Medicine and Pharmacology

Abstract: Background/Objectives: Hidden hearing loss (HHL) is defined as occurring when patients report difficulty processing auditory information despite having a normal audiogram at conventional frequencies (250-8000 Hz). Due to the lack of a standard physiological indicator for HHL, this study proposes a potential diagnostic method based on the broadband (BBN) advantage. We hypothesized that the BBN advantage is reduced in ears with underlying cochlear or auditory nerve dysfunction, despite having normal hearing thresholds at conventional frequencies of 250–8000 Hz. Methods: A Bayesian random-intercept linear regression model was employed to investigate this association. The primary outcome was the mean difference in acoustic reflex threshold (ART). The primary exposures were the three groups: normal controls (control), music students (exposed to prolonged noise), and the symptomatic group (participants who complained of difficulty hearing). Results: The sample included 67 participants and 133 ears. Comparisons suggested that symptomatic ears showed a greater loss of BBN acoustic reflex advantage than normal control ears (β = -6.99, 95% CI [-12.60, -1.46], Pr(β < 0) = 0.99) after adjusting for age and sex. ROC analysis reported that the AvgDiff had 71% sensitivity and 69% specificity. Conclusions: The hypothesis is supported, and this sheds light on the potential of using the loss of BBN acoustic reflex advantage as a potential physiological marker for HHL.

Abstract: The study considers the hypothesis (supported by a compatible theory) that the vibratory test (SVIN) corresponds to unilateral weakness (UW) in caloric tests and that the head-shaking test (HST) is directly proportional to directional preponderance (DP). A group of 76 patients with vestibular deficits at various stages of compensation, confirmed by bithermal tests using the Fitzgerald-Hallpike technique and evaluated with Jongkees' formulas, was studied and compared with SVIN and HST results. The statistical study shows a marked correlation between SVIN and UW and between HST and DP. At the same time, the cross-correlations between SVIN and DP, and between HST and UW, are significantly weaker, confirming the hypothesis. It is concluded that, in cases where caloric testing is not considered necessary, these two bedside functional tests can give a precise idea of the results of caloric testing and that this interpretation can highlight the great clinical potential of SVIN and HST performed in combination.

Abstract: Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is charac-terized by epithelial remodeling, impaired mucociliary clearance, and altered nitric oxide (NO) metabolism. However, the cell type–specific mechanisms of NO production and the functional roles of nitric oxide synthase (NOS) isoforms in sinonasal epithelial cells remain unclear. This study investigated NO production dynamics in air–liquid in-terface (ALI) cultures of human sinonasal epithelial cells. Methods: Human sinonasal epithelial cells were differentiated under ALI conditions. Expression of inducible NOS (iNOS) and endothelial NOS (eNOS) was analyzed by quantitative RT-PCR. Intracellular NO production was evaluated using the NO-sensitive fluorescent probe DAF-FM com-bined with laser scanning confocal microscopy. Cell type–specific NO production was examined in ciliated and non-ciliated epithelial cells using the NOS inhibitors L-NAME and 1400W. Results: CRSwNP tissues demonstrated significantly increased iNOS ex-pression and elevated iNOS/eNOS ratios compared with controls, whereas eNOS ex-pression showed no significant difference. ALI cultures successfully reproduced dif-ferentiated sinonasal epithelium containing ciliated and basal cells. DAF-FM fluores-cence revealed significantly greater NO production in ciliated epithelial cells than in non-ciliated cells. Non-selective NOS inhibition by L-NAME markedly suppressed NO production in both cell types, whereas selective iNOS inhibition by 1400W reduced but did not abolish NO production in ciliated cells. Conclusions: NO production mecha-nisms differ according to sinonasal epithelial cell subtype. Ciliated epithelial cells maintain both eNOS- and iNOS-dependent NO production, whereas non-ciliated cells predominantly rely on iNOS-derived NO. Dysregulated spatial NO signaling associated with ciliated cell loss may contribute to epithelial dysfunction and chronic inflammation in CRSwNP.

Abstract: Objective fitting measures offer a means to circumvent the subjectivity of cochlea implant programming, with the stapedius reflex representing one robust predictor of the maxi-mum comfortable loudness level. With the present study, it was investigated whether long-term electromyographic measurements of the stapedius muscle using implanted electrodes are feasible. In nine sheep, myoelectrical activities were recorded intraopera-tively and synchronized with middle-ear admittance as a reference signal. For acoustic stimulation pure tones with different frequencies were used. The electrodes were placed at the stapedius muscle surface after exposing it via the retrofacial approach. Measurements were performed over a period of six months. The treated muscles were subsequently ex-cised, cut and examined histologically. Long-term electromyographic measurements were possible. No signs of atrophy were found in the muscles examined. However, the histo-logical section series showed a clear division of the muscle from proximal to distal. The ratio between tendon and muscle fibers being most pronounced in favor of the muscle fi-bers in the proximal section. The integration of an electromyography-based measurement method for the objective determination of the stapedius reflex threshold and thus, for the long-term adjustment of cochlear implants, appears fundamentally possible and could potentially enable largely autonomous fitting of the implants.

Abstract: Background: The mucosal surfaces from the anterior nares to the anal canal are lined by a continuous liquid layer studied extensively in regional isolation — as airway surface liquid in pulmonary physiology, gastric mucus in gastroenterology, and nasal mucus in rhinology — but never conceptualized as a unified physiological system. Framework: This paper proposes that this continuous mucosal liquid layer functions as a "mucosal river" serving three critical roles: physical barrier protection, immune transport of secretory immunoglobulins and antimicrobial peptides, and maintenance of the hydrated microenvironment required for commensal microbial homeostasis. Nasal cilia function as the initial pump generating downstream momentum; pharyngeal and digestive peristalsis maintain flow; pulmonary cilia serve as tributary pumps feeding the main channel against gravity. The adenoid crypts function as immunological canyons — narrow, deep channels that use Venturi-effect flow dynamics and M-cell-mediated antigen transport to actively deliver antigen-laden mucus into immune processing centers. Waldeyer's ring forms a 360-degree antigen trap through which the river cannot pass without immune surveillance, and the first breath represents an immunological ignition event initiating adaptive immunity. Hypotheses: The framework generates testable predictions regarding pepsin as a pathologic passenger ascending the river against flow to cause posterior-predominant sinonasal inflammation, systemic dehydration disrupting the river through mucus hyperconcentration and ciliary compression, cigarette smoke damming the river via acquired CFTR dysfunction, and an antibiotic-dehydration "double hit" synergistically compromising mucosal barrier integrity. Each prediction is paired with a specific experimental design for validation. Conclusion: Understanding the mucosal river as a unified system may reshape approaches to chronic inflammatory diseases of the airway and digestive tract.

Abstract: Bitter taste receptors (T2Rs), specifically T2R38, are present in the respiratory epithelium and react with bacterial quorum-sensing molecules to induce an innate immunity response. Although T2R38 polymorphisms have been correlated with susceptibility to chronic rhinosinusitis (CRS), they have not yet been explored in odontogenic rhinosinusitis (ORS), a distinct form of CRS with particular microbial and inflammatory features. Objectives: We aim to establish a proof-of-concept methodology for investigating T2R38 genetic variants in ORS using direct maxillary sinus tissue analysis and demonstrate the feasibility of this translational approach. Methods: We conducted a prospective case-control study of 36 ORS patients and 37 controls undergoing septoplasty without sinonasal disease. Maxillary sinus mucosal biopsies were obtained intraoperatively with informed consent. Genomic DNA was extracted using the PureLink Genomic DNA Mini Kit and quantified via NanoDrop spectrophotometry. T2R38 haplotypes were determined and classified as taster (PAV/PAV), non-taster (AVI/AVI), or intermediate (PAV/AVI) phenotype. Results: T2R38 phenotype distributions between ORS patients and controls were: tasters 11.1% vs 18.9%, non-tasters 27.8% vs 18.9%, and intermediate phenotypes 50.0% vs 37.8%, respectively. Statistical analysis revealed no significant association between T2R38 phenotypes and ORS susceptibility (Pearson χ² = 0.372, df = 1, p = 0.542; Fisher's exact test p = 0.595). The effect size was minimal (φ = 0.07). Non-taster phenotype showed a non-significant trend toward higher prevalence in ORS patients (OR = 1.4, 95% CI: 0.5–3.9, p > 0.5), though this finding lacks statistical power given the sample size. Conclusion: This proof-of-concept study successfully demonstrates the feasibility of T2R38 genotyping from maxillary sinus mucosa in ORS patients, establishing a novel methodological framework for investigating genetic factors in odontogenic sinonasal disease. While preliminary findings suggest potential phenotype differences (non-taster prevalence: 27.8% vs 18.9%), the study's primary value lies in validating the translational approach and informing power calculations for definitive multicenter investigations. This methodology provides the foundation for future studies to elucidate the role of taste receptor genetics in ORS pathogenesis and potentially guide personalized therapeutic strategies.

Abstract: Objective: To describe a rare case of subglottic foreign body (FB) impaction in an adult, leading to subglottic stenosis, and to evaluate the effectiveness of Suspension Microlaryn-goscopy (SML) as a minimally invasive technique for its management. Methods: A single case of subglottic FB in an adult was managed using endotracheal intubation and SML. This approach allowed for precise visualization and extraction of the FB. When granula-tion tissue or mucosal overgrowth was encountered, targeted resection and controlled cauterization were performed. Results: The SML technique provided excellent exposure to the subglottic region, enabling safe removal of the FB while minimizing trauma to the surrounding tissues. Postoperative follow-up demonstrated successful resolution of sub-glottic stenosis without complications, confirming the efficacy and safety of this approach. Conclusions: Subglottic FB impaction is an exceptionally rare occurrence in adults, posing diagnostic and therapeutic challenges. SML is a valuable tool for managing such cases, offering precise visualization, safe FB extraction, and effective management of complica-tions such as granulation tissue, ensuring optimal patient outcomes.

Abstract: Head and neck lymphedema (HNL) is a common complication of head and neck cancer (HNC) treatment, with upwards of 70-90% of patients suffering from this condition. Surgery and radiation, the backbones of HNC treatment, disrupt lymphatic networks through direct injury and fibrosis, leading to accumulation of lymphatic fluid in interstitial spaces. This causes swelling of external and internal structures, leading to decreased quality of life, cosmetic distress, social withdrawal, and functional deficits such as dys-phagia, dysphonia, and reduced cervical mobility. Having a reliable assessment tool is key to diagnosing and monitoring HNL; however, few tools specific to HNL exist. Cur-rently, the cornerstone of HNL treatment is conservative management with complete decongestive therapy, which shows mixed efficacy. There is a lack of surgical options as well as prophylactic interventions. Imaging of lymphatic channels is a promising mo-dality that can help providers guide and plan personalized therapies. This paper provides a narrative review of the pathophysiology, assessment, and prevention of HNL, high-lighting future directions for improvement.

Abstract: Background/Objectives: Pediatric tracheotomy has evolved from an emergency procedure for acute infections to a planned intervention for chronic conditions requiring prolonged airway support. This study aims to describe the clinical characteristics, indications, and outcomes of pediatric tracheotomy over a 21-year period at a tertiary care center. Methods: A retrospective observational case series was conducted including 246 pediatric patients (0–18 years) who underwent tracheotomy between 2004 and 2024. Data were collected from medical records and included demographics, indications, procedural details, complications, decannulation, and mortality. Patients were categorized into airway obstruction (AO) and respiratory support (RS) groups. Statistical analyses were performed using the Mann–Whitney U test, Chi-square and Fisher’s exact test. Results: A significant increase in tracheotomy procedures was observed over time. Respiratory support was the predominant indication (75.2%), mainly due to neurological disorders, while airway obstruction accounted for 24.8%. Patients in the AO group were significantly younger and more likely to undergo urgent procedures (p < 0.001). Complication rates were comparable between groups (AO 16.4% vs. RS 21.1%; p = 0.295). Decannulation was significantly more successful in the AO group (16.4% vs. 5.4%; p = 0.012). Mortality did not differ significantly between groups and was associated with underlying comorbidities. Conclusions: Pediatric tracheotomy is increasingly performed for chronic respiratory support. While procedural safety is high, outcomes vary by indication, with better decannulation rates in airway obstruction cases. Multidisciplinary, individualized management is essential for optimizing patient outcomes.

Abstract: Background: Neo-adjuvant chemotherapy (NACT) has shown promise in reducing tumor size and in rendering onco-logically safe resections in borderline resectable head and neck cancers. In patients with squamous cell carcinoma (SCC) of the tongue, NACT may facilitate less extensive surgeries and preserve critical structures, one such being the hypo-glossal nerve. Methods: A retrospective audit was conducted of patients with tongue SCC who underwent NACT followed by surgery at our centre between May 2022 and December 2024. Outcomes of interest included tumor response, hypoglossal nerve preservation, and pathological response. Results: 31 patients requiring potential bilateral hypoglossal nerve sacrifice having a median age of 48 years were included in the analysis. All patients presented with advanced stage (Stage IVa/IVb/III) and 80.6% had clinical nodal involvement. Following NACT, 45.2% (14/31) of these patients showed sufficient tumor regression to allow for unilateral hypoglossal nerve preservation. The most common chemo-therapy regimen was DCF, with 83.9% of patients experiencing no grade III/IV toxicities. Post-NACT histopathology showed that 32.3% of patients had no residual tumor, and 93.6% achieved uninvolved margins. 32.3% of the patients achieved complete regression (Mandard Grade I). Conclusion: Functional preservation of at least one hypoglossal nerve in advanced OSCC of the tongue is feasible. In this study hypoglossal nerve preservation in nearly half of the patients with midline-crossing tumors was achieved by NACT. The favourable histopathological outcomes and manageable toxicity profiles suggest that NACT may be a viable approach for improving functional outcomes in locally advanced squamous cell carcinoma of the tongue.

Abstract: Background: Emerging evidence suggests that metabolic and lifestyle factors may contribute to the onset and progression of tinnitus. Nutritional deficiencies, obesity, and sedentary behavior have been hypothesized to modulate auditory function and neural excitability. This scoping review aimed to map and summarize the available evidence on the associations between dietary factors, nutrient intake, body mass index (BMI), obesity, and physical activity with the risk, severity, and management of tinnitus. Methods: A scoping review was conducted following the PRISMA-ScR reporting guidelines. A comprehensive search of PubMed, Web of Science, and Cochrane Library databases was performed. Eligible designs included randomized controlled trials, cohort, case control, and cross-sectional studies. Data were extracted and synthesized narratively due to methodological heterogeneity. Results: Twenty-four studies met the inclusion criteria. Higher protein intake and favorable lipid profiles were associated with reduced tinnitus risk and severity. Micronutrient deficiencies, particularly vitamins B2, B3, D3, B12, zinc, and iron, were consistently associated with greater symptom burden. Evidence on antioxidant supplementation was inconclusive, with some trials reporting symptomatic improvement and others showing no effect. Elevated BMI and obesity were associated with both tinnitus onset and greater symptom severity. Importantly, randomized trials reported that structured weightloss and physical activity programs were associated with reduced tinnitus severity and improved quality of life. Conclusions: The available literature suggests potential associations between dietary patterns, micronutrient status, obesity, and physical activity with tinnitus risk and symptom severity. Although the current evidence is largely observational, some interventional studies indicate that lifestyle based approaches, including weight management and increased physical activity, may contribute to improvements in tinnitus related symptoms and quality of life.

Abstract: GJB2-associated hearing loss is the most common form of non-syndromic hereditary deafness worldwide. However, it exhibits significant heterogeneity in terms of both clinical presentation and biological basis. This review focuses on mechanism-oriented therapeutic strategies for GJB2-associated hearing loss, investigating how different types of GJB2 variants correspond to distinct clinical phenotypes and underlying pathogenic mechanisms, and aims to determine appropriate treatments. Current evidence suggests that GJB2-associated hearing loss is not solely caused by channel dysfunction resulting from gap junction defects, but rather the result of multiple pathological processes, including impaired GJB2 transcriptional regulation, cochlear developmental abnormalities, sensory epithelial degeneration and secondary damage pathways such as inflammation. Consequently, emerging therapeutic approaches can be viewed as interventions targeting specific mechanisms, including gene therapy, restoration of protein transport and pharmacological modulation of damage to the cochlear microenvironment. Overall, this review highlights the importance of targeting therapeutic strategies at specific GJB2 variants, the underlying pathogenic mechanisms and the timing of intervention. This improves our understanding of the mechanisms underlying GJB2-associated hearing loss and the development of precision therapies.

Abstract: Background/Objectives: Diving exposure can cause auditory injury involving both middle and inner ear structures. Inner ear barotrauma (IEB) and inner ear decompression sickness (IEDCS) are the major inner ear disorders and frequently present with auditory and vestibular symptoms. This study examined how diving characteristics relate to patterns of auditory trauma. Methods: A retrospective chart review of 30 patients with 36 affected ears was performed. Diving depth, clinical manifestations, and treatment responses were analyzed to identify factors influencing relatively prognosis. Results: Diving depth was the important factor associated with symptom severity and type of injury. Dives deeper than 30 meters of sea water were linked to a higher incidence of sudden sensorineural hearing loss and vertigo. In contrast, transient symptoms with minimal objective abnormalities were typically observed in shallow dives. Patients with concomitant decompression sickness (DCS) showed poorer auditory and vestibular recovery following hyperbaric oxygen therapy, while those without DCS showed better hearing improvement. Vertigo was observed in 80% of IEB cases and 66.7% of IEDCS cases. Hearing recovery was more frequently observed in cases presenting with middle ear symptoms, suggesting a relatively favorable prognosis for IEB compared with IEDCS. Conclusions: Diving depth and DCS involvement may play a role in the severity and prognosis of diving-related inner ear injury. IEB generally demonstrates better auditory outcomes than IEDCS. Further studies with larger cohorts are needed to refine prognostic indicators and optimize management strategies.

Abstract: Background/Objectives: Auditory neuropathy spectrum disorder (ANSD) is a well-established hearing disorder in the pediatric population and is estimated to account for at least 10% of children with sensorineural hearing loss. Compared to auditory function, vestibular function in children with ANSD has not been well described in the past. The purpose of this study is to examine vestibular testing results in children with ANSD and to better characterize vestibular dysfunction in these children. Methods: A retrospective review of vestibular laboratory testing results was conducted in pediatric patients diagnosed with ANSD. Vestibular evaluation included vestibular evoked myogenic potential (VEMP), rotary chair test, video head impulse test (vHIT), and videonystagmography (VNG). Results: A total of 30 pediatric patients with ANSD were identified, including 18 boys and 12 girls, with a mean age of 4.6 years. Bilateral ANSD was found in 24 cases, while 6 cases were unilateral. Etiologies of ANSD included a history of hyperbilirubinemia in infancy, cochlear nerve dysplasia, and genetic-related conditions, etc. Vestibular dysfunction was found in 12 cases, as indicated by at least one abnormal outcome in VEMP, vHIT, or rotary chair testing. Nineteen children were cochlear implant candidates and eventually underwent unilateral or bilateral implantation. Conclusions: Vestibular dysfunction is significant in pediatric patients with ANSD, and vestibular outcomes appear to be associated with underlying etiologies. Formal vestibular evaluation is necessary to identify such vestibular losses, and these findings will be helpful to guide clinical management and rehabilitation strategies for these children.

Abstract: Background/Objectives: Facial paralysis is a debilitating condition managed with dy-namic (e.g., gracilis or temporalis transfer) and static (e.g., fascial sling) surgical inter-ventions. This study evaluates demographic factors associated with procedure selection and revision pathways. Methods: Using the TriNetX database, we identified patients with facial paralysis undergoing gracilis transfer, temporalis transfer, or fascial sling procedures. Demographics (sex, ethnicity, race) were compared across procedure types, and revision patterns were analyzed. Results: Dynamic procedures were more common among female patients (35.5% vs 23.8%, OR=1.76, 95% CI [1.47-2.11], p< 0.001). Non-Hispanic patients were less likely to undergo dynamic procedures than Hispanic patients (OR=0.36, 95% CI [0.26-0.50], p< 0.001), while non-White patients were more likely than White patients (OR=1.58, 95% CI [1.25-1.99], p< 0.001). Among patients un-dergoing initial static procedures, White patients were less likely to transition to dynamic revision compared to non-White patients (OR=0.134, 95% CI [0.07-0.228], p< 0.001). Gra-cilis transfer demonstrated the highest revision rate among procedures studied. Con-clusions: Demographic differences exist in both initial procedure selection and revision pathways for facial reanimation. These findings highlight potential disparities in surgical management and underscore the need to further investigate structural drivers of these differences.

Abstract:

Background/Objectives: The cochlea and vestibular organs develop concurrently during embryogenesis and share anatomical and functional pathways. As a result, congenital factors affecting the vestibulocochlear system may impair both hearing and vestibular function. Despite this, the relationship between congenital bilateral sensorineural hearing loss (SNHL) and vestibular dysfunction remains insufficiently defined. This study evaluated vestibular function in patients with congenital bilateral SNHL and investigated the association between hearing loss severity and vestibular function. Methods: A total of 202 participants aged 7–31 years were enrolled, including 102 patients with congenital bilateral SNHL and 100 healthy controls. Vestibular function was assessed using videonystagmography during three tests: sinusoidal harmonic acceleration (SHA) rotational testing, the video head impulse test (vHIT), and caloric testing according to the Fitzgerald–Hallpike protocol. Statistical analyses compared vestibular parameters between groups and assessed correlations with hearing loss severity. Results: Patients with congenital bilateral SNHL exhibited significantly lower vestibulo-ocular reflex (VOR) values in the SHA test compared to controls. Greater hearing loss severity was associated with lower VOR gain values. No statistically significant differences were observed between groups in caloric test results or vHIT VOR gain values. However, corrective saccades during vHIT were identified exclusively in patients with hearing loss and occurred in approximately 15% of cases. Furthermore, the age of independent walking was significantly delayed in the study group compared to controls. Conclusions: Congenital bilateral SNHL is associated with vestibular dysfunction, as evidenced by abnormal SHA test results and the presence of corrective saccades in vHIT. These patients may also experience delayed motor development. The findings underscore the importance of comprehensive vestibular assessment in individuals with congenital hearing loss.

Abstract: Background: Vestibular migraine (VM) is a common cause of episodic vertigo, yet its diagnosis remains primarily clinical and is often complicated by the absence of reliable objective biomarkers. Pupillary nystagmus, reflecting spontaneous oscillations of pupil diameter, has been proposed as a potential clinical sign of VM, but its quantitative characterization remains limited. Objective: To evaluate the diagnostic value of pupillary nystagmus in VM and to provide a quantitative assessment using infrared pupillometry. Methods: In this case–control study, 69 patients with vestibular migraine and 13 healthy controls underwent comprehensive neuro-otological evaluation, including vestibular testing and pupillometric assessment. Pupillary activity was recorded using a dedicated infrared pupillometer, and oscillatory dynamics were quantified using the Pupillary Unrest Activity Level (PUAL), derived through spectral analysis (Larson–Neice algorithm). Statistical comparisons were performed using non-parametric methods. Results: PUAL values differed significantly between VM patients and controls (Wilcoxon test, p = 2.265 × 10⁻¹¹), demonstrating a clear separation between groups. A cut-off value of 0.393 was identified as the upper limit of normality, suggesting that elevated PUAL values may indicate vestibular migraine. Conclusions: Pupillary nystagmus represents a clinically accessible sign that can be objectively quantified through infrared pupillometry. The PUAL index provides a measurable parameter reflecting altered vestibulo–autonomic dynamics in VM and may serve as a promising neuro-otological biomarker. The integration of pupillometric analysis with clinical evaluation may improve diagnostic accuracy and support the development of objective diagnostic tools in vestibular migraine.

Abstract: Objective: To propose Posterior Sinonasal Syndrome (PSS) as the etiological precursor to a defined subset of chronic rhinosinusitis (CRS), establish pepsin as a field carcinogen across the upper aerodigestive mucosal surface, and define the biological imperative for mucosal-preserving surgery in PSS-CRS patients. Methods: Synthesis of peer-reviewed evidence across four domains: pepsin endocytosis mechanisms in upper airway epithelium; pepsin detection in sinonasal, nasopharyngeal, and middle ear tissue; epidemiological trends in pediatric upper airway disease; and clinical outcomes in refractory CRS. Evidence is stratified as established, strongly inferred, or proposed requiring confirmatory study. Results: Pepsin, delivered via laryngopharyngeal reflux along a defined anatomical concentration gradient, produces receptor-mediated intracellular injury in posterior nasal epithelium — a mechanism established in laryngeal cells and strongly inferred in nasal cells. This injury lowers the posterior nasal mucosal inflammatory threshold, creating PSS as a priming state preceding clinical CRS. Pepsin has been detected within malignant tissue at two anatomically distinct sites: laryngeal and hypopharyngeal carcinoma, and nasopharyngeal carcinoma in 85.7% of cases versus 17.2% of controls — the two-site molecular fingerprint of a field carcinogen across the full upper aerodigestive surface. Pepsin detection in 83% of pediatric middle ear effusions and its correlation with adenoid hypertrophy grade establish that this process begins in childhood. PSS represents a third inflammatory driver of CRS, independent of allergy and anatomy, unrecognized by the 2025 AAO-HNS guideline. Five confirmatory studies and a nasal lavage pepsin assay validation pathway are defined. Conclusion: PSS is the etiological precursor to a misidentified subset of treatment-resistant CRS. Pepsin is both the primary driver of posterior nasal mucosal priming and a field carcinogen across the upper aerodigestive surface. Aggressive tissue-resecting FESS in this population is biologically counterproductive. The confirmatory studies are named, the clinical tools are within reach, and the patients are in rhinology practices now.

Abstract: Background: Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo and is diagnosed clinically, yet many patients initially present in primary care. Early identification may optimize referral and management. Objective: To perform a pilot Phase 1 validation of the BPPV-SQ, a brief screening questionnaire designed for future use in general practice, assessing its ability to identify BPPV, suggest canal involvement, and support progression to Phase 2 validation. Methods: In this prospective observational study, 108 patients with positional vertigo and no neurological signs were evaluated in a specialist setting. The 7-item dichotomous questionnaire (score 0–3 for diagnostic core) was administered prior to bedside examination, which served as the reference standard. Results: Confirmed BPPV increased with higher scores. Among patients with score 3, BPPV was confirmed in 73.5%, with 69.4% lateralization concordance. Lower scores (0–1) were associated with low confirmation rates (14.3%). Conclusions: In this pilot Phase 1 validation, the BPPV-SQ demonstrated score-dependent diagnostic reliability and acceptable lateralization agreement in high-score patients, supporting progression to Phase 2 validation in primary care.

Abstract: Background: Chronic rhinosinusitis (CRS) and obstructive sleep apnea (OSA) frequently coexist, sharing inflammatory and anatomical pathways consistent with the "United Airway" This review examines the synergistic dysfunction linking these conditions. Methods: We conducted a comprehensive review synthesizing literature on the epidemiology, pathophysiology—including cytokine cascades and microbiome dysbiosis—and therapeutic outcomes of surgical and medical interventions for comorbid CRS and OSA. Results: Large-scale datasets confirm CRS as an independent risk factor for OSA. Pathophysiologically, the disorders are linked by mechanical obstruction, systemic cytokine spillover (IL-6, TNF-a), and nasopharyngeal microbiome dysbiosis (e.g., S. aureus biofilms). Therapeutically, Endoscopic Sinus Surgery (ESS) significantly improves subjective sleep quality (SNOT-22) and reduces CPAP pressure requirements, although it yields only trivial reductions in the Apnea-Hypopnea Index (AHI). Biologics like Dupilumab demonstrate rapid efficacy in improving sleep domains for CRS with nasal polyps. Conclusion: CRS and OSA are inextricably linked via mechanical and inflammatory mechanisms. A holistic "United Airway" management approach—optimizing nasal patency to facilitate CPAP adherence and reduce systemic inflammatory burden—is critical for improving patient outcomes.