Azienda Sanitaria Unità Locale di Reggio Emilia

Women with aortic stenosis (AS) are underdiagnosed and undertreated compared to men and face a higher mortality risk despite similar symptoms and fewer comorbidities. Sex-specific differences in left ventricular (LV) remodeling may contribute to this disparity. We investigated whether a fully automated, machine-learning-based three-dimensional echocardiography (3DE) approach, the Dynamic Heart Model (DHM), improves the detection of these differences compared to conventional two-dimensional echocardiography (2DE). This study investigates sex-related differences in cardiac remodeling and hemodynamics in AS patients with a preserved ejection fraction (EF ≥ 50%), comparing results from 2D echocardiography (2DE) and 3D echocardiography (3DE) via the DHM. The study included 101 consecutive patients with AS (42% women) who were assessed with 2DE and DHM. Parameters such as LV volumes, mass (LVM), stroke volume (SV), and aortic valve area (AVA) were measured and indexed to body surface area (BSA). Sex-specific differences were analyzed, with a focus on identifying significant remodeling patterns. Women exhibited smaller LV end-diastolic volume (EDV) and end-systolic volume (ESV) by DHM compared to men (115 mL vs. 155 mL, p < 0.001; 51 mL vs. 66 mL, p < 0.001). Indexed EDV (EDVi) and ESV (ESVi) were also significantly lower in women (69 mL/m² vs. 84 mL/m², p < 0.001; 30 mL/m² vs. 34 mL/m², p = 0.002). LVM and indexed LV mass (LVMi) were significantly lower in women when measured by DHM (131g vs. 163g, p < 0.001; 75g/m² vs. 89g/m², p = 0.005), whereas 2DE did not reveal statistically significant differences. Women exhibited a more concentric LV geometry, as reflected by higher relative wall thickness than men (0.42 vs. 0.36; p = 0.04). Despite similar hemodynamic parameters, women had significantly smaller DHM-derived AVA (0.90cm² vs. 1.20cm², p < 0.001), correlating with reduced SV (64 mL vs. 90 mL, p < 0.001). This study highlights that significant sex-related differences in LV remodeling and AS severity are better captured by DHM than 2DE, emphasizing the importance of sex-specific considerations and accurate measurements in evaluating and managing AS.

Outpatient parenteral antimicrobial therapy (OPAT) enables effective infection management outside hospital settings, offering clinical and economic benefits. While widely adopted internationally, its implementation in Italy remains fragmented. This study aimed to systematically map the use of OPAT in Italy to identify research and policy priorities. A scoping review was conducted following the Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews guidelines. The protocol was registered on the Open Science Framework ( https://doi.org/10.17605/OSF.IO/GX8S6 ) in August 2025. Searches were performed across PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Scopus. Eligible studies included primary research on OPAT in Italy, with no restrictions on publication date or language. Data extraction focused on study characteristics, OPAT indications, antimicrobial agents, delivery models, and outcomes. Twenty-three studies were included, mostly observational and single-center, published between 2000 and 2025. OPAT was primarily delivered at home or in infusion centers. The most frequent indications were infections of bone and joint, skin and soft tissue, and the respiratory tract. Ceftriaxone was the most used antimicrobial. Delivery was mainly intravenous, often via elastomeric pumps and peripheral or central venous access. Reported outcomes were generally favorable, with cure or improvement rates exceeding 90% in several studies. Adverse events were infrequent, mostly associated with drug reactions or catheter-related complications. Patient satisfaction was consistently high. Economic evaluations were limited but suggested cost savings primarily driven by reductions in hospital stays. OPAT is feasible and increasingly used in Italy, but remains inconsistently implemented across regions. Broader adoption would benefit from national guidance, standardized protocols, and integrated stewardship frameworks. Future research should address comparative and cost-effectiveness, as well as equitable access, to support systematic scale-up aligned with national health priorities on antimicrobial resistance and community-based care.

There is a lack of high-quality data to inform risk-stratified long-term thrombosis prevention strategies in patients with persistently positive antiphospholipid antibodies (aPL). We aimed to determine independent clinical and biologic predictors of thrombosis among persistently aPL-positive patients. Patients positive for aPL according to the Revised Sapporo Classification Criteria are eligible for inclusion in the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry. Registrants with at least 1 year of follow-up were included in this study. We fit Cox proportional hazards models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for independent predictors of thrombosis. In unadjusted analyses, based on 1067 patients with a mean follow-up of 4.43 years (4,727 person-years), history of thrombosis, hematologic disease (autoimmune haemolytic anaemia and/or thrombocytopenia), microvascular disease, obesity, renal disease, sedentary lifestyle, baseline anticoagulant use, and family history of early cardiovascular disease occurred more frequently (P < .05) among patients with new thrombosis (n = 93) than among those without new thrombosis (n = 974). After adjustment, independent predictors of new thrombosis were history of thrombosis (HR 2.34, 95% CI 1.14 to 4.81, P = .02) and hematologic disease (HR 1.95, 95% CI 1.19 to 3.18, P = .01); there was a trend for history of microvascular disease (P = .06) and obesity (P = .08). In this prospective analysis, history of thrombosis and hematologic disease each conferred an approximately twofold increased risk of new thrombosis in persistently aPL-positive patients. These findings can guide future clinical trial designs and inform patient management decisions.

The clinical high-risk for psychosis (CHR-P) paradigm has been widely applied in youth mental health, yet its prognostic validity in minors remains debated. This study aimed to provide an updated meta-analysis of transition rates to psychosis in children and adolescents at CHR-P, and to assess the influence of baseline antipsychotic (AP) exposure on transition outcomes. We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO CRD420251064505). PubMed/MEDLINE and the Cochrane Library were searched through August 30, 2025. Eligible studies included participants ≤18 years or samples with mean age <18 years, defined CHR-P status with validated instruments, and reported longitudinal data on transition to psychosis. Transition prevalences were pooled using random-effects models. Subgroup analyses evaluated the impact of baseline AP exposure. Thirty-two independent cohorts were included, comprising 2951 CHR-P individuals, almost all in adolescence. Across studies restricted to minors, overall transition converged at ∼16-17%, while broader samples with mean age <18 years but including young adults reached ∼23%, approximating adult CHR-P estimates (∼25%). Baseline AP exposure was consistently associated with a higher risk of transition (risk ratio ≈1.5), supporting its role as a negative prognostic factor. CHR-P criteria demonstrate prognostic validity in developmental populations, with transition rates in adolescents comparable to young adult cohorts and significantly higher than in CHR-P negative adolescents. In line with previous research in adult CHR-P, the need of AP at baseline is substantially associated with an increased risk for transition. Future research should broaden prognostic focus beyond transition alone to capture remission, persistence, and functional outcomes in this vulnerable group.

151 Background: ARTO (NCT03449719) is a multicentre, randomized phase II trial testing the benefit of stereotactic body radiation therapy (SBRT) addition on top of abiraterone acetate (AA) and androgen deprivation therapy (ADT) in first line Oligometastatic Castrate Resistant Prostate Cancer (omCRPC) patients. Results already showed significant benefit in favour of the experimental arm in terms of biochemical progression free survival (bPFS) and radiological PFS (rPFS) after a median follow up of 24.9 months. Here we present an updated analysis comprehensive of long-term overall survival (OS) and prostate cancer specific survival (PCSS) data. Methods: Patients affected by omCRPC (≤ 3 non-visceral metastatic lesions) were randomized 1:1 to receive either AA+ADT alone (control arm) or the same systemic treatment associated with SBRT on all sites of disease (treatment arm). No previous treatment for mCRPC was allowed. Cox regression analysis was performed to compare bPFS, rPFS, OS and pCSS in the different arms of treatment. Results: One hundred fifty-seven patients were enrolled in ARTO trial. After a median follow up of 53 months (IQR 43-60), 103 bPFS events were recorded (41 vs 62 in the experimental vs control arm, respectively), 100 rPFS events occurred (40 vs 60 in the experimental vs control arm, respectively) and 65 patients died (24 vs 41 in the experimental vs control arm, respectively). Significant benefit in terms of bPFS and rPFS in favour of the experimental arm was confirmed (43 vs 17 months, HR 0.49, 95% CI 0.33-0.73, p&lt;0.001 and 44 vs 17 months, HR 0.48, 95% CI 0.32-0.72, p&lt;0.001, respectively). In terms of OS and PCSS, significant benefit was detected in favour of the experimental arm (Not reached vs 50 months, HR 0.55, 95%CI 0.33-0.92, p=0.02 and not reached, HR 0.37, 95%CI 0.18-0.78, p=0.008, respectively). Results were confirmed after adjusting for stratification variables (performance status 0 vs 1; 1 vs &gt; 2 lesions) (HR 0.54, 95%CI 0.36-0.81, p=0.003, HR 0.53, 95%CI 0.35-0.81, p=0.003, HR 0.6, 95%CI 0.36-0.99, p=0.04, HR 0.43, 95%CI 0.2-0.9, p=0.02 for bPFS, rPFS, OS and PCSS, respectively). No safety concerns emerged, with 64 vs 71 grade 1/2 and 13 vs 22 grade &gt;2 adverse events in the experimental vs control arm, respectively. Conclusions: After more than doubling the median follow up in this updated analysis, a significant OS and PCSS benefit were detected in patients undergoing concomitant SBRT with AA and ADT treatment compared to AA and ADT alone. These results warrant for confirmation in phase III trials. Clinical trial information: NCT03449719 .

526 Background: Sex-related biological differences may affect cancer immunity and outcomes with immune checkpoint inhibitors (ICIs). With conflicting evidence, female sex has been associated with higher rates of sarcomatoid dedifferentiation, worse OS in metastatic RCC, higher-grade toxicities, and greater steroid use. Other analyses suggest a survival advantage for younger women compared with men, supporting a possible hormonal role with a protective effects of estrogens. Methods: Meet-URO-33 (REGAL) is a multicenter ambispective observational trial including 1560 patients with advanced RCC treated with 1st line systemic therapy after January 2021. Data from electronic medical records included demographics, histology, metastatic sites, treatment, and response according to RECIST 1.1. Clinical-pathological features, hematological parameters (including NLR), toxicities, and outcomes were compared by sex and by menopausal age cut-off (&lt;50 vs ≥ 50 yrs). Results: Among 401 females (F) and 1159 males (M), F presented with worse baseline characteristics, such as ≥ 2 metastatic sites (35% vs 27%, p = 0.012), liver metastases (18% vs 11%, p = 0.002), and sarcomatoid variant (20.3% vs 14.5%, p = 0.025). F presented with lower BMI ≤ 25 kg/m2 (52% vs 43%, p = 0.008), and NLR &lt;4 (73% vs 67%, p = 0.027). First-line treatment distribution (IO–TKI, IO–IO, or TKI monotherapy) was well balanced. Grade 3–4 immune related adverse events (irAEs) were significantly more frequent in F (35% vs 28%, p = 0.012), with no sex-related differences in the pattern of irAEs, but a greater need for steroids (18% vs 12%, p = 0.025). Discontinuation rates were similar in F and M (20.5% vs 19.3%, p = 0.63). No significant differences were observed for F in PFS (15.8 vs 18.5 months, p = 0.23) or OS (39.5 vs 41.9 months, p = 0.93). The presence of sarcomatoid features did not influence the sex–outcome interaction (p = 0.43 for OS, p = 0.95 for PFS). Stratifying outcomes by age, patients ≥ 50 years had similar results, but F &lt; 50 years showed a markedly shorter PFS (8.5 vs 19.6 months, HR 2.02, p = 0.009). Conclusions: F presented with more adverse baseline features and higher severe toxicity rates, yet OS/PFS outcomes were similar, with unfavorable trends for F. The significantly worse PFS in younger F supports a possible hormonal influence, as the protective role of estrogens may vary before/after menopause. Higher steroid exposure, immune-related differences, and pharmacokinetics may also have contributed. The underrepresentation of F, consistent with other RCC trials, remains a limitation, reducing the reliability of subgroup analyses. These findings highlight the need to integrate sex and menopausal status into clinical practice and trial design. Dedicated translational research are essential to clarify biological and pharmacological mechanisms underlying sex-based disparities and to guide tailored strategies in advanced RCC. Clinical trial information: 33.