The effect of preoperative anxiety and ovarian stimulation on gastric antrum size: a prospective observational study.

Pulmonary aspiration is a potentially lethal perioperative complication related to gastric size and contents. Several perioperative factors are believed to increase gastric size, while others are less studied. This prospective observational study aimed to investigate the effect of preoperative anxiety and hormone-induced ovarian stimulation on gastric size examined by gastric ultrasound. We recruited 49 female patients undergoing hormone-induced ovarian stimulation and oocyte retrieval for in vitro fertilization at Rabin Medical Centre, Petah Tikva, Israel. Preoperatively, women ranked their anxiety level using a verbal numeric anxiety score (VNS). In addition, we recorded the extent of ovarian stimulation and measured the antral cross-sectional area (CSA) using gastric ultrasound. There was no substantial correlation between preoperative VNS anxiety and antral CSA (p = .697). Moreover, the number of follicles, blood estradiol, and progesterone levels did not correlate with antral CSA (p = .590, p = .104, and p = .511, respectively). In conclusion, neither preoperative anxiety nor extensive ovarian stimulation affects gastric size in fasting healthy patients. However, further studies are warranted in this area to define these findings better. Trial registration: Clinicaltrials.gov, identifier: NCT04833530.

A2E induces IL-1ß production in retinal pigment epithelial cells via the NLRP3 inflammasome.

AIMS: With ageing extracellular material is deposited in Bruch's membrane, as drusen. Lipofuscin is deposited in retinal pigment epithelial cells. Both of these changes are associated with age related macular degeneration, a disease now believed to involve chronic inflammation at the retinal-choroidal interface. We hypothesise that these molecules may act as danger signals, causing the production of inflammatory chemokines and cytokines by the retinal pigment epithelium, via activation of pattern recognition receptors. METHODS: ARPE-19 cells were stimulated in vitro with the following reported components of drusen: amyloid-ß (1-42), Carboxyethylpyrrole (CEP) modified proteins (CEP-HSA), Nε-(Carboxymethyl)lysine (CML) modified proteins and aggregated vitronectin. The cells were also stimulated with the major fluorophore of lipofuscin: N-retinylidene-N-retinylethanolamine (A2E). Inflammatory chemokine and cytokine production was assessed using Multiplex assays and ELISA. The mechanistic evaluation of the NLRP3 inflammasome pathway was assessed in a stepwise fashion. RESULTS: Of all the molecules tested only A2E induced inflammatory chemokine and cytokine production. 25 µM A2E induced the production of significantly increased levels of the chemokines IL-8, MCP-1, MCG and MIP-1α, the cytokines IL-1ß, IL-2, IL-6, and TNF-α, and the protein VEGF-A. The release of IL-1ß was studied further, and was determined to be due to NLRP3 inflammasome activation. The pathway of activation involved endocytosis of A2E, and the three inflammasome components NLRP3, ASC and activated caspase-1. Immunohistochemical staining of ABCA4 knockout mice, which show progressive accumulation of A2E levels with age, showed increased amounts of IL-1ß proximal to the retinal pigment epithelium. CONCLUSIONS: A2E has the ability to stimulate inflammatory chemokine and cytokine production by RPE cells. The pattern recognition receptor NLRP3 is involved in this process. This provides further evidence for the link between A2E, inflammation, and the pathogenesis of AMD. It also supports the recent discovery of NLRP3 inflammasome activation in AMD.

VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma.

Vascular endothelial growth factor A (VEGF-A) is a validated therapeutic target in several angiogenic- and vascular permeability-related pathological conditions, including certain cancers and potentially blinding diseases, such as age-related macular degeneration and diabetic retinopathy. We and others have shown that VEGF-A also plays an important role in neuronal development and neuroprotection, including in the neural retina. Antagonism of VEGF-A function might therefore present a risk to neuronal survival as a significant adverse effect. Herein, we demonstrate that VEGF-A acts directly on retinal ganglion cells (RGCs) to promote survival. VEGF receptor-2 signaling via the phosphoinositide-3-kinase/Akt pathway was required for the survival response in isolated RGCs. These results were confirmed in animal models of staurosporine-induced RGC death and experimental hypertensive glaucoma. Importantly, we observed that VEGF-A blockade significantly exacerbated neuronal cell death in the hypertensive glaucoma model. Our findings highlight the need to better define the risks associated with use of VEGF-A antagonists in the ocular setting.