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Background: The study of women exposures and child outcomes occurring in the first 1,000 days of life since conception enhances understanding of the relationships between environmental factors, epigenetic changes, and disease development, extending beyond childhood and spanning the entire lifespan. Generation Gemelli is a recently launched case-control study that enrolls mother-newborns pairs in one of the largest university hospitals in Italy, in order to examine the association between maternal environmental exposures and intrauterine growth restriction (IUGR) and the risk of premature birth. The study will also evaluate the association of maternal exposures and the health and growth of infants and children up to 24 months of age., Methods: The study entails the set-up of a case-control study within a birth cohort. With approximately 4,000 annual deliveries, we aim to enroll 140 cases (newborns with IUGR and premature birth) and 280 controls per year, from September 2022. A comprehensive questionnaire will be used to gather information about various types of maternal environmental exposures before and during pregnancy. We will collect biological samples from both mothers and newborns (including vaginal swab, placenta sample, blood, saliva, meconium, and bronchoalveolar lavage fluid) at birth and within the early hours of the newborn's life. We will perform laboratory examinations including dosage of heavy metals and essential elements, investigation of placental distress and fetal brain damage of biomarkers, analysis of microbiota and of DNA methylation profile. We will conduct clinical follow-up assessments in both cases and controls at months 12 and 24 and we will collect anthropometric data, feeding types with particular reference to breastfeeding and its duration, pediatric emergency room visits, hospitalizations, medication usage, known allergies, and neuropsychological development., Discussion: The Generation Gemelli case-control study holds the promise of significantly enhancing our comprehension of how maternal environmental exposures relate to the health of children and the broader population. The study of the exposome will provide insights into the relationships between environmental exposures, epigenetic changes and health outcomes during the first 1000 days of life and onward., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2025 Villani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The coronavirus disease 2019 (COVID-19) emergency has represented a profound upheaval in the dynamics of infectious diseases transmission worldwide. This phenomenon has been at least in part driven by the introduction of non-pharmaceutical interventions (NPIs), implemented to counteract viral transmission. Our study aimed to assess the magnitude and the features of the impact of the COVID-19 pandemic on the incidence of notifiable infectious diseases (NIDs) in the Lazio region, Italy., Methods: Data on NIDs in the Lazio Region with symptom onset date included in the time interval from 1 January 2017 to 31 December 2023 were collected from different surveillance system databases available at SERESMI/Lazio Region Unit and classified into five categories based on the main transmission route of the disease. Descriptive statistics were performed and interrupted time series (ITS) analysis was used to assess the effect of the COVID-19 pandemic and subsequent recovery period on monthly NIDs cases., Results: Immediately after the start of the COVID-19 pandemic, a significant, sharp and immediate reduction in monthly cases was recorded for all NIDs (-86.73%), regardless of the transmission route. The decrease was particularly significant for vector-borne, food-borne and respiratory-transmitted diseases (RDs), and in general in females. During the COVID-19 recovery phase, monthly cases of all NIDs showed a significant positive level change, particularly significant for sexually transmitted/blood-borne diseases, contact diseases and RDs., Discussion: The COVID-19 pandemic has been responsible for the disruption of all NIDs transmission patterns, while the magnitude and dynamics of its effects varied depending on the transmission route; furthermore, the impact of the pandemic wave was still noticeable during the post-COVID-19 era and the incidence trajectories of NIDs in this phase were peculiar for each disease category., Competing Interests: Declarations. Ethics approval and consent to participate: For studies of this type, approval from an Ethical Committee and formal consent are not required because patients’ information, which are pseudonymized, come from Regional surveillance systems for infectious diseases, all deriving from regulatory provision. For the same reason, the absence of informed consent (and an evaluation by an Ethics Committee) is legitimated by: Regulation (EU) 2016/679; Protection of Personal Data, Authorization 15 December 2016 n. 9/2016; Legislative Decree 10 August 2018, n. 101.” Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This paper presents the results of the human biomonitoring of ten urinary OH-PAHs (hydroxylated polycyclic aromatic hydrocarbon) in a cohort of workers at an incinerator in Turin, Italy. Long-term exposure was assessed through repeated measurements at three time points: before the startup (T0), after 1 year (T1), and after 3 years (T2). Paired data were available for 26 subjects, seven administrative workers (AWs) and 19 plant workers (PWs). Short-term exposure was assessed by comparing start-end shift measurements. Due to the non-normal distribution of the data, the nonparametric Cuzick's test for trend and the Wilcoxon signed-rank test for paired samples were used. Neither the trend nor the T0-T2 comparison tests resulted in statistically significant outputs in the two groups (q-value > 0.05), even when controlling for smoking habits. In relation to PWs, some of the metabolites were higher at T2 with respect to T0, but no linear increase was found. Conversely, 1-OH-PYR (ng/g creatinine) showed lower median values at T1 (61.5) and T2 (67) compared to the baseline (151.3). Similarly, short-term comparisons yielded no significant results, with rather overlapping distributions of values. Overall, no significant increases in metabolite levels were detected as a result of occupational exposure in the incinerator workers considered. These findings align with previous results for metals and ambient air measurements.

The COVID-19 pandemic has left an indelible mark globally, presenting numerous challenges to public health. This crisis, while disruptive and impactful, has provided a unique opportunity to gather precious clinical data extensively. In this observational, case-control study, we utilized data collected at the Azienda Sanitaria Universitaria Friuli Centrale, Italy, to comprehensively characterize the immuno-inflammatory features in COVID-19 patients. Specifically, we employed multicolor flow cytometry, cytokine assays, and inflammatory biomarkers to elucidate the interplay between the infectious agent and the host's immune status. We characterized immuno-inflammatory profiles within the first 72 hours of hospital admission, stratified by age, disease severity, and time elapsed since symptom onset. Our findings indicate that patients admitted to the hospital shortly after symptom onset exhibit a distinct pattern compared to those who arrive later, characterized by a more active immune response and heightened cytokine activity, but lower markers of tissue damage. We used univariate and multivariate logistic regression models to identify informative markers for outcome severity. Predictors incorporating the immuno-inflammatory features significantly outperformed standard baselines, identifying up to 59% of patients with positive outcomes while maintaining a false omission rate as low as 4%. Overall, our study sheds light on the immuno-inflammatory aspects observed in COVID-19 patients prior to vaccination, providing insights for guiding the clinical management of first-time infections by a novel virus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Margiotta, Sozio, Del Ben, Beltrami, Cesselli, Comar, Devito, Fabris, Curcio, Tascini and Sanguinetti.)

BackgroundToscana virus (TOSV) is transmitted to humans through bites of infected sand flies. Neuroinvasive TOSV infections are leading causes of meningitis/encephalitis in southern Europe and notifiable in Italy since 2016. In 2022-23, Italy experienced extreme climate anomalies and a concomitant increase in mosquito and tick-borne disease transmission.AimTo identify the spatiotemporal distribution and risk groups of neuroinvasive TOSV infections in Italy in 2022-23 vs 2016-21.MethodsWe retrospectively described all autochthonous, laboratory-confirmed neuroinvasive TOSV cases notified to the national surveillance system in 2016-23 using frequencies, proportions, incidences and incidence risk ratios (IRRs) with 95% CIs, stratified by year, sex, age, region/autonomous province (AP) of infection/exposure and infection/exposure municipality by urbanisation level.ResultsIn 2022-23, 276 cases were notified (average annual incidence: 2.34/1,000,000 population) vs 331 cases in 2016-21 (0.92/1,000,000), with increased incidence extending into September. In 2022-23, infections were acquired in 12/21 regions/APs, predominantly in Emilia Romagna (57.6%; 159/276) as in 2016-21, including four regions/APs with no local infections in 2016-21. Similar to 2016-21, during 2022-23 residence in rural municipalities (vs urban), male sex, working age (19-67 years) and age > 67 years (vs ≤ 18 years) were identified as risk factors with IRRs of 2.89 (95% CI: 2.01-4.17), 2.17 (95% CI: 1.66-2.84), 5.31 (95% CI: 2.81-10.0) and 5.06 (95% CI: 2.59-9.86), respectively.ConclusionItaly experienced a nearly 2.6-fold increase in neuroinvasive TOSV incidence in 2022-23 vs 2016-21. Raising public awareness on risk factors and personal protection measures may enhance prevention efforts.

Introduction: During the COVID-19 Pandemic, the use of digital devices during work activities has increased with important repercussions on the psychological and physical well-being of the employees. The aim of this study was to investigate the prevalence of musculoskeletal and visual disorders related to the use of computers and home workstation., Methods: The study is a cross-sectional study. A checklist, from the National Institute of Health, was administered to white collar workers of a large international pharmaceutical company based in Italy., Results: Our study showed that postural breaks have a protective effect on neck/shoulder pain (OR 0.32, CI 0.16-0.62), back and lower extremity pain (OR 0.35, CI 0.18-0.69), and eye burning (OR 0.50, CI 0.27-0.94) of study participants., Conclusions: The research recommends that remote employees who often change their workstations should establish a suitable work environment and obtaining enough risk training from an occupational physician. This is essential for maintaining their mental and physical well-being.

Introduction: The latest research in ischaemic stroke pathogenesis is directed to unveil what is inside embolic stroke of undetermined source (ESUS). Whether vulnerable non stenotic carotid plaques (NSTEPS), i.e. atherosclerotic lesions in carotid arteries determining a stenosis lower than 50%, may represent a cause of stroke in ESUS is a matter of debate. We aimed to study the prevalence of NSTEPS in an ESUS population., Patients and Methods: We retrospectively identified a consecutive ESUS population admitted to the Stroke-Unit of Careggi Hospital, Italy from 2019 to 2022. Characteristics of atherosclerotic plaques (thickness, ulceration, hypodensity) and their location (ipsilateral versus contralateral to the stroke) were studied on carotid CT angiography (CTA). Follow-up data were recorded up to 24 months after stroke., Results: We identified 57 ESUS patients with unilateral ischaemic lesions studied with CTA; 53 (93%) had an ipsilateral carotid plaque, 81% contralateral, (p = 0.754) and 74% both. Plaques ipsilateral to stroke were ≥ 3 mm thick in 15 (28%) patients; hypodense in 14 (26%) and ulcerated in 5 (9%). The frequency of hypodensity was higher in ipsilateral compared to contralateral plaques (26% vs. 13%, p = 0.039) and ulceration was around four times more frequent, although not statistically significant (9% vs. 2%, p = 0.219). At follow-up, six patients had stroke recurrence (11%), 2 of them were in the same vascular territory of the former., Discussion and Conclusions: Our data suggest that plaques ipsilateral to stroke seem to be more frequently vulnerable and consequently more prone to embolization. Prospective data are needed to clarify the causal role of NSTEPS in ESUS., Competing Interests: Declarations. Ethical approval: Ethical approval was waved because of the retrospective nature of the study. Informed consent: Written informed consent was obtained from the patients for their anonymized information to be published in this article. Conflicting interests: The authors have no conflicts of interest to declare., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Monitoring biologic drug therapy during pregnancy in women with immune-mediated inflammatory diseases (IMIDs) is crucial to ensure treatments align with evidence-based practices., Research Design and Methods: A retrospective cohort study based on healthcare claims data from eight Italian regions was conducted, analyzing deliveries between 2009 and 2021. The study included women receiving biologic drugs within nine months before their last menstruation. Exposures to biologics, conventional disease-modifying anti-rheumatic drugs (DMARDs) and symptom-relieving medications were assessed in the trimesters (T) before, during and after pregnancy. Factors influencing biologic treatment persistence during pregnancy were analyzed., Results: A cohort of 1,763 deliveries was considered. Biologic drugs were prescribed for rheumatic (33.6%), dermatological (32.6%), and gastrointestinal diseases (28.4%). Biologic use declined during pregnancy (TI = 37.3%; TII = 17.6%; TIII = 11.3%), increasing again postpartum. During pregnancy, there was increased use of symptom-relieving medications for rheumatic diseases and DMARDs for gastrointestinal diseases. Factors associated with continued biologic treatment included being older than 35 years and the region of delivery., Conclusions: This study found a decrease in biologics drug use during pregnancy and highlights the necessity for personalized therapeutic approaches. Geographic variations in biologic drug use emphasize the need for educational initiatives about the risk-benefit profiles of these therapies during pregnancy.

Introduction: West Nile Virus (WNV) is a significant public health concern in southern Europe, with meteorological, climatic, and environmental factors playing a critical role in its transmission dynamics. This study aims to assess the short-term effects of meteorological variables on the incidence of WNV in five Italian regions in Northern Italy from 2012 to 2021., Methods: Linking epidemiological data from the national surveillance system and local meteorological data, we conducted a Case-Time Series analysis to examine the association between WNV incident cases and temperature, humidity, and precipitation recorded up to ten weeks before case occurrence at the local administrative unit level. We employed conditional quasi-Poisson regression and distributed lag non-linear models to explore delayed effects., Results: Our study analyzed 1110 autochthonous human cases of WNV. We found a positive association between WNV incidence and weekly mean temperature recorded between one to nine weeks before the diagnosis, with the highest effect at one week lag (IRR: 1.16; 95% CI 1.11-1.21). An increase in weekly precipitations between the sixth and ninth weeks before diagnosis was also positively associated with WNV incidence. Variations in minimum weekly humidity did not show a consistent impact., Conclusions: Our findings underscore the influence of temperature and, to a lesser extent, precipitation on WNV incidence in Northern Italy, highlighting the potential of climatic data in developing early warning systems for WNV surveillance and public health interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This retrospective cohort study evaluated the effectiveness of maternal vaccination against COVID-19 in reducing the risk of SARS-CoV-2 infection in infants younger than 12 months. The study, conducted at the "Policlinico" University Hospital of Bari, included 3346 newborns and their mothers. The study explored the degree of protection offered by maternal vaccination depending on the timing, type, and trimester of vaccination, also taking into account the mother's history of infection. We compared the incidence rate of infection between children of vaccinated and unvaccinated mothers; the values were 10.2% and 18.1%, respectively, and the difference was statistically significant. The overall effectiveness of the vaccine against the infection was 45%. Further analysis revealed increasing efficacy as the doses of vaccine administered to the mother increased and in case of a previous history of maternal infection. Dual immune stimulation (vaccination and natural infection) was 83% effective in preventing infection among newborns. The multivariable models confirmed the protective effect of vaccination with all types of vaccines used. The analysis of infection's incidence in newborns revealed an interesting temporal trend, with increasing incidence with time, suggesting a possible correlation with the persistence of maternal antibodies or with the gradual weaning. The results on the protective capacity of vaccines are in line with the global literature. Strengths of study include sample size, robust methodology, and multivariate analyses. Institutions could intensify awareness campaigns to encourage both pregnant women and all those who would like to become pregnant to receive SARS-CoV-2 vaccination.

With the pandemic, there has been a global reduction in influenza virus circulation, with WHO reporting, during 2021/22 season, laboratory testing positivity rate for influenza of less than 3%. Influenza surveillance systems anticipated a peak of influenza cases in the Northern Hemisphere during 2022/2023 season and the Italian Ministry of Health recommended the routinary co-administration of influenza with bivalent COVID-19 vaccines for the 2022/2023 season. At the Vaccination Hub of the University Hospital (UH) of Palermo, more than 700 subjects received influenza and COVID-19 booster doses in co-administration, during the 2021/2022 season. A cross-sectional study analyzing attitudes and factors associated with adherence to influenza and COVID-19 seasonal vaccines co-administration was conducted at the Vaccination Hub of the UH of Palermo, from October to December 2022. Among the 1,263 respondents, 74.7% ( n  = 944) received the co-administration of seasonal influenza and COVID-19 vaccines. The main reason reported for accepting it was confidence in the recommendations of the Health Ministry (41.3%). At the multivariable analysis, subjects aged ≤ 59 y old (AdjOR: 2.48; CIs95%: 1.89-3.65), male (AdjOR: 1.51; CIs95%: 1.27-1.75), Health-care professionals (HCPs) (AdjOR: 1.66; CIs95%: 1.08-2.57) and those who received co-administration during 2021/2022 (AdjOR: 41.6; CIs95%: 25.5-67.9) were significantly more prone to receive co-administration during 2022/23 season. From data obtained, the role of HCPs in accepting and then promoting co-administration of COVID-19 and influenza vaccines is crucial, as well as receiving co-administration in the previous season that represented the main drive for accepting it in the following seasons, supporting safety and effectiveness of this procedure.

The age estimation of skeletal remains still represents a central issue not only for the reconstruction of the so-called "biological profile," but mostly for the palaeodemographic investigation. This research aims at verifying the feasibility of the adult age estimation method developed on living people by Pinchi et al. (2015 and 2018), for estimating the age at the death of 37 subjects from ancient populations found in two different Italian necropolis of archaeological interest (Mont'e Prama and Florence, X-IX century B.C and V-VI century A.D respectively). The method is conservative and based on a geometrical approximation of dental volumes of the upper central left incisors on CBCT scans. The statistical distribution of the age and errors followed the Bayesian approach proposed by Sironi et el. (2018) applying the "a priori" values according to the estimates/classification obtained with anthropological methods (morphological). Results show higher accuracy for Mont'e Prama remains than for the Florentine sample due to the different characteristics of the two ancient populations (estimates varying from 18.4 up to 28.7 years with a maximum error of 6,14 years for Mont'e Prama, and from 15.88 up to 43.37 years with a minimum error of 1 year up to a maximum error of 7,85 years for Florence). The method proposed and validated on modern living people can represent a reliable tool for estimating the age of ancient human remains with a significant palaeodemographic value for archaeologists/anthropologists. Mont'e Prama sample could be defined as a homogenous group of males aged around 20-30 years, probably warriors, soldiers, or athletes; Florentine sample as an inhomogeneous group of males and females from different families buried all together in a small area out of the city due to the probable occurrence of a special healthy emergency in the city., Competing Interests: The authors report no conflicts of interest in this work., (Copyright© 2024 IOFOS This work is published and licensed by International Organization for Forensic Odonto-Stomatology.)

Although body weight (BW) and body surface area (BSA) are utilized to establish the appropriate dosage of anticancer drugs, their distribution in cancer patients is poorly studied, making it challenging to predict the amount of drug use and related costs of BW or BAS-dosed regimens. This study investigates the distribution of BW and BSA in adults with selected cancers who initiated systemic anticancer treatment in the eastern Emilia-Romagna region hospitals between 2011 and 2021. BW and BSA were collected at the first cycle of each new treatment line, with multiple measurements for patients receiving various treatments or treating for other primary malignancies. Results were grouped by sex, tumor site and treatment setting, and the normal distribution hypothesis was tested for each group. Both linear regression model and quantile regression at the 50th, 25th and 75th percentiles were run to explore the factors influencing BSA. The analysis included 20,634 treatment lines and the corresponding BW and BSA measures from a sample of 13,036 patients. The average BW was 68.05kg (64.20kg for females and 75.07kg for males) and the average BSA was 1.76m2 (1.66m2 for females and 1.87m2 for males). In women, the highest BW was in breast and colon groups, while in men, it was associated with prostate and rectum cancers. The model indicated significant association between BSA, age, sex and tumor localization. Notably, stomach and lung cancers were linked to lower BSA for both sexes (for females -0.081 and -0.041m2 respectively compared to those with breast cancer). Advanced settings were related to lower BSA than neoadjuvant treatment, especially for stomach cancer patients, who experienced a weight loss of 3 to 6kg as therapy progressed. The regression models for predicting BSA can assist regulatory bodies in determining reimbursement for new chemotherapy drugs and help hospitals forecast drug utilization and expenditure more accurately., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2024 Danesi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The availability of care recommendations has improved survival and delayed the progression of clinical signs in Duchenne muscular dystrophy. The aim of the study was to perform a nationwide survey investigating the prevalence, age distribution, and functional status of Duchenne muscular dystrophyin Italy., Methods: The survey was performed by collecting data from all 31 reference centers for Duchenne muscular dystrophy in Italy using a structured form. We assessed age distribution, motor function, and the need for respiratory and nutritional support to evaluate their prevalence in different age and functional subgroups., Results: The estimated prevalence was 1.65/100,000 (3.4/100,000 males). There were 972 boys and adults with a confirmed diagnosis of Duchenne, of age ranging between 6 months and 48 years (mean = 16.5). Over 59% were below the age of 18 years and the remaining 41% were adults. Over 43% were ambulant and 57% non-ambulant; 14.7% were steroids naive (mean 20.6 years), 75% are currently on steroids (mean 14.6 years) with 604 on the daily regime, 126 intermittent. Nearly 73% did not require any ventilatory support, 16% had NIV ≤ 12 h, 9% > 12 h, and 1.4% had a tracheostomy. More than 82% did not require any nutritional support, 13% required food modification/semisolid and 4.4% had a G-tube., Conclusions: Our findings provide information to be used not only for epidemiological purposes but also for possible trial design to include older non-ambulant patients who until recently have been excluded and for whom clinical information is limited. What is Known • Duchenne muscular dystrophy is a progressive disorder associated with reduced survival. • As part of the disorder there is also a progressive loss of important milestones, including loss of ambulation, and increased need for respiratory and nutritional support. What is New • Our nationwide survey provides prevalence, age distribution, and functional status for Duchenne muscular dystrophyin Italy including both boys and adults. • Our findings can be used for epidemiological purposes and for possible trial design., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Catholic University of Rome. Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Among preterm newborns undergoing resuscitation, delayed cord clamping for 60 seconds is associated with reduced mortality compared with early clamping. However, the effects of longer durations of cord clamping with respiratory support are unknown., Objective: To determine whether resuscitating preterm newborns while keeping the placental circulation intact and clamping the cord after a long delay would improve outcomes compared with umbilical cord milking., Design, Setting, and Participants: This randomized clinical trial (PCI Trial) was conducted at 8 Italian neonatal intensive care units from April 2016 through February 2023 and enrolled preterm newborns born between 23 weeks 0 days and 29 weeks 6 days of gestation from singleton pregnancies., Interventions: Enrolled newborns were randomly allocated to receive at-birth resuscitation with intact placental circulation for 180 seconds or umbilical cord milking followed by an early cord clamping (within 20 seconds of life)., Main Outcomes and Measures: The primary outcome was the composite end point of death, grade 3 to 4 intraventricular hemorrhage, and bronchopulmonary dysplasia at 36 weeks of postconception age. Prespecified secondary end points were the single components of the composite primary outcome. An intention-to-treat analysis was conducted., Results: Of 212 mother-newborn dyads who were randomized, 209 (median [IQR] gestational age, 27 [26-28] weeks; median [IQR] birth weight, 900 [700-1070] g) were enrolled in the intention-to-treat population; 105 were randomized to the placental circulation intact group, and 104 were randomized to the cord milking group. The composite outcome of death, grade 3 to 4 intraventricular hemorrhage, or bronchopulmonary dysplasia occurred in 35 of 105 newborns (33%) in the placental circulation intact group vs 39 of 104 newborns (38%) in the cord milking group (odds ratio, 0.83; 95% CI, 0.47-1.47; P = .53)., Conclusions and Relevance: In a randomized clinical trial of preterm newborns at 23 to 29 weeks' gestational age, intact placental resuscitation for 3 minutes did not lower the composite outcome of death, grade 3 to 4 intraventricular hemorrhage, or bronchopulmonary dysplasia compared with umbilical cord milking., Trial Registration: Clinicaltrials.gov Identifier: NCT02671305.

Background: Celiac disease (CD) is an inflammatory enteropathy that has been associated to obstetric and gynecological disorders. However, it is still not adequately tested by gynecologists due to the misconception that it is solely a gastrointestinal disease. This underestimation requires the development of targeted interventions., Purpose: This study aims to evaluate the association between CD and obstetric/gynecological complications, highlight the importance of informing patients about CD manifestations, and assess the patient satisfaction with the information provided by healthcare professionals on the disease., Methods: A digital survey was administered to celiac women via the Italian Celiac Association's website., Results: We analyzed 493 questionnaires. Obstetric and gynecological disorders led to the diagnosis of CD in 11.7% of interviewed. The study revealed that untreated CD patients are more predisposed to miscarriages (41.8% vs 34% before/after diagnosis, respectively, p = 0.111), anemia in pregnancy (71.4% vs 40.4% before/after diagnosis, respectively, p < 0.001) and the risk of low birth weight (newborns weighing < 1500 g were 4.0% before and 1.1% after the gluten-free diet, p = 0.028). Women with CD, both before and after gluten-free diet, had higher infertility rates (about 19%) than the general population. Additionally, 73% of interviewees were dissatisfied with the information they received from health professionals about the reproductive implications of CD., Conclusion: Our research contributes to a deeper understanding of the intersection between CD and reproductive outcomes, highlighting the main obstetric and gynecological problems related to it. It emphasizes the importance of patient's perspective and the need for greater awareness about celiac disease from healthcare workers., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethics approval and consent to participate: The project was approved on 04/04/2023 and was performed in accordance with the ethical standard as laid down in the Declaration of Helsinki. The data were anonymized and a written informed consent was obtained from all the patients. Consent for publication: All authors have provided consent for publication., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Circular feeds, such as grain dry distillers, citrus pulp, cane molasses, and potatoes peels, are co-products of biomass processes. They are currently proposed in animal nutrition to improve the environmental and economic sustainability of the food production chain. In this paper, we report a case study involving fipronil, a pesticide currently not authorized for agriculture within the EU, but used in the Americas, Eastern Europe, and Asia. Fipronil was found at a mean level of 0.49 mg/kg, in a grain dry distiller batch administered to dairy cows. This finding, along with other evidence of potential fipronil presence in feed materials, prompted us to evaluate the risk to food safety and food security from 12 different conventional and sustainable feeding regimens. To this purpose, we considered a fipronil feed-to-milk carry-over rate of 0.52, the tolerance levels in fodders and food from The EU, Codex Alimentarius, and US-EPA, and the Acceptable Daily Intake (ADI) of 0.0002 mg/kg body weight for adverse effects on thyroid function in dairy cows. Under a conservative scenario, fipronil-contaminated potato peels and grain distillers in the feeding regimens may play a pivotal role in exceeding the EU Maximum Residue Level (MRL) in bovine milk and fat (0.005 and 0.030 mg/kg, respectively). Hay-based diets with soybean hulls and cane molasses show negligible risks (Hazard Index ∼ 1). In all cases, the ADI exceedance suggests the need to evaluate thyroid function in dairy cows exposed to fipronil as a food security factor.

Microplastics are ubiquitous in aquatic ecosystems and lakes are considered important sinks for this contaminant. In this study, we assessed for the first time the occurrence and spatial distribution of microplastics in surficial waters and sediment of a small alkaline lake located in the National Park of Pantelleria Island (Central Mediterranean Sea). The island is small, scarcely populated, not industrialized and ∼70 km far from the southern European and northern African shores. Water samples were collected in triplicates in different sectors of the lake using a 10 L metal bucket, while sediment sampling was carried out at seven stations along the lake shoreline, plus one station at 3.6 m depth. Results show a homogeneous distribution of microplastic in surface waters, dominated by fibers (∼90%), with a mean concentration of 0.13 ± 0.04 MP/L, which is lower than most of the lakes worldwide. Conversely, microplastics in sediment had a higher proportion of fragments and films (50%) and their concentrations range from 0 to 540 MP/kg. The highest abundance was recorded in the western sector, where most of touristic activities concentrate, and at the 3.6 m depth station, thus suggesting that the deeper parts of the lake may retain the majority of microplastics entering the system. This study shows that even in small lakes far from major anthropic pressures, sediment may contain microplastics in striking abundances, pointing out the need to assess rural and remote lakes, at present much understudied compared to lakes in highly populated regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aims: Since 2016, biallelic mutations in the membrane metalloendopeptidase (MME) gene have been associated with late-onset recessive CMT2 (CMT2T). More recently, heterozygous mutations have also been identified in familial and sporadic patients with late-onset axonal neuropathy, ranging from subclinical to severe. This indicates that the heterozygous MME variants may not be fully penetrant, or alternatively, that they may be a potential risk factor for neuropathy. Here, we describe the clinical, neurophysiological, and genetic findings of 32 CM2T Italian patients., Methods: The patients were recruited from four different Italian referral centers. Following a comprehensive battery of neurological, electrophysiological, and laboratory examinations, the patients' DNA was subjected to sequencing in order to identify any variants in the gene. Bioinformatic and modeling analyses were performed to evaluate the identified variants' effects., Results: We observe a relatively mild axonal sensory-motor neuropathy with a greater impairment of the lower extremities. Biallelic and monoallelic patients exhibit comparable disease severity, with an earlier onset observed in those with biallelic variants. When considering a subgroup with more than 10 years of disease, it becomes evident that biallelic patients exhibit a more severe form of neuropathy. This suggests that they are more prone to quick progression., Interpretation: CM2T has been definitively defined as a late-onset neuropathy, with a typical onset in the fifth to sixth decades of life and a more rapidly progressing worsening for biallelic patients. CMT2T can be included in the neuropathies of the elderly, particularly if MME variants heterozygous patients are included., (© 2024 The Author(s). Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.)

Background: COVID-19 overwhelmed all healthcare workers, especially nurses, who worked tirelessly in patient care in extremely stressful situations. Italy, with its hospital overcrowding and staff shortages, exacerbated these negative consequences., Design: A three-wave prospective longitudinal-design was adopted to use validated scales to examine the trend of stress, anxiety, depression and resilience on the professional quality of life of nurses who worked during the pandemic. During an 8-month period, a sample of 411 individuals was recruited and surveyed three times., Results: Resilience showed an increasing positive trend from the first to the third wave, increasing its effects on the outcomes and demonstrating its important protective role. The compassion fatigue showed progressively higher scores in the three waves, indicating greater workload perception and greater difficulty in managing the patients' perceived stress. Burnout increased in the first compared to second waves but decreased significantly in the third wave, due to the effect of resilience on burnout that was significantly stronger in the third wave., Conclusion: Our findings align with the literature about the role of resilience and emphasize the importance of investing in strategies aimed at developing resilience in healthcare workers and providing prevention and assistance to them in terms of job demands and unsustainable stressors., (© 2024 John Wiley & Sons Australia, Ltd.)

Influenza is an important public health issue given its significant burden of disease. In Italy, the unsatisfactory coverage rate in people ≥65 years underlines the need to improve the current vaccination pathway. This study aims to define an integrated pathway across primary and secondary care, facilitated by a digital clinical decision support system (CDSS), to enhance vaccination coverage in people ≥65 years by actively recruiting patients in hospitals and administering vaccination. Moreover, the study seeks to gauge the potential epidemiological and economic impact of this approach. The methodology consisted of two main phases: definition of the integrated pathway and CDSS and estimation of the potential epidemiological and economic impact resulting from the implementation of the pathway in the whole Lazio region. Assuming an increase of influenza vaccination coverage from the current rate of 60% to 65% in ≥65 years old population in the Lazio region thanks to the pathway implementation, an increase of 8% in avoided influenza cases, avoided influenza- or pneumonia-related hospitalizations and avoided influenza-related outpatient visits was estimated with a relative increase in savings for hospitalizations and outpatient visits of up to 11.85%. Setting the vaccination coverage at 70%, the impact is doubled. Alongside offering a predictive estimate of the pathway's potential impact, both epidemiological and economic, this project, with its robust methodology, may serve as a scalable and transferable model for enhancing vaccination coverage at national and international level., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Dengue virus (DENV) has been expanding its range to temperate areas that are not usually affected, where the spread of vectors has been facilitated by global trade and climate change. In Europe, there have been many cases of DENV imported from other regions in the past few years, leading to local outbreaks of DENV among people without travel history. Here we describe the epidemiological and molecular investigations of three transmission events locally acquired DENV infections caused by serotypes 1, 2 and 3, respectively, in the Latium Region from August to November 2023. Next-generation or Sanger sequencing was used to obtain the whole genomes, or the complete E-gene of the viruses, respectively. The structure of the DENV-1 and DENV-3 sequences was analysed to identify amino acid changes that were not found in the closest related sequences. The major cluster was supported by DENV-1 (originated in South America), with 42 autochthonous infections almost occurring in the eastern area of Rome, probably due to a single introduction followed by local sustained transmission. Seven DENV-1 subclusters have been identified by mutational and phylogenetic analysis. Structural analysis indicated changes whose meaning can be explained by the adaptation of the virus to human hosts and vectors and their interactions with antibodies and cell receptors.

Objective: This study aims to explore the association between liver steatosis and fibrosis, as assessed by Fibroscan, and the onset of type 2 diabetes in overweight, medication-free men and women., Methods: We analyzed data from 164 participants with overweight or obesity (41.4 % male), including 39 individuals (23.8 %) with type 2 diabetes. All participants underwent Fibroscan to evaluate liver steatosis (CAP > 275 dBm) and fibrosis (liver stiffness > 8.2 kPa). Diabetes was diagnosed using fasting glucose, 2-hour glucose tolerance test (OGTT), and HbA1c levels., Results: Liver steatosis was significantly more prevalent in individuals with diabetes (89.7 % vs 52 %, P < 0.001). Liver fibrosis was observed in 35.9 % of subjects with diabetes (vs 13.6 %, P = 0.002). Mean CAP (P < 0.001) and kPA (P = 0.006) values were significantly higher in the group with diabetes. Significant associations between CAP (MD: 30.87, P = 0.009) and liver stiffness (MD: 2.454, P = 0.006) with diabetes were found, independent of other variables. Additionally, liver steatosis was independently associated with elevated HOMA-IR levels (P = 0.001)., Conclusion: Elevated liver steatosis and fibrosis are both linked to type 2 diabetes, independent of traditional risk factors. These findings support screening for diabetes in individuals with significant steatosis and fibrosis and vice versa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Antimicrobial resistance (AMR) represents a critical global threat, compromising the effectiveness of antibacterial drugs as bacteria adapt and survive exposure to many classes of these drugs. This phenomenon is primarily fueled by the widespread overuse and misuse of antibacterial drugs, exerting selective pressure on bacteria and promoting the emergence of multi-resistant strains. AMR poses a top-priority challenge to public health due to its widespread epidemiological and economic implications, exacerbated not only by the diminishing effectiveness of currently available antimicrobial agents but also by the limited development of genuinely effective new molecules. In addressing this issue, our research aimed to examine the scientific literature narrating the Italian situation in the common European context of combating AMR. We sought to delineate the current state of AMR and explore future prospects through an analysis of strategies to counter antibacterial drug resistance. Adopting the "One Health" model, our objective was to comprehensively engage diverse sectors, integrate various disciplines, and propose programs, policies, and regulations. This narrative review, based on PubMed research related to antibiotic resistance, emphasizes the urgent need for a coordinated and proactive approach at both national and European levels to mitigate the impact of AMR and pave the way for effective strategies to counter this global health challenge., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: The authors consent to the publication of the manuscript. Competing interests: The authors declare no competing interests. Disclaimer: The authors declare that the opinions expressed are of a personal nature and do not in any way commit the responsibility of the Administrations to which they belong., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Abrocitinib is a JAK-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD). We conducted a 16-week multicenter retrospective study to assess the short-term effectiveness and safety of abrocitinib in patients with moderate-to-severe AD., Our retrospective study included 85 adult patients from 14 Italian Dermatology Units affected by moderate-to-severe AD treated with abrocitinib 100/200 mg., Methods: Effectiveness of abrocitinib at weeks 4 and 16 was assessed by using the Eczema Area and Severity Index (EASI), the Investigator Global Assessment (IGA), the peak pruritus and sleep- Numerical Rating Scale (PP-NRS and S-NRS, respectively)., Results: At week 16, improvement of at least 90% in EASI (EASI90) and IGA 0/1 was observed in 49.4% and 61.2% of patients, respectively. A reduction of at least 4 points in PP-NRS and S-NRS compared with baseline was achieved by 70.6% of patients for both endpoints. No significant safety reports were observed during the study period. Naïve patients had better rates of EASI 90 compared to patients who previously failed dupilumab. Conclusion: Our data confirm the effectiveness of abrocitinib in a real-world setting with better clinical responses at weeks 4 and 16, compared with Phase-III clinical trials. Longer analyses are required to further establish the safety profile of abrocitinib.

Purpose: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight., Materials and Methods: Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2., Results: After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively., Conclusions: Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.

Background: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long-term treatment outcomes is currently available to inform clinical decisions., Objectives: To describe the long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD., Methods: A multicentre, retrospective, dynamic cohort study was conducted to assess long-term effectiveness and safety of dupilumab in patients with moderate-to-severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria [defined as the simultaneous achievement of a 90% reduction in Eczema Area and Severity Index score, itch-numeric rating scale (NRS) score ≤ 1, sleep-NRS score ≤ 1 and Dermatology Life Quality Index ≤ 1] were investigated., Results: In total, 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506/2309 (21.9%), 769/1959 (39.3%), 628/1247 (50.4%), 330/596 (55.4%) and 58/106 (54.7%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AEs) were mild and were observed in 373/2364 (15.8%), 166/2066 (8.0%), 83/1291 (6.4%), 27/601 (4.5%) and 5/110 (4.5%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AEs led to treatment discontinuation in < 1% of patients during the evaluated time periods., Conclusions: The high long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate-to-severe AD, regardless of clinical phenotype and course (persisting or relapsing) at baseline. Further research will be needed to investigate the effect of T helper cell 2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Since the beginning of mass vaccination campaign for COVID-19 in Italy (December 2020) and following the rapidly increasing vaccine administration, sex differences have been emphasized. Nevertheless, incomplete and frequently incoherent sex-disaggregated data for COVID-19 vaccinations are currently available, and vaccines clinical studies generally do not include sex-specific analyses for safety and efficacy. We looked at sex variations in the COVID-19 vaccine's effectiveness against infection and severe disease outcomes. We conducted a nationwide retrospective cohort study on Italian population, linking information on COVID-19 vaccine administrations obtained through the Italian National Vaccination Registry, with the COVID-19 integrated surveillance system, held by the Istituto Superiore di Sanità. The results showed that, in all age groups, vaccine effectiveness (VE) was higher in the time-interval ≤120 days post-vaccination. In terms of the sex difference in vaccination effectiveness, men and women were protected against serious illness by vaccination in a comparable way, while men were protected against infection to a somewhat greater extent than women. To fully understand the mechanisms underlying the sex difference in vaccine response and its consequences for vaccine effectiveness and development, further research is required. The sex-related analysis of vaccine response may contribute to adjust vaccination strategies, improving overall public health programmes.

Objectives: To investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk-benefit profiles in clinical practice., Design: Retrospective multicentrer cohort study., Setting: Four Italian regions (Lombardy, Veneto, Lazio, Sardinia)., Methods: Data were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI)., Main Outcome Measures: Mortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use., Results: The study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk-benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65)., Conclusions: The study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To evaluate midwives' level of stress and burnout during the COVID-19 Omicron phase in Italy. Secondary aims were to explore the impact of the pandemic on midwives' personal dimensions and professional activities and potential supporting strategies., Design: A mixed-methods study was undertaken from July to December 2022., Methods: Data were collected using a national online observational survey. Descriptive and inferential analyses were performed to evaluate stress, burnout and the impact of the pandemic on personal and professional dimensions. A deductive qualitative approach was used to analyse open-ended responses, that were merged with quantitative data following a convergent mixed-methods approach., Results: A total of 1944 midwives participated in the survey. The stress summary score mean was 10.34, and 562 midwives (28.91%) experienced burnout. The intention to reduce working hours was reported by 202 midwives (10.39%), with 60.40% (n = 122) of them experiencing burnout. The intention to leave clinical practice within the following 2 years was reported by 239 (12.29%), with 68.20% (n = 163) of them experiencing burnout. All the personal dimensions and professional activities considered were defined by more than half of midwives as being impacted 'Moderately' or 'To a great extent' by pandemic. Stress and burnout frequencies increased when the midwives' perception of the pandemic effects was higher. Potential supporting strategies described by midwives as the most important in increasing their ability to cope with the pandemic were 'Women's awareness of the midwives' role' (n = 1072; 55.14%) and 'Family and friends' emotional support' (n = 746; 38.38%)., Conclusion: Our findings suggested strategies to support a positive and safe working environment for midwives during a pandemic emergency, with potential transferability to similar contexts when human resources are lacking. It is recommended that maternity services provide the necessary resources for a safe and supportive working environment to prevent high stress levels and chronic burnout., Impact: Studies conducted during the first COVID-19 pandemic wave showed an increased level of stress, anxiety, burnout, post-traumatic stress disorder and depression experienced by healthcare professionals; moreover, midwives experienced drastic changes in care pathways and policies with struggles identified when providing high-quality woman-centred care following pandemic restrictions. Although it is recommended, there is lack of knowledge about long-term psychological effects of COVID-19 for midwives. Our study highlights that during the Omicron wave midwives experienced a high level of stress and burnout with an impact on individual dimensions and professional activities. Their stress and burnout were influenced by several factors, including restrictions in place, lack of organizational acknowledgement, work overload and need for extra childcare cover. Maternity services should provide the necessary resources for a safe and supportive working environment to prevent high stress levels and chronic burnout. Recommendations on how to facilitate this are suggested., Reporting Method: During the writing process, we referred to 'The Strengthening the Reporting of Observational Studies Epidemiology Statement', the guidelines for reporting observational studies from the Equator network., Patient or Public Contribution: No patient or public contribution. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Work overload conditions negatively impacted on the quality of maternity services. Improving organizational aspects, reducing working hours, promoting family and friends' emotional support and improving women's awareness of midwife's role were the main strategies reported by midwives. These suggestions for ensuring a positive and safe working environment for midwives during a pandemic emergency could potentially be applied to similar situations where human resources are lacking., (© 2024 John Wiley & Sons Ltd.)

Background: Tunneled central venous catheter (tCVCs) is a vascular access frequently employed in hemodialysis patients. Catheter-related bloodstream infections (CRBSI) are potentially life-threatening complications., Methods: We performed a retrospective survey regarding tCVCs prevalence as well as the CRBSI incidence and management within five hospitals in the Brescia province belonging to the "East Lombardy Nephrological Network"; this study was based upon 18 queries regarding the years 2020 and 2021., Results: The data collected refer to an overall hemodialysis population of 736 patients in 2020 and 745 patients in 2021. The prevalence of tCVCs was respectively 22.1% and 24.2% with the initial placement being performed with fluoroscopy support in 80% of the centers. CRBSI incidence was respectively 0.88 and 0.77 episodes per 1000 days of tCVC use. When the CRBI was caused by Staphylococcus Aureus (SA) or Pseudomonas, differently from the recommendation of the KDOQI guidelines, the removal or the substitution of the tCVC did not occur immediately at the time of the diagnosis of the infection but only when the specific antibiotic therapy failed. A nose swab aimed at identifying SA carriers was performed in 60% of centers. The policy regarding the referral to other specialists (infectious disease specialist and microbiologist) was heterogenous across the centers according to their specific logistics., Conclusions: This retrospective survey performed by the "East Lombardy Nephrological Network" within the Brescia province describes the prevalence of tCVCs use as well as the incidence and management of CRBSIs in the hemodialysis patients of this area. The clinical impact of the differences in terms of clinical approach detected compared to the KDOQI guidelines will need to be clarified ideally in prospective studies., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Invasive group A streptococci infections are increasing worldwide, mainly due to the emm1 lineage M1 UK emergence. Although this variant has recently been described in adult Italian patients, its circulation in children has not yet been established. Characterizing by whole genome sequencing 6 invasive group A streptococci strains isolated between 2022 and 2023, we highlighted M1 UK lineage circulation in pediatric patients in Italy., Competing Interests: The authors have no conflicts of interest to disclose. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The clinical relevance of avian metapneumovirus (aMPV) is growing in the poultry sector, especially in broiler farming, where no vaccination is administered in Italy. Given the naïve status of the birds, a serological survey was conducted in a densely populated area of Northern Italy, to evaluate aMPV circulation. Seven farms were selected and sampled in summer/fall, then sampling was repeated in the following season (winter/spring) to assess a possible seasonal effect. In each farm, fifteen birds were blood sampled towards the end of the cycle and sera were analyzed with an ELISA test. Clinical signs were reported in 5 out of 7 farms, although all farms were positive at both sampling points, except for one, which was negative at the first sampling. The seroprevalence within farm ranged from 26.6% to 100%, and antibody titres appear to increase with age. No seasonality effect was evidenced, whereas a farm effect was more distinct. aMPV circulation appears wide in Northern Italian farms, with different clinical outcomes that could be modulated by intrinsic characteristics of the farms. In absence of vaccination, serological monitoring can be a useful tool for viral entrance monitoring, although sampling timing should be evaluated in order to spot seroconversion after late infections., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite global immunization efforts, rubella remains a public health concern, particularly in high- and middle-income countries. This study focused on rubella seroprevalence in the province of Florence, Italy, aiming to identify susceptibility clusters, especially among women in their childbearing age., Methods: A cross-sectional study was conducted between April 2018 and December 2019, enrolling 430 adult subjects (age over 18 years). Serum samples were collected, and anti-rubella antibodies were quantified using the ELISA test. Data were analyzed descriptively and compared by sex, nationality, and age groups using statistical tests., Results: The overall rubella seroprevalence was high (92.3%), with no significant differences between genders or nationalities. Among childbearing-age females (18-49 years), the highest seroprevalence was observed in the 30-39 age group (94.1%). However, susceptibility clusters exceeding the 5% threshold set by WHO were identified, especially in females aged 40-49 years (7.0%)., Conclusions: Despite high overall seroprevalence, the study identified pockets of susceptibility, even in childbearing age women. Continuous monitoring, targeted immunization strategies, and public health interventions are recommended to maintain rubella elimination, emphasizing the importance of sustained vaccination efforts to protect vulnerable populations.

This paper describes the complexity of the clinical management of foreign minors suffering from cancer, through the clinical experience of an Italian referral center. The study includes 50 patients less than 18 years (22% of the patients admitted to the unit in 2023), 32 foreigners who were Italian resident and 18 who had come to Italy specifically to receive cancer treatment. Patients who migrate for healthcare reasons often arrive at the referral center with advanced disease or relapse. Numerous socio-cultural issues were reported. To address them, specific strategies were implemented to ensure equal and high-quality care for all patients, respecting their needs., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Stuccoes are very delicate decorative elements of Roman age. Very few of them survived almost intact to present days and, for this reason, they are of great interest to restorers and conservators. In this study, we combined metabarcoding and untargeted metabolomics to characterise the taxonomic and metabolic profiles of the microorganisms forming biofilms on the stuccoes located on the ceiling of the laconicum, a small thermal environment in the archaeological park of Baia (southern Italy). We found that some samples were dominated by bacteria while others by eukaryotes. Additionally, we observed high heterogeneity in the type and abundance of bacterial taxa, while the eukaryotic communities, except in one sample (at prevalence of fungi), were dominated by green algae. The metabolic profiles were comparable across samples, with lipids, lipid-like molecules and carbohydrates accounting for roughly the 50% of metabolites. In vitro and in vivo tests to remove biofilms on stuccoes using essential oils blends were successful at a 50% dilution for one hour and half. This integrative study advanced our knowledge on taxonomic and metabolic profiles of biofilms on ancient stuccoes and highlighted the potential impacts of these techniques in the field of cultural heritage conservation., (© 2024. The Author(s).)

Assessing historical changes in marine biodiversity at regional or local scales is often challenging due to insufficient long-term data for most marine organisms. Yet, these assessments are crucial to understanding potential long-term variation in the species pool in response to complex and interacting local and global environmental changes. Here, we performed a comprehensive review of scientific and grey literature, archival records and floristic data spanning over the last two centuries to reconstruct an updated and revised taxonomic dataset of macroalgae in the Gulf of Trieste (Northern Adriatic Sea), one of the most exposed to human-driven pressures and climatically vulnerable regions in the Mediterranean Sea. The subset of data from 1960 to present, encompassing nearly all available records, was used to assess the contribution of species replacement and gain/loss to temporal β-diversity and to test for changes in the taxonomic distinctness of the species pool over the past six decades. We identified 68 species that have never been recorded again since 1990, indicating their likely local extinction. The major change, however, was due to species replacement and to a reduction in the taxonomic breadth of macroalgal diversity, as highlighted by a significant decrease in the Average Taxonomic Distinctness of the species pool, especially along the Italian coast. The loss of species has mainly affected habitat-formers (e.g., Cystoseira sensu lato) and species with Atlantic/Circumboreal and Mediterranean affinities, which were replaced by turf-formers and species with Pantropical/Cosmopolitan/IndoPacific affinities. While multiple human impacts (e.g., coastal artificialisation, unbalanced N/P ratios) might have contributed to the ongoing change in macroalgal diversity, the observed decline of cold-affinity species in favour of warm-affinity species pointed out a critical role of exacerbating climatic changes. Our study demonstrated that historical reconstructions of species records coupled with effective indicators for the analysis of presence/absence data can help quantify long-term biodiversity changes and provide valuable insights into their possible causes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Annalisa Falace reports financial support was provided by University of Trieste. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Scuole che promuovono salute (Sps) is a model promoted by the World Health Organization and recognized at the European and national levels for promoting health and well-being at school. Pause Attive is an effective and evidence-based intervention to promote physical activity and reduce sedentary behaviour of children in the school setting. In the 2023-2024 school year, 348 schools joined the "Rete Lazio Sps" of which 99 joined the intervention Pause Attive for a total of 1.200 classes, more than 21.200 children involved and 1.500 teachers trained by health professionals of Asl. Pause Attive is a sustainable intervention for local health authority and effective in increasing movement and promoting attention and learning of children in the school setting.

Introduction: Cannabinoids are approved for spasticity and pain in multiple sclerosis (MS). In 2017 the prevalence of current users in the Italian general population was 10.2%, while data on Italian MS patients are limited., Methods: From March 2022 to February 2023, we conducted a multicenter, cross-sectional study. Adult MS patients completed an anonymous online survey. The primary outcome was the estimated prevalence of unprescribed cannabis current use. Cannabis use patterns and associations with clinical and socio-demographical variables were investigated. The binomial method was used to estimate 95% confidence interval (95% CI) for primary outcome., Results: 5620 patients were invited and 2024 (36.0%) were included (mean age 45.2 years, females 64.5%). Relapsing remitting form was the most frequent (77.3%). Median expanded disability status scale (EDSS) was 2.0. The proportion of current users was 15.5% (95% CI 13.9-17.1) and 36.4% of them disclosed to their physician their unprescribed cannabis use. 15.0% patients were former users while 69.5% never used cannabis. Current users more frequently reported a medical use (i.e., current medical users) compared to former users (p < 0.001). 41.1% of never users would use cannabis if it was legal. Young age, being male, and a free marital status were associated with current use. Current medical users had higher disability, spasticity and pain, reduced quality of life, concomitant neurological/psychiatric drugs and analgesics use. Unprescribed cannabis appeared relatively safe, with limited addiction risk, and reported clinical benefits, including concomitant medications reduction., Conclusion: Unprescribed cannabis use is common in patients with MS in Italy, with observed prevalence seemingly superior to the general population, often intended for medical use and without the disclosure to the treating physician, although with potential clinical benefits., Competing Interests: Declarations Conflicts of interest Dr. R. Giossi received support for congress participation from Mylan and acted as a consultant for Daiichi-Sankyo, outside this work. Prof. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Horizon, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Horizon, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Horizon, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Dr. C. Zanetta received compensation for speaking activities, and/or consulting services, from Alexion, Astrazeneca, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi. Dr. C. Antozzi received funding for traveling from Teva, Merck and Biogen. Dr. L. Brambilla received honoraria for speaking from Novartis, Roche, Horizon, and for traveling from Sanofi-Genzyme, Merck-Serono, Novartis, Horizon and Roche; she acted as an Advisory Board member of Sanofi-Genzyme, Novartis and Merck-Serono and she is involved as principal investigator in clinical trials for Roche and Merck-Serono. Dr. P. Confalonieri has received honoraria for speaking or consultation fees from Novartis, Bristol Myers and Biogen, has received funding for travel to attend scientific events or speaker honoraria from Merck-Serono, Biogen Idec, Mylan and Roche. He has also received institutional research support from Merk-Serono, Novartis and Roche. He is also principal investigator in clinical trials for Novartis and Roche. Dr. S.G. Crisafulli received support for congress participation from Mylan, Merck-Serono, Novartis. He acted as an Advisory Board member for Novartis. Dr. P. Annovazzi received honoraria for lecturing and participation in advisory boards, and/or travel expenses for attending congresses and meetings from Alexion, Almirall, Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, Teva and Viatris. Dr. C. Barrilà participated in improvements groups for Biogen, Sanofi, Novartis, and Merck. Dr. M. Ronzoni received honoraria for congress participation and/or advisory board from Alexion, Almirall, Biogen, Bristol Meyers Squibb, Horizon, Genzyme, Merck, Novartis, Roche, Sanofi, and Teva. Dr. S. Gustavsen has received support for congress participation from Merck and Sanofi. Dr. V. Torri Clerici acted as an Advisory Board member of Biogen Idec and Novartis, and received funding for travelling and honoraria for speaking or writing from Teva, Novartis, Genzyme, Almirall. She received support for research project by Almirall. Other authors have nothing to disclose., (© 2024. The Author(s).)

Objective: To report real-world experience on the use of anifrolumab (ANI) in refractory systemic lupus erythematosus (SLE)., Methods: The present study is a multicenter, retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in adult patients with active SLE in whom all the available treatment choices failed, were not tolerated, or were contraindicated. At baseline and 1, 3, 6, 9, and 12 months of treatment, overall and organ-specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded., Results: A total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in the Systemic Lupus Erythematosus Disease Activity Index 2000 ( P = 0.01), Systemic Lupus Erythematosus-Disease Activity Score ( P = 0.01), and physician global assessment ( P = 0.001) was recorded, and the same trend was maintained over time. A significant reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity ( P < 0.001) and in tender ( P = 0.03) and swollen ( P = 0.02) joint counts was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, whereas 46% were in Lupus Low Disease Activity State (LLDAS); at 6 months, 50% were in remission and 80% were in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 ( P = 0.04). A total of 4 disease flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index were recorded (3 mild-moderate and 1 severe). Overall, 4/20 patients with at least 24 weeks of follow-up (20%) were considered nonresponders., Conclusion: This study provides real-world experience on the use of ANI in patients with refractory SLE, confirming its rapid effectiveness and an overall acceptable safety profile., (Copyright © 2024 by the Journal of Rheumatology.)

Background: Highly effective modulators of the CFTR channel have been demonstrated to dramatically impact disease progression and outcome. However, real-world data indicates that the magnitude of the clinical benefit is not equal among all patients receiving the treatment. We aimed to assess the variability in treatment response (as defined by the 6-month change in sweat chloride concentration, forced expiratory volume in one second [ppFEV1], body mass index [BMI], and CF Questionnaire-Revised [CFQ-R] respiratory domain score) and identify potential predictors in a group of patients receiving Elexacaftor-Tezacaftor-Ivacaftor (ETI) triple combination therapy., Methods: This was a single-center, prospective cohort study enrolling adults with CF at a major center in Italy. We used linear regression models to identify a set of potential predictors (including CFTR genotype, sex, age, and baseline clinical characteristics) and estimate the variability in treatment response., Results: The study included 211 patients (median age: 29 years, range: 12-58). Median changes (10-90th percentile) from baseline were: - 56 mEq/L (-76; -27) for sweat chloride concentration, +14.5 points (2.5; 32.0) for ppFEV1, +0.33 standard deviation scores (-0.13; 1.05) for BMI and +17 points (0; 39) for the CFQ-R respiratory domain score. The selected predictors explained 23 % of the variability in sweat chloride concentration changes, 18 % of the variability in ppFEV1 changes, 39 % of the variability in BMI changes, and 65 % of the variability in CFQ-R changes., Conclusions: This study highlights a high level of heterogeneity in treatment response to ETI, which can only be partially explained by the baseline characteristics of the disease., Competing Interests: Declaration of competing interest AG, CL, VD and FB reported honoraria for lectures from Vertex; AG reported honoraria for lectures from Zambon, Foodar, Insmed; FB reported honoraria for lectures from Viatris, Zambon, Foodar, Chiesi, Insmed; AG and VD reported travel support from Neupharma; AG and FB reported travel support from Viatris., (Copyright © 2024. Published by Elsevier B.V.)

In mental health promotion, recovery is a process that leads to personal strengthening, control over crucial life decisions, and participation in communities through relevant professional, educational, or family social roles. Co-production, a key aspect of the recovery-oriented approach, emphasizes collaboration and active participation of people with mental health first-hand experience, family members, and citizens. Even though studies on co-production are limited and fragmented, there is evidence that co-production leads to positive outcomes, including improved well-being, empowerment, social connectedness, inclusion, and personal competencies. This study aimed to contribute to the limited literature on co-production in mental health by evaluating the co-production process in a non-profit mental health organization and its impact on empowerment processes and personal recovery outcomes. The research team adopted a collaborative approach and conducted qualitative research, including 13 individual semi-structured interviews and four focus groups. Results showed how the different dimensions of empowerment are promoted in and by the organization: (a) co-production processes supported empowered outcomes on an individual level, such as self-awareness; (b) the organization was perceived to promote empowering processes, such as a sense of safeness and protection; (c) co-production was a mean to build and maintain a network with mental health services that acknowledges the dignity and value of each subjectivity and promotes participation and recovery. Peer support workers were seen as facilitators of mental illness management, and the organization as a place for sharing mental health experiences and fostering individual recovery journeys., Competing Interests: Declarations. Conflict of Interest: The authors declare no conflict of interest., (© 2024. The Author(s).)

Recurrent pericarditis, an inflammatory syndrome with a pathogenesis not fully elucidated, often presents diagnostic challenges. This study aims to assess the correlation of D-Dimer (D-D) and procalcitonin (PCT) levels with clinical, laboratory and imaging features in recurrent idiopathic pericarditis. We analyzed 412 patients with idiopathic recurrent pericarditis from 2019 to 2023 in our referral center. D-D and PCT values were obtained from emergency room in other Italian facilities. Among the cohort, PCT levels were assessed in 50 of 412 patients (12.1%), with only 4 showing marginal elevation. D-D levels were measured in 48 of 412 patients (11.6%), with 33 of them exhibiting elevated values. None of these patients had venous thromboembolism, and elevated D-D levels were significantly associated with pleural effusion, fever, higher CRP, increased white blood cell counts, higher neutrophil counts, reduced relative lymphocyte counts. Multivariate analysis revealed fever as the sole correlate of elevated D-D. PCT elevation was infrequent and unrelated to any variables. In idiopathic recurrent pericarditis unrelated to specific conditions, we observed a close association between elevated D-D levels and non-specific inflammation markers, including fever, increased CRP, and neutrophil leukocytosis. PCT levels were typically normal or mildly elevated., Competing Interests: Declarations. Conflict of interest: Prof Antonio Luca Brucato: Institution received funding from Kiniksa Pharmaceuticals, Ltd. as an investigative site; unrestricted research grants from SOBI and ACARPIA; travel and accommodation for the advisory committee from SOBI and Kiniksa. All other authors declare that they have no conflicts of interest. Ethical approval: Obtained. Human and animal rights statements and Informed consent: All participants provided informed consent prior to their participation., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Liver transplantation (LT) was considered an ineffective treatment for perihilar cholangiocarcinoma (pCCA) until the successful experience of the Mayo Clinic, proposing a protocol with strict inclusion criteria and neoadjuvant radio-chemotherapy. Since 2015, pCCA is considered an indication for LT in Italy only in the context of controlled prospective studies. We performed a survey among the 22 Italian Liver Transplant Centers to assess the results of LT for pCCA. Eight centers reported 53 cases from 1986 to 2021 (Bologna 12, Padova 10, Niguarda 10, Milano Tumori 8, Torino 5, Pisa 4, Ancona 2, Modena 2). Patients were divided according to whether they recieved neoadjuvant radio-chemotherapy (Group 1, 25 cases) or not (Group 2, 28 cases). Eleven patients were transplanted without neoadjuvant treatment after 2015. Overall survival at 1, 3 and 5 years was 83.8%, 56.6% and 50.6% in Group 1 and 72.4%, 41.4% and 35.5% in Gropu 2 (p = 0.13). Recurrence-free survival at 1, 3, and 5 years was 91.2%, 61.1% and 47.2% in Group 1 and 58.2%, 42.2%, and 36.1% in Group 2 (p = 0.16). A competing risk regression analysis showed a 5-year risk of cancer-related death of 19% for patients in Group 1 against 62.3% in Group 2, with a hazard ratio of 0.31 (95%CI [0.10-0.98], p 0.047). This survey promoted a discussion about the limitations of the Mayo protocol and set the basis for the adoption of a new nationwide protocol (LITHALICA-NCT06125769), having the same inclusion criteria but proposing standard of care chemotherapy as neoadjuvant regimen., Competing Interests: Declarations. Conflict of interest: The authors of this manuscript have no financial or non-financial conflict of interest to disclose. VM, UC, LDC, FDB, RR, MV are members of the editorial board or advisory boards of Updates in Surgery. Human and animal rights: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained for the surgical procedure prior to their participation., (© 2024. Italian Society of Surgery (SIC).)

Between August and 28 October 2024, 199 autochthonous cases of dengue virus serotype 2 were notified in the city of Fano, central Italy. We describe the ongoing epidemiological and microbiological investigation and public health measures implemented to contain the outbreak. The high transmissibility and the extension of the outbreak suggest that dengue should be expected in temperate regions during favourable seasons, highlighting the need for heightened awareness among healthcare providers and the public to ensure timely detection and response.

Human adenoviruses are the causative agents of 5-7% of viral respiratory infections, mainly caused by species B and C. They can infect all age groups, but children are usually at high risk of infections. Adenovirus epidemiology is well documented in East-Asian countries but little is known about adenovirus circulation in Europe in recent years. This multicentre retrospective study aimed to investigate the circulation and molecular epidemiology of hAdVs. This surveillance collected a total of 54463 respiratory specimens between January 1, 2022 and June 20, 2023 were tested for the presence of respiratory viruses. Our results showed that adenovirus was detected in 6.6 % of all cases of acute respiratory infection included in the study and the median age of positive patients was 3 years, with male children in 1-2 years age group being the most affected. 43.5 % of adenovirus cases were co-infected with at least one other respiratory virus, and rhinovirus was co-detected in 54 % of cases. Genotyping of adenovirus allowed the identification of 6 different genotypes circulating in Italy, among which type B3 was the most frequently detected., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate seasonality, epidemiologic characteristics, and clinical severity variations of respiratory syncytial virus (RSV)-associated hospitalizations following the easing of COVID-19 restrictions in Tuscany, Italy, up to the 2022-2023 season., Methods: From 2017 to 2023, a dynamic cohort consisting of all resident children aged ≤2 years was followed up in regional registries. The person-time incidence rate of RSV-associated hospitalizations per 1,000 person-years and risk of severe hospitalization (intensive care unit, continuous positive airway pressure, or mechanical ventilation) per 100 RSV hospitalizations were calculated. RSV seasonality was investigated with retrospective methods., Results: A total of 193,244 children were followed up. After the easing of restrictions, RSV epidemics showed earlier seasonality and shorter duration compared with pre-pandemic (2017 to 2019), with this deviation decreased in 2022-2023. In 2021-2022 and 2022-2023, the incidence rate of RSV-associated hospitalizations significantly increased compared with pre-pandemic (2022-2023 risk ratio 3.6, 95% confidence interval 3.3-4.0), with larger increases among older age groups. Among hospitalized children, only those aged ≥12 months showed an increased risk of severe hospitalization, particularly during 2021-2022 (risk ratio 4.7, 95% confidence interval 1.5-24.3)., Conclusions: Our findings suggest a gradual return of RSV epidemics to the pre-pandemic pattern, although relevant increases in disease incidence persist. Reduced regular RSV exposure among older children may lead to declining immunity and increased severe outcome risks., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: A routine preoperative assessment is considered both ineffective and inefficient. Despite the widespread application of lean thinking in healthcare, there is little evidence of successful experiences in preoperative admissions in order to reduce "No value added" activities. A conceptual framework reporting the drivers (clinic, tools, innovation, organization, and governance) and impacts (patient, efficiency, sustainability, time, learning and growth) was developed. Methodology: Drawing on the experience of an Italian high complexity hospital, this paper analyzes the case study by reporting evidence on how to implement lean in preoperative assessment and how to evaluate the positive results obtained. Results: Applying lean principles, the identification of value improved the appropriateness of care by creating 40 personalized pathways; the value stream resulted in a reduction of "No Value Added Time" from 37% to 28%, chest X-rays from 41% to 14% and cardiac visits from 49% to 37%; the pursuit of continuous flow through innovation contributed to increase the use of digitalization; the new pull organization helped to reduce the average time spent per year by 1.5 h; the continuous improvement was ensured through the governance of results. Conclusion: The proposed framework should be used to improve the quality of care in preoperative admissions by adopting the lean drivers for successful implementation and reporting the impacts., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To explore short-term mortality and its predictors among older patients hospitalized in a acute geriatric ward (AGW) in Northwestern Italy., Design: Retrospective observational single-center cohort study., Material and Methods: Patients consecutively admitted for any reason between June 2021 and May 2022 were included in the analysis. Along with sociodemographic, clinical, and functional variables, prognosis estimation (Palliative Prognostic Index; PPI) at the time of admission was registered. Short-term all-cause mortality (in-hospital and within 3 months of discharge) was the primary outcome., Results: About one-third of the total sample died in the short-term (32.4 %). Along with PPI score (OR 1.115, 95 %CI 1.034-1.202), short-term mortality was independently associated with functional dependency (OR 1.278, 95 %CI 1.170-1.395)., Conclusions: The high short-term mortality in our sample should call for the inclusion of palliative prognostic tools within the in-hospital comprehensive geriatric assessment to better recognize and appropriately manage older patients at the end of life., Competing Interests: Declaration of competing interest The Authors of this manuscript declare they have no conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score is the most important prognostic score to stratify patients with metastatic renal cell carcinoma (mRCC), helping to guide treatment choice in first line. We hypothesized that IMDC change may also exert a prognostic role in subsequent lines of mRCC therapy., Methods: Meet-URO 15 is a multicenter Italian study of patients with mRCC receiving nivolumab as a second or subsequent line of therapy. This posthoc analysis aimed to evaluate the overall survival (OS) and progression-free survival (PFS) from nivolumab start as primary endpoints, overall response rate (ORR) and disease-control rate (DCR) as secondary endpoints, according to the change in the IMDC category from the first-line setting (baseline) to nivolumab start. Patients with available prognostic IMDC category information at baseline and before nivolumab were included., Results: 492 patients were included in the analysis. At baseline, 165 (33.5%), 287 (58.3%), and 40 patients (8.2%) had favorable, intermediate, and poor IMDC categories, respectively. Before nivolumab, 364 patients (73.9%) remained in the same prognostic category as at baseline, 27 (5.5%) improved, and 101 (20.5%) deteriorated. Significantly longer mPFS (P = .01) and mOS (P < .01) were reached by patients with a stable favorable group compared to those worsening to intermediate/poor. A longer mOS was also achieved from intermediate/poor patients who improved their IMDC category before nivolumab compared to those remaining stable/worsening (P < .01 and P = .04, respectively). Maintaining IMDC category stability from baseline to nivolumab determined a more consistent DCR in favorable patients (P = .03). Overall, patients who improved their IMDC risk score reached better survival outcomes than those who remained stable/deteriorated., Conclusions: In our sub-analysis, the shift in the IMDC risk category appears to be a helpful prognostic tool for assessing the outcomes of patients with mRCC treated with ≥2nd line nivolumab., (Copyright © 2024 Elsevier Inc. All rights reserved.)