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Background: Despite the significant morbidity associated with chronic rhinosinusitis (CRS) in individuals with asthma (CRSwA), there is a paucity of codified, evidence‐based management strategies for CRS in this population. Methods: Using PubMed, Embase, and Cochrane Review Databases, a systematic review was performed covering management strategies for CRSwA. A total of 5903 articles were screened, and 70 were included for full‐text analysis. After application of exclusion criteria, 53 articles comprised the qualitative synthesis. The level of evidence was graded and benefit‐harm assessments, as well as value judgment and recommendations, were provided Results: Strong evidence confirms the benefit of oral and topical medications on sinonasal‐specific outcomes in individuals with CRSwA; there is low‐grade evidence demonstrating that these agents improve lung function and/or asthma control. Moderate to strong evidence suggests that endoscopic sinus surgery (ESS) improves both sinonasal‐ and asthma‐specific quality of life. Although there is insufficient to low evidence to indicate that ESS improves pulmonary function in this population, data indicate a positive impact of this intervention on asthma control. Biologic medications strongly improve both subjective and objective sinonasal‐ and asthma‐specific outcomes. Conclusion: Evidence supports managing CRS in individuals with CRSwA in a stepwise fashion, starting with traditional nonbiologic oral and topical medication, and escalating to second‐line treatments, such as ESS and biologics. Optimal treatment of individuals who have CRSwA often requires concurrent, directed management of asthma, as not all CRS interventions impact asthma status. [ABSTRACT FROM AUTHOR]

Keywords: chromosome; cytokines; gene expression; inflammation; microarray; Rhinosinusitis; signalling pathways EN chromosome cytokines gene expression inflammation microarray Rhinosinusitis signalling pathways 719 722 4 04/29/22 20220501 NES 220501 Key Messages Extra-sinus nasal tissue has been used to support mechanistic statements for pathogenesis of CRSsNP. .001 ht In the present investigation, although inflammation is present within both the nasal floor and ethmoid sinus of patients with CRSsNP, the inflammatory gene and pathway expression profiles manifest differently across the two subsites. There were 46 transcripts that were significantly different between the anterior ethmoid sinus mucosa and the floor of the nose using a cut-off of a >=4-fold change was implemented and presented (Gene Expression Omnibus contains the full dataset). These findings may provide useful insight into how sinus mucosa differs in its inflammatory response from nasal floor mucosa, while accounting for site-dependent differences in the inflammatory profile of patients with CRS. [Extracted from the article]

Introduction: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS. Methods and analysis: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines. Ethics and dissemination: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals. Trial registration: This study was registered on ClinicalTrials.gov (NCT04469439). [ABSTRACT FROM AUTHOR]

Background: Poor sleep quality is common in chronic rhinosinusitis (CRS). Prior studies have demonstrated improvements in patient‐reported measures of sleep quality following endoscopic sinus surgery (ESS). The purpose of this study was to evaluate the effect of ESS on objective sleep parameters and identify any associations between specific objective measures and patient characteristics, comorbidities, and patient‐reported outcome measures (PROMs). Methods: Adults with CRS undergoing ESS were prospectively enrolled from 4 centers across North America. Any subject previously diagnosed with a known primary sleep disorder was excluded. Objective sleep indices were recorded using a portable sleep diagnostic device preoperatively and postoperatively. Patient‐reported outcome instruments were completed including the Pittsburgh Sleep Quality Index (PSQI) and the 22‐item Sino‐Nasal Outcome Test (SNOT‐22). Results: Thirty‐six patients (mean age 47 years, 56% male) completed baseline and postoperative sleep studies with mean ± standard deviation (SD) follow‐up 9.6 ± 7.7 months. Mean PSQI and SNOT‐22 before and after ESS was 10.2 ± 3.9 vs 7.8 ± 4.4 (p = 0.001); and 54.6 ± 14.6 vs 28.5 ± 15.3 (p < 0.001), respectively. Total sleep time, sleep latency, and awakenings after sleep onset did not change following ESS (all p > 0.5) despite improvements in PSQI and SNOT‐22. Changes in PSQI did not correlate with comorbidities or objective sleep indices (all p > 0.1). Conclusion: In this multicenter prospective cohort, objective sleep indices were not improved following ESS for CRS despite significant improvements in patient‐reported sleep quality and CRS‐specific QOL. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have suggested that patients with chronic rhinosinusitis (CRS) report worse sleep quality than population norms. What remains unknown is whether these patients are actually experiencing measurable changes in objective sleep parameters. The goal of this study was to prospectively evaluate objective sleep measures in a cohort of patients with CRS. Methods: A prospective, multi‐institutional, case‐control study was designed to compare patients with CRS to nondiseased controls. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (EpSS). Home sleep studies were administered across all subjects and a battery of objective sleep measurements were recorded using a portable sleep diagnostic device. Regression models were used to control for any factors that differed across groups. Results: A total of 108 subjects were enrolled across 4 institutions, including 52 patients with CRS and 56 controls. Total PSQI scores were worse in patients with CRS when compared with controls (10.1 ± 4.3 vs 4.7 ± 2.5; p < 0.001). Similarly, daytime somnolence, as measured by the EpSS, was greater in patients with CRS (9.1 ± 5.3 vs 6.5 ± 3.7; p = 0.006). On home sleep studies, patients with CRS were found to have an increased number of awakenings during a night's sleep (8.6 ± 4.8 vs 6.3 ± 3.0; p = 0.004), lower average overnight oxygen saturation (93.2 ± 2.6% vs 94.3 ± 2.1%; p = 0.042), increased rapid eye movement sleep (REMS) latency (93.0 ± 67.1 vs 66.7 ± 35.3; p = 0.016), and spent a greater portion of the night snoring at >40 dB (24.7 ± 27.4% vs 14.6 ± 19.7%; p = 0.034). All differences except mean oxygen saturation remained significant after controlling for baseline differences. Conclusion: Differences in both patient‐reported and objective sleep measures exist between patients with CRS and controls. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is characterized by sustained mucosal inflammation, impaired mucociliary clearance, loss of cilia and epithelial barrier breakdown, and tissue remodeling. Certain glycosaminoglycans inhibit various inflammatory mediators, suppress bacterial growth, and provide important functions in mucosal tissue repair and mucociliary clearance. Herein, we evaluated the effects of a synthetic glycosaminoglycan, GM-1111, on the clinical signs and inflammatory tissue changes associated with CRS in mice. CRS was generated by repeated intranasal applications of Aspergillus fumigatus (A. fumigatus) extracts over 4 weeks. Mice were then intranasally administered GM-1111 (600 μg per dose, 5 times a week) or vehicle (phosphate buffered saline, PBS) for an additional 4 weeks while still being given A. fumigatus extracts to maintain a chronic inflammatory environment with acute exacerbations. Clinical signs indicative of sinonasal inflammation were recorded throughout the study. After 9 weeks, whole blood and sinonasal tissues were harvested for hematological, histological, and biochemical examination. The clinical signs, white blood cell counts, tissue markers of sinonasal inflammation, and histological changes caused by A. fumigatus extract administration were compared to the healthy (PBS vehicle) and GM-1111-treated groups (n = 12 per treatment group). Compared to vehicle-treated animals, animals treated with GM-1111 demonstrated significant reductions in clinical signs (p<0.05), degenerative tissue changes, goblet cell hyperplasia, inflammatory cell infiltration (p<0.01), innate immunity- (tlr2, tlr4, myd88, il1b, tnfa, il6, and il12) and adaptive immunity-associated (ccl11, ccl24, ccl5, il4, il5, and il13) cytokine gene expression (p<0.05 to p<0.0001) in sinonasal tissues, and serum IgE levels (p<0.01). Our data suggest that GM-1111 significantly reduces local and systemic effects of CRS-associated sinonasal inflammation. [ABSTRACT FROM AUTHOR]

Silver nanomaterials are widely used in clinically approved devices, consumer goods, and over-the-counter nutraceutical products. Despite the increase in silver nanomaterial research, few investigations have specifically distinguished the biological effects resulting from silver nanoparticles (AgNPs) versus silver ions released from AgNPs. This is in part, due to the complex analytical methods required to characterize silver ion release from AgNPs in biological media. This study sought to analyze silver ion release from AgNPs in biological media, compare silver transport from soluble AgNO 3 and AgNPs through ex vivo full thickness sinus human tissue explants and human nasal epithelium and determine fractional AgNP internalization by human nasal epithelial cells. Rapid silver ion release is observed from AgNPs in human nasal epithelial cell medium over 3 h (9.6% of total silver mass). Significantly lower translocation of AgNPs is observed through human nasal epithelial cell monolayers and ex vivo human sinus tissue explants compared to silver ion (AgNO 3 ). AgNP internalization is directly observed in AgNP-exposed human nasal epithelial cell monolayers by live cell scanning transmission electron microscopy (STEM), providing one potential mechanism for AgNP transcytosis. However, in vitro AgNP dissolution experiments suggest that silver in human nasal epithelium is primarily silver ion. Ionic AgNO 3 produces significantly higher silver translocation, supporting previous results claiming silver ion as primarily responsible for biological effects of AgNPs. [ABSTRACT FROM AUTHOR]

This article, published in the Journal of Neurological Surgery, explores the factors that contribute to the recurrence of Cushing's disease (CD) after transsphenoidal surgery. The study analyzed data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database, which included 383 CD patients. The results showed that patients who experienced recurrence had a longer postoperative hospital stay, larger tumor volumes, and a higher rate of failed prior treatment. Younger age and the absence of cavernous sinus invasion were identified as potential protective factors against recurrence. The findings suggest that early detection and treatment of tumors may improve outcomes for CD patients. [Extracted from the article]

Objective Otitis media requiring tympanostomy tubes (OMwTT) is a prevalent disease process that has been previously shown to have a strong familial link. The impact from the environmental versus genetic contributions to this link is unknown. The objective was to determine the environmental involvement in the development of OMwTT. Methods Using an extensive genealogical database linked to medical records, we evaluated the risk of OMwTT in children of probands as compared to children of controls, individually matched 5:1 on sex and birth year, from a conditional logistic regression model. The model included adjustments for geographic and socioeconomic environmental risk factors mapped to residence location of study subjects within 63 small health statistical areas of ∼33,500 persons each. Results 37,814 case probands diagnosed with OMwTT and 181,339 controls were included in our analysis. Children of probands with OMwTT had an overall 2.5× higher risk of also having OMwTT as compared to the children of controls ( p < 10 −9 ), independent of environmental factors (PM 2.5 [particulate matter] air pollution, education level of parents, and density of primary care providers). Conclusion After accounting for geographic and socioeconomic differences that may influence risk between cases and controls, our findings suggest evidence of a genetic predisposition in families of OMwTT patients. Further characterization of high-risk pedigrees is needed for future genomic studies. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is a highly prevalent inflammatory condition, with significant effects on morbidity and quality of life. Given that other chronic inflammatory conditions have been associated with increased mortality risk, we sought to evaluate the relationship between mortality and CRS including the influence of asthma. Our objective was to determine if CRS, with or without asthma, is associated with altered risk of mortality. Methods Using a statewide population database, we retrospectively identified 27,005 patients diagnosed with CRS between 1996 and 2012, and 134,440 unaffected controls matched 5:1 on birth year and sex. Risk of mortality was determined from Cox models and Kaplan-Meier curves were used to compare survival. Results A significant interaction between CRS and asthma status was observed in which CRS appeared to confer a protective effect in asthma patients. Asthma, when present, increased mortality in CRS-negative controls ( p-interaction < 0.0001). Independent of asthma status, CRS patients exhibited a decreased mortality risk (hazard ratio [HR] = 0.80; 95% confidence interval [CI], 0.74 to 0.85) compared to controls. However, in patients diagnosed at or before the median age of CRS onset (42 years) independent of asthma status, survival was not improved (HR = 0.98; 95% CI, 0.81 to 1.18). Risk of mortality was greater in CRS with nasal polyps (n = 1643) compared to 25,362 polyp-negative CRS patients (HR = 1.38; 95% CI, 1.09 to 1.77). Conclusion CRS was associated with lower risk of mortality compared to controls, and appeared to mitigate increased mortality from asthma. We posit that better survival conferred by CRS may be secondary to treatment. However, the etiology of this relationship and the effect of CRS treatment on mortality are unknown. [ABSTRACT FROM AUTHOR]

Background Endoscopic sinus surgery (ESS) has been shown to improve sleep in patients with chronic rhinosinusitis (CRS). However, it is unknown how this improvement compares with non-CRS control subjects' sleep, and medically treated CRS patients. Methods Patients meeting diagnostic criteria for CRS and controls from the same reference population were recruited from 4 academic centers. Patients chose either medical or surgical treatment. The Pittsburgh Sleep Quality Index (PSQI) was administered to patients before treatment and after 6 months, whereas controls received the PSQI at enrollment. Results The study population consisted of 187 cases (64 medical and 123 surgical) and 101 controls. Baseline PSQI scores for CRS patients (9.27 ± 4.76) were worse than for controls (5.78 ± 3.25), even after controlling for potential confounding factors such as asthma and allergy ( p < 0.001). There was no significant difference in baseline PSQI between patients choosing medical vs surgical treatment. The PSQI score in surgical patients improved from 8.36 ± 5.05 to 7.44 ± 5.09 ( p = 0.020). The PSQI score in medical patients demonstrated a nonsignificant increase with treatment from 8.71 ± 4.48 to 9.06 ± 4.80 ( p = 0.640). After controlling for allergy and asthma, 6-month PSQI scores in medical patients remained significantly higher than in controls ( p = 0.001), whereas a significant difference could not be demonstrated between surgical patients and controls ( p > 0.05). PSQI subdomain analysis mirrored the overall findings. Conclusion Patients with CRS report worse sleep compared with controls. Surgically treated CRS patients show significant improvement in PSQI scores, whereas those continuing with medical management fail to improve and remain worse than controls. [ABSTRACT FROM AUTHOR]

Background Patients with chronic rhinosinusitis (CRS) have been found to have cognitive deficit, as identified using the Cognitive Failures Questionnaire (CFQ), but the exact etiology of cognitive decline is unknown. In this study we aimed to determine whether improvement in concomitant inflammation and disease burden in CRS, using endoscopic sinus surgery (ESS), improves cognitive deficit. We also sought to identify comorbid conditions that effect improvement likelihood. Methods Study participants (n = 247) with and without nasal polyposis (CRSwNP, CRSsNP) were prospectively enrolled in this multi-institutional, observational outcomes study. Pre- and postoperative cognitive dysfunction was evaluated using the CFQ instrument. Quality of life (QOL) and disease burden was also evaluated using the Rhinosinusitis Disability Index (RSDI), the 22-item SinoNasal Outcome Test (SNOT-22), nasal endoscopy, computed tomography, and the 2-item Patient Health Questionnaire (PHQ-2). Results Average CFQ total scores improved significantly ( p = 0.012) after ESS for patients with follow-up (n = 141). Participants with CRSwNP (n = 51) reported significant postoperative improvements in mean CFQ total scores ( p = 0.002) and CFQ distractibility and blunders domain scores ( p ≤ 0.006). No significant postoperative improvement for any average CFQ score was found in CRSsNP ( p > 0.086). The magnitude of postoperative improvement in CFQ total and domain mean scores was statistically similar between CRSsNP and CRSwNP ( p > 0.115). Depressive disorder, identified using PHQ-2 screening, was the only comorbid condition significantly associated with measurable cognitive deficit ( p < 0.001). Conclusions Patients with CRS have measurable cognitive decline, and ESS may modestly improve cognitive deficit/CFQ scores. Future investigations are needed to further elucidate the underlying mechanisms responsible for cognitive deficit in patients with CRS and significant associations with depression. [ABSTRACT FROM AUTHOR]

Background Septoplasty and turbinate reduction (STR) is a common procedure for which cost reduction efforts may improve value. The purpose of this study was to identify sources of variation in medical facility and surgeon costs associated with STR, and whether these costs correlated with short-term complications. Methods An observational cohort study was performed in a multifacility network using a standardized cost-accounting system to determine costs associated with adult STR from January 1, 2008 to July 31, 2015. A total of 4007 cases, performed at 21 facilities, by 72 different surgeons were included in the study. Total costs, variable costs, operating room (OR) time, and 30-day complications (eg, epistaxis) were compared among surgeons, facilities, and specialties. Results Total procedure cost: (mean ± standard deviation [SD]) $2503 ± $790 (range, $852 to $10,559). Mean total variable cost: $1147 ± $423 (range, $400 to $5,081). Intersurgeon and interfacility variability was significant for total cost ( p < 0.0001) and OR time ( p < 0.0001). Intersurgeon OR supply cost variability was also significant ( p < 0.0001). Otolaryngologists had less total cost ( p < 0.0001), OR time/cost ( p < 0.0001), and complications ( p = 0.0164), but greater supply cost ( p < 0.0001), than other specialties. Conclusion There is wide variation in cost associated with STR. Significant variance in OR time and supply cost between surgeons suggests these are potential areas for cost reduction. Although no increased 30-day complications were seen with faster and less costly surgeries, further research is needed to evaluate how time and cost relate to quality of care. [ABSTRACT FROM AUTHOR]

Background Diagnostic strategies employed for cases of cerebrospinal fluid (CSF) rhinorrhea vary widely due to limited evidence-based guidance. Methods A systematic review of the literature was performed using PubMed, EMBASE, and Cochrane databases from January 1990 through September 2014, to examine 9 diagnostic and localization modalities for CSF rhinorrhea. Benefit-harm assessments, value judgments and recommendations were made based on the available evidence. Study exclusion criteria were language other than English, pre-1990 studies, case reports, and nonrhinologic leak. All authors agreed on recommendations through an iterative process. Results We reviewed 68 studies examining 9 practices pertinent to the diagnosis of CSF rhinorrhea, with a highest aggregate grade of evidence of C. The literature does not support the use of the ring sign, glucose testing, radionuclide cisternography (RNC), or computed tomography cisternography (CTC) for identification of CSF leak. Beta-2 transferrin is the most reliable confirmatory test for CSF leak. High-resolution CT (HRCT) is then recommended as the first-line study for localization. Magnetic resonance cisternography (MRC) should be used for CSF leak identification as a second line for each of these if beta-2 transferrin is not available or if HRCT is ambiguous. Intrathecal fluorescein (IF) may also be of benefit in certain clinical scenarios. Conclusion Despite relatively low levels of evidence, recommendations for the diagnosis and management of CSF rhinorrhea can be made based on the current literature. Higher-level studies are needed to better determine optimal diagnostic and clinical management approaches. [ABSTRACT FROM AUTHOR]

Background: Cathelicidin (LL-37) is an endogenous innate immune peptide that is elevated in patients with chronic rhinosinusitis (CRS). The role of LL-37 in olfactory epithelium (OE) inflammation remains unknown.We hypothesized that: (1) LL-37 topically delivered would elicit profound OE inflammation; and (2) LL-37 induced inflammation is associated with increased infiltration of neutrophils and mast cells. Methods: To test our hypothesis we challenged C57BL/6 mice intranasally with increasing concentrations of LL-37. At 24 hours tissueswere examined histologically and scored for inflammatory cell infiltrate, edema, and secretory hyperplasia. In separate experiments, fluorescently conjugated LL-37 was instilled and tissues were examined at 0.5 and 24 hours. To test our last hypothesis, we performed tissue myeloperoxidase (MPO) assays for neutrophil activity and immunohistochemistry for tryptase to determine the mean number of mast cells per mm². Results: LL-37 caused increased inflammatory cell infiltrate, edema, and secretory cell hyperplasia of the sinonasal mucosa, with higher LL-37 concentrations yielding significantly more inflammatory changes (p < 0.01). Fluorescent LL-37 demonstrated global sinonasal epithelial binding and tissue distribution. Further, higher concentrations of LL-37 led to significantly greater MPO levels with dose-dependent increases in mast cell infiltration (p < 0.01). Conclusion: LL-37 has dramatic inflammatory effects in the OE mucosa that is dose-dependent. The observed inflammatory changes in the olfactory mucosa were associated with the infiltration of both neutrophils and mast cells. Our biologic model represents a new model to further investigate the role of LL-37 in OE inflammation. [ABSTRACT FROM AUTHOR]

Background: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). Methods: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence‐based review (EBR), or evidence‐based review with recommendations (EBR‐R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. Results: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA‐associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. Conclusion: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence‐based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy. [ABSTRACT FROM AUTHOR]

Background Recent investigation has demonstrated that approximately 75% of patients with medically refractory chronic rhinosinusitis (CRS) report abnormal sleep quality, with strong correlation between worse sleep quality and more severe CRS disease severity. It remains unknown whether the treatment effect of endoscopic sinus surgery (ESS) for CRS results in appreciable sleep quality improvements. Methods Adult patients (aged ≥18 years) with a current diagnosis of recalcitrant chronic rhinosinusitis (CRS), who voluntarily elected ESS as the next treatment modality (n = 301), were prospectively evaluated within 4 academic, tertiary care centers using treatment outcome instruments: the Rhinosinusitis Disability Index, the 22-item Sinonasal Outcome Test, the 2-item Patient Health Questionnaire, and the Pittsburgh Sleep Quality Index (PSQI) both before and after ESS. Results Seventy-two percent (72%) of patients with CRS were found to have poor sleep (PSQI > 5) at baseline with a mean (standard deviation) global PSQI score of 9.4 (4.6). Surgery improved overall mean global PSQI scores (by 2.2 points), and all 7 subdomain scores of the PSQI. Similarly, the odds of good sleep quality (PSQI ≤ 5) in patients treated with sinus surgery increased significantly (odds ratio [OR] 5.94; 95% confidence interval [CI], 3.06 to 11.53; p < 0.001). Stepwise multivariate linear regression found that acetylsalicylic acid (ASA) intolerance (β [standard error], −1.94 [0.93]; 95% CI, −3.77 to −0.11; p = 0.038), history of prior sinus surgery (β [standard error], 1.10 (0.54); 95% CI, 0.03 to 2.16; p = 0.044), and frontal sinusotomy (β [standard error], −1.03 [0.62]; 95% CI, −2.26 to 0.20; p = 0.099) were found to significantly associate with improvement in PSQI sleep scores. Conclusion Among patients with CRS, reduced sleep quality, poor disease-specific quality of life, and greater disease severity were improved following ESS. [ABSTRACT FROM AUTHOR]

Background Patients with chronic rhinosinusitis (CRS) exhibit centrally mediated behavioral changes commonly referred to as 'sickness behavior.' Sleep alteration is a component of sickness behavior which is estimated to affect up to 70 million patients annually. Patients with CRS have poor sleep quality, and little is known about the underlying etiology and pathophysiology. This narrative review aims to further organize and present the current knowledge associating sleep and CRS. Methods A literature search was conducted of the OVID MEDLINE database using key search words including: 'chronic rhinosinusitis,' 'sleep,' 'sleep disorders,' and 'sleep dysfunction.' Additional keywords 'nasal obstruction,' 'nasal polyp,' and 'fatigue' were identified and used to further delineate relevant articles. Results The articles that specifically addressed sleep and CRS were dissected and presented as follows: (1) chronic rhinosinusitis and sleep; (2) chronic rhinosinusitis and fatigue; (3) chronic rhinosinusitis, nasal obstruction, and sleep; and (4) pathophysiology of sleep in chronic rhinosinusitis (cytokines in both sleep and chronic rhinosinusitis and their association to the neuroimmune biology of chronic rhinosinusitis). Conclusion Patients with CRS have sleep dysfunction that is associated with their disease severity and overall quality of life. The etiology of sleep dysfunction in CRS is most likely multifactorial. Increasing evidence suggests sleep dysfunction in patients with CRS is partly due to the inflammatory disease process, and sleep physiology in patients with CRS may be actively regulated by the inflammatory component of the disease. [ABSTRACT FROM AUTHOR]

Objective Although the role of intraoperative alcoholization of the pituitary gland has been examined for the management of malignant tumor metastases and Rathke's cleft cysts, no such studies have been conducted relating to growth hormone (GH) secreting pituitary tumors, despite the high rate of recurrence in this cohort of patients. Here, we sought to understand the impact of adjunctive intraoperative alcoholization of the pituitary gland on recurrence rates and perioperative complications associated with resection of GH-secreting tumors. Methods This is a single-institution retrospective cohort study analyzing recurrence rates and complications among patients with GH-secreting tumors who received intraoperative alcoholization of the pituitary gland postresection versus those that did not. Welch's t -tests and analysis of variance (ANOVA) analyses were employed to compare continuous variables between groups, whereas chi-squared tests for independence or Fisher's exact tests were used for comparing categorical variables. Results A total of 42 patients (n = 22 no alcohol and n = 20 alcohol) were included in the final analysis. The overall recurrence rates did not significantly differ between the alcohol and no alcohol groups (35 and 22.7%, respectively; p = 0.59). The average time to recurrence in the alcohol and no alcohol groups was 22.9 and 39 months, respectively (p = 0.63), with a mean follow-up of 41.2 and 53.5 months (p = 0.34). Complications, including diabetes insipidus, were not significantly different between the alcohol and no alcohol groups (30.0 vs. 27.2%, p = 0.99). Conclusion Intraoperative alcoholization of the pituitary gland after resection of GH-secreting pituitary adenomas does not reduce recurrence rates or increase perioperative complications. [ABSTRACT FROM AUTHOR]

Abstract: Influenza virus infection up-regulates cytokines such as interleukin-1β (IL-1β) and activates the somatotropic axis and the hypothalamic–pituitary axis. Mice with deficits in growth hormone releasing hormone (GHRH) signaling (lit/lit mice) respond to influenza virus challenge with a progressive decrease in sleep and lower survival rates. Current experiments characterize plasma glucocorticoid responses and hypothalamic and lung mRNA expression of sleep-related genes in lit/lit mice and their heterozygous controls after influenza virus challenge. lit/lit mice had higher basal and post-infection plasma corticosterone levels compared to controls. In contrast, the heterozygous mice increased hypothalamic GHRH-receptor, CRH-type 2 receptor, IL-1β, and tumor necrosis factor-α (TNF-α) mRNAs after virus treatment while the lit/lit mice failed to up-regulate these substances. In contrast, lung levels of IL-1β and TNF-α mRNAs were greater in the lit/lit mice. These data are consistent with the hypothesis that the sleep response to influenza infection is mediated, in part, by an up-regulation of hypothalamic sleep-related transcripts and they also show that a primary deficit in GHRH signaling is associated with enhanced corticosterone secretion and attenuated hypothalamic cytokine response to infection. [Copyright &y& Elsevier]

Previously we have shown, using two-dimensional electrophoresis, that mitochondrial ATP synthase (F[sup o]F[sup 1]-ATPase) β-subunit is the 55-kDa protein increased in cold-acclimated carp Cyprinus carpio (Kikuchi K, Itoi S, and Watabe S. Fisheries Sci 65: 629-636, 1999). To clarify the coordinate expression in various subunits of carp F[sub o]F[sub 1]-ATPase with temperature acclimation, we examined the differences in mRNA levels of mitochondrial proteins encoded by both nuclear and mitochondrial genes in fast muscle of carp acclimated to 10 and 30°C. The mRNA levels of nuclear genes per unit weight of total RNA were nearly twofold higher in the 10°C- than 30°C-acclimated carp. However, the transcripts of mitochondrial genes for the 10°C-acclimated carp in terms of the same comparing unit were six to seven times as much as those for the 30°C-acclimated carp. The F[sub o]F[sub 1]-ATPase activities measured at 10, 25, and 30°C were nearly twofold higher for the cold-acclimated fish than their warm-acclimated counterparts. Such quantitative and qualitative changes in carp F[sub o]F[sub 1]-ATPase may contribute to extra ATP production required to compensate for energy balance at suboptimal temperatures. [ABSTRACT FROM AUTHOR]

DISCUSSION Both English- and Spanish-speaking patients demonstrated a similar prevalence of sinonasal symptoms in a nonspecialty setting; however, English-speaking patients were significantly more likely to have seen a physician for their sinonasal symptoms compared with Spanish-speaking patients. Keywords: access to care; healthcare disparities chronic rhinosinusitis; inequity; sinonasal; social determinants of health EN access to care healthcare disparities chronic rhinosinusitis inequity sinonasal social determinants of health 76 79 4 01/06/23 20230101 NES 230101 INTRODUCTION Social determinants of health, such as education, income, insurance, and race/ethnicity, can significantly impact access to care and health outcomes for various otolaryngologic conditions.[1] Nevertheless, little is known regarding the impact of these social factors on access to care among patients with sinonasal symptoms. Similarly, White patients were more likely to have seen a physician compared with Hispanic and Native American patients ( I p i < 0.01). [Extracted from the article]

Background: Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied. Methods: In a prospective, multi‐institutional study, adult PwCF completed the 22‐Question SinoNasal Outcome Test (SNOT‐22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD‐NS), and Cystic Fibrosis Questionnaire‐Revised (CFQ‐R). Lund–Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression. Results: Seventy‐three PwCF participated with a mean age of 34.7 ± 10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (β = ‒4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p < 0.001), female sex (β = ‒2.14, 95% CI [‒4.11, ‒0.17], p = 0.034), and increasing age (β = ‒0.14, 95% CI [‒0.22, ‒0.05], p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (β = 17.76, 95% CI [5.20, 30.32], p = 0.006) and >16 educational years (β = 13.50, 95% CI [2.21, 24.80], p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ‐R respiratory scores, and ppFEV1 (all p < 0.017), and Hispanic/Latino ethnicity was associated with worse SNOT‐22 scores (p = 0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT‐22, QOD‐NS, or SIT scores. Conclusions: Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient‐reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF. Clinical Trials: NCT04469439 [ABSTRACT FROM AUTHOR]

Key points: EPX activity has been correlated with eCRS diagnosis and baseline disease severity.Herein, EPX activity is shown to correlate with post‐operative antibiotic and steroid use in CRS.EPX activity has potential to act as a prognostic biomarker of CRS disease severity and control. [ABSTRACT FROM AUTHOR]

Background: Olfactory groove meningiomas (OGMs) arise from the cribriform plate of the anterior fossa and account for 9–12% of all meningiomas. Giant OGMs are those larger than 6 cm and are technically challenging to resect. Method: Here we present the surgical decision-making and intraoperative details regarding the endonasal endoscopic resection of an OGM using a minimally invasive, endonasal approach in a 68-year-old female patient. Conclusion: Giant OGMs can be safely and effectively removed using an endonasal, transcribriform approach. [ABSTRACT FROM AUTHOR]

Background: Olfactory neuroblastoma, also known as esthesioneuroblastoma, accounts for only 3–6% of sinonasal malignancies but confers a 40% 5-year overall survival. Method: The authors describe techniques for the endonasal, minimally invasive resection of an esthesioneuroblastoma in a 69-year-old man who presented with headaches and anosmia and describe surgical nuances and their effect on adjuvant therapy planning. Conclusion: This approach, along with microsurgical techniques, helped increase tumor visualization, improved marginal resection, and reduced surgical risk, which may improve patient outcomes. Multilayered reconstruction with a synthetic dural substitute and creation of a nasoseptal flap were performed to reduce postoperative cerebrospinal fluid leak. [ABSTRACT FROM AUTHOR]

The formation of an intracranial abscess secondary to sphenoid sinus occlusion after nasoseptal flap skull base reconstruction has not been previously described. We report such a case that occurred at our institution in a 23-year-old man who underwent flap reconstruction for a cerebrospinal fluid leak. We determined that occlusion of the sphenoid sinus outflow might have played a role in this complication. The patient was treated via a combined surgical and medical approach that entailed a bur-hole craniotomy and endoscopic debridement followed by administration of an intravenous antibiotic. The patient recovered without long-term deficit. When closing a defect of the posterior ethmoid and sphenoid skull base, especially with a pedicled graft, care must be taken to reduce the potential for retention of secretions and blood because this may lead to an intracranial complication. [ABSTRACT FROM AUTHOR]

Objective: Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes. Methods: A total of 642 study participants with CRS were prospectively enrolled and self‐selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. The 22‐item SinoNasal Outcome Test (SNOT‐22) and Medical Outcomes Study Questionnaire Short‐Form 6‐D (SF‐6D) health utility value scores were recorded pre‐ and post‐treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearman's correlation coefficients (Rs) and Cramer's V effect size (φc) with 95% confidence interval (CI) were calculated. Results: A history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φc = 0.18; 95% CI: 0.10, 0.25; p < 0.001). Baseline total SNOT‐22 (Rs = 0.14; 95% CI: 0.06, 0.22; p < 0.001) and SF‐6D values (Rs = −0.20; 95% CI: −0.27, −0.12; p < 0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within‐subject improvement, or achievement of >1 minimal clinically important difference, in SNOT‐22 or SF‐6D scores after treatment were found. Conclusions: Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease‐specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied. Methods: Adult PwCF + CRS were enrolled at eight centers into a prospective, observational study (2019–2023). Participants were administered the 22‐SinoNasal Outcome Test (SNOT‐22) survey and a modified SNOT‐22 instrument examining symptom importance. We determined importance rankings for individual symptoms and SNOT‐22 symptom importance subdomains in two sets of subgroups—those pursuing ESS versus continuing medical management (CMT), and those on elexacaftor/tezacaftor/ivacaftor (ETI) versus not on ETI. Results: Among 69 participants, the highest priorities were nasal congestion (n = 48, 69.6% important), post‐nasal discharge (32, 46.4%), facial pain (29, 43.3%), waking up tired (27, 39.1%), and fatigue (26, 37.7%). Those electing surgery (n = 23) prioritized sleep and psychological dysfunction symptoms compared to those pursuing CMT (n = 49) (sleep median score = 19.0 [interquartile range: 12.0, 25.0] vs. 4.5 [0.0, 12.8]; p < 0.0001; psychological = 17.0 [7.0, 26.0] vs. 7.0 [0.0, 15.8]; p = 0.002). ETI users had comparable SNOT‐22 total symptom importance scores to non‐ETI users (p = 0.14). Non‐ETI users (n = 34) showed a trend toward prioritizing sleep symptoms compared to ETI users (n = 35) (13.0 [2.8, 22.3] vs. 6.0 [2.0, 17.0]; p = 0.055). Conclusions: Nasal congestion and post‐nasal discharge were top priorities reported by PwCF + CRS. Those electing surgery prioritized sleep and psychological symptoms, highlighting their importance in pre‐operative discussions. Non‐ETI users' prioritization of sleep improvement may highlight their unique disease impact and therapeutic needs; however, additional investigation is required. [ABSTRACT FROM AUTHOR]

Introduction: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory‐specific quality‐of‐life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. Methods: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution‐based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. Results: Of 129 PwCF included, 65 had QOD scores before and 3–6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was −1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). Conclusion: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner. [ABSTRACT FROM AUTHOR]

There is a limited understanding of site-specific, quality of life (QOL) outcomes in anterior skull base surgery (ASBS). The objective of the present investigation was to characterize postoperative change in QOL outcomes for anterior skull base lesions following open and endoscopic surgery. A comprehensive review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using the PubMed, Scopus, Embase, and Cochrane databases for studies reporting pre- and postoperative, site-specific, QOL outcome measures in ASBS using validated questionnaires. Studies utilizing the anterior skull base quality of life (ASBQ) questionnaire or the skull base inventory were included. Investigations focusing on skull base surgery for pituitary lesions, as well as survey validation and non-English studies, were excluded. A total of 112 studies were screened; 4 studies, comprising a total of 195 patients and focusing exclusively on the ASBQ, were included in the systematic review. Using a fixed effect model for the meta-analysis, the mean ASBQ score was similar at six (3.45, P = 0.312; −0.19, 95% confidence interval: −0.57, 0.18) and 12 months postoperatively (3.6, P = 0.147; 0.3, 95% confidence interval: −0.11, 0.72) compared to baseline (3.53). Across a variety of anterior skull base pathologies, skull base-specific QOL demonstrated no improvement at 6 months and 12 months postsurgery. Few studies to date have published pre- and postoperative QOL data for patients undergoing ASBS, highlighting a current shortcoming in the available literature. Long-term follow-up in patients undergoing open and endoscopic approaches will be necessary to better understand and optimize outcomes for patients having ASBS. [ABSTRACT FROM AUTHOR]

Background: Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality‐of‐life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied. Methods: Adult PwCF + CRS were enrolled into a prospective, observational, multi‐institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS. Results: Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT‐22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire‐9‐Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire‐Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p < 0.050). Multivariable regression identified that worse SNOT‐22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02–1.16, p = 0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004–0.34, p = 0.004) was associated with pursing medical therapy. Conclusions: Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden. [ABSTRACT FROM AUTHOR]

Background: Poor air quality increases the risk of developing chronic rhinosinusitis (CRS) and other airway diseases. However, there are limited data on air pollutants and CRS‐specific disease severity. We assessed the impact of air pollutants on sinonasal‐specific and general quality‐of‐life (QOL) measures in a multi‐institutional cohort of patients with CRS. Methods: Participants with CRS were prospectively enrolled in a cross‐sectional study and self‐selected continued appropriate medical therapy or endoscopic sinus surgery (ESS). The 22‐item SinoNasal Outcome Test (SNOT‐22) and Medical Outcomes Study Questionnaire Short‐Form 6‐D (SF‐6D) health utility value scores were recorded. Patient exposure to air pollutants was determined using residence zip codes. Unadjusted group differences were compared, and correlation coefficients were evaluated to identify the magnitude of bivariate association. Results: A total of 486 patients were enrolled and followed for a mean of 6.9 (standard deviation [SD] ± 2.3) months. Pollutant exposure did not significantly correlate with baseline SNOT‐22 or SF‐6D scores. Revision ESS was associated with higher median fine particulate matter (PM2.5; Δ = 0.12, [95% confidence interval {CI}: 0.003, 0.234]; p = 0.006) compared with primary surgery. PM2.5, PM10, and nitrogen dioxide concentrations (μg/m3) did not correlate with change in total SNOT‐22 or SF‐6D scores after treatment. Nevertheless, sulfur dioxide (SNOT‐22: ρ = –0.121 [95% CI: –0.210, –0.030]; p = 0.007; SF‐6D: ρ = 0.095 [95% CI: 0.002, 0.186]; p = 0.04) and carbon monoxide (SNOT‐22: ρ = ‐0.141 [95% CI: –0.230, 0.050]; p = 0.002) exposure did correlate with these outcome measures. Conclusion: Air pollutants may contribute, at least in part, to disease severity in CRS; future investigation is needed to further elucidate the nature of this relationship. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient‐reported and clinically measured post‐operative outcome measures. Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient‐reported outcome measures included the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund–Kennedy endoscopic score (LKES). Results: A total of 115 patients were clustered into type 2 inflammatory, non–type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT‐22 (−28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between‐group differences in SNOT‐22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures. Conclusions: All CRS endotype clusters responded favorably to surgery and showed improvements in patient‐reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes. [ABSTRACT FROM AUTHOR]

Objectives: Chronic rhinosinusitis (CRS) is a disease with significant impacts at both a societal and personal level. There has been an increase in emphasis on patient‐centered care and patient outcomes, with value becoming a commonplace concept in health care systems. This review seeks to better define the value that endoscopic sinus surgery (ESS) provides in the treatment of CRS. Data Sources: PubMed literature review. Review Methods: A review of published literature related to ESS and its effects on CRS patients from multiple perspectives (quality outcomes, patient satisfaction, cost‐effectiveness) was integrated and analyzed through the viewpoint of a value equation. Results: ESS provides long‐term quality outcomes in both patient‐reported outcome measures (PROMs) as well as in objective metrics for patients refractory to medical therapy. The vast majority undergoing ESS are satisfied both in the short and long‐term with their decision to pursue surgery. Treatment of CRS with ESS is generally more cost‐effective than continued medical therapy (CMT), especially in refractory patients. Taken together, the combination of improved outcomes as well as patient satisfaction after ESS in relation to the costs of surgery provides significant quantifiable value to CRS patients. Conclusion: ESS clearly provides value in the treatment of CRS. Understanding both quality and outcome metrics along with patient expectations and priorities will assist providers in generating a more personalized and value‐based approach to patients with CRS. Level of Evidence: 5. [ABSTRACT FROM AUTHOR]

Background: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses. [ABSTRACT FROM AUTHOR]

Background: The Relative Value Scale Update Committee, commonly known as the RUC, is responsible for defining the value of Current Procedural Terminology (CPT) codes. The RUC process uses survey responses reporting operative times to determine procedure reimbursement, but it is limited by low response rates, small sample sizes, and unclear generalizability of the results. By comparing actual reported intraoperative times to the times determined by the RUC process, in this study we sought to assess the performance of RUC methodology in endoscopic sinus surgery (ESS). Methods: The ESS CPT codes that were reassessed in 2016 using the RUC method were examined in this study. Intraoperative time data for these codes were retrospectively collected from 14 medical facilities, using time stamps in the electronic health record. These actual intraoperative times were compared with the 2016 RUC survey results. Results: There were 143 RUC physician survey responses and 446 actual procedure times included in the final analysis. There was significant variability within the RUC survey responses (ie, unilateral anterior ethmoidectomy times varied from 5 to 90 minutes). There was also a significant difference between the RUC survey results and actual intraoperative times (p < 0.001). For example, frontal sinus surgeries showed a particularly poor correlation between actual and RUC times. Conclusion: The RUC process may not accurately estimate or value actual intraoperative times. Real‐world intraoperative times are readily accessible and may be an alternative to survey‐based methodology in the future. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a chronic health condition affecting the sinonasal cavity. CRS-associated mucosal inflammation leads to sinonasal epithelial cell death and epithelial cell barrier disruption, which may result in recurrent bacterial infections and biofilm formation. For patients who fail medical management and elect endoscopic sinus surgery for disease control, bacterial biofilm formation is particularly detrimental, as it reduces the efficacy of surgical intervention. Effective treatments that prevent biofilm formation in post-operative patients in CRS are currently limited. To address this unmet need, we report the controlled release of silver nanoparticles (AgNps) with silk-elastinlike protein-based polymers (SELPs) to prevent bacterial biofilm formation in CRS. This polymeric network is liquid at room temperature and forms a hydrogel at body temperature, and is hence, capable of conforming to the sinonasal cavity upon administration. SELP hydrogels demonstrated sustained AgNp and silver ion release for the studied period of three days, potent in vitro antibacterial activity against Pseudomonas aeruginosa (**** p < 0.0001) and Staphylococcus aureus (**** p < 0.0001), two of the most commonly virulent bacterial strains observed in patients with post-operative CRS, and high cytocompatibility with human nasal epithelial cells. Antibacterial controlled release platform shows promise for treating patients suffering from prolonged sinonasal cavity infections due to biofilms. [ABSTRACT FROM AUTHOR]

The University of Utah Rhinology Research Team responds to comments made by Dr. Yadav regarding their study on chronic rhinosinusitis (CRS). They express gratitude for the suggestions and acknowledge the need to validate their findings. The team outlines ongoing investigations, including optimizing the peroxidase assay to differentiate between eosinophilic and neutrophilic inflammation, evaluating sample collection methods, and correlating tissue levels of eosinophil peroxidase (EPX) activity with cytokine levels and treatment outcomes. They emphasize the importance of diverse patient populations in future studies and express their commitment to continuing this research. [Extracted from the article]

Background: Despite significant morbidity, there remains a critical need for prospective analyses to investigate the impact of comorbid chronic rhinosinusitis (CRS) with asthma (CRSwA) on patient centered outcomes. The objective of this study was to ascertain critical stakeholder feedback from patients that could inform future study design based on patient preferences, in an effort to optimize patient enrollment. Methods: A prospective, descriptive study was performed in order to determine the importance of various factors on CRSwA treatment among critical stakeholders. A Likert-scale survey highlighting various aspects of treatment of CRSwA and elucidating patient enthusiasm for clinical enrollment was constructed and prospectively administered to patients with CRSwA. A univariate analysis was instituted to understand the significance of the different trial design preferences. Results: Survey responses were collected from a total of 17 patients with CRSwA. With Likert scores >4/5, responses indicated significant stakeholder interest in research focused on understanding symptom triggers, including the impact of air quality and allergens. Importantly, the highest mean scores noted were for studies focused on improving (1) overall quality of life (4.8/5) and (2) lung function (4.8/5). Patients appeared least interested in participation in a randomized trial, whereas the greatest support was communicated for a purely observational trial (P =.08). Conclusion: Patients with CRSwA demonstrate enthusiasm for participation in research that focuses on improving patient centered outcomes—specifically quality of life and lung function. Stakeholder feedback also indicates a preference for observational study design over randomized control trials. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a chronic inflammatory condition affecting the nasal and paranasal sinuses of approximately 11.5% of the United States adult population. Oral corticosteroids are effective in controlling sinonasal inflammation in CRS, but the associated adverse effects limit their clinical use. Topical budesonide has demonstrated clinical efficacy in patients with CRS. Herein, we investigated the systemic delivery of liposomes tethered with poly(ethylene glycol) (PEG) and loaded with budesonide in a murine model of CRS. PEGylated liposomes encapsulated with budesonide phosphate (L-BudP) were administered via tail vein injection, and the feasibility of L-BudP to reduce sinonasal inflammation was compared to that of free budesonide phosphate (F-BudP) and topical budesonide phosphate (T-BudP) treatment over a 14-day study period. Compared to a single injection of F-BudP and repeat T-BudP administration, a single injection of L-BudP demonstrated increased and prolonged efficacy, resulting in the significant improvement of sinonasal tissue histopathological scores (p < 0.05) with decreased immune cell infiltration (p < 0.05). Toxicities associated with L-BudP and T-BudP treatment, assessed via body and organ weight, as well as peripheral blood liver enzyme and differential white blood cell analyses, were transient and comparable. These data suggest that systemic liposomal budesonide treatment results in improved efficacy over topical treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid‐sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models. An intranasal formulation of amiloride will be highly beneficial to treat acute panic attacks due to advantages such as the rapid onset of action and patient compliance. The aim of this single‐center, open‐label trial was to evaluate the basic pharmacokinetics (PKs) and safety of amiloride after intranasal administration in healthy human volunteers at three doses (0.2, 0.4, and 0.6 mg). Amiloride was detected in plasma within 10 min of intranasal administration and showed a biphasic PK profile with an initial peak within 10 min of administration followed by a second peak between 4 and 8 h of administration. The biphasic PKs indicate an initial rapid absorption via the nasal pathway and later slower absorption by non‐nasal pathways. Intranasal amiloride exhibited a dose‐proportional increase in the area under the curve and did not exhibit any systemic toxicity. These data indicate that intranasal amiloride is rapidly absorbed and safe at the doses evaluated and can be further considered for clinical development as a portable, rapid, noninvasive, and nonaddictive anxiolytic agent to treat acute panic attacks. [ABSTRACT FROM AUTHOR]

Background Poor sleep has significant effects on health contributing to increased morbidity and mortality. The direct and indirect costs of sleep dysfunction total well in to the billions of dollars annually in the United States. Chronic rhinosinusitis (CRS) affects up to 16% of the US population and has been linked to poor sleep quality with up to three quarters of patients with CRS reporting poor sleep quality. There is a growing body of literature evaluating the relationship between sleep and CRS. In this review, we organize and present the current knowledge on the associations between sleep and CRS as well as identify areas for further investigation. Data sources A structured literature search from 1946 to 2016 was conducted in the English language using OVID MEDLINE database, PubMed, and EMBASE. Review methods Abstracts were reviewed for relevance and appropriate studies were included in the narrative review. Results Studies were analyzed and discussed as they pertained to the following categories of CRS and sleep: (1) subjective measures of sleep dysfunction, (2) objective measures of sleep dysfunction, and (3) outcomes on sleep quality following treatment of CRS. Articles on the pathophysiology of sleep dysfunction in CRS were separately reviewed. Conclusions An evolving body of research demonstrates that quality of sleep is compromised in the majority of patients with CRS. Following treatment of CRS, there is significant improvement in subjective sleep quality, but additional research investigating objective measures following treatment is still needed. Additionally, further investigation is required to better elucidate the underlying pathophysiology of the relationship between sleep dysfunction and CRS. Level of Evidence N/A. [ABSTRACT FROM AUTHOR]

Background: Although it has been postulated that tobacco use, as well as other environmental exposures, may contribute to chronic rhinosinusitis (CRS), the data remain limited. Here, we utilised a large state population database to assess the association between tobacco use and CRS prevalence among patients undergoing endoscopic sinus surgery (ESS). Methods: Employing a case–control study design, the Utah Population Database was queried for patients age >18 with a diagnosis of CRS and tobacco use who underwent ESS between 1996 and 2018. Smoking status was compared between patients with CRS (n = 34 350) and random population controls matched 5:1 on sex, birth year, birthplace, time residing in Utah, and pedigree (i.e., familial) information (n = 166 020). Conditional logistic regression models were used for comparisons between CRS patients and their matched controls. All analyses were repeated, additionally adjusting for race, ethnicity, tobacco use, asthma history, and interaction between tobacco use and asthma history. Results: A total of 200 370 patients were included in the final analysis. Patients with CRS were significantly more likely to demonstrate a history of tobacco use than controls (19.6% vs. 15.0%; p <.001), with an adjusted odds ratio (aOR) of 1.42, 95% confidence interval 1.37–1.47; p <.001. More patients with CRS and comorbid asthma used tobacco (19.5%) than controls with asthma (15.0%; p <.001). Conclusion: History of tobacco use may portend increased risk for the development of CRS among patients undergoing ESS compared to healthy controls. [ABSTRACT FROM AUTHOR]

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation fromthe full document. Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based reviewwith recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensuswas performed for each topic. The final document was then collated and includes the results of this work. Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment. [ABSTRACT FROM AUTHOR]

Background: Productivity loss and activity limitations due to chronic rhinosinusitis (CRS) are known to contribute to the significant economic and personal burden of disease. The purpose of this study was to assess productivity and activity impairment before and after endoscopic sinus surgery (ESS) for medically refractory CRS. Methods: This investigation was a prospective, multi‐institutional, observational cohort study. Patients diagnosed with medically refractory CRS completed the Work Productivity and Activity Impairment—Specific Health Problem (WPAI‐SHP) questionnaire before surgery and approximately 6 months after the procedure. Factors associated with minimal clinical important differences (MCIDs) for productivity and activity impairment were identified. Results: A total of 279 study participants were screened for inclusion, of whom 176 (63.1%) with postoperative follow‐up were included in the final cohort. Preoperative productivity and activity impairment were observed in 63.2% and 69.8% of the patients, respectively. Among these patients, postoperative improvement equaling at least 1 MCID was reported in both productivity (76.1%) and activity (76.4%) impairments. Multivariate regression identified sphenoidotomy (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.03‐17.02) as the only factor associated with increased likelihood of productivity improvement, whereas septoplasty during ESS (OR, 8.45; 95% CI, 2.33‐30.68) and migraine (OR, 0.35; 95% CI, 0.12‐0.96) were associated with differential odds of activity improvement. Conclusion: CRS is associated with a substantial burden on productivity and activity that significantly improves after treatment with ESS. These data may facilitate improved patient counseling and shared decision‐making regarding surgical management for CRS. [ABSTRACT FROM AUTHOR]

Esthesioneuroblastoma (ENB) is a rare sinonasal malignant neoplasm with 40% 5-year survival. Because of the rarity of the tumor, the optimal treatment and subsequent prediction of prognosis are unclear. We studied a modern series of patients with ENB to evaluate the association of immunohistochemical (IHC) markers and clinical stages/grades with outcomes. A single-center retrospective review of patients with ENB treated during a 25-year period was performed. A systematic literature review evaluating the prognostic benefits of current staging systems in evaluating survival outcomes in ENB was undertaken. Among 29 included patients, 25 (85%) were treated surgically at our institution, with 76% of those endoscopically resected; 7 (24.1%) received chemotherapy, and 18 (62.1%) received radiation therapy. The 5-year overall survival (OS) was 91.3%, and 10-year OS was 78.3%. Progression-free survival at 5 and 10 years was 85.6% and 68.2%, respectively. A total of 36 distinct IHC markers were used to diagnose ENB but were inconsistent in predicting survival. A systematic literature review revealed predictive accuracy for OS using the Kadish, TNM, and Hyams staging/grading systems was 68%, 42%, and 50%, respectively. This study reports the 5- and 10-year OS and progression-free survival in a modern series of patients with ENB. No traditional IHC marker consistently predicted outcome. Some novel reviewed markers show promise but have yet to enter clinical mainstream use. Our systematic review of accepted staging/grading systems also demonstrated a need for further investigation due to limited prognostic accuracy. [ABSTRACT FROM AUTHOR]