Euro-Mediterranean Integration and Cooperation: Prospects and Challenges

An overview of current institutional cooperation, economic conditions and challenges in the Mediterranean region.Mediterranean, Europe, Economic conditions, institutional cooperation

Euro-Mediterranean Integration and Cooperation: Prospects and Challenges

An overview of current institutional cooperation, economic conditions and challenges in the Mediterranean regio

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: A real-world experience

We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-na\uc3\uafve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-na\uc3\uafve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-na\uc3\uafve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p < 0.0001), while overall survival was positively affected by lower ECOG PS (p < 0.0001), absence of brain metastases (p 0.05), and clinical benefit (p < 0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order

Loneliness during the COVID-19 Pandemic in Patients with Burning Mouth Syndrome: A Multicentric Case-Control Italian Study

Background. Lockdown restrictions during the COVID-19 pandemic exerted a strong impact on people’s quality of life and increased loneliness. This study evaluates the effect of the pandemic on loneliness in patients with burning mouth syndrome (BMS) compared with the general population. Methods. 100 BMS patients versus 100 healthy controls (HC) were recruited in five Italian centers. The 12-Item General Health Questionnaire (GHQ-12), the Depression Anxiety Stress Scales-21 (DASS-21), the Insomnia Severity Index (ISI), the short-form UCLA Loneliness Scale-8 (ULS-8), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Suicidal Ideation Attribute Scale (SIDAS) were administered. Results. BMS patients and HC showed high scores (16 [14-20.25] and 16 [14-18]) in the ULS-8. Statistically significant differences have been found considering the BMS patients lived with fewer relatives during the lockdown compared with the HC (2 [2-3] and 3 [2-4]; p: 0.012) with a lower level of satisfaction in relationships with relatives (4 [1.75-5] and 5 [4-5]; p < 0 001) and also in the DASS-21 total scores between the BMS patients and HC (16 [10-24.2] and 10 [4-17]; p < 0 001). The multivariate logistic regression revealed that age, education, DASS-21, and MSPSS were the most predictive variables and could explain 34.68% of the variance in the ULS-8 score (p < 0 001) in the BMS group. However, only the DASS-21 was significant in the HC group, explaining 10.11% of the variance of the ULS-8 (p: 0.033). Conclusions. Both the patients and controls experienced deep loneliness during the pandemic. However, in the BMS group, loneliness was significantly correlated with age, a higher level of education and stress, and a lower level of satisfaction in relationships with relatives and social support perceived compared with the controls

Spectralités dans le roman contemporain

L’ambition de ce volume, qui rassemble des études sur des écrivains de la deuxième moitié du XXe siècle (Italo Calvino, Antonio Tabucchi) et du début du XXIe siècle (Bruno Arpaia, Rafael Chirbes, Julio Llamazares, Walter Siti, Gonçalo M. Tavares, Giorgio Vasta), est d’interroger le retour du refoulé historique dans la littérature contemporaine de l’Italie, de l’Espagne et du Portugal à partir du concept de spectralité forgé par Jacques Derrida. De nombreuses œuvres littéraires semblent recourir au spectre pour figurer un nouveau régime d’historicité mais aussi un temps présent désarticulé et hétérogène et perçu comme de plus en plus en manque de réel. En effet, « revenant » du passé ou projection paradoxale du présent, le spectre marque un point irrésolu de l’histoire tout en révélant les enjeux fondamentaux de notre temps

COVID‐19 impact on post‐traumatic stress symptoms in burning mouth syndrome: A multicentric study

Objectives This study investigates the psychological impact of COVID-19 on burning mouth syndrome (BMS) patients. It focuses on comparing post-traumatic stress symptoms (PTSS), post-traumatic growth (PTG), and resilience between BMS patients and Controls. Methods A total of 100 BMS patients and 100 Controls from five Italian centers participated in this observational cross-sectional study. They completed several assessments, including the General Health Questionnaire, Depression Anxiety and Stress Scale, Insomnia Severity Index, National Stressful Events Survey Short Scale, Impact of Event Scale-Revised, Post Traumatic Growth Inventory Short Form, and Connor-Davidson Resilience Scale. Results BMS patients had significantly higher stress, anxiety, and depression (DASS-21 score) and post-traumatic stress symptoms (IES-R-6 score), particularly in terms of intrusive thoughts. They showed lower post-traumatic growth (PTGI-SF score) compared to Controls. The resilience scale (CDRS-10) was a key predictor of PTG in both groups, explaining a significant variance in PTGI-SF scores. Conclusions BMS patients experienced heightened post-traumatic stress, stress, anxiety, and depression during the COVID-19 pandemic, with reduced post-traumatic growth. This highlights the need to prioritize their psychological well-being, focusing on stress management and fostering post-traumatic growth in challenging times

Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer Patients: What Is the Better Choice?

To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC)

Fatal cytokine release syndrome by an aberrant FLIP/STAT3 axis

Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state