Medicine and Pharmacology

Abstract: Sudden sensorineural hearing loss (SSNHL) is an otological emergency with complex and heterogeneous etiologies, and most cases remain unexplained and are therefore classified as idiopathic. Viral infection has long been considered an important potential cause of SSNHL; however, the mechanisms underlying virus-associated hearing loss and the causal relationship between viral infection and SSNHL have not been fully elucidated. Current evidence suggests that viruses may induce acute hearing loss through direct invasion of the inner ear, reactivation of latent viruses, immune-mediated injury, and cellular stress and inflammatory responses. This review describes the major viruses associated with SSNHL and their epidemiological and clinical characteristics, summarizes evidence from serological testing, molecular virology, imaging, temporal bone histopathology, and animal studies, and discusses recent advances in the pathogenic mechanisms, etiological diagnosis, and antiviral treatment of virus-associated SSNHL. This review aims to systematically clarify the current evidence and controversies surrounding the viral etiology of SSNHL and to provide a reference for etiological identification, patient stratification, and targeted treatment of virus-associated SSNHL.

Abstract: Background and Objectives: Outcomes after cochlear implantation are usually judged using audiological measures, although recipients' everyday benefit also depends on psychological and social functioning. This study characterized post-implant quality of life (QoL) across six patient-reported domains and explored factors associated with social integration. Methods: Fifty consecutive cochlear implant recipients completed a 35-item questionnaire covering speech perception, psychological self-esteem, media and music, environmental sound, listening effort, and social integration. Negatively framed items were reverse-scored, and domain scores were transformed to a 0-100 scale. Internal consistency, subgroup comparisons, inter-domain correlations, and multivariable regression were evaluated. Results: Mean overall QoL was 65.3 (95% CI, 60.5-69.7). Media and music received the highest mean score (77.9), whereas listening effort was lowest (56.6). The full questionnaire showed excellent internal consistency (Cronbach's alpha = 0.956). QoL scores did not differ significantly by sex, age group, time since implantation, surgical approach, or SMART NAV use, although several subgroup analyses were underpowered. Psychological self-esteem showed the strongest correlation with social integration (rho = 0.56, p < 0.001) and remained the only significant independent correlate in multivariable analysis (B = 0.456, 95% CI, 0.117-0.795; p = 0.010; R2 = 0.428). Conclusions: In this cohort, post-implant QoL varied across functional domains, with listening effort remaining a relative challenge. Social integration was more closely associated with psychological self-esteem than with individual auditory domains. These findings are exploratory and require confirmation in larger longitudinal studies with pre-implant measurements.

Abstract: Importance: Delayed clinical and molecular diagnoses of craniofacial malformations are common due to limited awareness and understanding of these conditions, leading to significant gaps in management and treatment. Objective: To describe the clinical characteristics of patients with craniofacial malformation, identify the most frequent genomic loci associated with these disorders in our population, and evaluate the time interval between clinical and molecular diagnoses. Design and Setting: This retrospective chart review included patients enrolled in the Estudio Colaborativo Latinoamericano para Malformaciones Congenitas (ECLAMC) cohort at the Fundacion Valle del Lili from 2011 to 2022. Participants: Patients were identified using ICD-11 codes for congenital malformations of the eye, ear, face, neck, cleft lip, and cleft palate. All patients with documented craniofacial malformation were included. Main Outcomes and Measures: The study assessed novel variants and genes associated with craniofacial malformations, characterized the phenotypic spectrum, and determined delays in molecular diagnosis. Results: A total of 145 patients were included; the median age was 13 years (IQR 6.6 to 18.7), and 85 (58.6%) were male. Syndromic phenotypes were identified in 42 of 145 patients, 72 of 145 had isolated craniofacial abnormalities, and 30 of 145 lacked a definitive phenotypic diagnosis. Common malformations included eyelid anomalies, cleft lip, macrocephaly, microcephaly, craniosynostosis, and microtia. Only 23 patients (15.8%) had a confirmed molecular diagnosis. Identified syndromes included Cowden, Pfeiffer, CHARGE, Meckel-Gruber, and Joubert syndromes. Pathogenic variants were observed in genes such as GLI3, CHD7, FGFR2, HEXA, YARS2, ACVR1, AHDC1, TYR, RAD50, BRCA2, ANKS6, TP63, SOX9, COCH, KATNIP, CREBBP, SHH, MITF, FGFR3, EFTUD2, RPS6KA3, RERE, PTEN, OTC, L1CAM, RELN, ETHE1, HS6ST2, EFNB1, AMER1, and PTPN11. VUS were detected in TP63, STAMBP, OCLN, and FRMPD4. In 13% of cases, molecular diagnosis was not established. Conclusions and Relevance: Clinical and molecular characterization distinguishes syndromic from non-syndromic craniofacial malformations and informs comprehensive care. Significant diagnostic delays highlight the need for early genetic testing to guide treatment and provide timely counseling for patients and their families.

Abstract: Background: Vertigo and dizziness are common neurological complaints in childhood, and increasing evidence suggests that a substantial proportion of recurrent vestibular symptoms may represent early manifestations of migraine-related disorders. However, current diagnostic criteria for pediatric vestibular migraine may underestimate migraine involvement in prepubertal children, in whom vestibular and autonomic symptoms often precede or occur independently of headache. Objectives: To reassess a large pediatric cohort of children with recurrent vestibular symptoms using a developmental migraine-spectrum model integrating vestibular manifestations, migraine precursors, and susceptibility markers. Methods: This retrospective multicenter study analyzed 146 children aged 3-12 years evaluated for recurrent vestibular symptoms between 1995 and 2022 at two Italian tertiary referral centers. All patients were initially classified according to the 2021 Bárány Society and International Headache Society criteria. A secondary structured evaluation assessed family history of migraine, headache characteristics, vestibular phenotype, benign paroxysmal torticollis, extra-vestibular migraine precursors (cyclic vomiting, recurrent abdominal pain, and related episodic syndromes), and migraine susceptibility markers including motion sickness and sensory hypersensitivity. Results: Of the 146 children, 144 fulfilled the Bárány Society criteria for Recurrent Vertigo of Childhood, whereas two presented with isolated benign paroxysmal torticollis, interpreted according to Pagnini’s model as a migraine-related manifestation of the descending vestibulo-cervical pathway [21]. None fulfilled the criteria for Vestibular Migraine of Childhood or probable Vestibular Migraine of Childhood. Headache was present in only 15.8% of patients and was generally mild to moderate. Most children exhibited recurrent isolated vestibular episodes with frequent autonomic symptoms, while a subgroup presented with benign paroxysmal torticollis. Motion sickness and sensory hypersensitivity were highly prevalent, and many patients showed additional developmental migraine precursors, including abdominal pain, cyclic vomiting, limb pain, and infant colic. Vestibular symptoms frequently preceded headache onset, supporting the hypothesis that migraine susceptibility may manifest predominantly through vestibular and autonomic pathways during childhood. Conclusions: Pediatric recurrent vertigo should be considered within a broader developmental migraine spectrum rather than as an isolated vestibular disorder. Current diagnostic criteria may lack sensitivity in prepubertal populations by emphasizing headache-related features. Integrating vestibular symptoms, developmental migraine equivalents, and susceptibility markers may improve early recognition of migraine-related vestibulopathy and provide a biologically plausible model for the developmental evolution of migraine-related vestibulopathy across childhood and adolescence.

Abstract: Background: Post-laryngectomy salivary leak and pharyngocutaneous fistula (PCF) are recognised complications that prolong hospitalisation, delay adjuvant treatment and, in severe cases, risk major vessel exposure; current management relies on conservative measures or systemic anticholinergic agents, which carry a substantial burden of unwanted effects. Case Series: We present four consecutive patients treated with a standardised regimen of botulinum toxin A (BoNT) injected into the parotid tail, parotid body and submandibular gland after failure of conservative management for post-laryngectomy salivary leak/PCF; all four achieved clinical and radiological resolution without significant local or systemic complications. Methods: We conducted a systematic review of the literature (PubMed, EMBASE, Cochrane, Google Scholar) in accordance with PRISMA 2020 guidelines, screening 1198 records (701 after deduplication) and identifying 13 eligible studies (>260 patients) evaluating BoNT for salivary leak/fistula across post-laryngectomy PCF and post-parotidectomy sialocele/fistula populations. Discussion: Across the case series and the wider literature, BoNT was consistently associated with rapid salivary suppression (up to ~95% reduction in one study), high fistula closure rates (54–100%), and accelerated healing, including a statistically significant reduction in healing time in one comparative study (18.5 vs. 26 days, p = 0.008), with adverse events rare and minor. Conclusions: BoNT injection is a low-risk, potentially high-yield adjunct for post-laryngectomy salivary leak and PCF, avoiding the systemic anticholinergic burden of alternative pharmacological treatments; multicentre studies with standardised dosing protocols are needed to establish its role in standard practice.

Abstract: Objective: Vestibular disorders are rarely diagnosed through imaging examinations intuitively. We try to explore a new approach to visualize peripheral vestibular disorders using pseudo-color perceptual enhancement. Methods : A total of 53 patients with unilateral abnormal caloric test results and 23 patients with normal results, treated at outpatient clinics between March 2025 and March 2026, were selected for analysis. All patients underwent magnetic resonance imaging examinations. We used the software to process T2 sequences from magnetic resonance images of patients and calculated the values of peripheral vestibular organs. Results : Eighteen patients had an abnormal caloric test result on one side but had pseudo-color perceptual enhancement on the other side, thirty five patients had the abnormal caloric test result and pseudo-color perceptual enhancement on the same side, it was statistically different. However, the comparison of differences between both sides in these two groups and the normal group showed no statistically significant difference. Conclusion : The pseudo-color perceptual enhancement on the peripheral vestibular organ may indicate the vestibular disorders. However further research is still needed for the results through more precise differentiation of vestibular disorders.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.