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Background & Aims: Proton pump inhibitor (PPI) use has been associated with increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes. However, meta-analyses show unclear results, leading to uncertainty regarding the safety of PPI use during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Methods: We conducted a nationwide observational study including all SARS-CoV-2 cases (n = 83,224) in Denmark as of December 1, 2020. The association of current PPI use with risk of infection was examined in a case-control design. We investigated the risk of severe outcomes, including mechanical ventilation, intensive care unit admission, or death, in current PPI users (n = 4473) compared with never users. Propensity score matching was applied to control for confounding. Finally, we performed an updated meta-analysis on risk of SARS-CoV-2 infection and COVID-19 mortality attributable to PPI use. Results: Current PPI use was associated with increased risk of infection; adjusted odds ratio, 1.08 (95% confidence interval [CI], 1.03–1.13). Among SARS-CoV-2 cases, PPI use was associated with increased risk of hospital admission; adjusted relative risk, 1.13 (1.03–1.24), but not with other severe outcomes. The updated meta-analysis showed no association between PPI use and risk of infection or mortality; pooled odds ratio, 1.00 (95% CI, 0.75–1.32) and relative risk, 1.33 (95% CI, 0.71–2.48). Conclusions: Current PPI use may be associated with an increased risk of SARS-CoV-2 infection and hospital admission, but these results with minimally elevated estimates are most likely subject to residual confounding. No association was found for severe outcomes. The results from the meta-analysis indicated no impact of current PPI use on COVID-19 outcomes.

Highlights • In general surgery locoregional anaesthesia increased laparoscopy advantages. • 28 women submitted to gynaecological laparoscopy for benign adnexal conditions. • 13 patients under spinal anaesthesia, 15 under general anaesthesia. • Less postoperative pain and reduced need f opioids in the spinal anaesthesia arm. • Earlier mobilization and return of bowel function in the spinal anaesthesia arm., Background Laparoscopic gynaecological surgery is commonly performed under general anaesthesia with endotracheal intubation. In general surgery, locoregional anaesthesia was applied to laparoscopic procedures, increasing minimally invasive surgery advantages. Aims To assess and compare postoperative pain after laparoscopic adnexal procedures for benign conditions under spinal anaesthesia (SA) versus general anaesthesia (GA). Furthermore, anaesthesiologic, surgical and clinical data were evaluated in both groups. Materials and Methods This is a prospective cohort study performed in a tertiary level referral centre for minimally invasive gynaecological surgery (Gynaecology and Human Reproduction Physiopathology, University of Bologna). Women scheduled for adnexal laparoscopic surgery for benign conditions between February and May 2019 were assigned to receive either SA or GA with endotracheal intubation. A sample size of 13 women per group was needed to detect a 2-point difference in pain scores. Main findings 13 women were enrolled in the SA arm, 15 in the GA arm. In the SA cohort, the most common intraoperative adverse event was shoulder pain, reported by 3/12 women. At 1, 8, 12, 24 and 48 h after surgery pain was significantly lower in the SA arm (p < .05). Patients submitted to SA experienced no need for opioid drugs administration, unlike those receiving GA. Patients’ mobilization and return of bowel function were noted significantly earlier in the SA group (p < .05). Conclusions SA is a feasible, safe and effective anaesthesiologic technique for laparoscopic gynaecological procedures for benign conditions, allowing a better control of postoperative pain. Women undergoing SA achieve earlier mobilization and bowel canalization. During the Covid-19 pandemics, SA could be useful in reducing the need for invasive procedures on respiratory tract.

Alzheimer's disease (AD) represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID) drugs, and genome wide association studies (GWAS) show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive.In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database) simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin). Gene expression signatures were derived for disease from both blood (n = 344) and post-mortem brain (n = 690), and for drugs from immortalised human cell lines exposed to drugs of interest as part of the Connectivity Map platform. Using this novel approach to combine datasets we find striking overlap between AD gene expression in blood and NSAID induced changes in KEGG pathways of Ribosome and Oxidative Phosphorylation. No overlap was found in non NSAID comparison drugs. In brain we find little such overlap, although Oxidative Phosphorylation approaches our pre-specified significance level.These findings suggest that NSAIDs might have a mode of action beyond inflammation and moreover that their therapeutic effects might be mediated in particular by alteration of Oxidative Phosphorylation and possibly the Ribosome pathway. Mining of such datasets might prove increasingly productive as they increase in size and richness. Keywords: Alzheimer's disease, NSAID, Inflammation, Fuzzy logic, Ribosome