Research Application of Laser-induced Shock Wave for Studying Blast-induced Cochlear Injury.

The ear is the organ most susceptible to explosion overpressure, and cochlear injuries frequently occur after blast exposure. Blast exposure can lead to sensorineural hearing loss (SNHL), which is an irreversible hearing loss that negatively affects the quality of life. Detailed blast-induced cochlear pathologies, such as the loss of hair cells, spiral ganglion neurons, cochlear synapses, and disruption of stereocilia, have been previously documented. However, determining cochlear sensorineural deterioration after a blast injury is challenging because animals exposed to blast overpressure usually experience tympanic membrane perforation (TMP), which causes concurrent conductive hearing loss. To evaluate pure sensorineural cochlear dysfunction, we developed an experimental animal model of blast-induced cochlear injury using a laser-induced shock wave. This method avoids TMP and concomitant systemic injuries and reproduces the functional decline in the SNHL component in an energy-dependent manner after LISW exposure. This animal model could be a platform for elucidating the pathological mechanisms and exploring potential treatments for blast-induced cochlear dysfunction.

Experiences of Percutaneous Endoscopic Approach for the Mastoid Lesions: A Novel Minimally Invasive Ear Surgery.

OBJECTIVES: We developed a novel keyhole surgery, named "percutaneous endoscopic ear surgery" (PEES), with the aim of further reducing the invasiveness of otologic surgery. We reported the cases we encountered and retrospectively analyzed the invasiveness of PEES. METHODS: We analyzed the ears of eight patients who underwent PEES for mastoid lesions that could not be manipulated with transcanal endoscopic ear surgery (TEES) at our hospital between July 2021 and November 2022. We performed PEES alone in three patients, including one case of type A (preauricular incision) and two cases of type B (retroauricular incision). The last five patients underwent combined endoscopic ear surgery, which is simultaneous PEES and TEES. In these cases, one patient underwent type A PEES, and four patients underwent type B PEES. RESULTS: PEES was performed in all patients without converting to conventional microscopic mastoidectomy. The mean length of skin incisions was 19.1 ± 4.5 mm, which was smaller than that in conventional mastoidectomy. In all cases, the average length of the major axis of the keyhole was <10 mm, indicating that sufficient minimally invasive surgery was achieved. The average depth from the keyhole to the deepest site was 21.6 ± 8.9 mm. There was no change in the mean hearing level before and after the surgery. CONCLUSION: PEES is a minimally invasive procedure for manipulating lesions in the mastoid. In addition, the combination of PEES and TEES is an ideal, minimally invasive procedure that can be used to treat all regions of the temporal bone.

Blast-Induced Central Auditory Neurodegeneration Affects Tinnitus Development Regardless of Peripheral Cochlear Damage.

Blast exposure causes serious complications, the most common of which are ear-related symptoms such as hearing loss and tinnitus. The blast shock waves can cause neurodegeneration of the auditory pathway in the brainstem, as well as the cochlea, which is the primary receptor for hearing, leading to blast-induced tinnitus. However, it is still unclear which lesion is more dominant in triggering tinnitus, the peripheral cochlea or the brainstem lesion owing to the complex pathophysiology and the difficulty in objectively measuring tinnitus. Recently, gap detection tests have been developed and are potentially well-suited for determining the presence of tinnitus. In this study, we investigated whether the peripheral cochlea or the central nervous system has a dominant effect on the generation of tinnitus using a blast-exposed mouse model with or without earplugs, which prevent cochlear damage from a blast transmitted via the external auditory canal. The results showed that the earplug (+) group, in which the cochlea was neither physiologically nor histologically damaged, showed a similar extent of tinnitus behavior in a gap prepulse inhibition of acoustic startle reflex test as the earplug (-) group, in which the explosion caused a cochlear synaptic loss in the inner hair cells and demyelination of auditory neurons. In contrast, both excitatory synapses labeled with VGLUT-1 and inhibitory synapses labeled with GAD65 were reduced in the ventral cochlear nucleus, and demyelination in the medial nucleus of the trapezoid body was observed in both groups. These disruptions significantly correlated with the presence of tinnitus behavior regardless of cochlear damage. These results indicate that the lesion in the brainstem could be dominant to the cochlear lesion in the development of tinnitus following blast exposure.

Effects of Unilateral Vagotomy on LPS-Induced Aspiration Pneumonia in Mice.

Respiratory-related dysphagia and aspiration pneumonia can be attributed to multiple causes. However, reproduction of multiple factor-related respiratory distress and aspiration pneumonia in a single animal model is challenging. To validate animals with vagal nerve palsy as novel models for severe aspiration pneumonia associated with respiratory distress, we investigated the effects of unilateral vagotomy on the swallowing function and severity of pneumonia after forced aspiration in mice. Unilateral vagotomy was performed in C57BL6 male mice that subsequently underwent evaluation of swallowing function by videofluoroscopic swallow study (VFSS) and histological assessments for aspiration pneumonia induced by lipopolysaccharide (LPS). VFSS examinations demonstrated that unilateral vagotomy did not cause apparent aspiration in mice, but it resulted in a significant loss of body weight (BW) due to decreased oral intake. In addition, when aspiration pneumonia was induced by forced administration of LPS, significantly prolonged BW loss and severe infiltration of inflammatory cells associated with aspiration pneumonia were observed in the mice that underwent unilateral vagotomy. In conclusion, the vagotomized mice showed appropriate characteristics as a model of aspiration pneumonia caused by multiple factors, including the paralysis of vocal fold movement and respiratory distress. This model can help elucidate the pathogenesis of aspiration pneumonia and the treatment methods for the respiration-compromised model.

Factors affecting the incidence of chorda tympani nerve transection in middle ear surgery.

Objective: To reveal the factors affecting the incidence of chorda tympani nerve (CTN) transection during middle ear surgery. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: We analyzed 232 ears (117 ears with cholesteatoma, 101 ears with chronic otitis media, and 14 ears with otosclerosis) that underwent tympanoplasty or stapes surgery during 2017-2020. Intervention: Eighty-four ears underwent transcanal endoscopic ear surgery (TEES), 103 ears underwent microscopic ear surgery (MES), and 45 ears underwent surgery using both endoscopy and microscopy (Dual). Main Outcome Measure: To confirm CTN transection, intraoperative endoscopic/microscopic video images were evaluated. We used the same video images to determine the anatomical variation of the CTN course in the middle ear. Results: In 18 ears (7.8%: 6/84 TEES ears [7.1%], 6/103 MES ears [5.8%], and 6/45 Dual ears [13.3%]), the CTN was cut during middle ear surgery. There was no significant difference in CTN transection among groups. In cholesteatoma patients, stapes involvement resulted in a significantly higher CTN transection incidence. CTN anatomical variants such as the "Attached Short type" and "Ultrashort type" showed a significantly higher CTN transection incidence. Conclusion: Although endoscopic surgery did not reduce the incidence of CTN transection during middle ear surgery, pathological involvement of the stapes and CTN anatomical variants, such as the "Attached Short type" and "Ultrashort type," may increase this incidence. Preoperative evaluation of stapes involvement and anatomical location of the CTN course could help identify patients at greater risk for iatrogenic CTN transection. Level of Evidence: 4.

Correlation of Blast-Induced Tympanic Membrane Perforation with Peripheral Cochlear Synaptopathy.

The auditory organs, including the tympanic membrane, cochlea, and central auditory pathway, are the most fragile components of the human body when exposed to blast overpressure. Tympanic membrane perforation (TMP) is the most frequent symptom in blast-exposed patients. The impact of TMP on the inner ear and central auditory system, however, is not fully understood. We aimed to analyze the effect of blast-induced TMP on the auditory pathophysiological changes in mice after blast exposure. Mice aged seven weeks were exposed to blast overpressure to induce TMP and allowed to survive for two months. All TMP cases had spontaneously healed by week three after the blast exposure. Compared with controls, blast-exposed mice exhibited a significant elevation in hearing thresholds and an apparent disruption of stereocilia in the outer hair cells, regardless of the occurrence or absence of TMP. The reduction in synapses in the inner hair cells, which is known as the most frequent pathology in blast-exposed cochleae, was significantly more severe in mice without TMP. A decrease in the number of excitatory central synapses labeled by VGLUT-1 in the cochlear nucleus was observed, however, regardless of the absence or presence of TMP. Our findings suggest that blast-induced TMP mitigates peripheral cochlear synaptic disruption but leaves the central auditory synapses unaffected, indicating that central synaptic disruption is independent of TMP and peripheral cochlear synaptic disruption. Synaptic deterioration in the peripheral and central auditory systems can contribute to the promotion of blast-induced hearing impairment, including abnormal auditory perception.

Y-27632, a ROCK inhibitor, improved laser-induced shock wave (LISW)-induced cochlear synaptopathy in mice.

Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells, it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.

Effect of shock wave power spectrum on the inner ear pathophysiology in blast-induced hearing loss.

Blast exposure can induce various types of hearing impairment, including permanent hearing loss, tinnitus, and hyperacusis. Herein, we conducted a detailed investigation of the cochlear pathophysiology in blast-induced hearing loss in mice using two blasts with different characteristics: a low-frequency dominant blast generated by a shock tube and a high-frequency dominant shock wave generated by laser irradiation (laser-induced shock wave). The pattern of sensorineural hearing loss (SNHL) was low-frequency- and high-frequency-dominant in response to the low- and high-frequency blasts, respectively. Pathological examination revealed that cochlear synaptopathy was the most frequent cochlear pathology after blast exposure, which involved synapse loss in the inner hair cells without hair cell loss, depending on the power spectrum of the blast. This pathological change completely reflected the physiological analysis of wave I amplitude using auditory brainstem responses. Stereociliary bundle disruption in the outer hair cells was also dependent on the blast's power spectrum. Therefore, we demonstrated that the dominant frequency of the blast power spectrum was the principal factor determining the region of cochlear damage. We believe that the presenting models would be valuable both in blast research and the investigation of various types of hearing loss whose pathogenesis involves cochlear synaptopathy.

Patency of Anterior Epitympanic Space and Surgical Outcomes After Endoscopic Ear Surgery for the Attic Cholesteatoma.

OBJECTIVE: To reveal the patency of the anterior epitympanic space (AES) and the surgical outcomes after transcanal endoscopic ear surgery (TEES) for attic cholesteatoma with a classification of anatomical variation of the AES. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Seventy-four ears (72 patients with early-stage (I or II) attic cholesteatoma) aged between 16 and 85 years (mean: 48.9 yr) who underwent TEES between 2015 and 2017 were analyzed. INTERVENTION: Tympanoplasty with atticoantrotomy was performed with TEES. TEES was performed using a rigid endoscope with an outer diameter of 2.7 mm. MAIN OUTCOME MEASURE: The tensor fold in the AES anatomical classification, the postoperative patency of the AES evaluated by computer tomography images, and hearing outcomes based on the American Academy of Otolaryngology and Head and Neck Surgery criteria were evaluated after TEES for early-stage attic cholesteatoma. RESULTS: There were 14 (18.9%) ears with a vertical tensor fold orientation, 29 (39.2%) ears with an oblique orientation, and 29 (39.2%) ears with a horizontal orientation. The total postoperative patency rate in the AES was 81.0%, without any significant difference in the anatomical variation in the AES, whereas the rate of preoperative complete tensor fold was 90.5%. Cholesteatoma recurrence was observed in three cases (4.1%), and all recurrent cases had obstructed AES. No significant difference was found in the postoperative air-bone gap regardless of the patency of the AES. CONCLUSION: Our findings indicate that TEES is useful in restoring ventilation in the AES, resulting in favorable management of cholesteatoma.

Tinnitus rat model generated by laser-induced shock wave; a platform for analyzing the central nervous system after tinnitus generation.

OBJECTIVE: Tinnitus is a phantom auditory sensation, which is mainly triggered by dysfunction of the peripheral auditory organ, such as cochlear disorders. Additionally, the central nervous system, specifically the limbic system, plays a crucial role in the generation and exacerbation of tinnitus. Therefore, to analyze the hypothesis that tinnitus has strong and specific association with the plastic changes in the limbic system, we assessed the neuronal plastic changes in the limbic system, including the hippocampus and the amygdala, in rats with single-sided tinnitus. METHODS: The cochlear damage was achieved by irradiating the cochlea with laser-induced shock wave (LISW). While both hearing loss and tinnitus were confirmed after exposure of rats to LISW, the degree of tinnitus was objectively measured using gap detection behavioral tests. Following the generation of hearing loss and tinnitus, plastic changes in the neurons of the limbic system were confirmed using a molecular marker (activity regulated cytoskeleton-associated protein; Arc). RESULTS: While the expression level of Arc-positive cells in the hippocampal CA1 showed an obvious increase in the hearing loss and tinnitus groups, a significant difference was found between the tinnitus and the control groups. In the dentate gyrus, although the largest number of Arc-positive cells was observed in the tinnitus group, there were no significant differences between the numbers of cells in the hearing loss and tinnitus groups compared to that in the control group. CONCLUSION: Although a significant increase of Arc-positive cells in the hippocampal CA1 was observed between the tinnitus group and control, no obvious tendencies of Arc-positive cells in the limbic system were observed between the rats with and without tinnitus behavior.

Regenerative Effect of a ROCK Inhibitor, Y-27632, on Excitotoxic Trauma in an Organotypic Culture of the Cochlea.

In the past, most inner ear diseases were thought to start with the impairment of the sensory epithelium of the cochlea before subsequently progressing to secondary neural degeneration. However, recent studies show that loss of primary synapses accompanied by excitotoxic degeneration of peripheral axons is likely to be the underlying pathology in sensorineural hearing loss. Rho-associated coiled-coil containing protein kinase (ROCK) inhibition has been reported to have neuroprotective and regenerative effects on synaptic pathways. Therefore, we analyzed the effect of ROCK inhibition using Y-27632 in a model of peripheral axonal damage in the spiral ganglion neurons created using the glutamate agonists, N-methyl-D-aspartate (NMDA) and kainic acid, to induce excitotoxic trauma in the explanted cochlea. The number of axons projecting to hair cells in the cochlea treated with Y-27632 was significantly greater than those in the cochlea treated only with NMDA + kainic acid. Furthermore, there was a significant increase in synapses between the spiral ganglion and the inner hair cells in the cochlea treated with Y-27632. The findings of this study suggest that ROCK inhibition could be a potential strategy for the regeneration of peripheral axons in the spiral ganglion and synapse formation in the inner hair cells of a cochlea that has sustained excitotoxic injury, which is one of the primary etiologies of inner ear disease.

Risk factors of post-tonsillectomy hemorrhage in adults.

OBJECTIVE: Tonsillectomy is an essential surgery and is conducted on both children and adults. However, the risk factors of post-tonsillectomy hemorrhage for adult patients remain unclear. In this study, we analyzed post-tonsillectomy hemorrhage in adult patients. METHODS: We retrospectively analyzed 325 adult patients who underwent a tonsillectomy between 2014 and 2018 in our facilities. RESULTS: The average age of this study's population was 31.7 ± 10.5 years (range: 19-70 years), and 250 (76.9%) patients were male. Overall, post-tonsillectomy hemorrhage occurred in 71 (21.8%) patients and 5 (1.5%) patients required a second surgery for hemostasis. Post-tonsillectomy hemorrhage often occurred on postoperative day zero or six. Using multiple logistic regression analysis, current smoking status (odds ratio 3.491; 95% confidence interval 1.813-6.723), male sex (odds ratio 3.924; 95% confidence interval 1.548-9.944), and perioperative non-steroidal anti-inflammatory drug administration (odds ratio 7.930; 95% confidence interval 1.004-62.64) were revealed as overall post-tonsillectomy hemorrhage risk factors. To analyze the hemorrhage period after tonsillectomy, we categorized the post-tonsillectomy hemorrhage patients into the primary (bleeding within postoperative day one) and secondary hemorrhage (bleeding on or after postoperative day two) groups. The current smoking status and older age were risk factors for primary hemorrhage and the current smoking status and sex (male) were risk factors for secondary hemorrhage. CONCLUSIONS: In this study, smoking status, sex, and perioperative non-steroidal anti-inflammatory drug administration were the clinical risk factors for adult post-tonsillectomy hemorrhage. Thus, smoking cessation is, at least, mandatory for patients who receive tonsillectomy to avoid post-tonsillectomy hemorrhage. LEVEL OF EVIDENCE: 4.

The influence of a noisy environment on hearing impairment and tinnitus: The hearing outcomes of 50-year-old male Japan ground self-defense force personnel.

OBJECTIVES: Hearing loss is one of the biggest health problems in the world and occupational noise-induced hearing loss is recognized as the most common work-related illness. However, many factors that result in hearing loss make it difficult to define the specific factor that induces noise-induced hearing loss. To access the exact effect of occupational noise exposure on hearing, we conducted a cross-sectional cohort study of the relationship between noise exposure and hearing impairment in 50-year-old male Japanese Self-Defense Force (JSDF) personnel who work in a noisy environment. This population is ideal for the detection of noise-induced hearing impairments due to the homogeneity of genetic and social backgrounds. METHODS: The data utilized in this study were collected from a "50-year-old milestone health examination" of the JSDF from July 2013 to October 2015. One thousand sixty-seven male personnel were enrolled in the study. Pure-tone audiometry was conducted with an audiometer. A survey questionnaire asked participants to self-report occupational noise exposure. RESULTS: This cohort revealed that noise-exposed personnel had a higher hearing threshold and a higher odds ratio in 1) the average threshold of 4 frequencies (500 + 1000 + 2000 + 4000 Hz / 4), 2) the average threshold of higher 3 frequencies (2000 + 4000 + 8000 Hz / 3), and 3) the threshold of 4 kHz compared to no noise-exposed control personnel. The prevalence of tinnitus was also significantly higher in the noise-exposed group. CONCLUSIONS: This study provides specific evidence for the relationship between noise exposure and noise-induced hearing impairments.

A Case of Gastric Meningeal Carcinomatosis Involving Bilateral Hearing Loss: The Difference between Clinical Images and Autopsy Findings.

We describe a rare case of meningeal carcinomatosis (MC) in a 66-year-old man who presented with bilateral deafness and vertigo, initially presumed to be neurofibromatosis type-2. Brain magnetic resonance imaging (MRI) of the patient revealed bilateral gadolinium enhanced masses at the cerebellopontine angle. However, multiple central nervous system symptoms, including loss of consciousness, gradually appeared. He had a history of gastric cancer; therefore, a lumbar puncture was performed. Cytological examination of the cerebrospinal fluid confirmed the presence of adenocarcinoma cells. The general condition of this patient worsened, and he died 46 days after the first onset of hearing loss. An autopsy was performed, and multiple infiltrations of adenocarcinoma cells in the brain were confirmed, though undetected by MRI. The prognosis of MC is extremely poor; therefore, rapid diagnosis is important to prevent mortality. Retrospectively, a lumbar puncture could have been conducted earlier to identify MC, especially in consideration of the clinical history of this patient.

Update on treatment options for blast-induced hearing loss.

PURPOSE OF REVIEW: The incidence of blast injuries has increased, and the ear is the highest risk organ. Ear injury induced by blast exposure is important in both military and civilian conditions. The permanent hearing loss caused by blast exposure is associated with a decline in the quality of life. In this review, I describe recent therapeutic strategies for each of the ear pathologies caused by blast exposure. RECENT FINDINGS: For tympanic membrane perforation after blast exposure, basic fibroblast growth factor (bFGF) has been used as a less invasive treatment to repair the tympanic membrane. The closure rates of tympanic membrane perforations treated with bFGF were reported to be comparable to those following conventional tympanoplasty.For sensorineural hearing loss after blast exposure, treatment with neurotrophic factors, such as nerve growth factor (NGF) or neurotrophin-3, antioxidants, and Atoh1 induction have recently been applied, and some of them were considered for clinical application. SUMMARY: Recent advances of therapeutics for blast-induced hearing loss, based on their pathologies, have been outlined. There are several promising therapeutic approaches for both middle and inner ear disorders after blast exposure; however, further research is needed to establish new treatments for blast-induced hearing dysfunction.

Blast-induced hearing loss.

The incidence of blast injury has increased recently. As the ear is the organ most sensitive to blast overpressure, the most frequent injuries seen after blast exposure are those affecting the ear. Blast overpressure affecting the ear results in sensorineural hearing loss, which is untreatable and often associated with a decline in the quality of life. Here, we review recent cases of blast-induced hearing dysfunction. The tympanic membrane is particularly sensitive to blast pressure waves, since such waves exert forces mainly at air-tissue interfaces within the body. However, treatment of tympanic membrane perforation caused by blast exposure is more difficult than that caused by other etiologies. Sensorineural hearing dysfunction after blast exposure is caused mainly by stereociliary bundle disruption on the outer hair cells. Also, a reduction in the numbers of synaptic ribbons in the inner hair cells and spiral ganglion cells is associated with hidden hearing loss, which is strongly associated with tinnitus or hyperacusis.

Protein transduction therapy into cochleae via the round window niche in guinea pigs.

Cell-penetrating peptides (CPPs) are short sequences of amino acids that facilitate the penetration of conjugated cargoes across mammalian cell membranes, and as such, they may provide a safe and effective method for drug delivery to the inner ear. Simple polyarginine peptides have been shown to induce significantly higher cell penetration rates among CPPs. Herein, we show that a peptide consisting of nine arginines ("9R") effectively delivered enhanced green fluorescent protein (EGFP) into guinea pig cochleae via the round window niche without causing any deterioration in auditory function. A second application, 24 hours after the first, prolonged the presence of EGFP. To assess the feasibility of protein transduction using 9R-CPPs via the round window, we used "X-linked inhibitor of apoptosis protein" (XIAP) bonded to a 9R peptide (XIAP-9R). XIAP-9R treatment prior to acoustic trauma significantly reduced putative hearing loss and the number of apoptotic hair cells loss in the cochleae. Thus, the topical application of molecules fused to 9R-CPPs may be a simple and promising strategy for treating inner ear diseases.

Pathophysiology of the inner ear after blast injury caused by laser-induced shock wave.

The ear is the organ that is most sensitive to blast overpressure, and ear damage is most frequently seen after blast exposure. Blast overpressure to the ear results in sensorineural hearing loss, which is untreatable and is often associated with a decline in the quality of life. In this study, we used a rat model to demonstrate the pathophysiological and structural changes in the inner ear that replicate pure sensorineural hearing loss associated with blast injury using laser-induced shock wave (LISW) without any conductive hearing loss. Our results indicate that threshold elevation of the auditory brainstem response (ABR) after blast exposure was primarily caused by outer hair cell dysfunction induced by stereociliary bundle disruption. The bundle disruption pattern was unique; disturbed stereocilia were mostly observed in the outermost row, whereas those in the inner and middle rows stereocilia remained intact. In addition, the ABR examination showed a reduction in wave I amplitude without elevation of the threshold in the lower energy exposure group. This phenomenon was caused by loss of the synaptic ribbon. This type of hearing dysfunction has recently been described as hidden hearing loss caused by cochlear neuropathy, which is associated with tinnitus or hyperacusis.

Recovery of endocochlear potential after severe damage to lateral wall fibrocytes following acute cochlear energy failure.

Reduction of endocochlear potential (EP) is one of the main causes of sensorineural hearing loss. In this study, we investigated changes in the EP using a mouse model of acute cochlear energy failure, which comprised severe cochlear lateral wall damage induced by the local administration of 3-nitropropionic acid to the inner ear. We also analyzed the correlation between EP changes and histological findings in the cochlear lateral wall. We detected the recovery of the EP and hearing function at lower frequencies after severe damage of the cochlear lateral wall fibrocytes at the corresponding region. Remodeling of the cochlear lateral wall was associated with EP recovery, including the re-expression of ion transporters or gap junctions (i.e. Na/K/ATPase-ß1 and connexin 26). These results indicate a mechanism for late-phase hearing recovery after severe deafness, which is frequently observed in clinical settings.

Markers of Overall Nutritional Status and Incident Hearing Impairment in Community-Dwelling Older Japanese: The Kurabuchi Study.

OBJECTIVES: To examine the association between four markers of overall nutritional status (a serum biomarker (albumin) and three anthropometric indices (body mass index (BMI), midarm circumference (MAC), calf circumference (CC))) and incident hearing impairment in older Japanese adults. DESIGN: Community-based prospective cohort study. SETTING: Kurabuchi Town, Gunma Prefecture, Japan. PARTICIPANTS: Individuals aged 65 and older (143 men, 195 women) without hearing impairment at baseline examination (2005-06) who participated in repeated examinations 4 years later (2009-10) (N = 338). MEASUREMENTS: The three anthropometric indices were measured at baseline, and nephelometry was used to assess serum albumin levels. Hearing impairment was defined as failure to hear a 30-dB hearing level signal at 1 kHz and a 40-dB signal at 4 kHz in the better ear on pure-tone audiometry. RESULTS: Over the 4-year period, 16.3% of participants developed hearing impairment. Those with lower marker values had greater risk of hearing impairment than those with higher marker values (multivariable adjusted odds ratio (aOR) = 2.18, 95% confidence interval (CI) = 1.05-4.57 for albumin ≤4.0 g/dL; aOR = 2.72, 95% CI = 1.10-6.71 for BMI <19.0 kg/m(2) ). The pattern of association showed a similar tendency for MAC and CC. Excluding obese participants did not changed the results substantially. CONCLUSION: Further research is needed to determine whether interventions that improve markers of nutritional status may help prevent age-related hearing loss in older adults.