Publications

Doxorubicin is an anthracycline chemotherapeutic that is widely used for treating various malignancies, including breast cancer, lymphomas, and sarcomas. Despite its efficacy, its clinical utility is limited by a well-documented risk of cardiotoxicity, which may manifest acutely or chronically. Doxorubicin works by intercalating DNA and inhibiting topoisomerase II, leading to DNA damage and cell death. However, this mechanism is not selective to cancer cells and can adversely affect cardiac myocytes. The introduction of doxorubicin into oncologic practice has revolutionized cancer treatment, but its cardiotoxic effects remain a significant concern. This systematic review aims to comprehensively examine the multifaceted impact of doxorubicin on cardiac structure and function through both preclinical and clinical lenses.

BACKGROUND: The long-term risk of cardiovascular (CV) events in individuals who develop new-onset type 2 diabetes (T2D) after having received statin therapy in primary prevention is mostly unknown.

METHODS: We designed a population-based cohort study in individuals without T2D and atherosclerotic CV disease (ASCVD), divided in two groups according to the presence or not of statin therapy. We also balanced the study groups for demographic and clinical factors using propensity score matching.

RESULTS: 119307 individuals without T2D and ASCVD were divided in statin users (N = 90906) or not (N = 28401) and followed-up for 70.1 ± 61.3 months. Yearly incidence of T2D rate was 0.3% in the control group and 2.2% in the statin treated group. A Cox regression analysis confirmed the association between incident T2D and statin therapy. In normotensive individuals, the presence of statin therapy led to a 2-fold risk to develop incident T2D with a HR 2.61 (95% CI 2.11-3.22, p < 0.001) which was also that of statin untreated hypertensive patients. In the hypertensive population statin therapy was associated with a HR of incident T2D of 4.62 (95% CI 3.75-5.69, p < 0.001). CV events rate, including coronary and cerebrovascular fatal and non-fatal events, was 1.9% in the statin group vs. 0.7% in the control group and a multiple regression analysis demonstrated an association between statin therapy and CV events. A further Cox regression performed only in the statin treated population revealed a significant association of CV events with age, serum creatinine levels, and incident T2D. Of note, the increased rate of new-onset T2D associated with statin use does not modify the class of CV risk of this population. All these findings were confirmed at the propensity score matched analysis.

CONCLUSIONS: Statin therapy in primary prevention is associated with a higher risk of incident T2D, especially in hypertensive patients. However, since the final CV risk of those who develop T2D during statin treatment was lower than the one required for statin prescription according to the ESC guidelines, indicating that this phenomenon does not impair the benefit in CV prevention associated with the lipid lowering effect of statins.

BACKGROUND: Delirium may develop in association with an underlying cardiovascular or cerebrovascular disease and complicates one out of three medical admissions representing a significant economic burden for healthcare systems. However, a clear relationship between delirium onset and diabetes mellitus has not been clarified. The purpose of this study was to explore the association between DM and delirium with the following aims: (a) to assess the incidence of delirium among DM patients (b) to assess the risk of delirium onset in patients with DM (c) to assess the role of anti-diabetic drugs on delirium onset.

METHODS: MEDLINE, Scopus, and Web of Science and ClinicalTrials.gov were searched from inception up to 30th of December 2024. Studies reporting the incidence of delirium in diabetic patients, delirium events in diabetic patients compared to non- diabetic patients, and the role of antidiabetic drugs on delirium development were considered.

RESULTS: The pooled incidence of delirium resulted 29% (95% CI 26.0%- 33.0% I2 = 99.6%). The OR for developing delirium resulted: 1.78 (95% CI 1.59-1.99 i2 = 88.3%) Intranasal insulin administration compared to placebo groups was characterized by a RR = 0.34 (95% CI 0.23-0.52). Metformin use compared to non-metformin use in diabetic patients was characterized by lower RR for delirium: pooled RR = 0.71 (95% CI 0.59-0.85, I2 = 84.8%).

CONCLUSIONS: The incidence of delirium in patients with diabetes is about 29% and patients with diabetes have higher odds of delirium. Chronic use of metformin, and intranasal insulin administration before surgery may offer benefits in the prevention of delirium. These findings are characterized by significant heterogeneity which hampers their interpretation. Future research for developing diabetes-specific delirium screening protocols, and evidence-based preventive interventions is needed.

Cardiac fibrosis and remodeling are critical contributors to heart failure, particularly in the context of diabetes, where hyperglycemia (HG) exacerbates pathological fibroblast activity. Despite the known cardiovascular benefits of canagliflozin (CANA), its specific effects on human cardiac fibroblasts (HCFs) under HG conditions remain unexplored. We investigated whether CANA could mitigate HG-induced detrimental responses in HCFs. Dose-response assays revealed that 100 nM CANA significantly reduced HG-induced proliferation and migration of HCFs. Furthermore, CANA attenuated mitochondrial reactive oxygen species (ROS) production, a key driver of myofibroblast differentiation, and suppressed HG-induced expression of SMAD2, a critical activator of cardiac fibroblasts. Additionally, HG disrupted calcium (Ca2+) homeostasis, which was ameliorated by CANA treatment. These findings collectively demonstrate that CANA exerts protective effects on HCFs by improving mitochondrial function, restoring Ca2+ handling, and reducing fibroblast proliferation, migration, and activation under HG conditions.

Prevention of dementia represents a public health priority. Hypertension is a risk factor for mild cognitive impairment (MCI), a precursor to progressive dementia. A great effort is underway to develop accurate and sensitive tools to detect the MCI condition in hypertensive patients. To investigate the potential association of subclinical left ventricular dysfunction expressed by the global longitudinal strain (GLS) with the MCI, defined by the Italian version of the quick mild cognitive impairment (Qmci-I). This multi-centric study included 180 consecutive hypertensive patients without medical diseases and/or drugs with known significant effects on cognition but with a not negligible comorbidity burden to avoid a possible "hyper-normality bias". The study cohort was classified into two main groups concerning the median value of the GLS. A weighted logistic regression model was employed after an inverse probability of treatment weighting (IPTW) analysis to characterize a potential association between GLS and MCI. Almost 41,1% of the whole study population was female. The mean age was 65,6 ± 7,2. 39 patients (21,7%) showed MCI. After IPTW, the GLS was significantly associated with the study endpoint (OR, 1,22; 95% CI: 1,07-1,39, P = 0.003). Our results highlight that the GLS is a potential predictor of MCI and, therefore, a valuable tool for establishing preventive strategies to arrest the progression toward a cognitive decline in hypertensive patients.