Non-invasive respiratory support for acute hypoxemic respiratory failure (AHRF) remains controversial. Continuous positive airway pressure (CPAP) provides sustained positive end-expiratory pressure, while helmet interface (H-CPAP) may improve tolerance and re-duce air leaks. We aimed to evaluate clinical outcomes of H-CPAP delivered in a respira-tory intermediate care unit (RICU) by pulmonologists and identify early predictors of treatment failure. We conducted a prospective single-centre observational cohort study in-cluding consecutive adults with community-acquired pneumonia (CAP)-AHRF treated with H-CPAP in a RICU. H-CPAP success was defined as hospital discharge without in-vasive mechanical ventilation (IMV). Clinical, radiological, gas exchange, laboratory var-iables were collected at baseline and after 1 hour of H-CPAP. Among 1100 screened pa-tients, 198 met inclusion criteria. H-CPAP success occurred in 158/198 patients (79.8%), while overall in-hospital mortality was 9.1%. Success rates decreased with increasing AHRF severity. Lower haematocrit, bilateral pulmonary infiltrates, lower PaO₂/FiO₂ dur-ing H-CPAP, higher alveolar–arterial oxygen gradient, and higher APACHE II score were the main predictors of treatment failure. In selected patients with CAP-AHRF, H-CPAP delivered in a RICU was associated with high rates of avoidance of IMV and low in-hospital mortality. Early physiological and radiological variables identified patients at increased risk of H-CPAP failure with acceptable predictive performance.
Researchers in biomedical research often analyse data that are subject to clustering. Development and validation of risk prediction models generally assumes independence of observations. For survival outcomes, the Cox proportional hazards regression model is commonly used to estimate an individual’s risk at fixed time horizons. The stratified Cox proportional hazards and the shared gamma frailty Cox proportional hazards regression models are two common approaches to account for the presence of clustering in the data. The accuracy of the predictions of these two approaches has not been examined. We conducted a set of Monte Carlo simulations to assess the impact of the number of clusters, the size of the clusters, and the within-cluster correlation in outcomes on the accuracy of the conditional predictions developed using the stratified and the shared gamma frailty Cox proportional hazards regression model. We compared the accuracy of the predictions in terms of discrimination, calibration and overall performance metrics. We found that the stratified and the shared gamma frailty model had similar performance, especially for larger size and higher number of clusters. For small cluster size, we observed slightly better discrimination and overall performance for the stratified model and better calibration for the shared gamma frailty model at shorter prediction horizons. The utility of the stratified Cox proportional hazards model for risk prediction is limited especially for high within-cluster correlation and when clusters are small, and at longer prediction horizons. Our results were accompanied with two applications using open source data on myelodysplastic syndrome and bladder cancer.
The overlap between the geographic distribution of COVID-19 outbreaks and pollution levels suggested a strong correlation between exposure to atmospheric particulate matter and an increased risk of developing severe forms of disease. This correlation has been highlighted by several epidemiological studies, indicating the existence of shared molecular mechanisms. Emerging evidence has highlighted the important role of lipid rafts in facilitating viral entry into cells. Specifically, the receptor binding domain of the SARS-CoV-2 spike protein interacts with sialylated glycans of the monosialic ganglioside GM1 and GM2 that are particularly enriched in lipid rafts. This interaction has been proposed to facilitate ACE2 recognition by the spike protein and may contribute to early events involved in viral attachment and entry. Here, we reveal that A549 alveolar lung cells, after DEP exposure, exhibit a significant shift in ACE2 into lipid rafts, accompanied by an increase in the immature form of ADAM17, the sheddase responsible for ACE2 cleavage. Additionally, DEP exposure results in a significant increase in IL-6 release, while no changes were observed in IL-8 and sACE2 release. This treatment does not cause significant alterations in protein levels or membrane redistribution of COX-2 and HO-1, proteins involved in the inflammatory response and oxidative stress following exposure to air pollution, and linked to COVID-19 pathogenesis. Finally, lipidomic analysis by UHPLC-MS revealed that DEP exposure induces a significant increase in GM2 levels, and a concomitant decrease in GM1 and GM3 levels. Together, these results indicate that DEP exposure remodels lipid raft-associated molecular features in A549 cells, including ACE2 membrane redistribution, altered ganglioside composition, and increased IL-6 release. Although these changes may be relevant to cellular mechanisms associated with SARS-CoV-2 susceptibility, the present study does not directly assess viral binding, viral entry, or infection, and further functional studies are required.
Background/Objectives: Unhealthy dietary behaviors and suboptimal oral hygiene practices remain common among Italian children, potentially affecting both nutritional and oral health. Dental caries, a preventable yet highly prevalent condition in pediatric populations, has a multifactorial etiology in which lifestyle factors play a key role. This study aimed to assess the prevalence of dental caries, dietary habits, and oral hygiene behaviors in school-aged children in Lombardy, and to identify factors associated with prevalent caries status. Methods: A cross-sectional study was conducted on 307 schoolchildren aged 9–10 years from ten schools in Northern Italy. Oral health status was evaluated through the plaque index and the DMFT/dmft index during school-based dental examinations. Dietary habits, lifestyle, and oral hygiene practices were collected through structured questionnaires. A mixed-effects logistic regression model was developed to explore potential associations between variables and prevalent caries status. Results: The dietary patterns, weight status, oral hygiene behaviors, and oral health conditions were generally consistent with the national data. Higher plaque index, skipping breakfast, consuming mid-morning snacks, and parental reports of previous caries experiences were retained in the final model. Internal validation suggested reasonable discriminatory ability overall, whereas calibration shows heterogeneity across schools. Conclusions: The findings highlight suboptimal dietary and oral hygiene behaviors among Lombardy schoolchildren and confirm their association with dental caries. Lifestyle-related factors, particularly oral hygiene practices and eating patterns, showed a relevant association with prevalent caries status in the analyzed sample. These results underscore the need for targeted preventive strategies integrating nutritional education and oral health promotion in pediatric populations.