Humanitas Gavazzeni

The therapeutic landscape of non–small cell lung cancer (NSCLC) has been profoundly transformed by the widespread adoption of molecular profiling and the development of targeted therapies, like tyrosine kinase inhibitors (TKIs), antibody–drug conjugates (ADCs), and bispecific antibodies (BsAbs). These agents have significantly improved survival and quality of life in molecularly selected subgroups, potentially converting NSCLC into a chronic disease requiring prolonged treatment exposure. However, extended survival has led to increasing recognition of cancer treatment–related cardiovascular (CV) disease as a clinically relevant and sometimes dose-limiting complication. Unlike conventional chemotherapy, CV toxicities associated with targeted therapies frequently arise from on-target or off-target interference with signaling pathways that are essential for myocardial survival, endothelial function, vascular regulation, and the cardiac conduction system. From common pathophysiological mechanisms, a broad spectrum of clinical manifestations arises, ranging from asymptomatic electrocardiographic changes to arterial hypertension, dyslipidemia, venous thromboembolism, arrhythmias, and heart failure. This review provides a comprehensive overview of CV toxicities associated with targeted therapies in NSCLC, integrating mechanistic insights with clinical evidence. We summarize class-specific CV risk profiles across EGFR, ALK/ROS1, RET, MET, NTRK, BRAF, and KRAS-G12C inhibitors, as well as ADCs and BsAbs, highlighting both shared and distinct patterns of cardiotoxicity. As targeted therapies continue to expand across disease stages and treatment lines, CV toxicity is expected to play an increasingly important role in therapeutic decision-making. Integrating CV considerations into oncologic care is therefore essential to preserve treatment continuity, optimize long-term outcomes, and maximize the benefits of modern targeted therapies in NSCLC.

To evaluate the clinical benefit of extended endocrine therapy (eET) after 5 years of adjuvant treatment with luteinizing hormone-releasing hormone agonists (LHRHa) in premenopausal women with node-positive, hormone receptor-positive early breast cancer (eBC). We conducted a cohort study analysis on two prospectively collected data sets (the Young Women's Breast Cancer Study and IEO Breast Cancer Cohort). Eligible patients were diagnosed with eBC at age ≤40 years (between 2005 and 2016), had node-positive, hormone receptor-positive disease, and remained premenopausal after 5 years of adjuvant LHRHa with no evidence of recurrence. The primary end point was invasive breast cancer-free survival (IBCFS), calculated from the sixth year after the initiation of adjuvant endocrine therapy (ET; study baseline), and adjusted through the propensity score (PS) weighting analysis. A total of 501 patients were included in the analysis: 287 received eET for a median duration of 3.7 years (IQR, 2.3-5.0), including 48% tamoxifen monotherapy and 52% LHRHa plus tamoxifen or aromatase inhibitor. After a median follow-up of 7.3 years from the study baseline, the PS weighted IBCFS rates at 5 years were 85% in the eET group and 78% in the non-eET group (hazard ratio [HR], 0.63 [95% CI, 0.44 to 0.89]; P = .0135). The PS weighted distant recurrence-free survival rates at 5 years were 91% and 83% in the eET and non-eET group, respectively (cause-specific HR, 0.49 [95% CI, 0.31 to 0.79]). In both groups, bone fractures and major cardiovascular events were reported in 1% of patients. In this cohort study analysis, extending ET in premenopausal patients with node-positive eBC after 5 years of LHRHa treatment was associated with a clinically meaningful reduction in both invasive and distant breast cancer recurrences.

ABSTRACTPurposeAtrial fibrillation (AF) is highly prevalent in patients with transfusion‐dependent beta‐thalassemia (TDT). Speckle tracking echocardiography (STE) provides detailed information about left ventricular (LV) and atrial function, however its role in TDT patients with AF has not been completely investigated. This study aimed to assess differences in cardiac mechanical parameters between thalassemia patients with and without history of AF.Methods and results223 TDT patients in sinus rhythm were enrolled and, among them, 26 (11%) had history of AF. A complete STE analysis with the evaluation of global longitudinal strain (GLS), peak atrial longitudinal strain (PALS) and myocardial work (MW) indices were performed. The primary endpoint was the difference in STE parameters. The secondary endpoint was the prevalence of cardiac mechanical dysfunction. Patients with history of AF showed significantly lower values of GLS (19% vs 21%, p = 0.01) and PALS (24% vs 35%, p < 0.001) compared to those without AF. AF patients showed higher prevalence of both ventricular and atrial mechanical dysfunction (respectively 27% vs 12%, p = 0.03 and 42% vs 11%, p < 0.001). PALS showed high discriminative ability (AUC 0.76, 95% CI 0.66–0.85) with an optimal cut‐off value of 25.9% to detect those with history of AF.ConclusionsAmong TDT patients, those with history of AF showed lower values of GLS and PALS. Both LV and atrial mechanical dysfunction were significantly prevalent in patients with history of AF and PALS showed high diagnostic accuracy for the detection of AF.Clinical trial registrationClinicalTrials.gov id NCT05508932

Discrete event simulation (DES) is used for the first time to improve the performance of robotic cardiac surgery (RCS), an application that presents unique challenges.The flexible DES model for RCS can parametrize various factors related to both operating rooms and procedures.The impact of these factors is evaluated on a set of KPIs.New insights into the positioning of equipment and personnel in the OR are provided, allowing to formulate informed recommendations for RCS providers.

Abstract Background The role of cardiac magnetic resonance imaging (CMR) in evaluating and managing non-ischemic dilated cardiomyopathy (NIDCM) is well recognised. A CMR-derived model for estimating pulmonary capillary wedge pressure (PCWP) has previously been validated in patients suspected of having heart failure (HF). However, the CMR characteristics linked to higher PCWP remains mostly not clarified. Purpose The present study aimed to evaluate the prevalence and association of late gadolinium enhancement (LGE) in NIDCM with increased PCWP. Methods The multicentric cohort study on cardiovascular multimodality imaging evaluation of dilated cardiomyopathy (MAGNIFICENCE) study is a retrospective and prospective, multicentric observational study of patients with newly diagnosed NIDCM aimed to evaluate the prevalence of the main cardiovascular imaging parameters of this cohort of patients. In the present analysis, patients were divided into those with elevated PCWP, defined as PCWP ≥ 15 mmHg, and those with normal PCWP. The CMR-derived PCWP was calculated using the following validated equation: PCWP (CMR) = 6.1352 + (0.07204 × LAV) + (0.02256 × LVM). The primary endpoint was the difference in LGE prevalence between patients with elevated and normal PCWP. The secondary endpoint was the one-year incidence of clinical events (death, HF, stroke or malignant arrhythmias) or ICD implantation. A uni and multivariate logistic regression model was used to assess the association between LGE and CMR-derived PCWP. A uni and multivariate Cox regression model was applied for the predictors of the secondary outcome. A p-value &amp;lt; 0.05 was considered significant. Results Between February 2024 and May 2025, 132 patients were enrolled in the MAGNIFICENCE study. 75 patients were included in the present analysis. 30 patients had a PCWP &amp;lt; 15 mmHg and 45 patients had a PCWP ≥ 15 mmHg. Patients with elevated PCWP had an higher indexed left end-diastolyc ventricular volumes (128 vs 115 ml/m2, p = 0,018), higher indexed left ventricular mass (81 vs 63 g/m2, p = 0,002), lower LVEF% (31 vs 37 %, p= 0,005), higher indexed left atrial volumes (58 vs 32 ml/m2, p &amp;lt; 0,001). LGE was more prevalent in patients with elevated PCWP (64% vs 40% of patients, OR: 2.625; 95% CI: 1.01–6.81; P: 0.047). At one year, the secondary outcome occurred in 34% of patients. After multivariate adjustement, baseline LVEF was the only parameter independentely associated to the outcome (HR 0,90, 95% CI 0,84-0,94, p= 0,001). Patients with LGE and elevated PCWP had the higher risk of the secondary endopoint at one year. (HR 8.714, 95% CI 1.12–67.5, P = 0.038). Conclusions In the present study, the prevalence of LGE was higher in patients with an elevated PCWP. Patients with both LGE and elevated PCWP were at a higher risk of clinical events or ICD implantation within a year.

SARS-CoV-2 infection is nowadays one of the most catastrophic disease affecting Italy in the last years. A very heterogenic manifestation range starts from lungs disease with extensive parenchymal involvement, to hepatic involvement with acute hepatitis, acute kidney insufficiency, myocardial involvement, but also coagulopathy (thrombotic or hemorrhagic).

The objective of this study was to describe a case of punctate inner choroidopathy (PIC) and secondary or epiphenomenon multiple evanescent white dot syndrome after surgery for high-myopic full-thickness macular hole. This was a case report. A 57-year-old high-myopic woman was diagnosed with cataract and full-thickness macular hole in the left eye. Her initial best-corrected visual acuity was 20/20 in the right eye and 20/80 in the left eye. She underwent routine combined phacoemulsification and 25-gauge pars plana vitrectomy with the inverted internal limiting membrane technique and twice-repeated epiretinal membrane and internal limiting membrane staining in the left eye. Two weeks postoperatively, the patient reported significant visual decline and photopsia in her left eye. Best-corrected visual acuity decreased to counting fingers. Anterior segment examination was unremarkable. Ophthalmoscopic examination showed multiple whitish-yellow lesions in the macular region compatible with PIC lesions in the left eye. Optical coherence tomography, blue-light fundus autofluorescence, fluorescein angiography, and indocyanine green angiography were performed and confirmed the diagnosis. The patient underwent oral steroid therapy for PIC treatment. One week after treatment initiation, blue-light fundus autofluorescence showed the occurrence of epiphenomenon multiple evanescent white dot syndrome. After 1 month, all lesions resolved and best-corrected visual acuity improved to 20/100. The authors report a rare case of PIC and epiphenomenon multiple evanescent white dot syndrome development after surgery for full-thickness macular hole. They hypothesize that several causes, including individual susceptibility (high myopia and female gender), postsurgical inflammation, and/or dye toxicity due to repeated staining, could have amplified this inflammatory chorioretinal response. Larger studies are needed to better understand the potential triggers of PIC development after surgery.