Multicentre cohort study of acute cholecystitis management during the COVID-19 pandemic.

PURPOSE: To analyse acute cholecystitis (AC) management during the first pandemic outbreak after the recommendations given by the surgical societies estimating: morbidity, length of hospital stay, mortality and hospital-acquired SARS-CoV-2 infection rate. METHODS: Multicentre-combined (retrospective-prospective) cohort study with AC patients in the Community of Madrid between 1st March and 30th May 2020. 257 AC patients were involved in 16 public hospital. Multivariant binomial logistic regression (MBLR) was applied to mortality. RESULTS: Of COVID-19 patients, 30 were diagnosed at admission and 12 patients were diagnosed during de admission or 30 days after discharge. In non-COVID-19 patients, antibiotic therapy was received in 61.3% of grade I AC and 40.6% of grade II AC. 52.4% of grade III AC were treated with percutaneous drainage (PD). Median hospital stay was 5 [3-8] days, which was higher in the non-surgical treatment group with 7.51 days (p < 0.001) and a 3.25% of mortality rate (p < 0.21). 93.3% of patients with SARS-CoV-2 infection at admission were treated with non-surgical treatment (p = 0.03), median hospital stay was 11.0 [7.5-27.5] days (p < 0.001) with a 7.5% of mortality rate (p > 0.05). In patients with hospital-acquired SARS-CoV-2 infection, 91.7% of grade I-II AC were treated with non-surgical treatment (p = 0.037), with a median hospital stay of 16 [4-21] days and a 18.2% mortality rate (p > 0.05). Hospital-acquired infection risk when hospital stay is > 7 days is OR 4.7, CI 95% (1.3-16.6), p = 0.009. COVID-19 mortality rate was 11.9%, AC severity adjusted OR 5.64 (CI 95% 1.417-22.64). In MBLR analysis, age (OR 1.15, CI 95% 1.02-1.31), SARS-CoV-2 infection (OR 14.49, CI 95% 1.33-157.81), conservative treatment failure (OR 8.2, CI 95% 1.34-50.49) and AC severity were associated with an increased odd of mortality. CONCLUSION: In our population, during COVID-19 pandemic, there was an increase of non-surgical treatment which was accompanied by an increase of conservative treatment failure, morbidity and hospital stay length which may have led to an increased risk hospital-acquired SARS-CoV-2 infection. Age, SARS-CoV-2 infection, AC severity and conservative treatment failure were mortality risk factors.

Intestinal Lipid Metabolism Genes Regulated by miRNAs.

MicroRNAs (miRNAs) crucial roles in translation repression and post-transcriptional adjustments contribute to regulate intestinal lipid metabolism. Even though their actions in different metabolic tissues have been elucidated, their intestinal activity is yet unclear. We aimed to investigate intestinal miRNA-regulated lipid metabolism-related genes, by creating an intestinal-specific Dicer1 knockout (Int-Dicer1 KO) mouse model, with a depletion of microRNAs in enterocytes. The levels of 83 cholesterol and lipoprotein metabolism-related genes were assessed in the intestinal mucosa of Int-Dicer1 KO and Wild Type C57BL/6 (WT) littermates mice at baseline and 2 h after an oral lipid challenge. Among the 18 genes selected for further validation, Hmgcs2, Acat1 and Olr1 were found to be strong candidates to be modulated by miRNAs in enterocytes and intestinal organoids. Moreover, we report that intestinal miRNAs contribute to the regulation of intestinal epithelial differentiation. Twenty-nine common miRNAs found in the intestines were analyzed for their potential to target any of the three candidate genes found and validated by miRNA-transfection assays in Caco-2 cells. MiR-31-5p, miR-99b-5p, miR-200a-5p, miR-200b-5p and miR-425-5p are major regulators of these lipid metabolism-related genes. Our data provide new evidence on the potential of intestinal miRNAs as therapeutic targets in lipid metabolism-associated pathologies.

Brain molecules and appetite: the case of oleoylethanolamide.

The neurobiological mechanisms of feeding involve the activity of several brain areas as well as the engagement of endogenous compounds such as ghrelin, melanin-concentrating hormone, orexin, neuropeptide Y, leptin, vasoactive intestinal peptide, cholecystokinin, among others. Furthermore, the family of food-intake modulators has been enlarged due to the inclusion of lipids such as N-arachidonoylethanolamide (anandamide), as well as oleoylethanolamide (OEA). In this regard, the food-intake suppressing properties of OEA have been described since pharmacological administration of this compound induces anorexia. It has been suggested that satiety induced by OEA may be through the activation of peroxisome proliferator-activated receptor-α (PPAR-α), a ligand-activated transcription factor that modulates several pathways of lipid metabolism. The mechanism of action of OEA remains unknown, it has been suggested that the ingestion of dietary fat stimulates epithelial cells of the small intestine and promotes the synthesis and release of OEA. Upon its release, this lipid acts within the gut engaging sensory fibers of the vagus nerve to diminish food-intake. Here, recent advances in our understanding of the neurobiological role of OEA in modulation of feeding will be reviewed. Also, we highlight the emerging molecular mechanism of anorexia induced by OEA.