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Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, and current risk scores based on personal history, physical examination and basic tests fail to identify a proportion of individuals who will experience cardiovascular events. In this context, handheld echocardiography (HHE) is an intermediate step between clinical assessment alone and comprehensive transthoracic echocardiography, with the potential to act as an imaging-based tool within cardiovascular prevention programmes. Through focused, bedside or outpatient examinations, HHE can detect early signs of hypertensive organ damage as well as left and right ventricular dysfunction and other structural cardiovascular abnormalities, beyond traditional clinical evaluation. Through an examination of current evidence, technological developments, and clinical implementation pathways, this review provides a comprehensive overview of the evolving role of HHE as an adjunct to standard cardiovascular assessment, highlighting its potential to enhance early risk stratification in preventive cardiology. In this context, it proposes a pragmatic worklist for focused HHE examinations in at-risk individuals and illustrates representative HHE use cases, with involvement of non-cardiologists and the potential contribution of teleconsultation and digital integration. Finally, unresolved challenges are highlighted, defining the research priorities for the systematic integration of HHE into cardiovascular prevention strategies.

To determine whether achieved sealing length (SL) at the first postoperative computed tomography angiography (CTA) and its subsequent change over time are associated with later endoleak type 1A (EL1A) after infrarenal endovascular aortic repair. Secondary aims were to describe longitudinal remodeling of SL and to assess the association between persistent type 2 endoleak (EL2) and SL trajectories. This retrospective study analyzed SL and sealing surface measured on postoperative CTA, using the first postoperative CTA as the reference examination. We examined whether the first postoperative seal, its subsequent change over time, and prior persistent EL2 were associated with later EL1A. Trajectories of &#x394;SL and &#x394;sealing surface were modeled using spline mixed-effects models. Time to EL1A was analyzed using Cox models with predictors at the first CTA and pre-event change, including a joint baseline-plus-change model. Landmark analyses were used to assess sealing behavior and EL1A risk. Type 2 endoleak was treated as a time-varying exposure, and its association with subsequent EL1A was evaluated using landmark Cox analyses at 12, 24, 36, and 60 months. Among 501 patients, 346 were included in the longitudinal cohort; after a median follow-up time of 56 months (interquartile range, 28-95 months), 73 developed EL2, 39 developed EL1A, and 8 experienced both events. Baseline sealing at the first postoperative CTA and sealing deterioration were independently associated with EL1A in joint models (SL and sealing surface). Type 2 endoleak was associated with differential SL remodeling (interaction P&#x2009;<&#x2009;.001), with progressive divergence after ~24 months. In exploratory landmark analyses, EL2 was associated with higher subsequent EL1A hazard (36-month hazard ratio [HR]&#x2009;=&#x2009;2.48; P&#x2009;=&#x2009;.030; 60-month HR&#x2009;=&#x2009;3.14; P&#x2009;=&#x2009;.008), persisting after adjustment for sealing state and change up to the landmark. Both the first postoperative infrarenal seal and its variation during follow-up were associated with later EL1A. Persistent EL2 was associated with sealing deterioration, whereas its association with subsequent EL1A should be considered exploratory because few patients experienced both events.Clinical ImpactIn infrarenal endovascular aneurysm repair, both the sealing length achieved at the first postoperative computed tomography angiography and its longitudinal change were associated with later type 1A endoleak (EL1A). Persistent type 2 endoleak was associated with less favorable sealing evolution and may identify patients with reduced seal stability and exploratory higher subsequent EL1A risk.

Cutaneous squamous cell carcinoma is a major cause of cancer-related mortality. Although immune checkpoint blockade improves outcomes, many patients fail to respond or develop resistance. Cancer-associated fibroblasts (CAFs) promote tumor progression and therapy resistance, but the signals that drive fibroblast reprogramming remain incompletely defined. Here, we show that thyroid hormone signaling, mediated by type 2 deiodinase (D2), regulates CAF activation. Single-cell transcriptomics and spatial RNA profiling identify a D2-positive fibroblast subpopulation that overlaps with immunomodulatory and matrix CAF states. RNA-seq analysis indicates that D2 supports activated and metabolically competent CAF programs. In vivo fibroblast-specific D2 deletion reduces CAF activation and limits tumor expansion. Spatial metabolomics further links D2-positive regions to metabolic remodeling of the tumor microenvironment and collagen-rich matrix deposition associated with aggressive tumor behavior. These findings support a role for D2-mediated thyroid hormone signaling in fibroblast reprogramming and suggest a therapeutic opportunity in cutaneous squamous cell carcinoma.

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The endoscopic endonasal approach (EEA) has undergone substantial evolution over the past three decades, largely driven by advances in visualization and the development of specialized instrumentation. Despite this technological progress, the long-term availability and ergonomics of dedicated tools remain limiting factors. In particular, safe dural incision within the confined nasal corridor continues to depend on instruments that are often difficult to maintain or replace. To describe a simple, reproducible technical modification aimed at improving safety, ergonomics, and sustainability during the dural incision phase of the EEA. A disposable microknife was mounted on a reusable straight titanium handle and covered with a standard suction catheter trimmed to the appropriate length, functioning as a partially retractable protective sheath. The technique was applied in 30 consecutive endonasal procedures for sellar and suprasellar lesions. The modified instrument was seamlessly integrated into the standard four-hand surgical workflow. It enabled safe introduction, controlled blade exposure, and secure withdrawal under continuous endoscopic visualization. The protective sheath effectively minimized inadvertent mucosal trauma during insertion and removal, while preserving tactile feedback and maneuverability. No additional setup time was required. Surgeons reported improved control and reduced cognitive workload, particularly in narrow or fibrotic corridors. This technical adaptation represents a safe, ergonomic, and cost-effective refinement of the dural incision step in endoscopic endonasal surgery. Beyond its immediate practical advantages, it exemplifies incremental, experience-driven innovation in skull base surgery, consistent with the "Idea-Development" stage of the IDEAL framework.

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Single-nucleus RNA sequencing (snRNA-seq) enables transcriptomic profiling of tissues that are difficult to dissociate. Here, we present an integrated protocol combining tissue-specific nuclei extraction and selective enrichment to isolate high-quality nuclei from fresh mouse liver and visceral adipose tissue (VAT). We describe steps for single-nucleus extraction, magnetic enrichment, BD Rhapsody capture, cDNA synthesis, whole-transcriptome amplification, index PCR, library quality control, and shallow sequencing-based assessment of cell-type recovery, while separating whole-liver and non-parenchymal cell workflows to reduce dissociation bias.

To compare cystectomy and ablative surgical techniques for the treatment of ovarian endometrioma, focusing on recurrence, ovarian reserve, and fertility outcomes. This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261342497). PubMed and Scopus were searched from January 2000 to September 2025. Studies comparing cystectomy with ablative techniques (CO2 laser, argon plasma coagulation, PlasmaJet, bipolar energy, or hybrid approaches) in women with ovarian endometrioma &#x2265;3&#xa0;cm were included. Random-effects models were used to calculate pooled risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Twelve studies were included, with 4-6 studies contributing to each meta-analysis depending on outcome availability. Cystectomy showed a trend toward lower recurrence compared with ablative techniques (RR 0.61, 95% CI 0.37-1.01; p&#xa0;=&#xa0;0.054), although this did not reach statistical significance. Ablative techniques were associated with better preservation of ovarian reserve, with a significantly smaller decline in antral follicle count (MD&#xa0;-&#xa0;1.96, 95% CI&#xa0;-&#xa0;3.04 to&#xa0;-&#xa0;0.88; p&#xa0;<&#xa0;0.001), while no significant difference was observed in anti-M&#xfc;llerian hormone levels (MD&#xa0;-&#xa0;0.24, 95% CI&#xa0;-&#xa0;0.69 to 0.21; p&#xa0;=&#xa0;0.30). No significant differences were found in overall pregnancy (RR 1.02), spontaneous conception (RR 1.02), or ART/IVF pregnancy rates (RR 0.83). Cystectomy may reduce recurrence risk, whereas ablative techniques better preserve ovarian reserve. However, neither approach appears to confer a significant advantage in fertility outcomes. Surgical management of ovarian endometrioma should be individualized based on patient characteristics and reproductive goals.

The uric acid to high-density lipoprotein-cholesterol ratio (UHR) has been associated with type 2 diabetes or hepatic steatosis in adults, while pediatric evidence is poor. We aimed to evaluate the association between UHR and several obesity-related comorbidities in youths with overweight or obesity (OW/OB). 1215 youths of the CARITALY study were enrolled. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were assessed by standard methods. The homeostasis model assessment of insulin resistance (HOMA-IR) and the whole-body insulin sensitivity index (WBISI) were calculated. A continuous cardiometabolic risk score (cCMR) was calculated. Metabolic-associated steatotic liver disease (MASLD) was defined by a standard method. Mild reduced-estimated glomerular filtration rate (MReGFR) was defined by eGFR value&#x202f;>&#x202f;60&#x202f;<&#x202f;90&#x202f;ml/min/1.73&#x202f;m2 White blood cell count (WBCc) was obtained. UHR was stratified into quartiles. Youths in the top UHR quartile showed a higher odds ratio (OR)(95%CI) of MReGFR: 2.03 (1.31-3.13) and cCMR: 2915 (1.60-4.24) vs the first quartile. Youths in the third UHR quartile showed significantly higher ORs of IFG 2.00 (1.01-3.94), IGT: 2.64 (1.37-5.10), HOMA-IR: 1.64 (1.17-2.29), and high WBCc: 2.49 (1.64-3.77), whereas youths yet in the second quartile showed significantly higher OR of low WBISI: 1.60 (1.04-2.50) and MASLD: 1.61 (1.13-2.28) vs the first quartile. UHR was associated with disrupted glucose homeostasis, high cardiometabolic risk, MASLD, reduced glomerular filtration, and low-grade inflammation in youths with OW/OB. UHR is a promising biomarker for detecting obesity-related comorbidities in this population.

Large dikes are the main mechanism of crustal extension in volcanic areas, but the processes in the underlying magma system that supply the required volumes remain unclear. We show that 1.4&#xa0;cubic kilometers of magma propagated under the Ethiopian rift in December 2024 and continued for ~3 months. Geodesy and seismicity reveal that the dike was fed from a network of magma reservoirs between 6 to 12&#xa0;kilometers in depth with pathways rapidly forming between them. We calculate pressure changes in the reservoirs and show that underpressure developed in the deeper portion, creating the conditions to drain large magma volumes. We find that tectonic stress and availability of magma alone are not enough to drive intrusion of massive dikes. These events will start only after magma connectivity and deep underpressure develop. Similar conditions may be important for the transfer of large magma volumes from the mantle and the formation of large igneous provinces.

Epigenetic alterations, including aberrant DNA hypermethylation and histone modifications, contribute to oncogenesis by disrupting normal gene expression programs. Unlike genetic mutations, these changes are potentially reversible, providing a strong biological rationale for the development of histone deacetylase inhibitors (HDACi) for therapy. Several HDACi are currently under investigation, either as monotherapy or in combination with other anticancer agents. A comprehensive understanding of toxicity is essential to appropriately balance risks and benefits, particularly because HDACi are most frequently evaluated within combination regimens. To date, no epigenetic agents have received regulatory approval for pediatric malignancies, and clinical development in this population remains at an early stage. The aim of this study was to systematically characterize the toxicity profiles associated with HDACi administration in pediatric patients with cancer, including both solid tumors and hematologic malignancies. To this end, we conducted a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Toxicity profiles were extracted from twelve studies investigating six HDACi: panobinostat, vorinostat, entinostat, pracinostat, valproic acid, and depsipeptide. Eleven studies were Phase I or Phase I/II clinical trials, and one was a retrospective study. Patients with solid central nervous system tumors represented the most frequently studied population. Overall, treatment-related toxicities were predominantly mild, with few severe (grade 4) adverse events, mainly within the hematologic category. According to the Common Terminology Criteria for Adverse Events grading system, hematologic toxicities were the most common adverse events across all HDACi, particularly thrombocytopenia, followed by mild gastrointestinal and metabolic toxicities. Cardiac, neurological, respiratory, and systemic toxicities were generally mild, less frequent, and considered treatment-related. Dose and route of administration influenced both the frequency and severity of toxicities. Pan-HDAC inhibitors were associated with the highest rates of toxicity. HDACi-related toxicities were moderate and manageable in pediatric patients. Differences in toxicity were observed among treatments, with higher doses linked to increased toxicity. These findings support further clinical trial development of HDACi in pediatric malignancies. However, Phase I design, small patient numbers, and heterogeneity in age, weight, and disease characteristics are major limitations in accurately assessing HDACi-induced toxicity.

Major depressive disorder is increasingly conceptualized as a condition involving brain network dysfunction, neuroimmune imbalance, sleep-circadian disruption, hypothalamic-pituitary-adrenal (HPA)-axis dysregulation, monoaminergic arousal instability, and impaired synaptic plasticity. In parallel, the glymphatic system has emerged as a plausible integrative mechanism linking these domains, because it is a glia-dependent pathway supporting cerebrospinal fluid-interstitial fluid exchange and metabolic-waste clearance, with activity strongly modulated by deep non-rapid eye movement (NREM) sleep. This narrative review synthesizes evidence that glymphatic-related magnetic resonance imaging (MRI) proxies, particularly diffusion tensor imaging along the perivascular space (DTI-ALPS), are altered in depression, while emphasizing that DTI-ALPS is an indirect marker of perivascular diffusion rather than a direct measure of glymphatic flow. We define four key research gaps: scarcity of treatment-resistant depression (TRD)-specific cohorts, regional and technical heterogeneity across MRI studies, and uncertainty about causal direction relative to sleep disturbance and inflammation. Altered indices appear to relate to fatigue, psychomotor retardation, cognitive impairment, rumination, suicidality, systemic inflammation, oxidative stress, and HPA-axis dysregulation. We integrate opposite-direction findings, including elevated ALPS in drug-naive somatic depression, into a state- and subtype-dependent working model rather than a unidirectional dysfunction framework. Therapeutic implications are organized by target specificity, including sleep-dependent clearance, perivascular exchange, aquaporin-4 (AQP4) polarization, vascular pulsatility, and neuroimmune modulation. We propose falsifiable predictions and negative-control analyses to distinguish a glymphatic-related model from additive effects of insomnia, inflammation, and vascular risk. Overall, the current evidence supports a cautious translational framework for biomarker-informed trials in TRD-relevant phenotypes rather than a validated diagnostic biomarker.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become pivotal in treating type 2 diabetes and obesity due to their ability to improve glycemic control and promote weight loss. Beyond their metabolic benefits, emerging evidence suggests that GLP-1 RAs may exert anticancer effects by modulating critical biological pathways involved in tumorigenesis, including insulin signaling, inflammation, and cellular proliferation. Current evidence derived from observational and secondary analyses suggests potential protective effects of GLP-1 RAs against several cancers-including prostate, breast, pancreatic, gynecological, glioma, and oral squamous cell cancer through both weight-dependent and independent mechanisms, but the absence of large-scale randomized controlled trials (RCTs) with cancer-specific endpoints remains a critical limitation. Moreover, safety concerns remain a major challenge. Although rodent studies raised concerns regarding medullary thyroid carcinoma, human data have not substantiated a significant risk. Similarly, initial signals of pancreatitis and pancreatic cancer risk have been largely attenuated by subsequent rigorous analyses. Common side effects, such as gastrointestinal discomfort, are usually manageable and transient, but rare adverse events warrant vigilance, particularly in vulnerable patient populations. GLP-1 RAs show emerging signals for cancer prevention and treatment, but their therapeutic application in oncology should proceed cautiously. Future research must prioritize well-designed, adequately powered cancer-focused RCTs that evaluate both efficacy and safety over extended periods.

Obstructive sleep apnea (OSA) and polycystic ovary syndrome (PCOS) share pathogenic pathways. Our review and meta-analysis estimated OSA prevalence in PCOS patients. Systematic search of four databases was performed: MEDLINE, Scopus, EMBASE, Cochrane Central Register of Controlled Trials from inception until 1 March 2024. Grey literature was explored via Google Scholar. The following keywords were adopted: "obstructive sleep apnea", "OSA", "sleep-disordered breathing", and "polycystic ovary syndrome". OSA was diagnosed through polysomnography. Observed heterogeneity was evaluated using both Cochran's Q test (p < 0.10) and the I2 statistic. A random-effects model was applied when significant heterogeneity was detected, with the between-study variance (&#x3c4;2) estimated using the DerSimonian-Laird method. We included 16 studies in the qualitative analysis and 13 in the quantitative analysis, comprising a total of 230,293 patients, including 148,378 in the control group and 81,915 in the PCOS group. Under the common effect model, the OSA pooled risk ratio in the PCOS group was 2.53 (95% confidence interval [CI]: 2.19-2.92), and 3.55 (95% CI: 1.98-6.37) under the random-effects model. Individual risk ratio ranged between 1.50-25.58. Significant heterogeneity was observed (I2 = 73.8%, &#x3c4;2 = 0.4605, p = 0.0004), suggesting potential publication bias based on funnel plot analysis. High prevalence of OSA was evidenced in PCOS women. These findings highlighted a significant association between these two conditions and the need for targeted screening or management in these high-risk patients. Further study to investigate these bidirectional relationships is needed. PROSPERO (CRD42024524008).

The Cyclothymic-Hypersensitive Temperament (CHT) is a multidimensional, transdiagnostic affective disposition characterized by mood instability, interpersonal sensitivity, heightened emotional reactivity and impulsive behaviors. The CHT Questionnaire (CHTQ) currently lacks of normative references and empirically derived thresholds. Study 1 established age- and sex-adjusted normative scores and derived percentiles, tolerance limits, and Equivalent Score (ES)-based risk categories. Study 2 tested the clinical relevance of these norms in 196 adolescents with bipolar spectrum disorders and propensity score-matched controls, examining group differences, ES-based risk distributions, and disorder-specific thresholds. In Study 1, regression analyses showed a significant age-by-sex interaction for Total and subscale scores. Age was positively associated with Total in females (R 2&#xa0;=&#xa0;0.029) and negatively in males (R 2&#xa0;=&#xa0;0.009). The same pattern emerged for Impulsiveness/Emotional Dysregulation (IED; females: R 2&#xa0;=&#xa0;0.029; males: ns) and Moodiness/Hypersensitivity (MHS; R 2&#xa0;=&#xa0;0.017 both sexes), supporting age- and sex-specific norms. Normative values and ES-based classifications enhanced score interpretability. Moderate- and high-risk thresholds were 15.32 and 17.24 for Total, 6.67 and 7.70 for IED, 9.80 and 10.87 for MHS. In Study 2, bipolar adolescents showed higher adjusted Total and IED than controls (Total: t&#xa0;=&#xa0;-3.33, p&#xa0;<&#xa0;0.001, d&#xa0;=&#xa0;0.34; IED: t&#xa0;=&#xa0;-4.42, p&#xa0;<&#xa0;0.001, d&#xa0;=&#xa0;0.45), with no MHS differences. Logistic regression showed Total (odds ratio [OR]&#xa0;=&#xa0;1.08, p&#xa0;=&#xa0;0.001) and IED (OR&#xa0;=&#xa0;1.20, p&#xa0;<&#xa0;0.001), but not MHS, predicted bipolar status. Receiver Operating Characteristic (ROC) analyses showed modest discrimination for Total (Area Under the Curve [AUC]&#xa0;=&#xa0;0.61; cut-off&#xa0;=&#xa0;13.50) and IED (AUC&#xa0;=&#xa0;0.63; cut-off&#xa0;=&#xa0;4.78), and chance-level performance for MHS. Integrating age- and sex-adjusted norms with risk categories and clinical thresholds, the CHTQ may support developmentally informed early risk stratification and longitudinal monitoring.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in children. Hypersensitivity reactions (HRs) to NSAIDs represent a diagnostic challenge, particularly because NSAIDs may act as aggravating factors or cofactors as in two phenotypes recently named NSAID-exacerbated food allergy (NEFA) and NSAID-induced food allergy (NIFA). To diagnose NSAID hypersensitivity/allergy (NH/A) and NEFA/NIFA phenotypes in children/adolescents, classify HRs to NSAIDs according to updated international guidelines, and identify clinical and immunologic predictors of true NH/A. We prospectively studied 336 children/adolescents with a history of HRs to NSAIDs, following international guidelines, which include challenges with the suspected NSAIDs. Primary outcomes were identification of NH/A phenotypes and their predictors. NH/A was diagnosed in 104 (31%) of 336 patients. The most frequent phenotypes were single-NSAID-induced urticaria/angioedema/anaphylaxis (55.8%) and NSAID-induced urticaria/angioedema/anaphylaxis (22.1%). NH/A was excluded in 232 patients (69%), 48 of whom were diagnosed with NEFA/NIFA. Sensitization to Pru p 3 was strongly associated with NEFA/NIFA. Non-hypersensitive/allergic reactions were associated with antipyretic use (OR, 5.92; 95% CI, 3.60-9.72), urticaria (OR, 3.06; 95% CI, 1.77-5.28), and younger age (OR per 6-year increment, 0.64; 95% CI, 0.47-0.89). Internal validation showed good discrimination (AUROC, 0.82; cross-validated AUROC, 0.79). Approximately one-third of children with suspected reactions had confirmed NH/A, whereas 14.3% had NEFA/NIFA. In 69% of patients, the NH/A label was removed. Many reactions during antipyretic use appear infection-related rather than true NSAID hypersensitivity.

Antibiotic-loaded cement spacers (ACS) are integral to two-stage revision total knee arthroplasty (TKA) for periprosthetic joint infection (PJI). While effective in infection eradication, concerns have emerged regarding nephrotoxicity due to systemic absorption of high-dose antibiotics. This study aimed to determine the incidence and risk factors for AKI following very high-dose ACS insertion in two-stage revision TKA using a within-patient controlled design. We conducted a retrospective cohort study of 152 patients who underwent two-stage revision TKA with a very high-dose ACS protocol (typically eight grams of antibiotics per 40 grams of cement) at a single high-volume academic center between 2004 and 2023. Patients with recorded pre- and postoperative creatinine values for both stages were included. An AKI was defined per KDIGO criteria. Each patient served as their own control to compare renal function changes between stages. The overall mean follow-up was 7.9 &#xb1; 4.3 years. Of the patients, 73% had a spacer with &#x2265; eight grams of antibiotics per bag of cement (mean = 8.5 grams/bag). An AKI occurred in 6.6% (10 of 152) of patients after the first stage and 2.6% (four of 152) after the second stage (P = 0.10). Repeated measures analysis of variance did not reveal a significant difference in the within-patient creatinine changes between the first and second stages. There were no patients who experienced AKI in both stages. Among AKI cases, 86% resolved to baseline within one month. Only two of the patients who had AKI (20%) had pre-existing chronic kidney disease. Vancomycin (87.1%) and ceftazidime (85.7%) were the most common antibiotics added to the very high-dose spacers. A very high-dose ACS protocol is safe and effective for managing PJI following TKA. Most AKI cases were transient and unrelated to chronic kidney disease, suggesting other modifiable perioperative factors may play a greater role. The precise dosage that optimizes both safety and efficacy has yet to be determined.

Lebrikizumab, a monoclonal antibody targeting interleukin-13, has demonstrated efficacy and safety in adults with moderate-to-severe atopic dermatitis (AD), but data in elderly patients remain limited. We conducted a retrospective multicentre study including 90 patients aged &#x2265;60 years with moderate-to-severe AD treated with lebrikizumab across 23 Italian dermatology centres. Clinical outcomes were assessed at baseline and at weeks (W)16, W24 and W52. Mean EASI decreased from 23.24 &#xb1; 7.93 at baseline to 6.33 &#xb1; 6.54 at W16, 3.57 &#xb1; 3.74 at W24 and 2.70 &#xb1; 4.83 at W52 (p < 0.0001). EASI75 was achieved by 58.4%, 82.0% and 87.0% of patients at W16, W24 and W52, respectively. Clinical responses were similar across age groups and independent of prior biologic or JAK inhibitor exposure. Adverse events occurred in 7.8% of patients and were mainly mild. These findings support the effectiveness and safety of lebrikizumab in elderly patients with AD in real-world clinical practice.

To investigate real-world psychopharmacological prescribing patterns among Italian adolescents with anorexia nervosa (AN) compared with psychiatric controls without eating disorders, and to examine whether AN diagnosis independently predicts medication use after accounting for psychiatric comorbidities. Participants were recruited from two Italian Child and Adolescent Neuropsychiatry services to improve the representativeness of prescribing practices across different clinical settings within the Italian healthcare system. This cross-sectional cohort study included 298 female adolescents (aged 12-18&#xa0;years) from 2017 to 2025. Participants were classified into AN (n&#xa0;=&#xa0;149) and control (n&#xa0;=&#xa0;149) groups based on DSM-5/DSM-5-TR diagnoses. Sociodemographic, clinical, and pharmacological data were collected. Multivariable logistic regression models examined associations between diagnosis and prescription of any psychotropic medication, specific drug classes, and polypharmacy (&#x2265;&#xa0;2 psychotropic classes), adjusting for psychiatric comorbidities while accounting for potential site-related differences in local prescribing practices. Psychotropic medication use was more frequent among controls in unadjusted analyses. In multivariable models, AN diagnosis was not independently associated with the prescription of any psychotropic medication, antipsychotics, or antidepressants. In contrast, AN group showed a significantly higher likelihood of receiving benzodiazepines (aOR&#xa0;=&#xa0;2.76, 95% CI 1.43-5.47) and polypharmacy (aOR&#xa0;=&#xa0;2.37, 95%CI 1.23-4.64) compared with controls. Polypharmacy was also independently associated with psychotic disorders, personality disorders, and depressive disorders. In this multicenter Italian real-world cohort, psychopharmacological treatment in adolescents with AN appeared to be primarily driven by psychiatric comorbidities rather than AN diagnosis itself. However, benzodiazepine use and higher rates of polypharmacy in AN may reflect disorder-specific clinical features and unmet treatment needs. These findings highlight the complexity of pharmacological management in adolescent AN and the need for more robust, disorder-specific evidence to guide clinical practice.