Results of Active Middle Ear Implantation in Patients With Mixed Hearing Loss After Middle Ear Surgery: A Prospective Multicenter Study (the ROMEO Study).

OBJECTIVES: This study was conducted to evaluate the user satisfaction, efficacy, and safety of round window (RW) vibroplasty using the Vibrant Soundbridge (VSB) in patients with persistent mixed hearing loss after mastoidectomy. METHODS: The study included 27 patients (mean age, 58.7 years; age range, 28-76 years; 11 men and 16 women) with mixed hearing loss after mastoidectomy from 15 tertiary referral centers in Korea. The VSB was implanted at the RW. The Korean translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire and the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire were used to evaluate user satisfaction as the primary outcome. The secondary outcome measures were audiological test results and complication rates. RESULTS: The mean scores for ease of communication (61.3% to 29.7% to 30.2%), reverberation (62.1% to 43.1% to 37.4%), and background noise (63.3% to 37.7% to 34.3%) subscales of the APHAB questionnaire significantly decreased after VSB surgery. The mean K-IOI-HA scores at 3 and 6 months after surgery were significantly higher than the mean preoperative score (18.6 to 27.2 to 28.1). The postoperative VSB-aided thresholds were significantly lower than the preoperative unaided and hearing aid (HA)-aided thresholds. There was no significant difference between preoperative unaided, preoperative HA-aided, and postoperative VSB-aided maximum phonetically balanced word-recognition scores. None of the 27 patients experienced a change in postoperative bone conduction pure tone average. One patient developed temporary facial palsy and two developed surgical wound infections. CONCLUSION: RW vibroplasty resulted in improved satisfaction and audiological test results in patients with mixed hearing loss after mastoidectomy, and the complication rate was tolerable.

Feasibility of Revision Cochlear Implant Surgery for Better Speech Comprehension.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the efficacy of revision cochlear implant (CI) surgery for better speech comprehension targeting patients with low satisfaction after first CI surgery. SUBJECT AND METHODS: Eight patients who could not upgrade speech processors because of an too early CI model and who wanted to change the whole system were included. After revision CI surgery, we compared speech comprehension before and after revision CI surgery. Categoies of Auditory Performance (CAP) score, vowel and consonant confusion test, Ling 6 sounds, word and sentence identification test were done. RESULTS: The interval between surgeries ranged from eight years to 19 years. Same manufacturer's latest product was used for revision surgery in six cases of eight cases. Full insertion of electrode was possible in most of cases (seven of eight). CAP score (p-value=0.01), vowel confusion test (p-value=0.041), one syllable word identification test (p-value=0.026), two syllable identification test (p-value=0.028), sentence identification test (pvalue=0.028) had significant improvement. Consonant confusion test (p-value=0.063), Ling 6 sound test (p-value=0.066) had improvement but it is not significant. CONCLUSIONS: Although there are some limitations of our study design, we could identify the effect of revision (upgrade) CI surgery indirectly. So we concluded that if patient complain low functional gain or low satisfaction after first CI surgery, revision (device upgrade) CI surgery is meaningful even if there is no device failure.

Effects of caffeic acid on cisplatin-induced hair cell damage in HEI-OC1 auditory cells.

INTRODUCTION: Cisplatin is a widely used anticancer chemotherapeutic agent. However, it is notorious for its ototoxicity and nephrotoxicity due to induction of reactive oxygen species (ROS). Caffeic acid is a naturally occurring polyphenol present in honey that is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the protective effects and mechanism underlying the effect of caffeic acid on cisplatin-induced ototoxicity in HEI-OC1 auditory cell lines. METHODS: Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by Hoechst 33258 staining and Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Cell cycle stages were analyzed by flow cytometry. The radical-scavenging activity of caffeic acid was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The expression levels of caspase-3, -8, and -9, as well as the activity of caspase-3, were evaluated. RESULTS: Caffeic acid showed a protective effect against cisplatin-induced HEI-OC1 cell damage as demonstrated by the MTT assay. Caffeic acid decreased cell death by apoptosis and necrosis. Caffeic acid showed strong scavenging activity against the radical DPPH and decreased intracellular ROS production. Caffeic acid decreased the expression of caspase-3 and -8 and increased the activity of caspase-3. CONCLUSIONS: Caffeic acid attenuated cisplatin-induced hair cell loss in HEI-OC1 cell lines; these effects were mediated by its radical scavenging activity and inhibition of apoptosis.

Effect of acrolein, a hazardous air pollutant in smoke, on human middle ear epithelial cells.

OBJECTIVE: Acrolein is a hazardous air pollutant. Tobacco smoke and indoor air pollution are the main causes of human exposure. Acrolein has been shown to cause cytotoxicity in the airways and induce inflammation and mucin production in pulmonary cells. We investigated whether acrolein caused cytotoxicity, induced inflammation or increased expression of mucin in immortalized human middle ear epithelial cell lines (HMEECs). METHODS: Cytotoxicity following acrolein treatment was investigated using the MTT assay, flow cytometry, and Hoechst 33342 staining of HMEECs. We measured expression of inflammatory cytokines tumor necrosis factor (TNF)-α and cyclo-oxygenase (COX)-2 and the mucin gene MUC5AC using semi-quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: Exposure to >50 µg/mL acrolein caused a decrease in cell viability. Acrolein induced apoptosis and necrosis at 50 µg/mL. Acrolein at 5-50 µg/mL increased expression of TNF-α and COX-2, as shown by RT-PCR and Western blotting. Acrolein exposure at 5-50 µg/mL for 2-24h increased MUC5AC expression, as determined by RT-PCR. CONCLUSION: Acrolein decreased cell viability, induced an inflammatory response, and increased mucin gene expression in HMEECs. These findings support the hypothesis that acrolein, a hazardous air pollutant in tobacco smoke and ambient air, is a risk factor for otitis media.

Effect of prostaglandin e2 on vascular endothelial growth factor production in nasal polyp fibroblasts.

PURPOSE: Angiogenesis is involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. We aimed to investigate the effects of prostaglandin E2 (PGE2) on vascular endothelial growth factor (VEGF) production, the role of E-prostanoid (EP) 4 receptors, and the signal transduction pathway mediating VEGF production in nasal polyp-derived fibroblasts (NPDFs). METHODS: Eight primary NPDF cultures were established from nasal polyps, which were incubated with or without PGE2. Reverse transcription-polymerase chain reaction amplification of EP receptors (EP1, EP2, EP3, and EP4) and immunofluorescence staining for VEGF production were performed. VEGF production via the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) pathways was evaluated by enzyme-linked immunosorbent assay. RESULTS: All EP receptors were expressed in NPDFs. PGE2 significantly increased VEGF production concentration- and time dependently, and VEGF production was regulated by an EP4 receptor. Activation of intracellular cAMP regulated VEGF production. VEGF production was decreased by PKA and PI3K inhibitors via intracellular cAMP. CONCLUSIONS: PGE2 stimulates VEGF production via the EP4 receptor in NPDFs. These results indicate that PGE2-induced VEGF production is mediated, at least partially, through cAMP-dependent signaling pathways. Therapies targeting the EP4 receptor may be effective in inhibiting the development of nasal polyps.

Development of animal models of otitis media.

Otitis media is defined as inflammation of the middle ear, including the auditory ossicles and the Eustachian tube. Otitis media is a major health problem in many societies. The causes of otitis media includes infection and anatomic/physiologic, host, and environmental factors. In general, otitis media is a childhood disease, and anatomic and physiologic changes have great effects on its development. Thus, in vitro or human experimental studies of otitis media are difficult. Several experimental animal models have been introduced to investigate the pathogenesis and treatment of otitis media. However, none are ideal. The aim of this review is to provide a brief overview of the current status of animal models of otitis media with effusion, acute otitis media, and cholesteatoma. This review will assist determination of the most appropriate animal models of otitis media.

Effect of diesel exhaust particles on human middle ear epithelial cells.

OBJECTIVE: In the present study, we investigate whether diesel exhaust particles (DEPs) cause cytotoxicity and induce inflammation or increase the expression of mucin in immortalized human middle ear epithelial cell lines (HMEECs). Several publications have shown an association between traffic-related air pollutants and otitis media. Additionally, DEP have been shown to cause inflammation and an allergic response in the airways. METHODS: Cell viability following DEP treatment was investigated in HMEECs using the MTT assay. We measured the expression of the inflammatory cytokines TNF-α and COX-2 and the mucin genes MUC5AC and MUC5B using semiquantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: Cell viability tests showed that exposure to more than 80 µg/mL of DEP caused a decrease in cell viability. DEP exposure also increased the expression of MUC5AC, but did not induce the expression of MUC5B in HMEECs. CONCLUSION: DEP decreased cell viability, induced an inflammatory response, and increased mucin gene expression in HMEECs. These findings support the hypothesis that environmental diesel exposure is a risk factor for otitis media.

The inhibitory effect of honokiol, a natural plant product, on vestibular schwannoma cells.

OBJECTIVES/HYPOTHESIS: As the molecular biology of vestibular schwannoma (VS) is better understood, new means of targeting the pathways involved for intervention in schwannoma cells are being developed. Honokiol, a bioactive constituent of Magnolia officinalis, has attracted attention due to its diverse biological effects. This study was conducted to determine the inhibitory effect of honokiol on schwannoma cell proliferation. METHODS: HEI 193 cells were used to investigate the growth-inhibitory effects of honokiol. Cell proliferation was assessed by MTT assays. Apoptosis was measured by flow cytometry analysis and immunofluorescence staining including Hoechst 33342 and TUNEL. Western blot analysis was used to assess the potential inhibition of extracellular signal-regulated kinase (ERK) and AKT signaling by honokiol. RESULTS: Honokiol exhibited significant antiproliferative activity in a dose-dependent manner on HEI 193 cells. Significant apoptosis was detected on schwannoma cells with 7 mg/mL(IC50) honokiol. Western blot analysis showed significant inhibition of ERK phosphorylation. CONCLUSIONS: Honokiol, a low molecular weight natural product, inhibits cell proliferation and promotes apoptosis in schwannoma cells by targeting the ERK pathway. Our data suggest that honokiol can be evaluated as a chemotherapeutic agent for VS.

Simultaneous versus subsequent intratympanic dexamethasone for idiopathic sudden sensorineural hearing loss.

OBJECTIVE: The authors compared the efficacy of simultaneous and subsequent intratympanic dexamethasone injections for the treatment of idiopathic sudden sensorineural hearing loss. STUDY DESIGN: Prospective randomized controlled multicenter study. SETTING: Three tertiary university hospitals. SUBJECTS AND METHODS: In the simultaneous intratympanic dexamethasone group, intratympanic dexamethasone was given initially with systemic steroids. In the subsequent intratympanic dexamethasone group, intratympanic dexamethasone was given 7 days after systemic treatment. The authors compared hearing outcomes between the groups according to Siegel's criteria and frequency (0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz). RESULTS: A total of 88 patients were analyzed in this study. There was no difference between the groups in hearing recovery according to Siegel's criteria or frequencies. Neither recovery time nor early recovery differed between the groups. In the subsequent intratympanic dexamethasone group, 15 patients showed hearing recovery within 7 days and did not need intratympanic dexamethasone treatment. After intratympanic dexamethasone treatment, >28% (25/88) of the patients complained of otalgia, transient dizziness, ear fullness, and headache. Five percent of the patients showed small, transient perforations and otorrhea during intratympanic dexamethasone treatment. CONCLUSIONS: Simultaneous intratympanic dexamethasone did not confer an additional hearing gain or earlier recovery rate compared with subsequent intratympanic dexamethasone. A considerable number of patients did not need intratympanic dexamethasone for idiopathic sudden sensorineural hearing loss, and some patients experienced unnecessary side effects due to intratympanic dexamethasone. Therefore, the use of intratympanic dexamethasone is recommended only for subsequent or salvage treatment of idiopathic sudden sensorineural hearing loss after systemic steroid treatment.

Repair of large traumatic tympanic membrane perforation with a Steri-Strips patch.

OBJECTIVE: To investigate the effects of the Steri-Strips patch (3M) on the treatment of large traumatic tympanic membrane perforations (TMP). STUDY DESIGN: Prospective, randomized, controlled. SETTING: Tertiary university hospital. SUBJECTS AND METHODS: A randomized prospective analysis was performed between February 2009 and January 2011 for the treatment of traumatic TMP larger than 50% of the entire tympanic membrane. The results of closure rate, closure time, hearing gain, and rate of otorrhea between conservative observation, paper patching, and Steri-Strips patching groups were compared. RESULTS: In total, 87 patients were analyzed in this study. The closure rates of the perforations in the Steri-Strips patching, paper patching, and observation groups were 93.3%, 84.2%, and 78.9%, respectively. There was no statistically significant difference in tympanic membrane closure rate between the 3 groups. The Steri-Strips technique decreased the need for repeat procedures. Overall, the Steri-Strips and paper patching groups showed shorter healing times compared with the observation group. However, there was an increased rate of otorrhea in the Steri-Strips group compared with the observation group. CONCLUSION: Steri-Strips patching reduced the healing time and need for repeat procedures in patients with large traumatic TMPs. However, the occurrence of otorrhea was significantly more common in patients treated with the Steri-Strips technique.

Otolith function in patients with head trauma.

This study evaluates the otolith function of patients with head trauma, postulating that otolith dysfunction is a cause of nonspecific dizziness after head trauma. We prospectively enrolled 28 patients referred within 3 months after head trauma between March 2007 and December 2009. Pure tone audiometry, caloric testing and otolith function tests, including cervical vestibular evoked myogenic potential (cVEMP) and subjective visual vertical (SVV) tests, were performed on all patients. The relationship between otolith function and otologic symptoms was analyzed. Of the 28 patients with head trauma, 18 complained of dizziness and 12 experienced hearing loss, including 6 patients who complained of both. On defining otolith dysfunction as an abnormal cVEMP or abnormal SVV, a significant difference in otolith dysfunction existed between the groups with and without dizziness [72 (13/18) vs. 20% (2/10)]. In contrast, no significant difference in otolith dysfunction was detected between the abnormal and normal hearing groups. A significant number of the patients who complained of nonspecific dizziness after trauma had abnormal otolith function. After trauma, when patients complain of dizziness, vestibular function tests, including otolith function tests, should be considered.

Vestibular schwannoma in patients with sudden sensorineural hearing loss.

Sudden sensorineural hearing loss (SSNHL) has several etiologies. It may be a presenting symptom of vestibular schwannoma (VS). This study aimed to establish the incidence of VS in patients with SSNHL, and we report several unusual cases among these patients. We reviewed retrospectively the charts and magnetic resonance imaging (MRI) findings of all adult patients who presented with SSNHL between 2002 and 2008. We utilized three-dimensional fast imaging with steady-state acquisition temporal MRI as a screening method. Of the 295 patients with SSNHL, VS was found in 12 (4%). All patients had intrameatal or small to medium-sized tumors. There were three cases with SSNHL in one ear and an incidental finding of intracanalicular VS in the contralateral ear. There were four cases of VS that showed good recovery from SSNHL with corticosteroid treatment. There were two cases that mimicked labyrinthitis with hearing loss and vertigo. A greater number of cases than expected of VS were detected in patients with SSNHL, as a result of increasing widespread use of MRI. Various unusual findings in these patients were identified. MRI would seem to be mandatory in all cases of SSNHL.

Comparison of Conventional Excision via a Sublabial Approach and Transnasal Marsupialization for the Treatment of Nasolabial Cysts: A Prospective Randomized Study.

OBJECTIVES: Surgical excision via a sublabial approach is considered the standard treatment for nasolabial cysts. Although transnasal marsupialization has been proposed as an alternative method, no prospective study has compared the effectiveness of these techniques. We thus compared the surgical procedure, operating time, postoperative pain, complications, and recurrence rate between the two surgical methods. METHODS: Twenty patients diagnosed with nasolabial cysts were allocated randomly into two groups according to the surgical technique. In the sublabial approach group, the cysts were excised completely using a sublabial approach, while in the transnasal marsupialization group, the cysts were marsupialized transnasally under the guidance of nasal endoscopes. The pure operating time was measured and postoperative pain was evaluated using a visual analog scale. Complications after the procedure were assessed and recurrence was determined according to the clinical symptoms and postoperative radiologic findings. RESULTS: The transnasal marsupialization group had significantly shorter operating times, less postoperative pain, lower complication rates, and shorter duration of side effects than the sublabial approach group. No recurrence occurred in either group after a 1-yr follow-up period. CONCLUSION: Although both methods are effective for treating nasolabial cysts, the transnasal marsupialization of nasolabial cysts has many benefits over the conventional sublabial approach. Therefore, we propose that transnasal marsupialization be the treatment of choice for nasolabial cysts.

Epigallocatechin-3-gallate inhibits interleukin-1beta-induced MUC5AC gene expression and MUC5AC secretion in normal human nasal epithelial cells.

It has been reported that the proinflammatory cytokine interleukin-1beta (IL-1beta) induces mucus hypersecretion in normal human nasal epithelial (NHNE) cells and that the MAP kinase pathway may be an important signal pathway in IL-1beta-induced MUC5AC gene expression. Green tea (Camellia sinensis) polyphenols are potent anti-inflammatory agents and have been shown to inhibit inflammation in tumor cell lines and cultured respiratory epithelial cells. In this study, we examined the effect of (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on IL-1beta-induced MUC5AC gene expression and secretion in NHNE cells. After cells had been treated with IL-1beta (10 ng/ml) and pretreated with EGCG (10, 50 and 100 microM), mRNA expression of MUC5AC was determined by real-time polymerase chain reaction. The suppression of each signal pathway protein was determined by Western blot analysis after treatment with IL-1beta and EGCG, respectively. IL-1beta increased MUC5AC gene expression and MUC5AC secretion. EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number. Our data suggest that EGCG may be an effective inhibitor of IL-1beta-induced mucus hypersecretion.