Summary
What is known and objective
The second‐generation direct‐acting antivirals represented the first major turning point for the eradication of HCV infection in almost all settings of patients. ...However, no data were available on use in gastro‐resected patients.
Case description
We report on a gastrectomized patient with chronic hepatitis C infection. She was treated with sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks, with measurement of blood levels of the drugs. She obtained sustained virological response at week 12 and 24 without dose adjustment.
What is new and conclusion
This case report can provide information useful for clinical practice in this set of patients and can open new perspectives in evaluating actual SOF/LDV bioavailability.
We describe the first reported case of treatment with direct antiviral agents in a gastrotomized patient. This report can provide information useful for clinical practice in this set of patients and can open new perspectives in evaluating Sofosbuvir/Ledipasvir bioavailability.
We studied the effect of leukotriene D(4) (LTD(4)) on a human bronchial epithelial cell line (16HBE) overexpressing the cysteinyl leukotriene (CysLT) (1) receptor (HBECysLT(1)R), looking at the ...associated signal transduction mechanisms as well as at effects on inflammatory cell adhesion. The results obtained showed that LTD(4) increases the phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 and of the signal transducer and activator of transcription 1 (STAT-1) in serine 727 (STAT-1Ser727), resulting in increased eosinophil adhesion to HBECysLT(1)R, associated with enhanced surface expression of intercellular adhesion molecule (ICAM) 1. Pretreatment with a CysLT(1)R-selective antagonist or with a selective inhibitor of protein kinase C (PKC) or with a selective inhibitor of the mitogen-activated protein kinase kinase (MEK) successfully suppressed both LTD(4)-induced STAT-1Ser727 phosphorylation and the associated increase in eosinophil adhesion. The use of the MEK inhibitor and of the selective CysLT(1)R antagonist in electrophoretic mobility shift assay experiments showed that LTD(4) promotes the nuclear translocation of STAT-1 through the activation of ERK1/2 pathway. The key role of STAT-1 in leukotriene D(4) transduction signaling was confirmed by RNA interference experiments, where silencing of STAT-1 expression abolished the effect of leukotriene D(4) on eosinophil adhesion. In conclusion, for the first time, we provide evidence of the involvement of STAT-1 in the signal transduction mechanism of the CysLT(1) receptor; phosphorylation of STAT-1, through PKC and ERK1/2 activation, causes enhanced ICAM-1 surface expression and eosinophil adhesion. Effective CysLT(1)R antagonism may therefore contribute to the control of the chronic inflammatory condition that characterizes human airways in asthma.
Cigarette smoke is a risk factor for COPD and lung cancer. In cancer, epigenetic modifications affect the expression of Enhancer of Zester Homolog 2 (EZH2), and silenced disabled homolog 2 ...interacting protein gene (DAB2IP) (onco-suppressor gene) by Histone H3 tri-methylation in lysine 27 (H3K27me3). In"ex vivo"studies, we assessed EZH2, H3K27me3 and DAB2IP immunoreactivity in bronchial epithelial cells from COPD patients (smokers, ex-smokers), Smoker and control subjects. In"in vitro" experiments we studied the effect of cigarette smoke extract (CSE) on EZH2/H3K27me3/DAB2IP expression, apoptosis, invasiveness, and vimentin expression in 16HBE, primary cells, and lung cancer cell lines (A549) long-term exposed to CSE. Finally, in "in vitro"studies, we tested the effect of GSK343 (selective inhibitor of EZH2). EZH2 and H3K27me3 expression was higher, while DAB2IP was lower levels, in bronchial epithelium from COPD and Smokers than in Controls. CSE increased EZH2, H3K27me3 expression and decreased DAB2IP, cell apoptosis and invasiveness in epithelial cells. GSK343 restored the effects of CSE. Cigarette smoke affects EZH2 expression, and reduced DAB2IP via H3K27me3 in COPD patients. The molecular mechanisms associated with EZH2 expression, generate a dysregulation of cell apoptosis, mesenchymal transition, and cell invasiveness in bronchial epithelial cells, encouraging the progression of airway inflammation toward lung cancer in COPD patients.
The correct time to perform an upper endoscopy is decisive in acutely GI bleeding patients. However, patients’ physical status may affect mortality. We speculated that the physical status and ...procedural time could be the principal factors accountable for death-risk. The primary aim was to verify the interaction between physical status and time to endoscopy on mortality; the secondary aim was to verify the interaction of the physical status and time to endoscopy on the length of stay (LOS).
Consecutive patients admitted to 50 Italian hospitals were included. Clinical and endoscopic data were recorded. A multiple logistic regression analysis was performed and the interaction of adjusted clinical physical status and time to endoscopy on mortality was calculated.
Complete data were available for 3.190 patients. The time frames did not interfere with outcomes but influenced LOS. Conversely, the ASA score correlated with mortality, LOS, need for transfusions and rebleeding risk.
Endoscopy time should be tailored to the patient's physical. In our experience, ASA 1–2–3 patients can be safely submitted to endoscopy to reduce the LOS; on the contrary, keen attention should be paid to ASA4 patients, following the ‘not too early-not too late’ rule (12–24 h from admission).
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