Alessio Gnerucci

Background: Pulmonary embolism (PE) is a life-threatening condition in which early diagnosis and prompt treatment are essential to reduce morbidity and mortality. Recent advances in radiomics have introduced software tools for PE detection on CT pulmonary angiography (CTPA), but their application to non-contrast chest CT remains unexplored. Methods: We retrospectively identified 57 CTPA examinations performed between January 2020 and March 2023. Patients were randomly assigned to training and validation cohorts; an additional 14 PE-negative patients were included in the validation cohort. Spherical regions of interest (ROIs) were manually placed within emboli and within normal-flow pulmonary arteries. From each ROI, 836 radiomic features were extracted. Statistically significant features were identified using the Wilcoxon test. A logistic regression classifier was then developed to discriminate between embolus and control ROIs based on their radiomic signatures. Results: Of the 836 features, 242 (all derived from wavelet-filtered images) showed significant differences between embolus and normal-flow ROIs on unenhanced CT. The classifier demonstrated high diagnostic performance in the validation cohort, with an AUC of 0.87 (95% CI: 0.86–0.88) and an accuracy of 0.77 (95% CI: 0.76–0.79), with only a limited number of misclassified ROIs. Conclusions: This preliminary study demonstrates the potential of radiomics to identify thrombi on unenhanced chest CT scans, offering a promising avenue for the early detection of acute PE. The proposed model showed satisfactory diagnostic accuracy with low few misclassifications, supporting further validation in larger cohorts.

Oxidative and inflammatory stresses contribute to the development of many intestinal pathologies. This study characterized the polyphenolic profile and biological activity of a hydroalcoholic extract obtained from the fruit pulp of Feijoa sellowiana on HT29 intestinal epithelial cells subjected to oxidative (H₂O₂) and inflammatory (cytokines) stress. HPLC-DAD-MS analysis revealed an interesting phenolic composition, rich in hydrolyzable tannins (HHDP-glucose, pedunculagin and other ellagic acid derivatives) and condensed tannins (procyanidin dimers), with a total polyphenol content of 8.07 mg/g GAE. The extract was non-cytotoxic up to 160 µg/mL and exerted a protective effect against the cytokine-induced reduction in cell viability. In vitro assays confirmed its strong antioxidant and scavenging capacity. The scratch assay suggested enhanced cell migration. The extract modulated the activity of key metabolic enzymes restoring glucose-6-phosphate dehydrogenase and enolase activity, while supporting glycolytic flux through pyruvate kinase and lactate dehydrogenase. PCA and Pearson correlation analyses confirmed a treatment-dependent modulation of the metabolic and redox profile, suggesting a regulatory role beyond a mere scavenging effect. These findings highlight the nutraceutical potential of feijoa polyphenols, not only as direct antioxidants but also as modulators of cellular metabolism and redox homeostasis, supporting their application in gastrointestinal disorders with oxidative or inflammatory components.

Fluctuations in emergency department (ED) utilization may be related to pollutant concentration variations that can heighten acute pathologies, exacerbate chronic conditions or indicate increased human activity. This study investigates the association between particulate matter (PM2.5-PM10) concentrations in patients’ residential areas and ED visits. Retrospective, single-centre, time-series cohort study on a 100km² urban area around a level 1 hospital in Florence, Italy, with 307,279 ED visits of patients of age > 14 years between 01/01/2019 and 31/12/2022. PM2.5 and PM10 daily concentrations, recorded by 14 air-quality stations, were interpolated at patients’ residences, in a 250m² grid, with inverse distance weighting and averaged on various time windows (lag) up to 30 days before ED visit. The association between ED visits and pollutant concentrations as percent excess of incidence rate (%Er) with 95% confidence intervals were investigated with generalized additive models. Significant association was found with short-term PM2.5 and PM10 fluctuations (PM2.5_Lag1: 1.24%Er, 0.59–1.99 95%CI; PM10_Lag2: 1.79%Er, 1.08–2.72). Such association was stronger for the subgroups of deceased patients (PM2.5_Lag1 5.71%Er, 1.44–8.99; PM10_Lag2 6.38%Er, 2.02–10.83), elderly patients presenting with dyspnoea (PM2.5_Lag1 4.18%Er, 2.36–6.33; PM10_Lag2 4.99%Er, 2.77–7.32) and younger patients suffering traumatic events (PM2.5_Lag1 1.29%Er, 0.32–2.51; PM10_Lag2 2.14%Er, 0.88–3.50). Exposure–response curves showed that particulate matter is associated with ED visits even at concentrations below the WHO guard levels. A short-term rise in PM2.5 and PM10, even below guard levels, was associated with increased ED utilization, particularly related to elderly patients with dyspnoea and the concomitant lurking occurrence of vehicle accidents in the younger population. Trial registration: NCT06491290; 09/07/2024; retrospectively registered.

Purpose The robustness of surface-guided (SG) deep-inspiration breath-hold (DIBH) radiotherapy (RT) for left breast cancer was evaluated by investigating any potential dosimetric effects due to the residual intrafractional motion allowed by the selected beam gating thresholds. The potential reduction of DIBH benefits in terms of organs at risk (OARs) sparing and target coverage was evaluated for conformational (3DCRT) and intensity-modulated radiation therapy (IMRT) techniques. Methods A total of 192 fractions of SGRT DIBH left breast 3DCRT treatment for 12 patients were analyzed. For each fraction, the average of the real-time displacement between the isocenter on the daily reference surface and on the live surface (“SGRT shift”) during beam-on was evaluated and applied to the original plan isocenter. The dose distribution for the treatment beams with the new isocenter point was then calculated and the total plan dose distribution was obtained by summing the estimated perturbed dose for each fraction. Then, for each patient, the original plan and the perturbed one were compared by means of Wilcoxon test for target coverage and OAR dose–volume histogram (DVH) metrics. A global plan quality score was calculated to assess the overall plan robustness against intrafractional motion of both 3DCRT and IMRT techniques. Results Target coverage and OAR DVH metrics did not show significant variations between the original and the perturbed plan for the IMRT techniques. 3DCRT plans showed significant variations for the left descending coronary artery (LAD) and the humerus only. However, none of the dose metrics exceeded the mandatory dose constraints for any of the analyzed plans. The global plan quality analysis indicated that both 3DCRT and IMRT techniques were affected by the isocenter shifts in the same way and, generally, the residual isocenter shifts more likely tend to worsen the plan in all cases. Conclusion The DIBH technique proved to be robust against residual intrafractional isocenter shifts allowed by the selected SGRT beam-hold thresholds. Small-volume OARs located near high dose gradients showed significant marginal deteriorations in the perturbed plans with the 3DCRT technique only. Global plan quality was mainly influenced by patient anatomy and treatment beam geometry rather than the technique adopted.

The effects of the phenolic compounds of extra virgin olive oil (EVOO) on AGS cells have never been studied so far, which is the aim of this study. The profiles of the main phenolic components in EVOOs, mainly secoiridoid compounds derived from the transformation of oleuropein during the olive milling process, were evaluated and compared. Oils of different origins were evaluated aiming at verifying whether chemical differences in the phenolic composition of the dry extracts played a role in the metabolism and in maintaining the cellular redox state of AGS cells. The following key enzymes of some metabolic pathways were studied: lactate dehydrogenase, enolase, pyruvate kinase, glucose 6-phosphate dehydrogenase, citrate synthase, 3-Hydroxyacyl-CoA dehydrogenase and hexokinase. As confirmed through PCA analysis, pretreatments with the dry extracts of EVOOs at different concentrations appeared to be able to counteract the enzymatic activity alterations due to oxidative stress induced by H₂O₂ 1 mM and 2 mM. The studied phytocomplexes showed the ability to protect AGS cells from oxidative damage and the secoiridoid derivatives from both oleuropein and ligstroside contributed to the observed effects. The results suggested that EVOOs with medium to high concentrations of phenols can exert this protection.

Pâté is a by-product of olive oil production which represents an abundant source of phenolic compounds and can be used for food formulation, reducing its environmental impact and promoting a circular economy. In this context, the effects of a hydroalcoholic extract of pâté were evaluated for the first time in an AGS human cell line commonly used as model of gastric mucosa. Pâté was obtained from Tuscan olives; the total phenolic content was 16.6 mg/g dried extract, with verbascoside and secoiridoid derivatives as the most abundant phenols. The phenolic pâté extract did not alter viability, distribution of cell cycle phases or proliferation and migration of AGS cells at the tested concentrations. Seven enzymes were chosen to investigate the metabolic effect of the pâté extract in the context of oxidative stress. Pâté produced a statistically significant increase in the activity of key enzymes of some metabolic pathways: Lactate dehydrogenase, Enolase, Pyruvate kinase, Glucose 6-phosphate dehydrogenase, Citrate synthase, 3-Hydroxyacyl-CoA dehydrogenase and Hexokinase. Pre-treatments with the extract of pâté at 100 µg/mL or 200 µg/mL, as observed through PCA analysis, appeared able to counteract the enzymatic activity alterations due to oxidative stress induced by H₂O₂ 1 mM and 2 mM. The results indicate that dried pâté, due to its phenolic components, can be proposed as a new functional food ingredient.