Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration.

Cell transplantation therapy has long been investigated as a therapeutic intervention for neurodegenerative disorders, including spinal cord injury, Parkinson's disease, and amyotrophic lateral sclerosis. Indeed, patients have high hopes for a cell-based therapy. However, there are numerous practical challenges for clinical translation. One major problem is that only very low numbers of donor cells survive and achieve functional integration into the host. Glial scar tissue in chronic neurodegenerative disorders strongly inhibits regeneration, and this inhibition must be overcome to accomplish successful cell transplantation. Intraneural cell transplantation is considered to be the best way to deliver cells to the host. We questioned this view with experiments in vivo on a rat glial scar model of the auditory system. Our results show that intraneural transplantation to the auditory nerve, preceded by chondroitinase ABC (ChABC)-treatment, is ineffective. There is no functional recovery, and almost all transplanted cells die within a few weeks. However, when donor cells are placed on the surface of a ChABC-treated gliotic auditory nerve, they autonomously migrate into it and recapitulate glia- and neuron-guided cell migration modes to repair the auditory pathway and recover auditory function. Surface transplantation may thus pave the way for improved functional integration of donor cells into host tissue, providing a less invasive approach to rescue clinically important neural tracts.

Histopathological evaluation and long-term results of soft tissue preservation technique in cholesteatoma surgery.

The goal of cholesteatoma surgery is total removal of the cholesteatoma matrix and prevention of recurrence. Preservation of soft tissue in the attic is reported to improve post-operative middle ear aeration, and thus prevents recurrence. However, the histology and nature of the preserved tissue have rarely been reported. The aim of this study is to clarify the histology of the preserved soft tissue in cholesteatoma surgery, and to show its relationship to the clinical course. Surgical specimens were obtained from ten patients with pars flaccida-type cholesteatoma. In these patients, cholesteatoma occupied the attic and the mastoid cavity. The cholesteatoma was removed so as not to expose the bone in the attic. After the removal of the lesions, soft tissue was harvested from the floor of the attic, using cupped forceps. The specimens were fixed with 10 % formalin, and stained with hematoxylin-eosin. The patients were followed-up for 8 years after the surgery. No patients showed post-operative inner ear disturbance or facial nerve palsy. In one patient, residual lesion was found during the revision surgery. The area of residual lesion was not explored during the first operation. Two other patients showed recurrent cholesteatoma in the pars tensa; one of these patients had accompanying otorrhea. The other seven patients showed no residual or recurrent cholesteatoma 8 years after the surgery. The histological examination showed that the harvested tissue was mainly composed of collagen fiber and fibroblasts. Ciliary epithelial cells were found in one patient. In three patients, cysts of mucosal remnants (glandular cysts), were embedded in the connective tissue. Two of these three patients experienced recurrent cholesteatoma, while the other seven patients were without recurrence at follow-up. Preservation of soft tissue behind the cholesteatoma matrix is a safe technique if the surgical field is fully visible. In most cases, the preserved tissue was fibrous connective tissue and lacked the characteristics of mucosa. The glandular cysts in the preserved soft tissue seem to be related to the recurrence of cholesteatoma.

The sensitivity and accuracy of a cone beam CT in detecting the chorda tympani.

The facial recess approach through posterior tympanotomy is the standard approach in cochlear implantation surgery. The size of the facial recess is highly variable, depending on the course of the chorda tympani. Despite their clinical importance, little is known about the sensitivity and accuracy of imaging studies in the detection of the chorda tympani. A total of 13 human temporal bones were included in this study. All of the temporal bones were submitted to a cone beam CT (Accuitomo, Morita, Japan). The multi-planar reconstruction images were rotated around the mastoid portion of the facial nerve to locate the branches of the facial nerve. A branch was diagnosed as the chorda tympani when it entered the tympanic cavity near the notch of Rivinus. The distance between the bifurcation and the tip of the short crus of the incus was measured. In all temporal bones, the canal of the chorda tympani or the posterior canaliculus was detected. In the CT-based evaluation, the average distance from the bifurcation to the incus short crus was 12.6 mm (8.3-15.8 mm). The actual distance after dissection was 12.4 mm (8.2-16.4 mm). The largest difference between the distances evaluated with the two procedures was 1.1 mm. Cone beam CT is very useful in detecting the course of the chorda tympani within the temporal bone. The measured distance is accurate.

A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment.

BACKGROUND: To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy. METHODS: We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events. RESULTS: In the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P = 0.001). CONCLUSIONS: The positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness. TRIAL REGISTRATION: UMIN Clinical Trials Registry Number UMIN000004366, October 30th, 2010.

Piezoelectric materials mimic the function of the cochlear sensory epithelium.

Cochlear hair cells convert sound vibration into electrical potential, and loss of these cells diminishes auditory function. In response to mechanical stimuli, piezoelectric materials generate electricity, suggesting that they could be used in place of hair cells to create an artificial cochlear epithelium. Here, we report that a piezoelectric membrane generated electrical potentials in response to sound stimuli that were able to induce auditory brainstem responses in deafened guinea pigs, indicating its capacity to mimic basilar membrane function. In addition, sound stimuli were transmitted through the external auditory canal to a piezoelectric membrane implanted in the cochlea, inducing it to vibrate. The application of sound to the middle ear ossicle induced voltage output from the implanted piezoelectric membrane. These findings establish the fundamental principles for the development of hearing devices using piezoelectric materials, although there are many problems to be overcome before practical application.

Impact of collagen matrix on reconstructive material selection and postoperative complications in endoscopic endonasal skull base surgery.

OBJECTIVE: The aim of this study was to investigate the impact of collagen matrix on reconstructive material selection and postoperative complications in endoscopic endonasal skull base surgery. METHODS: The authors retrospectively reviewed the data of consecutive patients who underwent purely endoscopic endonasal skull base surgery from January 2015 to March 2023. Intraoperative CSF leakage was classified according to the Esposito grade, and skull base repair was tailored to the leakage grade. The patients were divided into two groups: before (group A) and after (group B) collagen matrix implementation. The rates of autologous graft harvesting (fat, fascia, and nasoseptal flap), postoperative CSF leakage, and donor-site complications were compared between the two groups. RESULTS: In total, 270 patients were included. Group A included 159 patients and group B included 111 patients. There were no differences in patient characteristics, including age, pathology, and Esposito grade, between the two groups. The overall fat usage rate was significantly higher in group A (63.5%) than in group B (39.6%) (p = 0.0001), and the fascia usage rate was also significantly higher in group A (25.8%) than in group B (4.5%) (p < 0.0001). The nasoseptal flap usage rate did not differ between group A (32.7%) and group B (30.6%) (p = 0.79). Postoperative CSF leakage was similar between the two groups (0.63% in group A vs 1.8% in group B, p = 0.57), and the overall rate of CSF leakage was 1.1%. Donor-site complications occurred in 3 patients in group A, including 1 abdominal hematoma, 1 delayed abdominal infection, and 1 fluid collection after fascia lata harvesting. CONCLUSIONS: Collagen matrix implementation significantly decreased autologous graft harvesting without increasing postoperative CSF leakage, contributing to less invasive surgery.

A minimally invasive approach for cochlear implantation using a microendoscope.

Given the growing need for minimally invasive approaches to cochlear implantation surgery, we chose to examine the safety of a microendoscopic procedure for cochlear implantation. We performed cochlear implantation surgery on four human temporal bones using a microendoscope and evaluated the safety of the procedure. With a microendoscope, the facial recess was opened and electrodes were inserted into the cochlea. The size of the mastoidectomy ranged from 5 × 4 to 7 × 7 mm. For three of the temporal bones, the surgery was conducted without any damage to the surrounding structures. The chorda tympanic nerve was inadvertently sacrificed in one temporal bone, in which we skipped the identification of the incus. The microendoscope allowed cochlear implantation surgery to be performed with a mastoidectomy of minimal size.

A case of intraorbital malignant lymphoma biopsied using an endoscopic transnasal approach.

Background: While most orbital tumors are primary, some are secondary, including extension or invasion from adjacent sites. The diagnosis varies widely, and the treatment strategy depends on the pathological diagnosis. Transcranial and transorbital surgical approaches are typically used. Recently, a transnasal endoscopic approach has emerged as a viable option. We report a case of an intraorbital tumor treated with endoscopic transnasal biopsy and compare the results with those of other surgical approaches. Case Description: A 74-year-old woman visited a nearby hospital due to a right eye protrusion and decreased visual acuity. An intraorbital tumor was detected and the patient was referred to our hospital. Head computed tomography revealed a mass along the posterior wall of the right orbital apex. Contrast-enhanced magnetic resonance imaging showed a 37-mm lesion with a uniform contrast effect and no intracranial extension. Intraorbital lymphoma was considered a differential diagnosis, and a biopsy was performed using an endoscopic transnasal approach. The pathological diagnosis was B-cell lymphoma, and chemotherapy was administered. Conclusion: The endoscopic transnasal approach for intraorbital tumors is less invasive, highly cosmetic, and useful, especially for medial and inferior orbital lesions.

Laryngeal Cartilage Regeneration of Nude Rats by Transplantation of Mesenchymal Stem Cells Derived from Human-Induced Pluripotent Stem Cells.

Previous studies transplanted human-induced pluripotent stem cells (hiPSCs)-derived mesenchymal stem cells (iMSCs) into thyroid cartilage defect of X-liked severe combined immunodeficiency (X-SCID) rats and confirmed transplanted cell survival and cartilage regeneration. Thus, this study aimed to investigate the contribution of iMSC transplantation to thyroid cartilage regeneration of nude rats. iMSCs were induced from hiPSCs via a neural crest cell lineage. Then, clumps formed from an iMSC/extracellular matrix complex were transplanted into thyroid cartilage defects in nude rats. The larynx was removed and histological and immunohistochemical analyses were performed 4 or 8 weeks after the transplantation. Human nuclear antigen (HNA)-positive cells were observed in 11 of 12 (91.7%) rats, which indicated that transplanted iMSCs survived in thyroid cartilage defects in nude rats. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells in 8 of 12 rats (66.7%), which indicated cartilage-like regeneration. Cartilage-like regeneration in nude rats in this study was comparable to the previous report on X-SCID rats (HNA-positive cells were observed in all 14 rats and cartilage-like regeneration was observed in 10 of 14 rats). This result suggests that nude rats could be an alternative to X-SCID rats in thyroid cartilage regeneration experiments using iMSCs, and this nude rat cartilage transplantation model may develop cartilage regeneration research concerning fewer problems such as infection due to immunosuppression.

Trauma-specific insults to the cochlear nucleus in the rat.

The effect of acoustic overstimulation on the neuronal number of the cochlear nucleus (CN) was investigated by using unbiased stereological methods in rats. We found that, after 9 weeks of recovery, neurons in the anteroventral cochlear nucleus (AVCN) degenerated, whereas those in the posteroventral and dorsal cochlear nuclei (PVCN and DCN) were preserved. The noise trauma induced near complete loss of the outer hair cells throughout the cochlea, and the inner hair cells were preserved only in the more apical regions. This pattern of selective loss of AVCN neurons in this study was different from trauma induced by auditory deafferentation by mechanical compression of auditory neurons. In contrast to noise trauma, mechanical compression caused loss of neurons in the PVCN and DCN. After 5 weeks of recovery from mechanical compression, there was no loss of inner or outer hair cells. These findings indicate that auditory deprivation, induced by different experimental manipulations, can have strikingly different consequences for the central auditory system. We hypothesized that AVCN neuronal death was induced by excitotoxic mechanisms via AMPA-type glutamate receptors and that excitatory neuronal circuits developed after acoustic overstimulation protected the PVCN and DCN against neuronal death. The results of the present study demonstrate that hearing loss from different etiologies will cause different patterns of neuronal degeneration in the CN. These findings are important for enhancing the performance of cochlear implants and auditory brainstem implants, because diverse types of hearing loss can selectively affect neuronal degeneration of the CN.

Metformin Reduces the Incidence of Sensorineural Hearing Loss in Patients With Type 2 Diabetes Mellitus: A Retrospective Chart Review.

Introduction and objectives Acquired sensorineural hearing loss (SNHL) has become a critical societal issue in recent years. SNHL is considered a risk factor for type 2 diabetes mellitus (T2DM). Metformin is commonly used to treat T2DM. However, its effects on SNHL have not been reported yet. Hence, this study aimed to evaluate the association between the use of metformin and SNHL incidence. Patients and methods In this retrospective matched-cohort study, the medical records of 1219 patients with T2DM aged >18 years from our hospital's inpatient database from January 1, 2012, to December 31, 2019, were examined, and matched cohorts were generated (76 patients receiving metformin and 76 not receiving metformin). A multivariable logistic regression analysis was performed to investigate the factors influencing the incidence of SNHL. Results After adjustment by propensity matching, multivariable logistic regression analysis revealed that the non-use of metformin increased the risk of developing SNHL (odds ratio, 0.26; 95% confidence interval, 0.07-0.93; p = 0.03). Conclusions This study demonstrated an association between the use of metformin and a reduced incidence of SNHL among patients with T2DM.

Diagnosis of Spontaneous Cerebrospinal Fluid Rhinorrhea Using Thin-Slice Computed Tomographic Images With Multiplanar Reconstruction and Three-Dimensional Virtual View Endoscopy.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea represents an important clinical entity, which is associated with elevated intracranial pressure and is rarely treated successfully without surgical intervention. Here we report a case of spontaneous CSF rhinorrhea. The patient was a 54-year-old male, who presented with bacterial meningitis and was referred to the Department of Otorhinolaryngology for a detailed examination of the nose and sinuses. Reconstructed thin-slice computed tomography (CT) revealed multiple fistulae on the clivus. The defect was successfully repaired by transnasal endoscopic surgery, with the assistance of virtual endoscopic images, which were created by the surgical planning and navigation system from thin-slice CT images. This incremental improvement in the imaging technique helped with the diagnosis and surgical treatment of CSF rhinorrhea.

Disinfection of otorhinolaryngological endoscopes with electrolyzed acid water: A cross-sectional and multicenter study.

Glutaraldehyde, a germicide for reprocessing endoscopes that is important for hygiene in the clinic, might be hazardous to humans. Electrolyzed acid water (EAW) has a broad anti-microbial spectrum and safety profile and might be a glutaraldehyde alternative. We sought to assess EAW disinfection of flexible endoscopes in clinical otorhinolaryngological settings and its in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bacteria commonly isolated in otorhinolaryngology. Ninety endoscopes were tested for bacterial contamination before and after endoscope disinfection with EAW. The species and strains of bacteria were studied. The in vitro inactivation of bacteria and SARS-CoV-2 by EAW was investigated to determine the efficacy of endoscope disinfection. More than 20 colony-forming units of bacteria at one or more sampling sites were detected in 75/90 microbiological cultures of samples from clinically used endoscopes (83.3%). The most common genus detected was Staphylococcus followed by Cutibacterium and Corynebacterium at all sites including the ears, noses, and throats. In the in vitro study, more than 107 CFU/mL of all bacterial species examined were reduced to below the detection limit (<10 CFU/mL) within 30 s after contact with EAW. When SARS-CoV-2 was treated with a 99-fold volume of EAW, the initial viral titer (> 105 PFU) was decreased to less than 5 PFU. Effective inactivation of SARS-CoV-2 was also observed with a 19:1 ratio of EAW to the virus. EAW effectively reprocessed flexible endoscopes contributing to infection control in medical institutions in the era of the coronavirus disease 2019 pandemic.

Intraoperative Cerebrospinal Fluid Leak Graded by Esposito Grade Is a Predictor for Diabetes Insipidus After Endoscopic Endonasal Pituitary Adenoma Resection.

BACKGROUND: Diabetes insipidus (DI) is a well-known complication of transsphenoidal surgery. However, the risk factors for DI remain controversial. METHODS: We conducted a retrospective study of patients who underwent endoscopic transsphenoidal surgery for pituitary adenoma at our institution during a 5-year period. The patients were divided into a DI group and a non-DI group. Logistic regression analyses were used to identify risk factors for postoperative DI. In subgroup analysis, the DI group was divided into transient DI and permanent DI groups, and perioperative factors were compared between groups. RESULTS: Of 101 patients, 58 were in the non-DI group (57.4%) and 43 were in the DI group (42.6%). Permanent DI occurred in 7 patients (6.9%). In univariate analyses, statistically significant risk factors were suprasellar extension, tumor functionality, and intraoperative cerebrospinal fluid leaks by Esposito grade. In multivariate logistic regression analysis, Esposito grade was the only statistically significant risk factor (P = 0.015). The frequency of DI increased as the Esposito grade increased (P = 0.0002 for the trend). In subgroup analysis, postoperative nadir sodium concentration was lower in the permanent DI group (128.1 ± 2.78 mmol/L) than in the transient DI group (135 ± 1.22 mmol/L; P = 0.035), and the optimal cutoff value was 124.5 mmol/L, with a sensitivity of 57.1% and a specificity of 91.7% (area under the curve = 0.76, P = 0.034). CONCLUSIONS: Intraoperative cerebrospinal fluid leak by Esposito grade is associated with postoperative DI. These data can be applied to help identify high-risk patients who need more aggressive follow-up and fluid management.

[Clinical outcomes cochlear reimplantation].

To clarify the clinical features of cochlear reimplantation and surgical changes in auditory performance, we retrospectively reviewed 10 of 252 cochlear implantation surgeries-6 adults and 4 children-among 129 children and 123 adults done between April 1987 and May 2009. Mean duration from initial implantation to reimplantation was 50.3 months in children and 89 months in adults, most commonly due to hard failure and implant exposure/infection (33%) in children and to hard failure (75%) in adults. The initial device implanted was the Nucleus multichannel implant (CI22M, CI24M, or CI24R). The second implant in 7 was the same or an upgrade of the same manufacturer's device, and in 2 children the HiRes 90K (Hifocus 1j) and in 1 adult the Clarion 1.2. Full initial and reinsertion succeeded in 8 cases but reinsertion proved difficult in 2 due to severe intracochlear granulation and osteoneogenseis. Auditory performance analyzed in 7 cases was mostly equal to or better than before reimplantation, although differences were not statistically significant. Reinsertion is rarely difficult, but electrode choice is important in preparing for difficult reinsertion. Post reinsertion auditory performance is satisfactory with some exceptions.

Development of a Subjective Symptom Rating Scale for Postoperative Oral Dysfunction in Patients with Oral Cancer: Reliability and Validity of the Postoperative Oral Dysfunction Scale-10.

Currently, there is no scale to subjectively assess postoperative oral dysfunction in patients with oral cancer. The purpose of this study was to evaluate the reliability and validity of the Postoperative Oral Dysfunction Scale (POD-10) that we developed. Between September 2019 and August 2021, 62 eligible oral cancer patients (median age, 72 years; 42 men and 20 women) were enrolled in the study. The Cronbach's alpha coefficient, which indicates the internal consistency of the scale, was 0.94, and the intraclass correlation coefficient, which indicates reproducibility, was 0.85 (95% confidential interval: 0.40-0.96, p < 0.05). Concurrent validity testing showed a statistically significant correlation between POD-10 and Eating Assessment Tool (EAT-10) (r = 0.89, p < 0.05). To test discriminant validity, statistically significant differences were found between early-stage cancer (stage I and II) and advanced-stage cancer (stage III and IV) (p < 0.05). Twenty-four points were calculated as the cutoff value for POD-10 using receiver operating characteristic analysis to calculate the cutoff value. The POD-10 was shown to be a clinically reliable and valid scale that can be used to subjectively assess postoperative oral dysfunction in patients with oral cancer and is expected to be used as a simple diagnostic tool.

Postoperative oral dysfunction following oral cancer resection and reconstruction: A preliminary cross-sectional study.

OBJECTIVES: Oral cancer treatment reportedly causes decreased oral function, but few studies have examined the effects of oral cancer treatment on oral function in depth. This study aimed to comprehensively evaluate the oral function after treatment and classify the conditions related to oral dysfunction in patients with oral cancer. MATERIALS AND METHODS: We recruited participants, collected their background data, and evaluated their oral function from September 2019 to March 2021. Principal component analysis was used to identify the components of oral function measurement and oral health perception. Receiver operating characteristic analysis was performed to investigate the accuracy of oral function measurements in predicting oral intake and nutritional status. RESULTS: Fifty patients treated for oral cancer, including 33 (66.0%) males and 17 (34.0%) females, were included. Their median age was 71.0 years (interquartile range: 63.0-76.0). There were significant differences in oral dryness between males and females, occlusal force among different age groups, tongue pressure based on the tumor stage and performance of reconstructive procedures, and masticatory function and Eating Assessment Tool scores based on whether radiotherapy was performed (P < 0.05). The principal component analysis proposed that oral function measurements and subjective oral health perception could be divided into three main components (transport, oral hygiene, and occlusion type), which explain 61.5% of the variance of the phenomenon. CONCLUSION: A significant decrease in oral function after oral cancer treatment should be diagnosed as postoperative oral dysfunction. Postoperative oral dysfunction can be classified into three types, each of which may present with different pathologies.

In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells.

The laryngotracheal cartilage is a cardinal framework for the maintenance of the airway for breathing, which occasionally requires reconstruction. Because hyaline cartilage has a poor intrinsic regenerative ability, various regenerative approaches have been attempted to regenerate laryngotracheal cartilage. The use of autologous mesenchymal stem cells (MSCs) for cartilage regeneration has been widely investigated. However, long-term culture may limit proliferative capacity. Human-induced pluripotent stem cell-derived MSCs (iMSCs) can circumvent this problem due to their unlimited proliferative capacity. This study aimed to investigate the efficacy of iMSCs in the regeneration of thyroid cartilage in immunodeficient rats. Herein, we induced iMSCs through neural crest cell intermediates. For the relevance to prospective future clinical application, induction was conducted under xeno-free/serum-free conditions. Then, clumps fabricated from an iMSC/extracellular matrix complex (C-iMSC) were transplanted into thyroid cartilage defects in immunodeficient rats. Histological examinations revealed cartilage-like regenerated tissue and human nuclear antigen (HNA)-positive surviving transplanted cells in the regenerated lesion. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells. These results indicated that the transplanted C-iMSCs promoted thyroid cartilage regeneration and some of the iMSCs differentiated into chondrogenic lineage cells. Induced MSCs may be a promising candidate cell therapy for human laryngotracheal reconstruction.

Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid-resistant sudden sensorineural hearing loss: a prospective clinical trial.

BACKGROUND: Sudden sensorineural hearing loss (SSHL) is a common condition in which patients lose the hearing in one ear within 3 days. Systemic glucocorticoid treatments have been used as standard therapy for SSHL; however, about 20% of patients do not respond. We tested the safety and efficacy of topical insulin-like growth factor 1 (IGF1) application using gelatin hydrogels as a treatment for SSHL. METHODS: Patients with SSHL that showed no recovery to systemic glucocorticoid administration were recruited. We applied gelatin hydrogels, impregnated with recombinant human IGF1, into the middle ear. The primary outcome measure was the proportion of patients showing hearing improvement 12 weeks after the test treatment. The secondary outcome measures were the proportion of patients showing improvement at 24 weeks and the incidence of adverse events. The null hypothesis was that 33% of patients would show hearing improvement, as was reported for a historical control after hyperbaric oxygen therapy. RESULTS: In total, 25 patients received the test treatment at a median of 23 days (range 15-32) after the onset of SSHL, between 2007 and 2009. At 12 weeks after the test treatment, 48% (95% CI 28% to 69%; P = 0.086) of patients showed hearing improvement, and the proportion increased to 56% (95% CI 35% to 76%; P = 0.015) at 24 weeks. No serious adverse events were observed. CONCLUSIONS: Topical IGF1 application using gelatin hydrogels is well tolerated and may be efficacious for hearing recovery in patients with SSHL that is resistant to systemic glucocorticoids.