Repeated endoscopic ultrasound-guided fine-needle biopsy of solid pancreatic lesions after previous nondiagnostic or inconclusive sampling.

OBJECTIVES: Repeated endoscopic ultrasound (EUS)-guided tissue acquisition represents the standard practice for solid pancreatic lesions after previous nondiagnostic or inconclusive results. Since data are lacking, we aimed to evaluate the diagnostic performance of repeated EUS fine-needle biopsy (rEUS-FNB) in this setting. The primary outcome was diagnostic accuracy; sample adequacy, sensitivity, specificity, and safety were secondary outcomes. METHODS: Consecutive patients undergoing rEUS-FNB for solid pancreatic lesions at 23 Italian centers from 2019 to 2021 were retrieved. Pathology on the surgical specimen, malignant histology together with ≥6-month follow-up, and benign pathology together with ≥12-month follow-up were adopted as gold standards. RESULTS: Among 462 patients, 56.5% were male, with a median age of 68 (59-75) years, malignancy prevalence 77.0%. Tumor size was 26 (20-35) mm. Second-generation FNB needles were used in 89.6% cases. Diagnostic accuracy, sensitivity, and specificity of rEUS-FNB were 89.2%, 91.4%, and 81.7%, respectively (19 false-negative and 12 false-positive results). On multivariate analysis, rEUS-FNB performed at high-volume centers (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.10-3.17; P = 0.03) and tumor size (OR 1.03; 95% CI 1.00-1.06; P = 0.05) were independently related to diagnostic accuracy. Sample adequacy was 94.2%. Use of second-generation FNB needles (OR 5.42; 95% CI 2.30-12.77; P < 0.001) and tumor size >23 mm (OR 3.04; 95% CI 1.31-7.06; P = 0.009) were independently related to sample adequacy. CONCLUSION: Repeated EUS-FNB allowed optimal diagnostic performance after nondiagnostic or inconclusive results. Patients' referral to high-volume centers improved diagnostic accuracy. The use of second-generation FNB needles significantly improved sample adequacy over standard EUS-FNB needles.

Cardiac Computed Tomography Evaluation of Association of Left Ventricle Disfunction and Epicardial Adipose Tissue Density in Patients with Low to Intermediate Cardiovascular Risk.

Background and objectives: Epicardial adipose tissue density (EAD) has been associated with coronary arteries calcium score, a higher load of coronary artery disease (CAD) and plaque vulnerability. This effect can be related to endocrine and paracrine effect of molecules produced by epicardial adipose tissue (EAT), that may influence myocardial contractility. Using coronary computed tomography angiography (CCT) the evaluation of EAD is possible in basal scans. The aim of the study is to investigate possible associations between EAD and cardiac function. Material and Methods: 93 consecutive patients undergoing CCT without and with contrast medium for known or suspected coronary CAD were evaluated. EAD was measured on basal scans, at the level of the coronary ostia, the lateral free wall of the left ventricle, at the level of the cardiac apex, and at the origin of the posterior interventricular artery. Cardiac function was evaluated in post-contrast CT scans in order to calculate ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV). Results: A statistically significant positive correlation between EAD and ejection fraction (r = 0.29, p-value < 0.01) was found. Additionally, a statistically significant negative correlation between EAD and ESV (r = -0.25, p-value < 0.01) was present. Conclusion: EAD could be considered a new risk factor associated with reduced cardiac function. The evaluation of this parameter with cardiac CT in patients with low to intermediate cardiovascular risk is possible.

Radiological pitfalls associated with the diagnosis of usual interstitial pneumonia pattern on high-resolution computed tomography and associated findings: experience from a single Italian center.

BACKGROUND: The diagnostic algorithm for idiopathic pulmonary fibrosis (IPF) based on high-resolution computed tomography (HRCT) findings and multidisciplinary discussion (MDD) has been well established. PURPOSE: To identify the causes of disagreement between non-thoracic and thoracic radiologist involved in MDD for the imaging diagnosis of usual interstitial pneumonia (UIP) patterns and associated findings on HRCT and to improve the understanding of IPF by non-expert radiologists through a more systematic approach to HRCT. MATERIAL AND METHODS: This study included 68 patients who underwent MDD for suspected IPF. We compared the first reports generated before MDD by non-expert radiologists with the CT pattern and associated findings of IPF reported by thoracic radiologist involved in MDD. RESULTS: Regarding the diagnosis of CT pattern by non-expert radiologists, 30/68 patients received a discordant diagnosis, and in another 28 reports, all features of the CT pattern were described without reaching a diagnostic conclusion. The first report was concordant in only 10 patients. For 63 cases in which associated findings were reported by expert radiologists in MDD, we documented discrepancies in 47 cases where associated findings were considered absent by the first non-thoracic radiologist. CONCLUSION: We found significant discrepancies in the imaging diagnosis of UIP patterns and associated findings on HRCT between non-expert and thoracic radiologists included in MDD. Therefore, in this study, we analyzed and suggested diagnostic strategies to improve non-expert radiologists' approach to HRCT.

Ablation of Liver X receptors α and ß leads to spontaneous peripheral squamous cell lung cancer in mice.

The etiology of peripheral squamous cell lung cancer (PSCCa) remains unknown. Here, we show that this condition spontaneously develops in mice in which the genes for two oxysterol receptors, Liver X Receptor (LXR) α (Nr1h3) and ß (Nr1h2), are inactivated. By 1 y of age, most of these mice have to be euthanized because of severe dyspnea. Starting at 3 mo, the lungs of LXRα,ß(Dko) mice, but not of LXRα or LXRß single knockout mice, progressively accumulate foam cells, so that by 1 y, the lungs are covered by a "golden coat." There is infiltration of inflammatory cells and progressive accumulation of lipid in the alveolar wall, type 2 pneumocytes, and macrophages. By 14 mo, there are three histological lesions: one resembling adenomatous hyperplasia, one squamous metaplasia, and one squamous cell carcinoma characterized by expression of transformation-related protein (p63), sex determining region Y-box 2 (Sox2), cytokeratin 14 (CK14), and cytokeratin 13 (CK13) and absence of thyroid transcription factor 1 (TTF1), and prosurfactant protein C (pro-SPC). RNA sequencing analysis at 12 mo confirmed a massive increase in markers of M1 macrophages and lymphocytes. The data suggest a previously unidentified etiology of PSCCa: cholesterol dysregulation and M1 macrophage-predominant lung inflammation combined with damage to, and aberrant repair of, lung tissue, particularly the peripheral parenchyma. The results raise the possibility that components of the LXR signaling may be useful targets in the treatment of PSCCa.

CCR2-dependent monocyte-derived macrophages resolve inflammation and restore gut motility in postoperative ileus.

OBJECTIVE: Postoperative ileus (POI) is assumed to result from myeloid cells infiltrating the intestinal muscularis externa (ME) in patients undergoing abdominal surgery. In the current study, we investigated the role of infiltrating monocytes in a murine model of intestinal manipulation (IM)-induced POI in order to clarify whether monocytes mediate tissue damage and intestinal dysfunction or they are rather involved in the recovery of gastrointestinal (GI) motility. DESIGN: IM was performed in mice with defective monocyte migration to tissues (C-C motif chemokine receptor 2, Ccr2-/ - mice) and wild-type (WT) mice to study the role of monocytes and monocyte-derived macrophages (MΦs) during onset and resolution of ME inflammation. RESULTS: At early time points, IM-induced GI transit delay and inflammation were equal in WT and Ccr2 -/- mice. However, GI transit recovery after IM was significantly delayed in Ccr2 -/- mice compared with WT mice, associated with increased neutrophil-mediated immunopathology and persistent impaired neuromuscular function. During recovery, monocyte-derived MΦs acquire pro-resolving features that aided in the resolution of inflammation. In line, bone marrow reconstitution and treatment with MΦ colony-stimulating factor 1 enhanced monocyte recruitment and MΦ differentiation and ameliorated GI transit in Ccr2 -/- mice. CONCLUSION: Our study reveals a critical role for monocyte-derived MΦs in restoring intestinal homeostasis after surgical trauma. From a therapeutic point of view, our data indicate that inappropriate targeting of monocytes may increase neutrophil-mediated immunopathology and prolong the clinical outcome of POI, while future therapies should be aimed at enhancing MΦ physiological repair functions.

Handy Hints About Raynaud's Phenomenon in Children: A Critical Review.

Raynaud's phenomenon (RP) is a vasospastic disorder characterized by recurrent self-limited episodes of skin pallor, cyanosis, and hyperemia caused by paroxysmal spasms in the small arteries of the fingers and toes and can occur in any age group. Hands, feet, nose, ears, and nipples can be affected. The diagnosis is made clinically, assessing varying degrees of ischemia in the involved areas of skin, but this transient ischemia may also herald the onset of connective tissue disease. Investigation is recommended when RP starts in childhood to exclude an underlying autoimmune condition and close follow-up for its development. Management of RP in children includes conservative and pharmacologic treatments.

Lung Involvement in Children with Hereditary Autoinflammatory Disorders.

Short-lived systemic inflammatory reactions arising from disrupted rules in the innate immune system are the operating platforms of hereditary autoinflammatory disorders (HAIDs). Multiple organs may be involved and aseptic inflammation leading to disease-specific phenotypes defines most HAIDs. Lungs are infrequently involved in children with HAIDs: the most common pulmonary manifestation is pleuritis in familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively caused by mutations in the MEFV and TNFRSF1A genes, while interstitial lung disease can be observed in STING-associated vasculopathy with onset in infancy (SAVI), caused by mutations in the TMEM173 gene. The specific pleuropulmonary diseases may range from sub-clinical abnormalities during inflammatory flares of FMF and TRAPS to a severe life-threatening disorder in children with SAVI.

The role of cardiac computed tomography in diagnostic and prognostic assessment of pregnancy related spontaneous coronary artery dissection: a case report.

Spontaneous coronary artery dissection (SCAD) is the most common cause of myocardial infarction during pregnancy or the postpartum period and has a major impact on cardiovascular morbidity and death in pregnant women. A 38-year-old woman with sudden cardiac arrest ten days postpartum urgently underwent coronarography, which showed an intraparietal hematoma of the left anterior descending (LAD) artery. Two days later, coronary computed tomography angiography (CCTA) was performed, which showed the evidence of SCAD in the mid-distal tract of LAD and the presence of transmural ischemic infarction in the apex and mid antero-septal wall in delayed acquisition. The patient was treated with a beta-blocker. Four months later CCTA showed complete resolution of SCAD and evolution of the infarcted areas. Given the high accuracy and noninvasiveness of CCTA, our case highlights the potential role of this imaging modality in the diagnosis and follow-up of pregnancy associated SCAD.

The role of self-efficacy beliefs in dealing with misinformation among adolescents.

The present study aims to understand the processes involved in misinformation among adolescents by examining the role of self-efficacy beliefs in dealing with misleading news. Specifically, we argue that the perceived capability to analyze and reflect critically on the reliability of online information sources should be stayed with the perceived self-regulatory capability to resist online social pressures to share unverifiable news. Moreover, we posited that specific online self-efficacies beliefs can be promoted by the capabilities related to regulating emotions and reflecting on new problems. In a sample of 273, we tested a path analysis model. The results attest that self-efficacy beliefs in dealing with online misinformation refer to specific capabilities: an active one, related to checking the sources of the news in order to validate their content, and an inhibitory one, related to the capability to refrain from sharing the news that seems unreliable. Moreover, self-efficacy beliefs in self-control during online interaction spreading misleading news are supported by cognitive reflective capability and self-efficacy in regulating negative emotion. The relationship between active self-efficacy related to fact-checking and sharing misleading news is not significant. The role of regulation in sharing misinformation during activated online dynamics is discussed.

Assessing student engagement from facial behavior in on-line learning.

The automatic monitoring and assessment of the engagement level of learners in distance education may help in understanding problems and providing personalized support during the learning process. This article presents a research aiming to investigate how student engagement level can be assessed from facial behavior and proposes a model based on Long Short-Term Memory (LSTM) networks to predict the level of engagement from facial action units, gaze, and head poses. The dataset used to learn the model is the one of the EmotiW 2019 challenge datasets. In order to test its performance in learning contexts, an experiment, involving students attending an online lecture, was performed. The aim of the study was to compare the self-evaluation of the engagement perceived by the students with the one assessed by the model. During the experiment we collected videos of students behavior and, at the end of each session, we asked students to answer a questionnaire for assessing their perceived engagement. Then, the collected videos were analyzed automatically with a software that implements the model and provides an interface for the visual analysis of the model outcome. Results show that, globally, engagement prediction from students' facial behavior was weakly correlated to their subjective answers. However, when considering only the emotional dimension of engagement, this correlation is stronger and the analysis of facial action units and head pose (facial movements) are positively correlated with it, while there is an inverse correlation with the gaze, meaning that the more the student's feels engaged the less are the gaze movements.

Health Communication in the Time of COVID-19 Pandemic: A Qualitative Analysis of Italian Advertisements.

In the climate of great uncertainty characterizing the COVID-19 pandemic, health communication played a significant role: several communicative strategies and channels were used to inform, educate and alert. Entropy-related risks were soon translated into the "infodemic", a wide-spread phenomenon with psychosocial and cultural roots. Therefore, new challenges for public institutions occurred: public health communication, especially expressed through advertising and audiovisual spots, was engaged to offer key support in combatting the disease, mitigating its effects and supporting health and psychological wellbeing. This work aims to investigate how the Italian public institutions addressed those challenges by employing institutional spots. We tried to answer two main research questions: (a) in line with the literature concerning persuasive communication, what were the main variables that social advertising concerning health attitudes and behaviors relied on; and (b) how the different variables were combined to propose specific communicative pathways following both the different waves/phases of the COVID-19 pandemic and the elaboration likelihood model. To answer these questions, 34 Italian spots were analyzed by means of qualitative multimodal analysis (including scopes, major narratives themes, central and peripheral cues). The results enabled us to individuate different communicative pathways, oriented by inclusivity, functionality and contamination, in line with different rounds as well as with the holistic configurations of cultural narratives, central and peripheral cues.

Incidental finding of intrathoracic caudate lobe of the liver associated with an arterovenous malformation.

In this case report we describe an occasional finding of intrathoracic caudate lobe protruding through the diaphragm foramen in a 73-year-old woman who came to our attention for a screening for coronary artery disease, due to the presence of cardiovascular risk. The patient had no symptoms. The computed tomography showed, a circumscribed homogeneous soft tissue mass that protruding through the aortic diaphragmatic foramen that was as isodense as the liver. Moreover was revealed an abnormal artery emerging from the celiac tripod which, through the diaphragmatic foramen, ends in an inferior pulmonary vein creating an arteriovenous malformation.

Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn's Disease: A Retrospective, International Multicenter Study.

BACKGROUND: The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn's disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification. METHODS: We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein <5 mg/L, fecal calprotectin <150 µg/g, or absence of inflammation at endoscopy or imaging), and ADA failure were investigated. RESULTS: A total of 131 CD patients were included, with a median disease duration of 9 (interquartile range, 4-17) years. 51% were biologic exposed prior to ADA and 50% received concomitant immunomodulators. Baseline drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders at either 6 or 12 months post dose-intensification. However, both higher drug levels at 6 and 12 months and a higher increment from baseline were associated with improved outcomes. On receiver-operating characteristic analyses, post-escalation ADA drug levels >10.7 µg/mL (area under the receiver-operating characteristic curve [AUROC], 0.66; P = .013) and >10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively. CONCLUSIONS: Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission.

Literature supporting therapeutic drug monitoring at secondary loss of response and post dose-intensification of adalimumab is limited. Adalimumab drug levels following dose-intensification rather than at the time of secondary loss of response are associated with subsequent Crohn's disease remission.

The Impact of Nitroglycerin on the Evaluation of Coronary Stenosis in Coronary-CT: Preliminary Study in 131 Patients.

BACKGROUND: The sublingual administration of short-acting nitroglycerin (NTG) before coronary computed tomography (CCT) improves the visualization of coronary arteries, causing vasodilatation. The aim of this study was to evaluate whether and how nitroglycerin can influence the concordance between radiologists and cardiologists in the evaluation of vessel stenosis measured in CCT by the former and during the following coronarography by the latter. METHODS: We conducted a retrospective analysis of 131 patients who underwent CCT for cardiac symptoms in 2022, followed by coronarography performed six months later because of significant stenosis revealed by the CCT. First, the patients were divided into two groups: an NTG group who received sublingual nitroglycerin before CCT and a non-NTG group who did not because of contraindications. Second, 254 stenoses were measured by two radiologists after CCT and by two interventional cardiologists during the next coronarography; moreover, stenoses were classified on the basis of their location and plaque pattern (calcific, mixed and lipidic). Third, the strength of agreement was evaluated between the two radiologists, between the two cardiologists and finally between the radiologists and cardiologists in order to evaluate whether and how the interdisciplinary discrepancy in stenosis evaluation could change with or without the use of nitroglycerin before CCT and in relation to the different plaque pattern. RESULTS: In the NTG group, the use of nitroglycerine reduced the agreement between radiologists and cardiologists in calcific stenosis but did not change the concordance in the case of mixed or lipidic plaques on the same vessels. CONCLUSIONS: The use of sublingual nitroglycerin before CCT may lead to a radiological overestimation of calcific stenosis.

Social signals: a framework in terms of goals and beliefs.

The paper defines the notion of social signal, in terms of a cognitive model of mind and social interaction, as a communicative or informative signal or a cue that directly or indirectly provides information about "social facts": social interactions, social emotions, social attitudes, evaluations and stances, social relations, and social identities. This notion is compared with other connected notions in Semiotics, Ethology, and Psychology, several types of informative and communicative signals and cues are exemplified, and their process of production and interpretation is overviewed, while considering the role of context and previous knowledge in it. The implications of this model are outlined for the construction of systems for the analysis of social signals and their simulation in Virtual Agents.

Social signals: from theory to applications.

The Special Issue Editorial introduces the research milieu in which Social Signal Processing originates, by merging computer scientists and social scientists and giving rise to this field in parallel with Human-Computer Interaction, Affective Computing, and Embodied Conversational Agents, all similarly characterized by high interdisciplinarity, stress on multimodality of communication, and the continuous loop from theory to simulation and application. Some frameworks of the cognitive and social processes underlying social signals are identified as reference points (Theory of Mind and Intersubjectivity, mirror neurons, and the ontogenesis and phylogenesis of communication), while three dichotomies (automatic vs. controlled, individualistic vs. intersubjective, and meaning vs. influence) are singled out as leads to navigate within the theoretical and applicative studies presented in the Special Issue.

How Personal Values Count in Misleading News Sharing with Moral Content.

The present study investigates the personal factors underlying online sharing of moral misleading news by observing the interaction between personal values, communication bias, credibility evaluations, and moral emotions. Specifically, we hypothesized that self-transcendence and conservation values may differently influence the sharing of misleading news depending on which moral domain is activated and that these are more likely to be shared when moral emotions and perceived credibility increase. In a sample of 132 participants (65% female), we tested SEMs on misleading news regarding violations in five different moral domains. The results suggest that self-transcendence values hinder online sharing of misleading news, while conservation values promote it; moreover, news written with a less blatantly biased linguistic frame are consistently rated as more credible. Lastly, more credible and emotionally activating news is more likely to be shared online.