Clinical and Experimental Otorhinolaryngology最新文献

Head and neck cancer (HNC) is not only one of the deadliest malignant tumors but also significantly impacts patient quality of life because of its proximity to numerous critical organs. Radiotherapy is commonly used to treat HNC due to its effectiveness in targeting cancer cells while sparing adjacent organs. However, the emergence of radioresistance severely limits the efficacy of radiotherapy, frequently leading to poor prognosis and treatment failure. Consequently, an enhanced understanding of the underlying mechanisms of radioresistance could facilitate the development of novel treatment strategies aimed at reducing recurrence rates and improving survival outcomes. In this review, we summarize the primary mechanisms implicated in radioresistance in HNC from both cancer cell-intrinsic and tumor microenvironment perspectives. Furthermore, we discuss currently available radiation-sensitizing approaches to overcome radioresistance in HNC.

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

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

Results: Administration of sarpogrelate via an osmotic pump resulted in significant hearing preservation across all tested frequencies at 1 month post-surgery (P<0.05) compared with the control group, which underwent dummy electrode insertion only. Histological analysis revealed that cochlear fibrosis and inflammatory cell infiltration were markedly reduced in the sarpogrelate-treated groups, especially in the group receiving the higher pump volume. Gene expression analysis supported these findings by showing a significant reduction in inflammation-related markers in the sarpogrelate-treated groups.

Conclusion: Sarpogrelate exhibited a protective effect against the loss of residual hearing after CI, likely due to its anti-inflammatory and antifibrotic properties. In addition, the osmotic pump enabled controlled, sustained delivery of the drug over time. These findings indicate that administering sarpogrelate via an osmotic pump represents a promising pharmacological strategy for improving postoperative outcomes in CI patients by preserving residual hearing.

Objectives: 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 participants aged 40 years or older in the Korean National Health Insurance Service-Health Screening Cohort from 2002 through 2019 were used. Data for 13,769 patients with SSNHL were collected and matched with those for 55,076 control participants based on demographic and socioeconomic variables. The incidence of CP before the onset of SSNHL was recorded. The odds ratios (ORs) for SSNHL based on CP history were calculated using conditional logistic regression. ORs were analyzed according to the frequency of CP, specifically ≥1, ≥2, and ≥3 clinic visits for CP within 1 year and ≥1 visit within 2 years. Sensitivity analyses were also conducted for all covariables.

Results: The patients with SSNHL had a higher mean number of CP visits (0.71 within 1 year and 1.34 within 2 years) compared with control participants. CP was associated with increased odds of SSNHL, with an OR of 1.14 (95% CI, 1.10-1.19) for ≥1 CP visit, an OR of 1.09 (95% CI, 1.03-1.15) for ≥2 visits, and an OR of 1.09 (95% CI, 1.02-1.17) for ≥3 visits within 1 year. Furthermore, having experienced at least 1 visit for CP within 2 years was associated with 1.15 times greater odds of SSNHL (95% CI, 1.10-1.19). Higher rates of SSNHL were also observed in the subgroups of participants with underweight, overweight, and age ≥65 years, as well as those with comorbidities.

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

Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) demonstrates a high recurrence rate following endoscopic sinus surgery (ESS). The role of adjunctive biologic therapy remains incompletely understood. This study aims to assess the efficacy of dupilumab when used in conjunction with ESS for patients with CRSwNP.

Methods: We conducted a retrospective cohort study of type 2 CRSwNP patients who underwent ESS. The study compared patients receiving postoperative dupilumab with those receiving standard care. Changes in the Lund-Kennedy endoscopic score (LKES) and nasal polyp score (NPS) were recorded, and linear mixed models (LMMs) were employed for the primary outcome analysis.

Results: The study enrolled 49 CRSwNP patients, with 22 patients in the dupilumab group. Postoperative LKES and NPS decreased in both groups. LMM analysis revealed a significant improvement in LKES (B=-0.61; 95% CI, -0.90 to -0.31; P<0.001) and a more pronounced improvement in NPS (B=-0.14; 95% CI, -0.25 to -0.02; P=0.025) in the dupilumab group compared to controls from preoperative to postoperative measurements.

Conclusion: Compared to ESS alone, the adjunctive use of dupilumab in the postoperative period was associated with greater reductions in both NPS and endoscopic scores.

Objectives: Balloon eustachian tuboplasty (BET) is an emerging treatment for dilatory eustachian tube (ET) dysfunction, yet its efficacy in patients with chronic suppurative otitis media (COM) combined with ET dysfunction remains unclear. This trial aimed to evaluate the efficacy and safety of BET versus medical management (MM) alone in adult patients with COM and chronic dilatory ET dysfunction, as defined by a failed Valsalva maneuver.

Methods: This prospective, multicenter, randomized controlled trial enrolled 116 participants (121 ears) between January 2021 and June 2023. Participants were randomly assigned (1:1) to receive either BET combined with MM or MM alone (fluticasone furoate nasal steroid spray). The primary short-term outcome was the normalization of the Valsalva maneuver at 8 weeks, while secondary outcomes included improvements in Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) scores and reductions in the air-bone gap (ABG) measured at 8 weeks. Adverse events were monitored in both groups throughout the follow-up period.

Results: Of the 116 participants (121 ears), 60 participants (62 ears) received BET and 56 participants (59 ears) received MM alone. There were no significant differences in demographics, baseline characteristics, ETDQ-7 scores, bone conduction thresholds, or ABG between the groups. In the BET group, 46.8% of ears (29/62) achieved a successful Valsalva maneuver compared with 15.3% of ears (9/59) in the MM-only group (P<0.001). The BET group exhibited greater subjective symptom improvement, with an average ETDQ-7 score reduction of -6.2±9.4 compared to -2.6±8.6 in the MM-only group (P=0.028). Additionally, the ABG decreased more significantly in the BET group (-5.8±11.4 dB HL) than in the MM-only group (-1.2±10.5 dB HL) (P=0.023). No serious procedure- or device-related adverse events were observed during the 8-week follow-up.

Conclusion: This trial demonstrates that BET combined with MM is superior to MM alone in treating dilatory ET dysfunction in patients with COM, while also maintaining a favorable safety profile.

Objectives: Many studies have reported that patients with anosmia exhibit an increased incidence of dementia later in life. However, most of these studies have focused exclusively on individuals aged 65 or older, leaving a gap in research on middle-aged subjects (40-65 years).

Methods: We conducted a retrospective cohort study using Korea's National Health Insurance claims data. The study targeted participants aged 40 years and above by 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), comprising individuals diagnosed with anosmia between 2006 and 2008, and the control group (n=2,680,534), consisting of the remaining participants. Subsequently, we followed the participants to monitor the occurrence of Alzheimer and vascular dementia from 2011 to 2020.

Results: After adjusting for various factors, the incidence of Alzheimer dementia was significantly higher in the anosmia group compared to the control group (hazard ratio [HR], 1.15; 95% CI, 1.04-1.28). Stratification by age revealed that the risk of developing dementia was significantly elevated in anosmia patients under 65 years (HR, 1.28; 95% CI, 1.07-1.54), whereas no significant increase was observed in those over 65 years (HR, 1.10; 95% CI, 0.97-1.24). Vascular dementia was not statistically associated with anosmia.

Conclusion: A diagnosis of anosmia in middle age increases the risk of developing Alzheimer dementia, while no such increase is observed in older individuals.

Olfactory loss affects more than 12% of the population, with prevalence increasing in aging individuals. Multiple conditions can lead to a loss of smell (hyposmia or anosmia), including post-viral damage from coronavirus disease 2019 (COVID-19) or influenza, head injuries, sinusitis, or neurodegenerative conditions such as Alzheimer or Parkinson disease. Although treatments like surgery, anti-inflammatory medications, or olfactory training can be beneficial in certain cases, there remains an unmet need for effective therapies addressing many common causes of olfactory dysfunction. This is particularly true for cases attributed to damage of olfactory neurons that fail to spontaneously recover. Regenerative medicine approaches, aimed at either stimulating the regrowth of sensory neural structures or replacing them through cell-based therapies, have attracted considerable interest for treating various neurological disorders, including olfactory loss. Here, we summarize the intrinsic regenerative capabilities of the peripheral olfactory system, focusing on current research strategies and the existing barriers that must be overcome for successful translational applications. A major unmet need in this field involves the establishment of reliable and widely accepted culture models for expanding and differentiating olfactory stem or progenitor cells from rodents and humans, both for use in vitro assays and as potential material for cell-based therapies.

Objectives: This study evaluated the cost-effectiveness of using hearing aids among individuals aged 50 and older with varying levels of hearing loss in South Korea.

Methods: A state-transition Markov model was employed to assess the cost-effectiveness of hearing aid utilization from a societal perspective. We simulated a cohort of patients aged 50, tracking their progression through normal, mild, moderate, and severe stages of hearing loss until death or age 80. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year gained was determined using both published and calculated data on the costs and effectiveness of hearing aids.

Results: The respective ICERs were $8,571 for men and $10,635 for women. These figures are significantly below the willingness-to-pay (WTP) threshold of $31,721, which corresponds to the per capita gross domestic product (GDP) in 2020. The probabilities of cost-effectiveness were 83.6% for men and 73.4% for women at this WTP threshold. The lower ICERs observed in men can likely be attributed to the earlier onset of hearing loss and the rapid progression from normal, mild, moderate, and severe stages of hearing loss to death.

Conclusion: Hearing aids represent a highly cost-effective intervention for adults aged 50 and older in Korea, regardless of the degree of hearing loss, even in mild cases. In light of the rapidly aging population, it would be prudent for government policymakers to consider the cost-effectiveness of hearing aids in their decision-making processes.

Objectives: Hypopharyngeal cancer (HPC), originating from the hypopharyngeal mucosa, is associated with a poor prognosis. Extracellular matrix (ECM) stiffness is closely linked to tumor progression and patient outcomes. This study aimed to investigate the effects of matrix stiffness and to identify molecular markers relevant to HPC prognosis, with the goal of improving clinical outcomes.

Methods: Immunohistochemical analysis and cervical enhanced computed tomography (CT) data were used to evaluate correlations among CT values, matrix stiffness, and prognosis, and to develop a prognostic model for HPC. Cell culture models with varying matrix stiffness were established using polypropylene hydrogel. Western blotting, colony formation, EDU incorporation, and Transwell assays were employed to assess the effects of matrix stiffness on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). High-throughput sequencing identified differentially expressed genes in HPC cells cultured on matrices of differing stiffness. Gene editing, in vivo subcutaneous tumorigenesis studies, and Western blotting were performed to elucidate the molecular mechanisms by which high matrix stiffness influences HPC progression and the role of ephrin A2 (EFNA2) in proliferation, migration, and EMT.

Results: Arterial phase CT values were positively correlated with matrix stiffness. Increased matrix stiffness was associated with lymph node metastasis, diminished therapeutic response, and poorer prognosis. Furthermore, metastatic lymph nodes in HPC patients exhibited higher CT values than those in patients with nasopharyngeal carcinoma. A high-stiffness ECM promoted proliferation, migration, and EMT in HPC cells. Mechanistically, a stiff ECM enhanced EFNA2 expression, thereby promoting proliferation, migration, EMT, and tumor growth in vivo.

Conclusion: EFNA2 and elevated matrix stiffness jointly contribute to the malignant phenotype in HPC. EFNA2 may represent a potential therapeutic target for managing HPC progression induced by high matrix stiffness.