AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI.     

Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience

This study describes the largest clinical experience using ceftolozane/tazobactam (C/T) for different Pseudomonas aeruginosa infections. A retrospective study was performed at 22 hospitals in Italy (June 2016–March 2018). All adult patients treated with ≥4 days of C/T were enrolled. Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to P. aeruginosa infection and lack of microbiological evidence of infection. C/T treatment was documented in 101 patients with diverse infections, including nosocomial pneumonia (31.7%), acute bacterial skin and skin-structure infection (20.8%), complicated UTI (13.9%), complicated IAI (12.9%), bone infection (8.9%) and primary bacteraemia (5.9%). Over one-half of P. aeruginosa strains were XDR (50.5%), with 78.2% of isolates resistant to at least one carbapenem. C/T was used as first-line therapy in 39 patients (38.6%). When used as second-line or later, the most common reasons for discontinuation of previous antibiotics were in vitro resistance of P. aeruginosa and clinical failure of previous therapy. Concomitant antibiotics were reported in 35.6% of patients. C/T doses were 1.5 g q8h in 70 patients (69.3%) and 3 g q8h in 31 patients (30.7%); median duration of C/T therapy was 14 days. Overall clinical success was 83.2%. Significant lower success rates were observed in patients with sepsis or receiving continuous renal replacement therapy (CRRT). Mild adverse events were reported in only three patients. C/T demonstrated a favourable safety and tolerability profile regardless of the infection type. Clinicians should be aware of the risk of clinical failure with C/T therapy in septic patients receiving CRRT.     

Cystic echinococcosis in sheep in Sardinia. Changing pattern and present status

The epidemiological status of cystic echinococcosis (CE) in sheep in Sardinia over the 20 years since the last control attempt at the end of the 1980s has been assessed, comparing the results of two surveys carried out in abattoirs in southern Sardinia. In the first, conducted in 1995-1997 (5-7 years after the last control effort), CE prevalence of about 75% was observed in the 1375 sheep sampled, with intensity of 10.0 and mean abundance of 7.5. The most affected organ was the liver, whereas a large percentage of infected animals presented cysts in both the liver and lung. Overall, about 26% of parasitized sheep were found to be heavily infected and 12.15% of infected animals harboured fertile cysts. In the second survey, carried out ten years after the first, during the period 2005-2010 in absence of specific control measures, a total of 1414 sheep were examined. CE prevalence was 65%, 78% in the most rural Oristano province and 58% in the most "urbanised" province of Cagliari. Frequency of sheep infected in both the liver and lung had decreased slightly compared to the first survey, particularly in the Cagliari province, as had intensity and mean abundance, though to a lesser extent in the Oristano province. 14.6% of parasitized sheep were heavily infected, showing a general decline over the 10 years between the two surveys, particularly in the Cagliari area where the figure had more than halved. Conversely, about 14% of infected sheep hosted at least 1 fertile cyst, a slight increase compared to the 1st survey. Finally, the trend of CE transmission in Sardinian sheep according to surveys carried out from 1952 to 2010 has been analysed and the results are discussed in the light of the significant socio-economic and structural transformations that have actually modified the zoonosis scenario on the island.