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Case Report
Medicine and Pharmacology
Otolaryngology

Ioannis Chatzistefanou

,

Sophia Tsokkou

,

Sofia Karachrysafi

,

Kyriaki Papadopoulou

,

Ioannis Konstantinidis

,

Alexandros Liatsos

,

Vasiliki Theodorou

,

Antonia Sioga

,

Georgia-Alexandra Spyropoulou

,

Vasileios Petsinis

+1 authors

Abstract: Background/Objectives: Post-traumatic nasal pyramid reconstruction is challenging in patients with severe deformity and exhausted autologous graft options, particularly after multiple failed surgeries. Custom-made titanium implants may offer precise structural support, but data on their mucosal integration and ultrastructural tissue response in nasal reconstruction are lacking. The aim of this study is to describe the first case of nasal pyramid reconstruction using an IPS (Individual Patient Solutions) custom-made titanium implant and to evaluate peri-implant tissue response with transmission electron microscopy (TEM). Methods: A 50-year-old male military personnel with long-standing saddle-nose deformity, nasal obstruction, and prior failed graft-based reconstructions underwent open rhinoplasty with placement of a patient-specific titanium implant designed with three-dimensional virtual surgical planning. The implant reconstructed the nasal dorsum from nasion to tip and was stabilized with cortical screws; an additional thin titanium plate was used for tip support. Intraoperative biopsies of nasal mucosa and adjacent connective tissue were processed for TEM to assess epithelial, stromal, vascular, and implant–tissue interface characteristics. Results: Clinically, nasal airway patency improved immediately after packing removal, with restoration of nasal contour and stable functional and aesthetic outcomes at 24-month follow-up without complications. Ultra-structurally, the respiratory epithelium showed preserved stratification, intact basal and ciliated cells, normal nuclei and mitochondria, and organized extracellular matrix closely opposed to discrete titanium particles, without granulomatous foreign-body reaction, dense inflammatory infiltrate, or fibrotic encapsulation. Focal ciliary damage, cytoplasmic vacuolization, lamina propria thickening, and vascular elastic lamina remodeling were interpreted as adaptive or transient stress-related changes rather than chronic implant toxicity. Conclusions: Custom-made IPS titanium implants can provide stable structural support, satisfactory functional and aesthetic outcomes, and a well-tolerated mucosal interface in complex post-traumatic nasal pyramid reconstruction after failed graft-based surgeries. Ultrastructural analysis with TEM supports their biocompatibility, showing predominantly preserved epithelial and stromal architecture with only focal, adaptive stress-related changes rather than chronic implant-related toxicity.

Article
Medicine and Pharmacology
Otolaryngology

Fabian Paperlein

,

Markus Blaurock

,

Benjamin Fenske

,

Hendrik Möller

,

Verena Wagner

,

Lisa Schneider

,

Tatyana Ivanovska

,

Chia-Jung Busch

,

Christian Scharf

,

Achim Georg Beule

Abstract: Manual sinus magnetic resonance imaging (MRI) annotations are valuable but difficult to scale. We evaluated PARASIDE, an nnU-Net-based framework for automated sinus compartment segmentation on T1-weighted MRI, against independent manual and radiological assessments from the Study of Health in Pomerania. We linked 12,867 sinus sides from 3,217 participants. Analyses defined before outcome modelling evaluated soft-tissue fraction for healthy versus abnormal sides, inferior soft-tissue centroid position for basal versus apical maxillary opacification, and total frontal volume for aplasia/hypoplasia. Soft-tissue fraction discriminated abnormal sides in frontal (area under the receiver operating characteristic curve [AUC] 0.850, 95% confidence interval [CI] 0.834–0.866) and maxillary sinuses (AUC 0.828, 95% CI 0.818–0.839). The topographic marker discriminated basal from apical opacification (AUC 0.746 left; 0.782 right). Total frontal volume discriminated historical aplasia/hypoplasia ratings (AUC 0.988); a previously established near-absence threshold was highly specific but insensitive. Historical maxillary volumetric masks showed strong overlap and volume association for total and aerated compartments, whereas frontal comparisons reflected a predefined caudal boundary. The historical polyposis rating category remained weakly separable, and surgery-related features corresponded more closely to visible postoperative morphology than to self-reported surgery. PARASIDE reproduced anatomically measurable MRI phenotypes, whereas morphology-specific constructs required dedicated reference standards.

Review
Medicine and Pharmacology
Otolaryngology

Jindie Hu

,

Chenyang Kong

,

Yu Sun

Abstract: Hearing and vision are the most important sensory functions. Genetic studies have revealed that specific genetic mutations can concurrently induce auditory and visual dysfunction. The comorbid deafness-blindness prevent mutual sensory compensation, thereby severely delaying speech, cognitive, and intellectual development in affected pediatric patients and imposing a profound burden on their families. In this review, we summarize the currently identified genes that cause hearing and vision impairments and classify them based on their pathological mechanisms. Furthermore, recent advances in gene therapy have brought new hope for the definitive treatment of genetic hearing loss and visual impairment, and relevant clinical trials have demonstrated promising therapeutic efficacy. Therefore, we also summarize the latest progress of gene therapy and ongoing clinical trial programs targeting these otooculopathies, aiming to provide references and basis for the subsequent treatment of comorbid auditory and visual dysfunctions.

Article
Medicine and Pharmacology
Otolaryngology

Gianluca Savoia

,

Sarah B. Payne

,

Matthew Vaitzner

,

Saruchi Bandargal

,

Michael Hier

,

Marco A. Mascarella

,

Keith Richardson

,

Alex Mlynarek

,

Nader Sadeghi

,

Sabrina Daniela Silva Wurzba

+6 authors

Abstract: Background/Objectives: Since 2021, indeterminate thyroid nodules have been routinely assessed using molecular testing through Quebec’s provincial ThyroSeq v3 pilot project. The primary objective of our study was to compare the molecular and clinicopathological characteristics of Bethesda III and Bethesda IV thyroid nodules evaluated through the pilot project. The secondary objective was to assess the program’s economic impact. Methods: This retrospective study included 934 patients from two McGill University teaching hospitals in Quebec, comprising 593 Bethesda III and 341 Bethesda IV nodules that underwent molecular testing between 2021 and 2025. Eligible nodules were TI-RADS 3 or 4, measured 1–4 cm, and Bethesda III nodules required two consecutive cytology results before testing. Clinicopathological characteristics, histopathological diagnoses, molecular findings, and mutational profiles were analyzed. A projected 10-year cost analysis was also performed. Results: Of the 934 nodules tested, 280 demonstrated a genetic alteration. The risk of malignancy among surgically resected ThyroSeq v3-positive Bethesda III and IV nodules was 68% and 78%, respectively. Bethesda IV nodules demonstrated significantly greater vascular invasion (p = 0.029) and prevalence of oncocytic carcinomas (p = 0.010). Molecular testing was associated with an estimated CAD 1.49 million reduction in healthcare costs over 10 years. Conclusions: Although Bethesda IV nodules exhibited more oncocytic carcinomas and invasion, molecular mutation class distribution and the prevalence of aggressive pathological features were similar between Bethesda categories. Together with the demonstrated economic savings, these findings support continued implementation of publicly funded ThyroSeq v3 testing to improve management of indeterminate thyroid nodules while reducing unnecessary surgery.

Article
Medicine and Pharmacology
Otolaryngology

Dominik Pawlicki

,

Marta Gamrot-Wrzoł

,

Olga Karłowska-Bijak

,

Tomasz Stącel

,

Michał Napierała

,

Maciej Misiołek

,

Paweł Sowa

Abstract: Background: Effective voice restoration after total laryngectomy relies heavily on indwelling tracheoesophageal prostheses. This study describes our institutional experience with Provox device replacements over five years. This retrospective single-center study analyzed 147 Provox voice prosthesis replacements performed in 82 laryngectomized patients between December 2024 and February 2026. We also used data from the full institutional cohort (1059 procedures and 899 intervals from May 2020 to March 2026). Mixed-effects models with a random intercept for each patient were applied to evaluate factors influencing the time interval between replacements and binary outcomes (complications, prosthesis size change, and elective vs expedited status). Results: In this retrospective single-center study, 82 laryngectomized patients underwent a total of 147 voice prosthesis replacements (June 2024–February 2026). Analysis of the full historical cohort (1059 procedures, 899 intervals from May 2020 to March 2026) revealed a mean interval between replacements of 122.5 days (95% CI 114.5–130.4). Mixed-effects linear regression showed that a higher cumulative number of prior procedures was associated with shorter subsequent intervals (β = −3.70 days per procedure; 95% CI −5.84 to −1.56; p < 0.001), whereas planned elective replacements significantly prolonged the interval (β = +35.47 days; 95% CI 15.80–55.14; p < 0.001) and were less likely to require size change (OR = 0.33; p = 0.034). The overall complication rate was low, with complications occurring in 7 out of 147 voice prosthesis replacement procedures (4.8%). Central leakage accounted for ~50% of unscheduled replacements, peripheral leakage for 25%, and dysfunction of prostheses without phonation for 19%. Complications occurred in 7 of 147 voice prosthesis replacements (4.8%). They included granulation tissue formation (n=2), prosthesis displacement (n=3), and swallowing of the prosthesis (n=2). All were managed successfully without life-threatening events, confirming the high safety of outpatient voice prosthesis exchange. Conclusions: The complication rate was notably low, with adverse events occurring in only 7 out of 147 voice prosthesis exchanges (4.8%). These findings confirm the high safety profile of outpatient voice prosthesis replacement in a tertiary ENT setting. Moreover, our results suggest that proactive, scheduled prosthesis replacements are preferable, as they are associated with significantly longer device lifetimes, a reduced need for unscheduled emergency procedures, and an overall safer clinical course.

Case Report
Medicine and Pharmacology
Otolaryngology

Raquel Muñoz-Andrés

,

Carlos Carazo-Casas

,

Mayte Herrera

,

Alfonso Santamaría-Gadea

,

Mónica Garcia-Cosio Piqueras

,

Kadir Jesús Quintero-Gil

Abstract: Background: Respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH) are uncommon benign epithelial lesions of the sinonasal tract. Their clinical and endoscopic appearance may overlap with inflammatory nasal polyps, and definitive diagnosis usually requires histopathologic examination. Case presentation: A 37-year-old man presented with several years of nasal obstruction, hyposmia, and facial pressure over the paranasal sinus regions. He had no history of asthma or previous sinonasal surgery. Nasal endoscopy revealed bilateral polypoid lesions involving the middle meatus. Computed tomography showed extensive chronic sinonasal inflammatory disease, including complete opacification of the right maxillary sinus, bilateral frontal sinus involvement, and bilateral ethmoidal opacification. The patient underwent endoscopic sinonasal surgery with bilateral uncinectomy, bilateral antrostomy, and anterior and posterior ethmoidectomy. Polypoid tissue was excised and submitted for histopathologic examination. The final diagnosis was a hybrid epithelial hamartomatous lesion with features of both REAH and SH. At the 4 and 8 week postoperative visit, the patient reported clear symptomatic improvement, mainly in nasal obstruction, smell and nasal breathing. Conclusions: Hybrid REAH and SH may clinically resemble bilateral inflammatory nasal polyposis, especially in patients with chronic rhinosinusitis. This case highlights the importance of routine histopathologic examination of sinonasal polypoid lesions after endoscopic surgery.

Article
Medicine and Pharmacology
Otolaryngology

Francesco d’Onofrio

,

Letizia Neri

,

Enrico Armato

,

Giampiero Neri

Abstract: Background/Objectives: The Head Heave Test (HHT) was proposed approximately 25 years ago for the study of the linear translational vestibulo-ocular reflex (TVOR) of utricular origin. The exam consists of delivering a series of sudden, unpredictable movements along the interaural axis of the patient's head, with the patient asked to focus on the examiner's nose in front of them. It is considered abnormal if a clear corrective saccade is observed, visible only on one side, or significantly greater on one side compared to the other. The use of HHT has not become widespread due to the difficulties in assessing corrective saccades with the naked eye. The aim of this study is to propose a simple-to-use instrumental method that clearly documents corrective saccades following translational head impulses. To exclude the possibility that compensatory saccades could be due to simultaneous stimulation of the ipsilateral Lateral Semicircular Canal (LSC), we also recorded Video Head Impulse Test (VHIT). Methods: For this purpose, 110 consecutive outpatients evaluated for balance disorders underwent HHT, which was recorded using a VHIT device. The Video Head Heave Test (VHHT), performed in this manner, enabled the easy identification of compensatory saccades. Results: The patients were divided in three groups: A) without compensatory saccades (50,9%), B) with TVOR compensatory saccades on both sides (23,6%), C) with a prevalence of saccades on one side (25,5%). We found that VHHT compensatory saccades were present in patients without LSC deficit on VHIT, and conversely, we found patients with marked LSC impairment on VHIT without compensatory saccades at VHHT. Conclusions: The detected TVOR compensatory saccades are independent of any concomitant dysfunction of the ipsilateral LSC. We propose a simple method for evaluating utricular function that does not require dedicated equipment and instead uses the VHIT instruments commonly used in vestibular diagnostics.

Case Report
Medicine and Pharmacology
Otolaryngology

Tomohiro Kawasumi

,

Takao Hamamoto

,

Takashi Ishino

,

Tsutomu Ueda

,

Sachio Takeno

Abstract: Background and Clinical Significance: Eosinophilic sialodochitis (ES), also known as sialodochitis fibrinosa, is a rare disorder characterized by recurrent salivary gland swelling caused by intraductal eosinophilic mucous plugs. Typical histopathological findings include eosinophils and Charcot–Leyden crystals within ductal secretions, and characteristic imaging findings include salivary duct dilatation and glandular swelling. Although rare cases associated with sialolithiasis or calcification have been reported, high-attenuation material within the salivary duct on computed tomography (CT) has not been clearly described in ES. Case Presentation: A 56-year-old woman with allergic rhinitis presented with recurrent swelling and pain in the right submandibular area. CT and ultrasonography revealed a large sialolith in the right submandibular gland and dilatation of Wharton’s duct. She underwent right submandibular gland excision for presumed chronic submandibular sialadenitis with a sialolith. Soon after surgery, she developed recurrent swelling of the right floor of the mouth, and CT showed persistent high-attenuation material along Wharton’s duct without residual sialolith. Ductal mas-sage discharged a brownish gelatinous material. Histopathological examination revealed numerous eosinophils and Charcot–Leyden crystals in both the discharged mucous plug and decalcified sialolith, fulfilling Baer’s diagnostic criteria for ES. Physical extraction and anti-allergic medications were insufficient, whereas ductal irrigation with saline and triamcinolone acetonide markedly reduced mucous plug discharge. Symptoms were controlled during 18 months of follow-up. Conclusions: Retained eosinophilic mucin in ES may appear as high-attenuation ductal material on CT and contribute to salivary stasis and sialolith formation.

Review
Medicine and Pharmacology
Otolaryngology

Daniele Salvatore Paternò

,

Luigi La Via

,

Antonino Maniaci

,

Mario Lentini

,

Adriana Cordalonga

,

Caterina Maria Testa

,

Francesco Piccitto

,

Enrico Provinzano

,

Paolo Tummino

,

Emilia Lo Giudice

+1 authors

Abstract: Background. Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen at supra-atmospheric pressure, producing tissue hyperoxygenation, enhanced phagocytic killing, neoangiogenesis, and immunomodulation. Although HBOT is well established in head-and-neck practice, its specific role in sinonasal disease remains poorly systematised. Objective. To reappraise the rationale, evidence, and practical implementation of HBOT in two cardinal sinonasal indications—acute invasive fungal rhinosinusitis (AIFRS) and post-radiotherapy sinonasal damage—through a rhinology-centred, multidisciplinary lens. Methods. Narrative review of articles published in PubMed/MEDLINE, Scopus, Embase, and the Cochrane Library between 1 January 1980 and 31 March 2026, conducted following the SANRA framework and combining MeSH terms for HBOT with sinonasal, mucormycosis, osteoradionecrosis, and skull-base keywords. Results. In AIFRS, HBOT addresses the angioinvasive ischaemic core, restores oxidative neutrophil killing, and potentiates amphotericin B; observational data—including the recent COVID-19-associated mucormycosis (CAM) experience—suggest a survival benefit when HBOT is added early to surgical and antifungal therapy. In post-radiotherapy injury, HBOT reverses Marx's hypoxic–hypocellular–hypovascular triad, supporting healing of osteoradionecrosis (maxillary and skull-base), soft-tissue radionecrosis, and reconstructive procedures in the irradiated bed. Sinus barotrauma, the most frequent rhinological complication, is largely preventable with structured pre-treatment ENT assessment. Conclusions. HBOT is a mechanistically well-founded, well-tolerated adjunct with a favourable safety profile when delivered by a multidisciplinary team. Sinonasal-specific prospective registries and pragmatic randomised trials are urgently needed.

Article
Medicine and Pharmacology
Otolaryngology

Charlotte Kamrath

,

Markus Blaurock

,

Nadine Hopfner

,

Philipp Dittmann

,

Matthis Ebel

,

Fabian Paperlein

,

Chia-Jung Busch

,

Mark Oliver Wielpütz

,

Verena Wagner

Abstract: Background/Objectives: To evaluate whether automated three-dimensional (3D) volumetric body composition metrics derived from the Body and Organ Analysis (BOA) algorithm provide prognostic information beyond body mass index (BMI) for overall survival (OS) in patients with surgically treated head and neck squamous cell carcinoma (HNSCC), and to compare cervical (C1–C7) measurements with thoracic and abdominal benchmarks. Methods: This single-center retrospective cohort study included 391 surgically treated HNSCC patients at Universitätsmedizin Greifswald (2010–2019). Patients with definitive (chemo)radiation (no surgery) or non-standard adjuvant chemotherapy alone (n=13) were excluded; thus, all included patients had primary surgical management. Tumor staging was retrieved from institutional records for all 391 patients. For patients with documented ongoing follow-up but without a specific last-contact date, survival status was verified by chart review where possible, and patients confirmed alive at the institutional database snapshot date were administratively censored on 28 January 2025. Pretreatment CT scans were processed using the open-source BOA algorithm (v0.1.3) to obtain volumetric tissue measurements of muscle, bone, and adipose compartments across abdominal, thoracic, and cervical (C1–C7) regions. Composite indices — Sarcopenia Index (SI = Muscle/Bone) and Myosteatotic Fat Index (MFI = IMAT/TAT) — were derived. Univariate and multivariate Cox proportional hazards models were used. The primary clinically adjusted model included cervical SI, age, sex, tumor site, UICC stage, treatment modality, the Head and Neck Charlson Comorbidity Index (HN-CCI), and secondary malignancy; a minimally adjusted model (HN-CCI and secondary malignancy) was retained as a supportive analysis. Leukocytes and postoperative CRP were examined in a sensitivity model. Reporting followed the STROBE checklist. Results: Of 391 evaluable cases (91% male, median follow-up 5.0 years, 141 deaths), BMI showed only a weak univariate association with overall survival (HR 0.84, p=0.052) and was not independently associated with OS after adjustment (multivariate HR 0.88, p=0.15). In contrast, in the minimally adjusted supportive model the cervical Sarcopenia Index (Cerv SI, Muscle/Bone) was associated with overall survival (HR 0.71, 95% CI 0.58–0.88, p=0.002); in the primary clinically adjusted model including age, sex, tumor site, UICC stage, treatment modality, HN-CCI, and secondary malignancy, cervical SI remained independently associated with OS (HR 0.75, 95% CI 0.61–0.92, p=0.007; n=254). Thoracic Myosteatotic Fat Index (Thor MFI) was associated with worse overall survival in the minimally adjusted supportive model (HR 1.35, p=0.002) and remained associated after extended oncologic adjustment (HR 1.26, p=0.013). Harrell's concordance index for overall survival prediction was 0.60 for cervical SI and 0.55 for BMI; the difference was modest. Inter-regional SI correlations were strong between abdomen and thorax (r=0.69) but only moderate for cervical–thoracic (r=0.42). An in-sample comparison showed that a BOA-derived single-level C3 Sarcopenia Index was non-prognostic (C-index 0.52) and weakly correlated with the volumetric C1–C7 SI (r=0.04), suggesting that the volumetric and single-vertebra-level metrics derived from the BOA pipeline capture different information. In paired bootstrap comparisons, cervical SI showed a modest but significant C-index improvement over BMI (ΔC = +0.087, p = 0.038) but did not significantly outperform the BOA-derived C3 SI, ASA classification, or thoracic SI. Conclusions: BOA-derived volumetric body composition indices, particularly the cervical Sarcopenia Index, are associated with overall survival in surgically treated HNSCC patients and remain prognostic after adjustment for established oncologic confounders, whereas BMI is not. Cervical C1–C7 BOA analysis enables body composition assessment from routine head and neck CT and may provide an objective imaging-derived marker for future risk-stratification studies. Prospective validation and formal comparison with established C3/L3 methods are warranted before routine clinical use.

Article
Medicine and Pharmacology
Otolaryngology

Yongqing Liang

,

Navid Shahnaz

,

Valter Ciocca

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.

Article
Medicine and Pharmacology
Otolaryngology

Mauro Gufoni

,

Giampiero Neri

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.

Article
Medicine and Pharmacology
Otolaryngology

Sakura Hirokane

,

Keiichiro Kiyohara

,

Sachio Takeno

,

Tsuyoshi Sugimoto

,

Tomohiro Kawasumi

,

Yukako Okamoto

,

Rikuto Fujita

,

Chie Ishikawa

,

Yuichiro Horibe

,

Takashi Ishino

+2 authors

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.

Article
Medicine and Pharmacology
Otolaryngology

Dirk Arnold

,

José Luis Vargas Luna

,

Orlando Guntinas-Lichius

,

Gerd Fabian Volk

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.

Hypothesis
Medicine and Pharmacology
Otolaryngology

Franklyn R. Gergits

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.

Article
Medicine and Pharmacology
Otolaryngology

Andra-Lavinia Greța-Oanță

,

Alexandra Roman

,

Ioana Berindan-Neagoe

,

Ștefan Strilciuc

,

Stefan Cristian Vesa

,

Laura-Ancuta Pop

,

Veronica-Elena Trombitaș

,

Silviu Albu

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.

Case Report
Medicine and Pharmacology
Otolaryngology

Giada Cavallaro

,

Domenico Cifarelli

,

Margherita Laguardia

,

Guglielmo Larotonda

,

Camilla Gallipoli

,

Giuseppe De Cillis

,

Giacinto Asprella-Libonati

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.

Review
Medicine and Pharmacology
Otolaryngology

Micah K. Harris

,

Joshua D. Smith

,

Jenny Kim

,

Wesley Cai

,

Kevin J. Contrera

,

Steven B. Chinn

,

Marci L. Nilsen

,

Shaum S. Sridharan

,

Matthew E. Spector

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.

Article
Medicine and Pharmacology
Otolaryngology

Katarina Stanković

,

Vladan Šubarević

,

Mladen Novković

,

Sandra Šipetić-Grujičić

,

Ivana Fajertag

,

Slađana Vasiljević

,

Jadranka Maksimović

,

Isidora Vujčić

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.

Article
Medicine and Pharmacology
Otolaryngology

Meghna Kumar

,

Srinjeeta Garg

,

Zikki Hasan Fatima

,

Gaurav Kumar

,

Burhanuddin Qayyumi

,

Vanita Noronha

,

Kumar Prabhash

,

Pankaj Chaturvedi

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.

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