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Objective: This study aims to estimate the incidence of Vestibular neuritis (VN) in three different districts in Italy, its epidemiological features, and the prevalence of comorbidities associated with it., Methods: An observational prospective study of 198 patients referred to ENT departments in Siena, Grosseto, and Cuneo was carried out over a 2-year period. Each patient underwent a complete otoneurologic examination in the first 48 h from the onset of symptoms and a brain MRI in the early stages of the disease. The follow-up lasted for 1 year., Results: The total VN incidence rate of the three municipalities was 48.497 (95% CI: 48.395-48.598) and its standardized value was 53.564 (95% CI: 53.463-53.666). The total VN incidence rate for the whole sample (municipality and district of the three centers) was 18.218 (95% CI: 18.164-18.272), and its standardized value was 20.185 (95% CI: 20.129-20.241). A significant difference was highlighted between patients living in the city compared to those living in the surrounding area ( p < 0.000), this may be due to the ease of reaching the otoneurological referral center., Conclusion: The total incidence rate for the three municipalities was 48.497. This result is higher than previously reported studies., 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 © 2023 Mandalà, Salerni, Ferretti, Bindi, Gualtieri, Corallo, Viberti, Gusinu, Fantino, Ponzo, Astore, Boccuzzi and Nuti.)

AbstractOtitis media (OM) is a very common disease in children, which results in a significant economic burden to the healthcare system for hospital-based outpatient departments, emergency departments (EDs), unscheduled medical examinations, and antibiotic prescriptions. The aim of this retrospective observational study is to investigate the association between climate variables, air pollutants, and OM visits observed in the 2007-2010 period at the ED of Cuneo, Italy. Measures of meteorological parameters (temperature, humidity, atmospheric pressure, wind) and outdoor air pollutants (particulate matter, ozone, nitrous dioxide) were analyzed at two statistical stages and in several specific steps (crude and adjusted models) according to Poisson's regression. Response variables included daily examinations for age groups 0-3, 0-6, and 0-18. Control variables included upper respiratory infections (URI), flu (FLU), and several calendar factors. A statistical procedure was implemented to capture any delayed effects. Results show a moderate association for temperature (T), age 0-3, and 0-6 with P < 0.05, as well as nitrous dioxide (NO 2 ) with P < 0.005 at age 0-18. Results of subsequent models point out to URI as an important control variable. No statistical association was observed for other pollutants and meteorological variables. The dose-response models (DLNM-final stage) implemented separately on a daily and hourly basis point out to an association between temperature (daily model) and RR 1.44 at age 0-3, CI 1.11-1.88 (lag time 0-1 days) and RR 1.43, CI 1.05-1.94 (lag time 0-3 days). The hourly model confirms a specific dose-response effect for T with RR 1.20, CI 1.04-1.38 (lag time range from 0 to 11 to 0-15 h) and for NO 2 with RR 1.03, CI 1.01-1.05 (lag time range from 0 to 8 to 0-15 h). These results support the hypothesis that the clinical context of URI may be an important risk factor in the onset of OM diagnosed at ED level. The study highlights the relevance of URI as a control variable to be included in the statistical analysis in association with meteorological factors and air pollutants. The study also points out to a moderate association of OM with low temperatures and NO 2 , with specific risk factors for this variable early in life. Further studies are needed to confirm these findings, particularly with respect to air pollutants in larger urban environments.

An early molecular response has a strong predictive value in chronic myeloid leukemia (CML). Recently, the halving time (velocity of early BCR-ABL1 transcript elimination) has been shown to represent an additional prognostic index. Our objective was the evaluation of the prognostic significance of the 3-month point in our population. We retrospectively collected BCR-ABL1 transcript data at different time points, events, and survival data of patients with CML treated at the Division of Hematology, San Luigi Hospital, University of Turin, Turin, Italy. Of 71 patients diagnosed from January 2005 to March 2015 in our center and treated with front-line tyrosine kinase inhibitors (imatinib, nilotinib and dasatinib), we selected those who had undergone a molecular evaluation at 3 months. The event-free survival (EFS) by the median follow-up time was the primary endpoint. The data from 50 patients with CML chronic phase were analyzed. Overall, 34 of the 50 patients (68%) had a transcript ≤ 10% at 3 months. Of those in the > 10% group, 63% had experienced an event compared with 12% in the ≤ 10% group by the median follow-up point (P < .001). The halving time threshold for discriminating between EFS was 17 days. None of the patients with a transcript > 10% at 3 months had a halving time of ≤ 17 days. Patients with BCR-ABL1 ≤ 10% and a halving time of ≤ 17 days had significantly better EFS than that of patients with BCR-ABL1 ≤ 10% and a halving time > 17 days and of patients with BCR-ABL1 > 10% (96% group 1 vs. 60% group 2 vs. 27% group 3; P < .001). Irrespective of the tyrosine kinase inhibitor used, the prognosis was significantly superior for patients with BCR-ABL1 ≤ 10% and halving time of ≤ 17 days. Our data revealed that the use of ABL1 as a control gene is reliable for the determination of the halving time in the clinical setting and highlight the importance of measuring the BCR-ABL1 transcript at CML diagnosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The profound clinical consequences of Gram-positive toxic shock are hypothesized to stem from excessive Th1 responses to superantigens. We used a new superantigen-sensitive transgenic model to explore the role of TCRalphabeta T cells in responses to staphylococcal enterotoxin B (SEB) in vitro and in two different in vivo models. The proliferative and cytokine responses of HLA-DR1 spleen cells were 100-fold more sensitive than controls and were entirely dependent on TCRalphabeta T cells. HLA-DR1 mice showed greater sensitivity in vivo to two doses of SEB with higher mortality and serum cytokines than controls. When d-galactosamine was used as a sensitizing agent with a single dose of SEB, HLA-DR1 mice died of toxic shock whereas controls did not. In this sensitized model of toxic shock there was a biphasic release of cytokines, including TNF-alpha, at 2 h and before death at 7 h. In both models, mortality and cytokine release at both time points were dependent on TCRalphabeta T cells. Anti-TNF-alpha pretreatment was protective against shock whereas anti-IFN gamma pretreatment and delayed anti-TNF-alpha treatment were not. Importantly, anti-TNF-alpha pretreatment inhibited the early TNF-alpha response but did not inhibit the later TNF-alpha burst, to which mortality has previously been attributed. Splenic T cells were shown definitively to be the major source of TNF-alpha during the acute cytokine response. Our results demonstrate unequivocally that TCRalphabeta T cells are critical for lethality in toxic shock but it is the early TNF-alpha response and not the later cytokine surge that mediates lethal shock.

There is much interest in therapeutic manipulation of cytokine responses in autoimmunity, yet studies in mouse models have sometimes produced conflicting findings as to the role of particular mediators in disease. Examples include the contradictory findings regarding susceptibility to experimental allergic encephalomyelitis (EAE) or diabetes in knockout mice for various individual Th1 or Th2 cytokines or their receptors. An alternative approach to the analysis of Th1 and Th2 mechanisms in these diseases is to investigate strains carrying a null mutation for molecules involved in cytokine receptor signal transduction, signal transducer and activator of transcription (Stat4) and Stat6. Stat4 is pivotal in Th1 polarization, being activated when IL-12 binds the IL-12R and leading to the production of IFNgamma. We here report disease susceptibility in non-obese diabetic mice carrying a Stat4-null mutation. Knockout mice were almost completely protected from diabetes, only rarely showing pancreatic peri-islet infiltrates. Furthermore, there was near complete protection from the induction of EAE by either of the two encephalitogenic myelin epitopes. Despite this protection, Stat4-null mice showed clear epitope spread compared with controls during myelin oligodendrocyte glycoprotein-induced EAE as judged by T cell proliferation, although this was not associated with a strong Th1 response to the initial or spread epitope and, furthermore, there was no evidence of a switch to Th2 cytokines.