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Abstract Background Operators in the obituary and necropsy sectors are exposed to various environmental hazards during specific tasks. Despite this exposure, occupational risks have often been underestimated, resulting in a lack of substantial evidence. The primary objectives of this study were to identify sources of chemical risk, establish procedures for monitoring and quantifying exposure during necropsy activities, and recommend adjustments to regulatory guidelines to protect the health of the operators. The study was conducted at the Legal Medicine Unit of the Umberto I General Hospital in Rome, focusing on the quantitative measurement of particulate matter (PM) exposure among at-risk operators during necropsy activities. Environmental levels of total suspended particles, PM10, PM4, PM2.5, and PM1 were assessed by evaluating the average, minimum, and maximum instantaneous indoor concentrations using an airborne analyzer. Results The monitoring activities revealed that the PM concentrations were significantly lower than the recognized reference values. However, bone sawing, body removal, and cleaning were identified as high-risk maneuvers for dust suspension. Conclusions Our study highlighted specific risks associated with necropsy activities, particularly concerning timing and certain maneuvers. These results may lead to interventions for improving current prevention procedures, implementing good practices, and developing specific guidelines to enhance operator safety.

Precision agriculture (PA) is a farming management concept that aims to provide agronomic, economic, and environmental benefits. One of the fields of research in PA is the delineation of Management Unit Zones (MUZs). MUZs are the sub-division of fields featuring an inter-zonal variation delineated by agronomists for on-field PA operations. To develop MUZs, three factors typically need to be considered: input multi-dimensional data, procedures to process the information, and the optimal number of zones a field should be divided into. PA uses digital technologies to collect and analyze a large amount of data, outline MUZs, monitor crops, and carry out site-specific crop management. Web-based spatial decision support systems (WB-SDSS) can provide users with tools that ease the complex procedures for PA. The objective of this study is twofold: on the one hand, we developed a free and open source (FOSS) WB-SDSS to facilitate the implementation and use of such tools for delineating MUZs and monitoring crops; on the other, a MUZs outline procedure was developed based on Sentinel-2 and Planetscope time series data, and spatio-temporal dynamic clustering model using fuzzy c-means. Our study highlighted that the WB-SDSS might be a helpful solution for harmonizing data collected from different sources, easing the implementation and use of complex geospatial procedures for PA, and delineating MUZs. We tested the system on a particularly representative farm in the Emilia Romagna region (Northern Italy), with 512 hectares of durum wheat crops. Using the WB-SDSS, we quickly delineated homogeneous zones for 27 fields in the study area during the phenological cycle of durum wheat (November 2018-June 2019).

The first expansion of Opus Dei in Italy, in 1949, is described: this consists of an overview together with the criteria given by St. Josemaría for undertaking the trips to make Opus Dei known. With the help of the notes of Luigi Tirelli, one of the people involved in the trips, we focus on the activities carried out in Sicily (Palermo and Catania) up until the opening of the first center of the Work in Palermo (1949). To conclude, an outline of the trips to Italian cities is presented.

Establishing the manner of death is one of the most challenging tasks for forensic pathologists. We present the case of a 24-year-old woman found dead in the early morning on a flyover. The body was sitting on the ground with the back leaning against a wall. The neck was encircled by a white phone charger cable knotted to the staircase’s handrail. The victim had argued with her boyfriend and tried to jump out of his car while coming home from a wedding party the night before. After that, she left home alone with her phone charger in her hand. Due to self-harm behaviors, the first hypothesis was suicide by hanging. However, the ligature crossed immediately beneath the thyroid cartilage and encircled the neck twice horizontally; the two ends of the cable overlapped, forming a cross-over point in the front-right of the neck. Then, the ligature passed obliquely through the nape, gradually disappearing, forming a gap in the mark. The mark was sharply defined, stiff, yellow, and parchment-like. The investigators performed a three-dimensional scene reconstruction using the Trimble X7 Laser Scanner and the PC-Crash Multibody System. Even though the geometry of the ligature mark in the present case raised doubts about the manner of death, the three-dimensional reconstruction confirmed that the hanging was feasible without any external intervention.

Objective: While most of the evidence in CTO interventions emerge from Western and Japanese studies, few data have been published up today from the Middle East. Objective of this study was to evaluate technical success rates and clinical outcomes of an Iranian population undergoing CTO PCI in a tertiary referral hospital. Moreover, we sought to evaluate the efficacy of our CTO teaching program. Methods: This is a retrospective single-center cohort study including 790 patients who underwent CTO PCI performed by operators with different volumes of CTOs PCI performed per year. According to PCI result, all patients have been divided into successful (n = 555, 70.3 %) and unsuccessful (n = 235, 29.7 %) groups. Study endpoints were Major Adverse Cardiovascular Events and Health Status Improvement evaluated using the Seattle Angina Questionnaire at one year. Results: A global success rate of 70 % for antegrade and 80 % for retrograde approach was shown despite the lack of some CTO-dedicated devices. During the enrollment period, the success rate increased significantly among operators with a lower number of CTO procedures per year. One-year MACE rate was similar in both successful and unsuccessful groups (13.5 % in successful and 10.6 % in unsuccessful group, p = 0.173). One year patients’ health status improved significantly only in successful group. Conclusions: No significant differences of in-hospital and one-year MACE were found between the successful and unsuccessful groups. Angina symptoms and quality of life significantly improved after successful CTO PCI. The RAIAN registry confirmed the importance of operator expertise for CTO PCI success.

Introducción: La prevalencia de infecciones periprotésicas luego de una artroplastia total de cadera primaria es aproximadamente del 2%. El objetivo de este estudio fue determinar si existen diferencias estadísticamente significativas entre la tasa de infecciones periprotésicas agudas ante una profilaxis antibiótica extendida (7 días) y una profilaxis antibiótica estándar (24 h). Materiales y Métodos: Se realizó un estudio clínico prospectivo, entre julio de 2021 y mayo de 2022, que incluyó a 28 adultos con fractura de cadera sometidos a una artroplastia primaria que recibieron profilaxis antibiótica con cefalosporinas de primera generación durante 7 días a quienes se comparó con 95 adultos con fracturas de cadera con una artroplastia primaria y profilaxis antibiótica de 24 h, extraídos de una base de datos secundaria del registro del hospital. Resultados: La tasa de infecciones periprotésicas agudas fue del 10,71% en el grupo con profilaxis extendida y del 17,89% en quienes recibieron profilaxis estándar, sin diferencias estadísticamente significativas (p = 0,36). Conclusiones: Si bien, según la bibliografía disponible, la prolongación de la profilaxis antibiótica puede ser una medida simple, segura y rentable para contrarrestar los factores no modificables del paciente y así reducir las infecciones periprotésicas; en este estudio, no se demostró que la profilaxis antibiótica extendida disminuya la tasa de infecciones periprotésicas agudas a los 30 días en pacientes con artroplastias de cadera primarias.

Despite the increasing efficacy of modern medicine in diagnosing and treating cancer, survivors often face discrimination in employment, economics, insurance, and society. Law no. 193/2023, also known as the “Oncological Oblivion Law”, aims to provide an initial legislative response to discrimination against cancer survivors in Italy. After defining oncological oblivion in Article 1, the Law provides, in Articles 2, 3, and 4, directives to prevent discrimination against cancer survivors in the area of access to banking and insurance services, adoption procedures and access to or retention in employment. The aim of this work is to illustrate the content and the critical aspects of the recent Law 193/2023 in the landscape of European directives. The legislative process at the Chamber of Deputies and the Senate of the Italian Republic has been retraced through the consultation of preparatory works and bills registered on institutional databases. Law 193/2023 represents the first initiative in Italy aimed at the recognition of the right to oncological oblivion, not only in access to banking and insurance services as in other countries, but also in adoption, employment, and re-employment. Our opinion piece highlights the need for further clarification and expansion to prevent discrimination and protect the social–work–relational rights of people who have been affected by oncological diseases.

The demand for bioactive secondary metabolites of natural origin is increasing every day. Micropropagation could be a strategy to respond more quickly to market demands, regardless of seasonality. This research aims to evaluate in vitro-grown plants of two hop varieties, namely Columbus and Magnum, as a potential source of bioactive compounds. The extracts were characterized in terms of total phenolic content by a Folin–Ciocalteu assay and antioxidant capacity by DPPH•, ABTS+, and FRAP assays. The bioactive compound profile of the extracts from both varieties was determined by using UPLC-ESI-QqQ-MS/MS. The results confirmed richness in (poly)phenols and other secondary metabolites of the in vitro-grown hop plantlets. Thirty-two compounds belonging to the major families of phytochemicals characteristic of the species were identified, and twenty-six were quantified, mainly flavonoids, including xanthohumol and isoxanthohumol, phenolic acids, as well as α- and β-acids. This study confirms the validity of in vitro-derived hop plantlets as source of bioactive compounds to be used in the nutraceutical, pharmaceutical, and food industries.

Currently, one of the most important challenges for the conservation of stone artworks is the removal of metal corrosion products on their surfaces. Traditional cleaning methods, which typically involve the application of aqueous solutions containing chelating agents capable of complexing these metal ions, have shown some weaknesses. These weaknesses become apparent when such methods are applied to statues and other vertical surfaces or when aiming to limit the cleaning process to a specific area with controlled application times. Furthermore, the porosity of the stone surface plays a role concerning the cleaning efficiency. To address these issues, chelating agents can be incorporated into gel-like materials. This study is a proof of concept to evaluate the cleaning efficacy of various gel formulations composed of polyvinyl alcohol (PVA), borax (B), and agarose (AG), loaded with two chelators: ethylenediaminetetraacetic acid (EDTA) and potassium sodium tartrate (PST or Rochelle salt). Three types of carbonate stones (travertine, Lecce stone, and Carrara marble) characterized by different porosities were artificially stained with copper sulphates and treated with the different PVA-B-AG formulations. The effectiveness of the treatment was directly monitored on the stones using a multi-technique approach that included scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) and non-invasive portable nuclear magnetic resonance (NMR). Additionally, the rheological properties of the gels were investigated, and the Fourier transform infrared attenuated total reflection spectroscopy (FTIR ATR) was used to analyse the chemical structure of the gel before and after treatment, aiming to understand the changes induced by the cleaning process.

Background and Objectives: Fibromyalgia is a multifaceted and frequently misunderstood chronic pain disease marked by widespread musculoskeletal pain and cognitive/somatic dysfunction. This trial aims to contribute to the existing knowledge on treating fibromyalgia (FM) with medical cannabis (Cannabis sativa L.) and explore a safer and more effective cannabis administration method. The goal is to provide evidence-based findings that can guide alternative treatment options for FM patients by assessing a pilot study. Materials and Methods: The trial was performed at the pain therapy unit of the San Carlo Hospital (Potenza, Italy) by administrating to 30 FM patients 100 mg/day of Bedrocan® (Bedrocan International, Veendam, The Netherlands) as a decoction. The Numerical Rating Scale (NRS) and SF-12 short-form health questionnaire were used to evaluate pain intensity and the quality of life at the beginning of the study and the 6th-month follow-up. A systematic review of all clinical studies investigating the use of cannabis to reduce FM was also undertaken to place this study in the context of the existing evidence base. Results: Pain intensity evaluated with the NRS lowered from a median of 8 [95% CI 7.66–8.54] at a baseline to a median of 4 (95% CI 3.28–4.79) after 6 months of follow-up (p-value < 0.001; t-test). Similarly, significant physical and mental state improvement, evaluated with the SF-12 questionnaire, was found in 96.67% and 82.33% of patients, respectively (95% CI 44.11–51.13 for the physical state, and 53.48–58.69 for mental state assessed after the 6th-month follow-up; p-value < 0.001; t-test). The systematic analysis of the literature identified 10 clinical trials concerning the treatment of fibromyalgia with cannabis. Conclusions: Considering results from the present pilot study and systematic review, it is possible to assume that medical cannabis may be considered an alternative therapy for FM patients who do not respond to conventional pharmacological therapy.

The elderly represent an increasing proportion of patients presenting with acute coronary syndrome (ACS). Various data have shown that the benefits of percutaneous coronary revascularization are maintained in elderly patients presenting with ACS. Conversely, the management of antiplatelet therapy remains challenging and controversial, because older patients are usually at a high risk of both ischemia and bleeding. Moreover, the recommended ischemic and bleeding risk scores in patients with ACS were developed from studies with a low representation of older patients. New antiplatelet strategies have been developed, but their evidence in elderly patients is limited because they are usually underrepresented in randomized clinical trials due to their clinical complexity. The aim of this review is to summarize the different factors associated with increased ischemic and/or bleeding risk and the scientific evidence about the different antiplatelet strategies in elderly patients presenting with ACS and undergoing percutaneous coronary revascularization.

IntroductionThe competence assessment to give informed consent in the legal and healthcare settings is often performed merely through clinical judgment. Given the acknowledged limited reliability of clinician-based evaluation in the mental health sector, particularly for the assessment of competence to consent, our objective was to ascertain the dependability of clinical judgment when evaluating the ability of schizophrenia patients to make choices about their health.MethodsThe potential convergence between clinical evaluation and scores from a new standardized assessment (the “Evaluation of Informed Consent to Treatment” - “EICT” scale) was therefore tested. The scale assesses four dimensions of competence, specifically how patients normally understand information relating to care (Understanding); how they evaluate the choice of treatment in terms of risk/benefit ratio (Evaluating); how they reason coherently in the decision-making process (Reasoning); and, finally, their ability to make a choice between treatment alternatives (Expressing a choice). Thirty-four outpatients with schizophrenia were evaluated for their competence to consent by five referring clinicians with different backgrounds (psychiatrist, forensic psychiatrist, geriatrician, anesthetist, and medico-legal doctor). Inter-raters variability was tested through correlation analyses between the scores obtained by the clinicians on a modified version of the Global Assessment of Functioning scale (GAF) designed specifically to subjectively assess functioning in each of the four competence dimensions. Two validated competence scales (Mac-CAT-T, SICIATRI-R), and a neuropsychological battery were also administered along with scales for evaluating neuropsychiatric symptoms severity and side effects of medication.ResultsClinical judgments of the individual specialists showed great inter-rater variability. Likewise, only weak/non-significant correlations were found between the EICT subscales and the respective clinicians-rated GAF scales. Conversely, solid correlations were found between the EICT and MacCAT-T subscales. As expected, healthy controls performed better in the ability to give informed consent to treatment, as measured by the three scales (i.e., EICT, MacCAT-T, and SICIATRI-R), and neuropsychological test performance. In the comparisons between patients who, according to the administered EICT, were able or not able to give informed consent to treatment, significant differences emerged for the Phonemic verbal fluency task (p = 0.038), Verbal judgments (p = 0.048), MacCAT-T subscales, and SICIATRI-R total score. Moreover, EICT exhibited excellent internal consistency (Cronbach’s alphas ranging from 0.96 to 0.98 for the four subscales) while the Item Analysis, by measuring the correlation between each item of the EICT and the total score, was excellent for all items of all subscales (alphas ranging from 0.86 to 0.98).DiscussionIn conclusion, our findings highlighted that the assessment of competence exclusively through clinical judgment is not fully reliable and needs the support of standardized tools. The EICT scale could therefore be useful in assessing general competence to consent both in healthcare and legal contexts, where it might be necessary to evaluate the effective competence of patients with psychiatric disorders. Finally, this scale could serve as a valuable tool for decisions regarding whether and to what extent a patient needs support.

Background and Objectives: Healthcare facilities are complex systems due to the interaction between different factors (human, environmental, management, and technological). As complexity increases, it is known that the possibility of error increases; therefore, it becomes essential to be able to analyze the processes that occur within these contexts to prevent their occurrence, which is the task of risk management. For this purpose, in this feasibility study, we chose to evaluate the application of a new safety walkaround (SWA) model. Materials and Methods: A multidisciplinary working group made up of experts was established and then the subsequent phases of the activity were divided into three stages, namely the initial meeting, the operational phase, and the final meeting, to investigate knowledge regarding patient safety before and subsequently through visits to the department: the correct compilation of the medical record, adherence to evidence-based medicine (EBM) practices, the overall health and the degree of burnout of the various healthcare professionals, as well as the perception of empathy of staff by patients. Results: This working group chose to start this pilot project in the vascular surgery ward, demonstrating the ability of the tool used to capture the different aspects it set out to collect. In detail, the new version of SWA proposed in this work has made it possible to identify risk situations and system vulnerabilities that have allowed the introduction of corrective tools; detect adherence to existing company procedures, reschedule training on these specific topics after reviewing, and possibly update the same procedures; record the patient experience about the doctor–patient relationship and communication to hypothesize thematic courses on the subject; evaluate workers’ perception of their health conditions about work, and above all reassure operators that their well-being is in the interest of the management of the healthcare company, which is maintained. Conclusions: Therefore, the outcome of the present study demonstrates the versatility and ever-present usefulness of the SWA tool.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical situation characterized by evidence of acute myocardial infarction (AMI)—according to the Fourth Universal Definition of Myocardial Infarction—with normal or near-normal coronary arteries on angiographic study (stenosis < 50%). This condition is extremely variable in etiology, pathogenic mechanisms, clinical manifestations, prognosis and consequently therapeutic approach. Objective: The objective of the study was the evaluation of remnant cholesterol (RC), monocyte/high-density lipoprotein cholesterol ratio (MHR), platelet/lymphocyte ratio (PLR) and various lipoprotein ratios in patients with MINOCA in order to establish their validity as predictors of this event. Materials and Methods: We included 114 patients hospitalized in the Intensive Coronary Care Unit (ICCU) and Hospital Wards of our Hospital Center from 2015 to 2019 who received a diagnosis of MINOCA compared to a control group of 110 patients without previous cardiovascular events. RC was calculated with the following formula: RC = total cholesterol (TC) − HDL-C − LDL-C. MHR was calculated by dividing the monocyte count in peripheral blood by high-density lipoprotein cholesterol (HDL-C) levels; PLR was obtained by dividing platelet count by lymphocyte count. We also calculated various lipoprotein ratios, like total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), triglycerides/high-density lipoprotein cholesterol (TG/HDL-C), and non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol (non-HDL-C/HDL-C) ratios. Results: The MINOCA group had higher mean levels of RC (21.3 ± 10.6 vs. 13.2 ± 7.7 mg/dL), MHR (23 ± 0.009 vs. 18.5± 8.3) and PLR (179.8 ± 246.1 vs. 135 ± 64.7) than the control group. Only the mean values of all calculated lipoprotein ratios were lower in MINOCA patients. Statistical significance was achieved only in the RC evaluation. Conclusions: Higher levels of RC and MHR were found in patients with MINOCA. We also observed higher levels of PLR than in the control group. Only various lipoprotein ratios were lower, but this could reflect the extreme heterogeneity underlying the pathogenic mechanisms of MINOCA. In patients who receive a diagnosis of MINOCA with a baseline alteration of the lipid profile and higher levels of cholesterol at admission as well, the evaluation of these parameters could play an important role, providing more detailed information about their cardiometabolic risk.

Background: Mental capacity is a fundamental aspect that enables patients to fully participate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients’ capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in decision-making capacity within the healthcare context among groups of patients with bipolar disorders (BD) and schizophrenia spectrum disorders (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Additionally, Google Scholar was manually inspected, and a manual search of emerging reviews and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving patients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges’ g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better compared to patients with SSD, with the difference being statistically significant in the domain of Appreciation (ES = 0.23, 95% CI: 0.01 to 0.04, p = 0.037). There was no statistically significant difference between the two groups for Understanding (ES = 0.09, 95% CI:−0.10 to 0.27, p = 0.352), Reasoning (ES = 0.18, 95% CI: −0.12 to 0.47, p = 0.074), and Expression of a choice (ES = 0.23, 95% CI: −0.01 to 0.48, p = 0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES = 0.21, 95% CI: −0.04 to 0.46, p = 0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.

This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.

Background: Healthcare systems represent complex organizations within which multiple factors (physical environment, human factor, technological devices, quality of care) interconnect to form a dense network whose imbalance is potentially able to compromise patient safety. In this scenario, the need for hospitals to expand reactive and proactive clinical risk management programs is easily understood, and artificial intelligence fits well in this context. This systematic review aims to investigate the state of the art regarding the impact of AI on clinical risk management processes. To simplify the analysis of the review outcomes and to motivate future standardized comparisons with any subsequent studies, the findings of the present review will be grouped according to the possibility of applying AI in the prevention of the different incident type groups as defined by the ICPS. Materials and Methods: On 3 November 2023, a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out using the SCOPUS and Medline (via PubMed) databases. A total of 297 articles were identified. After the selection process, 36 articles were included in the present systematic review. Results and Discussion: The studies included in this review allowed for the identification of three main “incident type” domains: clinical process, healthcare-associated infection, and medication. Another relevant application of AI in clinical risk management concerns the topic of incident reporting. Conclusions: This review highlighted that AI can be applied transversely in various clinical contexts to enhance patient safety and facilitate the identification of errors. It appears to be a promising tool to improve clinical risk management, although its use requires human supervision and cannot completely replace human skills. To facilitate the analysis of the present review outcome and to enable comparison with future systematic reviews, it was deemed useful to refer to a pre-existing taxonomy for the identification of adverse events. However, the results of the present study highlighted the usefulness of AI not only for risk prevention in clinical practice, but also in improving the use of an essential risk identification tool, which is incident reporting. For this reason, the taxonomy of the areas of application of AI to clinical risk processes should include an additional class relating to risk identification and analysis tools. For this purpose, it was considered convenient to use ICPS classification.

IntroductionThe hemodynamic management of septic patients involves initial fluid therapy, followed by the use of vasoconstrictors in case of treatment failure. The latest Surviving Sepsis Campaign guidelines suggest the synergistic use of argipressin in addition to norepinephrine when hemodynamic optimization is not achieved with norepinephrine alone.MethodsIn our single-center retrospective observational study, the primary endpoint is the safety of initial norepinephrine-argipressin association treatment, assessed through a reduction in Resistance Index. Our secondary endpoint includes the efficacy of this combination, measured by an increase in Mean Arterial Pressure and a reduction in Resistance Index as an indicator of organ perfusion. The Resistance Index (RI) is evaluated through Power Doppler ultrasound. RI is crucial for assessing multi-district vascular tone and multiorgan perfusion. Patients were categorized into three groups based on their treatment. In Group 1, we analyzed patients treated with norepinephrine alone in incremental doses; in Group 2, we analyzed patients receiving the initial norepinephrine-argipressin association treatment (norepinephrine 0.05 mcg/kg/min-argipressin 0.03 IU/min); in the third group (Group 3), we analyzed patients given argipressin (0.03 IU/min) after norepinephrine ( 65 mmHg). RI measurements were taken in the Renal Artery (ARE), Radial Artery (AR), Central Retinal Artery (CRA), and Superior Mesenteric Artery (AMS) at four different time points: T0 before vasopressor therapy, T1 at 1 h, T2 at 24 h, and T3 at 48 h after vasopressor infusion.ResultsA total of 48 patients were divided into three groups: 17 patients in Group 1, 16 in Group 2, and 15 in Group 3. In Group 1, an increase in Mean Arterial Pressure (MAP) was observed, but there was an increase in RIs in the right CRI and left ARE. In Group 2, there was an improvement in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR. In Group 3, there was an increase in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR.ConclusionEarly norepinephrine-argipressin association treatment appears to be a valid strategy for hemodynamic optimization in this patient population.

Immunotherapy has revolutionized the treatment paradigm of non-small cell lung cancer and improved patients’ prognosis. Immune checkpoint inhibitors have quickly become standard frontline treatment for metastatic non-oncogene addicted disease, either as a single agent or in combination strategies. However, only a few patients have long-term benefits, and most of them do not respond or develop progressive disease during treatment. Thus, the identification of reliable predictive and prognostic biomarkers remains crucial for patient selection and guiding therapeutic choices. In this review, we provide an overview of the current strategies, highlighting the main clinical challenges and novel potential biomarkers.

In this article, we investigate an active plasmonic element which will act as the key building block for future photonic devices. This element operates by modulating optical constants in a localised fashion, thereby providing an external control over the strength of the electromagnetic near field above the element as well as its far-field response. A dual experimental approach is employed in tandem with computational methods to characterise the response of this system. First, an enhanced surface plasmon resonance experiment in a classical Kretschmann configuration is used to measure the changes in the reflectivity induced by an alternating electric current. A lock-in amplifier is used to extract the dynamic changes in the far-field reflectivity resulting from Joule heating. A clear modulation of the materials’ optical constants can be inferred from the changed reflectivity, which is highly sensitive and dependent on the input current. The changed electrical permittivity of the active element is due to Joule heating. Second, the resulting expansion of the metallic element is measured using scanning Joule expansion microscopy. The localised temperature distribution, and hence information about the localisation of the modulation of the optical constants of the system, can be extracted using this technique. Both optical and thermal data are used to inform detailed finite element method simulations for verification and to predict system responses allowing for enhanced design choices to maximise modulation depth and localisation.

In this study, a new micro delivery system based on an anionic methacrylate copolymer, able to improve the biological response of myo-inositol by daily oral administration, was manufactured by spray-drying. It has an ideal dose form for oral administration, with an experimental drug loading (DL)% of 14% and a regulated particle size of less than 15 µm. The new formulation features an improvement on traditional formulations used as a chronic therapy for the treatment of polycystic ovary syndrome. The microparticles’ release profile was studied and ex vivo porcine intestinal mucosa permeation experiments were performed to predict potential improvements in oral absorption. Batch n. 3, with the higher Eudragit/MI weight ratio (ratio = 6), showed the best-modified release profiles of the active ingredient, ensuring the lowest myo-inositol loss in an acidic environment. The in vivo evaluation of the myo-inositol micro delivery system was carried out in a rat animal model to demonstrate that the bioavailability of myo-inositol was increased when compared to the administration of the same dosage of the pure active ingredient. The AUC and Cmax of the loaded active molecule in the micro delivery system was improved by a minimum of 1.5 times when compared with the pure substance, administered with same dosage and route. Finally, the increase of myo-inositol levels in the ovary follicles was assessed to confirm that a daily administration of the new formulation improves myo-inositol concentration at the site of action, resulting in an improvement of about 1.25 times for the single administration and 1.66 times after 7 days of repeated administration when compared to pure MI.

Traumatic intracranial aneurysms (TICAs) are rare, accounting for less than 1% of all intracranial aneurysms. However, they are associated with a mortality rate of over 50%. The case presented herein focuses on a posterior communicating artery TICA caused by violent aggression. A 41-year-old man with massive subarachnoid hemorrhage (SAH), on admission to hospital, had a CT angiography that showed a ruptured left posterior communicating artery aneurysm with continuous blood loss and underwent neurosurgical cooling. The CT scan also showed fractures of the mandible, mastoid and left styloid process, as well as brain contusions caused by blows and kicks. Despite medical treatment and surgery, after four days, he died. The assault dynamics were recorded by a camera in the bar. The damage was caused by kicks to the neck and head. The forensic neuropathological examination showed the primary injury (SAH, subdural hemorrhage, cerebral contusions, head–neck fractures), as well as secondary damage following the attack (cerebral infarcts, edema, supratentorial hernia, midbrain hemorrhage). The coil was intact and well positioned. In this case, circumstantial information, medical records, and the type of injury could shed light on the mechanism of the production of a TICA. In addition, the CT angiography and histological investigations helped to distinguish a recent and traumatic aneurysm from a pre-existing one. Following precise steps, the study of aneurysms can be helpful in clarifying their traumatic origin even when the victim was taking drugs. The aim of this study is also to share the diagnostic process that we used in the forensic field for the assessment of suspected traumatic aneurysms.

Fear extinction is a phenomenon that involves a gradual reduction in conditioned fear responses through repeated exposure to fear-inducing cues. Functional brain connectivity assessments, such as functional magnetic resonance imaging (fMRI), provide valuable insights into how brain regions communicate during these processes. Stress, a ubiquitous aspect of life, influences fear learning and extinction by changing the activity of the amygdala, prefrontal cortex, and hippocampus, leading to enhanced fear responses and/or impaired extinction. Glucocorticoid receptors (GRs) are key to the stress response and show a dual function in fear regulation: while they enhance the consolidation of fear memories, they also facilitate extinction. Accordingly, GR dysregulation is associated with anxiety and mood disorders. Recent advancements in cognitive neuroscience underscore the need for a comprehensive understanding that integrates perspectives from the molecular, cellular, and systems levels. In particular, neuropharmacology provides valuable insights into neurotransmitter and receptor systems, aiding the investigation of mechanisms underlying fear regulation and potential therapeutic targets. A notable player in this context is cortisol, a key stress hormone, which significantly influences both fear memory reconsolidation and extinction processes. Gaining a thorough understanding of these intricate interactions has implications in terms of addressing psychiatric disorders related to stress. This review sheds light on the complex interactions between cognitive processes, emotions, and their neural bases. In this endeavor, our aim is to reshape the comprehension of fear, stress, and their implications for emotional well-being, ultimately aiding in the development of therapeutic interventions.

IntroductionCalcitonin-producing pancreatic neuroendocrine neoplasms (CT-pNENs) are an extremely rare clinical entity, with approximately 60 cases reported worldwide. While CT-pNENs can mimic the clinical and diagnostic features of medullary thyroid carcinoma, their molecular profile is poorly understood.MethodsWhole-exome sequencing (WES) was performed on tumor and corresponding serum samples of five patients with increased calcitonin serum levels and histologically validated calcitonin-positive CT-pNENs. cBioPortal analysis and DAVID gene enrichment analysis were performed to identify dysregulated candidate genes compared to control databases. Immunohistochemistry was used to detect the protein expression of MUC4 and MUC16 in CT-pNEN specimens.ResultsMutated genes known in the literature in pNENs like MEN1 (35% of cases), ATRX (18-20% of cases) and PIK3CA (1.4% of cases) were identified in cases of CT-pNENs. New somatic SNVs in ATP4A, HES4, and CAV3 have not been described in CT- pNENs, yet. Pathogenic germline mutations in FGFR4 and DPYD were found in three of five cases. Mutations of CALCA (calcitonin) and the corresponding receptor CALCAR were found in all five tumor samples, but none of them resulted in protein sequelae or clinical relevance. All five tumor cases showed single nucleotide variations (SNVs) in MUC4, and four cases showed SNVs in MUC16, both of which were membrane-bound mucins. Immunohistochemistry showed protein expression of MUC4 in two cases and MUC16 in one case, and the liver metastasis of a third case was double positive for MUC4 and MUC16. The homologous recombination deficiency (HRD) score of all tumors was low.DiscussionCT-pNENs have a unique molecular signature compared to other pNEN subtypes, specifically involving the FGFR4, DPYD, MUC4, MUC16 and the KRT family genes. However, a major limitation of our study was the relative small number of only five cases. Therefore, our WES data should be interpreted with caution and the mutation landscape in CT-pNENs needs to be verified by a larger number of patients. Further research is needed to explain differences in pathogenesis compared with other pNENs. In particular, multi-omics data such as RNASeq, methylation and whole genome sequencing could be informative.

Due to recent events, professional liability for psychiatrists in Italy is currently a matter of lively debate. Specifically, overwhelming pressure on psychiatrists’ duties has been brought by regulatory developments, such as the closure of forensic psychiatric hospitals, with the consequent return of offenders to community-based care, and the mental health consequences of the pandemic. According to Italian courts, psychiatrists are not only responsible for diagnostic and therapeutic appropriateness but also for the effects of their interventions on patients, and their behaviors. The aim of this study was to explore the attitude and behaviors of Italian psychiatrists regarding defensive medicine and professional liability. A total sample of 254 psychiatrists was surveyed by means of a quantitative online questionnaire. Most psychiatrists reported practicing defensive medicine (no. 153/254, 60.2%) and felt that their position of guarantee compromised their work in healthcare for patients (no. 138/253, 54.3%). Age correlated inversely with acknowledgment of defensive practices (r = −0.245, p 0.05). Anxiety, anger, and restlessness were common reactions to legal complaints, involving no. 50/254 (19.7%) respondents, with 40% reporting impaired functioning. Most psychiatrists (no. 175/253, 68.9%) were concerned about both civil and criminal laws regarding their professional responsibility, but many were not fully informed about recent legislative regulations and younger physicians resulted scarcely trained in risk management (p

Objective Stellate cells are responsible for liver and pancreas fibrosis and strictly correlate with tumourigenesis. Although their activation is reversible, an exacerbated signalling triggers chronic fibrosis. Toll-like receptors (TLRs) modulate stellate cells transition. TLR5 transduces the signal deriving by the binding to bacterial flagellin from invading mobile bacteria.Design Human hepatic and pancreatic stellate cells were activated by the administration of transforming growth factor-beta (TGF-β). TLR5 was transiently knocked down by short-interference RNA transfection. Reverse Transcription-quantitativePCR and western blot were performed to analyse the transcript and protein level of TLR5 and the transition players. Fluorescence microscopy was performed to identify these targets in spheroids and in the sections of murine fibrotic liver.Results TGF-β-activated human hepatic and pancreatic stellate cells showed an increase of TLR5 expression. TLR5 knockdown blocked the activation of those stellate cells. Furthermore, TLR5 busted during murine liver fibrosis and co-localised with the inducible Collagen I. Flagellin suppressed TLR5, COL1A1 and ACTA2 expression after the administration of TGF-β. Instead, the antagonist of TLR5 did not block the effect of TGF-β. Wortmannin, a specific AKT inhibitor, induced TLR5 but not COL1A1 and ACTA2 transcript and protein level.Conclusion TGF-β-mediated activation of hepatic and pancreatic stellate cells requires the over-expression of TLR5. Instead, its autonomous signalling inhibits the activation of the stellate cells, thus prompting a signalling through different regulatory pathways.