Viral uptake and pathophysiology of the lung endothelial cells in age-associated severe SARS-CoV-2 infection models.

Thrombosis is the major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the pathology of vascular endothelial cells (ECs) has received much attention. Although there is evidence of the infection of ECs in human autopsy tissues, their detailed pathophysiology remains unclear due to the lack of animal model to study it. We used a mouse-adapted SARS-CoV-2 virus strain in young and mid-aged mice. Only mid-aged mice developed fatal pneumonia with thrombosis. Pulmonary ECs were isolated from these infected mice and RNA-Seq was performed. The pulmonary EC transcriptome revealed that significantly higher levels of viral genes were detected in ECs from mid-aged mice with upregulation of viral response genes such as DDX58 and IRF7. In addition, the thrombogenesis-related genes encoding PLAT, PF4, F3 PAI-1, and P-selectin were upregulated. In addition, the inflammation-related molecules such as CXCL2 and CXCL10 were upregulated in the mid-aged ECs upon viral infection. Our mouse model demonstrated that SARS-CoV-2 virus entry into aged vascular ECs upregulated thrombogenesis and inflammation-related genes and led to fatal pneumonia with thrombosis. Current results of EC transcriptome showed that EC uptake virus and become thrombogenic by activating neutrophils and platelets in the aged mice, suggesting age-associated EC response as a novel finding in human severe COVID-19.

Risk factors for postoperative nausea and vomiting in patients of orthognathic surgery according to the initial onset time: a cross-sectional study.

Background: A high incidence (40-73%) of postoperative nausea and vomiting (PONV) has been reported following orthognathic surgery, and various risk factors have been associated with it. Identifying PONV risk factors based on initial onset time will help establish preventive measures. This study aimed to identify factors that are significantly related to PONV based on the initial onset time after orthognathic surgery. Methods: This study included 590 patients who underwent orthognathic surgery. Multivariate logistic regression analysis was performed to identify the risk factors that are significantly related to PONV. The objective variables were classified into three categories: no PONV, early PONV (initial onset time: 0-2 h after anesthesia), and late PONV (initial onset time: 2-24 h after anesthesia). The explanatory variables included relevant risk factors for PONV, as considered in previous studies. Results: Total intravenous anesthesia with propofol was a significant depressant factor for early PONV (adjusted odds ratio [aOR] = 0.340, 95% confidence interval [CI] = 0.209-0.555) and late PONV (aOR = 0.535, 95% CI = 0.352-0.814). The administration of a combination of intraoperative antiemetics (vs. no administration) significantly reduced the risk of early PONV (aOR = 0.464, 95% CI = 0.230-0.961). Female sex and young age were significant risk factors for late PONV (aOR = 1.492, 95% CI = 1.170-1.925 and unit aOR = 1.033, 95% CI = 1.010-1.057, respectively). Conclusion: We identified factors that are significantly related to PONV based on the initial onset time after orthognathic surgery. Total intravenous anesthesia with propofol significantly reduced the risk of PONV not only in the early period (0-2 h after anesthesia) but also in the late period (2-24 h after anesthesia).

Cross-sectional Study of PONV Risk Factors for Oral Surgery After Intubated General Anesthesia With Total Intravenous Anesthesia.

OBJECTIVE: The incidence of postoperative nausea and vomiting (PONV) after general anesthesia with total intravenous anesthesia (TIVA) was reported to be significantly lower than with volatile inhalational agents (13.3% vs 25%). However, no investigation of PONV risk factors associated with TIVA has ever been reported. This cross-sectional retrospective study aimed to investigate whether known risk factors influenced PONV in intubated general anesthetics utilizing TIVA for dental or oral and maxillofacial surgery. METHODS: Subjects were 761 patients who underwent dental or oral and maxillofacial surgery under TIVA with propofol, fentanyl, and remifentanil. Univariate and multivariable logistic regression analyses were performed using PONV (within 24 hours) as the dependent variable and previously reported risk factors as independent variables. RESULTS: Age (odds ratio [OR]: 1.020 per year decrease; 95% confidence interval [CI]: 1.0002-1.0418; P = .047) and female sex (OR: 2.73; 95% CI: 1.60-4.84; P < .001) were positively associated with PONV. Sagittal split ramus osteotomy (SSRO) (OR: 2.28; 95% CI: 1.21-4.33; P = .011) and bimaxillary osteotomy (OR: 5.69; 95% CI: 2.09-15.99; P < .001) were more likely to be associated with PONV than operations that were neither bimaxillary osteotomy nor SSRO. Late PONV (2-24 hours) had an ∼2.7 times higher incidence than early PONV (0-2 hours). CONCLUSION: These findings suggest further PONV countermeasures, aside from TIVA with propofol and prophylactic antiemetics for orthognathic surgeries especially bimaxillary osteotomy, are needed.

Prolonged Washout Period for Avoiding Azilsartan-Induced Refractory Hypotension During General Anesthesia for a Patient With Renal Impairment.

Angiotensin receptor blockers (ARBs) are widely used to treat hypertension, but severe refractory hypotension during general anesthesia is a well-known complication associated with the continuation of ARBs during the perioperative period. It has therefore been recommended that ARBs be withheld for 24 hours before induction of general anesthesia. However, impaired renal function affects the pharmacokinetics of each ARB differently. The half-life of azilsartan is prolonged in accordance with the degree of renal impairment. Herein, we describe a patient with chronic kidney disease grade 3B who experienced severe refractory hypotension after induction of general anesthesia requiring administration of dopamine following inadequate responses to ephedrine and phenylephrine despite a 24-hour azilsartan washout period. When the same patient underwent general anesthesia for a subsequent surgery, azilsartan was withheld for 48 hours before induction, resulting in mild intraoperative hypotension that responded adequately to phenylephrine. Severe refractory hypotension during general anesthesia cannot always be avoided by holding azilsartan for 24 hours in patients with significant renal impairment. Therefore, a longer washout period may be preferable for patients regularly taking azilsartan who also have concurrent substantial renal impairment.