BACKGROUND: The human microbiome plays an emerging role in cancer biology, yet its contribution to endometrial cancer (EC) remains poorly defined. This study investigates the microbial composition of the vaginal, rectal, and endometrial sites in women with and without EC, aiming to uncover microbial signatures associated with the disease. RESULTS: We performed shotgun metagenomic sequencing on vaginal, rectal, and endometrial samples from 25 patients with EC and 27 control women undergoing hysterectomy for benign conditions. Vaginal and rectal swabs were collected before surgery, while endometrial swabs were obtained post-hysterectomy using a sterile brushing technique to prevent cross-contamination. Vaginal microbiota in patients with EC showed significantly higher microbial diversity and distinct community composition compared to controls. These differences remained significant after adjusting for age and body mass index. Several bacterial species, including Peptococcus niger, Anaerococcus murdochii, Mobiluncus, Porphyromonas, and Prevotella, were more abundant in the vaginal microbiota of patients with cancer. In contrast, Lactobacillus spp. were more abundant in vaginal and rectal samples of control subjects. CONCLUSIONS: This work represents one of the few studies to comprehensively examine the relationship between the vaginal, rectal, and endometrial microbiomes in the context of EC, suggesting a potential role for microbial imbalance in disease development. The findings underscore the importance of site-specific microbial analyses in gynecologic oncology and support further investigation into the microbiome as a possible biomarker for early detection and a target for preventive strategies.

Here, we aim to improve our understanding of various colorectal cancer (CRC) risk factors (obesity, unhealthy diet, and gut microbiota/metabolome alteration), analyzing 120 patients with colon polyps, divided in normal-weight (NW) or overweight/obese (OB). Dietary habits data (validated EPIC questionnaires) revealed a higher consumption of processed meat among OB vs. NW patients. Both mucosa-associated microbiota (MAM) on polyps and lumen-associated microbiota (LAM) analyses uncovered distinct bacterial signatures in the two groups. Importantly, we found an enrichment of the pathogenic species Finegoldia magna in MAM of OB patients, regardless of their polyp stage. We observed distinct mucosal-associated metabolome signatures, with OB patients showing increased pyroglutamic acid and reduced niacin levels, and performed microbiota-metabolome integrated analysis. These findings support a model where different risk factors may contribute to tumorigenesis in OB vs. NW patients, highlighting the potential impact of processed meat consumption and F. magna on CRC development among OB patients.

Pleural mesothelioma (PM) is a lethal cancer primarily caused by asbestos exposure. Not all exposed individuals develop PM, suggesting the involvement of additional factors. This underscores the need for robust predictive models integrating biomarkers from multi-omic domains to improve risk stratification and early detection. We developed and evaluated polygenic risk scores (PRS) and methylation risk scores (MRS) using a retrospective case-control study (749 participants: 387 PM cases, 362 controls) and a nested case-control European Prospective Investigation into Cancer and Nutrition (EPIC)-Meso study (268 participants: 134 preclinical PM cases, 134 matched controls) within the EPIC cohort. Genome-wide association analyses in the retrospective case-control study identified PM-associated variants. The PRS (1123 SNPs with p < 0.001) in the retrospective training subset stratified disease risk in the test set (ORs 3.46-9.54 across top percentiles) and improved model discrimination (AUC = 0.75 vs. 0.71 in baseline model, p = 0.04). In EPIC-Meso, PRS performance was limited (AUC = 0.52). External validation in the UK-Biobank (UKBB) confirmed a modest but consistent association with PM-risk. A Meta-PRS derived from the UKBB-FinnGen meta-analysis replicated this trend in the full retrospective dataset, showing higher OR across top percentiles (2.5-12.3) and improved discrimination (AUC 0.74 vs. 0.72, p = 0.016). MRS, with 68 differentially methylated CpGs (effect-size >|0.10|, FDR p < 0.05) in the retrospective training set, increased the AUC from 0.66 to 0.85 (p < 0.001) in the test set and from 0.51 to 0.62 in EPIC-Meso. PRS was most predictive in low-exposure groups, while MRS remained robust across exposure levels. Combined PRS-MRS models improved discrimination. Integrating multi-omic biomarkers can enhance PM-risk stratification and support earlier, targeted interventions in high-risk asbestos-exposed groups.

The International Agency for Research on Cancer classifies formaldehyde as a human carcinogen, with sufficient evidence for nasopharyngeal cancer and leukaemia. However, the association with lymphoma subtypes has been less thoroughly investigated. We explored this link in an Italian multicentre case-control study. A total of 867 incident lymphoma cases, histologically confirmed using the WHO classification, and 774 controls participated in the study. Occupational experts classified the probability, frequency, and intensity of exposure to formaldehyde for each study subject based on detailed questionnaire data and literature information. We used unconditional regression analysis to model the risk of lymphoma and its main subgroups and subtypes associated with different formaldehyde exposure metrics, adjusting for age, gender, education, and study centre. Ever exposure to formaldehyde was not associated with risk of all lymphomas combined, the non-Hodgkin lymphoma (NHL) and B-cell lymphoma (BCL) subgroups, or the most prevalent BCL subtypes, but multiple myeloma (MM) (OR = 2.0, 95

INTRODUCTION:The prognostic potential of history of allergy and atopy in glioblastoma (GBM) patients has been poorly evaluated until now. In the present work, we studied the association between history of allergy/atopy and survival length in a cohort of GBM patients. We also evaluated the association between already suggested demographic, anamnestic, clinicopathologic and molecular prognostic variables for GBM and survival. METHODS:The study was conducted retrospectively on a cohort of 145 patients diagnosed with GBM between 2015 and 2021. Data were retrieved from clinical charts. Information on history of allergy and atopy was self-reported. RESULTS:Median overall survival was 9.1 months (IQR 4.3-17). Patients with positive history of allergic/atopic diseases were 33 (22.8%). From univariable analysis, patients with allergies had a longer survival time than those with no allergies; however, this result was not statistically significant (HR:0.72; 95%CI 0.49-1.07). Instead, from multivariable analysis, patients aged ≥65 years resulted to have a shorter survival than the others; (HR:2.10; 95%CI 1.35-2.84), while an increased survival length is observed for patient who underwent tumor surgical resection (HR:0.46; 95%CI 0.30-0.72) and receiving adjuvant therapy (HR:0.25; 95%CI 0.17-0.38). CONCLUSION:Although the result was not statistically significant, we found a trend of protective effect of allergies/atopies in GBM patients. In addition, the study confirmed positive effects on GBM survival of some well-known variables, such as surgical resection, adjuvant therapy, and age.

Italy has been significantly impacted by the COVID-19 pandemic, particularly in its early stages, resulting in healthcare strain, societal restrictions, and disruption. Understanding the long-term effects, notably excess mortality beyond the initial peaks, remains important. Prior studies have focused on the early phase, leaving out subsequent and updated mortality trends. This study analyzes Italian mortality rates from 2015 to 2023, employing Generalized Additive Models for Location, Scale, and Shape (GAMLSS), the Generalized Gamma Overdispersion model. Data analysis considered factors such as gender, age groups (under 65 and 65 or older), and geographical differences (Northern versus Central-Southern Italy) as key characteristics of the mortality trend. The study identified several phases of the pandemic, characterized by a significant early 2020 mortality peak and subsequent smaller peaks. Mortality rates were higher in Northern Italy, with males and the elderly being the most affected. Overall, mortality rates increased during the pandemic, particularly among these groups, and then returned to normal levels in 2023. An increase in the overdispersion parameter, estimated via the GAMLSS model, is evident in the post-pandemic phase and persists until 2023. The findings highlight the complex nature of COVID-19’s impact on mortality in Italy. They reveal the temporal phases, regional disparities, and demographic vulnerabilities that contribute to the overall mortality picture. The overdispersion component indicates more significant variability and unpredictability of mortality patterns until 2023. This highlights the intricate interplay of factors, including healthcare capacity, viral mutations, and the effectiveness of public health responses. This study emphasizes the need for targeted interventions and protective measures in the most affected groups.

Extracellular vesicles (EVs) could be involved in the onset of systemic sclerosis (SSc) through the modulation of vascular function. Anyway, available data are contradictory, and further investigation would be necessary to clarify this aspect. Here, we characterized circulating EVs isolated from SSc patients and evaluated their effects on human vascular endothelial cells (HUVECs) and smooth muscle cells. In EVs from 13 complicated and 27 uncomplicated SSc patients and five healthy controls (HCs), we analyzed the size, concentration, and surface marker expression. In addition, EVs were used to stimulate HUVECs, and we evaluated cell viability, mitochondrial membrane potential, and nitric oxide (NO) and mitochondrial reactive oxygen species (MitoROS) release. In smooth muscle cells, the effects of EVs on calcium movement were examined. The results showed that the EVs of SSc patients expressed markers of T-lymphocyte/platelet/endothelial cell origin and were larger and more concentrated than those from HCs. In addition, the EVs of SSc patients reduced cell viability and mitochondrial membrane potential and increased NO and MitoROS release in HUVECs and intracellular calcium in smooth muscle cells. In conclusion, we found a specific pattern for EVs isolated from SSc patients, which could have a pathogenic role through direct actions on endothelial and smooth muscle cells.

The Novara Cohort Study (NCS) is the first multidisciplinary cohort study on aging in Northern Italy. It is designed to explore aging trajectories and health outcomes in the general population. This study involves the collection of biological samples and extensive data, including socioeconomics, medical history, lifestyle habits, quality of life, and physical function. This paper outlines the rationale, objectives, and preliminary findings of the NCS pilot phase. It discusses baseline characteristics, initial biological characterization, and identifies key areas for improvement to ensure the successful implementation of the full-scale study. The NCS pilot phase enrolled participants aged 35 and older residing in Novara, Italy. The study involved the collection of biological samples, medical examinations, questionnaires, and functional tests. Data collected included demographic information, physical activity, sleep quality, diet, quality of life, mental health, medical history, and medication use. Key blood parameters were analyzed alongside clinical data.The pilot phase enrolled 123 participants, 68 (55.3%) females and 55 (44.7%) males with a median age of 65 years old. The NCS pilot participants had higher education levels, lower smoking rates, and higher physical activity levels than the general population. Blood biomarker profiling revealed significant variability across participants, offering exploratory and preliminary findings to guide the design and implementation of the larger cohort phase aimed at studying aging trajectories. The NCS pilot provided valuable initial insights into participant characteristics and identified areas for study protocol enhancement. These findings will guide refinements to optimize future study processes and outcomes, ultimately aimed at investigating the biological, social, and environmental determinants of aging in the Northern Italy area population.

Chromogranin B (CgB) is involved in the control of the cardiovascular system through the regulation of catecholamine release. Whether CgB can exert direct actions on the endothelium has not yet been clarified. Here, we aimed to investigate the effects of CgB on cell viability, mitochondrial membrane potential, reactive oxygen species (ROS), glutathione (GSH), nitric oxide (NO) release, and the cytosolic calcium concentration ([Ca2+]c) in human vascular endothelial cells (HUVECs) cultured under both physiological and peroxidative conditions. In HUVECs, experiments were conducted to establish the proper concentration and timing of CgB stimulation. Thereafter, specific assays were used to evaluate the response of HUVECs cultured in physiologic or oxidative stress conditions to CgB in the presence or absence of β-adrenergic receptor agonists and antagonists and intracellular pathways blockers. Analysis of cell viability, mitochondrial membrane potential, and NO release revealed that CgB was able to cause increased effects in HUVECs cultured in physiological conditions. Additionally, the same analyses performed in HUVECs cultured with H2O2, showed protective effects exerted by CgB, which was also able to counteract ROS release and maintain GSH levels. Furthermore, CgB played a dual role on the [Ca2+]c depending on the physiological or peroxidative cell culturing conditions. In conclusion, our data provide new information about the direct role of CgB in the physiological regulation of endothelial function and highlight its potential as a protective agent against peroxidative conditions, such as those found in cardiovascular diseases.

Patients intoxicated with alcohol or other substances are often assessed and assisted in the context of the Emergency Department (ED) by emergency physicians, who usually require a psychiatric assessment. This study aims to analyse the characteristics of a sample of patients receiving a psychiatric consultation in the ED setting of the Maggiore della Carità University Hospital in Novara, Italy, in the period from 1 January 2021 to 31 December 2023, to find out whether and how patients screening positive for alcohol/drugs differ from those screening negative. Socio-demographic and clinical history information and clinical data related to the ED psychiatric consultations were extracted from the PsNet database, a collection of data extracted from the application that serves as the electronic medical record for patients accessing the ED. Statistical analyses were performed using SAS 9.4 and STATA version 17 software. Chi-square/Fisher tests, t-tests, and both univariate and multivariate logistic models were employed. Most of the findings regarding socio-demographic characteristics, symptoms observed during the 1362 psychiatric consultations, and treatments received by a total of 922 patients in the ED were consistent with the literature on this topic. However, some results only partially aligned with previous studies, particularly concerning the higher frequency of anxiety and psychotic symptoms, as well as cognitive impairments, observed in consultations for patients who tested negative for alcohol or substances. Interpreting these findings is complex and raises important questions, which may be addressed more effectively by expanding the sample size (extending the research to other EDs) and analysing its characteristics in greater detail. In this regard, improving diagnostic methods for detecting substance use through laboratory tests would also be beneficial.

Background: Pulmonary function assessment is mandatory before oncological lung resection surgery. To do so, subjects undergo a pulmonary function test (PFT) and the calculation of predicted postoperative (PPO) values to estimate the residual lung function after surgery. The aim of this study is to evaluate the use of anatomical formulae in estimating postoperative pulmonary function in patients undergoing minimally invasive surgery (MIS). Methods: This is a retrospective study. Patients affected by lung cancer who underwent pulmonary lobectomy or segmentectomy with MIS or thoracotomy approach at our center from June 2020 to May 2021 were considered. Exclusion criteria were: subjects who underwent atypical pulmonary resection surgery or pneumonectomy; and patients who underwent adjuvant therapy (chemotherapy or immunotherapy). PFT data measured before and 1 year after surgery were collected. In particular, postoperative PFT data, especially forced expiratory volume in the first second (FEV1) and diffusing capacity for carbon monoxide (DLCO), and PPO values calculated by the anatomical formulae were compared. Secondary endpoints were: analysis of the postoperative pulmonary function in patients who underwent lung resection with the standard approach (thoracotomy) and evaluation of the anatomical formulae accuracy in subjects operated through thoracotomy. Results: The sample consisted of 48 patients operated on MIS (video-assisted thoracoscopic surgery and robotic-assisted thoracoscopic surgery) and 20 subjects who underwent thoracotomy for stage I-IIA and I-IIB lung cancer in both groups. The anatomical formula seemed to underestimate the postoperative FEV1% by 8.65% [interquartile range (IQR), 0.5-17.28%; P<0.001]. Furthermore, when comparing postoperative PPODLCO% and post-operative DLCO%, a significant difference was shown with an underestimation of the actual postoperative value of 2.78% (IQR, -3.63% to 10.47%; P=0.045). Conclusions: Our results confirmed that the anatomical formulae currently used to predict postoperative pulmonary function are reliable in the case of the standard approach (thoracotomy), while they tend to overestimate the loss of FEV1 and DLCO in the postoperative period in patients who were operated on MIS, thus excluding some subjects from the operation.

BACKGROUND:Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS:The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS:47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION:Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

Kidney transplant recipients (KTRs), like other solid organ transplant recipients display a suboptimal response to mRNA vaccines, with only about half achieving seroconversion after two doses. However, the effectiveness of a booster dose, particularly in generating neutralizing antibodies (NAbs), remains poorly understood, as most studies have mainly focused on non-neutralizing antibodies. Here, we have longitudinally assessed the humoral response to the SARS-CoV-2 mRNA vaccine in 40 KTRs over a year, examining changes in both anti-spike IgG and NAbs following a booster dose administered about 5 months post-second dose. We found a significant humoral response increase 5 months post-booster, a stark contrast to the attenuated response observed after the second dose. Of note, nearly a quarter of participants did not achieve protective plasma levels even after the booster dose. We also found that the higher estimated glomerular filtration rate (eGFR) correlated with a more robust humoral response postvaccination. Altogether, these findings underscore the effectiveness of the booster dose in enhancing durable humoral immunity in KTRs, as evidenced by the protective level of NAbs found in 65% of the patients 5 months post- booster, especially those with higher eGFR rates.

ObjectivesIn Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose-response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks.MethodsCohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause-specific (CS) Cox-regression models were used to evaluate the dose-exposure relationship between asbestosis mortality and the time-dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death.ResultsThe cohort included 12,963 asbestos cement workers. During the follow-up period (1960-2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose-response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL-years. Lung cancer and circulatory diseases were the main competing causes of death.ConclusionsAsbestos exposure among Italian asbestos-cement workers has led to a very high number of deaths from asbestosis and asbestos-related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal–fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy.