Keywords:High-flow nasal therapy Pathogen transmission Droplet infection S U M M A R YHigh-flow nasal therapy is increasingly used in hospitals because of its effectiveness and patient comfort. However, pathogens in the patient's nasal and oral cavities may be dispersed by forced air. This study aimed to investigate the risk of pathogen dispersal during high-flow nasal therapy. Liquid and bacterial dispersal were assessed via in-vitro experimental set-ups using a manikin. Thickened water or fresh yeast solution mimicked saliva and nasal mucus secretions. Dispersal was limited to the proximal area of the face and nasal cannula, suggesting that high-flow nasal therapy does not increase the risk of droplet and contact infection.

Inflammation is emerging as a critical factor in the pathophysiology of intracranial aneurysm. TLR4 (toll-like receptor 4) contributes not only to the innate immune responses but also to the inflammatory processes associated with vascular disease. Therefore, we examined the contribution of the TLR4 pathway to the development of the rupture of intracranial aneurysm. We used a mouse model of intracranial aneurysm. TLR4 inhibition significantly reduced the development of aneurysmal rupture. In addition, the rupture rate and levels of proinflammatory cytokines were lower in TLR4 knockout mice than the control littermates. Macrophage/monocyte-specific TLR4 knockout mice had a lower rupture rate than the control littermate mice. Moreover, the deficiency of MyD88 (myeloid differentiation primary-response protein 88), a key mediator of TLR4, reduced the rupture rate. These findings suggest that the TLR4 pathway promotes the development of intracranial aneurysmal rupture by accelerating inflammation in aneurysmal walls. Inhibition of the TLR4 pathway in inflammatory cells may be a promising approach for the prevention of aneurysmal rupture and subsequent subarachnoid hemorrhage.

Potential roles for neutrophils in the pathophysiology of intracranial aneurysm have long been suggested by clinical observations. The presence of neutrophil enzymes in the aneurysm wall has been associated with significant increases in rupture risk. However, the mechanisms by which neutrophils may promote aneurysm rupture are not well understood. Neutrophil extracellular traps (NETs) were implicated in many diseases that involve inflammation and tissue remodeling, including atherosclerosis, vasculitis, and abdominal aortic aneurysm. Therefore, we hypothesized that NETs may promote the rupture of intracranial aneurysm, and that removal of NETs can reduce the rate of rupture. We employed both pharmacological and genetic approaches for the disruption of NETs and used a mouse model of intracranial aneurysm to investigate the roles of NETs in the development of intracranial aneurysm rupture. Here, we showed that NETs are detected in human intracranial aneurysms. Both global and granulocyte-specific knockout of peptidyl arginine deiminase 4 (an enzyme essential for NET formation) reduced the rate of aneurysm rupture. Pharmacological blockade of the NET formation by Cl-amidine also reduced the rate of aneurysm rupture. In addition, the resolution of already formed NETs by deoxyribonuclease was effective against aneurysm rupture. Inhibition of NETs formation with Cl-amidine decreased mRNA expression of proinflammatory cytokines (intercellular adhesion molecule 1 (ICAM-1), interleukin 1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α)) in cerebral arteries. These data suggest that NETs promote the rupture of intracranial aneurysm. Pharmacological removal of NETs, by inhibition of peptidyl arginine deiminase 4 or resolution of already-formed NETs, may represent a potential therapeutic strategy for preventing aneurysmal rupture.

Background and Purpose: Tobacco cigarette smoking is considered to be a strong risk factor for intracranial aneurysmal rupture. Nicotine is a major biologically-active constituent of tobacco products. Nicotine’s interactions with vascular cell nicotinic acetylcholine receptors containing α7 subunits (α7*-nAChR) are thought to promote local inflammation and sustained angiogenesis. In this study, using a mouse intracranial aneurysm model, we assessed potential contributions of nicotine exposure and activation of α7*-nAChR to the development of aneurysmal rupture. Methods: Intracranial aneurysms were induced by a combination of deoxycorticosterone-salt induced hypertension and a single elastase injection into cerebrospinal fluid in mice. Results: Exposure to nicotine or an α7*-nAChR-selective agonist significantly increased aneurysm rupture rate. Co-exposure to an α7*-nAChR antagonist abolished nicotine’s deleterious effect. Additionally, nicotine’s promotion of aneurysm rupture was absent in smooth muscle cell-specific α7*-nAChR subunit knockout mice, but not in mice lacking α7*-nAChR on endothelial cells or macrophages. Nicotine treatment increased the mRNA levels of vascular endothelial growth factor, platelet-derived growth factor-B, and inflammatory cytokines. α7*-nAChR antagonist reversed nicotine-induced up-regulation of these growth factors and cytokines. Conclusion: Our findings indicate that nicotine exposure promotes aneurysmal rupture through actions on vascular smooth muscle cell α7*-nAChR.

Background We evaluated the change of cerebral regional tissue oxygen saturation (rSO 2 ) along with the pneumoperitoneum and the Trendelenburg position. We also assessed the relationship between the change of rSO 2 and the changes of mean arterial blood pressure (MAP), heart rate (HR), arterial carbon dioxide tension (PaCO 2 ), arterial oxygen tension (PaO 2 ), or arterial oxygen saturation (SaO 2 ). Methods Forty-one adult patients who underwent a robotic assisted endoscopic prostatic surgery under propofol and remifentanil anesthesia were involved in this study. During the surgery, a pneumoperitoneum was established using carbon dioxide. Measurements of rSO 2 , MAP, HR, PaCO 2 , PaO 2 , and SaO 2 were performed before the pneumoperitoneum (baseline), every 5 min after the onset of pneumoperitoneum, before the Trendelenburg position. After the onset of the Trendelenburg position, rSO 2 , MAP, HR were recorded at 5, 10, 20, 30, 45, and 60 min, and PaCO 2 , PaO 2 , and SaO 2 were measured at 10, 30, and 60 min. Results Before the pneumoperitoneum, left and right rSO 2 were 67.9 ± 6.3% and 68.5 ± 7.0%. Ten minutes after the onset of pneumoperitoneum, significant increase in the rSO 2 was observed (left: 69.6 ± 5.9%, right: 70.6 ± 7.4%). During the Trendelenburg position, the rSO 2 increased initially and peaked at 5 min (left: 72.2 ± 6.5%, right: 73.1 ± 7.6%), then decreased. Multiple regression analysis showed that change of rSO 2 correlated with MAP and PaCO 2 . Conclusions Pneumoperitoneum and the Trendelenburg position in robotic-assisted endoscopic prostatic surgery did not worsen cerebral oxygenation. Arterial blood pressure is the critical factor in cerebral oxygenation. Trial registration Japan Primary Registries Network (JPRN); UMIN-CTR ID; UMIN000026227 (retrospectively registered).