Epstein-Barr nuclear antigen 1 induces expression of the cellular microRNA hsa-miR-127 and impairing B-cell differentiation in EBV-infected memory B cells. New insights into the pathogenesis of Burkitt lymphoma.

Epstein-Barr Virus (EBV) is a γ-herpesvirus that infects > 90% of the human population. Although EBV persists in its latent form in healthy carriers, the virus is also associated with several human cancers. EBV is strongly associated with Burkitt lymphoma (BL), even though there is still no satisfactory explanation of how EBV participates in BL pathogenesis. However, new insights into the interplay between viruses and microRNAs (miRNAs) have recently been proposed. In particular, it has been shown that B-cell differentiation in EBV-positive BL is impaired at the post-transcriptional level by altered expression of hsa-miR-127. Here, we show that the overexpression of hsa-miR-127 is due to the presence of the EBV-encoded nuclear antigen 1 (EBNA1) and give evidence of a novel mechanism of direct regulation of the human miRNA by this viral product. Finally, we show that the combinatorial expression of EBNA1 and hsa-miR-127 affects the expression of master B-cell regulators in human memory B cells, confirming the scenario previously observed in EBV-positive BL primary tumors and cell lines. A good understanding of these mechanisms will help to clarify the complex regulatory networks between host and pathogen, and favor the design of more specific treatments for EBV-associated malignancies

Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome

RATIONALE: Oxygen is commonly administered after extubation. Although several devices are available, data about their clinical efficacy are scarce. OBJECTIVES: To compare the effects of the Venturi mask and the nasal high-flow (NHF) therapy on PaO2/FiO2SET ratio after extubation. Secondary endpoints were to assess effects on patient discomfort, adverse events, and clinical outcomes. METHODS: Randomized, controlled, open-label trial on 105 patients with a PaO2/FiO2 ratio less than or equal to 300 immediately before extubation. The Venturi mask (n = 52) or NHF (n = 53) were applied for 48 hours postextubation. MEASUREMENTS AND MAIN RESULTS: PaO2/FiO2SET, patient discomfort caused by the interface and by symptoms of airways dryness (on a 10-point numerical rating scale), interface displacements, oxygen desaturations, need for ventilator support, and reintubation were assessed up to 48 hours after extubation. From the 24th hour, PaO2/FiO2SET was higher with the NHF (287 \ub1 74 vs. 247 \ub1 81 at 24 h; P = 0.03). Discomfort related both to the interface and to airways dryness was better with NHF (respectively, 2.6 \ub1 2.2 vs. 5.1 \ub1 3.3 at 24 h, P = 0.006; 2.2 \ub1 1.8 vs. 3.7 \ub1 2.4 at 24 h, P = 0.002). Fewer patients had interface displacements (32% vs. 56%; P = 0.01), oxygen desaturations (40% vs. 75%; P < 0.001), required reintubation (4% vs. 21%; P = 0.01), or any form of ventilator support (7% vs. 35%; P < 0.001) in the NHF group. CONCLUSIONS: Compared with the Venturi mask, NHF results in better oxygenation for the same set FiO2 after extubation. Use of NHF is associated with better comfort, fewer desaturations and interface displacements, and a lower reintubation rate. Clinical trial registered with www.clinicaltrials.gov (NCT 01575353)

Depression is associated with poor control of symptoms in asthma and rhinitis: A population-based study

Although many studies have highlighted the link between asthma/rhinitis and depression, it is still unclear which characteristics of these diseases are associated with the risk of depression. We aimed to explore the relationship between depression and asthma or rhinitis in a representative sample of the Italian general population

Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients

PURPOSE: Our aim was to identify the clinical profile of intensive care unit (ICU) patients with Pseudomonas aeruginosa (PA) pneumonia and the impact on ICU mortality and duration of mechanical ventilation (MV) of multidrug resistance (MDR) in the PA isolate and inadequate initial antibiotic therapy (IIAT). METHODS: We conducted a retrospective analysis of data prospectively collected in the 18-bed general ICU of a major teaching hospital in Rome, Italy. The study cohort consisted of 110 adult patients with culture-confirmed PA pneumonia consecutively diagnosed in 2008-2010. ICU survivor and nonsurvivor groups were compared to identify factors associated with ICU mortality. RESULTS: In 42 (38\ua0%) of the 110 cases of PA pneumonia analyzed, the PA isolate was MDR. Fifty-six (50.9\ua0%) of the patients received IIAT, and 49 (44.5\ua0%) died in ICU. In logistic regression analysis, IIAT, diabetes mellitus, higher Simplified Acute Physiology Score (SAPS) II scores, and older age were independently associated with ICU mortality. Among survivors, those who received IIAT or had MDR PA pneumonia had significantly longer median (interquartile ranges, IQR) periods of post-pneumonia onset MV (16.5 [14.5-20] and 15 [12-18] days, respectively) compared with those whose initial therapy was adequate (8 [6-13] days, P\ua0<\ua00.001) and those whose infections were caused by non-MDR PA (10.5 [6.5-13] days, P\ua0=\ua00.01). CONCLUSIONS: Our findings highlight the importance of IIAT as a risk factor for mortality in ICU patients with PA pneumonia. MDR in the PA isolate, like IIAT, can significantly increase the need for MV

Impact of asthma and comorbid allergic rhinitis on quality of life and control in patients of Italian general practitioners.

OBJECTIVE: Asthma is a disease with elevated prevalence within the general population. Although general practitioners (GPs) are among the first health-care professionals to whom patients refer for their symptoms, there are few evaluations of this disease based on data provided by the GPs. The aim of this observational study is to assess the impact of asthma and comorbid allergic rhinitis on individual/social burden, quality of life, and disease control in asthmatic patients of Italian GPs. METHODS: Throughout Italy, 107 GPs enrolled 995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions, or with asthma-like symptoms during the previous 12 months. Data were collected through questionnaires filled out by GPs and patients. RESULTS: Of the 995 asthmatic patients, 60.6% had concomitant allergic rhinitis (R+A), 39.4% had asthma alone. The latter, compared to those with R+A, showed significantly lower prevalence of intermittent asthma (37.5% vs. 55.6%) and higher prevalence of mild, moderate, and severe persistent asthma (28.4% vs. 23.2%, 28.7% vs. 18.8%, and 5.4% vs 2.4%, respectively). Individual/social burden due to asthma was frequent and increased with disease severity: 87.5% of severe persistent asthma patients reported at least one medical consultation in the last 12 months, 37.5% emergency department visits, 26.7% hospitalization, and 62.5% limitations in daily activities. Control and quality of life were inversely associated with disease severity and were worse in patients with R+A than in those with asthma alone. CONCLUSIONS: This study showed the negative impact of high severity levels and comorbid allergic rhinitis on quality of life of asthmatic patients and on individual/social burden due to asthma in an Italian GPs setting

Impact of asthma and comorbid allergic rhinitis on quality of life and control in patients of Italian general practitioners.

OBJECTIVE: Asthma is a disease with elevated prevalence within the general population. Although general practitioners (GPs) are among the first health-care professionals to whom patients refer for their symptoms, there are few evaluations of this disease based on data provided by the GPs. The aim of this observational study is to assess the impact of asthma and comorbid allergic rhinitis on individual/social burden, quality of life, and disease control in asthmatic patients of Italian GPs. METHODS: Throughout Italy, 107 GPs enrolled 995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions, or with asthma-like symptoms during the previous 12 months. Data were collected through questionnaires filled out by GPs and patients. RESULTS: Of the 995 asthmatic patients, 60.6% had concomitant allergic rhinitis (R+A), 39.4% had asthma alone. The latter, compared to those with R+A, showed significantly lower prevalence of intermittent asthma (37.5% vs. 55.6%) and higher prevalence of mild, moderate, and severe persistent asthma (28.4% vs. 23.2%, 28.7% vs. 18.8%, and 5.4% vs 2.4%, respectively). Individual/social burden due to asthma was frequent and increased with disease severity: 87.5% of severe persistent asthma patients reported at least one medical consultation in the last 12 months, 37.5% emergency department visits, 26.7% hospitalization, and 62.5% limitations in daily activities. Control and quality of life were inversely associated with disease severity and were worse in patients with R+A than in those with asthma alone. CONCLUSIONS: This study showed the negative impact of high severity levels and comorbid allergic rhinitis on quality of life of asthmatic patients and on individual/social burden due to asthma in an Italian GPs setting