Ospedale G.B. Morgagni - L.Pierantoni

Breast surgery is a cornerstone of breast cancer (BC) treatment and has distinctive features that distinguish it from other subspecialties within general surgery. BC management requires multidisciplinary competencies, with specialized training and dedicated care shown to improve patient outcomes. Breast surgery training should become a critical priority within residency programs. We conducted a cross-sectional survey during the 2025 Italian Society of Breast Surgeon (ANISC) annual meeting, to explore the opinions of breast surgery consultants and residentsregarding the current state of breast surgery training, as well as future perspectives for its improvement. A total of 126 participants (77% consultants, 23% residents) completed the survey. Most of the participants (49.2%) worked in medium-volume Breast Units and had > 10 years of clinical practice (45.2%). Overall, 67.5% of respondents judged their training only partially satisfactory, while 23.8% were completely dissatisfied. The majority (58.7%) supported a hybrid model with three years of general surgery followed by two years exclusively dedicated to breast surgery. Most respondents endorsed mandatory training periods in complementary specialties (79.4%) and rotations in peripheral Breast Units (69.8%). Notably, 88.1% favored the development of a vertical breast surgeon profile, capable of independently managing both oncologic and reconstructive procedures. This is the first national survey exploring breast care professionals’ perspectives on surgical training in Italy. Only 8.7% considered the current system adequate to meet clinical needs. The strong demand for structured and specialized programs, together with the recognition of a vertical breast surgeon figure, highlights the urgent need to redefine breast surgery training pathway.

Background/Objectives: Systemic sclerosis (SSc) patients frequently develop osteoporosis; however, vertebral fracture risk factors remain poorly characterized. This study identifies general and SSc-specific predictors of vertebral fractures in SSc patients undergoing osteoporosis evaluation. Methods: This multicenter cross-sectional study enrolled consecutive SSc patients meeting ACR/EULAR 2013 criteria with suspected osteoporosis. Data included demographics, disease characteristics, bone density (DXA), and vertebral imaging. Stepwise logistic regression analyzed fracture associations (p ≤ 0.05 significant). Results: The majority of 103 enrolled patients were female and all were post-menopausal. The prevalence of osteoporosis was 52.4%, that of vertebral fractures was 38.8%, and that of osteopenia was 28.1%. General risk factor analysis identified family history of fragility fractures (OR 11.8, p = 0.008) and vertebral T-scores (OR 0.6, p = 0.049) as significant predictors. When adding SSc-specific factors, only family history (OR 13.8, p = 0.03) and gastrointestinal (GI) involvement (OR 4.8, p = 0.05) remained significant. Conclusions: Vertebral fractures in SSc patients are strongly linked to a family history of fractures. The suggestive association with GI involvement may imply a significant role for malabsorption-related metabolic impairment. Prioritizing bone density screening in SSc patients with GI symptoms may enable earlier intervention and reduce fracture risk.

Evidence directly comparing ocrelizumab (OCR) and ofatumumab (OFA) after sphingosine-1-phosphate receptor modulators (S1PRMs) withdrawal is limited, even though this transition period carries an increased risk of disease reactivation and the two anti-CD20 agents differ in molecular properties that may influence post-S1PRM outcomes. We compared effectiveness, safety, and tolerability of OFA versus OCR in relapsing-remitting multiple sclerosis (RRMS) after S1PRM therapy. We retrospectively analyzed adult (> 18 years) patients with RRMS from 23 Italian centers who switched from S1PRMs to OCR or OFA (October 2016 to July 2024). Clinical outcomes included annualized relapse rate (ARR), cumulative relapse incidence, confirmed disability progression (CDP), progression independent of relapse activity (PIRA), confirmed disability improvement (CDI), and variation in the expanded disability status scale score (ΔEDSS) from baseline to last follow-up. Magnetic resonance imaging (MRI) outcomes included time to overall MRI activity, new/enlarging T2 lesions, and new T1 Gd-enhancing lesions. Persistence on anti-CD20 and safety were also assessed. We applied inverse probability of treatment weighting (IPTW) to balance baseline covariates, and used Cox, Andersen-Gill, and regression models, further adjusted for variables with residual imbalance, to compare outcomes. We included 225 subjects (mean age 43.3 ± 10.6 years; OCR = 131, OFA = 94), with a median follow-up of 33 months. After IPTW, groups were well balanced. Compared with OCR, OFA was associated with lower ARR (adjusted relative risk [aRR] 0.22, 95% CI 0.06-0.86, p = 0.030) and relapse hazard (adjusted hazard ratio [aHR] 0.21, 95% CI 0.05-0.83, p = 0.026). When restricting washout to ≤ 10 weeks and applying spline-based Andersen-Gill models, results remained consistent, with OFA showing a lower relapse risk than OCR across short-to-intermediate washout intervals. CDP hazard was lower (aHR 0.38, 95% CI 0.15-0.94, p = 0.038), while PIRA and CDI did not differ. ΔEDSS favored OFA (adjusted mean difference [aMD] -0.26, 95% CI -0.51 to -0.02, p = 0.046). OFA showed a lower hazard of overall MRI activity (aHR 0.41, 95% CI 0.19-0.92, p = 0.030), with similar risk for new T1 Gd+ lesions. A sensitivity analysis restricted to patients who switched to OFA or OCR during the same availability window yielded results consistent with the primary analysis. Treatment persistence was shorter on OFA, but absolute discontinuation rates were low in both groups. Severe AEs were rare and did not differ. In S1PRM-exposed RRMS, OFA was associated with reduced relapse risk, disability accumulation, EDSS worsening, and MRI activity compared with OCR, with overall good tolerability and safety.

To assess the 1-year natural history of liver imaging reporting and data system (LI-RADS) 3 observations on contrast-enhanced MRI in cirrhotic patients across multiple international centers, and to identify clinical and imaging predictors of progression using multivariable and machine learning models. This retrospective study included 347 cirrhotic patients with 540 LI-RADS 3 observations from six centers across three countries, each with 12 (±3) months of follow-up MRI. Observations were reassessed using LI-RADS v2018 criteria. Generalized linear mixed-effects models and machine learning (LASSO, random forest) evaluated predictors of progression. Area under the curve (AUC) analysis assessed the predictive performance of clinical and imaging variables. Within one year, 28% of LI-RADS 3 observations progressed: 14% to LI-RADS 4 and 14% to LI-RADS 5. Independent predictors of progression included lesion size, with an odds ratio (OR: 1.12, 95% CI: 1.01-1.24), Child-Pugh Class C (OR: 8.36, 95% CI: 1.01-69.27), and alcohol-related liver disease (OR: 0.24, 95% CI: 0.06-0.94). Enhancing capsule and untreated hepatitis C virus were significant in univariable analysis. Imaging features improved predictive accuracy, increasing AUC from 0.65 to 0.72 (p = 0.01). A lesion size cut-off of 9.5 mm was associated with increased progression risk. One in four LI-RADS 3 observations progress within one year. Lesion size, liver function, and etiology are key predictors. Integration of imaging features enhances risk stratification and supports more personalized follow-up strategies for indeterminate liver lesions. Question Identifying which LI-RADS 3 liver observations progress to malignancy remains challenging; evidence from large, standardized, multicenter MRI cohorts is lacking. Findings In this large multinational study, 28% of LI-RADS 3 observations progressed within one year; lesion size, liver dysfunction, and disease etiology were key independent predictors. Clinical relevance LI-RADS 3 observations show significant progression risk, with imaging features improving prediction models and guiding surveillance strategies for early HCC detection.

Inverted sinonasal papilloma (ISP) is a benign epithelial neoplasm with potential for malignant transformation into squamous cell carcinoma (ISP-SCC). While high-risk HPV infection has been studied as a possible driver, other factors, including occupational exposures, may play a role. Thirty-two cases (n = 32) of ISP and ISP SCC were retrospectively analysed. These cases had been diagnosed between 2010 and 2022. We assessed their occupational history through the Italian Sino-Nasal Cancer Registry questionnaire and performed p16/p53 immunohistochemistry, HPV DNA and RNA testing. Overall, 41% of ISP and 40% of ISP-SCC cases reported exposure to IARC Group 1–2 A carcinogens, and 69% had a history of smoking. Transcriptionally active HPV was detected in only one case (3.1%). Conventional bivariate analyses did not reveal significant associations between occupational exposure and malignant transformation. However, hierarchical cluster analysis identified three distinct phenotypes. Cluster 1 included predominantly male smokers with high cumulative occupational and non-occupational exposure, with ISP-SCC in 17%. Cluster 2, characterized by the highest occupational exposure and lowest smoking prevalence, consisted exclusively of ISP-SCC cases (100%), suggesting occupational carcinogens as a possible independent driver. Cluster 3 had minimal exposure, inflammatory features, and no malignant transformation. These findings highlight the potential of multidimensional analytical approaches to identify high-risk subgroups and inform targeted preventive and surveillance strategies in exposed populations.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-33299-7.

To evaluate the association of anatomical, clinical, and procedural factors with endovascular treatment failure, including both proximal and distal splenic artery embolization (SAE). In 11 centers, all patients following blunt splenic injury (BSI) were retrospectively evaluated, and those who had received SAE were selected. Data collected included: patient demographics and characteristics, mechanism and grading of BSI, endovascular management, and outcomes. Technical and clinical success were defined as successful embolization of the bleeding artery and stabilization of the haemodynamic status and laboratory data in 1 or 2 sessions, respectively. Rebleeding during follow-up and subsequent splenectomy were considered as treatment failure. The rate of complications related to the endovascular procedure was evaluated. The management of two hundred and forty-seven participants was evaluated. Technical and clinical success were 100% and 91.9% (227/247), respectively. A second embolization was performed in 5 cases. Rescue splenectomy occurred in 20 (8.1%) patients. Statistically significant associations were identified between endovascular treatment failure and GCS and the presence of other lesions at CT at patient presentation. No anatomical or procedural factors were found to be statistically significant; in the surgical group, a larger diameter of the splenic artery was observed. The complication rate was 15.2% (26/171), all relating to the vascular access, e.g., hematoma or pseudoaneurysm, and all managed conservatively. SAE is a safe and effective procedure; unsuccessful cases resulted statistically associated with some clinical factors, but no correlation with anatomical factors was observed.

Personalized treatment specifically tailored to the patient's needs is nowadays a successful and necessary therapeutic approach [...].

ABSTRACTAging is a key driver of cardiac dysfunction, promoting structural remodeling, metabolic alterations, and loss of cellular resilience. In aged hearts, extracellular matrix remodeling and collagen accumulation reduce ventricular compliance, impairing both diastolic function and stress adaptability. Cardiomyocytes exhibit diminished regenerative capacity and dysregulated stress responses, with mitochondrial dysfunction emerging as a central contributor to energy imbalance, oxidative stress, and fibrosis. Traditional single‐omics approaches are insufficient to capture the complexity of these interconnected changes. To address this, we employed an integrative multi‐omics strategy—combining spatial transcriptomics, proteomics, and metabo‐lipidomics with electron microscopy—to investigate cardiac aging in mice at three life stages: adult (12 months), middle‐aged (24 months), and elderly (30 months). Electron microscopy revealed enlarged, structurally compromised mitochondria. Spatial transcriptomics showed reduced expression of cardioprotective genes (MANF, CISH, and BNP) and increased expression of profibrotic markers like CTGF. Proteomics revealed widespread mitochondrial dysregulation and impaired ATP production. Metabolic and lipidomic profiling identified reduced antioxidant metabolites and accumulation of lipotoxic species, such as ceramides and diacylglycerols. This multiscale analysis highlights key molecular and metabolic alterations driving cardiac aging, identifying potential therapeutic targets to mitigate age‐related functional decline. Overall, our findings highlight the value of integrated, system‐level approaches for uncovering the complex mechanisms that drive organ aging. Although our study was conducted in mice, validation in human models will be crucial to establish the translational relevance of these results and to guide future research with potential impact across diverse biomedical fields.