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 induced pluripotent stem cell-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.

Modified method for tracheoesophageal fistula closure in intractable cases.

OBJECTIVE: Tracheoesophageal puncture (TEP) is one of the most established methods for voice reacquisition following total laryngectomy. The most difficult complication following TEP is the management of saliva leakage or secretion into the trachea due to TE fistula enlargement. In this study, we devised a new strategy to close TE fistulas and confirmed its safety and effectiveness. METHODS: Skin incision: If the tracheal mucosa around the voice prosthesis appears intact and normal, an arcuate incision, from 10 to 2 o'clock, is made on the skin 5 mm superior to the edge of the stoma. However, if the surrounding tracheal mucosa is fragile because of leaking, the incision is made on the superior edge of the stoma, with later reconstruction of the posterior tracheal wall. Separation of the trachea and esophagus: If the esophagotracheal spatium appears normal and is easy to dissect, the connective pipes can be found easily. After cutting the pipe, a ligature alone is sufficient for the tracheal side; however, the esophageal wall is closed with Gambee sutures. If the esophagotracheal spatium is compromised and the posterior tracheal wall is fragile (due to saliva leakage), we remove the posterior wall and reconstruct the area using the superior skin flap. We performed our novel method on four patients with intractable conditions; postradiotherapy for laryngeal cancer, total pharyngo-laryngo-esophagectomy (TPLE) with jejunum reconstruction, TPLE with gastric lifting reconstruction, and in a patient who underwent cervicothoracic incisional drainage for descending necrotizing mediastinitis. RESULTS: None of the cases showed postoperative leakage from the fistula, and oral intake was resumed without difficulty. CONCLUSION: This study showed that this strategy based on TE fistula conditions is effective even in difficult-to-treat cases.

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.

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.

Novel evaluation method for facial nerve palsy using 3D facial recognition system in iPhone.

OBJECTIVE: While subjective methods like the Yanagihara system and the House-Brackmann system are standard in evaluating facial paralysis, they are limited by intra- and inter-observer variability. Meanwhile, quantitative objective methods such as electroneurography and electromyography are time-consuming. Our aim was to introduce a swift, objective, and quantitative method for evaluating facial movements. METHODS: We developed an application software (app) that utilizes the facial recognition functionality of the iPhone (Apple Inc., Cupertino, USA) for facial movement evaluation. This app leverages the phone's front camera, infrared radiation, and infrared camera to provide detailed three-dimensional facial topology. It quantitatively compares left and right facial movements by region and displays the movement ratio of the affected side to the opposite side. Evaluations using the app were conducted on both normal and facial palsy subjects and were compared with conventional methods. RESULTS: Our app provided an intuitive user experience, completing evaluations in under a minute, and thus proving practical for regular use. Its evaluation scores correlated highly with the Yanagihara system, the House-Brackmann system, and electromyography. Furthermore, the app outperformed conventional methods in assessing detailed facial movements. CONCLUSION: Our novel iPhone app offers a valuable tool for the comprehensive and efficient evaluation of facial palsy.

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.

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.

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.

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.

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.

Safety and efficacy of high tracheostomy with inferior retraction of the thyroid isthmus.

OBJECTIVE: In typical surgical tracheostomy, the thyroid isthmus is divided or retracted superiorly and preserved. However, at our institution, the thyroid isthmus is retracted inferiorly and preserved. Thereafter, a tracheal incision is made above the thyroid isthmus. This method, hereinafter defined as high tracheostomy, has the advantage of facilitating immediate access to the trachea in a superficial position; moreover, it can be quickly replaced with cricothyrotomy in emergency situations. However, tracheotomies placed too high can potentially damage the cricoid cartilage, thereby causing subglottic granulation and tracheal stenosis. We aimed to validate the safety and efficacy of high tracheostomy with inferior retraction of the thyroid isthmus. METHODS: This was a retrospective cohort analysis. We analyzed the operative method and other relevant characteristics of 90 patients who underwent surgical tracheostomy between April 2016 and June 2022. For those who underwent high tracheostomies, we analyzed the duration of surgery, amount of intraoperative bleeding, occurrence of complications, problems with stoma closure, and perioperative mortality. RESULTS: High tracheostomy was performed in 73 patients. Subglottic granulation occurred in one patient, and the granulation tissue spontaneously shrank. Subcutaneous emphysema occurred in two patients. No patient developed wound infection or tracheoinnominate artery fistula. Moreover, no patient experienced false route tracheotomy tube insertion because the thyroid glands were located under the stoma. CONCLUSION: The frequency of complications was comparable to that reported in other studies on tracheostomy. Additionally, no patient developed tracheal stenosis secondary to tracheostomy above the thyroid isthmus. Therefore, high tracheostomy with inferior retraction and preservation of the thyroid isthmus is safe and advantageous.

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.

Parathyroid carcinoma: impact of preoperative diagnosis on the choice of surgical procedure.

The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.

Hemostasis for a Post-tonsillectomy Hemorrhage in a Patient With Coronavirus Disease.

During the coronavirus disease 2019 (COVID-19) pandemic, otolaryngologists should be careful when performing upper airway surgery because of the risk of aerosol generation. This paper describes the case of a 23-year-old male who was diagnosed with COVID-19 four days after undergoing tonsillectomy. COVID-19 was complicated by pulmonary thromboembolism, and anticoagulation was administered, which caused postoperative hemorrhage. The patient had to undergo another surgery for the control of hemorrhage, during the infective period of COVID-19. COVID-19 is sometimes associated with venous embolism, and for postoperative patients, treatment should be carefully considered because of the risk of bleeding. The administration of heparin as an anticoagulant would be preferable because heparin allows for dosage adjustment by measuring activated partial thromboplastin time and also allows the rapid cessation of the anticoagulant effect when the administration is discontinued together with antagonization by protamine administration, even if bleeding occurs. When performing surgery for patients with COVID-19, special care is necessary in order not to spread the infection. Even if the preoperative polymerase chain reaction (PCR) test is negative, the patient may be in the incubation period of COVID-19; therefore, caution should be exercised when performing upper respiratory tract surgery such as tonsillectomy.

Characteristics of oral squamous cell carcinoma focusing on cases unaffected by smoking and drinking: A multicenter retrospective study.

BACKGROUND: Some oral squamous cell carcinoma (OSCC) cases are unaffected by smoking or drinking. This study aimed to clarify distinctive groups among OSCC patients and examine the characteristics of multiple primary carcinomas (MPCs). METHODS: We analyzed data from 970 patients. The patients were divided into three groups: all individuals <45 years (<45 y), smokers/drinkers ≥45 years (SD ≥45 y), and non-smokers/non-drinkers ≥45 years (NSND ≥45 y). RESULTS: Tongue cancers were more common in the <45 y group than in the other groups (p < 0.001). The NSND ≥45 y group was significantly older and more likely to be female than the SD ≥45 y group (p < 0.001). MPCs in the upper aerodigestive tract were more common in men and smokers/drinkers, whereas women were at risk for multiple primary OSCCs (p = 0.022). CONCLUSIONS: The "young tongue" and "elderly female" subgroups and characteristics of MPCs suggest carcinogenic factors of OSCC other than smoking and drinking.

Validation of indications for enucleation for benign parotid gland tumors.

BACKGROUND: Enucleation has been reported as a minimally invasive surgery for Warthin's tumor (WT). However, the definite indications for enucleation have not been clarified. METHODS: Enucleation was indicated by the following findings: findings of WT, cystic fluid, or benign leukocytes by fine-needle aspiration cytology; a well-margined and homogeneous pattern on imaging; and a tumor location in the tail or preauricular area of the parotid gland. We reviewed 552 cases treated with parotid gland surgery in our hospital. RESULTS: A total of 108 tumors were treated with enucleation and included no malignant solid tumors or pleomorphic adenoma. Enucleation demonstrated low invasiveness and complication rates. Revision surgery for WT reappearance after enucleation was rare and showed minimal scarring, with a lower risk of facial weakness. CONCLUSIONS: The indication criteria for enucleation were validated. Such enucleation is useful, as it is associated with minimal invasiveness, low complication rates, and safety in revision surgery.

Difference in muscle synergies of the butterfly technique with and without swimmer's shoulder.

This study aimed to investigate whether muscle synergy differs between swimmers with and without swimmer's shoulder in the butterfly technique. Muscle synergies, which can assess muscle coordination, were analyzed using surface electromyography. Twenty elite swimmers were included in this study (swimmer's shoulder: n = 8; control: n = 12). The motions involved in executing the butterfly technique were classified into the early pull-through, late pull-through, and recovery phases. Muscle synergy data analyzed using the nonnegative matrix factorization method were compared between the two groups.The swimming velocities were 1.66 ± 0.09 m・s -1 and 1.69 ± 0.06 m・s -1 for the control and swimmer's shoulder groups, respectively. Four muscle synergies in both groups were identified: synergy #1, which was involved in the early pull; synergy #2, involved in the late pull; synergy #3, involved in the early recovery; and synergy #4, involved in pre- and posthand entry. Compared to the control group, the swimmer's shoulder group had a small contribution from the pectoralis major (p = 0.032) and a high contribution from the rectus femoris during the early pull phase (p = 0.036). In the late pull phase, the contribution of the lower trapezius muscle in the swimmer's shoulder group was low (p = 0.033), while the contribution of the upper trapezius muscle in the pre- and postentry phases was high (p = 0.032). In the rehabilitation of athletes with swimmer's shoulder, it is therefore important to introduce targeted muscle rehabilitation in each phase.

Real-world 2-year long-term outcomes and prognostic factors in patients receiving nivolumab therapy for recurrent or metastatic squamous cell carcinoma of the head and neck.

OBJECTIVE: Real-world outcomes and prognostic factors in Japanese patients receiving nivolumab therapy for recurrent or metastatic head and neck carcinoma (RMHNC) with an observation period of 1 year have been previously reported. The 1-year follow-up data have been subsequently accumulated, and the long-term real-world outcomes have been analyzed. This study aimed to investigate the 2-year long-term outcomes and prognostic factors associated with the response to nivolumab. METHODS: This was a multi-institutional retrospective study. In total, 88 RMHNC Japanese patients with squamous cell carcinoma who received nivolumab between May 2017 and May 2018 were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and best overall response (BOR) were evaluated. Univariate and multivariable analyses were performed to identify the prognostic factors. RESULTS: The median follow-up periods for monitoring OS and PFS were 73.1 and 48.1 weeks, respectively. The median OS was 74.1 weeks, and the 2-year survival rate was 33.4%. The median PFS was 18.5 weeks, and the 2-year PFS rate was 22.5%. The BOR rate was 10.2%, 19.3%, 25.0%, and 44.3% in patients who achieved complete response, partial response, stable disease, and progressive disease (PD), respectively. Among the 88 patients with RMHNC, a total of 40 immune-related adverse events (irAEs) were reported in 30 patients. Four patients continued nivolumab, while 84 patients discontinued nivolumab at the data cut-off date. The most common reason for discontinuation was PD in 61 patients, irAEs in 14 patients, and patients' wishes in 7 patients. Of the 61 patients who discontinued nivolumab because of PD, 28 patients received subsequent treatment. Statistical analyses revealed radiotherapy history, performance status, platinum-refractory carcinoma, irAEs, age, and post-nivolumab treatment as the important prognostic factors associated with OS in patients with RMHNC, and the magnitude of BOR was significantly associated with OS. Additionally, patients with subsequent treatment, including molecular targeted therapy and/or chemotherapy, had significantly prolonged OS compared to patients without subsequent treatment in cases with nivolumab discontinuation because of PD. CONCLUSION: These findings could be a useful guide for future treatment strategies for head and neck carcinoma. Considering the limitations of our cohort, further larger-scale studies with long-term follow-up are needed to substantiate the results of this study.

Classification of Voice Disorders Using a One-Dimensional Convolutional Neural Network.

OBJECTIVES: Auditory-perceptual voice analysis is a standard method for quantifying pathological voice quality, but perceptual ratings are based on subjective evaluations and therefore may vary among examiners. Although many acoustic metrics have been studied for potential use in the objective evaluation of pathological voices, the interpretation of acoustic metrics in individual cases is difficult and the technique is not widely used by clinicians. The aim of this study was to establish standardized methods to discriminate grade, roughness, breathiness, asthenia, strain (GRBAS) scale scores of pathological voices directly using one-dimensional convolutional neural network (1D-CNN) models. METHODS: We constructed an original dataset utilizing 1,377 voice samples of sustained phonation of the vowel /a/. Each voice sample was rated by three experts according to the GRBAS scale and the median values were used as the correct answer label. We designed an end-to-end 1D-CNN model with a raw voice waveform input having a frame width of 9,600 samples. The models were trained with our original dataset for each GRBAS category individually and the model performance was tested by the five-fold cross validation method. RESULTS: The accuracy, F1 score, and quadratic weighted Cohen's kappa for the testing dataset were determined. The metrics for the G scale showed the most balanced model performance, with high accuracy (0.771) and substantial agreement (kappa = 0.710). The model for the R scale had relatively high accuracy (0.765) and F1 score (0.743) with moderate agreement (kappa = 0.536). The accuracy (0.883) and the F1 score (0.865) for the S scale were the highest among the five categories, whereas the Cohen's kappa was the lowest (0.190). CONCLUSIONS: The end-to-end 1D-CNN models can evaluate overall pathological voice quality with a reliability comparable to human evaluations. The efficiency with which the machine learning models can be trained and evaluated is closely related to the dataset quality.