Clinical and Experimental Otorhinolaryngology最新文献

Objective: The vestibular aqueduct (VA) shows significant anatomical variability. These anatomical variations and their relationship with neighboring structures may present technical challenges during endolymphatic sac surgery. We aimed to characterize the anatomical features of the vestibular aqueduct (VA) and its relationship with surrounding structures in patients with severe Ménière's disease compared to controls, using high-resolution computed tomography (CT).

Methods: This retrospective study included 65 patients (126 ears) who underwent temporal bone CT. The Ménière's group consisted of 26 patients (26 affected ears) meeting AAO-HNS criteria with intractable disease, the contralateral ears group included 24 ears, and the control group included 39 patients (76 ears) with unrelated conditions. Measurements included VA thickness (A), width (B/B'), distance between the posterior semicircular canal (PSCC) and posterior fossa (C), PSCC depth (D/D'), and operculum depth (E/E'). Correlations were analyzed, and k-means clustering was applied to classify anatomical variations. Reliability was assessed using intra- and inter-observer tests.

Results: VA width (B) correlated positively with PSCC-meningeal distance (C) (r=0.683, p<0.001) and negatively with PSCC depth (D') (r=-0.290, p<0.01) and operculum depth (E') (r=-0.520, p<0.001). Patients with narrower VA exhibited reduced PSCC-meningeal distance and deeper operculum positions. The Ménière's group showed significantly narrower VA and shorter PSCC-dura distances compared to controls (p<0.001). Cluster analysis identified three anatomical patterns, with 61.5% of intractable Ménière ears versus 14.5% of controls and 41.6% of the contralateral ears, in the cluster exhibiting smaller VA dimensions, shorter PSCC-dura distances, and deeper operculum positions.

Conclusion: Narrow VA correlates with reduced PSCC-meningeal distance and deeper operculum position, presenting potential challenges for endolymphatic sac surgery. These anatomical variations are more prevalent in patients with severe Ménière's disease, highlighting the need for tailored surgical approaches.

Objective: Chronic periodontitis (CP) has been linked to an increased risk of sudden sensorineural hearing loss (SSNHL). This study aimed to delineate the causal relationships between CP and SSNHL.

Methods: Data from 40-year-old participants in the Korean National Health Insurance Service-Health Screening Cohort from 2002 through 2019 were used. The data of 13,769 patients with SSNHL were collected and matched with those of 55,076 control participants in terms of demographic and socioeconomic variables. The incidence of CP before the onset of SSNHL was recorded. The odds ratios (ORs) of CP for SSNHL were analyzed via conditional logistic regression. The ORs for SSNHL were analyzed according to the frequency of CP, ≥ 1, 2, and 3 times within 1 year and ≥ 1 within 2 years. In addition, sensitivity analyses were conducted for all the covariables.

Results: CP patients had a higher mean CP occurrence (0.71 within one year, 1.34 within two years) than controls. CP was associated with increased odds of SSNHL (OR = 1.14 [95% confidence intervals (CI) = 1.10-1.19] for CP ≥ 1 within one year, OR = 1.09 [95%CI = 1.03- 1.15] for CP ≥ 2, and OR = 1.09 [95% CI = 1.02-1.17] for CP ≥ 3). CP ≥ 1 within two years was related to a 1.15 (95% CI = 1.10-1.19) times greater odds for SSNHL. Higher SSNHL rate was also observed in subgroups of underweight, overweight, elderly, and comorbid individuals.

Conclusion: CP was linked with an elevated incidence of SSNHL. Individuals with comorbidities, advanced age, or abnormal body weight were more likely to have CP with SSNHL.

Objective: Hypopharyngeal cancer (HPC) originates from the hypopharyngeal mucosa with poor prognosis. The stiffness of extracellular matrix (ECM) is closely associated with tumor progression and prognosis. This study aimed to investigate the impact of matrix stiffness and identify molecular markers that are relevant to the prognosis of HPC, with the goal of improving prognosis.

Methods: Immunohistochemical and cervical enhanced CT data were used to analyze the correlation between CT value, matrix stiffness, and prognosis, and to establish prognosis prediction model of HPC. Cell culture models with different matrix stiffness were constructed by polypropylene hydrogel. Western blotting, clone formation, EDU, and Transwell were used to investigate the effects of matrix stiffness on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). High-throughput sequencing was used to identify differential genes in HPC cells cultured in different matrix stiffness. Gene editing technique, in vivo subcutaneous tumorigenesis studies, and western blotting were conducted to investigate molecular mechanisms underlying the impact of high-stiffness matrix on HPC, and the influence of EFNA2 on proliferation, migration, and EMT.

Results: The arterial CT value was positively correlated with matrix stiffness. Matrix stiffness is associated with lymph node metastasis, therapeutic effect, and prognosis. Additionally, metastatic lymph nodes in HPC patients had higher CT values compared to those in patients with nasopharyngeal carcinoma (NPC). High-stiffness ECM could promote the proliferation, migration and EMT of HPC cells. Mechanistically, highstiffness ECM infuenced EFNA2 expression to promote proliferation, migration, EMT, and tumor growth in vivo.

Conclusion: EFNA2 and high matrix stiffness jointly promoted the malignant phenotype in HPC. EFNA2 may serve as potential therapeutic target for high matrix stiffnessinduced HPC progression.

Objective: This study evaluated the effects of sarpogrelate, a selective 5-hydroxytryptamine (5-HT) 2A receptor antagonist, on residual hearing preservation and inflammatory responses after cochlear implantation (CI) in an animal model.

Methods: The damaging effects of CI were simulated in male albino guinea pigs by using a dummy electrode. Animals were divided into three groups: control (n=12, dummy electrode insertion only), SPG-1004 (n=7, low-capacity pump with sarpogrelate), and SPG-2004 (n=6, high-capacity pump with sarpogrelate). Sarpogrelate was administered via osmotic pumps at two different volumes and its effect on hearing thresholds, histological outcomes, and the expression of inflammation-related genes were evaluated. Hearing was evaluated using auditory brainstem response (ABR) thresholds at baseline (preoperatively) and at 1-, 7-, and 30-days postoperatively.

Results: Sarpogrelate administration through an osmotic pump led to significant hearing preservation across all tested frequencies at 1-month post-surgery (p<0.05), as compared with the control group, which only underwent dummy electrode insertion. Histological analysis revealed that cochlear fibrosis and inflammatory cell infiltration were significantly reduced in the sarpogrelate-treated groups, and more so in the group with the higher pump volume. Gene expression analysis supported these findings, showing a significant reduction in inflammationrelated markers in the sarpogrelate-treated groups.

Conclusion: Sarpogrelate demonstrated a protective effect against loss of residual hearing after CI, likely due to its anti-inflammatory and antifibrotic properties. Moreover, the use of an osmotic pump allowed controlled and sustained delivery of the drug over time. These findings suggest that sarpogrelate administered via an osmotic pump is a promising pharmacological approach for improving postoperative outcomes in patients with CI by preserving residual hearing.

Introduction: Many studies have reported that patients with anosmia have an increased incidence of dementia later in life. However, most of these were conducted only on older people aged 65 or older, and there was a lack of research on middle-aged subjects aged 40-65.

Methods: We conducted a retrospective cohort study utilizing Korea's National Health Insurance claims data. The study targeted participants aged 40 years and above, randomly selecting 40% of individuals who underwent the 2009 national health check-up. The cohort was divided into two groups: the anosmia group (n = 8,023), consisting of individuals diagnosed with anosmia between 2006 and 2008, and the control group (n = 2,680,534), comprising the remaining participants. Subsequently, we followed up on the participants, monitoring the occurrence of Alzheimer's and vascular dementias from 2011 to 2020.

Results: After adjusting for various factors across all subjects, the incidence of Alzheimer's dementia increased in the anosmia group compared to the control group [hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04-1.28]. When comparing the two groups based on age 65, the risk ratio for developing dementia in patients with anosmia compared to controls of the same age significantly increased in those under 65 years of age (HR 1.28, 95% CI 1.07-1.54), but did not increase in those over 65 years of age (HR 1.10, 95% CI 0.97-1.24). Vascular dementia was not statistically associated with anosmia.

Conclusion: Anosmia diagnosed in middle age increases the risk of Alzheimer's dementia, whereas this is not the case in old age.

Objective: The aim of this study was to investigate the auditory and vestibular consequences of congenital cytomegalovirus (cCMV) infection in a C57BL/6 mouse model established by intraperitoneal inoculation and designed to mimic clinical phenotypes.

Methods: A cCMV infection model was established by intraperitoneal inoculation of murine cytomegalovirus into C57BL/6 mice. Auditory and vestibular function were assessed by auditory brainstem response, open field, swim, and rotarod tests. Histologic evaluation of the inner ear was also performed.

Results: The study successfully established a model of cCMV infection in C57BL/6 mice. Auditory deficits of varying severity and laterality were observed, reflecting the clinical spectrum in humans. Vestibular function was minimally affected and did not correlate with auditory deficits. Histopathologic examination revealed predominant damage to spiral ganglion neurons with relatively intact vestibular organs.

Conclusion: Our optimized mouse model effectively recapitulates the inner ear manifestations of human cCMV infection. The predominance of auditory over vestibular deficits provides valuable insights for the development of targeted therapeutic interventions for inner ear sequelae of cCMV infection.

Objective: Current state-run newborn hearing screening (NBHS) programs have limitations in identifying children with mild or late-onset sensorineural hearing impairment (SNHI). As more than 50% of pediatric SNHI cases are attributed to genetic causes, these limitations may be addressed by the increasing accessibility of high-throughput, low-cost genomic sequencing. This study aims to investigate the feasibility of integrating a next-generation sequencing (NGS)-based genomic screening protocol into conventional NBHS and to examine its potential benefits and challenges.

Methods: A total of 8,261 newborns who underwent simultaneous NBHS and NGSbased genomic screening targeting 46 deafness genes were prospectively enrolled in this study. The genotypes of the subjects were determined, and newborns with conclusive genetic diagnoses were subjected to audiological assessments.

Results: A total of 164 subjects were confirmed to have conclusive genetic diagnoses, with 112 subjects carrying variants in GJB2 and MTRNR1, and 52 subjects carrying variants in other deafness genes. Of these, 126 subjects with conclusive genetic diagnoses passed the NBHS, suggesting that an additional 1.5% (126/8,261) of children at risk for SNHI but not detected by conventional physiological NBHS could be identified through targeted genomic screening in the general population. Notably, the father of one subject with the COL4A5 variant and three paternal relatives of another subject with the EDNRB variant, who were unaware of their conditions prior to this study, were diagnosed with Alport and Waardenburg syndromes, respectively, highlighting the benefit to families.

Conclusion: Targeted genomic sequencing in newborns may complement the conventional NBHS in identifying children at risk for SNHI and facilitate early diagnosis in families with non-syndromic mimics.

Objectives: Balloon eustachian tuboplasty (BET) is an emerging treatment for dilatory eustachian tube (ET) dysfunction. However, its efficacy in patients with both chronic suppurative otitis media (COM) and ET dysfunction remains unclear. The objective of the trial was to assess the efficacy and safety of BET versus medical management (MM) alone in adult patients with COM and chronic dilatory ET dysfunction, which was defined by a failed Valsalva maneuver.

Methods: In this prospective, multicenter, randomized controlled trial, a total of 116 participants (121 ears) treated between January 2021 and June 2023 were randomly assigned (1:1) to receive either BET with MM or MM alone (fluticasone furoate nasal steroid spray). The short-term primary outcome was the normalization of the Valsalva maneuver at the 8-week follow-up. Secondary outcomes were improved Eustachian Tube Dysfunction Questionnaire- 7 (ETDQ-7) scores and decreased air-bone gap (ABG) analyzed at 8 weeks. Adverse events were monitored in both groups during the follow-up period.

Results: Among the 116 participants (121 ears), 60 participants (62 ears) received BET and 56 participants (59 ears) received MM alone. Demographics, baseline characteristics, ETDQ-7 scores, bone conduction thresholds, and ABG did not differ significantly between the groups. In the BET group, 46.8% (29/62, ears) achieved a successful Valsalva maneuver compared with 15.3% (9/59, ears) in the MM-only group (p<0.001). BET group (-6.2±9.4) showed greater subjective symptom improvement than the MM-only group (-2.6±8.6) regarding ETDQ-7 scores (p=0.028). ABG decreased more in the BET group (-5.8±11.4 dB) compared with the MM-only group (-1.2±10.5 dB) (p=0.023). No serious procedure-related or device-related adverse events occurred in either group during the 8-week follow-up.

Conclusion: Our trial suggests that BET, combined with MM, demonstrated superiority over MM alone, along with its safety, in treating dilatory ET dysfunction in patients with COM.

Objectives: Branchio-oto syndrome (BOS) is a group of autosomal dominant genetic diseases, multisystem disorders excluding renal anomalies. There are clinical heterogeneity and ethnic diversity in BOS, which reported in more studies in European populations than in Asian populations, with a prevalence rate of approximately 1/40000. As the most common disease-causing gene, the mutation types of EYA1 range from missense to various frameshift, splicing and nonsense variants. Although splicing mutations are one of the important factors in the disease, existed research has paid less attention to the novel mutations causing aberrant RNA splicing and their pathogenic mechanisms. Reproductive interventions that actively block the transmission of the disease to future generations have also not been reported.

Methods: We had collected research samples from a three-generation Chinese family with BOS. Whole exome sequencing was applied for the screening of candidate causing gene. Minigene assay was performed to identify the aberrant splicing products, and molecular biology techniques were used to analyze the pathogenicity of potentially mistranslated proteins. pre-implantation genetic testing (PGT) has been employed to prevent hearing loss in this family based on SNP analysis.

Results: A novel mutation EYA1:c.1598-2AG>TA was identified by whole-exome sequencing and classified as harmful refer to ACMG's evidence. An aberrant RNA splicing was verified and suggested that might prematurely terminates the translation of EYA1 protein, through the minigene assay. The EYA1 truncated protein presented unstable and difficultly translocated to the nucleus, also impaired EYA1-SIX1 interactions in cytological experiments. PGT helped the proband give birth to a healthy boy.

Conclusion: A novel splicing variant of EYA1 gene was identified in this study, and the potential molecular pathogenic mechanism was elucidated by several functional experiments. On basis above findings, we successfully implemented the first instance of using PGT to ensure the birth of a healthy offspring free from this genetic disorder.