Impact of direct acting antivirals (DAAs) on cardiovascular events in HCV cohort with pre-diabetes

Background and aimsBeyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort.Methods and resultsIn this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19–34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148–1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44–53.95; p = 0.016).ConclusionsHCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors.     

Cerebral involvement in COVID-19 is associated with metabolic and coagulation derangements: an EEG study

Journal of Neurology -     

Expansion of KPC-producing Klebsiella pneumoniae with various mgrB mutations giving rise to colistin resistance: the role of ISL3 on plasmids

mcr-1 has been reported as the first plasmid-encoded gene conferring colistin resistance. In KPC-producing Klebsiella pneumoniae (KPC-KP), however, colistin resistance is rapidly emerging through other mechanisms. Resistance is frequently due to disruption of the mgrB gene by insertion sequences, e.g. ISL3. The aim of this study was to investigate the expansion of mgrB-mutated KPC-KP isolates. In addition, the localisation and targets of ISL3 sequences within the core and accessory genome of common KPC-KP lineages were identified. A total of 29 clinical K. pneumoniae isolates collected from Italian patients were randomly selected. Whole genome sequences were analysed for resistance genes, plasmids and insertion sequences. In addition, 27 colistin-resistant KPC-KP isolates from a previous study from Crete (Greece) were assessed. Clonal expansion of KPC-KP isolates with various mutations in mgrB among all lineages was observed. In two Italian MLST ST512 isolates and eight Greek ST258 isolates, an identical copy of ISL3 was inserted in mgrB nucleotide position 133. ISL3, a transposable restriction–modification system of 8154 nucleotides, was located on pKpQIL-like plasmids and may transpose into the chromosome. In four isolates, chromosomal integration of ISL3 in diverse inner membrane proteins other than mgrB was identified. Colistin resistance is most often explained by clonal expansion of isolates with mutated mgrB. pKpQIL-like plasmids, which are omnipresent in KPC-KP, carry insertion sequences such as ISL3 that have mgrB as a target hotspot for transposition. Transposition of insertion sequences from plasmids and subsequent clonal expansion may contribute to the emerging colistin resistance in KPC-KP.     

The in vitro effects of cetyltrimethylammonium naproxenate on oral and pharyngeal microorganisms of various ecological niches

The purpose of this study was to determine the in vitro susceptibility to cetyltrimethylammonium naproxenate for various aerobic and anaerobic micro-organisms responsible for oral and pharyngeal diseases by assessing the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) or minimum fungicidal concentrations (MFCs) and by determining kill-times. The MICs of cetyltrimethylammonium naproxenate for 46 tested strains (25 reference strains and 21 clinical isolates) ranged from 8 to 500 micrograms/ml. The MIC was found to be 31.25 micrograms/ml for 36% of the reference strains. Even lower MIC values (15.63 micrograms/ml) were observed for some anaerobic strains, for Haemophilus influenzae and for Candida tropicalis. MIC and MBC values corresponded for the majority of strains tested while the MFC for C. tropicalis and C. albicans was much higher. Only 9.5% of the clinical isolates gave a MIC value of 31.25 micrograms/ml. Enterococcus faecalis, Streptococcus pyogenes and Staphylococcus aureus showed MIC at 62.5 micrograms/ml. The MIC and MBC values among the isolates were comparable, while the MFC value for the yeasts was greater. A concentration of 125 micrograms/ml of cetyltrimethylammonium naproxenate inhibited the growth of all bacteria, except Enterobacteriaceae and Pseudomonaceae, and yeasts. Cetyltrimethylammonium naproxenate shows very rapid kill-time for S. sanguis (0"), and rapid (15") for S. pyogenes, S. dysgalactiae and S. mutans and for Moraxella catarrhalis, while a longer kill-time was necessary for the other microbes tested.