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Bacterial infections result in 7,700,000 deaths per year globally, with intracellular bacteria causing repeated and resistant infection. No drug is currently licenced for the treatment of intracellular bacteria. A new screening platform mimicking the host milieu has been established to explore phytochemical antibiotic adjuvants. Previously neglected isoprenylated flavonoids were found to be effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Specifically, the synergistic effect between glabrol and streptomycin against intracellular bacteria was observed for the first time. The glabrol-streptomycin combination targets bacterial inner membrane phospholipids, disrupts arginine biosynthesis, inhibits cell wall proteins and biofilm formation genes (agrA/B/C/D), and promotes ROS production, causing subsequent membrane and wall damage. To enhance the selective uptake of combination drug into infected cells, hyaluronic acid-streptomycin-lipoic acid-glabrol nanoparticles (HSLGS-S) were designed and synthesized to trigger the intracellular delivery of the glabrol-streptomycin combination. Thus, the treatment can be transported into the infected intracellular region and selectively release the glabrol-streptomycin combination to the bacterial at site. The bioactivity of HSLGS-S in clearing intracellular bacteria was 20-fold higher than that of the glabrol-streptomycin combination alone in vitro and 2- to 10-fold higher in vivo., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Key Points: Asian-American (AA) patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have comparable rates of tissue eosinophilia compared to Caucasians when defined as >10 eosinophils/high-powered field (HPF). AA patients with CRSwNP have significantly higher incidence of mixed inflammation defined as >10 eosinophils/HPF and >10 neutrophils/HPF., (© 2024 ARS‐AAOA, LLC.)

Vancomycin-resistant Enterococcus (VRE) is an important nosocomial opportunistic pathogen that is associated with multidrug resistance. Here, we demonstrate that morellic acid inhibits VRE by restoring its sensitivity to vancomycin and ampicillin with low drug resistance and efficient biofilm clearance effects. Morellic acid binds to inner membrane phospholipids, such as phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) of VRE, such that the fluidity and proton-motive force (PMF) interfere with the damaged inner membrane, causing intracellular reactive oxygen species (ROS) accumulation and bacterial death. Transcriptional analyses supported this effect on inner membrane-related pathways such as fatty acid biosynthesis and glycerophospholipid metabolism. Moreover, morellic acid significantly eliminated residual bacteria in the spleen, liver, kidneys, and abdominal effusion in mice. Our findings indicate the potential applications of morellic acid as an antibacterial agent or adjuvant for treating VRE infections.

Key Points: Nasal valve treatment with TCRF results in NAO symptom improvement in the presence of septal deviation. Severe septal deviation does not impact the beneficial effect of TCRF nasal valve treatment. Symptoms improve with TCRF nasal valve treatment even if septal deviations involve the nasal valve., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Objective: Critical components of the nasal endoscopic examination have not been definitively established for either the normal examination or for clinical disorders. This study aimed to identify concordance among rhinologists regarding the importance of examination findings for various nasal pathologies., Study Design: A consortium of 19 expert rhinologists across the United States was asked to rank the importance of findings on nasal endoscopy for 5 different sinonasal symptom presentations., Setting: An online questionnaire was distributed in July 2023., Methods: The questionnaire utilized JotForm® software and featured 5 cases with a set of 4 identical questions per case, each covering a common indication for nasal endoscopy. Rankings were synthesized into Normalized Attention Scores (NASs) and Weighted Normalized Attention Scores (W-NASs) to represent the perceived importance of each feature, scaled from 0 to 1., Results: General concordance was found for examination findings on nasal endoscopy within each case. The perceived features of importance differed between cases based on clinical presentation. For instance, in evaluating postnasal drip, the middle meatus was selected as the most important structure to examine (NAS, 0.73), with mucus selected as the most important abnormal finding (W-NAS, 0.66). The primary feature of interest for mucus was whether it was purulent or not (W-NAS, 0.67). Similar analyses were performed for features in each case., Conclusion: The implicit framework existing among rhinologists may help standardize examinations and improve diagnostic accuracy, augment the instruction of trainees, and inform the development of artificially intelligent algorithms to enhance clinical decision-making during nasal endoscopy., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Immune checkpoint inhibitors (ICIs) are a rapidly expanding class of oncologic therapies whose mechanism of action can result in unique immune-related adverse events (irAEs) not seen in other cancer therapeutics. The objective of this study was to determine the presence of sinonasal irAEs with these medications., Methods: A case report of chronic rhinosinusitis with nasal polyps (CRSwNP) caused by an ICI is presented and was the impetus for this review. Review of the literature using Pubmed and Cochrane Database of Systematic Reviews was performed. Additionally, we searched the FDA adverse event reporting system (FAERS) database for sinonasal AEs in the 7 FDA-approved ICIs., Results: We demonstrate an emerging scientific literature describing cases of CRS associated with multiple ICIs with a particular predilection toward TH2 driven phenotypes. Review of the FAERS also demonstrates a small percentage of patients who report sinonasal complaints after initiating ICI therapy., Conclusion: Sinonasal symptoms and the development of CRS, in particular, are not currently well recognized as potential irAEs for ICIs. Increased awareness and further study may help to elucidate if these are more common than currently reported and if irAE-related CRS is a unique phenotype., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Elucidating the growth mechanism of carbon nanotubes (CNTs) is critical to obtaining CNTs with desired structures and tailored properties for their practical applications. With atomic resolution imaging, in situ transmission electron microscopy (TEM) has been a key technique to reveal the microstructure and dynamics of CNTs in real time. In this review, recent advances in the development of in situ TEM with different types of environmental reactors will be introduced. The catalytic growth mechanisms of CNTs revealed by in situ TEM under realistic conditions are discussed from fundamental thermodynamics and kinetics to the detailed nucleation, growth, and termination mechanisms, including the state and phase of active catalysts, interfacial connections between catalyst and growing CNTs, and catalyst-related growth kinetics of CNTs. Great progresses have been made on how a CNT nucleates, grows and terminates, focusing on the interface dynamics and kinetic fluctuations. Finally, challenges and future directions for understanding the atomic dynamics under the real growth conditions are proposed. It is expected that breakthroughs in the fundamental growth mechanisms will pave the way to the ultimate goal of designing and controlling the atomic structures of CNTs for their applications in various devices., (© 2024 Wiley‐VCH GmbH.)

Objective: To use an artificial intelligence (AI)-powered large language model (LLM) to improve readability of patient handouts., Study Design: Review of online material modified by AI., Setting: Academic center., Methods: Five handout materials obtained from the American Rhinologic Society (ARS) and the American Academy of Facial Plastic and Reconstructive Surgery websites were assessed using validated readability metrics. The handouts were inputted into OpenAI's ChatGPT-4 after prompting: "Rewrite the following at a 6th-grade reading level." The understandability and actionability of both native and LLM-revised versions were evaluated using the Patient Education Materials Assessment Tool (PEMAT). Results were compared using Wilcoxon rank-sum tests., Results: The mean readability scores of the standard (ARS, American Academy of Facial Plastic and Reconstructive Surgery) materials corresponded to "difficult," with reading categories ranging between high school and university grade levels. Conversely, the LLM-revised handouts had an average seventh-grade reading level. LLM-revised handouts had better readability in nearly all metrics tested: Flesch-Kincaid Reading Ease (70.8 vs 43.9; P < .05), Gunning Fog Score (10.2 vs 14.42; P < .05), Simple Measure of Gobbledygook (9.9 vs 13.1; P < .05), Coleman-Liau (8.8 vs 12.6; P < .05), and Automated Readability Index (8.2 vs 10.7; P = .06). PEMAT scores were significantly higher in the LLM-revised handouts for understandability (91 vs 74%; P < .05) with similar actionability (42 vs 34%; P = .15) when compared to the standard materials., Conclusion: Patient-facing handouts can be augmented by ChatGPT with simple prompting to tailor information with improved readability. This study demonstrates the utility of LLMs to aid in rewriting patient handouts and may serve as a tool to help optimize education materials., Level of Evidence: Level VI., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

A novel bioresorbable agent on the market is PuraGel® (3-D Matrix, Tokyo, Japan), a RADA-16 product that acts as a synthetic hemostatic and space-filling gel that promotes wound healing and prevents adhesion formation. Given the reported benefits of accelerated wound healing and scar tissue prevention, there are multiple otolaryngologic applications where RADA-16 might improve outcomes. Our study highlights current utilization and associated post-operative complications with this product., Competing Interests: We have no conflicts of interest to disclose., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: The goals of this study were to understand the trends in recent and past rhinology fellows concerning their demographics, goals, and experiences., Methods: An anonymous web-based survey was sent to graduates of the 35 rhinology fellowship programs. The survey included questions regarding the scope of practice, research contribution, societal involvement, fellow satisfaction with training, and current practice patterns. Chi-square testing and logistic regression were used to compare variables across cohorts: 0-5 years versus 6+ years from fellowship graduation, gender, and practice settings., Results: Based on 171 respondents, we found no significant differences in 0-5 versus 6+ year graduates in their desire for an academic job post-fellowship. However, those who graduated 6+ years ago had significantly more success securing one (74% vs 96%, P  = 0.004). Between males and females, there were no differences in goal of obtaining an academic job or success in obtaining an academic career. Females were more likely to report they attend academic society meetings regularly. Female rhinologists also reported less satisfaction with overall work-life balance and decreased satisfaction with clinical practice. Physicians in academic settings have poorer work-life balance., Conclusions: Our findings suggest that finding an academic job may be more difficult for recent rhinology fellowship graduates, although still very possible for the majority of graduates. Understanding the reason for these changes may provide insight to current rhinology fellowship directors and trainees interested in pursuing fellowship training., Competing Interests: Declaration of Conflicting InterestsThe authors would like to declare the following conflict of interest with respect to the research, authorship, and/or publication of this article: Dr. Dennis M. Tang is a Consultant for Aerin Medical, Acclarent, and 3D Matrix. Dr. Arthur Wu is a consultant for 3D Matrix, consultant for SoundHealth, speaker for Sanofi-Reneron, and has research grant support from Optinose and Aerin Medical. Dr. Raj Sindwani is a consultant for Styrker, Acclarent, and Optinose, and receives royalties/payment from Elsevier and Sage Publications. These are not relevant to this article.

Background: Obtaining insurance approval is a necessary component of healthcare in the United States and denials of these claims have been estimated to result in a loss of 3% to 5% of revenue., Objective: Examine the trends in insurance denials for rhinological procedures., Methods: A retrospective review of deidentified financial data of patients who were treated by participating physicians across 3 institutions from January 1, 2021, to June 30, 2023. The data was queried for rhinological and non-rhinological procedures via CPT codes. Cumulative insurance denials were calculated and stratified by procedure and insurance type. Write-offs were dollar amounts associated with final denials., Results: A sample of 102,984 procedures and visits revealed a final denial rate between 2.2% and 2.9% across institutions ( p  = .72). The top three rhinological procedures for final write-offs were: nasal endoscopy (16.24%, $111,836.87), nasal debridement or polypectomy (6.48%, $79,457.51), and destruction of intranasal lesion (2.11%, $56,932.20). The write-off percentage for each procedure was highest among commercial insurance payers as opposed to Medicare or Medicaid., Conclusion: Final denial rates of rhinology procedures ranged between 2% and 3%. Common procedures such as nasal endoscopy and nasal debridement are among the highest written-off procedures. Insurance denials can lead to notable revenue loss. Rhinology practices must continue to remain knowledgeable of the changes and effects of insurance reimbursement on their practice., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Omar G. Ahmed is a consultant for Aerin Medical and Medtronic ENT, which are not affiliated with this study. Mas Takashima is a consultant for Neurent Medical and Medtronic ENT, which are not affiliated with this study. Dennis Tang is a consultant for Acclarent, 3-D Matrix, and Aerin Medical, which are not affiliated with this study. Thomas Higgins is a speaker for Regeneron/Sanofi, consultant for Medtronic, Stryker, and Optinose, and investigator for GSK, AstraZeneca, Neurent Medical, Optinose, Biohaven, and Gossamer, which are not affiliated with this study. All other authors declare that there is no conflict of interest.

Objectives: Fungal tissue invasion in the setting of sinonasal malignancy has been rarely described in the literature. Only a handful of studies have discussed cases of suspected chronic and acute IFS (CIFS and AIFS, respectively), having an underlying undifferentiated sinonasal carcinoma, sinonasal teratocarcinosarcoma, and NK/T-cell lymphoma., Methods: Here, we describe 3 cases of carcinoma mimicking IFS from a single institution., Results: Each of our patients presented with sinonasal complaints as an outpatient in the setting of immunosuppression. Intranasal biopsies consistently were predominated by necrotic debris, with and without fungal elements, ultimately leading to a delay of oncologic care. The final pathologies included NK/T-cell lymphoma and SNEC. All patients were followed by radiation and chemotherapy, with 1 case of mortality., Conclusions: We aim to emphasize the importance of obtaining viable tissue as pathology specimens as the presence of necrosis with fungal elements may limit the diagnosis and ultimately delay the care of an underlying sinonasal carcinoma., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality., Methods: We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis., Results: A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017-1.099, p  = 0.005), MI (HR = 1.139, 95%CI: 1.061-1.222, p  < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003-1.105, p  = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results., Conclusion: The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality.

Objectives: Chronic rhinosinusitis and related rhinologic disorders are common in routine otolaryngologic practice. Common presenting symptoms include nasal obstruction, facial pain, facial pressure, headache, and a subjective feeling of the face feeling "swollen," a perceptual distortion. No validated scale exists to assess facial pain in addition to perceptual distortion or headache. The objective was to develop a novel scale for assessment of facial symptoms experienced by patients presenting for rhinologic evaluation., Methods: This was a prospective validation cross-sectional study. A patient questionnaire, the 12-item Facial Complaints Evaluation Scale (FaCES-12), was created to evaluate facial symptoms based on clinical experience and the literature, including severity and timing of facial pain, facial pressure, facial perceptual swelling, and headache. Each item was assessed utilizing an 11-point Likert scale ranging from 0 to 10 in severity. Data was collected prospectively from 210 patients in 1 private and 2 academic otolaryngologic practices from August to December 2019 along with the PROMIS Pain Intensity Scale 3a and 22-Item Sino-nasal Outcome Test. Construct validity was determined using Pearson correlation and exploratory factor analysis. Internal consistency and test-retest reliability were assessed by calculating Cronbach's alpha and assessing test-retest scores., Results: A new 12-item scale named FaCES-12 was developed. FaCES-12 demonstrated high reliability with a Cronbach's alpha of .94 and high test-retest reliability ( r  = .90). The scale revealed very strong correlation with the PROMIS Pain Intensity Scale 3a ( r  = .81) and moderate correlation with the Sino-nasal Outcome Test ( r  = .48). Exploratory factor analysis demonstrated the scale contained interrelated variables that measured unique components of facial sensations., Conclusion: The FaCES-12 is a valid and reliable instrument for use in the evaluation of facial symptoms. Further research into the application of this scale is warranted., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Thomas Higgins is a speaker and advisor for Optinose, Regeneron/Sanofi, and Genentech. Dr. Arthur Wu is a speaker and investigator for Regeneron/Sanofi and an investigator for Optinose. None of the authors have published, presented, or submitted any related papers from the same study or have any conflicts of interest to report.

Background: Commonly used endoscopic nasal polyp grading scales have been shown to correlate poorly with symptom scores and quality of life metrics. The recently described Postoperative Polyp Scale (POPS) is a grading system that more accurately characterizes polyp recurrence in postoperative sinus cavities by describing incremental recurrence in relation to the surgically opened sinus cavities., Objective: The objective of this study was to determine if the POPS correlated with sinonasal symptoms., Methods: CRSwNP patients were prospectively administered SNOT-22 questionnaires and graded according to the POPS starting at their 1-month postoperative appointments. Total POPS scores (sum of each side) and Max POPS score (larger value of left and right) were correlated with SNOT-22 total scores and subdomains using Kendall correlation testing., Results: A total of 127 patients were enrolled in the study. Both Total POPS or Max POPS were significantly correlated to the SNOT-22 total score ( P  < .001, P  < .001), Rhinologic ( P  < .001, P  < .001), Extra-Nasal Rhinologic ( P  < .001, P  < .001), Ear/Facial ( P  < .001, P  < .001), and Psychologic ( P  = .028, P  = .017) subdomains. Kendall's tau indicated strong correlation (≥0.3) with Rhinologic subdomain, moderate correlation (.21-.29) with Extra-Nasal Rhinologic and Ear/Facial subdomains, and weak correlation (.1-.19) with Psychologic subdomain., Conclusion: Previous endoscopic nasal polyp grading scales poorly correlate with symptoms and patient reported outcome measures. The new POPS moderately correlates with the total SNOT-22 score and strongly correlates with the Rhinologic subdomain, indicating that it may have good potential as a tool to evaluate postoperative CRSwNP patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Arthur Wu is a speaker for Sanofi/Regeneron, a consultant for 3D Matrix, a consultant for SoundHealth, and has a research grant with Optinose and Aerin Medical. Dennis Tang is a consultant for 3D Matrix, SoundHealth, and Acclarent. Thomas Higgins is a speaker and consultant for Sanofi/Regeneron, Optinose, Genentech, and GSK; an investigator for Optinose, Lyra, and Biohaven. Philip Chen is a consultant with Medtronic and Integra and a speaker for GlaxoSmithKline and Optinose. Satyan Sreenath is a consultant for 3D Matrix and Acclarent and a speaker for Optinose

Key Points: Hispanic-American patients with chronic rhinosinusitis with nasal polyps have a comparable level of tissue eosinophilia compared to their Caucasian counterparts in the United States. Mixed inflammation involving both neutrophils and eosinophils is more common in this population compared to Caucasians. Findings from this study may indicate that Hispanic-American patients have a unique endotype or endotypes that deserves further investigation., (© 2023 ARS‐AAOA, LLC.)

Objectives: Among patients with chronic rhinosinusitis (CRS), gender differences in epidemiology as well as quality of life have been reported. However, whether gender differences in endoscopic sinus surgery (ESS) preoperative concerns exist is unclear., Methods: CRS patients undergoing ESS at 3 tertiary care centers in Los Angeles completed the validated Western Surgical Concern Inventory - ESS assessing ESS preoperative concerns., Results: Of the 75 patients included, female patients expressed greater concern than male patients in regard to nasal packing, undergoing anesthesia, impact of surgery on daily activities, and pain and discomfort following surgery., Conclusion: This study suggests there are gender differences in ESS preoperative concerns and otolaryngologists should be aware of these possible concerns during preoperative discussions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate the utility of answers generated by ChatGPT, a large language model, to common questions parents have for their children following tonsillectomy., Methods: Twenty Otolaryngology residents anonymously submitted common questions asked by parents of pediatric patients following tonsillectomy. After identifying the 16 most common questions via consensus-based approach, we asked ChatGPT to generate responses to these queries. Satisfaction with the AI-generated answers was rated from 1 (Worst) to 5 (Best) by an expert panel of 3 pediatric Otolaryngologists., Results: The distribution of questions across the five most common domains, their mean satisfaction scores, and their Krippendorf's interrater reliability coefficient were: Pain management [6, (3.67), (0.434)], Complications [4, (3.58), (-0.267)], Diet [3, (4.33), (-0.357)], Physical Activity [2, (4.33), (-0.318)], and Follow-up [1, (2.67), (-0.250)]. The panel noted that answers for diet, bleeding complications, and return to school were thorough. Pain management and follow-up recommendations were inaccurate, including a recommendation to prescribe codeine to children despite a black-box warning, and a suggested post-operative follow-up at 1 week, rather than the customary 2-4 weeks for our panel., Conclusion: Although ChatGPT can provide accurate answers for common patient questions following tonsillectomy, it sometimes provides eloquently written inaccurate information. This may lead to patients using AI-generated medical advice contrary to physician advice. The inaccuracy in pain management answers likely reflects regional practice variability. If trained appropriately, ChatGPT could be an excellent resource for Otolaryngologists and patients to answer questions in the postoperative period. Future research should investigate if Otolaryngologist-trained models can increase the accuracy of responses., Competing Interests: Declaration of competing interest No conflict., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eight undescribed alkaloids named corydalisine D-K (1-7), including one isoquinoline benzopyranone alkaloid (1), one benzocyclopentanone alkaloid (2), four benzofuranone alkaloids (3, 4, and 5a/5b) and two protoberberine alkaloids (6 and 7), along with fourteen known ones, were isolated from the Corydalis saxicola. Their structures, including absolute configurations, were unambiguously identified using spectroscopic techniques, single-crystal X-ray diffraction and electron circular dichroism calculation. Compounds 2, 14 and 21 exhibit antiproliferative activity against five cancer cell lines. The aporphine alkaloid demethylsonodione (compound 14), which exhibited the best activity (IC 50  = 3.68 ± 0.25 μM), was subjected to further investigation to determine its mechanism of action against the T24 cell line. The molecular mechanism was related to the arrest of cell cycle S-phase, inhibition of CDK2 expression, accumulation of reactive oxygen species (ROS), induction of cell apoptosis, inhibition of cell migration, and activation of p38 MAPK signaling pathway. The results indicated that 14 could be used as a potential candidate agent for further development of anti-bladder transitional cell carcinoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Practical techniques to identify heat routes at the nanoscale are required for the thermal control of microelectronic, thermoelectric, and photonic devices. Nanoscale thermometry using various approaches has been extensively investigated, yet a reliable method has not been finalized. We developed an original technique using thermal waves induced by a pulsed convergent electron beam in a scanning transmission electron microscopy (STEM) mode at room temperature. By quantifying the relative phase delay at each irradiated position, we demonstrate the heat transport within various samples with a spatial resolution of ~10 nm and a temperature resolution of 0.01 K. Phonon-surface scatterings were quantitatively confirmed due to the suppression of thermal diffusivity. The phonon-grain boundary scatterings and ballistic phonon transport near the pulsed convergent electron beam were also visualized.

Background: Sphenoid and frontal sinuses have narrow ostia and are prone to stenosis. However, their relative rates of patency are not well established, and descriptive rates of sphenoid stenosis have never been reported. The objective is to measure the patency of the sphenoid and frontal sinus ostia postoperatively., Methods: A prospective multi-institutional cohort study was performed. Ostial patency was measured at surgery and 3 and 6 months postoperatively. Pertinent clinical history such as the presence of nasal polyps and prior history of ESS as well as the use of steroid eluting stents were recorded. Overall stenosis rates were calculated for both the sphenoid and frontal sinuses, and Wilcoxon-Signed Rank Test was used to compare intraoperative and postoperative ostial areas. Factorial Analysis of Variance (ANOVA) was performed to determine effects of 5 clinical factors., Results: Fifty patients were included. The mean sphenoid sinus ostial area decreased 42.2% in size from baseline to 3 months postoperatively (T0 55.2 ± 28.7 mm vs T3 m 31.8 ± 25.5 mm, P  < .001). The mean frontal sinus ostial area decreased 39.8% in size from baseline to 3 months postoperatively (T0 33.7 ± 17.2 mm vs T3 m 19.9 ± 15.1 mm, P  < .001). Neither the sphenoid nor the frontal sinus ostial patency demonstrated statistically significant change from 3 to 6 months postoperatively., Conclusion: Both sphenoid and frontal sinus ostia routinely narrow postoperatively, predominately from baseline to 3 months. These findings can serve as a reference for both clinical outcomes and future studies of these surgeries., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chondrosarcoma is a type of an endochondral bone malignancy that is primarily treated surgically with radiation therapy used in the adjuvant setting or in cases of unresectable disease. Proton therapy has potential advantages compared with traditional photon therapy for the treatment of tumors in close proximity to critical structures due to the theoretic lower exit dose. Studies have shown improved survival in patients with skull base chondrosarcoma who undergo proton therapy. However, there is a lack of randomized data. Further studies are needed to define the role of proton therapy in the treatment of skull base chondrosarcoma., Competing Interests: Conflict of Interest D.M.T. is a consultant for Acclarent, Inc. and 3-D Matrix. A.W.W. is a consultant for 3-D Matrix., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Only a limited number of studies have focused on the results of the Endoscopic Endonasal Approach (EEA) for treatment of prolactinomas. We sought to assess the effectiveness of EEA for prolactinoma surgery, identify factors for disease remission, and present our approach for the management of persistent disease. Forty-seven prolactinomas operated over 10 years, with a mean follow-up of 59.9 months, were included. The primary endpoints were early disease remission and remission at last follow-up. Resistance/intolerance to DA were surgical indications in 76.7%. Disease remission was achieved in 80% of microprolactinomas and 100% of microprolactinomas enclosed by the pituitary. Early disease remission was correlated with female gender (p=0.03), lower preoperative PRL levels (p=0.014), microadenoma (p=0.001), lack of radiological hemorrhage (p=0.001), absence of cavernous sinus (CS) invasion (p<0.001), and extent of resection (EOR) (p<0.001). Persistent disease was reported in 48.9% of patients, with 47% of them achieving remission at last follow-up with DA therapy alone. Repeat EEA and/or radiotherapy were utilized in 6 patients, with 66.7% achieving remission. Last follow-up remission was achieved in 76.6%, with symptomatic improvement in 95.8%. Factors predicting last follow-up remission were no previous operation (p=0.001), absence of CS invasion (p=0.01), and EOR (p<0.001). Surgery is effective for disease control in microprolactinomas. In giant and invasive tumors, it may significantly reduce the tumor volume. A multidisciplinary approach may lead to long-term disease control in three-quarters of patients, with symptomatic improvement in an even greater proportion., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plumula Nelumbinis, the green embryo of a lotus seed, is widely consumed in China as a well-known food with medicinal effects. In this study, 14 alkaloids, including 4 new and 10 known alkaloids, were isolated from it, which were elucidated by comprehensive spectroscopic analysis, and were investigated for their antimelanogenic effects in vitro and in vivo. As a result, melanogenesis in α-MSH-stimulated B16F10 cells was reduced significantly by a new compound 4 and known compound 12 at a concentration of 0.5 μg/mL, and the tyrosinase (TYR) activities were inhibited by 78.7 and 82.0% at 4 μg/mL, prior to α-arbutin (41.3%). Additionally, compounds 4 and 12 also exhibited superior antimelanogenic effects compared to α-arbutin on a zebrafish assay model at equivalent concentrations. Mechanistically, our preliminary findings suggested that compounds 4 and 12 exerted antimelanogenesis effect probably by inhibiting key proteins involved in melanin production such as microphthalmia-associated transcription factor, TYR, TRP-1, and TRP-2. The findings highlight the potential use of Plumula Nelumbinis containing compounds 4 and 12 as functional foods for treating hyperpigmentation.

Objective: Commonly used endoscopic grading scales, such as the nasal polyp scale, inadequately describe the degree of polyposis found postoperatively in the paranasal sinus cavities. The purpose of this study was to create a novel grading system that more accurately characterizes polyp recurrence in postoperative sinus cavities, the Postoperative Polyp Scale (POPS)., Methods: A modified Delphi method was utilized to establish the POPS using consensus opinion among 13 general otolaryngologists, rhinologists, and allergists. Postoperative endoscopy videos from 50 patients with chronic rhinosinusitis with nasal polyps were reviewed by 7 fellowship-trained rhinologists and scored according to the POPS. Videos were rated again 1 month later by the same reviewers, and scores were assessed for test-retest and inter-rater reliability., Results: Overall inter-rater reliability for the first and second reviews of the 52 videos was Kf = 0.49 (95% CI 0.42-0.57) and Kf = 0.50 (95% CI 0.42-0.57) for the POPS. Intra-rater reliability showed near-perfect test-retest reliability for the POPS with Kf = 0.80 (95% CI 0.76-0.84)., Conclusion: The POPS is an easy-to-use, reliable, and novel objective endoscopic grading scale that more accurately describes polyp recurrence in the postoperative state which will be useful in the future for measuring the efficacy of various medical and surgical interventions., Level of Evidence: 5 Laryngoscope, 133:2885-2890, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

The structure and configuration of reaction centers, which dominantly govern the catalytic behaviors, often undergo dynamic transformations under reaction conditions, yet little is known about how to exploit these features to favor the catalytic functions. Here, we demonstrate a facile light activation strategy over a TiO 2 -supported Cu catalyst to regulate the dynamic restructuring of Cu active sites during low-temperature methanol steam reforming. Under illumination, the thermally deactivated Cu/TiO 2 undergoes structural restoration from inoperative Cu 2 O to the originally active metallic Cu caused by photoexcited charge carriers from TiO 2 , thereby leading to substantially enhanced activity and stability. Given the low-intensity solar irradiation, the optimized Cu/TiO 2 displays a H 2 production rate of 1724.1 μmol g -1 min -1 , outperforming most of the conventional photocatalytic and thermocatalytic processes. Taking advantages of the strong light-matter-reactant interaction, we achieve in situ manipulation of the Cu active sites, suggesting the feasibility for real-time functionalization of catalysts.

Invasive pituitary adenomas can infiltrate the dura mater, sphenoid sinus, or cranial bone. Endoscopic transsphenoidal sinus surgery is considered the standard of care; however, several potential complications must be noted. These complications can include cerebrospinal fluid leaks, infection, bleeding, optic nerve damage, and endocrinological complications such as diabetes insipidus. We present a case of a 69-year-old female with multiple recurrent invasive pituitary adenomas who has previously undergone 5 transsphenoidal procedures. Intraoperatively, the patient suffered from a left-sided carotid artery injury that was repaired with a muscle graft. Management of carotid artery injury during transsphenoidal surgery is optimized in a step-by-step approach which includes early recognition of the injury, briefing the surgical team, immediate control using compression, use of additional tissue graft for wound repair, and postoperative care. Through the use of the approach mentioned above, we were able to control the complication successfully.

Acoustic neuromas are the most common tumor of the cerebellopontine angle that are associated with a number of symptoms that negatively impact a patient's quality of life. While the mainstay of treatment for these benign tumors remains microsurgical resection, there is limited research exploring how certain modifiable risk factors (MRFs) may affect the perioperative course. The purpose of this study was to investigate how MRFs including malnutrition, obesity, dyslipidemia, uncontrolled hypertension, and smoking may affect postoperative rates of readmission and nonroutine discharges. We utilized the 2016 and 2017 Healthcare Cost and Utilization Project Nationwide Readmissions Database. MRFs were queried using appropriate International Classification of Diseases, Tenth Revision (ICD-10) coding for categories including malnutrition, obesity, dyslipidemia, smoking, alcohol, and hypertension. The statistical analysis was done using RStudio (Version 1.3.959). Chi-squared tests were done to evaluate differences between categorical variables. The Mann-Whitney U- testing was utilized to evaluate for statistically significant differences in continuous data. The "Epitools" package was used to develop logistic regression models for postoperative complications and post hoc receiver operating characteristic curves were developed. Pertaining to nonroutine discharge, predictive models using malnutrition outperformed all other MRFs as well as those with no MRFs ( P < .05). In the case of readmission, models using malnutrition outperformed those of obesity and smoking ( P < .05). Again, an increase in predictive power is seen in models using dyslipidemia when compared to obesity, smoking, or uncontrolled hypertension. Lastly, models using no MRFs outperformed those of obesity, smoking, and uncontrolled hypertension ( P < .05). This is the first study of its kind to evaluate the role of MRFs in those undergoing surgical resection of their acoustic neuroma. We concluded that certain MRFs may play a role in complicating a patient's perioperative surgical course., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SS has conflicts of interest, including being: Consultant for the Mac Parkman Foundation for Adolescent Concussive Trauma. Stock/Equity holder in StrokeDx.

Objective: There is currently no consensus on the appropriate timing of noninvasive positive pressure ventilation (PPV) resumption in patients with obstructive sleep apnea (OSA) after endoscopic pituitary surgery. We performed a systematic review of the literature to better assess the safety of early PPV use in OSA patients following surgery., Methods: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases in English were searched using the keywords: "sleep apnea," "CPAP," "endoscopic," "skull base," "transsphenoidal" and "pituitary surgery." Case reports, editorials, reviews, meta-analyses, unpublished and abstract-only articles were all excluded., Results: Five retrospective studies were identified, comprising 267 patients with OSA who underwent endoscopic endonasal pituitary surgery. The mean age of patients in four studies (n = 198) was 56.3 years (SD = 8.6) and the most common indication for surgery was pituitary adenoma resection. The timing of PPV resumption following surgery was reported in four studies (n = 130), with 29 patients receiving PPV therapy within two weeks. The pooled rate of postoperative cerebrospinal fluid leak associated with PPV resumption was 4.0% (95% CI: 1.3-6.7%) in three studies (n = 27) and there were no reports of pneumocephalus associated with PPV use in the early postoperative period (<2 weeks)., Conclusions: Early resumption of PPV in OSA patients after endoscopic endonasal pituitary surgery appears relatively safe. However, the current literature is limited. Additional studies with more rigorous outcome reporting are warranted to assess the true safety of re-initiating PPV postoperatively in this population., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Monolayer ruthenate nanosheets obtained by exfoliating layered ruthenium oxide exhibit excellent electrical conductivity, redox activity, and catalytic activity, which render them suitable for advanced electronic and energy devices. However, to fully exploit the benefits, we require further structural insights into a complex polymorphic nature and diversity in relevant electronic states of two-dimensional (2D) ruthenate systems. In this study, the 2D structures, stability, and electronic states of 2D ruthenate are investigated on the basis of thermal and chemical phase engineering approaches. We reveal that contrary to a previous report, exfoliation of an oblique 1T phase precursor leads to nanosheets having an identical phase without exfoliation-induced phase transition to a 1H phase. The oblique 1T phase in the nanosheets is found to be metastable and, thus, transforms successively to a rectangular 1T phase upon heating. A phase-controllable synthesis via Co doping affords nanosheets with metastable rectangular and thermally stable hexagonal 1T phases at a Co content of 5-10 and 20 at%, respectively. The 1T phases show metallic electronic states, where the d-d optical transitions between the Ru 4d (t 2g ) orbital depend on the symmetry of the Ru framework. The Co doping in ruthenate nanosheets unexpectedly suppresses the redox and catalytic activities under acidic conditions. In contrast, the Co 2+/3+ redox pair is activated and produces conductive nanosheets with high electrochemical capacitance in an alkaline condition.

Background: ClariFix for posterior nasal nerve ablation has been approved for use since 2017, and this is the first study attempting to synthesize and assess the efficacy of this new device on the management of chronic rhinitis., Objective: The primary objective of this meta-analysis is to assess the efficacy of ClariFix in the symptomatic management of patients with chronic rhinitis. The main outcome measure is the mean difference in the reflective total nasal symptom score (rTNSS)., Methods: A systematic search of Pubmed/Medline, Web of Science, and EBSCOhost was conducted from inception to May 2022. Peer-reviewed clinical trials reporting postcryotherapy rTNSS at both 1- and 3-month intervals for patients with chronic rhinitis were included. A random-effects model was utilized for meta-analysis. Study heterogeneity, bias, and overall quality were all assessed. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The primary outcome measures included mean differences in rTNSS from baseline to both 1- and 3-month postoperative time points. Secondary measures included other questionnaires including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)., Results: There were 5 studies that met the criteria (247 individuals). The pooled rTNSS mean difference from baseline to 1 and 3 months postoperatively was found to be -3.48 points (95% CI: -3.73 to -3.23, I 2  = 0.13). and -3.50 (95% CI: -3.71 to -3.29, I 2  = 0.00), respectively. The mean difference from baseline to 3 months postoperatively regarding the RQLQ was found to be -1.53 (95% CI: -1.74 to -1.31, I 2  = 0.00). The most common adverse effects included facial or surgical site pain (40.4%), followed by headache (18.2%), oral numbness (11.1%), and sinusitis (4.0%)., Conclusions: The findings of this systematic review suggest that cryoablation with Clarifix is an effective treatment modality for chronic rhinitis. However, higher-quality randomized controlled trials will need to be performed to affirm the findings of this study.

Background: The ability to reliably and accurately cannulate the natural ostium of the maxillary sinus during balloon sinus dilation (BSD) has been criticized. Conventional computed tomography (CT)-guided navigation systems are helpful when dilating other sinuses, but they fail to provide meaningful feedback to guide accurate dilation of the maxillary sinus., Objective: This study explores the potential impact of a new navigation system with virtual reality (VR) functionality on successful BSD of the maxillary sinus., Methods: Using the established methodology, a cadaveric evaluation of the accuracy of maxillary BSD with a VR-equipped navigation system and balloon was undertaken. The natural ostium was landmarked on CT images with a beacon, and a VR intrasinus camera view was used to guide balloon dilation by a team of 2 rhinologists. Following the procedure, uncinectomies were performed to directly assess the accuracy of dilation. Standardized video clips with a 30° endoscopic view of the area were reviewed by 3 blinded rhinologists from different institutions who were not part of the procedures. Dilation of the natural ostium was scored as "successful," "unsuccessful," or "unsure.", Results: Sixteen maxillary BSDs were completed in 8 cadavers using VR navigation. The medial wall of the maxillary sinus showing the natural ostium as well as any accessory ostia were readily visualized and labeled with a beacon in all cases using the 3D virtual rendering feature. Dilations were scored using a standardized rubric. Any "unsure" responses from the reviewers were categorized as "unsuccessful" for analysis purposes. The accuracy rate for dilation of the maxillary sinus natural ostium was 77%. Despite the use of cadaveric tissues, a fair interrater agreement (kappa 0.21) was achieved., Conclusion: Using VR navigation appears to improve the accuracy of cannulating the natural ostium during maxillary BSD, which could lead to better outcomes. Further study in live subjects is warranted.

Objectives: Osteoradionecrosis (ORN) of the skull base and craniovertebral junction is a challenging complication of radiation therapy (RT). Severe cases often require surgical intervention through a multi-modal approach. With the evolution in endoscopic surgery and advances in skull base reconstruction, there is an increasing role for microvascular free tissue transfer (MFTT). We describe an endoscopic-assisted approach for the management of ORN of the skull base using fascia lata for MFTT., Study Design: Retrospective case series., Methods: Between 2017 and 2021, a review of all cases in which fascia lata MFTT was utilized for skull base ORN was performed. Patient demographics, preoperative characteristics, and postoperative outcomes with long-term follow-up were reviewed., Results: Five patients were identified. Mean duration to onset of ORN was 17 months following RT. A trial of antibiotics, hyperbaric oxygen (HBO), and/or limited debridement was attempted without success. Refractory pain and progressive osteomyelitis were unifying symptoms. All patients underwent endoscopic debridement of the affected region of ORN prior to MFTT. Vascularized fascia lata was inset through a combined endonasal and transoral corridor. There was improvement in chronic pain in the postop setting with no patients requiring continued antibiotics or HBO therapy. Mean post-op follow-up was 23 months., Conclusions: With continued evolution in endoscopic, minimally invasive approaches, there is an expanding indication for early surgical management in refractory ORN. Fascia lata MFTT is a novel and effective strategy for the management of ORN of the skull base and upper cervical spine with excellent postoperative outcomes and limited patient morbidity., Level of Evidence: 4 Laryngoscope, 133:562-568, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

High-melting point alloy catalysts have been reported to be effective for the structure-controlled growth of single-wall carbon nanotubes (SWCNTs). However, some fundamental issues remain unclear because of the complex catalytic growth environment. Here, we directly investigated the active catalytic phase of Co-W-C alloy catalyst, the growth kinetics of CNTs, and their interfacial dynamics using closed-cell environmental transmission electron microscopy at atmospheric pressure. The alloy catalyst was precisely identified as a cubic η-carbide phase that remained unchanged during the whole CNT growth process. Rotations of the catalyst nanoparticles during CNT growth were observed, implying a weak interfacial interaction and undefined orientation dependence for the solid catalyst. Theoretical calculations suggested that the growth kinetics are determined by the diffusion of carbon atoms on the surface of the η-carbide catalyst and through the interface of the catalyst-CNT wall.

This case study demonstrates a 58-year-old female who contracted COVID-19 post-vaccination presenting with severe left-sided facial pain, headaches, and dyspnea. A computed tomography was ordered and showed acute sinusitis, and upon bedside endoscopy, the patient was shown to have necrosis of the left-sided middle turbinate with no discoloration, palate necrosis, or facial changes. All samples of the necrotic tissue were reported to be invasive fungal sinusitis. The entire turbinate was resected in the operating room and ethmoid, frontal, and maxillary sinuses were healthy. Chest x-rays post-operatively showed pulmonary effusions and edema although the patient was not stable enough for a lung examination to rule out a pulmonary fungal infection. A bedside endoscopy showed no further necrosis post-operatively although a repeat endoscopy showed duskiness at the lateral attachment of the basal lamella right at the most posterior resection of the middle turbinate. The patient was placed on multiple antifungal agents. The patient remained in hypoxemic respiratory failure and septic shock while on pressors and 2 weeks following this, expired. Post-COVID-19 patients have been shown in the literature to have an increased risk of developing invasive fungal sinusitis (IFS) and all IFS cases during active COVID-19 infection have had a 100% mortality rate.

Background: Chronic rhinosinusitis (CRS) and eosinophilic esophagitis (EoE) are immune-mediated inflammatory conditions that share common histopathologic features. Once considered two separate pathologies, preliminary data has suggested that a higher prevalence of EoE may exist in patients with CRS., Objectives: We aimed to expand the base of evidence across geographic regions and investigate the association between EoE and CRS, including CRS with nasal polyposis (CRSwNP)., Methods: Quantitative data detailing the prevalence of CRS, CRSwNP, and EoE were pooled from 6 large academic institutions spread across the United States using Epic electronic medical record system. One-way analysis of variance was then used to analyze the data., Results: The mean prevalence of EoE in our general population sample of over 26 million individual records was 0.058% (range, 0.013%-0.103%). The mean prevalence of EoE in our sub-populations of individual with diagnoses of CRS and CRSwNP was 0.43% (F(1,12)  =  [8.194], P   =  .01) and 0.84% (F(1,12)  =  [23.61], P  < .01) respectively., Conclusion: This study reveals an 8-fold greater prevalence of concurrent EoE in patients with CRS. Importantly, this is the first study to describe the association of EoE and the CRSwNP subtype, and we demonstrate a 14-fold greater prevalence of EoE in patients with CRSwNP.

Background and Objective: This study aims to evaluate the medicolegal trends related to 2 common orbital surgeries: orbital decompression and dacryocystorhinostomy (DCR). These procedures are performed by ophthalmologists, otolaryngologists, and multidisciplinary teams of both specialists., Methods: The Westlaw database was reviewed from 1980 to 2020 for medical malpractice cases involving orbital decompression and DCR surgeries. Data were compiled on plaintiff and defendant demographics, procedure performed, legal allegation, nature of injury, and verdict or settlement awards. The Ophthalmic Mutual Insurance Company was also queried for all malpractice cases pertaining to orbital decompression and DCR from 1995 to 2021., Results: The Westlaw database included 60 cases (34 orbital decompression, 26 DCR); of these, 8 orbital decompression and 6 DCR cases met inclusion criteria. Of the 7 orbital decompression cases that were tried, a verdict in favor of the plaintiff occurred in 4 cases (57%). Of the 5 DCR cases that were tried, a verdict in favor of the plaintiff occurred in 2 cases (40%). A search of all claims at OMIC yielded 31 cases (15 orbital decompression, 16 DCR). 22 of 31 cases were either dismissed or resulted in no payment. The remainder was settled out of court, with only one case being tried and the verdict supporting the defendant., Conclusion: Despite several thousand orbital decompressions and DCR surgeries being performed annually in the US, very few lawsuits involving these complex surgeries have gone to trial. However, of the cases that did go to trial, a relatively high proportion of verdicts for plaintiffs was observed.