An infection model for SARS-CoV-2 using rat transplanted with hiPSC-airway epithelial cells.

Investigating the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the airway epithelium and developing effective defense strategies against infection are important. To achieve this, establishing appropriate infection models is crucial. Therefore various in vitro models, such as cell lines and primary cultures, and in vivo models involving animals that exhibit SARS-CoV-2 infection and genetically humanized animals, have been used as animal models. However, no animal model has been established that allows infection experiments with human cells under the physiological environment of airway epithelia. Therefore, we aimed to establish a novel animal model that enables infection experiments using human cells. Human iPSC-derived airway epithelial cell-transplanted nude rats (hiPSC-AEC rats) were used, and infection studies were performed by spraying lentiviral pseudoviruses containing SARS-CoV-2 spike protein and the GFP gene on the tracheae. After infection, immunohistochemical analyses revealed the existence of GFP-positive infected transplanted cells in the epithelial and submucosal layers. In this study, a SARS-CoV-2 infection animal model including human cells was established mimicking infection through respiration and we demonstrated that the hiPSC-AEC rat could be used as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.

Outcomes of laryngeal framework surgeries for unilateral vocal cord paralysis in the elderly patients.

OBJECTIVE: Laryngeal framework surgery is a widely accepted treatment for unilateral vocal fold paralysis with good functional outcomes. Recently, with the aging of the population, opportunities to perform this procedure in elderly patients have increased; however, the safety and efficacy of this procedure in elderly patients has not been established. Therefore, this study aimed to investigate the safety and functional outcomes of laryngeal framework surgery in elderly patients. METHODS: Between January 2008 and December 2017, 97 patients with unilateral vocal fold paralysis underwent laryngeal framework surgery, and 71 among them completed pre- and post-operative voice function evaluations. The clinical course of these 71 patients were retrospectively reviewed. RESULTS: Out of 71 patients, 35 were assigned to the younger group (< 65 years) and 36 to the elderly group (≥ 65 years). Complications included post-operative edema and submucosal hematoma that were safely managed in all cases, and no differences were identified between the groups. Significant improvements were observed in maximum phonation time (MPT), mean flow rate, alternating current/direct current ratio, pitch perturbation quotient, amplitude perturbation quotient, and noise-to-harmonic ratio in both groups, and multivariate analysis of variance revealed greater improvement in the younger group in MPT. CONCLUSION: Laryngeal framework surgeries for unilateral vocal fold paralysis are safe and effective, regardless of age. Better improvement was observed in the younger group in the MPT suggesting that the effects of laryngeal framework surgeries is more likely to be present in the younger group than in the elderly.

Phonosurgery training using Japanese deer larynx.

OBJECTIVE: To develop phonosurgery skills, surgical training of the actual larynx is essential. In our institution, the Japanese deer (Cervus Nippon aplodontids) larynx is used in phonosurgery training. This study aimed to examine the similarities and differences between the Japanese deer and human larynx and to demonstrate their utility in vocal surgery practice. METHODS: A comparative study was conducted using 30 Japanese deer larynges and 51 human donor larynges, evaluating the overall framework, dimensions, and angle of the thyroid cartilage, vocal cord length, and location of the arytenoid cartilage muscular process. The changes and movements of the vocal folds during contraction and relaxation of each internal laryngeal muscle were also visually analyzed. RESULTS: The larynx size of Japanese deer is intermediate between that of human males and females. The adduction and abduction of the vocal folds induced by contraction of the posterior and lateral cricoarytenoid muscles, as well as the extension of the vocal folds induced by contraction of the cricothyroid muscle, behaved in the same manner as in the human larynx. CONCLUSION: The morphology of the Japanese deer larynx is similar to that of the human larynx, making it suitable for use in dissection and surgical practice. Owing to the recent animal damage problem and the popularity of gibier cuisine, large quantities of Japanese deer larynx are available at low prices. We believe that the Japanese deer larynx is the most appropriate animal for phonosurgery training so far.

Thyroid Lobectomy Under Local Anesthesia Before Lung Transplantation Owing to Diffuse Panbronchiolitis: A Case Report.

We herein report a case of thyroid lobectomy performed under local anesthesia for thyroid cancer in a patient who was at a high risk for general anesthesia due to diffuse panbronchiolitis. Although thyroid surgery has been performed in the past under local anesthesia in low-risk patients, thyroid surgery is now rarely performed under local anesthesia. If they are performed, thyroid surgery under local anesthesia is usually performed under monitored anesthesia care; sedation is considered safe and does not cause discomfort to patients. The present patient's respiratory function was poor, raising concerns that once intubated, extubation may not be possible because of the potential deterioration of respiratory function caused by the suppression of spontaneous breathing. Therefore, sedatives were avoided to maintain spontaneous breathing as much as possible. In such high-risk patients, additional care is required to ensure that the procedure is completed with minimal discomfort from pain or dyspnea. Maintaining a slightly upright position and raising the anesthesia screen are necessary to ensure a large space in front of the patient's face. In addition, an appropriate skin incision should be made to obtain a wide field of vision, and local anesthetic injections should be administered frequently to preemptively counter pain. Atropine sulfate was administered to reduce salivation and swallowing. Energy devices effectively reduced blood loss and operative time. Controlling intraoperative pain and bleeding is important, and the methods and techniques are also beneficial in surgery under general anesthesia.

Complications including dysphagia following transoral non-robotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

OBJECTIVE: Transoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy. METHODS: We compared clinical information, surgical complications, and swallowing function in patients who underwent transoral nonrobotic surgery for laryngo-pharyngeal squamous cell carcinoma between 2015 and 2021 in a multicenter retrospective study. RESULTS: Six hundred and forty patients were included. Postoperative bleeding was observed in 20 cases (3.1%), and the risk factor was advanced T category. Postoperative laryngeal edema was observed in 13 cases (2.0%), and the risk factors were prior radiotherapy, advanced T stage, and concurrent neck dissection in patients with resected HPC. Dysphagia requiring nutritional support was observed in 29 cases (4.5%) at 1 month postoperatively and in 19 cases (3.0%) at 1 year postoperatively, respectively. The risk factors for long-term dysphagia were prior radiotherapy and advanced T category. Short-term risk factors for dysphagia were prior radiotherapy, advanced T category, and concurrent neck dissection, while long-term risk factors for dysphagia were only prior radiotherapy and advanced T category. CONCLUSION: Prior radiotherapy, advanced T stage, and concurrent neck dissection increased the incidence of postoperative laryngeal edema and short-term dysphagia, but concurrent neck dissection did not affect long-term dysphagia. Such features should be considered when considering the indication for transoral surgery and postoperative management.

Anatomical variations in the superficial venous system of the neck: an image-based study using contrast-enhanced computed tomography.

PURPOSE: The superficial venous system (SVS) of the neck receives blood from the face and oral cavity. The SVS comprises the anterior jugular vein (AJV), external jugular vein (EJV), and facial vein (FV). Comprehensive knowledge of the normal anatomy and potential variations in the venous system is valuable in surgical and radiological procedures. This study aimed to update the anatomic knowledge of the SVS using a radiographic approach, which is a beneficial data source in clinical practice. METHODS: Contrast-enhanced computed tomography images of the neck of patients with head and neck cancer treated between 2017 and 2020 were retrospectively evaluated. Each side of the neck was counted separately. A total of 302 necks of 151 patients were enrolled in this study. RESULTS: The medial AJV was absent in 49.7% (75/151) of the patients on the left side, which was significantly greater than the 19.2% (29/151) on the right (p < 0.001). The left AJV drained into the right venous system in 6.6% (10/151) of the necks. In 48.3% (146/302) of the necks, the FV did not flow into the internal jugular vein but rather into the EJV or AJV; these findings were significantly more frequent than those reported in previous studies. The diameters of the veins were significantly larger when they received blood from the FV than when they were not connected to the FV. CONCLUSION: These findings indicate that the AJV has a rightward preference during its course. The course of the FV is diverse and affects the diameter of connected veins.

Interactive effects of hearing aid use and cognitive function in patients with hearing loss.

BACKGROUND: There has been a significant increase in scientific investigations of the hearing-dementia association among the research on potentially modifiable risk factors for cognitive impairment. We tested two clinical questions. Analysis 1: does persistent hearing aid (HA) use decrease the decline in cognitive function caused by ageing? Analysis 2: does cognitive function at the time of HA fitting predict future persistent HA use? METHODS: This case-control study performed at two referral centres reported data obtained over a 4.5-year period. We recruited a group of patients with cognitive decline, aged 65 or older with or without hearing loss. The intervention consisted of the use of HAs. The primary outcome measures were adherence to continuous HA use and cognitive function measured using the Japanese version of the Mini-Mental State Examination Test and the Reading Cognitive Test Kyoto. RESULTS: Eighteen HA users and 18 controls were included in the first analysis. HA use was associated with a deceleration of cognitive decline 12 months later. In the second analysis, 11 participants with good adherence to HA use were compared with 12 participants who showed poor adherence to HA use. Among the variables employed in this study, cognitive function measured using the Reading Cognitive Test Kyoto was significantly lower in participants with poor adherence to HA. CONCLUSIONS: HA use in cognitively impaired individuals with hearing loss can slow age-related cognitive decline. Cognitively impaired people with hearing loss who fail to commit to HA use tend to have lower cognitive measurement scores before HA fitting. HA use is generally more challenging as people age and their cognitive abilities decline. Therefore, it is desirable that HAs be used when hearing loss and dementia are in their early stages.

Utility of Diffusion-weighted MR Imaging for Evaluating the Depth of Invasion in Oral Tongue Squamous Cell Carcinoma.

PURPOSE: The 8th edition of the American Joint Committee on Cancer staging system included the depth of invasion (DOI) for the T classification of oral cancer. However, no standardized method has been established to clinically measure the DOI. This study aimed to investigate the accuracy of MRI-based DOI for oral tongue squamous cell carcinoma (OTSCC) in each MRI sequence. METHODS: We enrolled 49 patients with histologically proven OTSCC, treated surgically between April 2017 and February 2021. We divided the DOI into three groups using 5 and 10 mm, the thresholds for determining the T stage, and retrospectively evaluated the agreement between MRI-based DOI and pathological DOI (pDOI) for each MRI sequence, axial T1-weighted imaging (T1WI), T2-weighted imaging with fat suppression (FS-T2WI), contrast-enhanced T1WI with fat suppression (CE-T1WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps. We also divided the DOI into two groups using 3 mm, the threshold for considering elective neck dissection, and evaluated the overestimation rate of MRI-based DOI in lesions with pDOI ≤ 3 mm. RESULTS: With 5-mm and 10-mm divisions, the accuracy of the DOI assessment was highest on DWI (0.82, weighted kappa = 0.85). With a 3-mm division, the accuracy was also highest on DWI (0.87, kappa = 0.73). The overestimation rate of the MRI-based DOI in lesions with pDOI ≤ 3 mm was lowest on DWI (27.8%). CONCLUSION: DOI on DWI exhibits a comparatively higher rate of concordance with pDOI. DWI may be more useful than other MRI sequences in evaluating the DOI of OTSCC.

Mucosal melanoma of the head and neck: a retrospective analysis of 34 cases in Japan.

PURPOSE: Mucosal melanoma of the head and neck (MMHN) is a rare condition. This study aimed to investigate oncological outcomes of surgical intervention in patients with MMHN. MATERIALS AND METHODS: The study included 34 patients with MMHN who underwent surgical resection as initial treatment at 10 institutions in Japan between July 2005 and June 2015. Results: The 5-year overall survival (OS), local control rate (LCR), disease-free survival (DFS), and disease-specific survival (DSS) rates were 48.7%, 53.4%, 32.4%, and 55.1%, respectively. Based on multivariate analysis, no independent prognostic factors for the 5-year OS and DSS were found. Based on univariate analysis, the 5-year LCR was worse in patients with lesions in the nasal cavity and paranasal sinuses than in the oral cavity and pharynx. However, no differences in oncological outcomes were identified in relation to primary sites, and postoperative radiotherapy (PORT) and adjuvant systemic therapy did not contribute to improvements in the 5-year OS. CONCLUSIONS: No independent prognostic factors for the 5-year OS or DSS were identified. Regional or distant recurrences are often identified, regardless of local control with surgical resection. Difficult control of MMHN with conventional therapeutic strategies, such as surgical intervention, PORT, and systemic therapy, has been suggested.

Changes in the Proportion of Each Cell Type After hiPSC-Derived Airway Epithelia Transplantation.

No radical treatment is available for the regeneration of dysfunction and defects in airway epithelia. Artificial tracheae made of polypropylene and collagen sponge were used in clinical studies to reconstitute tracheae after resection. For early epithelialization of the luminal surface of the artificial trachea, a model was established, that is, an artificial trachea covered with human-induced pluripotent stem cell-derived airway epithelial cells (hiPSC-AECs) was transplanted into a tracheal defect in an immunodeficient rat. Unlike the cell types of hiPSC-derived cells that are currently used in clinical studies, AECs maintain tissues by proliferation and differentiation of basal cells into various cell types that constitute AECs constantly. Therefore, post-transplantation, the proportion of each cell type, such as ciliated and goblet cells, may change; however, no studies have examined this possibility. In this study, using our hiPSC-AEC-transplanted rat model, we investigated changes in the proportion of each cell type in hiPSC-AECs pre-transplantation and post-transplantation. As a result, the proportion of each cell type changed post-transplantation. The proportion of ciliated, basal, and club cells increased, and the proportion of goblet cells decreased post-transplantation. In addition, the proportion of each cell type in engrafted hiPSC-AECs is more similar to the proportion of each cell type in normal proximal airway tissue than the proportion of each cell type pre-transplantation. The results of this study are useful for the development of therapeutic techniques using hiPSC-AEC transplantation.

EBF1 Limits the Numbers of Cochlear Hair and Supporting Cells and Forms the Scala Tympani and Spiral Limbus during Inner Ear Development.

Early B-cell factor 1 (EBF1) is a basic helix-loop-helix transcription factor essential for the differentiation of various tissues. Our single-cell RNA sequencing data suggest that Ebf1 is expressed in the sensory epithelium of the mouse inner ear. Here, we found that the murine Ebf1 gene and its protein are expressed in the prosensory domain of the inner ear, medial region of the cochlear duct floor, otic mesenchyme, and cochleovestibular ganglion. Ebf1 deletion in mice results in incomplete formation of the spiral limbus and scala tympani, increased number of cells in the organ of Corti and Kölliker's organ, and aberrant course of the spiral ganglion axons. Ebf1 deletion in the mouse cochlear epithelia caused the proliferation of SOX2-positive cochlear cells at E13.5, indicating that EBF1 suppresses the proliferation of the prosensory domain and cells of Kölliker's organ to facilitate the development of appropriate numbers of hair and supporting cells. Furthermore, mice with deletion of cochlear epithelium-specific Ebf1 showed poor postnatal hearing function. Our results suggest that Ebf1 is essential for normal auditory function in mammals.

The Effect of Noise on Deep Learning for Classification of Pathological Voice.

OBJECTIVE: This study aimed to evaluate the significance of background noise in machine learning models assessing the GRBAS scale for voice disorders. METHODS: A dataset of 1406 voice samples was collected from retrospective data, and a 5-layer 1D convolutional neural network (CNN) model was constructed using TensorFlow. The dataset was divided into training, validation, and test data. Gaussian noise was added to test samples at various intensities to assess the model's noise resilience. The model's performance was evaluated using accuracy, F1 score, and quadratic weighted Cohen's kappa score. RESULTS: The model's performance on the GRBAS scale generally declined with increasing noise intensities. For the G scale, accuracy dropped from 70.9% (original) to 8.5% (at the highest noise), F1 score from 69.2% to 1.3%, and Cohen's kappa from 0.679 to 0.0. Similar declines were observed for the remaining RBAS components. CONCLUSION: The model's performance was affected by background noise, with substantial decreases in evaluation metrics as noise levels intensified. Future research should explore noise-tolerant techniques, such as data augmentation, to improve the model's noise resilience in real-world settings. LEVEL OF EVIDENCE: This study evaluates a machine learning model using a single dataset without comparative controls. Given its non-comparative design and specific focus, it aligns with Level 4 evidence (Case-series) under the 2011 OCEBM guidelines Laryngoscope, 2024.

Impact of cervical lymph node metastasis on transoral surgery for hypopharyngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. METHODS: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. RESULTS: Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). CONCLUSIONS: In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.

Pharmacokinetics of monoclonal antibodies locally-applied into the middle ear of guinea pigs.

Countless therapeutic antibodies are currently available for the treatment of a broad range of diseases. Some target molecules of therapeutic antibodies are involved in the pathogenesis of sensorineural hearing loss (SNHL), suggesting that SNHL may be a novel target for monoclonal antibody (mAb) therapy. When considering mAb therapy for SNHL, understanding of the pharmacokinetics of mAbs after local application into the middle ear is crucial. To reveal the fundamental characteristics of mAb pharmacokinetics following local application into the middle ear of guinea pigs, we performed pharmacokinetic analyses of mouse monoclonal antibodies to FLAG-tag (FLAG-mAbs), which have no specific binding sites in the middle and inner ear. FLAG-mAbs were rapidly transferred from the middle ear to the cochlear fluid, indicating high permeability of the round window membrane to mAbs. FLAG-mAbs were eliminated from the cochlear fluid 3 h after application, similar to small molecules. Whole-body autoradiography and quantitative assessments of cerebrospinal fluid and serum demonstrated that the biodistribution of FLAG-mAbs was limited to the middle and inner ear. Altogether, the pharmacokinetics of mAbs are similar to those of small molecules when locally applied into the middle ear, suggesting the necessity of drug delivery systems for appropriate mAb delivery to the cochlear fluid after local application into the middle ear.

Effects of high-dose betahistine on intractable dizziness in patients with uncompensated unilateral vestibulopathy.

OBJECTIVE: In the present study, we examined the effects of high-dose betahistine on dizziness handicap inventory (DHI) scores in patients with unilateral vestibulopathy. METHODS: An uncontrolled, open-label, multicenter clinical trial was conducted. Fifteen patients with unilateral vestibulopathy, such as vestibular neuritis, who complained of intractable dizziness for more than three months were enrolled. Initially, all patients were orally administered betahistine at a dose of 36 mg/day for four weeks, which is the standard dose and dosing period for the treatment of dizziness in Japan. The patients were then administered betahistine at a double dose of 72 mg/day for four weeks. Six patients who became aware of the benefits of high-dose betahistine were further administered betahistine at 72 mg/day for an additional 12 weeks (a total of 16 weeks). Perceived disability due to dizziness was assessed by DHI scores. RESULTS: In all 15 patients, short-term administration with high-dose (72 mg/day) betahistine for four weeks, but not low-dose betahistine (36 mg/day) for four weeks significantly decreased DHI scores. In particular, in six responding patients with self-reported benefits after short-term administration with high-dose betahistine, long-term administration with high-dose betahistine for 16 weeks further significantly decreased DHI scores. However, DHI scores of the remaining nine non-responding patients were not changed after short-term administration with high-dose betahistine for four weeks. CONCLUSION: Short-term administration with the standard dose and dosing period of betahistine did not improve DHI scores in the enrolled patients, indicating that they were not compensated for unilateral vestibulopathy with intractable dizziness. The present findings suggest that long-term administration with high-dose betahistine facilitates vestibular compensation to improve intractable dizziness in some, but not all patients with uncompensated unilateral vestibulopathy.

A multi-institutional retrospective study of 340 cases of sinonasal malignant tumor.

OBJECTIVE: Sinonasal malignant tumors (SNMT) are relatively rare among head and neck malignant tumors. Most are squamous cell carcinomas, and malignant melanomas, olfactory neuroblastomas, adenoid cystic carcinomas, sarcomas, and others also occur. The most common primary site of nasal sinus squamous cell carcinoma is the maxillary sinus. In recent years, a decrease in incidence of maxillary sinus squamous cell carcinoma (MSSCC) has been reported along with a decrease in the incidence of sinusitis. MSSCC is treated with a combination of surgery, radiation, and chemotherapy. Treatment decisions are made according to the progression of the disease, the patient's general condition, and the patient's own wishes. There are variations in treatment policies among facilities due to the specialty of staff and cooperation with other departments at each facility. We conducted a multi-institutional retrospective study to compare outcomes by treatment strategy. METHODS: In this study, 340 patients with SNMT who were treated at 13 Hospitals (Head and Neck Oncology Group (Kyoto-HNOG) ) during the 12-year period from January 2006 to December 2017 were included. There were 220 patients with squamous cell carcinoma, 32 with malignant melanoma, 21 with olfactory neuroblastoma, and 67 with other malignancies. Of the squamous cell carcinomas, 164 were of maxillary sinus origin. One hundred and forty cases of MSSCC that were treated radically were included in the detailed statistical analysis. RESULTS: There were 5 cases of cStage I, 9 cases of cStage II, 36 cases of cStage III, 74 cases of cStage IVa, and 16 cases of cStage IVb. There were 92 cases without clinical lymph node metastasis (cN(-)) and 48 cases with clinical lymph node metastasis(cN(+)). Primary tumors were treated mainly by surgery in 85 cases (Surg) and by radical radiation therapy (with or without chemotherapy) of 6-70 Gy in 55 cases(non-Surg). The 5-year overall/disease-free survival rate (OS/DFS) for MSSCC was 65.1%/51.6%. Old age, renal dysfunction, and clinical T progression were independent risk factors for OS, and renal dysfunction was an independent risk factor for DFS. In cN(-) patients, OS and DFS were significantly better in Surg group than in non-Surg group. In cN(+) patients, there was no significant difference in OS and DFS between Surg and non-Surg groups. CONCLUSION: For patients with MSSCC without lymph node metastasis, aggressive surgery on the primary tumor contributes to improved prognosis.

Comparative Study of Immunodeficient Rat Strains in Engraftment of Human-Induced Pluripotent Stem Cell-Derived Airway Epithelia.

The airway epithelia (AE) play a role in the clearance of foreign substances through ciliary motility and mucus secreted. We developed an artificial trachea that is made of collagen sponges and polypropylene mesh for the regeneration of the tracheal defect, and it was used for a clinical study. Then, a model in which the luminal surface of an artificial trachea was covered with a human-induced pluripotent stem cell-derived AE (hiPSC-AE) was transplanted into the tracheal defect of nude rats to promote epithelialization. In the future, this model was expected to be applied to research on infectious diseases and drug discovery as a trachea-humanized rat model. However, at present, sufficient engraftment has not been achieved to evaluate functional recovery in transplanted cells. Therefore, this study focused on immunosuppression in recipient rats. Nude rats lack T cell function and are widely used for transplantation experiments; however, more severe immunosuppressed recipients are preferred for xenotransplantation. Several strains of immunodeficient rats were created as rats that exhibit more severe immunodeficiency until now. In this study, to establish a trachea-humanized rat model in which human AE function can be analyzed to improve engraftment efficiency, engraftment efficiency in nude rats and X-linked severe combined immunodeficiency (X-SCID) rats following hiPSC-AE transplantation was compared. In the analysis of the proportion of engrafted cells in total cells at the graft site, the engraftment efficiency of epithelial cells tended to be high in X-SCID rats, although no statistical difference was found between the two groups, whereas the engraftment efficiency of mesenchymal cells was higher in X-SCID rats. Furthermore, the number of immune cells that accumulated in the grafts showed that a pan T cell marker, that is, CD3-positive cells, did not differ between the two strains; however, CD45-positive cells and major histocompatibility complex (MHC) class II-positive cells significantly decreased in X-SCID rats. These results indicate that X-SCID rats are more useful for the transplantation of hiPSC-AE into the tracheae to generate trachea-humanized rat models.

Long-term effects of second cochlear implantation with sequential bilateral cochlear implantation in Japanese children.

OBJECTIVE: This study aimed to longitudinally evaluate speech perception ability and sound-field thresholds with the first, second, or bilateral cochlear implants (CIs) and MAP parameters of second CI in children. METHODS: Eighteen children who underwent bilateral cochlear implantation at Kyoto University Hospital were included. We evaluated speech perception under quiet and noisy conditions using the first, second, or bilateral CIs, CI-aided sound-field thresholds using the first or second CI, and MAP parameter values (C-levels, T-levels, and dynamic range) of the second CI of more than 5 years after the second implantation. RESULTS: Patients with a second CI after 7 years of age had significantly worse speech perception ability with the second CI even long after the surgery than those with a second CI before 7 years of age. CI-aided sound-field thresholds using the first or second CI were similar, regardless of the second implantation timing. Speech perception in noise with bilateral CIs was enhanced by the addition of a second CI, even after 7 years of age. Patients undergoing second cochlear implantation before 3.5 years of age showed significantly higher C-levels and wider dynamic ranges in the second CI MAP parameters. CONCLUSIONS: When the second implantation was performed after 7 years of age, the second CI effects were limited even with long-term use, which is attributed to unstable MAP parameters. The second CI-aided sound-field threshold contributed to the better outcome of bilateral CIs in noise, even if the second implantation was performed at age of ≥7 years.

Local recurrence and metachronous multiple cancers after transoral nonrobotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Late laryngopharyngeal cancers after transoral surgery include not only local recurrences but also metachronous multiple cancers. METHODS: We compared clinical information, surgical outcomes, and late laryngopharyngeal cancers in patients who underwent transoral nonrobotic surgery for laryngopharyngeal squamous cell carcinoma without lymph node metastases between 2015 and 2021 in a multicenter retrospective study. RESULTS: Four hundred and fifty-seven patients were included. Positive surgical margins were found in 121 patients (26.5%). Twenty-two patients (4.8%) received additional treatment. Positive horizontal margins of invasive carcinoma (p = 0.003) and positive horizontal margins of carcinoma in situ only (p = 0.032) were independent risk factors for local recurrence, and prior radiotherapy (p = 0.001) for metachronous multiple cancers. Local control was significantly worse without additional treatment (p = 0.049), but there was no significant difference in survival. CONCLUSIONS: Patients with positive margins had an increased frequency of local recurrence, but salvage therapy was effective.