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To explore the changes in blood inflammatory cells (neutrophils, monocytes, platelets) and adaptive immune cells (lymphocytes) during chemotherapy, we retrospectively analysed medical records from 66 patients with unresectable Pancreatic Ductal Adenocarcinoma (PDAC) treated with the Gemcitabine-nab-Paclitaxel (GnP) regimen. Evaluations were conducted at baseline (pre-GnP, TA), after the first cycle (TB), and after the third cycle (TC) of treatment. In metastatic PDAC (mPDAC), the monocyte-to-lymphocyte ratio significantly increased at both TB and TC compared to TA, whereas no such change was observed in locally advanced PDAC (laPDAC) (interaction: p = 0.006). Platelet levels rose over time in both phenotypes, with a more pronounced increase in mPDAC (intergroup: p = 0.008). When stratified by gender, males with mPDAC showed an increase in monocyte percentages among total white blood cells (intergroup: p = 0.018), while both phenotypes exhibited rising platelet-to-lymphocyte ratios over time. In females, the platelet-to-lymphocyte ratio increased more significantly in laPDAC than in mPDAC (interaction: p = 0.046). GnP treatment notably increased circulating inflammatory cells and their relationships with lymphocytes in a manner dependent on both disease phenotype and gender. Pretreatment factors such as monocyte counts < 0.6 × 10 3 /µl, lymphocyte counts > 1 × 10 3 /µl, and a monocyte-to-lymphocyte ratio < 0.43 were identified as independent predictors of survival.

Background: Trastuzumab–deruxtecan (T-DXd), a new-generation antibody drug conjugate, has greatly improved the survival and clinical benefit rates of patients affected by advanced HER2-positive/HER2-low breast cancer according to the results of controlled clinical trials with a manageable safety profile. Data from randomized clinical trials can provide valuable information for the management of patients in everyday clinical practice, including those who would typically be excluded from such trials due to not meeting the inclusion criteria. Methods: In this narrative review, we describe and discuss real-world studies in the literature on the use of T-Dxd in HER2-positive and HER2-low MBC patients, providing a critical analysis of the specific settings of clinical interest. Results: Using a PubMed search, we identified nine real-world studies on T-DXd that are available in the literature. A total of 7146 patients have been included in these retrospective studies. A total of 5/9 studies also included HER2-low MBC patients. In the majority of cases, patients had high disease burden with lung and liver involvement. We then reviewed and discussed clinical areas of interest, including heavily pretreated patients, poor performance status, HER2-positive versus HER2-low disease, brain metastasis, elderly patients, lung toxicity, safety profile, and dose modifications. Conclusions: Our analysis confirms the activity of the drug described in real-world studies and shows a favorable safety profile, with manageable adverse effects.

Introduction The gut microbiota (GM) can influence the pathogenesis of immune‐mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. Methods In this retrospective single‐center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). Results Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty‐three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11–56.10, p < 0.000). This HR was confirmed after weighting for the propensity score (HR15.13 95% CI 3.22–71.03, p < 0.000). Conclusion Chronic PPI use is associated with an increased risk of GI irAES.

Background/Objectives: Cancer represents an important risk factor for acquiring severe acute respiratory syndrome by Coronavirus-2 (SARS-CoV-2) and subsequent hospitalization. The utility of early antiviral therapies, including their protective effect on long COVID outcomes, in cancer patients has not yet been clearly demonstrated. We conducted the CO.THER study (COVID-19 THErapies in patients with canceR) to address this knowledge gap. Methods: We designed an ambispective single-center cohort study. We collected clinical and oncological data from the hospital’s electronic patient records at the start of COVID-19 therapy (T0), seven days after T0 (T1), two weeks after T0 (T2), one month after T0 (T3), three months after T0 (T4), six months after T0 (T5), and twelve months after T0 (T6). The primary endpoint of this ambispective single-center cohort study was the rate of hospitalization for COVID-19 disease within 14 days in cancer patients using anti-SARS-CoV-2 early therapies. The proportion of hospitalizations within 14 days (primary endpoint) was computed together with its exact binomial 95% confidence interval (95%CI). Results: 131 patients’ records (53M [40.5%], 78F, [59.5%]; median age 62.45, interquartile range [IQR] 56–71) were enrolled. As shown by the Kaplan–Meier hospitalization-free estimate, only three patients (2.1%) were hospitalized for a COVID-19 related cause within 14 days of starting early treatment (95%CI 0.5–6.6%). The cumulative survival probability beyond 12 months in hospitalization-free patients was 98% (95%CI 93–99%). Twelve patients (9.2%) reported another COVID-19 infection during the follow-up and they were all retreated with Nirmatrelvir–Ritonavir. The cumulative reinfection-free survival was 90% at 12 months (95%CI 83–95%). Further, 15 patients of the 123 evaluable at 3 months (median age 51 years, IQR 40–68) reported long COVID symptoms (12.2%, 95%CI 7.0–19.3%). Conclusions: Our data demonstrate a low rate of hospitalization and reassuring data on safety in this cohort of high-risk subjects.

The incidence of long COVID in a cohort of patients with cancer with or without previous treatment with early therapies anti-SARS-CoV-2 in an out-of-hospital setting have to be elucidated. We prospectively enrolled all patients treated for a solid tumor at the department of Medical Oncology of the Fondazione IRCCS Policlinico San Matteo with a positive SARS-CoV-2 antigen or polymerase chain reaction test from January to September 2022 (Omicron surge). Ninety-seven patients answered the survey questions by telephone at least 12 weeks after COVID-19 diagnosis in order to evaluate the incidence of long COVID symptoms. Only twelve patients (12.4%) reported long COVID. No significant difference between early therapies anti-SARS-CoV-2 31 and long COVID (p = 0.443) was seen. The female sex (p = 0.024) and diabetes mellitus (p = 0.014) are significantly associated with long COVID. No statistically significant difference between the two groups (Long COVID vs. No Long COVID) according to the time to nasal swab viral clearance (p = 0.078). The overlap between the symptoms related to the oncological disease/oncological treatment and the symptoms of long COVID is one of the main future challenges that oncologists will have to manage.

The issue of sustainability is greatly debated and one of the main points in the institutional agenda, but what is the opinion of the young generations and what is their behaviour? The aim of this work is twofold: to identify young people’s behaviour, perceptions and how they get information about sustainability, and to define young people’s different profiles and features. A CAWI survey addressed to the students attending the fourth and fifth year of high school all over Italy was carried out. The answers of 1013 students who filled out the questionnaire on the web were then collected. The evidence that comes out is that high school students care about the issue of sustainability, which, however, varies depending on the geographical area where they live and the school attended. A basic idea of sustainability, particularly widespread in the North and among the students of classical, scientific and linguistic schools consists in a significant effort to reduce pollution, protect natural resources, preserve food resources and improve waste management. The other idea of sustainability widespread in the South of Italy and among students of technical and professional institutes, combines the idea of sustainability with that of the economic development of the territory.

In-place automatic inclinometers are typical devices used to monitor displacements of extremely slow to slow-moving landslides. The significance of these measurements requires methodologies able to distinguish real measures from anomalous ones, to quantify significant moments of acceleration in deformation trends and to determine the main factors that influence the kinematic behavior measured by an automatic inclinometer. This work aimed at developing a novel method, which allows to cover all the steps of analysis of data acquired by automatic inclinometers. The methodology is composed by five steps: (I) evaluation of the reliability of the instruments; (II) identification and elimination of anomalous measures from displacement time-series; (III) recognition of significant moments of acceleration in the rate of displacement, through thresholds based on the mean rate of displacement and on the cumulated amount of the deformation; (IV) clustering of the events of significant acceleration, to characterize different typologies of events according to different landslides kinematic behaviors; (V) identification of the main meteorological and groundwater parameters influencing the deformation pattern measured by an automatic inclinometer. The methodology was developed and tested using displacement time-series of 89 automatic inclinometers, belonging to the regional monitoring network of Piemonte region (northern Italy), managed by Arpa Piemonte. Two representative inclinometric time-series were selected to validate all the steps of the methodology for different types of monitored slow-moving landslides. The developed method is reliable in the estimation of anomalous measures and in the identification of significant accelerations, helping in the comprehension of the response of displacement trends during activity phases. Moreover, it is able to identify the factors which influence more the deformation pattern measured in correspondence of an automatic inclinometer.

Conduction disorders and permanent pacemaker implantation are common complications in patients who undergo transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the incidence and clinical significance of new bundle branch block in patients who underwent TAVI with the Medtronic CoreValve Revalving System (MCRS) or the Edwards SAPIEN valve (ESV). Data from 238 patients with no previous pacemaker implantation, left bundle branch block (LBBB) or right bundle branch block at baseline electrocardiography who underwent TAVI with either MCRS (n = 87) or ESV (n = 151) bioprostheses from 2007 to 2011 were analyzed. New-onset LBBB occurred in 26.5% patients (n = 63): 13.5% with the ESV (n = 20) and 50.0% with the MCRS (n = 43) (p = 0.001). Permanent pacemaker implantation was required in 12.7% of patients (n = 8) because of complete atrioventricular block (ESV n = 2, MCRS n = 4), LBBB and first degree atrioventricular block (MCRS n = 1) and new-onset LBBB associated with sinus bradycardia (MCRS n = 1). At discharge, LBBB persisted in 8.6% of ESV patients (n = 13) and 32.2% of MCRS patients (n = 28) (p = 0.001). On multivariate analysis, the only predictor of LBBB was MCRS use (odds ratio 7.2, 95% confidence interval 2.9 to 17.4, p <0.001). Persistent new-onset LBBB at discharge was not associated with overall (log-rank p = 0.42) or cardiovascular (log-rank p = 0.46) mortality. New-onset right bundle branch block was documented in 4.6% of patients (n = 11), with no statistically significant differences between the ESV and MCRS. In conclusion, new-onset LBBB is a frequent intraventricular conduction disturbance after TAVI with a higher incidence with the MCRS compared with the ESV. LBBB persists in most patients, but in this cohort, it was not a predictor of overall or cardiovascular mortality or permanent pacemaker implantation.

In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome. •Recently developed diffusion MRI methods quantify white matter micro-structure.•Combination of tractography and micro-structural measures define better of the connectome.•CONNECT established the first in-vivo atlas of brain micro-structural features.

Background. A combination of TLR9 agonists and an anti-PD-1 antibody has been reported to be effective in immunocompetent mice but the role of innate immunity has not yet been completely elucidated. Therefore, we investigated the contribution of the innate immune system to this combinatorial immunotherapeutic regimens using an immunodeficient mouse model in which the effector functions of innate immunity can clearly emerge without any interference from T lymphocytes. Methods. Athymic mice xenografted with IGROV-1 human ovarian cells, reported to be sensitive to TLR9 agonist therapy, were treated with cytosine–guanine (CpG)-oligodeoxynucleotides (ODNs), an anti-PD-1 antibody or their combination. Results. We found that PD-1 blockade dampened CpG-ODN antitumor activity. In vitro studies indicated that the interaction between the anti-PD-1 antibody fragment crystallizable (Fc) domain and macrophage Fc receptors caused these immune cells to acquire an immunoregulatory phenotype, contributing to a decrease in the efficacy of CpG-ODNs. Accordingly, in vivo macrophage depletion abrogated the detrimental effect exerted by the anti-PD-1 antibody. Conclusion. Our data suggest that if TLR signaling is active in macrophages, coadministration of an anti-PD-1 antibody can reprogram these immune cells towards a polarization state able to negatively affect the immune response and eventually promote tumor growth.