A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3 alpha, by gut epithelial cells

Background & Aims: Interleukin (IL)-21, a T-cell-derived cytokine, is produced in excess in inflammatory bowel diseases (IBD). The IL-21 receptor (IL-21R) is expressed by immune and nonimmune cells, raising the possibility that IL-21 has broad effects in gut inflammation. In this study we examined whether intestinal epithelial cells express IL-21R and respond to IL-21 in IBD. Methods: IL-21R was evaluated in intestinal samples of IBD patients and controls by immunohistochemistry and Western blotting. Intestinal epithelial cells were stimulated with IL-21, and cell-free supernatants were evaluated by a protein array and enzyme-linked immunosorbent assay. The effect of IL-21-treated epithelial cell supernatants on blood lymphocyte migration was assessed using a chemotaxis assay. Finally, we evaluated the effect of a neutralizing IL-21 antibody on MIP-3 alpha synthesis in ex vivo organ cultures of IBD mucosal explants. Results: Constitutive expression of IL-21R was seen in intestinal epithelial cells, but was higher in IBD patients than in controls. Stimulation of intestinal epithelial cells with IL-21 resulted in enhanced phosphorylation of ERK1/2 and p38 and increased synthesis of macrophage inflammatory protein-3 alpha (MIP-3 alpha), a T-cell chemoattractant. Inhibition of ERK1/2 but not p38 suppressed IL-21-induced MIP-3 alpha production. IL-21-treated cell culture supernatants enhanced in vitro lymphocyte migration, and this effect was inhibited by anti-MIP-3 alpha antibody. Treatment of IBD explants with anti-IL-21 reduced MIP-3 alpha production. Conclusions: These data show that intestinal epithelial cells are a target of IL-21 and that IL-21 is involved in the cross-talk between epithelial and immune cells in the gut

Sleepiness at the time of testing impairs olfactory performance

We aimed to investigate the differential roles of hypocretin versus dopamine dysfunction versus excessive daytime sleepiness (EDS) in the development of hyposmia. Olfaction in patients with Parkinson disease, restless leg syndrome, narcolepsy with cataplexy, EDS, and healthy controls was compared

Aspiration risk factors, microbiology, and empiric antibiotics for patients hospitalized with community-acquired pneumonia

Background: Aspiration community-acquired pneumonia (ACAP) and community-acquired pneumonia (CAP) in patients with aspiration risk factors (AspRFs) are infections associated with anaerobes, but limited evidence suggests their pathogenic role. Research question: What are the aspiration risk factors, microbiology patterns, and empiric anti-anaerobic use in patients hospitalized with CAP? Study design and methods: This is a secondary analysis of GLIMP, an international, multicenter, point-prevalence study of adults hospitalized with CAP. Patients were stratified into three groups: (1) ACAP, (2) CAP/AspRF+ (CAP with AspRF), and (3) CAP/AspRF- (CAP without AspRF). Data on demographics, comorbidities, microbiological results, and anti-anaerobic antibiotics were analyzed in all groups. Patients were further stratified in severe and nonsevere CAP groups. Results: We enrolled 2,606 patients with CAP, of which 193 (7.4%) had ACAP. Risk factors independently associated with ACAP were male, bedridden, underweight, a nursing home resident, and having a history of stroke, dementia, mental illness, and enteral tube feeding. Among non-ACAP patients, 1,709 (70.8%) had CAP/AspRF+ and 704 (29.2%) had CAP/AspRF-. Microbiology patterns including anaerobes were similar between CAP/AspRF-, CAP/AspRF+ and ACAP (0.0% vs 1.03% vs 1.64%). Patients with severe ACAP had higher rates of total gram-negative bacteria (64.3% vs 44.3% vs 33.3%, P = .021) and lower rates of total gram-positive bacteria (7.1% vs 38.1% vs 50.0%, P 50% in all groups) independent of AspRFs or ACAP received specific or broad-spectrum anti-anaerobic coverage antibiotics. Interpretation: Hospitalized patients with ACAP or CAP/AspRF+ had similar anaerobic flora compared with patients without aspiration risk factors. Gram-negative bacteria were more prevalent in patients with severe ACAP. Despite having similar microbiological flora between groups, a large proportion of CAP patients received anti-anaerobic antibiotic coverage

Changes in surgicaL behaviOrs dUring the CoviD-19 pandemic. The SICE CLOUD19 Study

BACKGROUND: The spread of the SARS-CoV2 virus, which causes COVID-19 disease, profoundly impacted the surgical community. Recommendations have been published to manage patients needing surgery during the COVID-19 pandemic. This survey, under the aegis of the Italian Society of Endoscopic Surgery, aims to analyze how Italian surgeons have changed their practice during the pandemic.METHODS: The authors designed an online survey that was circulated for completion to the Italian departments of general surgery registered in the Italian Ministry of Health database in December 2020. Questions were divided into three sections: hospital organization, screening policies, and safety profile of the surgical operation. The investigation periods were divided into the Italian pandemic phases I (March-May 2020), II (June-September 2020), and III (October-December 2020).RESULTS: Of 447 invited departments, 226 answered the survey. Most hospitals were treating both COVID-19-positive and -negative patients. The reduction in effective beds dedicated to surgical activity was significant, affecting 59% of the responding units. 12.4% of the respondents in phase I, 2.6% in phase II, and 7.7% in phase III reported that their surgical unit had been closed. 51.4%, 23.5%, and 47.8% of the respondents had at least one colleague reassigned to non-surgical COVID-19 activities during the three phases. There has been a reduction in elective (>200 procedures: 2.1%, 20.6% and 9.9% in the three phases, respectively) and emergency (<20 procedures: 43.3%, 27.1%, 36.5% in the three phases, respectively) surgical activity. The use of laparoscopy also had a setback in phase I (25.8% performed less than 20% of elective procedures through laparoscopy). 60.6% of the respondents used a smoke evacuation device during laparoscopy in phase I, 61.6% in phase II, and 64.2% in phase III. Almost all responders (82.8% vs. 93.2% vs. 92.7%) in each analyzed period did not modify or reduce the use of high-energy devices.CONCLUSION: This survey offers three faithful snapshots of how the surgical community has reacted to the COVID-19 pandemic during its three phases. The significant reduction in surgical activity indicates that better health policies and more evidence-based guidelines are needed to make up for lost time and surgery not performed during the pandemic