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Long-acting muscarinic antagonists (LAMA) in association with inhaled corticosteroids (ICS) plus long-acting beta-2 agonists (LABA) are recommended by the GINA report as further option in step 4 and first choice in step 5 treatment. Despite consistent evidence of its efficacy and safety, inhaled triple therapy (ITT) is still not largely used in patients with asthma. With the aim to explore belief and behaviours of asthma specialists, an ad hoc survey has been developed by a panel of Interasma Scientific Network (INESnet) experts and subsequently defined by two Delphi rounds among an international group of physicians. The questionnaire has been distributed through Interasma social media between June and September 2023. Besides a descriptive analysis, to assess the responses gathered from the questionnaire, Spearman's non-parametric statistical method was employed. Totally, three hundred fourteen questionnaires were completed. Clinicians' attitudes and behaviours toward timing and methodologies adopted in prescribing ITT, were analysed. 35.7% specialists consider ITT as a relevant therapeutic option, 61.8% that is second option after reaching high dose of ICS-LABA and 89.2% agreed that optimization of inhaled therapy should be attempted before the use of biological drugs. Persistent flow limitation and high reversibility are considered predictive factors of response. Specialists consider ITT a resource in asthma management. Although its efficacy in decreasing exacerbation rate and improving lung function were well known, the survey revealed persistent uncertainties among clinicians in positioning it highlighting the need for further measures to effectively integrate research findings into day-to-day clinical practice., 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. ☐ The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Ltd.)

Background: The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection., Methods: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas., Results: Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]., Conclusions: The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection., Competing Interests: The authors have declared that no competing interests exist.

Here we describe the first molecular test developed in the early stage of the pandemic to diagnose the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sardinian patients in February-March 2020, when diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The " Caterina assay " is a SYBR ® Green real-time reverse-transcription polymerase chain reaction (rRT-PCR), designed to detect the nucleocapsid phosphoprotein (N) gene that exhibits high discriminative variation RNA sequence among bat and human coronaviruses. The molecular method was applied to detect SARS-CoV-2 in nasal swabs collected from 2110 suspected cases. The study article describes the first molecular test developed in the early stage of the declared pandemic to identify the coronavirus disease 2019 (COVID-19) in Sardinian patients in February-March 2020, when a diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The assay presented high specificity and sensitivity (with a detection limit ≥50 viral genomes/μL). No false-positives were detected, as confirmed by the comparison with two certified commercial kits. Although other validated molecular methods are currently in use, the Caterina assay still represents a valid and low-cost detection procedure that could be applied in countries with limited economic resources.

Aim: SARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome., Method and Materials: We recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies., Results: Male sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0-0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8-8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7-220.6), Pc = 0.024]., Conclusion: The data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease., 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 © 2020 Littera, Campagna, Deidda, Angioni, Cipri, Melis, Firinu, Santus, Lai, Porcella, Lai, Rassu, Scioscia, Meloni, Schirru, Cordeddu, Kowalik, Serra, Ragatzu, Carta, Del Giacco, Restivo, Deidda, Orrù, Palimodde, Perra, Orrù, Conti, Balestrieri, Serra, Onali, Marongiu, Perra and Chessa.)

Background: This study assesses attitudes towards vaccination in mothers of new-born babies and explores its association with different exposures to communication. Methods: Data were collected through questionnaires administered by means of interviews. Results: Data highlighted that 20% of mothers showed an orientation towards vaccine hesitancy. As for the reasons behind the attitude to vaccine hesitancy, data showed that concern is a common feature. As for the different exposures to communication, 49% of mothers did not remember having received or looked for any information about vaccination during pregnancy and post-partum; 25% stated they received information from several healthcare and non-healthcare sources; 26% declared having received or looked for information by means of healthcare and non-healthcare sources, as well as having taken part in a specific meeting during antenatal classes or at birth centres. The attitude towards vaccine hesitancy tends to reduce as exposure to different communication increases. Conclusions: This study supports the hypothesis that participation in interactive meetings in small groups focused on vaccination during the prenatal course or at the birth point may act as an enabling factor contributing to a decrease in the tendency to experience vaccine hesitation.

Based on hospital discharges in 1001-2010, we calculated risk of tumours with an elevated occupational and environmental etiological fraction by health district of residence within the Local Health Unit (LHU) N. 8 of Sardinia. With reference to the age and gender-specific hospitalization rates of the whole LHU, residents in the urban Cagliari health district showed an excess risk of haemolymphopoietic cancer (RR = 1.07; 95% CI 1.03-1.12) and bladder cancer (RR = 1.10; 95% CI 1.05-1.16); in both instances, risks were higher among female residents. The highest excess risk for lung cancer was observed among residents in the Quartu-Parteolla health district (RR = 1.13; 95% CI 1.05-1.21), and it was slightly higher among male residents. The results appear to confirm the role of urban factors in increasing cancer risk.

In an attempt to identify lymphocyte subsets possibly involved in the response to malignant cells, we have studied the lymphocyte surface phenotype by using a panel of monoclonal antibodies on both peripheral blood lymphocytes (PBL) and histologically proven metastatic and nonmetastatic (i.e., "hyperplastic") axillary lymph node lymphocytes (LNL) from eight breast cancer patients. Furthermore, we carried out a functional study by evaluating the response to polyclonal mitogens of the PBL and of the LNL of the same patients. A group of 30 healthy subjects, age and sex matched, were selected as controls for PBL. Six of them, who underwent surgery for nonneoplastic conditions, were selected as controls for LNL. The responsiveness of breast cancer patients' PBL to polyclonal mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) was significantly lower as compared with the control response. The responsiveness of breast cancer patients' metastatic LNL was not different from control LNL for PHA, and it was lower than control LNL for Con A, while the responsiveness of the same metastatic LNL was higher than that of nonmetastatic (i.e., hyperplastic) LNL of patients. Furthermore, the response of hyperplastic LNL was always lower than that of control LNL. The responsiveness of patients' PBL was always lower than that of metastatic LNL, while the responsiveness of patients' PBL vs. hyperplastic LNL was at variance. Regarding the surface phenotype of PBL, there was no difference between those of breast cancer patients and controls concerning the T-cells subsets, while the Leu 7, CD 21 and DR antigens were significantly higher among the breast cancer patients. No significant differences were found between patient metastatic and hyperplastic LNL or between control LNL and patient metastatic or hyperplastic LNL, respectively; only the CD 4 antigen was higher in metastatic than in hyperplastic LNL. A comparison of this surface phenotype between PBL and either metastatic or hyperplastic LNL of breast cancer patients showed values almost constantly significantly higher for PBL vs. either metastatic or hyperplastic LNL, respectively. The results of our study suggest that there is no change in the local-regional immunocompetent cell subsets that may be related to metastasis of breast cancer to regional nodes and to the progression of disease and that circulating T cells in breast cancer include cells expressing activation markers but not showing significant changes in the proportion of entire subpopulations.