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Spagnolo F.,IRCCS AOU San Martino | Picasso V.,U.O. Oncologia Medica 2 | Lambertini M.,U.O. Oncologia Medica 2 | Ottaviano V.,St. Georges Hospital | And 2 more authors.
Cancer Treatment Reviews | Year: 2016

Background: The incidence of brain metastases (BM) in melanoma patients is common and associated with poor prognosis. MAP-kinase inhibitors and immunologic checkpoint blockade antibodies led to improved survival of metastatic melanoma patients; however, patients with BM are under-represented or excluded from the majority of clinical trials and the impact of new drugs on their survival is less clear. With the present systematic review, we aimed to analyze outcomes of patients with melanoma BM treated with the new drugs, both in the setting of phase I-II-III clinical trials and in the "real world". Methods: An electronic search was performed to identify studies reporting survival outcomes of patients with melanoma BM treated with MAP-kinase inhibitors and/or immunologic checkpoint blockade antibodies, regardless of study design. Results: Twenty-two studies were included for a total of 2153 patients. Median OS was 7.9 months in phase I-II-III trials and 7.7 months in "real world" studies. In clinical trials, median OS was 7.0 months for patients treated with immunotherapy and 7.9 months for patients treated with BRAF inhibitors. In "real world" studies, median OS was 4.3 months and 7.7 months for patients treated with immunotherapy and BRAF inhibitors, respectively. Evidence of clinical activity exists for both immunotherapy and MAP-kinase inhibitors. Conclusions: MAP-kinase inhibitors and immunologic checkpoint blockade antibodies have clinical activity and may achieve improved OS in patients with metastatic melanoma and BM. These results support the inclusion of patients with BM in investigations of new agents and new treatment regimens for metastatic melanoma. © 2016 Elsevier Ltd. Source

Sorbello V.,University of Turin | Ciprandi G.,IRCCS AOU San Martino | Di Stefano A.,Laboratorio Of Citoimmunopatologia Dellapparato Cardio Respiratorio | Massaglia G.M.,San Luigi Hospital | And 7 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2015

Severe asthma (SA) is associated with neutrophil recruitment and T helper (TH)17 chemokine overexpression in bronchial biopsies. We aimed to evaluate IL-17A and IL-17F expression in nasal/bronchial lamina propria of atopic mild-to-severe asthmatics and controls in relation to neutrophilia and asthma exacerbations. Cryostat sections of nasal/bronchial biopsies obtained from 14 SA and 14 mild asthma (MA) stable atopic patients with rhinitis, and seven healthy controls were analyzed by immunohistochemistry for neutrophils, IL-17A and IL-17F expression. Atopic SA showed an increase in asthma exacerbations number, IL-17F and IL-17A expression in nasal/bronchial lamina propria compared to MA and controls, and a higher expression of bronchial neutrophils in SA compared to MA and controls. In all asthmatics, significant relationships were found between bronchial IL-17F and neutrophils/FEV1, nasal IL-17F and bronchial neutrophil/IL-17 markers and between the latter and exacerbations, suggesting that nasal IL-17F might be informative on bronchial IL17-driven neutrophilia in atopic SA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Ciprandi G.,IRCCS AOU San Martino | Sivestri M.,Pediatric Pulmonology and Allergy Unit
Journal of Investigational Allergology and Clinical Immunology | Year: 2014

Background: Allergen immunotherapy (AIT) has proven to be effective. However, no biomarkers capable of predicting the clinical response to AIT have been detected. The aim of the present study was to determine a cutoff value for serum specific IgE that could be associated with effective AIT. Methods: We evaluated 174 allergic patients (83 males) with ages ranging between 6 and 77 years. All patients were monsensitized and received sublingual immunotherapy (SLIT) for at least 3 years with a single allergen extract. Symptom severity was assessed using the visual analog scale (VAS). Drug use was also evaluated. A responder was defined as a patient whose VAS score fell by at least 30% over baseline. Results: The response to SLIT was considered effective in 145 patients (83.3%). The use of allergen-specific IgE levels >9.74 kUA/L as a biomarker of effective SLIT yielded a sensitivity value of 96.4%, specificity of 100%, and an area under the receiver operator characteristic curve of 0.987. Conclusions: Assessment of serum specific-IgE before AIT could be a useful biomarker for predicting response to AIT. © 2014 Esmon Publicidad. Source

Ciprandi G.,IRCCS AOU San Martino | Incorvaia C.,Allergy Pulmonary Rehabilitation | Scurati S.,Stallergenes | Puccinelli P.,Stallergenes | And 2 more authors.
International Journal of Immunopathology and Pharmacology | Year: 2012

Allergic rhinitis is characterized by troublesome symptoms that may be particularly severe. Most of rhinitics are dissatisfied with drug treatments. The dissatisfaction level depends on symptoms severity, but not on the type of causal allergen. Copyright © by BIOLIFE, s.a.s. Source

Valgimigli M.,Erasmus Medical Center | Gagnor A.,Cardiology Unit | Calabro P.,The Second University of Naples | Frigoli E.,Cardiology Unit | And 32 more authors.
The Lancet | Year: 2015

Summary Background It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. Methods We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. Findings We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). Interpretation In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. Funding The Medicines Company and Terumo. © 2015 Elsevier Ltd. Source

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