Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 A Higher Liver Fibrosis-4 Index Is Associated With More Severe Hearing Loss in Idiopathic Sudden Sensorineural Hearing Loss e89864 EN Yukihide Maeda Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Liver fibrosis is an important medical issue increasing over time in developed countries. Aims/objectives This study aimed to investigate whether liver fibrosis, as indicated by routine blood test parameters, influences the risk and severity of idiopathic sudden sensorineural hearing loss (ISSNHL). Material and methods Sixty-six patients with ISSNHL and 198 patients with benign parotid gland tumors (BPTs) (controls) were enrolled. Indices for liver fibrosis (Liver Fibrosis-4 index (FIB-4 index) and aspartate aminotransferase-to-platelet ratio index (APRI)) were calculated from the blood laboratory data. The pure tone average (PTA) was calculated as the mean of hearing levels at the six frequencies at the onset of ISSNHL. Severe hearing loss was defined as PTA≥60 decibels Hearing Level (dB HL). Results In risk evaluation, the FIB-4 index did not differ significantly between ISSNHL patients and controls. Regarding the severity of ISSNHL, the FIB-4 index was significantly higher in ISSNHL patients with severe hearing loss than in those with PTA<60 dB HL (P<0.05) on univariate comparison. After adjusting for age, sex, and indices of inflammation, both the FIB-4 index and APRI showed a significant association with severe hearing loss (odds ratio (OR): 5.9, 95% confidence interval (CI): 1.3-25.7, and OR: 2.2, 95% CI: 1.1-4.7). Conclusions and significance Higher liver fibrosis indices (FIB-4 index and APRI), derived from routine blood laboratory data, are associated with a more severe phenotype of ISSNHL. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2378-8038 10 1 2025 Short‐process incudo‐stapedioplasty in congenital ear malformation e70055 EN Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medical School Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Objectives: Although various stapedotomy and stapedectomy techniques exist, anchoring the piston can be challenging. We present a novel surgical approach for treating congenital stapes malformations with an atypical facial nerve trajectory. Methods: This is a case of a 7-year-old boy presenting with bilateral conductive hearing loss. Prior attempts at tympanoplasty had proven unsuccessful in improving his hearing. Presurgical imaging studies revealed an unusual anatomical configuration, with the facial nerve positioned inferior to the oval window. This anatomical variation precluded the use of conventional prosthesis-anchoring techniques typically employed in stapedotomies. Thus, we devised an innovative approach, opting to anchor the prosthesis to the short process of the incus. Results: This novel technique circumvented the atypical course of the facial nerve, allowing for successful reconstruction of the ossicular chain. The patient demonstrated an acceptable improvement (30 dB gain) in hearing 1-year post-surgery, with no reported complications. Conclusion: This case underscores the critical importance of adapting surgical techniques to address the unique anatomical challenges that may arise in the context of congenital ear malformations. It also highlights the potential of the short process of the incus as a viable alternative anchoring site for stapes prostheses, thereby improving the outcomes of such complex cases. This technique not only restored the patient's hearing but also contributed valuable insights into the management of similar cases, potentially improving the quality of life for individuals with rare and challenging anatomical variations. Level of evidence: 5. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 4 2025 Bilateral Scleritis and Neutrophilic Dermatosis With Cytogenetic Chromosomal Aberrancy Related to Pyoderma Gangrenosum: A Case Report of a 20-Year Follow-Up e82348 EN Toshihiko Matsuo Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noboru Asada Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mikako Obika Department of General Internal Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryotaro Omichi Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keiji Iwatsuki Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Pyoderma gangrenosum is a non-infectious autoimmune disease with skin plaques and ulcers in the entity of neutrophilic dermatosis and may have a background of myelodysplastic syndromes. This study reported a 20-year follow-up of a patient with pyoderma gangrenosum and scleritis who showed chromosomal aberrancy from the initial phase and later in the course developed thrombocythemia. A 51-year-old man presented with widespread indurated erythematous plaques with scaling and pustules on the forehead, bilateral eyelids, and nasal bridge, in addition to nodular scleritis in the left eye and ulcer formation of the plaques in the lower legs. Skin biopsy revealed massive dermal infiltration mainly with neutrophils in the absence of neutrophilic vasculitis. Suspected of myelodysplastic syndromes, bone marrow biopsy was normal, while chromosomal aberrancy, 46, XY, del (20) (q11q13.3), was detected. In the diagnosis of neutrophilic dermatosis, probably of pyoderma gangrenosum, he began to have oral prednisolone 20 mg daily and colchicine 1 mg daily, leading to the subsidence of skin lesions. Four months later, he developed nodular scleritis in the right eye and began to use topical 0.1% betamethasone in both eyes. He was stable with only prednisolone 12.5 mg daily until the age of 55.5 years, when he showed an increase of serum lactate dehydrogenase. The bone marrow aspirate disclosed neither blast cell increase nor atypical cells. The same chromosomal aberrancy was repeatedly detected. One year later, he developed breathing difficulty and underwent tracheostomy. Laryngeal lesion biopsy disclosed squamous cell papilloma with human papillomavirus-6. At 60 years old, he showed marginal corneal infiltration in the left eye, and at 61 years old, hypopyon in the right eye. Platelets tended to increase up to 1000 × 103/µL, and bone marrow examinations were recommended but refused by the patient. At the latest follow-up at 71 years old, he was ambulatory in health and stable with a tracheostomy cannula. In conclusion, pyoderma gangrenosum with scleritis occurred in an undetermined hematological malignancy with chromosomal aberrancy. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 A glucocorticoid-regulating molecule, Fkbp5, may interact with mitogen-activated protein kinase signaling in the organ of Corti of mice cochleae 7506 EN Asuka Sato Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihide Maeda Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences FKBP5 is a 51-Da FK506-binding protein and member of the immunophilin family involved in controlling the signaling of glucocorticoid receptor from the cytosol to nucleus. Fkbp5 has previously been shown to be expressed in murine cochlear tissue, including the organ of Corti (i.e., the sensory epithelium of the cochlea). Fkbp5-/- mice as used in this study show hearing loss in the low-frequency (8-kHz) range and click-evoked auditory brainstem response (ABR) threshold compared to wild-type mice. Both Fkbp5-/- and wild-type mice showed hearing loss at all frequencies and click-ABR thresholds at 24 h and 14 days following acoustic overexposure (AO). Tissues of the organ of Corti were subjected to RNA sequencing and KEGG pathway analysis. In Fkbp5-/- mice before AO, the mitogen-activated protein kinase (MAPK) signaling pathway was dysregulated compared to wild-type mice. In wild-type mice at 12 h following AO, the most significantly modulated KEGG pathway was the TNF signaling pathway and major MAPK molecules p38 and Jun were involved in the TNF signaling pathway. In Fkbp5-/- mice at 12 h following AO, the MAPK signaling pathway was dysregulated compared to wild-type mice following AO. In conclusion, Fkbp5 interacts with MAPK signaling in the organ of Corti in mice cochleae. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice 589 593 EN Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medial University Yukihide Maeda Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunihiro Fukushima Hayashima Clinic of Otolaryngology and Dermatology Yuko Kataoka Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66150 Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of ‘better-hearing ear’ was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient’s age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and −0.33, 95% confidence intervals [11.75-37.45] and [−0.58 to −0.09], respectively), but the CI surgery side did not (−6.76, [−14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 16 10 2021 Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss e0258977 EN Kensuke Uraguchi Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihide Maeda Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Takahara Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-kappa B subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-kappa B would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-kappa B-interacting inflammatory molecules, TNF alpha and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL. No potential conflict of interest relevant to this article was reported.

日本耳鼻咽喉科感染症研究会 Acta Medica Okayama 09133976 31 1 2013 耳漏を主訴に来院した扁桃周囲膿瘍の1例 175 178 EN The patient was a 79-year-old woman. Her left ear was being treated with otitis externa at her nearby clinic by eardrop. Her otorrhea did not improve after one week. The otorrhea still kept outflowing during food intake. That is the reason of her visiting our hospital. Her past medical histories were sigmoid colon perforation with stoma placement, rheumatoid arthritis, diabetes mellitus, hypertension, right hip prosthesis placement. At the first visit to our hospita!, She had a remarkable erosion of the left ear canal, fistula was found in front of the ear canal skin. She showed pus leakage due to her chewing. Strongly swelling surrounded the left tonsil and soft palate, and oropharynx had been narrowed. T he CT scan revealed the low density area with a contrast effect from the lower ear to the left tonsil, was diagnosed with left peritonsillar abscess. On admission to our hospital, drainage and the administration of antibiotics were performed. She was discharged in satisfactory progress on day 10. Peritonsillar abscess, but there is a frequently encountered disease, being the chief complaint otorrhea is rare. As reported case seems to be similar as far as we have searched is only reported as "one case of deep neck abscess in the throat and ear canal causing self-destruction" is Tomohiro Anno 1961. We report this case with the literature about peritonsillar abscess. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 23290501 17 2020 Hair cell transduction efficiency of single- and dual-AAV serotypes in adult murine cochleae 1167 1177 EN Ryotaro Omichi Department of Otolaryngology–Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidekane Yoshimura Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa Seiji B. Shibata Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa Luk H. Vandenberghe Grousbeck Gene Therapy Center, Ocular Genomics Institute, Schepens Eye Research Institute and Mass Eye and Ear Richard J.H. Smith Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells, but the efficacy of dual transduction remains unclear. Herein, we investigated cellular tropism of single injections of AAV serotype 1 (AAV1), AAV2, AAV8, AAV9, and Anc80L65, and quantitated dual-vector co-transduction rates following co-injection of AAV2 and AAV9 vectors in adult murine cochlea. We used the combined round window membrane and canal fenestration (RWM+CF) injection technique for vector delivery. Single AAV2 injections were most robust and transduced 96.7% ± 1.1% of inner hair cells (IHCs) and 83.9% ± 2.0% of outer hair cells (OHCs) throughout the cochlea without causing hearing impairment or hair cell loss. Dual AAV2 injection co-transduced 96.9% ± 1.7% of IHCs and 65.6% ± 8.95% of OHCs. Together, RWM+CF-injected single or dual AAV2 provides the highest auditory hair cell transduction efficiency of the AAV serotypes we studied. These findings broaden the application of cochlear gene therapy targeting hair cells. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1323-8930 65 4 2016 Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts 414 419 EN Kengo Kanai Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Okano Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tazuko Fujiwara Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takenori Haruna Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sei-ichiro Makihara Department Otorhinolaryngology, Kagawa Rosai Hospital Yuji Hirata Department Otorhinolaryngology, Kagawa Prefectural Central Hospital Kazunori Nishizaki Department Otorhinolaryngology, Kagawa Prefectural Central Hospital Background: Vascular endothelial growth factor (VEGF) is known to be associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). VEGF is produced by a variety of cells including fibroblasts. It was recently reported that prostaglandin (PG) E-2 induces VEGF release by nasal polyp fibroblasts. However, little is known regarding possible regulation of VEGF by other PGs. We have reported that molecules that regulate PGD(2) metabolism play roles in the pathogenesis of CRS including in local eosinophilia and type 2 cytokine production. In the present study, we sought to determine whether PGD(2) regulates VEGF release by nasal polyp fibroblasts. Methods: Nasal polyp fibroblasts were established from nasal polyps. These fibroblasts were stimulated with serial dilutions of PGD(2) or PGD(2) receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. The concentration of VEGF in the culture supernatants was determined using ELISA. Results: 5 mM of PGD(2) significantly induced VEGF release by nasal polyp fibroblasts. VEGF release was also obtained by stimulation with a DP receptor-selective, but not with a CRTH2 receptor-selective agonist. In addition, PGD(2)-induced VEGF release was significantly inhibited by pre-treatment with DP receptor-selective antagonists. In contrast, pre-treatment with a CRTH2 receptor-selective antagonist significantly enhanced PGD(2)-induced VEGF release. Conclusions: PGD(2) stimulates VEGF production via DP but not CRTH2 receptors in nasal polyp fibroblasts. Copyright (C) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. No potential conflict of interest relevant to this article was reported.