Azienda Ospedaliera San Gerardo

The management of cancer risk for BRCA pathogenic variants (PV) carriers varies depending on countries, with different strategies. However, some strategies lack of cost-effectiveness evidence. This study fills this gap assessing the cost-effectiveness of a combined ovarian cancer (OC) surveillance and prevention strategy in BRCA1/2 PV carriers. The developed Markov decision model simulated the progression of breast cancer and OC in BRCA1/2 PV carriers separately. The model estimated benefits and costs associated with three OC surveillance strategies: Surveillance-Surgery (SS), annual surveillance until salpingo-oophorectomy (SO) and radical mastectomy (RM) at appropriate age; Only-Surgery (OS), without surveillance, and No preventive Intervention (NI). Extensive literature review informed the model. The analysis adopted the Italian NHS perspective and a lifetime horizon, with direct healthcare costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio as outcome measures. Base-case, deterministic and probabilistic sensitivity analyses were performed. In BRCA1 PV carriers, SS yielded lifetime cost savings of €8 382 and €2 008 compared to NI and OS, respectively, while also gaining 2.65 and 0.45 QALYs per patient. Similar trends were observed for BRCA2 PV carriers. Sensitivity analyses confirmed SS as the dominant strategy across all scenarios, with a > 80% probability of being most cost-effective at a willingness-to-pay threshold of €20 000 per QALY gained. Combined OC surveillance and prevention strategy for BRCA1/2 PV carriers at appropriate age represents a highly cost-effective approach compared to surgical prophylaxis alone or no intervention. Periodical counselling in a multidisciplinary team affects high surgical acceptance rates, that are crucial for maximizing the effectiveness of such programs. Some countries advise transvaginal ultrasound and CA125 tests every 6 months from age 30, along with risk-reducing surgery. Annual surveillance until salpingo-oophorectomy and mastectomy saves costs over surgery alone or no preventive measures. High surgical acceptance rates are crucial for maximizing the effectiveness of this programs.

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Patient and public involvement and engagement (PPIE) in research is crucial for producing knowledge that is meaningful to the participating community. Sharing PPIE principles into practical tools and strategies enriches the development of participatory research methodologies. This article describes the co-creation process of ProSafe, a Community-Based Participatory Research (CBPR) project conducted in Italy, which explores community perspectives on the reorganization of territorial healthcare toward proximity care. The aims are: (1) to describe the co-creation process, (2) to examine its successes and challenges, and (3) to propose strategies and practical recommendations for fostering partnerships and engagement throughout all research stages. The project is based on an explanatory sequential mixed-method design. A Patient Safety Council (PSC) acted as a co-researcher. The five-level spectrum of public engagement developed by the International Association for Public Participation (IAP2) guided the analysis of the decision-making power balance between academics and the PSC at each phase. Emphasis was given to the process of survey co-creation. A SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis was performed to identify strategies and practical recommendations to strengthen engagement. The SWOT analysis results informed the development of OPERA-PACT (Opening a Participatory and Equitable Research Agreement based on Partnership, Awareness, Collaboration, and Trust), a framework co-created with the PSC to formalize shared principles, values, and attitudes that sustain collaborative partnerships. The framework also includes a commitment to continuous monitoring, verification, and feedback to reinforce partnership over time. All instruments, strategies, and methodological insights proposed in the article may serve as practical support tools to strengthen the voice of communities in research and to contribute to the production of valid and translational results. Implementing the OPERA-PACT framework may further help align team members with PPIE principles and lay the foundation for effective and sustainable collaboration.

Background: Intravenous fluids modify acid-base balance by changing plasma strong ion difference (SIDPL) and total non-volatile weak acids. Experimental data suggest that pre-infusion plasma bicarbonate (HCO3-) may further modulate these effects. We tested this hypothesis in a large cohort of postoperative ICU patients receiving intravenous fluids. Methods: We retrospectively analyzed all-consecutive post-operative ICU admissions over a 21-month period who received fluid therapy. Fluid inputs/outputs, plasma electrolytes, and arterial blood gases were collected from admission to 9:00 A.M. of postoperative day one. Average SID of infused fluids (SIDINF) was calculated, and SIDPL and standard base excess variations (ΔSBE) were assessed. Patients were stratified by SIDINF tertiles (low, <41.0 mEq/L; medium, 41.2-54.6 mEq/L; high, ≥55.0 mEq/L), median pre-infusion HCO3- (24.3 [22.4-26.3] mmol/L), and tertiles of SIDINF-HCO3- difference. Results: Among 650 admissions, 641 were included (83% elective surgery). Pre-infusion acid-base was, as average, within normal ranges. Total infused volume averaged 2327 ± 1111 mL. Across SIDINF tertiles, ΔSBE increased from 1.2 ± 3.4 to 3.0 ± 3.0 and 3.4 ± 3.0 mmol/L (p < 0.001), paralleled by ΔSIDPL rise (0.6 ± 2.3, 1.3 ± 2.4 and 1.4 ± 2.3 mEq/L, respectively; p = 0.004). For any given SIDINF, patients with lower pre-infusion HCO3- showed greater ΔSBE and ΔSIDPL (p < 0.001). When analyzed by tertiles of SIDINF-HCO3- difference, ΔSBE rose from 1.0 ± 3.2 to 2.7 ± 2.9 and 4.0 ± 3.0 mmol/L (p < 0.001), with amplified effects at higher infused volume (>2500 mL). Conclusions: In postoperative ICU patients, fluid-induced acid-base changes are largely driven by SIDINF-HCO3- difference, supporting individualized fluid selection based on baseline HCO3-.

Prospective data of a large randomized multi-international leukaemia trial revealed an incidence of 1.1% of invasive yeast infections (IYIs) in children with acute lymphoblastic leukaemia. IYIs occurred predominantly during induction chemotherapy, presented as bloodstream infection ± tissue involvement, were due to a variety of yeast and had an attributable mortality of 5.9%.

Abstract Background: Vepdegestrant is an oral PROTAC ER degrader. The VERITAC-2 study (NCT05654623), the first phase 3 trial of a PROTAC, demonstrated statistically significant and clinically meaningful prolongation of progression-free survival (PFS) with vepdegestrant versus fulvestrant in patients (pts) with ER+/HER2- aBC who were previously treated with endocrine therapy (ET) and a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and had ESR1 mutations (ESR1m). Here, we report the results of prespecified subgroup analyses of PFS among pts with ESR1m. Methods: Eligible pts (aged ≥18 years) with ER+/HER2- aBC had received 1 prior line of CDK4/6i + ET, and ≤1 additional line of ET (the most recent line of ET must have been given for ≥6 months before disease progression); pts with prior chemotherapy in the metastatic setting or prior fulvestrant were excluded. Pts were randomized (1:1) to receive vepdegestrant 200 mg orally once daily or fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles; randomization was stratified by ESR1m status and the presence of visceral disease. The primary endpoint, PFS by blinded independent central review (BICR), was assessed across prespecified clinically relevant subgroups without adjustments for multiplicity. Results: In total, 270 pts with ESR1m were randomized to vepdegestrant (n=136) or fulvestrant (n=134). Across groups, the median age was 60.0 years, 21% of pts were premenopausal or perimenopausal, 80% had received prior CDK4/6i therapy for ≥12 months, 45% had liver metastases, and 42% had a PIK3CA, AKT1, or PTEN mutation at baseline. Consistent with the primary analysis, benefit was observed in PFS by BICR with vepdegestrant versus fulvestrant across all prespecified subgroups ( Table ). Conclusions: Vepdegestrant demonstrated PFS benefit compared with fulvestrant across all prespecified, clinically relevant subgroups of previously treated pts with ESR1m ER+/HER2- aBC. These analyses provide further information in key prognostic patient subgroups that may inform clinical treatment decisions for pts with ESR1m. Citation Format: E. P. Hamilton, M. De Laurentiis, K. Jhaveri, X. Hu, S. Ladoire, A. Patsouris, C. Zamagni, J. Cui, M. Cazzaniga, T. Cil, K. J. Jerzak, C. Fuentes, T. Yoshinami, A. Rodriguez-Lescure, O. Valota, D. R. Lu, M. Martignoni, S. Dychter, M. Lachowicz, X. Zhi, M. Campone. Subgroup analyses of VERITAC-2: A phase 3 trial of vepdegestrant, a PROTAC estrogen receptor (ER) degrader, versus fulvestrant in ER-positive/ human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (aBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD10-03.

Digital twins, dynamic, patient-specific virtual replicas of physical systems are gaining momentum across various medical fields. Their capacity to simulate and predict biological behavior offers unprecedented opportunities for personalized care. While their utility has been demonstrated in oncology, their application in urology remains nascent, and there is still a significant gap in literature findings. This review explores the theoretical framework, current evidence, and future potential of digital twins technology in managing urological conditions such as urolithiasis, benign prostatic hyperplasia (BPH), and nonmuscle invasive bladder cancer. A narrative literature review, guided by SANRA criteria, was conducted using PubMed and Scopus databases to identify relevant studies on the application of digital twins in healthcare, with a focus on urology and related fields. Additional sources from AI, imaging, and computational modelling were incorporated to support technological and theoretical concepts. Real-world use cases and clinical scenarios were constructed to illustrate the conceptual application of digital twins in endourology. Although limited in number, preliminary studies have shown promising results in uro-oncology, particularly for prostate and renal cancers. No models have yet been developed for benign urological diseases. Hypothetical applications in endourology include personalized procedural planning, dynamic follow-up, prediction of obstruction or recurrence, and real-time intraoperative guidance. Integration of imaging, functional data, and AI algorithms could create continuously adaptive simulations to support decision-making and improve treatment outcomes. However, barriers such as data complexity, cost, lack of validation frameworks, and clinician trust persist. Digital twins hold transformative potential for the future of urology, promising to personalize care across diagnosis, treatment, and surveillance. While the path to clinical integration is challenged by technical, ethical, and infrastructural hurdles, collaborative efforts and real-world validation studies are critical to realizing their full potential in clinical practice.

Patient self-care and caregiver contribution to self-care in chronic illnesses should be considered together as a dyadic phenomenon called "dyadic illness management." The possibility of classifying dyadic engagement in chronic conditions care may uncover behavioral patterns useful for improving disease management. Mixed-effects models have been used to obtain dyadic scores, which serve as inputs for latent class analysis. However, the advantages of this approach over simpler synthetic dyadic measures remain unclear. The aim of this study was to compare two methods for obtaining dyadic scores to serve as inputs for identifying distinct patterns of dyadic illness management for type 2 diabetes (T2D) through latent class analysis. This work uses data from a cross-sectional study on 251 patients with T2D and their informal caregivers. Patient self-care and caregiver contribution to self-care were measured by the Self-Care of Diabetes Inventory and the Caregiver Contribution to Self-Care of Diabetes Inventory, respectively. To assess dyadic illness management, we first adopted the incongruence model, a mixed-effects model with a specific codification that enables the estimation of both the average and incongruence in the outcome within each dyad, through random intercepts and random slopes. These estimated coefficients were then used to perform a latent class analysis that was able to identify patterns of dyadic management. As an alternative approach, we calculated the dyadic average and incongruence using the raw means and the difference between patient and caregiver scores. These values were then used as inputs for latent class analysis. The latent class analysis clustered the same dyads into the same classes across both approaches, with identical fit indices. The three-class model showed the best performance in terms of both fit and characterization of the dyads. Mixed-effects models account for interdependence within the dyad and measurement error, returning predicted measures that are shrunk toward the overall mean. However, this approach yielded the same clusters as the simpler method based on observed measures.

Blood has long held a central place in both religious symbolism and medical practice, carrying meanings that range from life, purity, and covenant to danger, impurity, and death. This article examines the historical relationship between blood, medicine, and Christian thought, focusing especially on how Christian traditions interpreted the emergence of blood transfusion. The study adopts a historical narrative approach, analyzing primary and secondary sources from Europe and North America. After outlining the theological meanings of blood-covenant, sacrifice, redemption, purity, and danger-the article traces key milestones in the scientific development of transfusion from early modern legends to twentieth-century advances. Particular attention is given to the ways in which various Christian denominations responded to transfusion as it entered clinical practice. While Catholic, Orthodox, Anglican, Lutheran, Reformed, and Methodist communities gradually embraced transfusion as a legitimate therapeutic act aligned with principles of charity and the preservation of life, other groups, most notably Jehovah's Witnesses, adopted a restrictive interpretation of biblical texts that led to the rejection of transfusion and generated significant ethical and legal debates. By integrating medical history with theological perspectives, this article demonstrates that the reception of transfusion within Christian cultures was shaped not only by scientific progress but also by enduring religious understandings of blood as a symbol of life, redemption, and moral responsibility.