RESUMO
BACKGROUND: Hyperglycemia is commonly seen in critically ill patients. This disorder was also seen in coronavirus disease 2019 (COVID-19) patients and was associated with a worse prognosis. The current study determined the prevalence, risk factors, and prognostic implications of hyperglycemia in COVID-19 patients. METHOD: This was a retrospective observational study performed in an intensive care unit for COVID-19 patients. Electronic data of COVID-19 patients admitted to the intensive care unit from August 2nd to October 15th, 2021, were collected. Patients were divided into non-hyperglycemia, hyperglycemia in diabetic patients, and hyperglycemia in non-diabetic patients. Primary outcomes were 28-day and in-hospital mortalities. Multinomial logistic regression and multivariable Cox regression models were used to determine the risk factors for hyperglycemia and mortality, respectively. RESULTS: Hyperglycemia was documented in 65.6% of patients: diabetic patients (44.8%) and new-onset hyperglycemia (20.8%). In-hospital and 28-day mortality rates were 30.2% and 26.1%, respectively. Respiratory failure, corticosteroid therapy, and a higher level of procalcitonin were risk factors for hyperglycemia in diabetic patients, whereas cardiovascular diseases, respiratory failure, and higher aspartate aminotransferase/glutamate aminotransferase ratio were risk factors for hyperglycemia in non-diabetic patients. The risk of the 28-day mortality rate was highest in the new-onset hyperglycemia (hazard ratio [HR] 3.535, 95% confidence interval [CI] 1.338-9.338, p=0.011), which was higher than hyperglycemia in type 2 diabetes mellitus patients (HR 1.408, 95% CI 0.513-3.862, p=0.506). CONCLUSION: Hyperglycemia was common in COVID-19 patients in the intensive care unit. Hyperglycemia reflected the disease severity but was also secondary to therapeutic intervention. New-onset hyperglycemia was associated with poorer outcomes than that in diabetic patients.
RESUMO
Very little is known about chemical interactions between fungi and their mollusc host within marine environments. Here, we investigated the metabolome of a Penicillium restrictum MMS417 strain isolated from the blue mussel Mytilus edulis collected on the Loire estuary, France. Following the OSMAC approach with the use of 14 culture media, the effect of salinity and of a mussel-derived medium on the metabolic expression were analysed using HPLC-UV/DAD-HRMS/MS. An untargeted metabolomics study was performed using principal component analysis (PCA), orthogonal projection to latent structure discriminant analysis (O-PLSDA) and molecular networking (MN). It highlighted some compounds belonging to sterols, macrolides and pyran-2-ones, which were specifically induced in marine conditions. In particular, a high chemical diversity of pyran-2-ones was found to be related to the presence of mussel extract in the culture medium. Mass spectrometry (MS)- and UV-guided purification resulted in the isolation of five new natural fungal pyran-2-one derivatives-5,6-dihydro-6S-hydroxymethyl-4-methoxy-2H-pyran-2-one (1), (6S, 1'R, 2'S)-LL-P880ß (3), 5,6-dihydro-4-methoxy-6S-(1'S, 2'S-dihydroxy pent-3'(E)-enyl)-2H-pyran-2-one (4), 4-methoxy-6-(1'R, 2'S-dihydroxy pent-3'(E)-enyl)-2H-pyran-2-one (6) and 4-methoxy-2H-pyran-2-one (7)-together with the known (6S, 1'S, 2'S)-LL-P880ß (2), (1'R, 2'S)-LL-P880γ (5), 5,6-dihydro-4-methoxy-2H-pyran-2-one (8), (6S, 1'S, 2'R)-LL-P880ß (9), (6S, 1'S)-pestalotin (10), 1'R-dehydropestalotin (11) and 6-pentyl-4-methoxy-2H-pyran-2-one (12) from the mussel-derived culture medium extract. The structures of 1-12 were determined by 1D- and 2D-MMR experiments as well as high-resolution tandem MS, ECD and DP4 calculations. Some of these compounds were evaluated for their cytotoxic, antibacterial, antileishmanial and in-silico PTP1B inhibitory activities. These results illustrate the utility in using host-derived media for the discovery of new natural products.