This study comprises the comprehensive toxicological assessment of thiolated organosilica nanoparticles (NPs) synthesised from 3-mercaptopropyltrimethoxysilane (MPTS). We investigated the influence of three different types of nanoparticles synthesised from 3-mercaptopropyltrimethoxysilane: the starting thiolated silica (Si-NP-SH) and their derivatives prepared by surface PEGylation with PEG 750 (Si-NP-PEG750) and 5000 Da (Si-NP-PEG5000m) on biological subjects from in vitro to in vivo experiments to explore the possible applications of those nanoparticles in biomedical research. As a result of this study, we generated a comprehensive understanding of the toxicological properties of these nanoparticles, including their cytotoxicity in different cell lines, hemolytic properties, in vitro localisation, mucosal irritation properties and biodistribution in BALB/c mice. Our findings indicate that all three types of nanoparticles can be considered safe and have promising prospects for use in biomedical applications. Nanoparticles did not affect the viability of HPF, MCF7, HEK293 and A549 cell lines at low concentrations (up to 100 µg/mL); moreover, they did not cause organ damage to BALB/c mice at concentrations of 10 mg/kg. The outcomes of this study enhance our understanding of the impact of organosilica nanoparticles on health and the environment, which is vital for developing silica nanoparticle-based drug delivery systems and provides opportunities to expand the applications of organosilica nanoparticles.

Background/Objectives: Most survivors of out-of-hospital cardiac arrest (OHCA) may suffer from cognitive, mental difficulties, and fatigue, which negatively impact their quality of life, despite a good physical recovery. However, no definitive data are available on this topic, so this study aims to assess the feasibility and acceptability of a centralized, sub-regional screening system for OHCA survivors in Italy and the prevalence of these disorders. Methods: OHCA survivors discharged with good neurological outcomes (Cerebral Performance Category (CPC) ≤ 2 and modified Ranking Scale (mRS) ≤ 3) from hospitals in the “Lombardia CARe” registry will be evaluated by a clinical psychologist using the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), EQ-5D-5L for quality of life, and the Impact of Event Scale-Revised (IES-R) at pre-discharge or within 15 days and then at 1, 3, 6, and 12 months. Patients with clinical issues will be referred for psychological support or to a community rehabilitation program. Feasibility will be defined as a recruitment rate ≥ 80% and acceptability as a retention rate ≥ 50% over 12 months. Results: Based on historical data from the Lombardia CARe, an estimated 350 eligible survivors are expected, which will allow estimation of a prevalence ranging between 20% and 30% with 5% precision and 95% confidence. Conclusions: This study will be the first in Italy to evaluate the feasibility and acceptability of a centralized, sub-regional system for pre-/post-discharge evaluation of cognitive impairment, mental health, and quality of life in a large cohort of OHCA survivors, documenting the prevalence of these disorders.

Background/Objectives: A structured follow-up after out-of-hospital cardiac arrest (OHCA) is recommended, but implementation across regional networks remains challenging. REVIVE introduced a hub-and-spoke survivorship pathway in Lombardy. This 12-month formative implementation evaluation aimed to describe staged pathway progression, operational reach, attrition points, centre-level variation, and documented barriers to assessment completion. Methods: Adult OHCA survivors with Cerebral Performance Category (CPC) 1–2 or Modified Rankin Scale (mRS) ≤ 3 were considered eligible. The evaluation was structured using Proctor et al.’s implementation outcomes framework. Implementation outcomes were operationalised using prospectively collected pathway indicators: eligibility ascertainment, successful contact, T0 assessment completion, completion of planned assessment components, timeliness where available, and documented reasons for non-progression. Analyses were descriptive and used chi-square or Fisher’s exact tests for unadjusted centre-level comparisons. Results: Of the 1663 patients hospitalised, 1458 (87.7%) were recorded as deceased or having an unfavourable neurological outcome and were therefore outside the intended REVIVE target population. Among the remaining 205 patients, eligibility could not be determined for 78 (4.7% of the total cohort), and 127 (7.6%) met eligibility criteria. Of eligible survivors, 96 (75.6%) were contacted and 64 completed the T0 assessment (66.7% of contacted; 50.4% of eligible). Pavia showed higher observed rates of eligibility ascertainment, contact, and assessment completion than spoke centres, but these differences were unadjusted and should be interpreted as centre-level implementation variation rather than evidence of causal superiority. Conclusions: REVIVE initiated a structured regional pathway for post-OHCA follow-up, but first-year implementation was partial rather than definitive. The 50.4% T0 completion rate among eligible survivors should be interpreted as an initial internal implementation indicator, not as evidence of established feasibility, effectiveness, or regional benchmarking. Priorities for further optimisation include eligibility ascertainment, transfer of contact information, patient engagement, and spoke-site support for assessment delivery.

Introduction Cardiac arrest is the loss of mechanical cardiac function and the absence of systemic circulation. When it occurs out-of-hospital it is defined out-of-hospital cardiac arrest (OHCA). Survival after OHCA does not fully capture recovery, as survivors often experience persistent cognitive, psychological, and functional consequences. Patient-reported outcome measures (PROMs) are essential to assess these domains, but their longitudinal collection in routine survivorship care depends on patient engagement and retention over time. REVIVE is a regional hub-and-spoke survivorship pathway implemented within the Cardiac Arrest Registry of the Lombardy Region (LombardiaCARe) network to coordinate post-discharge follow-up after OHCA and standardize the assessment of patient-reported outcomes. Objectives To describe the structure of PROM collection within REVIVE and to evaluate patient retention, evaluability, and follow-up completeness over the 2025 calendar year. Methods We conducted a descriptive analysis of the REVIVE study between January and December 2025. During this period, 1,663 OHCA events were admitted to participating hospitals, 127 patients were eligible for the REVIVE pathway, 99 were contacted by the hub psychologist after signing informed consent, and 67 completed at least one assessment. REVIVE is structured as a hub-and-spoke pathway, with a specialist hub coordinating post-discharge follow-up and outcome assessment across participating hospitals. PROMs and related outcomes were collected at predefined timepoints and included discharge, 1 month, 3 months, and 6 months after the OHCA event. The PROMs assessed were anxiety and depression (HADS), post-traumatic stress symptoms (IES-R), cognitive performance (MoCA), and health-related quality of life (EQ-5D-5L), together with a clinical semi-structured interview. The analysis focused on the number of patients contributing at each timepoint and on the availability of at least one evaluable PROM per patient. Results Among the 99 consenting patients, 67 (67.7%) were evaluable and formed the analytic denominator. At the visit level, 46 patients had at least one PROM recorded at discharge, 49 at 1 month, 52 at 3 months, and 49 at 6 months. Domain-level completeness was high: HADS was available in 66 of 67 evaluable patients (98.5%), while MoCA and EQ-5D VAS were available in all evaluable patients (67/67, 100%). These results suggest that the main methodological challenge was not baseline collection, but maintaining patient engagement across repeated assessments, which in PROM-based survivorship care is inherently patient-driven rather than passive. Conclusions PROMs add value beyond survival by capturing outcomes that matter to OHCA survivors, but their validity depends on sustained patient engagement throughout follow-up. In REVIVE, the main challenge was not baseline collection, but maintaining retention in a patient-driven and psychologically sensitive assessment process, where readiness to participate may vary over time. These findings support clear definition of the evaluable cohort, transparent reporting of timepoint-specific completeness, and retention-oriented strategies to improve the quality and interpretability of longitudinal PROM data.

Introduction Cardiac arrest is the loss of mechanical cardiac function and systemic circulation; when it occurs outside hospital settings, it is defined as out-of-hospital cardiac arrest (OHCA). OHCA is influenced by both individual and contextual factors, including population structure, socioeconomic disadvantage, and access to emergency care. Geographic approaches offer a framework to investigate spatial inequalities and support place‑based decision making. Objectives This study assesses spatial inequalities in OHCA incidence in relation to demographic (ageing index, population density) and socioeconomic (low income) determinants in Lombardy between 2021 and 2024. Methods A municipal‑level retrospective ecological study was conducted in Lombardy (2021–2024). The outcome was an OHCA event. Data were obtained from the Lombardia Cardiac Arrest Registry (CARe), covering 924 municipalities across seven provinces. The eligible population included residents of municipalities in the CARe registry (cumulative at‑risk population: 17,612,296 inhabitants). Due to incomplete registry coverage in 296 municipalities, analyses focused on 628 municipalities forming the South‑East (SE) macro‑area (Pavia, Lodi, Cremona, Mantua, Brescia). Determinants included: proportion of taxpayers with annual income <€10,000 (proxy for socioeconomic vulnerability), ageing index (proxy for demographic imbalance), and population density (proxy for rurality/urbanization). Contextual covariates were: bystander cardiopulmonary (CPR) rate (proxy for community response) and EMS response time (minutes from emergency call to first vehicle arrival, proxy for geographic isolation).The analytical strategy combined global and local spatial autocorrelation (Global Moran’s I; Local Indicators of Spatial Association, LISA), hotspot analysis (Getis‑Ord Gi*), and geographically weighted regression (GWR) to identify clustering patterns and spatially varying associations between OHCA and determinants, adjusting for covariates. Results The cumulative OHCA incidence was 126 per 100,000 inhabitants. OHCA incidence was not randomly distributed, but showed significant spatial heterogeneity. Global Moran’s I confirmed clustering (I = 0.27; p < 0.001). Municipalities characterized by high- and low-incidence aggregation patterns were identified (Getis-Ord Gi* z-scores > |1.96|): a hot-spot cluster located in the south-western hilly area of the region and a cold-spot cluster in the south-eastern flat area. GWR showed that the strength and direction of associations varied across the region, highlighting spatial non-stationarity in the relationship between OHCA incidence and the area-level determinants, independently of community response, response time, and geographic isolation. Specifically, increasing the ageing index and the proportion of low-income individuals significantly increased OHCA incidence, whereas population density was inversely correlated with OHCA incidence. Conclusions OHCA incidence hot spots were concentrated in mountainous and hilly areas, especially in remote areas distant from hospitals. Indicators of social inequality showed spatially heterogeneous associations with OHCA, confirming that territorial disparities extend beyond demographic composition alone. Considering both structural determinants and contextual covariates improved interpretation of spatial patterns and highlighted the contribution of place‑based factors to OHCA burden. The integration of geographic data with health information represents a robust methodological approach for studying spatial inequalities in healthcare. Cardiac arrest findings may be translated into public health impact and guide equity-oriented planning by identifying priority areas and informing geographically targeted interventions.