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  • Hair cell regeneration, reinnervation, and restoration of hearing thresholds in the avian hearing organ. Cell reports Sato, M. P., Benkafadar, N., Heller, S. 2024; 43 (3): 113822


    Hearing starts, at the cellular level, with mechanoelectrical transduction by sensory hair cells. Sound information is then transmitted via afferent synaptic connections with auditory neurons. Frequency information is encoded by the location of hair cells along the cochlear duct. Loss of hair cells, synapses, or auditory neurons leads to permanent hearing loss in mammals. Birds, in contrast, regenerate auditory hair cells and functionally recover from hearing loss. Here, we characterized regeneration and reinnervation in sisomicin-deafened chickens and found that afferent neurons contact regenerated hair cells at the tips of basal projections. In contrast to development, synaptic specializations are established at these locations distant from the hair cells' bodies. The protrusions then contracted as regenerated hair cells matured and became functional 2 weeks post-deafening. We found that auditory thresholds recovered after 4-5 weeks. We interpret the regeneration-specific synaptic reestablishment as a location-preserving process that might be needed to maintain tonotopic fidelity.

    View details for DOI 10.1016/j.celrep.2024.113822

    View details for PubMedID 38393948

  • Hair cell regeneration, reinnervation, and restoration of hearing thresholds in the avian hearing organ Cell Reports Sato, M. P., Benkafadar, N., Heller, S. 2024; 43
  • An essential signaling cascade for avian auditory hair cell regeneration. Developmental cell Benkafadar, N., Sato, M. P., Ling, A. H., Janesick, A., Scheibinger, M., Jan, T. A., Heller, S. 2023


    Hearing loss is a chronic disease affecting millions of people worldwide, yet no restorative treatment options are available. Although non-mammalian species can regenerate their auditory sensory hair cells, mammals cannot. Birds retain facultative stem cells known as supporting cells that engage in proliferative regeneration when surrounding hair cells die. Here, we investigated gene expression changes in chicken supporting cells during auditory hair cell death. This identified a pathway involving the receptor F2RL1, HBEGF, EGFR, and ERK signaling. We propose a cascade starting with the proteolytic activation of F2RL1, followed by matrix-metalloprotease-mediated HBEGF shedding, and culminating in EGFR-mediated ERK signaling. Each component of this cascade is essential for supporting cell S-phase entry in vivo and is integral for hair cell regeneration. Furthermore, STAT3-phosphorylation converges with this signaling toward upregulation of transcription factors ATF3, FOSL2, and CREM. Our findings could provide a basis for designing treatments for hearing and balance disorders.

    View details for DOI 10.1016/j.devcel.2023.11.028

    View details for PubMedID 38128539

  • Prognostic significance of the harmonized maximum standardized uptake value of 18F-FDG- PET/CT in patients with resectable oral tongue squamous cell carcinoma: a multicenter study DENTOMAXILLOFACIAL RADIOLOGY Kaida, H., Kitajima, K., Sekine, T., Ito, K., Daisaki, H., Kimura, T., Sato, M. P., Enomoto, A., Otsuki, N., Ishii, K. 2023; 52 (7): 20230083


    To investigate the usefulness of harmonized 18F-FDG-PET/CT parameters for predicting the postoperative recurrence and prognosis of oral tongue squamous cell carcinoma (OTSCC).We retrospectively analyzed the cases of 107 OTSCC patients who underwent surgical resection at four institutions in Japan in 2010-2016 and evaluated the harmonized PET parameters of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumor as the pSUVmax, pMTV, and pTLG. For lymph node metastasis, we used harmonized PET parameters of nodal-SUVmax, nodal-total MTV (tMTV), and nodal-total TLG (tTLG). The associations between the harmonized PET parameters and the patients' relapse-free survival (RFS) and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox proportional hazard regression analysis for model 1 (preoperative stage) and model 2 (preoperative  +  postoperative stages).The harmonized SUVmax values were significantly lower than those before harmonization (p=0.012). The pSUVmax was revealed as a significant preoperative risk factor for RFS and OS. Nodal-SUVmax, nodal-tMTV, and nodal-tTLG were significant preoperative risk factors for OS. The combination of pSUVmax + nodal-SUVmax significantly stratified the patients into a low-risk group (pSUVmax <3.97 + nodal-SUVmax <2.85 or ≥2.85) and a high-risk group (pSUVmax ≥3.97 + nodal-SUVmax <2.85 or pSUVmax ≥3.97 + nodal-SUVmax ≥2.85) for recurrence and prognosis (RFS: p=0.001; OS: p<0.001).The harmonized pSUVmax is a significant prognostic factor for the survival of OTSCC patients. The combination of pSUVmax and nodal-SUVmax identified OTSCC patients at high risk for recurrence and poor prognosis at the preoperative stage.

    View details for DOI 10.1259/dmfr.20230083

    View details for Web of Science ID 001100849800001

    View details for PubMedID 37494001

    View details for PubMedCentralID PMC10552130

  • COVID-19 presenting as acute epiglottitis: A case report and literature review AURIS NASUS LARYNX Iwamoto, S., Sato, M. P., Hoshi, Y., Otsuki, N., Doi, K. 2023; 50 (1): 165-168


    Coronavirus disease 2019 (COVID-19) occasionally causes acute laryngitis, requiring emergency treatment. Understanding the characteristic laryngeal findings can help diagnose COVID-19 earlier, prevent worsening infection, and properly manage airway obstruction. Herein, we report the case of a 44-year-old male with acute epiglottitis likely caused by COVID-19. On presentation, chest computed tomography (CT) showed no signs of pneumonia. However, the larynx had extensive necrotic-like erosive lesions resembling those of tuberculous laryngitis. COVID-19 was diagnosed by reverse-transcription polymerase chain reaction, and secondary bacterial superinfections were suspected after blood testing. The symptoms improved after administration of antibiotics (sulbactam sodium/ampicillin sodium), steroids (dexamethasone), and favipiravir. The patient developed a high fever on the sixth day of hospitalization, and pneumonia was identified on CT. Various culture tests, including tuberculosis, were negative. Thus, remdesivir was administered for COVID-19-induced pneumonia. The patient gradually recovered, was transferred to another hospital, and was discharged on the 35th day of hospitalization. Six previous case reports of COVID-19-induced acute epiglottitis suggested that acute epiglottitis preceded the onset of pneumonia. The laryngeal findings from this report may be useful for diagnosing COVID-19 that does not cause pneumonia and for bringing attention to pneumonia after a COVID-19 diagnosis.

    View details for DOI 10.1016/j.anl.2021.12.007

    View details for Web of Science ID 001026288500001

    View details for PubMedID 34986973

    View details for PubMedCentralID PMC8683275

  • Three Cases of Hematoma in the Retropharyngeal Space. Ear, nose, & throat journal Sato, M. P., Otsuki, N., Koike, S., Yasumatsu, R. 2022: 1455613221141231


    OBJECTIVES: Hematoma in the retropharyngeal space (RPS) is a life-threatening condition that leads to rapid airway obstruction. However, the indication for airway management remains unclear. Additionally, the requirement for surgical hematoma evacuation remains undetermined. Therefore, we attempt to suggest some criteria for the management of hematoma in such cases.METHODS: We report three cases of hematoma in the RPS wherein one patient was treated without surgery and the other two underwent tracheotomy followed by hematoma evacuation.RESULTS: We found that airway management should be based on whether the glottis could be visible on laryngoscopy and dyspnea severity. The degree of hematoma, swelling, subcutaneous bleeding in the anterior neck, and emotional stability should also be considered. Proper management during the acute phase may allow for conservative treatments. Hematomas extending below the tracheal bifurcation may help ease upper airway obstruction due to pressure distribution, allowing for conservative treatment. When hematomas are surgically evacuated, tracheotomy should be performed simultaneously. Our report suggests that mediastinal hematoma evacuation could be avoided.CONCLUSION: We should determine a therapeutic strategy for hematoma in RPS based on glottis visualization, patient's condition, and extent of hematoma growth under careful observation.

    View details for DOI 10.1177/01455613221141231

    View details for PubMedID 36416101

  • Predictive factors for malignant neoplasms veiled in deep neck infections ACTA OTO-LARYNGOLOGICA Sato, M. P., Otsuki, N., Kimura, T., Doi, K. 2022; 142 (2): 202-205


    Background: Malignant neoplasms (MNs) in the head and neck are occasionally hidden in deep neck infections (DNIs) that require emergency treatment, which potentially leads to delayed diagnosis of MNs.Objectives: This study aimed to identify predictive factors that can prevent delays in diagnosing MNs in patients with DNIs.Methods: We retrospectively analysed data from 83 patients admitted to our hospital who were diagnosed with DNIs.Results: Four patients (4.8%) had DNIs veiling MNs in the head and neck. Statistical analyses revealed a significant association (p = .0481) of platelet to albumin ratio (PAR; ≥ 98.9 × 103) with hidden MNs in DNIs. Furthermore, concomitant cervical lymphadenopathy, especially multiple lymphadenopathies and excluding abscesses, was higher in patients with DNIs veiling MNs (p = .0142 and p = .0023, respectively).Conclusions and Significance: The PAR, which can be easily measured and readily detected, was a potential predictive factor. Moreover, performing fine-needle aspiration for lymphadenopathies could help diagnose hidden MNs in DNIs.

    View details for DOI 10.1080/00016489.2022.2030880

    View details for Web of Science ID 000750764500001

    View details for PubMedID 35112650

  • Middle-ear carcinoid tumour metastasising to the parapharyngeal space and the parotid gland JOURNAL OF LARYNGOLOGY AND OTOLOGY Sato, M. P., Otsuki, N., Iwamoto, S., Doi, K. 2022: 1-5


    Background. Middle-ear carcinoid tumour is a rare malignant tumour with an indolent course occasionally causing regional or distant metastasis. This paper presents a case of middle-ear carcinoid tumour metastasising to the parapharyngeal space and the parotid gland 20 years after the first surgery.Case report. A 35-year-old woman who underwent multiple tympanomastoidectomies for middle-ear carcinoid presented with tumours of both the parapharyngeal space and parotid gland, detected by regular imaging. Based on the clinical course, metastatic relapse of middle-ear carcinoid was suspected. This was treated with subtotal parotidectomy with elective neck dissection (levels II and III), leading to the pathological diagnosis of carcinoid tumour. A cervico-parotid approach was selected to avoid complications associated with parapharyngeal space tumour removal. Transient facial palsy (House-Brackmann grade III) occurred, which completely recovered two months after surgery.Conclusion. Awareness of parapharyngeal space tumours possibly caused by metastasis from a middle-ear tumour is necessary.

    View details for DOI 10.1017/S0022215122000287

    View details for Web of Science ID 000868924300001

    View details for PubMedID 35094719

  • A novel parotid carcinoma with a prominent ghost cell population: a masquerading tumor or "salivary ghost cell carcinoma"? MEDICAL MOLECULAR MORPHOLOGY Harada, H., Sato, M. P., Otsuki, N., Kawamura, M., Kurose, A., Satou, T. 2022; 55 (1): 76-83


    Ghost cell is one of several unique cellular morphologies associated with aberrant keratinization. We encountered a novel parotid tumor containing numerous ghost cells and herein describe its histological features and discuss diagnostic problems. The patient was a 90-year-old Japanese male, who complained of swelling of the left parotid area for four months. Positron emission tomography indicated no cervical lymph node metastasis or distant metastasis. The tumor was successfully resected with no signs of recurrence or metastasis for six months after surgery. Histologically, the tumor was mainly composed of squamous cells forming irregularly shaped nests with a mixture of pleomorphic giant or multinucleated cells and bland basaloid cell. Keratinized areas were occupied by a prominent ghost cell population. Immunohistochemically, CK5/6 and CK19 were widely positive as well as AE1/AE3, p40 and p63. Nuclear expression of β-catenin was also observed. The present case can be regarded as a particular form of squamous cell carcinoma and is believed to contain a large number of ghost cells resulting from an unclear mechanism. However, it seems difficult to consider such tumors as a clinicopathologically independent entity at present. Applying a term such as "salivary ghost cell carcinoma" would be premature.

    View details for DOI 10.1007/s00795-021-00302-9

    View details for Web of Science ID 000684899200001

    View details for PubMedID 34392428