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Akt is an important kinase in metabolism. Akt also phosphorylates and activates endothelial and neuronal nitric oxide (NO) synthases (eNOS and nNOS, respectively) expressed in M0 (unpolarized) macrophages. We showed that e/nNOS NO production downstream of bitter taste receptors enhances macrophage phagocytosis. In airway epithelial cells, we also showed that the activation of Akt by a small molecule (SC79) enhances NO production and increases levels of nuclear Nrf2, which reduces IL-8 transcription during concomitant stimulation with Toll-like receptor (TLR) 5 agonist flagellin. We hypothesized that SC79's production of NO in macrophages might likewise enhance phagocytosis and reduce the transcription of some pro-inflammatory cytokines. Using live cell imaging of fluorescent biosensors and indicator dyes, we found that SC79 induces Akt activation, NO production, and downstream cGMP production in primary human M0 macrophages. This was accompanied by a reduction in IL-6, IL-8, and IL-12 production during concomitant stimulation with bacterial lipopolysaccharide, an agonist of pattern recognition receptors including TLR4. Pharmacological inhibitors suggested that this effect was dependent on Akt and Nrf2. Together, these data suggest that several macrophage immune pathways are regulated by SC79 via Akt. A small-molecule Akt activator may be useful in some infection settings, warranting future in vivo studies. [ABSTRACT FROM AUTHOR]

Objective: Surgical frailty estimates a patient's ability to withstand the physiologic stress of an intervention. There is limited data regarding the impact of frailty on endoscopic cerebrospinal fluid (CSF) leak repair. Methods: Patients undergoing CSF leak repair at two tertiary academic skull base programs were retrospectively reviewed. Demographic, treatment, and postoperative outcomes data were recorded. Frailty was calculated using validated indices, including the American Society of Anesthesiologists (ASA) classification, Charlson Comorbidity Index (CCI), and the Modified 5‐Item Frailty Index (mFI‐5). Outcomes included 30‐day medical and surgical complications and readmission. Results: A total of 185 patients were included with 128 (69.2%) female patients and average age of 54 ± 14 years. The average body mass index was 34.6 ± 8.5. The most common identified etiology was idiopathic intracranial hypertension (IIH) in 64 patients (34.6%). A total of 125 patients (68%) underwent perioperative lumbar drain placement (primarily to measure intracranial pressures and diagnose IIH). Most patients were ASA class 3 (48.6%) with mean CCI 2.14 ± 2.23 and mFI‐5 0.97 ± 0.90. Three patients had postoperative CSF leaks, with an overall repair success rate of 98.4%. There was no association between increased frailty and 30‐day medical outcomes, surgical outcomes, or readmission (all p > 0.05). Conclusions: Endoscopic CSF leak repair in a frail population, including lumbar drain placement and bed rest, was not associated with an increased rate of complications. Previous data suggests increased complications in open craniotomy procedures in patients with significant comorbidities. This study suggests that the endoscopic approach to CSF leak repair is well tolerated in the frail population. Level of Evidence: IV Laryngoscope, 134:2713–2717, 2024 [ABSTRACT FROM AUTHOR]

Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine malignancy arising from the olfactory neuroepithelium. ONB frequently presents with nonspecific sinonasal complaints, including nasal obstruction and epistaxis, and diagnosis can be obtained through a combination of physical examination, nasal endoscopy, and computed tomography and magnetic resonance imaging. Endoscopic resection with negative margins, with or without craniotomy, as necessary, is the standard of care for definitive treatment of ONB. Regional metastasis to the neck is often detected at presentation or may occur in a delayed fashion and should be addressed through elective neck dissection or radiation. Adjuvant radiotherapy should be considered, particularly in the case of high grade or tumor stage, as well as positive surgical margins. Systemic therapy is an area of active investigation in both the neoadjuvant and adjuvant setting, with many advocating in favor of induction chemotherapy for significant orbital or intracranial involvement prior to surgical resection. Various targeted immunotherapies are currently being studied for the treatment of recurrent or metastatic ONB. Prolonged locoregional and distant surveillance are indicated following definitive treatment, given the tendency for delayed recurrence and metastasis. [ABSTRACT FROM AUTHOR]

This article discusses the secondary repair of iatrogenic cerebrospinal fluid (CSF) leaks during functional endoscopic sinus surgery (FESS) in a tertiary-care center. The study included 12 patients who underwent secondary repair of CSF leaks. The average time from initial surgery to presentation at the institution was 8.25 days, and CSF leaks were recognized intraoperatively in 33.3% of cases. The management included updated CT scans, intravenous ceftriaxone, and operative repair tailored to each patient. Acetazolamide was started postoperatively for patients with a BMI greater than 40, and there were no cases of persistent CSF leaks or meningitis. [Extracted from the article]

This article discusses the use of an endoscopic endonasal approach (EEA) for the resection of anterior skull base tumors in young children. Traditionally, these tumors have been treated with open craniotomy, but the EEA has become more common in pediatric patients. The article reviews a retrospective study of ten patients aged 5 or younger who underwent EEA for tumor resection. The results showed that the EEA was safe and effective, with successful reconstruction of the skull base in all cases. Further research is needed to evaluate the EEA in this population. [Extracted from the article]

This article examines the impact of frailty on postoperative outcomes in patients undergoing open and endoscopic resection of olfactory groove meningiomas. The study included 19 patients, with 6 undergoing endoscopic resection and 13 undergoing open craniotomy. The results showed that frailty metrics, such as the Charlson Comorbidity Index and modified 5-item frailty index, were not associated with postoperative complications or poor neurologic outcomes. However, a prior history of cranial radiation was associated with complications in open cases. The study suggests a need to reconsider traditional frailty measures in these surgical procedures. [Extracted from the article]

This article explores the impact of patient demographics and socioeconomic status on surgical outcomes in endonasal endoscopic pituitary surgery. The study reviewed 187 patients who underwent this surgery between 2017 and 2019. The findings revealed that male patients were more likely to have larger tumors and higher comorbidity scores, while Hispanic patients had smaller tumors and lower comorbidity scores. Black patients experienced longer hospital stays, higher costs, and higher rates of readmission, regardless of income. These results suggest that racial health disparities are not solely due to socioeconomic status and emphasize the importance of considering social determinants of health in clinical practice. [Extracted from the article]

Objective: Frailty metrics estimate a patient's ability to tolerate physiologic stress and there are limited frailty data in patients undergoing expanded endonasal approaches (EEA) for suprasellar pathologies. Elevated frailty metrics have been associated with increased perioperative complications in patients undergoing craniotomies. We sought to examine this potential relationship in EEA. Study Design: Retrospective cohort study. Setting: Two tertiary academic skull base centers. Methods: Cases of patients undergoing EEA for suprasellar pathologies were reviewed. Demographic, treatment, survival, and postoperative outcomes data were recorded. Frailty was calculated using validated indexes, including the American Society of Anesthesiologists (ASA) classification, the modified 5‐item frailty index (mFI‐5), and the Charlson comorbidity index (CCI). Primary outcomes included 30‐day medical and surgical complications. Results: A total of 88 patients were included, with 59 (67%) female patients and a mean age of 54 ± 15 years. The most common pathologies included 53 meningiomas (60.2%) and 21 craniopharyngiomas (23.9%). Most patients were ASA class 3 (54.5%) with mean mFI‐5 0.82 ± 1.01 and CCI 4.18 ± 2.42. There was no association between increased frailty and 30‐day medical or surgical outcomes (including postoperative cerebrospinal fluid leak), prolonged length of hospital stay, or mortality (all P >.05). Higher mFI‐5 was associated with an increased risk for 30‐day readmission (odds ratio: 2.35, 95% confidence Interval: 1.10‐5.64, P =.04). Conclusion: Despite the patient population being notably frail, we only identified an increased risk for 30‐day readmission and observed no links with deteriorating surgical, medical, or mortality outcomes. This implies that conventional frailty metrics may not effectively align with EEA outcomes. [ABSTRACT FROM AUTHOR]

A study published in the journal Laryngoscope discusses the use of a combined transnasal, transoral approach for the removal of odontogenic cysts. The study found that this approach resulted in reduced recurrence rates and favorable sinonasal outcomes compared to traditional transoral-only approaches. The study included a retrospective review of patients who underwent the combined approach and collected data on demographic information, clinical history, and sinonasal outcomes. The results showed a low recurrence rate and improvement in sinonasal symptoms. The study recommends considering this approach for the management of odontogenic cysts involving the maxillary sinus. [Extracted from the article]

Objective: We sought to quantify trends in operative volumes and complications of endoscopic sellar surgery before and after the COVID‐19 pandemic onset. Study Design: We performed a retrospective analysis. Setting: TriNetX database analysis. Methods: All adults undergoing neuroendoscopy for resection of pituitary tumor (Current Procedural Terminology code 62165) with diagnosis of benign/malignant neoplasm of pituitary gland (D35.2/C75.1) or benign/malignant neoplasm of craniopharyngeal duct (D35.3/C75.2) were included using the TriNetX database for 2 years before (pre‐COVID group) and 2 years after (post‐COVID group) February 17, 2020. Results: A total of 1238 patients in the pre‐COVID group and 1186 patients in the post‐COVID group were compared. Age, gender, and race were statistically similar between the groups (P >.05). Surgical volume decreased by 6% in the post‐COVID group. In 2020 Q2, operative volume decreased by 19%, and in 2021 Q4 (peak COVID‐19 caseload in the United States), operative volumes decreased by 29% compared to 2 years prior. Postoperative complications including meningitis (P =.49), cerebrospinal fluid leak (P =.36), visual field deficits (P =.07), postoperative pneumonia or respiratory failure (P =.42), and 30‐day readmission rates (P =.89) were similar between the 2 groups. Conclusion: Overall, endoscopic sellar surgery may continue to fluctuate with increased COVID‐19 outbreaks. Patient outcomes do not appear to be worsened by decreased operative volumes or delays in nonurgent surgeries. [ABSTRACT FROM AUTHOR]

This article discusses the long-term effects of aspirin desensitization on the inflammatory response in patients with aspirin-exacerbated respiratory disease (AERD). The study found that after long-term aspirin desensitization, there were significant increases in interferon-gamma (IFN-γ) and interleukin-10 (IL-10), suggesting a shift in the inflammatory response. These cytokines are associated with immune tolerance and may play a role in the mechanism of aspirin desensitization. However, the specific cells producing these cytokines and the role of lipid mediators in aspirin desensitization were not addressed in this study. Further research is needed to understand the cellular context and mechanisms associated with these cytokine shifts. [Extracted from the article]

Background Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy with a poor prognosis, and multimodal therapy is the standard of care. We sought to characterize treatment delays in SNUC managed with surgery and adjuvant radiation and to determine the impact on survival using the National Cancer Database (NCDB). Methods This was a retrospective, population-based cohort study of patients with SNUC between 2004 and 2016 in the NCDB. The intervals of diagnosis to surgery (DTS), surgery to radiation (SRT), and radiation duration (RTD) were examined. Recursive partitioning analysis (RPA) was performed to identify the variables with the greatest impact on survival. The association between treatment delay and overall survival (OS) was then assessed using multivariate Cox proportional hazards regression. Results Of 173 patients who met inclusion criteria, 65.9% were male, average age at diagnosis was 56.6 years, and 5-year OS was 48.1%. Median durations of DTS, SRT, and RTD were 18, 43, and 46 days, respectively. Predictors of treatment delay included Black race, government insurance excluding Medicare/Medicaid, and positive margins. RPA-derived optimal thresholds were 29, 28, and 38 days for DTS, SRT and RTD, respectively. On multivariate analysis, positive margins (hazard ratio [HR]: 4.82; 95% confidence interval [CI]: 2.28–10.2) and DTS less than 29 days (HR: 2.41; 95% CI: 1.23–4.73) were associated with worse OS. Conclusion Our results likely reflect the aggressive nature of the disease with surgeons taking more invasive disease to the operating room more quickly. Median treatment intervals described may serve as relevant national benchmarks. [ABSTRACT FROM AUTHOR]

Background: The extended endonasal approach has been utilized in the resection of anterior skull base lesions in the pediatric population. There are unique challenges to these patients in the post‐operative setting, including patient compliance with medical therapy and post‐operative debridements, and a smaller nasal airway that may increase propensity toward scarring. Our objective for this study is to evaluate the incidence of post‐operative radiographic inflammation in this patient population using the Lund‐Mackay (LM) score. Methods: A single‐center, retrospective review of pediatric patients undergoing endoscopic approach to the skull base between 2009 and 2021 was performed. Demographic and clinicopathologic data and pre‐ and post‐operative imaging were analyzed. One‐way ANOVA followed by Tukey multiple pairwise comparisons statistical tests were used to compare mean LM scores between groups. Results: Seventy‐two patients (52 males, 20 females) were identified with a median follow‐up of 27 months. All patients underwent an extended endonasal approach for resection of skull base lesions. The mean LM scores were compared between pre‐operative MRI, first post‐operative MRI > 30 days after surgery, and most recent post‐operative MRI. One‐way ANOVA was performed with significant differences noted between the groups (p < 0.001). Tukey multiple pairwise comparisons test was then performed and noted significant differences between the pre‐operative and first post‐operative LM (p < 0.0001) and the first post‐operative and most recent LM (p < 0.0001). There was no significant difference noted between the pre‐operative LM score and most recent LM score (p = 0.14). Conclusion: Despite concerns regarding possible subsequent development of chronic rhinosinusitis following endoscopic skull base surgery in pediatric patients, the current study suggests that transient radiographic evidence of sinus inflammation can be seen up to six months postoperatively, which appears to resolve by approximately two years after surgery. Level of Evidence: 4 Laryngoscope, 133:2014–2017, 2023 [ABSTRACT FROM AUTHOR]

Objectives Although adjuvant radiotherapy may be indicated in patients with sinonasal squamous cell carcinoma (SNSCC) following primary surgery, some patients choose to forgo recommended postoperative radiation therapy (PORT). This study aimed to elucidate factors associated with patient refusal of recommended PORT in SNSCC and examine overall survival. Methods Retrospective analysis of patients with SNSCC treated with primary surgery from the National Cancer Database diagnosed between 2004 and 2016. A multivariable logistic regression model was created to determine the association between clinical or demographic covariates and likelihood of PORT refusal. Unadjusted Kaplan–Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival. Results A total of 2,231 patients were included in the final analysis, of which 1,456 (65.3%) were males and 73 (3.3%) refused recommended PORT. Patients older than 74 years old were more likely to refuse PORT than those younger than 54 (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.84–6.62). Median survival among the entire cohort, those who received recommended PORT, and those who refused PORT was 83.0 months (95% CI: 74.6–97.1), 83.0 months (95% CI: 74.9–98.2), and 63.6 months (95% CI: 37.3–101.4), respectively. Refusal of PORT was not associated with overall survival (hazard ratio: 0.99, 95% CI: 0.69–1.42). Conclusions PORT refusal in patients with SNSCC is rare and was found to be associated with several patient factors. The decision to forgo PORT is not independently associated with overall survival in this cohort. Further study is required to determine the clinical implications of these findings as the treatment decisions are complex. [ABSTRACT FROM AUTHOR]

Objective: Image‐guided surgery (IGS) devices have become widely used for anatomic localization during functional endoscopic sinus surgery (FESS). However, there are no studies that analyze the post‐market complications associated with IGS device use during FESS. The objective of this study was to better characterize post‐market complications associated with the use of IGS devices during sinus surgery. Methods: The US Food and Drug Administration's Manufacturer and User Facility Device Experience database was queried for event reports associated with neurological stereotaxic devices utilized in IGS between the dates of January 1, 2016 and December 31, 2020. Medical device reports that were analyzed for this study pertained strictly to FESS. Results: There were 1873 reports involving IGS devices for FESS included in this study. Fifty‐five reports involved adverse events to patients (2.9%) and 1818 (97.1%) involved device malfunctions. Of the adverse events to patients, the most common included cerebrospinal fluid leakage (45.6%), tissue damage (12.7%), and nervous system injury (3.6%). The most commonly reported device malfunction was imprecision (21.1%). Conclusion: IGS devices are widely utilized in FESS. Of the medical device reports between 2016 and 2020, less than 3% resulted in adverse events. Further studies of the infrequent post‐market complications of IGS devices used in FESS can help guide surgeons on the risks of their clinical use. Level of Evidence: 4—Retrospective database survey without controls Laryngoscope, 133:1310–1314, 2023 [ABSTRACT FROM AUTHOR]

Objective: To determine the in-hospital cost implications of an endoscopic expanded endonasal approach (EEEA) for meningioma resection relative to the open transcranial approach. Methods: All anterior skull base meningioma surgeries performed over a period from January 1st, 2015 to October 31th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using R software. All cost data were converted into August 2021-equivalent dollar amounts using the United States Bureau of Labor Statistics consumer price index. Results: Thirty-five patients met study criteria, including 27 patients undergoing an open transcranial approach and 8 undergoing an EEEA. Average length of stay for patients undergoing an open approach was 9.3 days compared to 5.6 within the EEEA group (P =.126). The average total in-hospital cost of patient undergoing an EEEA was $35417.1 compared to $46406.9 among patients undergoing an open transcranial approach (P =.168). On univariate analysis, the cost of an open transcranial approach relative to the EEEA was $10989.8 (P =.411). Conclusions: The open transcranial approach remained the dominant surgical approach to anterior skull base meningiomas over our study time period. However, despite limited patient numbers the EEEA was associated with decreased total in-hospital costs. [ABSTRACT FROM AUTHOR]