On account of the widespread development and propagation of antimicrobial-resistant (AMR) bacteria, essential oils (EOs) have emerged as potential alternatives to antibiotics. However, as already ...observed for antibiotics, recent studies have raised concerns regarding the potential emergence of resistant variants (RVs) to EOs. In this study, we assessed the emergence of RVs in Escherichia coli and Salmonella enterica Typhimurium after evolution assays under extended exposure to subinhibitory doses of two commercial EOs (AEN and COLIFIT) as well as to two antibiotics (amoxicillin and colistin). Phenotypic characterization of RVs from evolution assays with commercial EOs yielded no relevant increases in the minimum inhibitory concentration (MIC) of E. coli and did not even modify MIC values in S. Typhimurium. Conversely, RVs of E. coli and S. Typhimurium isolated from evolution assays with antibiotics showed increased resistance. Genotypic analysis demonstrated that resistance to commercial EOs was associated with enhanced protection against oxidative stress and redirection of cell energy toward efflux activity, while resistance to antibiotics was primarily linked to modifications in the cell binding sites of antibiotics. These findings suggest that AEN and COLIFIT could serve as safe alternatives to antibiotics in combating the emergence and dissemination of antimicrobial resistance within the agrifood system.
•In a cohort of patients with locally advanced Non-Small Cell Lung Cancer and associated Central Airways Obstruction interventional bronchoscopy as a part of an integrated treatment improved 1-year ...survival.•Interventional bronchoscopy reduced new hospitalizations, increased symptom-free interval and prevented atelectasis.•Genetic and anatomic phenotyping might identify patients who may gain life expectancy from the endoscopic intervention.
Despite new therapeutic perspectives, the presence of central airways occlusion (CAO) in patients with locally advanced non-small cell lung cancer (NSCLC) is associated with poor survival. There is no clear evidence on the clinical impact of interventional bronchoscopy as a part of an integrated treatment to cure these patients.
This retrospective cohort study was conducted in two teaching hospitals over a 10 years period (January 2010-January 2020) comparing patients with NSCLC at stage IIIB and CAO at disease onset treated with chemotherapy/radiotherapy (standard therapy-ST) with those receiving interventional bronchoscopy plus ST (integrated treatment-IT). Primary outcome was 1-year survival. The onset of respiratory events, symptoms-free interval, hospitalization, need for palliation, and overall mortality served as secondary outcomes.
A total of 100 patients were included, 60 in the IT and 40 in the ST group. Unadjusted Kaplan-Meier estimates showed greater effect of IT compared to ST on 1-year survival (HR = 2.1 95%CI1.1-4.8, p = 0.003). IT showed a significantly higher survival gain over ST in those patients showing KRAS mutation (7.6 VS 0.8 months,<0.0001), a lumen occlusion >65% (6.6 VS 2.9 months,<0.001), and lacking the involvement of left bronchus (7 VS 2.3 months,<0.0001). Compared to ST, IT also showed a favorable difference in terms of new hospitalizations (p = 0.03), symptom-free interval (p = 0.02), and onset of atelectasis (p = 0.01).
In patients with NSCLC stage IIIB and CAO, additional interventional bronchoscopy might impact on 1-year survival. Genetic and anatomic phenotyping might allow identifying those patients who may gain life expectancy from the endoscopic intervention.
Purpose
To assess the effect of tezosentan, a parenteral dual ET receptor antagonist, on splanchnic and systemic hemodynamics in patients with cirrhosis. In addition, the safety, pharmacokinetics, ...and pharmacodynamics of tezosentan were evaluated.
Methods
The population consisted of patients with cirrhosis with clinically significant portal hypertension. This was a randomized, double-blind, multicenter study. The patients were randomized 3:1 to tezosentan (3 mg/h for 2–3 h) or placebo. HVPG, hepatic blood flow (HBF, ICG method), and systemic arterial pressures were measured before and after tezosentan administration. Plasma concentrations of tezosentan and ET-1 were determined peripherally and in the hepatic vein.
Results
Eighteen patients received tezosentan and six placebo. Baseline clinical, biochemical, and hemodynamic characteristics were balanced between the two groups. There was no significant treatment effect on HVPG. The extraction ratio (0.31), the plasma clearance of ICG (280 ml/min), and the HBF (1,430 ml/min) did not show any relevant changes during the infusion of tezosentan, and there were no differences between placebo- and tezosentan-treated patients. A linear relationship was observed between the maximum-fold increase in ET-1 concentration and the steady-state tezosentan plasma concentration (
r
= 0.82). There was a strong correlation (
r
= 0.88) between plasma clearance of ICG and that of tezosentan (10.2 l/h). Arterial pressure and heart rate did not significantly change in either group.
Conclusion
In patients with cirrhosis, a 2- to 3-h tezosentan infusion was safe and well tolerated but did not change the HVPG. Tezosentan infusion had no influence on the extraction ratio and plasma clearance of ICG and did not change HBF.
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