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Purpose: There is debate about the optimal management of borderline resectable (bRe) and resectable (Re) pancreatic ductal adenocarcinoma (PDAC). Both preclinical and clinical evidence showed that carbon ion radiotherapy (CIRT) produces superior control on radioresistant histologies compared to conventional photon beam radiotherapy (RT). However, so far there is a lack of data concerning the integration of CIRT in a multimodal approach with chemotherapy and surgery for bRe/Re., Methods: We recently presented the first analysis of a multicenter prospective phase II clinical study aimed at assessing the feasibility and effectiveness of a neoadjuvant chemotherapy + short course of CIRT followed by surgery and adjuvant chemotherapy in the management of bRe/Re PDAC. The study was terminated early due to low patient enrollment.Herein, we reported a post-hoc analysis focusing on toxicity, dosimetry and translational assessment., Results: In our experience, CIRT can be integrated into a multimodal treatment strategy for bRe/Re PDAC, alongside chemotherapy and surgery. A case of fatal liver failure occurring three months post-surgery has been documented, likely related to the combination approach. Although the treatment plans were satisfactory according to the Local Effect Model (LEM) model, recalculations using the modified Microdosimetric Kinetic Model (mMKM) revealed suboptimal target coverage. Additionally, we observed an increased expression of PD-L1 following CIRT., Conclusions: This multimodal approach was well tolerated; however, clinicians should carefully monitor for vascular disorders during follow-up and further investigate surgical techniques after CIRT. The increased PD-L1 expression supports the immunogenic effects of particle therapy and lays the groundwork for future studies. To enhance the therapeutic ratio of CIRT treatments, integrating dose-averaged LETd (LETd-based objectives into the plan optimization process should be considered., Trial Registration Number: ClinicalTrials.gov Identifier: NCT03822936., 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.

The corrosion behavior of the TiTaNbZrAg alloys with different amounts of tantalum (0%, 10% and 20%) and with distinct surface topography (smooth and rough) was investigated in phosphate buffer solution (PBS) for long-time immersion (1000 h). By this approach, we expect to bring about new insights into the influence of both the amount of Ta in the alloy composition and the surface topography on the corrosion behavior of the Ti-based alloys. The corrosion resistance was studied by Open Circuit Potential (OCP), Potentiodynamic Polarization (PP), and Electrochemical Impedance Spectroscopy (EIS). From the potentiodynamic investigations, it was observed that all types of samples showed good corrosion resistance (i.e., R corr < 10 µm y -1 ) and may be used successfully for medical applications. However, the samples with smooth surfaces and with a certain amount of Ta (10% and 20%) exhibit the best corrosion performance ( R corr < 1 µm y -1 ). As regards the samples with rough surfaces, the results evidenced that they showed lower corrosion resistance (1 < R corr < 3 µm y -1 ), suggesting that the Ta presence does not necessarily hinder the corrosion processes. Actually, the synergetic effect of both the presence of Ta and surface roughness plays an important role in corrosion resistance.

Cancer prehabilitation is the process between the time of cancer diagnosis and the beginning of the active acute treatment; prehabilitation consists of various need-based interventions, e.g., physical activity, a nutritional program, and psychological support. It can be delivered as unimodal or multimodal interventions. Physical activity, including resistant exercise and aerobic activities, has to be tailored according to the patient's characteristics; nutritional support is aimed at preventing malnutrition and sarcopenia; while psychological intervention intercepts the patient's distress and supports specific intervention to address it. In addition, multimodal prehabilitation could have a potential impact on the immune system, globally reducing the inflammatory processes and, as a consequence, influencing cancer progression. However, many challenges are still to be addressed, foremost among them the feasibility of prehabilitation programs, the lack of adequate facilities for these programs' implementation, and the fact that not all prehabilitation interventions are reimbursed by the national health system.

Introduction: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in the treatment of recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) Keynote 048 highlighted the relevance of PD-L1 Combined Positive Score (CPS) as a predictive biomarker for ICIs treatment, but challenges persist regarding ideal assessment and concordance between primary and relapsing tumor has not been determined., Material and Methods: This is a retrospective multicentric study that included HNSCC patients with locoregional and/or metastatic relapses after curative treatment. Histological samples of primary tumors and corresponding relapses were collected. The primary objective was to evaluate PD-L1 CPS concordance between primary and recurrent tumors, with secondary objective of exploring the impact of clinical-pathological variables., Results: Out of 86 evaluated patients, 30 cases were excluded due to insufficient histological material, with a final enrollment of 56 patients. Concordance analysis revealed a 66.1% agreement in PD-L1 CPS between primary and recurrent tumors. Only 3.6% of cases exhibited a change from negative to positive PD-L1 CPS status, and 7.2% showed the reverse. Factors analyzed, including primary tumor site, treatment modality, and recurrence type, did not significantly influence PD-L1 CPS concordance level., Conclusion: While significant changes in PD-L1 CPS expression are rare, the study underscores the importance of confirmatory biopsies on relapse. However, reliance on archival tumor tissue for initial PDL1 assessment may be considered in cases where obtaining additional biopsies poses risks to patients or urgent therapeutic decisions are required., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [PB: participation to advisory board or conference honoraria for: Merck, Sanofi-Regeneron, Merck Sharp & Dohme, Sun Pharma, Angelini, Nestlè, Elevar. Other authors have nothing to declare]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This article describes how the transcriptional alterations of the innate immune system divide dysplasias into aggressive forms that, despite the treatment, relapse quickly and more easily, and others where the progression is slow and more treatable. It elaborates on how the immune system can change the extracellular matrix, favoring neoplastic progression, and how infections can enhance disease progression by increasing epithelial damage due to the loss of surface immunoglobulin and amplifying the inflammatory response. We investigated whether these dysregulated genes were linked to disease progression, delay, or recovery. These transcriptional alterations were observed using the RNA-based next-generation sequencing (NGS) panel Oncomine Immune Response Research Assay (OIRRA) to measure the expression of genes associated with lymphocyte regulation, cytokine signaling, lymphocyte markers, and checkpoint pathways. During the analysis, it became apparent that certain alterations divide dysplasia into two categories: progressive or not. In the future, these biological alterations are the first step to provide new treatment modalities with different classes of drugs currently in use in a systemic or local approach, including classical chemotherapy drugs such as cisplatin and fluorouracile, older drugs like fenretinide, and new checkpoint inhibitor drugs such as nivolumab and pembrolizumab, as well as newer options like T cell therapy (CAR-T). Following these observed alterations, it is possible to differentiate which dysplasias progress or not or relapse quickly. This information could, in the future, be the basis for determining a close follow-up, minimizing surgical interventions, planning a correct and personalized treatment protocol for each patient and, after specific clinical trials, tailoring new drug treatments.

Purpose: Radiomics is an emerging field that utilizes quantitative features extracted from medical images to predict clinically meaningful outcomes. Validating findings is crucial to assess radiomics applicability. We aimed to validate previously published magnetic resonance imaging (MRI) radiomics models to predict oncological outcomes in oral tongue squamous cell carcinoma (OTSCC)., Materials and Methods: Retrospective multicentric study on OTSCC surgically treated from 2010 to 2019. All patients performed preoperative MRI, including contrast-enhanced T1-weighted (CE-T1), diffusion-weighted sequences and apparent diffusion coefficient map. We evaluated overall survival (OS), locoregional recurrence-free survival (LRRFS), cause-specific mortality (CSM). We elaborated different models based on clinical and radiomic data. C-indexes assessed the prediction accuracy of the models., Results: We collected 112 consecutive independent patients from three Italian Institutions to validate the previously published MRI radiomic models based on 79 different patients. The C-indexes for the hybrid clinical-radiomic models in the validation cohort were lower than those in the training cohort but remained > 0.5 in most cases. CE-T1 sequence provided the best fit to the models: the C-indexes obtained were 0.61, 0.59, 0.64 (pretreatment model) and 0.65, 0.69, 0.70 (posttreatment model) for OS, LRRFS and CSM, respectively., Conclusion: Our clinical-radiomic models retain a potential to predict OS, LRRFS and CSM in heterogeneous cohorts across different centers. These findings encourage further research, aimed at overcoming current limitations, due to the variability of imaging acquisition, processing and tumor volume delineation., (© 2024. The Author(s).)

Cutaneous squamous cell carcinoma (SCC) is the second most frequent skin cancer, accounting for approximately 20% of all cutaneous malignancies, and with an increasing incidence due to the progressive increment of the average age of life. The diagnosis is usually firstly suspected based on clinical manifestations; however, dermoscopic features may improve diagnostic sensitivity in cases of an uncertain diagnosis and may guide the biopsy, which should be performed to histopathologically prove the tumor. New diagnostic strategies may improve the sensitivity of the cutaneous SCC, such as reflectance confocal microscopy and line-field confocal optical coherence, for which increasing data have been recently published. Imaging has a central role in the staging of the diseases, while its exact role, as well as the choice of the best techniques, during the follow-up are not fully clarified. The aim of this literature review is to describe diagnostic clinical and instrumental tools of cutaneous SCC, with an insight into the role of imaging in the diagnosis and follow-up of cutaneous SCC.

Objectives: Orthodontists are often asked to remove fixed retainers before patients undergo magnetic resonance imaging (MRI). The present in vitro study was designed to analyze the heating and bonding efficacy of stainless steel multibraided fixed retainers after 1.5- and 3-tesla (T) MRI., Materials and Methods: A total of 180 human mandibular incisors were used to create 45 specimens of four teeth each, divided into nine groups. Handmade multibraided fixed retainers of three different sizes, defined by the diameter of the initial wire used (0.008″, 0.010″ and 0.012″), were tested. Three groups underwent MRI at 1.5 T, another three groups underwent MRI at 3 T and the last three groups did not undergo MRI. Temperature was assessed before and after MRI. Shear bond strength (SBS) and adhesive remnant index (ARI) were assessed after MRI for all groups. Data were statistically analyzed ( p < 0.05)., Results: After 1.5 T exposure, no significant temperature increase from T0 to T1 was observed in any of the groups ( p > 0.05). Regarding the 3 T groups, a significant difference from T0 to T1 was found for all the groups ( p < 0.05). Temperature changes were not clinically relevant, as they were less than 1 °C for all groups except for group 3 (ΔT0-T1: 1.18 ± 0.3 °C) and group 6 (ΔT0-T1: 1.12 ± 0.37 °C). Furthermore, there were no significant differences between the temperature variations associated with different wire diameters ( p > 0.05)., Conclusions: No significant changes in SBS or ARI were found ( p > 0.05)., Clinical Significance: Since overheating was irrelevant and adhesion values did not change, the tested devices were concluded to be safe for MRI examinations at 1.5 T and 3 T.

Background: Radiology reports are typically written in a free-text format, making clinical information difficult to extract and use. Recently, the adoption of structured reporting (SR) has been recommended by various medical societies thanks to the advantages it offers, e.g. standardization, completeness, and information retrieval. We propose a pipeline to extract information from Italian free-text radiology reports that fits with the items of the reference SR registry proposed by a national society of interventional and medical radiology, focusing on CT staging of patients with lymphoma., Methods: Our work aims to leverage the potential of Natural Language Processing and Transformer-based models to deal with automatic SR registry filling. With the availability of 174 Italian radiology reports, we investigate a rule-free generative Question Answering approach based on the Italian-specific version of T5: IT5. To address information content discrepancies, we focus on the six most frequently filled items in the annotations made on the reports: three categorical (multichoice), one free-text (free-text), and two continuous numerical (factual). In the preprocessing phase, we encode also information that is not supposed to be entered. Two strategies (batch-truncation and ex-post combination) are implemented to comply with the IT5 context length limitations. Performance is evaluated in terms of strict accuracy, f1, and format accuracy, and compared with the widely used GPT-3.5 Large Language Model. Unlike multichoice and factual, free-text answers do not have 1-to-1 correspondence with their reference annotations. For this reason, we collect human-expert feedback on the similarity between medical annotations and generated free-text answers, using a 5-point Likert scale questionnaire (evaluating the criteria of correctness and completeness)., Results: The combination of fine-tuning and batch splitting allows IT5 ex-post combination to achieve notable results in terms of information extraction of different types of structured data, performing on par with GPT-3.5. Human-based assessment scores of free-text answers show a high correlation with the AI performance metrics f1 (Spearman's correlation coefficients>0.5, p-values<0.001) for both IT5 ex-post combination and GPT-3.5. The latter is better at generating plausible human-like statements, even if it systematically provides answers even when they are not supposed to be given., Conclusions: In our experimental setting, a fine-tuned Transformer-based model with a modest number of parameters (i.e., IT5, 220 M) performs well as a clinical information extraction system for automatic SR registry filling task. It can extract information from more than one place in the report, elaborating it in a manner that complies with the response specifications provided by the SR registry (for multichoice and factual items), or that closely approximates the work of a human-expert (free-text items); with the ability to discern when an answer is supposed to be given or not to a user query., 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 B.V. All rights reserved.)

Objectives: Chest high-resolution computed tomography (HRCT) is conditionally recommended to rule out conditions that mimic or coexist with severe asthma in children. However, it may provide valuable insights into identifying structural airway changes in pediatric patients. This study aims to develop a machine learning-based chest HRCT image analysis model to aid pediatric pulmonologists in identifying features of severe asthma., Methods: This retrospective case-control study compared children with severe asthma (as defined by ERS/ATS guidelines) to age- and sex-matched controls without asthma, using chest HRCT scans for detailed imaging analysis. Statistical analysis included classification trees, random forests, and conventional ROC analysis to identify the most significant imaging features that mark severe asthma from controls., Results: Chest HRCT scans differentiated children with severe asthma from controls. Compared to controls (n = 21, mean age 11.4 years), children with severe asthma (n = 20, mean age 10.4 years) showed significantly greater bronchial thickening (BT) scores (p < 0.001), airway wall thickness percentage (AWT%, p < 0.001), bronchiectasis grading (BG) and bronchiectasis severity (BS) scores (p = 0.016), mucus plugging, and centrilobular emphysema (p = 0.009). Using AWT% as the predictor in conventional ROC analysis, an AWT% ≥ 38.6 emerged as the optimal classifier for discriminating severe asthmatics from controls, with 95% sensitivity, specificity, and overall accuracy., Conclusion: Our study demonstrates the potential of machine learning-based analysis of chest HRCT scans to accurately identify features associated with severe asthma in children, enhancing diagnostic evaluation and contributing to the development of more targeted treatment approaches., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare medium-term outcomes according to the presence of PE, as well as to explore their potential predictors. A total of 141 patients (56 with PE) were followed up during a median of 6 months. Post-COVID-19 radiological lung abnormalities (PCRLA) and impaired diffusing capacity for carbon monoxide (DLCOc) were found in 55.2% and 67.6% cases, respectively. A total of 7.3% had PE, and 6.7% presented an intermediate-high probability of pulmonary hypertension. No significant difference was found between PE and non-PE patients. Univariate analysis showed that age > 65, some clinical severity factors, surfactant protein-D, baseline C-reactive protein, and both peak red cell distribution width and Interleukin (IL)-10 were associated with DLCOc < 80%. A score for PCRLA prediction including age > 65, minimum lymphocyte count, and IL-1β concentration on admission was constructed with excellent overall performance. In conclusion, reduced DLCOc and PCRLA were common in COVID-19 patients after hospital discharge, but PE did not increase the risk. A PCRLA predictive score was developed, which needs further validation.

Background: Radiomics is a quantitative approach that allows the extraction of mineable data from medical images. Despite the growing clinical interest, radiomics studies are affected by variability stemming from analysis choices. We aimed to investigate the agreement between two open-source radiomics software for both contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) of lung cancers and to preliminarily evaluate the existence of radiomic features stable for both techniques., Methods: Contrast-enhanced CT and MRI images of 35 patients affected with non-small cell lung cancer (NSCLC) were manually segmented and preprocessed using three different methods. Sixty-six Image Biomarker Standardisation Initiative-compliant features common to the considered platforms, PyRadiomics and LIFEx, were extracted. The correlation among features with the same mathematical definition was analyzed by comparing PyRadiomics and LIFEx (at fixed imaging technique), and MRI with CT results (for the same software)., Results: When assessing the agreement between LIFEx and PyRadiomics across the considered resampling, the maximum statistically significant correlations were observed to be 94% for CT features and 95% for MRI ones. When examining the correlation between features extracted from contrast-enhanced CT and MRI using the same software, higher significant correspondences were identified in 11% of features for both software., Conclusions: Considering NSCLC, (i) for both imaging techniques, LIFEx and PyRadiomics agreed on average for 90% of features, with MRI being more affected by resampling and (ii) CT and MRI contained mostly non-redundant information, but there are shape features and, more importantly, texture features that can be singled out by both techniques., Relevance Statement: Identifying and selecting features that are stable cross-modalities may be one of the strategies to pave the way for radiomics clinical translation., Key Points: • More than 90% of LIFEx and PyRadiomics features contain the same information. • Ten percent of features (shape, texture) are stable among contrast-enhanced CT and MRI. • Software compliance and cross-modalities stability features are impacted by the resampling method., (© 2024. The Author(s).)

Background: Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected., Methods: All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed., Results: We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations., Conclusions: Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE"., (© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Benign nerve sheath tumors presenting as solitary retroperitoneal masses (RBNSTs) pose a complex diagnostic challenge for multidisciplinary teams regarding differential diagnosis, staging, and treatment planning. This article reviews the role played by different imaging techniques in assessing RBNSTs and elucidates their typical pathological features with a particular emphasis on the correlation between imaging and histological findings. Furthermore, some examples of retroperitoneal tumors that merit consideration in the process of differential diagnosis based on cross-sectional investigations (CSIs) are reported. The correlation between tissue architecture and appearance on imaging can help increase the accuracy of differential diagnosis with other retroperitoneal neoplasms at CSIs., Critical Relevance Statement: This educational review critically examines the correlation between imaging and histological features in solitary retroperitoneal benign nerve sheath tumors, offering valuable insights for improving the accuracy of differential diagnosis in clinical radiology., Key Points: RBNSTs are challenging to diagnose because they lack specific radiological features. Differential diagnosis of RBNSTs from other retroperitoneal neoplasms on imaging is complex. Surgical removal of RBNSTs is recommended for an accurate diagnosis., (© 2024. The Author(s).)

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are "black box" to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffers from poor generalization ability in the presence of dataset shifts. Here, we present a comparison between an explainable-by-design ("white box") model (Bayesian Network (BN)) versus a black box model (Random Forest), both studied with the aim of supporting clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

Artificial intelligence (AI) approaches have been introduced in various disciplines but remain rather unused in head and neck (H&N) cancers. This survey aimed to infer the current applications of and attitudes toward AI in the multidisciplinary care of H&N cancers. From November 2020 to June 2022, a web-based questionnaire examining the relationship between AI usage and professionals' demographics and attitudes was delivered to different professionals involved in H&N cancers through social media and mailing lists. A total of 139 professionals completed the questionnaire. Only 49.7% of the respondents reported having experience with AI. The most frequent AI users were radiologists (66.2%). Significant predictors of AI use were primary specialty (V = 0.455; p < 0.001), academic qualification and age. AI's potential was seen in the improvement of diagnostic accuracy (72%), surgical planning (64.7%), treatment selection (57.6%), risk assessment (50.4%) and the prediction of complications (45.3%). Among participants, 42.7% had significant concerns over AI use, with the most frequent being the 'loss of control' (27.6%) and 'diagnostic errors' (57.0%). This survey reveals limited engagement with AI in multidisciplinary H&N cancer care, highlighting the need for broader implementation and further studies to explore its acceptance and benefits., Competing Interests: The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Purpose: Lung cancer screening (LCS) by low-dose computed tomography (LDCT) demonstrated a 20-40% reduction in lung cancer mortality. National stakeholders and international scientific societies are increasingly endorsing LCS programs, but translating their benefits into practice is rather challenging. The "Model for Optimized Implementation of Early Lung Cancer Detection: Prospective Evaluation Of Preventive Lung HEalth" (PEOPLHE) is an Italian multicentric LCS program aiming at testing LCS feasibility and implementation within the national healthcare system. PEOPLHE is intended to assess (i) strategies to optimize LCS workflow, (ii) radiological quality assurance, and (iii) the need for dedicated resources, including smoking cessation facilities., Methods: PEOPLHE aims to recruit 1.500 high-risk individuals across three tertiary general hospitals in three different Italian regions that provide comprehensive services to large populations to explore geographic, demographic, and socioeconomic diversities. Screening by LDCT will target current or former (quitting < 10 years) smokers (> 15 cigarettes/day for > 25 years, or > 10 cigarettes/day for > 30 years) aged 50-75 years. Lung nodules will be volumetric measured and classified by a modified PEOPLHE Lung-RADS 1.1 system. Current smokers will be offered smoking cessation support., Conclusion: The PEOPLHE program will provide information on strategies for screening enrollment and smoking cessation interventions; administrative, organizational, and radiological needs for performing a state-of-the-art LCS; collateral and incidental findings (both pulmonary and extrapulmonary), contributing to the LCS implementation within national healthcare systems., (© 2024. The Author(s).)

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double-blind, placebo-controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age ≤ 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6-OH-ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6-OH-ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6-OH-ME were not detectable in the placebo group at any study time-point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6-OH-ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6-OH-ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns., (© 2023 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd.)

Background: Artificial intelligence (AI) has proved to be of great value in diagnosing and managing Sars-Cov-2 infection. ALFABETO (ALL-FAster-BEtter-TOgether) is a tool created to support healthcare professionals in the triage, mainly in optimizing hospital admissions., Methods: The AI was trained during the pandemic's "first wave" (February-April 2020). Our aim was to assess the performance during the "third wave" of the pandemics (February-April 2021) and evaluate its evolution. The neural network proposed behavior (hospitalization vs home care) was compared with what was actually done. If there were discrepancies between ALFABETO's predictions and clinicians' decisions, the disease's progression was monitored. Clinical course was defined as "favorable/mild" if patients could be managed at home or in spoke centers and "unfavorable/severe" if patients need to be managed in a hub center., Results: ALFABETO showed accuracy of 76%, AUROC of 83%; specificity was 78% and recall 74%. ALFABETO also showed high precision (88%). 81 hospitalized patients were incorrectly predicted to be in "home care" class. Among those "home-cared" by the AI and "hospitalized" by the clinicians, 3 out of 4 misclassified patients (76.5%) showed a favorable/mild clinical course. ALFABETO's performance matched the reports in literature., Conclusions: The discrepancies mostly occurred when the AI predicted patients could stay at home but clinicians hospitalized them; these cases could be handled in spoke centers rather than hubs, and the discrepancies may aid clinicians in patient selection. The interaction between AI and human experience has the potential to improve both AI performance and our comprehension of pandemic management., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Preda Prof Lorenzo reports financial support was provided by Lombardy Region., (© 2023 The Authors.)

Hydrothermally formed mesoporous SnO 2 was used as a support for nickel chemical deposition and, after subsequent thermal treatment, a high specific surface area (36 m 2 g -1 ) Ni/SnO 2 material was obtained. XPS analysis has shown that in the Sn 3d region the spectrum is similar to that of pristine SnO 2 , whereas Ni species are present on the surface as NiO, Ni 2 O 3 and Ni(OH) 2 . Mixing Ni/SnO 2 with a small amount of Black Pearls (BP) leads to a significant enhancement of the resulting Ni/SnO 2 -BP composite activity for nitrite anodic oxidation, presumably due to the higher surface area (115 m 2 g -1 ), to better electrical conductivity and to a certain contribution of the BP to an increase in surface density of the active sites. Ni/SnO 2 -BP also outperforms pristine BP (in terms of Tafel slopes and electron-transfer rates), most likely due to the fact that the Ni(II)/Ni(III) couple can act as an electrocatalyst for nitrite oxidation. A voltammetric method is proposed for the determination of nitrite, over a concentration range of three orders of magnitude (0.05 to 20 mM), with good reproducibility, high stability and excellent sensitivity. The high upper limit of the dynamic range of the analytically useful response might provide a basis for the reliable quantification of nitrite in wastewater.

Salivary gland cancers (SGCs) are rare, accounting for less than 5% of all malignancies of the head and neck region, and are morphologically heterogeneous. The diagnosis is mainly based on histology, with the complementary aid of molecular profiling, which is helpful in recognizing some poorly differentiated, borderline, or atypical lesions. Instrumental imaging defines the diagnosis, representing a remarkable tool in the treatment plan. Ultrasound and magnetic resonance are the most common procedures used to describe the primary tumour. The treatment of SGCs is multimodal and consists of surgery, radiotherapy, and systemic therapy; each treatment plan is, however, featured on the patient and disease's characteristics. On 24 June 2022, in the meeting "Current management and future challenges in salivary gland cancers" many experts in this field discussed the state of the art of SGCs research, the future challenges and developments. After the meeting, the same pool of experts maintained close contact to keep these data further updated in the conference proceedings presented here. This review collects the insights and suggestions that emerged from the discussion during and after the meeting per se., Competing Interests: LDL received conference honoraria/advisory board fees from: Lilly, MSD, EISAI, Roche, Bayer, Merck Serono, Istituto Gentili Srl, New Bridge; RF had consulting or Advisory Role in Regeneron, Sanofi, Prelude Therapeutics, Elevar Therapeutics, Guidepoint, Expert Connect, Remix, Eisai, Bioatla, Coherus in the past 24 months and received Research Funds Inst from Prelude, Ayala, Merck, Genentech, Pfizer, Rakuten, Nanobiotix, EMD Serono, ISA, Viracta, and Gilead in the past 24 months; LL received Research funds donated directly to the institution for clinical trials from: Adlai Nortye, Astrazeneca, BMS, Debiopharm International SA, Eisai, Eli Lilly and Company, Exelixis, Hoffmann-La Roche ltd, Isa Therapeutics, Kura Oncology, Merck-Serono, MSD, Merck Sharp&Dome Corp, Nektar Therapeutics, Novartis, Regeneron, Roche, Sanofi, Syneos, Sun Pharmaceutica and received occasional fees for participation as a speaker at conferences/congresses or as a scientific consultant for advisory boards from: Adlai Nortye, Astrazeneca, Bicara Therapeutics, DRG part of Clarivate, Genmab US, GlaxoSmithKline, Bayer, Mirati Therapeutics, MSD, Merck-Serono, Merck Healthcare KGaA, Neutron Therapeutics Inc, Seagen International BmbH. The remaining 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., (Copyright © 2023 Locati, Ferrarotto, Licitra, Benazzo, Preda, Farina, Gatta, Lombardi, Nicolai, Vander Poorten, Chua, Vischioni, Sanguineti, Morbini, Fonseca, Sozzi, Merlotti and Orlandi.)

We investigated the association of T1/T2 mapping values with programmed death-ligand 1 protein (PD-L1) expression in lung cancer and their potential in distinguishing between different histological subtypes of non-small cell lung cancers (NSCLCs). Thirty-five patients diagnosed with stage III NSCLC from April 2021 to December 2022 were included. Conventional MRI sequences were acquired with a 1.5 T system. Mean T1 and T2 mapping values were computed for six manually traced ROIs on different areas of the tumor. Data were analyzed through RStudio. Correlation between T1/T2 mapping values and PD-L1 expression was studied with a Wilcoxon-Mann-Whitney test. A Kruskal-Wallis test with a post-hoc Dunn test was used to study the correlation between T1/T2 mapping values and the histological subtypes: squamocellular carcinoma (SCC), adenocarcinoma (ADK), and poorly differentiated NSCLC (PD). There was no statistically significant correlation between T1/T2 mapping values and PD-L1 expression in NSCLC. We found statistically significant differences in T1 mapping values between ADK and SCC for the periphery ROI ( p -value 0.004), the core ROI ( p -value 0.01), and the whole tumor ROI ( p -value 0.02). No differences were found concerning the PD NSCLCs.

Pulmonary hypertension (PH) is a pathophysiological disorder, defined by a mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, as assessed by right heart catheterization (RHC). PH is not a specific disease, as it may be observed in multiple clinical conditions and may complicate a variety of thoracic diseases. Conditions associated with the risk of developing PH are categorized into five different groups, according to similar clinical presentations, pathological findings, hemodynamic characteristics, and treatment strategy. Most chronic lung diseases that may be complicated by PH belong to group 3 (interstitial lung diseases, chronic obstructive pulmonary disease, combined pulmonary fibrosis, and emphysema) and are associated with the lowest overall survival among all groups. However, some of the chronic pulmonary diseases may develop PH with unclear/multifactorial mechanisms and are included in group 5 PH (sarcoidosis, pulmonary Langerhans' cell histiocytosis, and neurofibromatosis type 1). This paper focuses on PH associated with chronic lung diseases, in which radiological imaging-particularly computed tomography (CT)-plays a crucial role in diagnosis and classification. Radiologists should become familiar with the hemodynamical, physiological, and radiological aspects of PH and chronic lung diseases in patients at risk of developing PH, whose prognosis and treatment depend on the underlying disease.

Background: The role of computed tomography (CT) in the diagnosis and characterization of coronavirus disease 2019 (COVID-19) pneumonia has been widely recognized. We evaluated the performance of a software for quantitative analysis of chest CT, the LungQuant system, by comparing its results with independent visual evaluations by a group of 14 clinical experts. The aim of this work is to evaluate the ability of the automated tool to extract quantitative information from lung CT, relevant for the design of a diagnosis support model., Methods: LungQuant segments both the lungs and lesions associated with COVID-19 pneumonia (ground-glass opacities and consolidations) and computes derived quantities corresponding to qualitative characteristics used to clinically assess COVID-19 lesions. The comparison was carried out on 120 publicly available CT scans of patients affected by COVID-19 pneumonia. Scans were scored for four qualitative metrics: percentage of lung involvement, type of lesion, and two disease distribution scores. We evaluated the agreement between the LungQuant output and the visual assessments through receiver operating characteristics area under the curve (AUC) analysis and by fitting a nonlinear regression model., Results: Despite the rather large heterogeneity in the qualitative labels assigned by the clinical experts for each metric, we found good agreement on the metrics compared to the LungQuant output. The AUC values obtained for the four qualitative metrics were 0.98, 0.85, 0.90, and 0.81., Conclusions: Visual clinical evaluation could be complemented and supported by computer-aided quantification, whose values match the average evaluation of several independent clinical experts., Key Points: We conducted a multicenter evaluation of the deep learning-based LungQuant automated software. We translated qualitative assessments into quantifiable metrics to characterize coronavirus disease 2019 (COVID-19) pneumonia lesions. Comparing the software output to the clinical evaluations, results were satisfactory despite heterogeneity of the clinical evaluations. An automatic quantification tool may contribute to improve the clinical workflow of COVID-19 pneumonia., (© 2023. The Author(s).)

Background: Radiomics represents an emerging field of precision-medicine. Its application in head and neck is still at the beginning., Methods: Retrospective study about magnetic resonance imaging (MRI) based radiomics in oral tongue squamous cell carcinoma (OTSCC) surgically treated (2010-2019; 79 patients). All preoperative MRIs include different sequences (T1, T2, DWI, ADC). Tumor volume was manually segmented and exported to radiomic-software, to perform feature extraction. Statistically significant variables were included in multivariable analysis and related to survival endpoints. Predictive models were elaborated (clinical, radiomic, clinical-radiomic models) and compared using C-index., Results: In almost all clinical-radiomic models radiomic-score maintained statistical significance. In all cases C-index was higher in clinical-radiomic models than in clinical ones. ADC provided the best fit to the models (C-index 0.98, 0.86, 0.84 in loco-regional recurrence, cause-specific mortality, overall survival, respectively)., Conclusion: MRI-based radiomics in OTSCC represents a promising noninvasive method of precision medicine, improving prognosis prediction before surgery., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Aims: Arrhythmogenic cardiomyopathy with left ventricular involvement (ACM-LV), particularly in case of isolated left ventricular involvement (i.e. left dominant arrhythmogenic cardiomyopathy, LDAC) and previous infectious myocarditis (pIM) may have overlapping clinical and cardiac magnetic resonance (CMR) features. To date, there are no validated CMR criteria for the differential diagnosis between these conditions. The present study aimed to identify CMR characteristics to distinguish ACM-LV from pIM., Methods and Results: This observational, retrospective, single-centre study included 30 pIM patients and 30 ACM-LV patients. In ACM-LV patients CMR was performed at diagnosis; in patients with pIM, CMR was performed six months after acute infection. CMR analysis included quantitative assessment of left ventricle (LV) volumes, systolic function and wall thicknesses, qualitative and quantitative assessment of late gadolinium enhancement (LGE) sequences. Compared with pIM, ACM-LV patients showed slightly larger LV volumes, more frequent regional wall motion anomalies and reduced wall thicknesses. ACM-LV patients had higher amounts of LV LGE and extension. Notably, the LDAC subgroup had the highest amount of LV LGE. LV LGE amount > 15 g and a LV LGE percentage > 30% of LV mass discriminated ACM-LV from pIM with a 100% specificity. LGE segmental distribution was superimposable among the groups, except for septal segments that were more frequently involved in ACM-LV and LDAC patients., Conclusions: A great extension of LV LGE (a cut-off of LGE >15 g and a percentage above 30% of LV LGE in relation to total myocardial mass) discriminates ACM-LV from pIM with extremely high specificity., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Magnetic resonance imaging (MRI) is a widely used diagnostic technique. Patients wearing orthodontic devices are often requested to remove their appliances before an MRI exam, even when the exam involves anatomical areas far from the head, in order to prevent the heating and detachment of the appliances. The present report aims to evaluate changes in temperature and adhesive forces of molar bands after MRI at two different strength outputs. Sixty stainless steel molar bands were bonded on permanent human upper molars using two different cements: Unitek Multi-Cure Glass Ionomer Band Cement (3M Unitek, Monrovia, CA, USA) and Transbond Plus Light Cure Band Adhesive (3M Unitek). Appliances were subjected to MRI with two different strengths (1.5 Tesla and 3 Tesla). Tubes and band temperature was measured before and after MRI. Subsequently, the shear bond strength (SBS) test was calculated. Data underwent statistical analysis (p < 0.05). After MRI, molar bands exhibited significant heating, even though not clinically relevant, with a temperature increase ranging between 0.48 °C and 1.25 °C (p < 0.05). SBS did not show significant differences (p > 0.05). The present study suggests that, under MRI, the molar bands tested are safe; therefore, their removal could be not recommended for non-head and neck MRI exams. Removal would be necessary just in artifact risk areas.

Objectives: More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups., Methods: A total of 407 consecutive COVID-19 patients who were admitted to the Fondazione IRCCS Policlinico San Matteo, Pavia and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest CT study, which was evaluated for specific lung alterations and morphological patterns., Results: The most frequently observed lung CT alterations, in order of frequency, were ground-glass opacities (81%), linear opacities (74%), bronchiolectases (64.81%), and reticular opacities (63.88%). The most common morphological pattern was the non-specific interstitial pneumonia pattern (63.88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29.62%)., Conclusions: Our work showed that recovered COVID-19 patients who were hospitalized and who exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations., Advances in Knowledge: This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19.

Objective: The space comprised between tumor and neck lymph nodes (T-N tract) is one of the main routes of tumor spread in oral cavity tumors. Aim of the study was to investigate the impact of T-N tract involvement on the postoperative radiotherapy (PORT) outcomes., Materials and Methods: Patients (pts) treated between 2000 and 2016 with indication to PORT were retrospectively retrieved. Inclusion criteria were: (a) locally advanced tumors of the oral cavity, (b) who received with indication to PORT (c) with a minimum follow-up of six months., Results: One hundred and fifty-seven pts met the inclusion criteria (136 pts treated with PORT and 21 pts not treated with PORT). In the PORT cohort, the T-N tract involvement had no impact on both OS (p = .09) and LRFS (p = .2). Among the non-PORT cohort, both OS (p = .007) and LRFS (p = .017) were worse for pts with positive T-N tract compared to those with negative T-N tract. PORT improved both OS (p = .008) and LRFS (p = .003) in pts with positive T-N tract but not in those with negative T-N tract (p = .36 and p = .37, respectively)., Conclusions: Our results suggest that involvement of T-N tract should be considered as prognostic factors informing the indication to PORT., (© 2021 Wiley Periodicals LLC.)

High-resolution CT-scan (HRCT) plays a major role in the diagnosis of Nontuberculous mycobacteria lung disease (NTM-LD), but its role in follow-up is controversial. Our aim was first to conceive a radiological score able to quantify the severity of pulmonary involvement by NTM infection and, second, to check its association with the NTM-LD clinical burden. We also intended, if possible, to verify the potential influence of NTM specific treatment on the radiological score. We retrospectively collected the clinical, microbiological and radiological data of all patients who were admitted to our hospital from 1 January 2012 to 1 January 2020 with a confirmed diagnosis of NTM-LD. A radiological score was applied to evaluate lung involvement on HRCT at diagnosis and at 6-18 months follow-up. Twenty-eight patients with NTM-LD performed follow-up HRCT. No association was found between radiological and clinical score (Spearman R -0.05, 95%CI -0.41 to 0.33). Repeated measures analysis showed a significant increase in radiological score over time (change 1.11, 95%CI 0.10 to 2.11; p-value 0.032), while Mann-Whitney test did not show any difference between treated and untreated patients (p value 0.922). Further studies are needed to assess the usefulness of routine radiological follow-up in patients with NTM-LD.

This study aims to investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in magnetic resonance imaging (MRI) and programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC). Twenty-one patients diagnosed with stage III NSCLC from April 2021 to April 2022 were included. The tumors were distinguished into two groups: no PD-L1 expression (<1%), and positive PD-L1 expression (≥1%). Conventional MRI and IVIM-DWI sequences were acquired with a 1.5-T system. Both fixed-size ROIs and freehand segmentations of the tumors were evaluated, and the data were analyzed through a software using four different algorithms. The diffusion (D), pseudodiffusion (D*), and perfusion fraction (pf) were obtained. The correlation between IVIM parameters and PD-L1 expression was studied with Pearson correlation coefficient. The Wilcoxon−Mann−Whitney test was used to study IVIM parameter distributions in the two groups. Twelve patients (57%) had PD-L1 ≥1%, and 9 (43%) <1%. There was a statistically significant correlation between D* values and PD-L1 expression in images analyzed with algorithm 0, for fixed-size ROIs (189.2 ± 65.709 µm²/s × 104 in no PD-L1 expression vs. 122.0 ± 31.306 µm²/s × 104 in positive PD-L1 expression, p = 0.008). The values obtained with algorithms 1, 2, and 3 were not significantly different between the groups. The IVIM-DWI MRI parameter D* can reflect PD-L1 expression in NSCLC.

The use of artificial intelligence (AI) and radiomics in the healthcare setting to advance disease diagnosis and management and facilitate the creation of new therapeutics is gaining popularity. Given the vast amount of data collected during cancer therapy, there is significant concern in leveraging the algorithms and technologies available with the underlying goal of improving oncologic care. Radiologists will attain better precision and effectiveness with the advent of AI technology, making machine-assisted medical services a valuable and important option for future oncologic medical care. As a result, it is critical to figure out which specific radiology activities are best positioned to gain from AI and radiomics models and methods of oncologic imaging, while also considering the algorithms' capabilities and constraints. Our purpose is to overview the current evidence and future prospects of AI and radiomics algorithms used in oncologic imaging efforts with an emphasis on the three most frequent cancers worldwide, i.e., lung cancer, breast cancer and colorectal cancer. We discuss how AI and radiomics could be used to detect and characterize cancers and assess therapy response., (© 2022. Italian Society of Medical Radiology.)

Aim: To evaluate the association between pretreatment diffusion-weighted MRI (DW-MRI) and 12-month radiological response in locally recurrent rectal cancer treated with carbon ion radiotherapy. Methods: Histogram analysis was performed on pretreatment DW-MRI for patients re-irradiated with carbon ion radiotherapy for local recurrence of rectal cancer. Results: A total of 17 patients were enrolled in the study. Pretreatment DW-MRI b-value of 1000 s/mm 2 (b1000) and apparent diffusion coefficient (ADC) lesion median values for 1-year nonresponders (six patients) and responders (11 patients) demonstrated a median (interquartile of median values) of 62.5 (23.9) and 34.0 (13.0) and 953.0 (277.0) and 942.5 (339.0) μm 2 /s, respectively. All b1000 histogram features (h-features) and ADC h-kurtosis showed statistically significant differences, whereas only b1000 h-median, b1000 h-interquartile range and ADC h-kurtosis demonstrated remarkable diagnostic accuracy. Conclusion: DW-MRI showed promising results in predicting carbon ion radiotherapy outcome in local recurrence of rectal cancer, particularly with regard to b1000 h-median, b1000 h-interquartile range and ADC h-kurtosis.

Objective: To report the personalized decision-making pro- cess adopted for a cochlear implant (CI) candidate requiring magnetic resonance imaging (MRI) brain surveillance., Study Design: Clinical capsule report., Setting: Tertiary academic referral center., Patient: A 23-year-old man affected by posttraumatic bilat- eral profound hearing loss, already in radiological follow-up for a suspected small left cuneal low-grade glioma., Interventions: A multidisciplinary approach involving preoperative MRI simulations and 3D printed (3DP) models aiming to adapt the CI position to facilitate MRI brain lesion visibility., Main Outcome Measures: MRI visibility and surgical approach., Results: Preoperative MRI scans with the placement of an Ultra 3D CI were performed simulating different implant location to assess the brain lesion visibility in MRI. CI was positioned 9 cm away from the external auditory canal with an angle of 90 degrees. To assess the technical feasibility of the surgical procedure, a patient-specific 3DP head model was produced preoperatively. The postoperative course was uneventful, the patient showed a significant benefit from CI, and the brain lesion was highly visible at the MRI follow-up., Conclusions: The employment of strategies aimed at improving the MRI quality in CI recipients still represents a topic requiring attention. Thanks to multidisciplinary team collaboration, in our case, the CI position was successfully determined to allow unhindered MRI visibility of a specific intracranial structure., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Rationale: Abnormal values of hypercoagulability biomarkers, such as D-dimer, have been described in Coronavirus Disease 2019 (COVID-19), which has also been associated with disease severity and in-hospital mortality. COVID-19 patients with pneumonia are at greater risk of pulmonary embolism (PE). However, the real incidence of PE is not yet clear, since studies have been limited in size, mostly retrospective, and PE diagnostic procedures were only performed when PE was clinically suspected., Objectives: (1) To determine the incidence, clinical, radiological, and biological characteristics, and clinical outcomes of PE among patients hospitalized for COVID-19 pneumonia with D-dimer > 1,000 ng/mL. (2) To develop a prognostic model to predict PE in these patients., Methods: Single-center prospective cohort study. Consecutive confirmed cases of COVID-19 pneumonia with D-dimer > 1,000 ng/mL underwent computed tomography pulmonary angiography (CTPA). Demographic and laboratory data, comorbidities, CTPA scores, treatments administered, and clinical outcomes were analyzed and compared between patients with and without PE. A risk score was constructed from all these variables., Results: Between 6 April 2020 and 2 February 2021, 179 consecutive patients were included. The overall incidence of PE was 39.7% (71 patients) (CI 95%, 32-47%). In patients with PE, emboli were located mainly in segmental/subsegmental arteries (67%). Patients with PE did not differ from the non-PE group in sex, age, or risk factors for thromboembolic disease. Higher urea, D-Dimer, D-dimer-to-ferritin and D-dimer-to-lactate dehydrogenase (LDH) ratios, platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR) values were found in patients with PE when compared to patients with non-PE. Besides, lymphocyte counts turned out to be lower in patients with PE. A score for PE prediction was constructed with excellent overall performance [area under the ROC curve-receiver operating characteristic (AUC-ROC) 0.81 (95% CI: 0.73-0.89)]. The PATCOM score stands for Pulmonary Artery Thrombosis in COVID-19 Mallorca and includes platelet count, PDW, urea concentration, and D-dimer-to-ferritin ratio., Conclusion: COVID-19 patients with pneumonia and D-dimer values > 1,000 ng/mL were presented with a very high incidence of PE, regardless of clinical suspicion. Significant differences in urea, D-dimer, PDW, NLR, and lymphocyte count were found between patients with PE and non-PE. The PATCOM score is presented in this study as a promising PE prediction rule, although validation in further studies is required., Competing Interests: AA-F reports personal fees from Astrazeneca, GSK, Chiesi, and Menarini, from outside the submitted work. JS reports personal fees, as a speaker, from Roche and Boehringer-Ingelheim, with no relationship with the submitted work. ES-L reports personal fees from Astrazeneca, GSK, and Boehringer-Ingelheim, personal and advisory board fees from MSD, and grants, personal, and advisory board fees from Actelion and Janssen, from outside the submitted work. BN reports personal fees from Roche, Brystol, and Boehringer-Ingelheim, with no relationship with the submitted work. The remaining 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., (Copyright © 2022 Suarez Castillejo, Toledo-Pons, Calvo, Ramon-Clar, Martínez, Hermoso de Mendoza, Morell-García, Bauça, Berga, Núñez, Preda, Sauleda, Argente Castillo, Ballesteros, Martín, Sala-Llinas and Alonso-Fernández.)

Purposes: To investigate the effects for Ultra 3D cochlear implant (CI) positioning on MR imaging quality, looking at a comprehensive description of intracranial structures in cases of unilateral and bilateral CI placement., Methods: Four CI angular positions (90°, 120°, 135° and 160°) at 9 cm distance from the outer-ear canal were explored. The 1.5 T MRI assessment included our institutional protocol for the investigation of brain pathologies without gadolinium application. Three investigators (two experienced neuroradiologists and one experienced otoneurosurgeon) independently evaluated the MR findings. A 4-point scale was adopted to describe 14 intracranial structures and to determine which CI positioning allowed the best image quality score and how bilateral CI placement modified MRI scan visibility., Results: A high positive correlation was found between the three blinded observers. Structures situated contralateral from the CI showed high-quality values in all four placements. Structures situated ipsilaterally provided results suitable for diagnostic purposes for at least one position. At 90°, artifacts mainly involved brain structures located cranially and anteriorly (e.g., temporal lobe); on the contrary, at 160°, artifacts mostly influenced the posterior fossa structures (e.g., occipital lobe). For the bilateral CI condition, MR imaging examination revealed additional artifacts involving all structures located close to either CI, where there was a signal void/distortion area., Conclusions: Suitable unilateral CI positioning can allow the visualization of intracranial structures with sufficient visibility for diagnostic purposes. Bilateral CI positioning significantly deteriorates the anatomical visibility. CI positioning might play a crucial role for patients who need post-operative MRI surveillance., (© 2021. The Author(s).)

Smoking is the main risk factor for lung cancer (LC), which is the leading cause of cancer-related death worldwide. Independent randomized controlled trials, governmental and inter-governmental task forces, and meta-analyses established that LC screening (LCS) with chest low dose computed tomography (LDCT) decreases the mortality of LC in smokers and former smokers, compared to no-screening, especially in women. Accordingly, several Italian initiatives are offering LCS by LDCT and smoking cessation to about 10,000 high-risk subjects, supported by Private or Public Health Institutions, envisaging a possible population-based screening program. Because LDCT is the backbone of LCS, Italian radiologists with LCS expertise are presenting this position paper that encompasses recommendations for LDCT scan protocol and its reading. Moreover, fundamentals for classification of lung nodules and other findings at LDCT test are detailed along with international guidelines, from the European Society of Thoracic Imaging, the British Thoracic Society, and the American College of Radiology, for their reporting and management in LCS. The Italian College of Thoracic Radiologists produced this document to provide the basics for radiologists who plan to set up or to be involved in LCS, thus fostering homogenous evidence-based approach to the LDCT test over the Italian territory and warrant comparison and analyses throughout National and International practices., (© 2022. The Author(s).)

Objectives: Although antisynthetase antibodies (ARS) are the established markers of the so-called antisynthetase syndrome (ASSD), in these patients the concomitant positivity of anti-Ro52 antibodies, reported in up to the 50% of cases, is not rare. Several studies focused on the effect of different ARS specificities on the evolution of ASSD, the most recent showing no effects. On the contrary, the role of co-occurring anti-Ro52 antibodies in ASSD is still debated. We investigated the potential of anti-Ro52 antibodies in identifying a clinical phenotype of ASSD or influencing prognosis, irrespectively to the underlying ARS specificity., Methods: Retrospective analysis of clinical, imaging and laboratory characteristics, therapeutic approaches and outcome at baseline and at last follow-up, of 60 ASSD patients progressively enrolled at our Hospital., Results: We identified 34 anti-Ro+ and 26 anti-Ro- ASSD patients. Classic triad prevalence at baseline was similar between the two groups, whereas interstitial lung disease (ILD) (p value=0.01) and myositis (p value=0.03) were significantly more prevalent in anti-Ro52+ and in anti-Ro52- patients at last follow up, respectively. No differences in therapeutic approaches, oxygen need and ILD patterns were observed. Overall mortality was 25% (15 subjects). No differences in mortality, overall and disease related, between anti-Ro52+ and anti-Ro52- patients were observed (p value=0.764), despite the more frequent ILD occurrence in anti-Ro52+ patients. Survival curves were not different at any time point (Log-rank test, p value 0.98)., Conclusions: Anti-Ro52 antibodies affect time course and clinical characteristics of ASSD. Although ILD is significantly more associated to anti-Ro52 antibodies, no difference in mortality was observed compared to anti-Ro52 negative patients.

Objectives: To evaluate the quality of the reports of loco-regional staging computed tomography (CT) or magnetic resonance imaging (MRI) in head and neck (H&N) cancer., Methods: Consecutive reports of staging CT and MRI of all H&N cancer cases from 2018 to 2020 were collected. We created lists of quality indicators for tumor (T) for each district and for node (N). We marked these as 0 or 1 in the report calculating a report score (RS) and a maximum sum (MS) of each list. Two radiologists and two otolaryngologists in consensus classified reports as low quality (LQ) if the RS fell in the percentage range 0-59% of MS and as high quality (HQ) if it fell in the range 60-100%, annotating technique and district. We evaluated the distribution of reports in these categories., Results: Two hundred thirty-seven reports (97 CT and 140 MRI) of 95 oral cavity, 52 laryngeal, 47 oropharyngeal, 19 hypo-pharyngeal, 14 parotid, and 10 nasopharyngeal cancers were included. Sixty-six percent of all the reports were LQ for T, 66% out of all the MRI reports, and 65% out of all CT reports were LQ. Eight-five percent of reports were HQ for N, 85% out of all the MRI reports, and 82% out of all CT reports were HQ. Reports of oral cavity, oro-nasopharynx, and parotid were LQ, respectively, in 76%, 73%, 100% and 92 out of cases., Conclusion: Reports of staging CT/MRI in H&N cancer were LQ for T description and HQ for N description., (© 2022. Italian Society of Medical Radiology.)

Background and Purpose: In the retrospective-prospective multi-center "Blue Sky Radiomics" study (NCT04364776), we plan to test a pre-defined radiomic signature in a series of stage III unresectable NSCLC patients undergoing chemoradiotherapy and maintenance immunotherapy. As a necessary preliminary step, we explore the influence of different image-acquisition parameters on radiomic features' reproducibility and apply methods for harmonization., Material and Methods: We identified the primary lung tumor on two computed tomography (CT) series for each patient, acquired before and after chemoradiation with i.v. contrast medium and with different scanners. Tumor segmentation was performed by two oncological imaging specialists (thoracic radiologist and radio-oncologist) using the Oncentra Masterplan® software. We extracted 42 radiomic features from the specific ROIs (LIFEx). To assess the impact of different acquisition parameters on features extraction, we used the Combat tool with nonparametric adjustment and the longitudinal version (LongComBat)., Results: We defined 14 CT acquisition protocols for the harmonization process. Before harmonization, 76% of the features were significantly influenced by these protocols. After, all extracted features resulted in being independent of the acquisition parameters. In contrast, 5% of the LongComBat harmonized features still depended on acquisition protocols., Conclusions: We reduced the impact of different CT acquisition protocols on radiomic features extraction in a group of patients enrolled in a radiomic study on stage III NSCLC. The harmonization process appears essential for the quality of radiomic data and for their reproducibility. ClinicalTrials.gov Identifier: NCT04364776, First Posted:April 28, 2020, Actual Study Start Date: April 15, 2020, https://clinicaltrials.gov/ct2/show/NCT04364776 ., (© 2022. The Author(s).)

Background: The present study aims to evaluate dosimetric and clinical risk factors for the development of maxillary osteoradionecrosis (ORN) in head and neck adenoid cystic carcinoma (ACC) patients treated with carbon ion radiotherapy (CIRT)., Methods: Clinical data and treatment plans of ACC patients, consecutively treated from January 2013 to September 2016 within the phase II clinical trial CNAO S9/2012/C, were retrospectively reviewed. ORN and other treatment-related toxicity were graded according to the Common Terminology Criteria for Adverse Events (CTACE), version 4.0. The maxillary bone was contoured on the planning CT, and only patients receiving more than 10% of the prescription dose at their maxilla were considered for the analysis (67 patients). The volumes of maxilla receiving doses from 10 Gy (RBE) to 60 Gy (RBE) (V D ), with an increment of 10 Gy (RBE), and additional clinical factors were correlated to the incidence of ORN with univariate analysis (Chi-square test). The logistic regression model was subsequently applied for multivariate analysis. Treatment plans calculated with a local effect model (LEM)-based optimization were recalculated with the modified microdosimetric kinetic model (MKM), and compared with literature data from the Japanese experience., Results: The median time interval from the start of CIRT to ORN appearance was 24 months (range, 8-54 months). Maxillary ORN was observed in 11 patients (16.4%). Grade 1 ORN was observed in 2 patients (18.1%), G2 in 4 (36.3%), G3 in 4 (36.3%) and G4 in 1 (9.3%). From univariate analysis, the site of the tumor, the presence of teeth within the PTV and acute mucositis correlated with the development of maxillary ORN. V D were significantly higher for all the dose levels tested in patients with maxillary ORN than patients without necrosis, according to both radiobiological models. The multivariate analysis showed that V60 significantly correlated with ORN risk., Conclusion: The volume of maxilla irradiated with high dose values was relevant for ORN development in our cohort of ACC patients. These results are in line with previously published data obtained with a different radiobiological model. Our findings might be helpful to prevent the risk of ORN in patients receiving CIRT., 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 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., (Copyright © 2022 Vischioni, Russo, Meuli, Bonora, Ronchi, Ingargiola, Camarda, Imparato, Preda, Ciocca, Molinelli and Orlandi.)

Recent epidemiological data report that worldwide more than 53 million people have been infected by SARS-CoV-2, resulting in 1.3 million deaths. The disease has been spreading very rapidly and few months after the identification of the first infected, shortage of hospital resources quickly became a problem. In this work we investigate whether artificial intelligence working with chest X-ray (CXR) scans and clinical data can be used as a possible tool for the early identification of patients at risk of severe outcome, like intensive care or death. Indeed, further to induce lower radiation dose than computed tomography (CT), CXR is a simpler and faster radiological technique, being also more widespread. In this respect, we present three approaches that use features extracted from CXR images, either handcrafted or automatically learnt by convolutional neuronal networks, which are then integrated with the clinical data. As a further contribution, this work introduces a repository that collects data from 820 patients enrolled in six Italian hospitals in spring 2020 during the first COVID-19 emergency. The dataset includes CXR images, several clinical attributes and clinical outcomes. Exhaustive evaluation shows promising performance both in 10-fold and leave-one-centre-out cross-validation, suggesting that clinical data and images have the potential to provide useful information for the management of patients and hospital resources., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Carbon ion radiation therapy (CIRT) is an emerging radiation technique with advantageous physical and radiobiologic properties compared to conventional radiotherapy (RT) providing better response in case of radioresistant and hypoxic tumors. Our aim is to critically review if functional imaging techniques could play a role in predicting outcome of CIRT-treated tumors, as already proven for conventional RT., Methods: 14 studies, concerning Magnetic resonance imaging (MRI) and Positron Emission Tomography (PET), were selected after a comprehensive search on multiple electronic databases from January 2000 to March 2020., Results: MRI studies (n = 5) focused on diffusion-weighted MRI and, even though quantitative parameters were the same in all studies (apparent diffusion coefficient, ADC), results were not univocal, probably due to different imaging acquisition protocols and tumoral histology. For PET studies (n = 9), different tracers were used such as [ 18 F]FDG and other uncommon tracers ([ 11 C]MET, [ 18 F]FLT), with a relevant heterogeneity regarding parameters used for outcome assessment., Conclusion: No conclusion can be drawn on the predictive value of functional imaging in CIRT-treated tumors. A standardization of image acquisition, multi-institutional large trials and external validations are needed in order to establish the prognostic value of functional imaging in CIRT and to guide clinical practice., Advances in Knowledge: Emerging studies focused on functional imaging's role in predicting CIRT outcome. Due to the heterogeneity of images acquisition and studies, results are conflicting and prospective large studies with imaging standardized protocol are needed.

Internal or common carotid artery encasement (CAE) is observed in almost 2-7% of head and neck cancers (HNC) and designates the tumor with the T4b category. This clinical scenario is associated with a dismal prognosis, owing to the risk for thrombosis and bleeding that usually characterizes such an advanced cancer. Standardized radiological criteria to infer invasion of the carotid artery are lacking. Complete surgical resection in the context of a multimodality treatment is supposed to offer the greatest chances of cure. Surgery can either be carotid-sparing or include carotidectomy. Data on probability of cerebrovascular and non-cerebrovascular complications, risk of carotid blowout, poor oncologic outcomes, and less-than-certain efficacy of diagnostic and interventional preventive procedures against cerebral infarction make it difficult to define surgery as the recommended option among other therapeutic strategies. Non-surgical therapies based on radiation therapy possibly combined with chemotherapy are more frequently employed in HNC with CAE. In this context, carotid blowout is the most feared complication, and its probability increases with tumor stage and cumulative radiation dose received by the vessel. The use of highly conformal radiotherapies such as intensity-modulated particle therapy might substantially improve the manageability of HNC with CAE by possibly reducing the risk of late sequalae. Despite evidence is frail, it appears logical that a case-by-case evaluation through multidisciplinary decision making between head and neck surgeons, radiation oncologists, medical oncologists, diagnostic and interventional radiologists, and vascular surgeons are of paramount value to offer the best therapeutic solution to patients affected by HNC with CAE., 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., (Copyright © 2021 Orlandi, Ferrari, Lafe, Preda, Benazzo, Vischioni, Bonora, Rampinelli, Schreiber, Licitra and Nicolai.)

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