The Burden of NSAID-ERD: Interplay between Quality of Life and Economic Implications.

NSAID-Exacerbated Respiratory Disease (NSAID-ERD) presents a significant challenge in clinical management, owing to recalcitrant disease with accompanying profound impacts on patient quality of life. Though asthma represents a significant component of this disease, quality of life disruptions are driven primarily by recalcitrant sinonasal complaints, olfactory dysfunction, and the associated psychosocial and dietary implications. This review delves into specific quality of life metrics used to assess NSAID-ERD and the associated healthcare burden and financial implications of this disease, offering insights into the comparative challenges in chronic rhinosinusitis with nasal polyps (CRSwNP) where available. The article reviews the associated costs and cost-effectiveness of NSAID-ERD-directed therapies, including endoscopic sinus surgery, aspirin desensitization, and biologic therapy. While some of these emerging treatment approaches show promise, they also present numerous unanswered questions, reflecting the dynamic nature of this field. As the landscape of NSAID-ERD management continues to evolve, this review provides insights into the challenges faced by clinicians and underscores the need for further research to optimize patient care and quality of life outcomes.

Molecular patterns and mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal squamous cell carcinoma.

Mechanisms of tumorigenesis in sinonasal squamous cell carcinoma (SNSCC) remain poorly described due to its rare nature. A subset of SNSCC are associated with the human papillomavirus (HPV); however, it is unknown whether HPV is a driver of HPV-associated SNSCC tumorigenesis or merely a neutral bystander. We hypothesized that performing the first large high-throughput sequencing study of SNSCC would reveal molecular mechanisms of tumorigenesis driving HPV-associated and HPV-independent SNSCC and identify targetable pathways. High-throughput sequencing was performed on 64 patients with HPV-associated and HPV-independent sinonasal carcinomas. Mutation annotation, viral integration, copy number, and pathway-based analyses were performed. Analysis of HPV-associated SNSCC revealed similar mutational patterns observed in HPV-associated cervical and head and neck squamous cell carcinoma, including lack of TP53 mutations and the presence of known hotspot mutations in PI3K and FGFR3. Further similarities included enrichment of APOBEC mutational signature, viral integration at known hotspot locations, and frequent mutations in epigenetic regulators. HPV-associated SNSCC-specific recurrent mutations were also identified including KMT2C , UBXN11 , AP3S1 , MT-ND4 , and MT-ND5 . Mutations in KMT2D and FGFR3 were associated with decreased overall survival. We developed the first known HPV-associated SNSCC cell line and combinatorial small molecule inhibition of YAP/TAZ and PI3K pathways synergistically inhibited tumor cell clonogenicity. In conclusion, HPV-associated SNSCC and HPV-independent SNSCC are driven by molecularly distinct mechanisms of tumorigenesis. Combinatorial blockade of YAP/TAZ and vertical inhibition of the PI3K pathway may be useful in targeting HPV-associated SNSCC whereas targeting MYC and horizontal inhibition of RAS/PI3K pathways for HPV-independent SNSCC. One Sentence Summary: This study solidifies HPV as a driver of HPV-associated SNSCC tumorigenesis, identifies molecular mechanisms distinguishing HPV-associated and HPV-independent SNSCC, and elucidates YAP/TAZ and PI3K blockade as key targets for HPV-associated SNSCC.

Patient Questions Surrounding Posterior Nasal Nerve Ablation for Chronic Rhinitis.

Objective: In-office ablation of the posterior nasal nerve (PNN) has emerged as an effective treatment option for chronic rhinitis patients. This study explored questions patients commonly search online regarding this therapy and the quality of content available. Study Design: A retrospective analysis of online search criteria and sources was performed with subsequent analysis of results. Setting: Search and data acquisition was in September of 2023. Methods: Most common search terms related to cryotherapy and radiofrequency neurolysis of the PNN were identified with associated People Also Ask (PAA) questions. Questions were categorized and organized into subtopics and sources evaluated using readability and quality metrics. Results: A total of 255 unique PAA questions and 175 unique websites were identified. The most common subtopics were related to facts about chronic rhinitis (26.7%) and rhinitis treatment options (25.1%). Nearly a quarter (24.3%) of websites were from commercial sources. Quality metrics indicate difficult-to-read and low-quality materials. Conclusion: Existing online resources need improvement to provide patients material that is easier to read. Physicians counseling patients should be aware of these areas for adequate shared decision making.

Air pollution, genetic factors, and chronic rhinosinusitis: A prospective study in the UK Biobank.

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent upper respiratory condition that manifests in two primary subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While previous studies indicate a correlation between air pollution and CRS, the role of genetic predisposition in this relationship remains largely unexplored. We hypothesized that higher air pollution exposure would lead to the development of CRS, and that genetic susceptibility might modify this association. METHODS: This cohort study involving 367,298 adult participants from the UK Biobank, followed from March 2006 to October 2021. Air pollution metrics were estimated at residential locations using land-use regression models. Cox proportional hazard models were employed to explore the associations between air pollution exposure and CRS, CRSwNP, and CRSsNP. A polygenic risk score (PRS) was constructed to evaluate the joint effect of air pollution and genetic predisposition on the development of CRS. RESULTS: We found that the risk of CRS increased under long-term exposure to PM2.5 [the hazard ratios (HRs) with 95 % CIs: 1.59 (1.26-2.01)], PM10 [1.64 (1.26-2.12)], NO2 [1.11 (1.04-1.17)], and NOx [1.18 (1.12-1.25)], respectively. These effects were more pronounced among participants with CRSwNP, although the differences were not statistically significant. Additionally, we found that the risks for CRS and CRSwNP increased in a graded manner among participants with higher PRS or higher exposure to PM2.5, PM10, or NOx concentrations. However, no multiplicative or additive interactions were observed. CONCLUSIONS: Long-term exposure to air pollution increases the risk of CRS, particularly CRSwNP underscoring the need to prioritize clean air initiatives and environmental regulations.

The association between olfactory subdomains and frailty: A prospective case‒control study investigation.

BACKGROUND: Amidst the rise of frailty among a globally aging population, olfactory decline has emerged as a harbinger of frailty and mortality in population-level studies. However, the relationships between frailty and the olfactory subdomains of identification (OI), discrimination (OD), and threshold (OT) remain unexplored. This study prospectively examined the association between olfactory subdomains and the physical frailty phenotype (PFP) to investigate olfactory evaluation as a means of frailty screening. METHODS: A case‒control study of 45 frail and 45 non-frail individuals matched by age and sex. OT, OD, OI (range 0‒16), and composite sum (threshold, discrimination, and identification scores [TDI], range 0‒48) were measured with Sniffin' Sticks. PFP was defined by presence of three or more criteria: physical inactivity, self-reported exhaustion, muscle weakness, slow gait, and unintentional weight loss. Conditional logistic regression evaluated associations between olfactory subdomains and frailty. RESULTS: Ninety individuals with mean age of 83.1 ± 4.9 years, 60% female (n = 54), and 87.8% white (n = 79) were included. Olfactory scores were significantly lower in the frail group for OI (9.2 vs. 12.1, p < 0.001), OD (8.1 vs. 11.6, p < 0.001), OT (4.4 vs. 8.5, p < 0.001), and TDI (21.7 vs. 32.2, p < 0.001) than in the non-frail group. A single-point decrease in olfactory score was associated with increased odds of frailty in OT (odds ratio [OR]: 2.21, 95% confidence interval: [1.22, 3.98]), OD (OR: 2.19, 95% CI: [1.32, 3.65]), OI (OR: 2.29, 95% CI: [1.19, 4.39]), and TDI (OR: 1.54, 95% CI: [1.14, 2.08]). CONCLUSION: The robust association between olfactory subdomain scores and frailty suggests that olfaction may be an accessible signifier of frailty. Future studies should investigate this relationship longitudinally to assess predictive relationships.

Quality of life in chordoma survivors: results from the Chordoma Foundation Survivorship Survey.

OBJECTIVE: Chordomas are rare malignant bone tumors whose location in the skull base or spine, invasive surgical treatment, and accompanying adjuvant radiotherapy may all lead patients to experience poor quality of life (QOL). Limited research has been conducted on specific demographic and clinical factors associated with decreased QOL in chordoma survivors. Thus, the aim of the present study was to investigate several potential variables and their impact on specific QOL domains in these patients as well the frequencies of specific QOL challenges within these domains. METHODS: The Chordoma Foundation (CF) Survivorship Survey was electronically distributed to chordoma survivors subscribed to the CF Chordoma Connections forum. Survey questions assessed QOL in three domains: physical, emotional/cognitive, and social. The degree of impairment was assessed by grouping the participants into high- and low-challenge groups designated by having ≥ 5 or < 5 symptoms or challenges within a given QOL domain. Bivariate analysis of demographic and clinical characteristics between these groups was conducted using Fisher's exact test and the Mann-Whitney U-test. RESULTS: A total of 665 chordoma survivors at least partially completed the survey. On bivariate analysis, female sex was significantly associated with increased odds of significant emotional (p = 0.001) and social (p = 0.019) QOL burden. Younger survivors (age < 65 years) were significantly more likely to experience significant physical (p < 0.0001), emotional (p < 0.0001), and social (p < 0.0001) QOL burden. Skull base chordoma survivors had significantly higher emotional/cognitive QOL burden than spinal chordoma survivors (p = 0.022), while the converse was true for social QOL challenges (p = 0.0048). Survivors currently in treatment were significantly more likely to experience significant physical QOL challenges compared with survivors who completed their treatment > 10 years ago (p = 0.0074). Fear of cancer recurrence (FCR) was the most commonly reported emotional/cognitive QOL challenge (49.6%). Only 41% of the participants reported having their needs met for their physical QOL challenges as well as 25% for emotional/cognitive and 18% for social. CONCLUSIONS: The authors' findings suggest that younger survivors, female survivors, and survivors currently undergoing treatment for chordoma are at high risk for adverse QOL outcomes. Additionally, although nearly half of the participants reported a FCR, very few reported having adequate emotional/cognitive care. These findings may be useful in identifying specific groups of chordoma survivors vulnerable to QOL challenges and bring to light the need to expand care to meet the QOL needs for these patients.

Modified technique improves efficacy for in-office posterior nasal nerve ablation.

Objectives: Posterior nasal nerve (PNN) ablation is a minimally invasive treatment option for patients with chronic rhinitis. Recent evidence shows that parasympathetic innervation of the nasal cavity is more extensive and there are many fibers posterior to the lateral attachment of the middle turbinate. We describe a modified ablative technique that targets the extensive innervation of the posterior nasal nerves. Methods: Description of the technique and retrospective cohort analysis. In addition to the traditional radiofrequency and cryoablation targets, three additional treatment sites posterior to the middle turbinate were targeted using radiofrequency ablation, as well as one focused treatment posteroinferior to the middle turbinate attachment using cryotherapy ablation. The primary outcome collected was a 30% improvement in overall rhinitis symptoms. Results: Forty-five patients received treatment and completed 3-month follow-up using the modified technique for radiofrequency and cryotherapy PNN ablation. Previously, our institution documented a 64.5% responder rate at 3 months. After introducing the modified technique, the response rate at 3 months significantly improved (64.5% vs. 91.1%, p = .004). Conclusions: This report suggests improved efficacy with implementation of the modified technique for in-office PNN ablation. Given the extensive nature of the post-ganglionic parasympathetic fibers of the nasal cavity which often emerge posterior to the middle turbinate attachment, a modified technique to target these branches should be considered. Prospective randomized studies comparing this modified technique to the traditional technique are needed. Level of Evidence: III.

Delivering Therapy to the Olfactory Cleft: A Comparison of the Various Methods of Administering Topical Nasal Medications.

Background and objective Chronic rhinosinusitis (CRS) is an inflammatory condition affecting the nasal mucosa, and it causes olfactory dysfunction (OD) in up to 78.2% of patients. Corticosteroids are the mainstay of treatment to shrink nasal polyposis, reduce inflammation, and improve olfactory function. While many delivery methods for topical nasal corticosteroids exist, there is scarce data on the efficacy of the various medication delivery methods to the olfactory cleft (OC). In light of this, this study aimed to compare the following delivery methods to the OC: conventional nasal spray (NS), nasal drops in the Kaiteki position (KP), and exhalation delivery system (EDS). Methods We evaluated 16 sinonasal cavities from eight cadaver specimens in this study. Each sinonasal cavity was administered fluorescein dye solution via NS, KP, and EDS. Following administration, nasal endoscopy was employed to capture staining patterns in the OC. OC staining was rated with scores ranging from 0 (no staining) to 3 (heavy staining) after each administration of dye solution. Mean OC staining ratings were calculated and compared using the Kruskal-Wallis rank sum test and the Wilcoxon signed-rank test. Results The mean OC staining score for the different delivery methods was as follows - NS: 1.095 ± 1.008, EDS: 0.670 ± 0.674, and KP: 2.038 ± 1.097. Nasal drops in the KP had a significantly higher staining score compared to NS (p=0.041) and EDS (p=0.003). However, there was no significant difference in staining scores between NS and EDS. Conclusions Nasal drops in the KP are more effective at reaching the OC than NS or EDS and should be considered as a first-line modality for administering topical medications when treating OD.

Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants.

SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in nasal tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variant revealed that SARS-CoV-2 WA1 or Delta infect a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possessed broader cellular invasion capacity into the submucosa, while Omicron displayed enhanced nasal respiratory infection and longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon were more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa were accompanied by a decline of phagocytosis-related genes. Further, robust basal stem cell activation contributed to neuroepithelial regeneration and restored ACE2 expression postinfection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration after infection. The shifting characteristics of viral infection at the airway portal provide insight into the variability of COVID-19 clinical features, particularly long COVID, and may suggest differing strategies for early local intervention.

Operative Corridors in Endoscopic Skull Base Tumor Surgery.

Advances in technology, instrumentation, and reconstruction have paved the way for extended endoscopic approaches to skull base tumors. In the sagittal plane, the endonasal approach may safely access pathologies from the frontal sinus to the craniocervical junction in the sagittal plane, the petrous apex in the coronal plane, and extend posteriorly to the clivus and posterior cranial fossa. This review article describes these modular extended endoscopic approaches, along with crucial anatomic considerations, illustrative cases, and practical operative pearls.

Site-Specific Quality of Life Outcomes Following Anterior Skull Base Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Inflation Reduction Act: Implications for Medicare spending and access to biologic therapies for chronic rhinosinusitis with nasal polyposis and asthma.

KEY POINTS: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA). Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%. Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%-60%.

Physical Function Trajectories and Mortality in Older Adults With Multisensory Impairment.

Importance: Single sensory impairment is associated with reduced functional resilience and increased mortality, though the effects of multiple sensory deficits are not known. Objective: To investigate longitudinal associations of the type, severity, and number of sensory impairments with physical function trajectories and mortality in older adults. Design, Setting, and Participants: This retrospective analysis of a longitudinal cohort study, the Health, Aging, and Body Composition (Health ABC) study, incorporated data from April 1997 to July 2013, featuring a 16-year follow-up with annual examinations and questionnaires. The cohort comprised 3075 men and women, aged 70 to 79 years at baseline, residing in Memphis, Tennessee, and Pittsburgh, Pennsylvania. All participants with complete sensory testing and covariate data at analytical baseline (year 5, 2002) were included. The data were analyzed September 1, 2022. Exposures: Visual, olfactory, auditory, and touch sensory functions were assessed between 2000 and 2002. Main Outcomes: The main outcomes included physical functioning trajectories and mortality risk. Physical function was assessed longitudinally using the Health ABC physical performance battery (HABCPPB). Results: A total of 1825 individuals (mean [SD] age, 77.4 [3.2] years; 957 [52%] female) were included in this study. Multivariable analysis of HABCPPB decline indicated that having 1 sensory impairment (ß estimate, -0.01 [95% CI, -0.02 to -0.001]); 2 sensory impairments (ß estimate, -0.01 [95% CI, -0.02 to -0.01]); 3 sensory impairments (ß estimate, -0.03 [95% CI, -0.04 to -0.02]); or 4 sensory impairments (ß estimate, -0.04 [95% CI, -0.05,-0.03]) was significantly associated with a steeper HABCPPB score decline in a dose-dependent manner. Adjusted Cox proportional hazards models indicated that having 1 sensory impairment (hazard ratio [HR], 1.35 [95% CI, 1.01-1.81]), 2 sensory impairments (HR, 1.58 [95% CI, 1.19-2.11]), 3 sensory impairments (HR, 1.79 [95% CI, 1.33-2.42]), or 4 sensory impairments (HR, 1.97 [95% CI, 1.39-2.79]) was significantly associated with increased mortality risk in a similarly dose-dependent manner. Conclusion: In this retrospective cohort study, the degree and number of multiple sensory impairments were associated with worse physical functioning and increased mortality risk. These findings represent an opportunity for further investigation into the value of screening, prevention, and treatment of sensory impairments to reduce morbidity and mortality in older adults.

Accessing the Eustachian tube: Conventional nasal spray vs. exhalation delivery system and the impact of targeted endoscopic sinus surgery on topical distribution patterns.

BACKGROUND: Eustachian tube dysfunction (ETD) may occur distinct from, or in conjunction with, chronic rhinosinusitis (CRS+ETD). Intranasal corticosteroid sprays are often prescribed for ETD, although ET distribution may be limited. To date, no anatomic studies compare nasopharynx (NP) distribution between conventional nasal sprays (NS) and exhalation delivery systems (EDS) after surgery. This study utilizes a cadaver model to examine topical NP delivery using EDS vs. NS before and after targeted endoscopic sinus surgery (ESS). METHODS: Sixteen sinonasal cavities were administered fluorescein solution via NS and EDS before and after maxillary antrostomy and anterior ethmoidectomy, followed by nasal endoscopy of the NP and ET orifice. Seven blinded experts submitted staining ratings of endoscopy images on a 0- to 3-point scale, with ratings averaged for analysis. RESULTS: Interrater reliability was excellent (intraclass correlation, 0.956). EDS was associated with significantly greater NP staining vs. NS in a pooled cohort of nonsurgical and ESS specimens (1.19 ± 0.81 vs. 0.78 ± 1.06; p = 0.043). Using a logistic regression model, EDS significantly outperformed NS in nonsurgical (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.21-10.09; p = 0.021) and post-ESS (OR, 9.00; 95% CI, 1.95-41.5; p = 0.005) specimens, with the greatest relative staining observed for EDS after targeted ESS (OR, 18.99; 95% CI, 3.44-104.85; p = 0.001). CONCLUSIONS: EDS is more effective than NS in topical delivery to the NP and ET orifices in cadavers. Targeted ESS may facilitate greater NP penetration by EDS compared with NS, with possible synergism after ESS for augmented delivery. These findings suggest a role for EDS delivery methods for ETD management and in CRS+ETD patients undergoing sinus surgery.

Reduction in olfactory dysfunction prevalence among patients with diabetes taking metformin.

KEY POINTS: Metformin treatment is associated with reduced olfactory dysfunction (OD) in diabetic patients Metformin may possess potential protective effects on olfaction beyond glycemic control.

Staying Virtual: A Survey Study of the Virtual Lecture Experience in Academic Medicine.

BACKGROUND: Increasing clinical demands can adversely impact academic advancement, including the ability to deliver lectures and disseminate scholarly work. The virtual lecture platform became mainstream during the height of the coronavirus-19 pandemic. Lessons learned from this period may offer insight into supporting academic productivity among physicians who must balance multiple demands, including high clinical workloads and family care responsibilities. We evaluated perceptions on delivering virtual lectures to determine whether virtual venues merit continuation beyond the pandemic's initial phase and whether these perceptions differ by gender and rank. METHODS: In a survey study, faculty who spoke in 1 of 3 virtual lecture programs in the Departments of Anesthesiology and Critical Care Medicine, Otolaryngology, and Radiology at a university hospital in 2020 to 2022 were queried about their experience. Speakers' motivations to lecture virtually and the perceived advantages and disadvantages of virtual and in-person lectures were analyzed using descriptive statistics and qualitative analyses. RESULTS: Seventy-two of 95 (76%) faculty members responded (40% women, 38% men, and 22% gender undisclosed). Virtual lectures supported the speakers "a lot" to "extremely" with the following goals: enhancing one's reputation and credibility (76%), networking (70%), receiving feedback (63%), and advancing prospects for promotion (59%). Virtual programs also increased the speakers' sense of accomplishment (70%) and professional optimism (61%) by at least "a lot," including instructors and assistant professors who previously had difficulty obtaining invitations to speak outside their institution. Many respondents had declined prior invitations to speak in-person due to clinical workload (66%) and family care responsibilities (58%). Previous opportunities to lecture in-person were also refused due to finances (39%), teaching (26%), and research (19%) requirements, personal medical conditions or disabilities (9%), and religious obligations (5%). Promotion was a stronger motivating factor to lecture virtually for instructors and assistant professors than for associate and full professors. By contrast, disseminating work and ideas was a stronger motivator for associate and full professors. Associate and full professors also reported greater improvement in work-related well-being than earlier career faculty from the virtual lecture experience. Very few differences were found by gender. CONCLUSIONS: Virtual lecture programs support faculty who might not otherwise have the opportunity to lecture in-person due to multiple constraints. To increase the dissemination of scholarly work and expand opportunities to all faculty, virtual lectures should continue even as in-person venues are reestablished.

Potential Role for Diet in Mediating the Association of Olfactory Dysfunction and Cognitive Decline: A Nationally Representative Study.

In the context of a growing body of evidence associating olfactory dysfunction (OD) with cognitive decline, this cross-sectional study used data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) sample in order to explore the role of dietary intake in this association. Leveraging a nationally representative sample of U.S. adults aged 60 years and older, this study analyzed dietary patterns using exploratory factor analysis. OD was categorized based on the NHANES Pocket Smell Test, and cognitive function was measured with a battery of tests. Survey-weighted multivariable regressions and causal mediation analysis were used to examine the relationship between dietary patterns, OD, and cognitive function. Results indicated that a poor adherence to a diet rich in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs) was independently associated with both cognitive and olfactory dysfunctions, after adjusting for sociodemographic and health factors. Moreover, the relationship between OD and cognitive decline was found to be partly mediated by adherence to such a diet. This study proposes a potential link between diet, olfactory function, and cognitive decline, highlighting the role of nutritional interventions in mitigating cognitive decline, particularly in individuals with olfactory impairment.

Exploring Olfactory Dysfunction as a Marker of Frailty and Postoperative Outcomes in Head and Neck Cancer.

Importance: Olfactory dysfunction (OD) is increasingly recognized as a robust marker of frailty and mortality. Despite broad recognition of frailty as a critical component of head and neck cancer (HNC) care, there is no standardized frailty assessment. Objective: To assess the prevalence of OD and its association with frailty and postoperative outcomes in HNC. Design, Setting, and Participants: In this prospective cohort study with enrollment between February 17, 2021, to September 29, 2021, at a tertiary academic medical center, 85 eligible adult patients with primary, treatment-naive HNC of mucosal or cutaneous origin were included. Patients with a history of COVID-19, neurocognitive, or primary smell/taste disorders were excluded. Exposures: Prospective olfactory assessments (self-reported, visual analog scale [VAS] and psychophysical, University of Pennsylvania Smell Identification Test [UPSIT]) with concurrent frailty assessment (Risk Analysis Index [RAI]) were used. Olfactory-specific quality of life (QOL) was examined with brief Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). Main Outcome(s) and Measure(s): The primary outcome was the prevalence of OD as assessed by VAS (0-10, no to normal smell) and UPSIT (0-40, higher scores reflect better olfaction) and its association with frailty (RAI, 0-81, higher scores indicate greater frailty). For surgical patients, secondary outcomes were associations between OD and postoperative length of stay (LOS), 30-day postoperative outcomes, and QOD-NS (0-21, higher scores indicate worse QOL). Results: Among 51 patients with HNC (mean [SD] age, 63 [10] years; 39 [77%] male participants; 41 [80%] White participants), 24 (47%) were frail, and 4 (8%) were very frail. Despite median (IQR) self-reported olfaction by VAS of 9 (8-10), 30 (59%) patients demonstrated measured OD with psychophysical testing. No meaningful association was found between self-reported and psychophysical testing (Hodges-Lehmann, <0.001; 95% CI, -2 to 1); a total of 46 (90%) patients did not report decreased olfaction-specific QOL. Median UPSIT scores were lower in frail patients (Hodges-Lehmann, 6; 95% CI, 2-12). Multivariate modeling demonstrated severe microsmia/anosmia was associated with 1.75 (95% CI, 1.09-2.80) times odds of being frail/very frail and approximately 3 days increased LOS (ß, 2.96; 95% CI, 0.29-5.62). Conclusions and Relevance: Although patients with HNC are unaware of olfactory changes, OD is common and may serve as a bellwether of frailty. In this prospective cohort study, a dose-dependent association was demonstrated between increasing degrees of OD and frailty, and the potential utility of olfaction was highlighted as a touchstone in the assessment of HNC frailty.

The Association of Multiple Sensory Impairment and Telomere Length: The Health ABC Study.

OBJECTIVES: The objective of this study was to characterize the associations of sensory impairments, including olfaction (OI), vision (VI), hearing (HI), and touch (TI), with telomere length (TL) in a group of community-dwelling older adults who participated in the Health ABC study. METHODS: Across 1603 participants, OI was classified with the Brief Smell Identification Test (<11), HI with pure-tone averages (<25 dB), VI with visual acuity (20/50 or worse), and TI with monofilament testing (inability to detect three of four touches). Shorter TL was defined as the lowest quartile of sample TLs. Adjusted multivariable regressions were used to examine the cross-sectional association between the modality, severity, and number of sensory impairments with TL. RESULTS: Participants had an average age of 77.4 ± 2.84 years, and 89.7% (n = 1438) had at least one or more sensory impairments. Severe OI (odds ratio [OR] = 1.73, 95% confidence interval [CI] = [1.19, 2.6]) was independently associated with increased odds of shorter TL. Additionally, having one (OR = 2.79, 95% CI = [1.69, 4.70]), two (OR = 2.5, 95% CI = [1.51, 4.26]), three (OR = 3.04, 95% CI = [1.79, 5.36]), or four impairments (OR = 3.72, 95% CI = [1.52, 7.33]) was associated with increased odds of shorter TL in a dose-dependent manner. CONCLUSION: Severe OI and TI appear to be particularly robust markers of shortened TL. Additionally, multiple sensory impairment is strongly associated with shortened TL, suggesting that sensory dysfunction may represent a unique biomarker of unhealthy aging. LEVEL OF EVIDENCE: Level II Laryngoscope, 133:3132-3138, 2023.