Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

No abstract

No abstract

The finding that oral NO is increased in OSA and is related to upper airway obstructive episodes and to hypoxemia severity, strengthens the clinical and pathogenic role of oral inflammation in OSA.

No abstract

Buckwheat allergy is considered a rare food allergy outside of Asia. In Europe, buckwheat has been described mainly as a hidden allergen. Data on the prevalence of buckwheat hypersensitivity in non-Asian countries is very poor. The aim of this multicenter study was to evaluate the prevalence of buckwheat sensitization and its association with other sensitizations among patients referred to allergy clinics in different geographic areas of Italy. All patients referred to 18 Italian allergy clinics from February through April 2011 were included in the study and evaluated for sensitization to buckwheat and other allergens depending on their clinical history. A total of 1,954 patients were included in the study and 61.3% of them were atopic. Mean prevalence of buckwheat sensitization was 3.6% with significant difference between Northern (4.5%), Central (2.2%) and Southern (2.8%) regions. This is, to our knowledge, the largest epidemiological survey on buckwheat allergy reported outside of Asia. Buckwheat is an emerging allergen in Italy, being more frequently associated to sensitization in Northern regions.

There are wide differences in estimated incidence and prevalence of anaphylaxis because of the absence, until recently, of a universal consensus on the definition of anaphylaxis and the different source of collected data. We aimed to estimate the incidence of food anaphylaxis based on the database of Piemonte Region (Italy) Reference Center for Severe Allergic Reactions. All cases of severe food allergic reactions reported in 2010 were studied. Clinical data associated to the reports were evaluated according to National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network diagnostic criteria of anaphylaxis. 75 % of the 778 cases were classified as food anaphylaxis (incidence of 13/100,000 personyears, ranging from 9.9 in adults to 29/100,000 person-years in children). Nuts were the most frequent foods causing anaphylaxis. Milk and eggs were responsible for anaphylaxis more often in children, while peach, vegetables and crustaceans were in adults. Cardiovascular symptoms were more frequent in adults. Gastrointestinal involvement was more frequent in children. A high prevalence of respiratory allergic comorbidities was observed. Food is an important cause of anaphylaxis, particularly in subjects with respiratory allergic comorbidities. Children and adults differ in triggers and clinical presentation of anaphylaxis.Keywords: Anaphylaxis, Food allergy, Epidemiology, Allergy Introduction Population-based studies estimate the incidence of anaphylaxis in western countries to be in the range of 4-50 per 100,000 person-years [1, 2], with a true lifetime prevalence in the range of 0.05-2 % [3]. Foods are reported to be the most important trigger of anaphylaxis, being responsible for 33.2-56 % of all anaphylaxis cases [4]. The other two principal triggers of anaphylaxis are insect stings and drugs [1,5]. The relative contribution of each of these triggers to anaphylaxis may differ according to the study design, study population, or geographic area. The wide differences in the estimated incidences and prevalences of anaphylaxis are the direct result of the absence, until recently, of a universal consensus on the definition of anaphylaxis and the different source of collected data. For this reason in 2005 the National Institute of Allergy and Infectious Disease (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN) developed a very useful preliminary definition, based on diagnostic criteria [6]. The symposium defined anaphylaxis as: "a serious allergic reaction that is rapid in onset and may cause death". Clinically, involvement of at least two organs (skin or mucosal tissue, cardiovascular apparatus, breathing apparatus, gastrointestinal tract) is required, or a sudden reduced blood pressure along with a temporal relationship (generally minutes) to a potential causative agent. A problematic issue with this definition, which may explain the under-reporting or misreporting of anaphylaxis cases, is the failure to agree among health care providers on the severity threshold for classi...

Functional imbalance in Th1/Th2 cell response toward allergens is a recognized hallmark of allergic patients and a major role of dendritic cells (DCs) in redirecting T-cell phenotypes after specific immunotherapy has been suggested. This study investigates the proliferative and cytokine responses of T cells cocultured with monocyte-derived DCs (MoDCs) after allergen stimulation in birch-allergic patients compared with controls and investigates whether sublingual immunotherapy (SLIT) could change the DC-driven immune response. T cells were stimulated with the major birch pollen allergen (nBet v1) and MoDCs from eight birch-allergic patients with seasonal allergic rhinitis and eight nonallergic controls. Proliferation and cytokine production were measured before and after one course of SLIT with birch allergoid. Significantly lower levels of proinflammatory (IL-1beta, p = 0.027; IL-6, p = 0.030; TNF-alpha, p = 0.019) and Th1 (interferon gamma, p = 0.032; IL-12, p = 0.05) cytokines were measured in supernatants of T cells and MoDCs cultures from allergic patients compared with nonallergic controls. After SLIT, significant increase in IL-12 (p = 0.039), IL-1beta (p = 0.040), IL-6 (p = 0.041), TNF-α (p = 0.048), and IL-10 (p = 0.048) and significant decrease in IL-13 (p = 0.001) were observed. MoDCs/T-cell cocultures, pulsed with the specific allergen, produced lower quantities of proinflammatory and Th1 cytokines in allergic patients compared with healthy subjects, suggesting an allergen-specific impairment of natural immunity and Th1 immune response. A single course of SLIT was able to enhance allergen-specific innate immunity and to modify lymphocyte response, promoting Th1 and T-cell regulatory activity.