HER2 isoforms co-expression differently tunes mammary tumor phenotypes affecting onset, vasculature and therapeutic response

Full-length HER2 oncoprotein and splice variant Delta16 are co-expressed in human breast cancer. We studied their interaction in hybrid transgenic mice bearing human full-length HER2 and Delta16 (F1 HER2/Delta16) in comparison to parental HER2 and Delta16 transgenic mice. Mammary carcinomas onset was faster in F1 HER2/Delta16 and Delta16 than in HER2 mice, however tumor growth was slower, and metastatic spread was comparable in all transgenic mice. Full-length HER2 tumors contained few large vessels or vascular lacunae, whereas Delta16 tumors presented a more regular vascularization with numerous endothelium-lined small vessels. Delta16-expressing tumors showed a higher accumulation of i.v. injected doxorubicin than tumors expressing full-length HER2. F1 HER2/Delta16 tumors with high full-length HER2 expression made few large vessels, whereas tumors with low full-length HER2 and high Delta16 contained numerous small vessels and expressed higher levels of VEGF and VEGFR2. Trastuzumab strongly inhibited tumor onset in F1 HER2/Delta16 and Delta16 mice, but not in full-length HER2 mice. Addiction of F1 tumors to Delta16 was also shown by long-term stability of Delta16 levels during serial transplants, in contrast full-length HER2 levels underwent wide fluctuations. In conclusion, full-length HER2 leads to a faster tumor growth and to an irregular vascularization, whereas Delta16 leads to a faster tumor onset, with more regular vessels, which in turn could better transport cytotoxic drugs within the tumor, and to a higher sensitivity to targeted therapeutic agents. F1 HER2/Delta16 mice are a new immunocompetent mouse model, complementary to patient-derived xenografts, for studies of mammary carcinoma onset, prevention and therapy

Are PID-5 personality traits and self-harm attitudes related? A study on a young adult sample pre-post COVID-19 pandemic

Introduction: Different studies confirm a stronger link between maladaptive personality traits and Non-suicidal Self-injury (NSSI). Additionally, the interest in the relationship between the experience of the COVID-19 pandemic and NSSI is growing. The present study aims (a) to investigate differences in personality traits between individuals with NSSI, suicidal ideation, NSSI and suicidal ideation co-occurrence and none; (b) to observe which personality traits predominantly influence the occurrence of self-harm acts; (c) to evaluate the difference in self-harm attitudes pre and post COVID-19 pandemic Method: 270 (108 males and 162 females) participants aged between 18 and 25 were included in the study. Everyone participated in a clinical interview and completed an assessment consisting of the Personality Inventory for DSM-5 (PID-5) and the Health of the Nation Outcome Scales (HoNOS). A multivariate analysis of variance (MANOVA), a multiple hierarchical regression analysis, controlling for age and gender and a T-test for independent samples were conducted. Results: The individuals with the highest levels of negative affectivity, detachment, antagonism, and psychoticism are those who simultaneously present suicidal ideation and NSSI. Moreover, age and detachment predicted higher scores in self-harm attitudes. Our results unexpectedly do not confirm an upward trend of NSSI and suicidal ideation during the pandemic period. Limitations: The study is cross-sectional, and no causal links can be assumed; the groups involved were not homogeneous for numerosity. Conclusions: The results testify that the study of maladaptive traits is fundamental to a greater understanding of NSSIs. Working clinically on those could potentially reduc

Personality traits and transition to psychosis one year after the first assessment

IntroductionSeveral studies have identified ultra-high-risk criteria that may characterize an at-risk mental state and predict the transition of psychotic evolution. Personality traits may play a crucial role in this process.AimsThe current study aims to: (a) explore the evolution of an initial diagnosis over 12 months; (b) assess differences in social and occupational functioning; (c) identify common (trans-diagnostic) personality traits of psychotic risk.MethodsThe sample includes 97 (44 males and 53 females) young adults. They completed an assessment that consists of socio-demographic data, the Social and Occupational Functioning Scale, the Early Recognition Inventory-retrospective assessment onset of schizophrenia, and the Personality Inventory for DSM-5 (PID-5). According to the tests’ assessment, the sample was divided into three different groups: Ultra-High Risk (UHR), At-Risk, and Not at risk. One year after the first evaluation, psychiatrists administered the QuickSCID-5 to verify the diagnostic trajectories of the sample.ResultsOverall, the most prevalent category diagnoses were anxiety/depression, personality disorders, and psychosis. Specifically, the most common diagnosis in the UHR group was psychosis. Moreover, in the UHR group, the social and occupational functioning score was the lowest. In terms of differences in PID-5 personality traits, the At-risk and UHR groups scored highest in detachment and disinhibition. No statistically significant differences were found between the groups for negative affectivity, antagonism, and psychoticism traits.ConclusionResults obtained by the current study should be considered an attempt to better understand the diagnostic trajectories and trans-diagnostic personality traits in a group of young help-seekers, specifically in UHR. Findings highlight both the importance of diagnosis and personality traits evaluation to customize a specific intervention based on the level of psychotic risk. Clinical suggestions are reported

At-risk mental states and personality traits: A cluster analysis approach on a group of help-seeking young adults

IntroductionResearch on the relationship between personality and psychosis onset is growing, with the goal of preventing or intervening early in patients' vulnerability. The identification of individuals with at-risk mental states has enabled the development of early intervention strategies, such as Programma 2000, a youth mental health service that was implemented in Milan (Italy). AimsFocusing on the 18-25 age range-the time window with the highest incidence of psychotic onset-this study aims to identify the personality traits that may characterize the at-risk mental states and the social functioning of a group of help-seeking young adults. MethodsThe sample includes 169 people (48.5% males and 51.5% females). Data were collected during an initial assessment that comprised the Social and Occupational Functioning Assessment Scale, the Personality Inventory for DSM-5, the Checklist ERIraos and a clinical session. ResultsResults identified a three-cluster solution based on the Checklist scores: Cluster 1 'Not at psychotic risk'; Cluster 2 'At intermediate risk'; Cluster 3 'With psychotic onset'. The multivariate analysis of the variance of personality traits shows significant differences among the clusters in negative affect, detachment and disinhibition. Higher scores in these traits may distinguish individuals, not at psychotic risk from those at intermediate risk or with psychotic onset. Moreover, social functioning was found to be negatively associated with clusters of psychotic risk. ConclusionFindings from this study highlighted the need to evaluate personalized interventions targeting such personality traits that could prevent psychotic transition and promote psychological well-being

The interferon landscape along the respiratory tract impacts the severity of COVID-19

International audienc

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Effects of pre‐operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or >= 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care