A double-blinded, randomized controlled clinical trial of hydrogen inhalation therapy for idiopathic sudden sensorineural hearing loss.

Background: Hydrogen (H2) has been reported to be effective in reducing hearing loss due to several causes in animal studies. However, no study has examined the effectiveness of H2 in treating hearing loss in humans. Thus, we investigated whether H2 is effective for the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). Materials and methods: We conducted a double-blind randomized controlled trial at six hospitals between June 2019 and March 2022. The study protocol and trial registration have been published in the Japan Registry of Clinical Trials (jRCT, No. jRCTs06119004). We randomly assigned patients with ISSNHL to receive either H2 (H2 group) or air as a placebo (control group) through inhalation combined with the administration of systemic glucocorticoids and prostaglandin E1. The primary outcome was the hearing threshold and changes in hearing threshold 3 months after therapy. In contrast, the secondary outcomes included the proportion of patients with a good prognosis (complete recovery or marked improvement). Results: Sixty-five patients with ISSNHL (31 and 34 in the H2 and control groups, respectively) were included in this study. The hearing threshold 3 months after treatment was not significantly different between the groups; 39.0 decibels (dB) (95% confidence interval [CI]: 28.7-49.3) and 49.5 dB (95% CI: 40.3-58.7) in the H2 and control groups, respectively. In contrast, the changes in hearing threshold 3 months after treatment was 32.7 dB (95% CI: 24.2-41.3) and 24.2 dB (95% CI: 18.1-30.3) in the H2 and control groups, respectively. Consequently, the changes in hearing threshold were significantly better in the H2 group than in the control group (P = 0.048). However, no adverse effects due to the inhalation of H2 gas have been reported. Conclusion: This is the first study to investigate the efficacy of H2 for the treatment of ISSNHL in humans. The results suggest that H2 therapy may be effective for ISSNHL treatment. Clinical trial registration: [https://jrct.niph.go.jp/re/reports/detail/10442], identifier [jRCTs06119004].

Cartilage tympanoplasty for recurrent cholesteatoma using a single sliced cartilage graft: Our experience in 14 ears.

Our procedure may provide a useful alternative in cases where previous surgeries have failed to eradicate the cholesteatoma.

Volume-rendered computed tomography images of the surgical field for endolymphatic sac surgery.

PURPOSE: Identification of the endolymphatic sac has failed occasionally. Postoperative complications have also rarely been reported. Given a safer and more reliable surgery, preoperative anatomical assessments are valuable, however, the vestibular aqueduct has seldom been seen with multi-planar reconstruction (MPR) computed tomography (CT) images yet. Our study aimed to determine the significance and utility of volume-rendered (VR) CT images of the surgical field for identifying the vestibular aqueduct, compared with MPR CT images. SUBJECTS AND METHODS: 14 patients with Meniere's disease who underwent endolymphatic sac surgery between 2008 and 2011. Location and size of the vestibular aqueduct were assessed using VR and MPR CT images, independently. RESULTS: Accuracy of identifying the location differed significantly between VR and MPR CT images (rate of total correct evaluations: 100% by VR CT images vs 75% by MPR CT images, p = 0.02). Size was correctly identified in cases with a small endolymphatic sac using VR CT images (rate of total correct evaluations for size of the vestibular aqueduct: 100% by VR CT vs 57% by MPR CT, p = 0.046). VR CT images also demonstrated clearly the relationship between the endolymphatic sac and high jugular bulb. In two cases, the endolymphatic sac was identified by VR images, not by MPR images. CONCLUSION: Accurate information about the location and size of vestibular aqueduct can allow sac surgeons to identify a tiny endolymphatic sac more easily and certainly, and also aids surgical trainees to learn sac surgery safely.

Japanese translation, cross-cultural adaption and multicentre validation of the Zurich chronic middle ear inventory (ZCMEI-21-Jap).

OBJECTIVE: In the assessment of chronic otitis media (COM) and its treatment, patient-reported outcomes are becoming increasingly important. The aim of the present study was to translate and validate the Zurich chronic middle ear inventory (ZCMEI-21) in Japanese in order to provide the first Japanese-language instrument for measuring health-related quality of life (HRQoL) in COM. METHODS: The ZCMEI-21 was translated into Japanese according to published guidelines. In order to assess validity, the ZCMEI-21-Jap total score was compared to a question directly addressing HRQoL as well as the five-level version of the EQ-5D questionnaire, a generic measure of HRQoL. RESULTS: Demographic data and validity were assessed in a total of 91 COM patients. The ZCMEI-21-Jap total and subscale scores were well comparable to those of the original validation study. Cronbach's α of the ZCMEI-21-Jap was 0.85, indicating an excellent internal consistency. The ZCMEI-21-Jap total score showed a strong correlation (r=0.68, p<0.0001) to the question directly addressing HRQoL and, as expected, only a moderate correlation to the EQ-5D scores (r=0.49, p<0.0001 for descriptive system score and r=0.44, p<0.0001 for VAS score). CONCLUSION: We successfully translated the ZCMEI-21 into Japanese and were able to obtain sufficient information during the validation process for the use of the ZCMEI-21-Jap to quantify HRQoL in patients with COM. With the current study, we aim to take a step forward towards an international standardization of reporting HRQoL in COM.

The gray scale value of ear tissues undergoing volume-rendering high-resolution cone-beam computed tomography.

OBJECTIVE: When the thresholds for VR reconstruction from multi-slice CT images are changed, problems develop when assessing pathologies in the absence of standardized thresholds. The advantages of CBCT include lower radiation exposure compared with other techniques and better visualization of small ear structures. However, a disadvantage is that the scanner provides unstandardized gray scale values, thus not CT numbers (Hounsfield units, HU). METHODS: We analyzed 88 sets of volume data obtained from temporal bones. The gray scale values were measured in aerated areas (two sites), along the ossicular chain (four sites) and in a bone area (one site) in the external and middle ears, and in soft tissue areas (five sites) and bone areas (two sites) in the inner ear. RESULTS: The standard male and female gray scale values were 2448-2970 and 2585-3091 for the aerated areas, 3248-4945 and 3359-5223 for the ossicular chains, 3368-4109 and 3371-4147 for soft tissues, and 4790-5776 and 5044-5959 for bone, respectively. Sex significantly affected the values (p<0.05). Significant differences between aerated areas and ossicular chains, and between soft tissues and bone, were evident (all p<0.0001). CONCLUSION: Volume-rendering (VR) images obtained by cone-beam computed tomography (CBCT) can be standardized simply by using fixed thresholds.

Five-year postoperative outcomes of modified staged canal wall up tympanoplasty for primary acquired cholesteatoma.

OBJECTIVE: For successful canal wall up tympanoplasty (CWUT) for the treatment of cholesteatoma, the restoration of stable middle ear aeration is also important; however, little is known about the dynamics of such aeration or the optimal surgical procedure. In this study, alternative additional surgical procedure was selected based on the grade of middle ear aeration during the second-stage operation. SUBJECTS AND METHODS: Patients included in this study underwent staged CWUT surgeries with mastoid cortex plasty (MCP) for well-aerated ears (grade 3) and bony mastoid obliteration (BMO) for poorly aerated ears (grade 2-0). Of the 115 ears included in this study, 62 were followed for more than 5 years. Recurrence rates with deep retraction pocket formation were assessed using the Kaplan-Meier survival analysis. The aeration was graded as: 0, no aeration; 1, aeration of only the mesotympanum; 2, aeration of the entire tympanic cavity; and 3, aeration of both the tympanic and mastoid cavities. RESULTS: No recurrence was observed in ears associated with grade 3 aeration that underwent MCP or in ears with grade 2 aeration that underwent BMO during second-stage surgery. For grades 0 and 1 aeration ears, the recurrence rates were 8.1% after 5 years and 12.5% after 10 years (p < 0.05), and the aeration of recurrent ears deteriorated to grade 0. CONCLUSION: Aeration during second-stage surgery predicts the final outcome.

Osseous eustachian tube and peritubal cells in patients with unilateral cholesteatoma comparison between healthy and diseased sides using high-resolution cone-beam computed tomography.

OBJECTIVES: We investigated the factors that may possibly cause primary acquired cholesteatoma. SETTING: University-affiliated hospital. SUBJECTS AND METHODS: In 20 adult patients with unilateral cholesteatoma, the sizes of the osseous eustachian tubes (ETs) and the extent of peritubal and mastoid cell development in healthy and diseased ears were examined using high-resolution cone-beam computed tomography. The height and width of the ET were measured at the tympanic orifice, the isthmus, and the midpoint, as was the length of its axis. We also assessed the extent of development of peritubal and mastoid cells. RESULTS: There were no significant differences in the size of the osseous ET between the healthy and cholesteatoma sides, but significant correlations were found in height and width between the sides at the tympanic orifice and at the isthmus. In 80% of ears with cholesteatoma, the development of both peritubal and mastoid cells was poor and, in 5% more, one or the other was poor. Mastoid and peritubal cell development was good in 60% of healthy ears and poor in 20%. In the remaining 20%, only peritubal cell development was poor. CONCLUSION: There were no significant differences in the size of the osseous ET between the healthy and diseased sides of patients with unilateral cholesteatoma. Our results indicate that inhibition of air cell development in not only the mastoid region but also the peritubal region may contribute to cholesteatoma development.

Clinical features, presenting symptoms, and surgical results of congenital cholesteatoma based on Potsic's staging system.

CONCLUSIONS: Potsic's staging system is a clinically useful procedure for evaluating the extent of congenital cholesteatoma (CC). OBJECTIVES: We investigated the clinical features, presenting symptoms, and surgical results of CC according to Potsic's staging system. METHODS: A total of 71 patients who had undergone surgery at our hospital were retrospectively analyzed for presenting symptoms, the location of cholesteatoma, and surgical results according to Potsic's staging system. RESULTS: Of the 71 patients, 21 were classified as Potsic stage I, 9 as stage II, 31 as stage III, and 10 as stage IV. More than half of the patients with early-stage CC (stages I and II) were diagnosed asymptomatically by a chance visit to a clinic or on ear screening. Others were diagnosed following a complaint of hearing loss, acute otitis media, or otitis media with effusion. The location of CC varied somewhat by stage. In stage I CC, the most frequent location was behind the anterior-superior quadrant of the tympanic membrane; however, in stage III CC, it was behind the posterior-superior quadrant. All patients were treated surgically. Recurrence was detected in 2 of the 71 patients (2.8%); both had stage II CC. Recurrent lesions were removed during revision surgery.

Liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear ischemia: an experimental study in the gerbil.

The effects of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier, were experimentally investigated in gerbils in the context of alleviation of hearing loss after transient cochlear ischemia. Animals were randomly assigned to receive 2 mL/kg of either LEH (P50O2=15 mmHg) or saline 1h after the experimental induction of 15 min of ischemia. Sequential recordings of auditory brainstem response (ABR) showed that administration of LEH prevented hearing loss due to cochlear ischemia. The mean ABR threshold at 32 kHz on day 1 was 21 ± 7 dB in the LEH group (n=6) and 45 ± 6 dB in the saline group (n=6). Thereafter, hearing impairment gradually improved up to day 7 in both groups. The animals were then subjected to histological study, which revealed that there was more substantial loss of the inner hair cells, but not the outer hair cells, in the saline group as compared to the LEH group. These results suggest that LEH is an efficient agent with regard to protection against hearing loss and underlying hair cell damager due to ischemic insult.

A case of pneumolabyrinth induced by Eustachian tube air inflation.

OBJECTIVES: Here, we report a case of pneumolabyrinth induced by Eustachian tube air inflation (ETAI) with a catheter and present evidence that multiple air bubbles entered the perilymphatic space through a preexisting oval window fistula. SETTING: Tertiary referral center. PATIENT: Sixty-six-year-old woman. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Air bubbles in the perilymphatic space revealed by cone beam computed tomography (CT) volume rendering imaging. RESULTS: The patient was referred to us because of vertigo, unsteadiness, and right hearing loss after ETAI using a Eustachian tube catheter. On Day 2, an audiogram showed right total deafness, and the perilymphatic space could not be identified on T2-weighted magnetic resonance imaging. A high-resolution cone beam CT scan obtained on Day 3 showed multiple air bubbles in the labyrinth. The volume rendering images clearly revealed a larger air bubble in the vestibule inside the footplate of the stapes and small air bubbles in the horizontal semicircular canal, superior semicircular canal, and basal and second turns of the cochlea. This finding indicates that the air bubbles entered the perilymphatic space through an oval widow fistula caused by a sudden elevation in intratympanic air pressure. Two months later, the air bubbles had disappeared, and the patient's high tone hearing had improved slightly. CONCLUSION: ETAI can cause a pneumolabyrinth if the intratympanic pressure rises beyond a certain critical level. In this situation, volume rendering imaging of high-resolution cone beam CT can be used to quantify and identify the air bubbles present. The images taken in this study suggest that air bubbles entered the perilymphatic space through a perilymphatic fistula.

Position of TORP on the stapes footplate assessed with cone beam computed tomography.

OBJECTIVE: To improve hearing outcomes of ossiculoplasty with a total ossicular replacement prosthesis (TORP) in ears lacking a footplate superstructure, 3-dimensional computed tomography (3D CT) images were reconstructed to verify the position of the TORP on the footplate and contact between the TORP and the stapes footplate. STUDY DESIGN: Retrospective study. SETTING: University-affiliated tertiary referral center. PATIENTS: Six ears of 6 patients who underwent ossiculoplasty with TORP and were followed for greater than 3 years postoperatively. INTERVENTION: Cone beam CT (CBCT) images. MAIN OUTCOME MEASURES: An en face view of the stapes footplate and a volume-rendered 3D image were reconstructed. RESULTS: The en face view of the stapes footplate showed whether the TORP was centered on the stapes footplate. Volume-rendered 3D CBCT images revealed TORP malpositioning or migration, which were not detected on 2-dimensional CBCT images. In such cases, the TORP shaft was in contact with the wall of the oval window niche or the TORP had moved from the stapes footplate. CONCLUSION: Accurate visualization of TORP location on the footplate is important. Images that accurately show the position of the TORP on the stapes footplate will help improve hearing outcomes.

Liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear ischemia and reperfusion in the gerbil.

To test liposome-encapsulated hemoglobin (LEH) in transient cochlear ischemia/reperfusion as a model of sudden deafness, Mongolian gerbils were randomly assigned to receive 2 mL/kg of either low-affinity LEH (l-LEH, P5002 = 40 mm Hg), high-affinity LEH (h-LEH, P5002 = 10 mm Hg), homologous red blood cells (RBCs), or saline (each group n = 6) 30 min before 15-min occlusion of the bilateral vertebral arteries and reperfusion. Sequential changes in hearing were assessed by auditory brain response 1, 4, and 7 days after ischemia/reperfusion, when the animals were sacrificed for pathological studies. h-LEH was significantly more protective than l-LEH in suppressing hearing loss, in contrast to RBC or saline treatment, at 8, 16, and 32 kHz, where hearing loss was most severe (P < 0.05 between any two groups) on the first day after cochlear ischemia/reperfusion. Thereafter, hearing loss improved gradually in all groups, with a significant difference among groups up to 7 days, when morphological studies revealed that the inner hair cells but not the outer hair cells, were significantly lost in the groups in the same order. The results suggest that pretreatment with h-LEH is significantly more protective than l-LEH in mitigating hearing loss and underlying pathological damage, in contrast to transfusion or saline infusion 7 days after transient cochlear ischemia/reperfusion.

Clinical features and outcomes of four patients with invasive fungal sinusitis.

OBJECTIVE: The frequency of invasive fungal sinusitis (IFS) has increased in recent years with the use of steroids, onset of diabetes mellitus, and the administration of antibacterial agents. We report on the clinical features and outcomes of four patients with IFS involving the cavernous sinus and orbit. Prognostic factors facilitating an early diagnosis are described, and the usefulness of combination therapy involving systemic administration of antifungal agents and surgical intervention is discussed. METHODS: We treated four patients with IFS between March 2003 and November 2007 at Ehime University Hospital. Patients were two males and two females, aged from 61 to 74 years (mean 67.8 years). RESULTS: With regard to clinical symptoms, headache was observed in all patients, and cranial nerve paralysis (visual disturbance, blindness, cheek paresthesia) was seen in 3 patients. ß-D-Glucan levels in four patients were high compared with normal values. Aspergillus was histopathologically identified from biopsy specimens in all patients. One patient was complicated with Candida in addition to the Aspergillus infection. Orbital exenteration and ESS were performed in 2 patients as surgical debridement. In all patients, systemic administration of antifungal agents was initiated after surgery. CONCLUSIONS: All patients received strategic treatment with surgery and systemic administration of anti-fungal agents. The single fatality was due to brain infarction caused by the spread of Aspergillus, and the remaining three patients are still alive. Our observations in these patients suggest that early diagnosis and strategic treatment may improve the prognosis of IFS.

Local hypothermia in the treatment of idiopathic sudden sensorineural hearing loss.

OBJECTIVE: The additive effects of local hypothermia and restricted activity in the treatment of idiopathic sudden sensorineural hearing loss (ISSHL) were investigated by case-matched study as a multicenter (13 hospitals) pilot trial. PATIENTS AND METHODS: In a preliminary experiment, we evaluated the effects of cooled water pillow (15 degrees C). Cooling the neck and mastoid with the pillow decreased the tympanic membrane temperature for 1.4 degrees C in 2h without causing uncomfortable sensation or frostbite. In this study, 86 patients with ISSHL were enrolled in the hypothermic group, which received hypothermic treatment with restricted activity in addition to medication, and 86 ISSHL patients constituted the control group, which received the same medication but without cooling and rest. Control patients were selected retrospectively from case records by matching the experimental patients with respect to age, gender, days until the start of treatment, hearing loss, shape of the audiogram, and accompanying vertigo. The patients in the hypothermic group were admitted and treated with a cooled water pillow for 48h, in addition to conventional drug treatment (e.g., 60 mg of prednisone) for 7 days. The water pillow was cooled to 15 degrees C and was changed 4-5 times per day. The patients used the water pillow for the first 48 h after admission, with restricted activity. The control patients received only the medications. RESULTS: Hearing results were evaluated using criteria proposed by the Sudden Sensorineural Hearing Loss Research Group of the Japanese Ministry of Health and Welfare. The recovery rates were judged 6 months after onset. The recovery rate in the hypothermic group was significantly (p<0.05) better than that in the control group. When the comparison was limited to younger patients, the use of the cooled water pillow was effective in facilitating the recovery of hearing. CONCLUSIONS: Hearing restoration in ISSHL may be improved by adding mild hypothermia and restricted activity to the conventional treatment.

Prednisolone prevents transient ischemia-induced cochlear damage in gerbils.

CONCLUSIONS: Prednisolone protects against inner ear damage, even when administered after ischemic injury in Mongolian gerbils. OBJECTIVE: The effect of prednisolone on ischemia-induced cochlear damage was investigated in Mongolian gerbils. MATERIALS AND METHODS: The bilateral vertebral arteries were occluded for 15 min to transiently induce cochlear ischemia, followed by an intraperitoneal injection of prednisolone (1 mg/kg) or physiological saline (control). Sequential changes in hearing were evaluated by recording the auditory brainstem response (ABR) before and at 1, 4, and 7 days after treatment. In our histologic analysis, the numbers of dead and intact inner hair cells (IHCs) were counted in specimens stained with rhodamine-phalloidin. RESULTS: In control animals, transient ischemia increased the ABR threshold (24.2 +/- 8.6 dB) within 7 days of treatment, whereas prednisolone-treated animals exhibited a threshold of 14.2 +/- 9.2 dB. Furthermore, the percent IHC loss at the basal turn of the cochlea was 26.5 +/- 11.4% in control animals compared with 5.3 +/- 3.0% in the prednisolone-treated group.

Glutamate agonist causes irreversible degeneration of inner hair cells.

Glutamate neurotoxicity in cochlear hair cells was investigated by administering the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) into the scala tympani of Mongolian gerbils. AMPA administration caused the formation of large number of vacuoles in the inner hair cells (IHCs) and dendritic terminals. The number of degenerated hair cells was counted using rhodamine-phalloidin and Hoechst 33342 staining. The administration of 50 microM AMPA caused reversible elevation of the auditory brainstem response threshold without loss of IHCs. In contrast, 200 microM AMPA induced a substantial elevation of the auditory brainstem response threshold with the characteristic disappearance of IHCs. As cochlear ischemia involves excessive glutamate release, these results suggest that an elevated glutamate level in the cochlea is responsible for the progressive IHC death related to ischemic injury.

Insulin-like growth factor 1 treatment via hydrogels rescues cochlear hair cells from ischemic injury.

This study was designed to investigate the protective effects of recombinant human insulin-like growth factor 1 (rhIGF1), applied locally via a hydrogel, against ischemic damage of the cochleae in gerbils. A hydrogel was immersed in rhIGF1 or saline and was applied on the round window membrane 30 min after the ischemia. Local rhIGF1 treatment significantly reduced the elevation of auditory brain responses thresholds at a frequency of 8 kHz on days 1, 4, and 7 after ischemia. A histological analysis revealed increased survival of inner hair cells in the animals treated with rhIGF1 via the hydrogel 7 days after ischemia. These findings showed that local rhIGF1 application using a hydrogel has the potential to protect the cochleae from ischemic injury.

Postischemic mild hypothermia alleviates hearing loss because of transient ischemia.

The effect of postischemic mild hypothermia on the inner ear has not been clarified. In this study, we investigated whether hypothermia after transient ischemia could prevent cochlear damage and its therapeutic time window. Mongolian gerbils were divided into six groups: a sham-operation group, a normothermia group, and four hypothermia groups in which hypothermia was induced 1-7, 1-4, 3-6, and 6-9 h after reperfusion. Animals subjected to postischemic mild hypothermia within 3 h after reperfusion had attenuated hearing loss and inner hair cell loss. The protective effect was greater when hypothermia was induced earlier and had a longer duration. This implies that mild hypothermia after ischemia could have therapeutic effects for inner ear ischemic damage.

Ischemic damage increases nitric oxide production via inducible nitric oxide synthase in the cochlea.

The present study was designed to elucidate the dynamic changes of nitric oxide (NO) production in the perilymph and to investigate the immunostaining for inducible nitric oxide synthase (iNOS) in the cochlea for 7 days after transient cochlear ischemia. Moreover, aminoguanidine, which is a selective iNOS inhibitor, was administrated immediately following ischemia and every 24h thereafter for 7 days to investigate whether the production of NO is dependent on the iNOS pathway. Significant increases in the oxidative NO metabolites, nitrite (NO(2)(-)) and nitrate (NO(3)(-)), were measured on day 1 using an in vivo microdialysis and on-line high performance liquid chromatography (HPLC) system. The immunostaining for iNOS was strongly expressed on days 1 and 4 and returned to normal on day 7 after the ischemia. The administration of aminoguanidine reduced the oxidative NO metabolites on day 1 and suppressed the expression of iNOS. These findings suggest that transient ischemia causes a remarkable increase in NO production in the perilymph, which might be attributable to the iNOS pathway.

Kanamycin ototoxicity in glutamate transporter knockout mice.

Glutamate-aspartate transporter (GLAST), a powerful glutamate uptake system, removes released glutamate from the synaptic cleft and facilitates the re-use of glutamate as a neurotransmitter recycling system. Aminoglycoside-induced hearing loss is mediated via a glutamate excitotoxic process. We investigated the effect of aminoglycoside ototoxicity in GLAST knockout mice using the recorded auditory brainstem response (ABR) and number of hair cells in the cochlea. Kanamycin (100 mg/mL) was injected directly into the posterior semicircular canal of mice. Before the kanamycin treatment, there was no difference in the ABR threshold average between the wild-type and knockout mice. Kanamycin injection aggravated the ABR threshold in the GLAST knockout mice compared with the wild-type mice, and the IHC degeneration was more severe in the GLAST knockout mice. These findings suggest that GLAST plays an important role in preventing the degeneration of inner hair cells in aminoglycoside ototoxicity.