clinical and biochemical parameters. mRNA levels of genes promoting insulin sensitivity, APP and PTPN2, were significantly (p < 0.05) decreased in adipose tissue from patients with obesity, in both visceral (VAT) and subcutaneous (SAT) depots. After stratification by the triglyceride/high-density lipoprotein ratio (an indirect marker of insulin sensitivity), we found that individuals diagnosed with insulin resistance had lower VAT and SAT APP and PTPN2 mRNA levels, whereas APP expression was significantly decreased in VAT from patients with both obesity and type 2 diabetes compared to normoglycemic individuals with obesity, too. We also observed significant positive correlations between the mRNA levels of these genes and the expression of the above-mentioned adipokines. Finally, we analysed the levels of miRNAs targeting the mRNAs of the genes studied and observed significant negative correlations between APP mRNA levels and hsa-miR-579-5p and hsa-miR-142-3p, and between PTPN2 mRNA levels and hsa-miR-142-3p. Adipose tissues of patients with obesity are characterised by altered expression of genes that are key for both insulin action and neuronal metabolism, and miRNAs may be involved in this phenomenon. However, due to the descriptive nature of our experiments, these results require verification in functional studies.
Background Simulation-based education improves procedural competence and patient safety; however, most programs remain locally implemented and are rarely integrated into national training systems. Reports describing sustainable national-scale implementation remain limited. We describe a national governance reform that embedded bronchoscopy simulation within postgraduate medical education at the national level. Methods We conducted a national implementation study evaluating the integration of bronchoscopy simulation training into postgraduate medical education. Bronchoscopy served as the index procedure within a broader reform of procedural training. The intervention combined mastery learning and deliberate practice with objective structured assessment. Governance mechanisms included the development of nine national Standard Operating Procedures (SOPs), instructor certification through a train-the-trainer pathway, establishment of a coordinated network of simulation centers, external quality assurance processes, and integration into postgraduate certification requirements. Implementation was interpreted using the Consolidated Framework for Implementation Research (CFIR) and the RE-AIM framework. Results The national program trained 402 physicians, supported by 85 nationally certified instructors. A total of 184 structured training cycles were delivered, representing 5,999 instructional hours. Bronchoscopy training was implemented as a specialty-specific component of the national simulation program through a structured, multi-stage scale-up process. The training involved 186 enrolled physicians, of whom 185 completed the program. Post-course evaluation demonstrated high acceptability and perceived educational value: 89.5% of participants rated the training as highly relevant to clinical practice, and 98.5% reported increased procedural confidence. Faculty evaluations indicated strong agreement regarding instructional standardization and clarity of assessment procedures. In addition, 46 instructors were certified for the bronchoscopy training component, supporting delivery across a multi-centre simulation network. Following national evaluation, bronchoscopy simulation became a mandatory training requirement in 2024 for physicians specializing in pulmonary diseases. Over €75 million in EU structural funding supported the development of a national network of simulation centers and training capacity for endoscopic procedures. Conclusions National-scale integration of simulation depends less on technology than on governance architecture, standardized faculty development, and alignment with regulatory frameworks. When educational theory is integrated with implementation science and patient-safety priorities, simulation can transition from local innovation to a sustainable national training standard.
The first-trimester combined screening test (CST) increases aneuploidy risk but results in a substantial false-positive burden, with most CST-positive pregnancies ultimately being euploid. Optimizing decision-making within this already risk-enriched population remains a major clinical challenge. This retrospective observational study evaluated a phenotype-guided post-triage (PGT) model applied exclusively to CST-positive pregnancies using the use of routinely collected maternal, biochemical, and ultrasound markers. An interpretable classification and regression tree (CART) model was developed to distinguish true-positive aneuploid pregnancies from false-positive euploid pregnancies. The dataset was split into training, validation, and independent test cohorts, and model performance was assessed in the test cohort. A prespecified positive predictive value–priority operating point was selected to minimize false-positive classification while maintaining acceptable aneuploidy detection. Among the 5,015 CST-positive pregnancies, the aneuploidy prevalence was 4.0% in the test cohort. The PGT model demonstrated strong discrimination comparable to baseline CST risk (area under the receiver operating characteristic curve of 0.93 for both), indicating unchanged global discrimination despite post-triage refinement. At the conventional CST cutoff of 1:300, 52% of euploid pregnancies were classified as screen-positive; application of the PGT model reduced false-positive classification to 3%. A false-positive reduction was observed across guideline-defined CST risk bands, and all aneuploid pregnancies misclassified as negative were detectable by cell-free DNA testing. Phenotype-guided post-triage substantially reduces false-positive classification among CST-positive pregnancies without altering global discrimination, supporting a decision-focused evaluation paradigm for postscreening tools and more efficient use of downstream prenatal testing.
