Benralizumab improves patient reported outcomes and functional parameters in difficult-to-treat patients with severe asthma: Data from a real-life cohort

In the last decade, an increasing number of randomized controlled trials (RCTs) on biologic therapy in patients with severe asthma have included patient-reported outcomes (PROs) as secondary efficacy measures. The majority of these RCTs showed a benefit in symptoms and quality of life. However, the magnitude of this benefit remains uncertain, because it rarely exceeded the minimal important difference (MID), owing to a significant improvement in the control group (placebo effect). Real-life studies on biologic therapies assessing PRO are scarce. They may support and integrate RCT results through their different experimental design. This real-life retrospective study provides data on 15 patients with difficult-to-treat severe eosinophilic asthma treated with benralizumab up to 6 months. Asthma quality of life questionnaire (AQLQ) and asthma control test (ACT) were assessed and administered at each visit to minimize the Hawthorne effect. Changes in general accepted efficacy measures, such as forced expiratory volume in 1 s (FEV1), peak expiratory flux (PEF), exacerbation rate and blood eosinophils, from baseline were also assessed. AQLQ and ACT improved from 3.9 ± 0.4 to 5.2 ± 0.4 and from15.6 ± 5.7 to 18.1 ± 5.6, respectively. FEV1 increased of about 250 ml (+14%). PEF increased from 288 ± 107 to 333 ± 133 l/min. The number of exacerbations requiring OCS courses decreased from 2.8 ± 2.2 to 0.5 ± 0.8. Eosinophil counts dropped to 25.6 ± 15 cells/microliter. In conclusion, most patients reported improvements in AQLQ and ACT greater than MID, suggesting that these outcome represent a sensitive tool in real-life effectiveness studies. Our approach reduced the limitations of transition questions and the Hawthorne effect, increasing findings reliability

Application of average volume assured pressure support (AVAPS) and ultrasound assessment in COVID-19 infection: real-life observation.

BACKGROUND: ARDS in COVID-19 patients admitted to Emergency Departments (ED) is characterized by reduced diaphragm motility and increased work of breathing (WOB) by accessory respiratory muscles. Reduced perfusion of compliant lungs as consequence of vascular abnormalities has been highlighted as possible explanation of typical hypoxemia. Non-invasive mechanical ventilation (NIMV) has been proposed to treat ARDS. AVAPS is a hybrid modality of NIMV combining features of pressure and volume ventilation. METHODS: we enrolled 38 patients with COVID-19 ARDS to whom we applied NIMV with AVAPS modality. We assessed Tidal Volume (TV), diaphragm excursion (DE) and PaO2/FiO2 before starting NIMV and after three (T3) and six hours (T6) of ventilation. RESULTS: Admissions to ICU were avoided in 68% of our patients. TV (627±147.6 vs. 747.1±226 mL, P<0.00005) and DE (21.8±5.4 vs. 17.9±6.1 mm, P<0.00005) already improved after three hours of AVAPS. TV (521.5±120 mL, P<0.00005), DE (25.8±6.9 mm, P<0.00005) and PaO2/FiO2 (197.3±75.3 vs. 158±67.7, P<0.005) significantly improved in our cohort of patients after six hours. CONCLUSIONS: NIMV with AVAPS modality can be confidently used in the clinical management of COVID-19 patients with ARDS, since AVAPS has positive effects on ventilation-perfusion matching and WOB. We recommend low PEEP value and ultrasound assessment of diaphragm motility and lung characteristics, although further studies are needed to individuate clinical features of NIMV best-responder patients

Mast cell disorders, melanoma and pancreatic carcinoma: from a clinical observation to a brief review of the literature.

Mastocytosis can be associated with other clonal or non-clonal hematologic diseases as well as a variety of non-hematologic malignancies. A 75-year-old Caucasian male patient was referred to us with a 5-month history of neutrophilic leukocytosis and mild splenomegaly. He had developed a cutaneous melanoma sixteen years ago. According to the clinical and pathological features, a final diagnosis of systemic mastocytosis was established. The patient started treatment with interferon-α at a dose of 3 MIU/day, combined with low doses of prednisone. We observed a rapid disappearance of symptoms. Unfortunately, after 3 months a diagnosis of pancreatic adenocarcinoma was established. A review of the literature suggests that mastocytes could have a pivotal role in several malignancies. Different chemokines, mitogenic factors, chemical mediators of inflammation, and specific gene mutations could explain the association between mastocytosis and other hematologic and non-hematologic disorders. </p

Safety and treatment compliance of subcutaneous immunotherapy: A 30-year retrospective study

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Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Proceedings of the Fifth Italian Conference on Computational Linguistics CLiC-it 2018

On behalf of the Program Committee, a very warm welcome to the Fifth Italian Conference on Computational Linguistics (CLiC-­‐it 2018). This edition of the conference is held in Torino. The conference is locally organised by the University of Torino and hosted into its prestigious main lecture hall “Cavallerizza Reale”. The CLiC-­‐it conference series is an initiative of the Italian Association for Computational Linguistics (AILC) which, after five years of activity, has clearly established itself as the premier national forum for research and development in the fields of Computational Linguistics and Natural Language Processing, where leading researchers and practitioners from academia and industry meet to share their research results, experiences, and challenges

Récepteurs, cellules et mécanismes impliqués dans la thérapie anti-tumorale à base d'anticorps monoclonaux

Monoclonal antibodies (mAbs) can be used to specifically target tumor cells over-expressing specific antigens. In most of the cases, the binding of the mAbs on the target antigen enables via the Fc portion of mAbs the recruitment of phagocytic and/or cytotoxic immune cells bearing receptors for the Fc portion of IgG (FcγR). Several FcγRs exist that differ from each other for both their functional activity and expression pattern among immune cells. Moreover, numerous differences exist between mouse and human FcγRs. However, which of the different FcγRs and which cell population is required for in vivo tumor regression following mAb therapy is not known. During my PhD, I have set up two mouse models of cancer mAb therapy: a syngenic (B16 melanoma) and a xenogenic model (BT474 human breast cancer). In the B16 melanoma model, an intravenous injection of B16 melanoma cells in wt mice leads to the development of lung metastases, whereas a subcutaneous injection leads to a solid tumor. A treatment with the mAb TA99 that targets the glycoprotein gp75 expressed on the B16 cells, results in a reduction of the tumor load. Likewise, the subcutaneous engraftment of BT474 human breast cancer cells in immunodeficient mice leads to a development of a solid tumor. Recurrent injections of the humanized mAb Trastuzumab, that targets the HER2 antigen expressed on the BT474 cells, leads to a reduction of the tumor load. Using these models I have identified the mouse (FcγRI and FcγRIII) and human (hFcyRI and hFcyRIIA) FcyRs involved in mAb anti-tumor activity. Moreover I have identified neutrophils as cell population responsible for the anti-tumor effect of therapeutic mAbs.Les antigènes exprimés sur les cellules cancéreuses peuvent être ciblées par des anticorps monoclonaux thérapeutiques (mAbs) capables, d'induire une réduction de la masse tumorale. Dans la plupart des cas, la fixation des mAbs à la surface des cellules tumorales induit, par la portion Fc, le recrutement de cellules phagocytaires et cytotoxiques qui expriment des récepteurs pour la pour la portion Fc des IgG (RFcy). Chez l'homme et chez la souris plusieurs RFcy existent et ont différentes fonctions et expression à la surface des cellules hématopoïétiques. En revanche, lequel parmi les multiples RFcy est responsable pour l'activité thérapeutique des anticorps monoclonaux n'est pas connu, ni quelle population cellulaire qui les exprime est responsable de la destruction des cellules tumorales. Au cours de ma thèse j'ai développé deux modèles d'immunothérapie à base d'anticorps monoclonaux chez la souris : un modèle syngenique (Melanome B16) et un modèle xenogenique (Cancer du sein humain BT474). Dans ces modèles, l'injection de l'anticorps murin TA99 qui reconnaît la protéine gp75 exprimée par les cellules tumorales B16, d'une part, et l'injection de l'anticorps humanisé Trastuzumab qui reconnaît le récepteur HER2 exprimé par les cellules BT474, d'autre part, induit une réduction de la masse tumorale. En utilisant ces deux modèles j'ai identifié des récepteurs murins (RFcyI/RFcyIII) et humains (RFcyI/RFcyIIA) responsables de l'activité anti tumorale de ces anticorps. De plus, j'ai identifié les neutrophiles comme population cellulaire responsable de la destruction des cellules tumorales en présence des anticorps thérapeutiques