Parasomnia induced by lemborexant: a case report.

Lemborexant, an orexin receptor antagonist, is effective not only for sleep disorders but also for preventing and treating delirium. To date, no complex sleep-related behaviors due to lemborexant have been reported. Herein, we present the case of a 69-year-old male patient who was hospitalized for oral floor and tongue cancer and developed delirium after surgery; however, upon lemborexant dosage increase, used to treat insomnia, he developed abnormal nocturnal behavior. This symptom rapidly improved when lemborexant was discontinued. Distinguishing parasomnia from delirium is important because the treatment of these two conditions differs. Although rapid eye movement sleep behavior or sleepwalking was the cause of this parasomnia, a definitive diagnosis could not be established. If qualitatively distinct abnormal behavior is observed compared to delirium after increasing lemborexant dosage, the possibility of parasomnia should be considered.

Post-treatment Neutrophil/Lymphocyte Ratio Is a Prognostic Factor in Head and Neck Cancers Treated With Nivolumab.

Background/Aim: Inflammation and nutrition-based biomarkers, such as the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI), have prognostic value for several types of malignancies. Markers that precisely reflect the prognosis of patients with head and neck cancers (HNCs) treated with immune-checkpoint inhibitors remain unclear. This retrospective study aimed to investigate the prognostic value of hematological markers before and after treatment with nivolumab in patients with recurrent or metastatic HNC (RM-HNC). Patients and Methods: We evaluated the clinical data of 44 patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab between April 2017 and April 2023 at Shinshu University Hospital. Values of hematological biomarkers (NLR, LMR, PLR, CAR, PNI, SII, and SIRI) were calculated before and 4-6 weeks after nivolumab initiation. Receiver operating characteristic curves were constructed to determine the cutoff values of pre- and post-treatment markers for overall survival (OS) and progression-free survival (PFS). Results: Among all pre- and post-treatment markers, post-treatment NLR showed the highest area under the curve (AUC=0.702). A high post-treatment NLR (cutoff value, 4.01) was associated with a poor OS (p=0.027) and a tendency for shorter PFS (p=0.117). Multivariate analysis showed that a high post-treatment NLR was significantly associated with poor OS (p=0.026). Conclusion: A high post-treatment NLR was associated with poor response to nivolumab in head and neck cancers.

A Spatial Transcriptome Reveals Changes in Tumor and Tumor Microenvironment in Oral Cancer with Acquired Resistance to Immunotherapy.

Although anti-programmed death-1 (PD-1) antibody therapy improves the prognosis in patients with head and neck squamous cell carcinoma (HNSCC), some patients exhibit disease progression even after showing a good response to the treatment initially because of acquired resistance. Here, we aimed to reveal the dynamic changes in the tumor and tumor microenvironment (TME) in a 77-year-old man diagnosed with oral squamous cell carcinoma who developed acquired resistance after the administration of nivolumab using spatial transcriptomics. The results showed that, before immunotherapy, the activated pathways in the tumor area were mainly related to the cancer immune system, including antigen processing cross-presentation, interferon-gamma signaling, and the innate immune system. After immunotherapy, the activated pathways were mainly related to epigenetic modification, including RMTs methylate histone arginine and HDAC deacetylates histones. Before immunotherapy, the activated pathways in the TME were mainly related to the metabolism of proteins, including SRP-dependent co-translational protein targeting the membrane. After immunotherapy, the activated pathways in the TME were related to sensory perception and signal transduction. Our study revealed that epigenetic-modification-related pathways were mainly activated after establishing acquired resistance, suggesting that epigenetic modification in the tumor may prevent cancer immune system activation via the anti-PD-1 antibody.

A case of hematohidrosis successfully treated with a beta-blocker.

Hematohidrosis is a rare disorder characterized by bloody sweating on the skin without trauma. The ear, nose, and other facial areas are the most commonly affected sites. This study shows usefulness of beta-blockers in the treatment of hematohidrosis.

Prognostic significance of pre- and post-treatment hematological biomarkers in patients with head and neck cancer treated with chemoradiotherapy.

This study aimed to investigate the prognostic value of hematological biomarkers measured before and after treatment in patients with head and neck cancer (HNC). This study reviewed 124 patients with HNC who received chemoradiotherapy. Hematological biomarkers assessed before and after treatment were investigated. The pretreatment C-reactive protein/albumin ratio (pre-CAR) and post-treatment prognostic nutritional index (post-PNI) showed the highest area under the curve with cutoff values of 0.0945 and 34.9, respectively. Patients in the high pre-CAR group showed significantly worse prognosis than those in the low pre-CAR group with respect to the progression-free survival (PFS) (3-year PFS: 44.8% vs. 76.8%, p < 0.001) and overall survival (OS) (3-year OS: 65.8% vs. 94.0%, p < 0.001). Patients in the low post-PNI group showed significantly worse prognosis than those in the high post-PNI group with respect to the PFS (3-year PFS: 58.6% vs. 77.4%, p = 0.013) and OS (3-year OS: 75.2% vs. 96.9%, p = 0.019). Multivariate analysis revealed that advanced N stage (p = 0.008), high pre-CAR (p = 0.024), and low post-PNI (p = 0.034) were significantly associated with poorer OS. We suggest that the evaluation of hematological markers before and after treatment is useful for predicting disease progression and survival.

Sound localization in patients with idiopathic sudden hearing loss.

BACKGROUND: Patients with unilateral hearing loss have difficulty localizing sound. Severe-to-profound unilateral hearing loss is most commonly caused by idiopathic sudden sensorineural hearing loss (SSNHL). AIMS/OBJECTIVES: To assess the sound localization ability of patients with idiopathic unilateral SSNHL and examine the factors affecting the results. MATERIAL AND METHODS: We retrospectively enrolled 141 patients with idiopathic unilateral SSNHL. The assessment stimuli were speech-shaped noise from one of the nine loudspeakers in a 180° arc. Multiple regression analysis was used to examine the factors that affected sound localization ability. RESULTS: There was a strong correlation between the hearing level on the affected side post-treatment and the deviation score as the index of sound localization ability. The results of the multiple regression analysis suggested that sound localization may be partially affected by hearing level on the unaffected side and age. CONCLUSIONS AND SIGNIFICANCE: The results showed that sound localization ability decreased in idiopathic SSNHL patients with severe-to-profound hearing loss post-treatment. This study provides important data for future interventions for unilateral hearing loss, including cochlear implants.

Impact of Low Skeletal Muscle Mass on the Prognosis of Patients with Head and Neck Cancer Treated Nonsurgically.

INTRODUCTION: Sarcopenia, characterized by low skeletal muscle mass, and the outcome of cancer therapy are closely related based on recent research. This study aimed to evaluate the correlation between skeletal muscle mass and prognosis in head and neck cancer (HNC) patients. METHODS: In this study, 51 male patients with HNC treated nonsurgically between January 2016 and April 2018 at Shinshu University Hospital were evaluated. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and the skeletal mass index (SMI) was calculated to classify the patients. RESULTS: The low-SMI group had a significantly worse overall survival (OS) than the normal-SMI group (3-year OS: 72.0% vs. 93.0%, p = 0.014), and there was a trend toward worse progression-free survival (PFS) in the low-SMI group (3-year PFS: 49.6% vs. 79.3%, p = 0.064). Multivariate analysis also showed that low SMI (p = 0.04) and severe N stage (p = 0.009) were significantly associated with poorer OS. CONCLUSION: The pretreatment assessment of SMI using bioelectrical impedance analysis is useful for identifying patients with poor prognoses. To improve the treatment outcome in HNC, we need to think of the intervention, such as cancer rehabilitation and nutritional support, during or before treatment, especially for patients with low SMI.

Perioperative management of a patient with a giant thyroglossal duct cyst: a case report.

Thyroglossal duct cysts (TGDC) are the most common type of congenital neck masses, which generally present in young adults. We present a rare case of a giant TGDC in a 77-year-old patient who required atypical perioperative management. The patient presented with a large soft mass on his anterior neck. Computed tomography showed a lobulated cystic mass measuring 18 × 16 cm, extending from the tongue base to the inferior level of the clavicle. Because difficult intubation was expected, the cyst was punctured and most of the fluid was drained prior to surgery. The swelling of the tongue base was remarkably reduced, and intubation was performed safely. The cyst was extracted using the Sistrunk procedure and tracheotomy was performed. Histopathological examination confirmed the diagnosis of TGDC. Preoperative volume reduction of the cyst and tracheotomy should be considered for oral intubation and postoperative airway management, respectively, in patients with large TGDC.

Speech perception in noise in patients with idiopathic sudden hearing loss.

BACKGROUND: Patients with unilateral hearing loss have difficulties perceiving speech in a noisy environment. Unilateral severe to profound hearing loss is most commonly caused by idiopathic sudden sensorineural hearing loss (SSNHL). OBJECTIVES: To assess speech perception in noise among patients with idiopathic unilateral SSNHL, and examine the factors affecting the results. MATERIAL AND METHODS: We retrospectively enrolled 93 patients with idiopathic unilateral SSNHL. The speech signal was presented at a constant sound pressure level, while the noise signal varied from +5 dB to -5 dB signal-to-noise ratio (SNR) in units of 5 dB (S0/Nhe). RESULTS: As the SNR decreased, the percentage of correct answers also decreased. The correct answer rate decreased with increased hearing level at post-treatment. There was a correlation between age and speech perception, especially when dividing the patients into two groups: <65 years old and ≥65 years old. CONCLUSIONS AND SIGNIFICANCE: The results showed that speech perception clearly decreased in a noisy environment rather than in a quiet environment, and the correct answer rate of the speech perception test in noise was significantly correlated with hearing level at post-treatment. This study provides important data for future interventions for unilateral hearing loss, including cochlear implants.

Factors Affecting Nivolumab Therapy Outcome in Patients with Head and Neck Cancer: A Single-Center Analysis.

BACKGROUND: Nivolumab, a programmed death-1 antibody, is an immune checkpoint inhibitor approved in Japan in March 2017 for the treatment of recurrent or metastatic head and neck cancers (RM-HNCs) after platinum drug administration. This study aimed to evaluate the effectiveness and safety of nivolumab and to determine the prognostic factors affecting the treatment outcome, in a real-world setting in Japanese RM-HNCs. METHODS: Forty-six patients with RM-HNCs treated with nivolumab between April 2017 and April 2021 at Shinshu University Hospital were retrospectively assessed in this cohort study. RESULTS: The overall response rate was 17.4%, and the disease control rate was 41.3%. The median first and second progression-free survival (PFS1 and PFS2) were 2.6 and 10.3 months, respectively. The median overall survival (OS) was 14.8 months. Multivariate analysis showed that performance status (PS) (p = 0.003) and a decrease in neutrophil-lymphocyte ratio (NLR) (p = 0.02) were significantly associated with a better OS, and a decrease in NLR (p = 0.035) was associated with a better PFS2. CONCLUSIONS: This study is the first report of PFS2 in RM-HNCs treated with nivolumab; the long PFS2 may contribute to prolonged OS. We propose that the PS and a decrease in NLR could be useful clinical prognostic markers of nivolumab therapy, which can easily be evaluated in the clinical setting.

Impact of upgraded radiotherapy system on outcomes in postoperative head and neck squamous cell carcinoma patients.

Background: This study was performed to evaluate the impact of upgrade of radiotherapy system, including launch of intensity-modulated radiation therapy (IMRT), on the therapeutic outcomes. Materials and methods: Patients with head and neck (H&N) squamous cell carcinoma (SCC) who underwent postoperative radiotherapy at our hospital between June 2009 and July 2019 were retrospectively reviewed. In July 2014, we converted the radiotherapy technique for these patients from a 3-dimensional conformal radiotherapy (3D-CRT) to IMRT, along with the adoption of a meticulous planning policy and a few advanced procedures, including online imaging guidance. Results: A total of 136 patients (57 treated with the previous system and 79 treated with the upgraded system) were reviewed. There were significantly more patients with extracapsular extension in the upgraded-system group than the previous-system group (p = 0.0021). There were significantly fewer patients with ≥ Grade 2 acute and late adverse events in the upgraded-system group than the previous-system group. The differences in progression-free survival (PFS), distant metastasis-free survival (DFFS), locoregional progression-free survival (LRPFS), and overall survival (OS) between the two groups were not statistically significant (p = 0.8962, 0.9926, 0.6244, and 0.4827, respectively). Multivariate analysis revealed that the upgrade had neither positive nor negative impact on survival outcomes. Extracapsular extension was independently associated with decreased LRPFS and OS (p = 0.0499 and 0.0392, respectively). Conclusions: The IMRT-centered upgrade was beneficial for the postoperative patients with H&N SCC, because survival outcomes were sustained with less toxicities.

The availability of an adhesive bone conduction hearing device: a preliminary report of a single-center experience.

Background: An adhesively attached bone conduction hearing device has been newly developed. This novel bone conduction hearing device is placed behind the ear and has an audio processor connected to the adapter to transmit sound through vibrations.Objective: To obtain preliminary results regarding the use of this device, we sought to apply it to patients with various types of hearing loss.Methods: Nine patients aged over 18 years and with hearing loss due to bilateral middle ear anomaly (n = 1), bilateral aural atresia (n = 3), unilateral aural atresia (n = 2), and single-sided deafness (n = 3) were recruited.Results: The functional gain provided by the adhesive bone conduction hearing device for the aided side was found to be sufficient. Although the results on speech perception in noise showed significant improvement for patients with conductive hearing loss, no improvement was found for patients with single-sided deafness. Subjective assessment showed that speech and spatial hearing-related issues were improved.Conclusion: The adhesive bone conduction hearing device was thought to provide a feasible option. Additionally, in patients considering the use of a surgically implanted hearing device, this device is a preferable option for preoperative assessment due to its non-invasiveness.

Treatment algorithm for idiopathic sudden sensorineural hearing loss based on epidemiologic surveys of a large Japanese cohort.

Background: To date, there have been few conventional algorithms for the treatment of idiopathic sudden sensorineural hearing loss (SSNHL), as there have been only limited reports with high evidence levels.Objectives: To propose an evidence- and trend-based treatment algorithm for SSNHL.Methods: We referred not only to the evidence for each treatment, but also to trends related to treatment selection in Japan based on epidemiologic surveys, and considered the balance of the advantages and disadvantages with regard to each patient's condition.Results: We propose an algorithm that begins with the grade of SSNHL severity as the prognosis of SSNHL is strongly related to the severity of hearing loss. We selected systemic corticosteroid therapy as the first-line therapy, and Intra-tympanic corticosteroid therapy as salvage therapy. We also proposed the use of prostaglandin E1 with corticosteroids for the treatment of SSNHL patients with severe hearing loss. According to the data obtained from an epidemiologic survey, we decided time limits for the application of each treatment.Conclusion: An algorithm for the treatment for SSNHL is presented according to the results of epidemiologic surveys in Japan. It is expected that this algorithm can provide a guide to choosing the suitable treatment for SSNHL patients.

Prognostic impact of gene polymorphisms in patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: To investigate whether genetic polymorphisms (single-nucleotide polymorphism [SNPs]) have a prognostic influence on hearing recovery after standardized corticosteroid therapy. METHODS: A total of 192 gene samples from idiopathic sudden sensorineural hearing loss (SSNHL) patients registered in the Intractable Inner Ear Disease Gene Bank were enrolled and, as the candidate genes, 16 SNPs from 13 genes were selected for this study. Fischer's exact test was used to compare allele frequencies in each SNP between the patients with good hearing recovery and patients with poor hearing recovery. RESULTS: The SNPs of the GSR gene (rs2251780 and rs3779647) and NOS3 gene (rs1799983) were associated with treatment outcome (p < .05). Furthermore, there was a marginal correlation between the SNP of the NR3C1 gene (rs4912910) and treatment outcome (p = .05). CONCLUSIONS: The results of this study indicate that the analysis of genetic factors might make it possible to predict the treatment outcome, at least in part, in patients with idiopathic SSNHL.

Etiology of single-sided deafness and asymmetrical hearing loss.

CONCLUSIONS: The present study revealed that various etiologies are involved in single-sided deafness (SSD), and that the cause of SSD and asymmetrical hearing loss (AHL) differed greatly between congenital/early-onset cases and adult cases. Clarification of the etiology is the first step toward providing appropriate intervention. OBJECTIVES: The study aimed to clarify the etiology of SSD and AHL patients. METHODS: The etiology of a total of 527 SSD or AHL patients who visited Shinshu University Hospital between 2006 and 2016 were analyzed by imaging as well as serological tests for mumps virus, and CMV DNA testing. RESULTS: In our cohort of congenital/early-onset SSD (n = 210), the most prevalent cause in children was cochlear nerve deficiency (43.7%; 87 of 199 patients undergoing CT and/or MRI), followed by CMV infection, mumps infection, anomalies of the inner ear, ANSD, and other rare etiologies. In contrast, half of the adult SSD patients presented with idiopathic sensorineural hearing loss, followed by various types of otitis media, cerebellopontine angle tumor and other rare etiologies.

Epidemiological survey of acute low-tone sensorineural hearing loss.

OBJECTIVES: A nationwide epidemiological survey involving 23 hospitals in Japan was conducted and the predictive values of demographic data were examined statistically. METHODS: A total of 642 patients from 23 hospitals, including 20 university hospitals, in Japan were enrolled in the study. Age ranged from 8 to 87 years, and all were diagnosed with acute low-tone sensorineural hearing loss (ALHL) between 1994 and 2016. Demographic data for the patients, such as symptoms, gender, mean age, and distribution of ALHL grading, were collected and analyzed in relation to prognosis using Student's t-test, χ2 test and logistic regression. RESULTS: Female gender (p < .013), younger age (p < .001), low-grade hearing loss (p < .001), and shorter interval between onset and initial visit (p < .004) were significantly predictive of a good prognosis. The prognosis for definite ALHL was significantly better than that for probable ALHL (p < .007). CONCLUSIONS: The severity of initial hearing loss, interval between onset and initial visit and age were important prognostic indicators for ALHL, while female gender was an important prognostic indicator peculiar to ALHL.

Idiopathic sudden sensorineural hearing loss and acute low-tone sensorineural hearing loss: a comparison of the results of a nationwide epidemiological survey in Japan.

OBJECTIVES: The aim of this study was to investigate the differences between idiopathic sudden sensorineural hearing loss (SSNHL), and acute low-tone sensorineural hearing loss (ALHL) using the results of a nationwide survey database in Japan and to analyze the variables associated with their clinical features and the severity of hearing impairment, treatment, and prognosis. METHODS: Participants were patients registered between April 2014 and March 2016 in a multicenter epidemiological survey database involving 30 university hospitals and medical centers across Japan. Statistical analysis was performed to clarify the factors associated with their clinical characteristics and the severity of hearing impairment, treatment, and prognosis. RESULTS: Idiopathic SSNHL and ALHL differed significantly in terms of male-to-female ratio, age distribution, and time from onset to start of treatment. The treatment methods and hearing prognosis also differed markedly between the two diseases. A majority (92%) of idiopathic SSNHL patients were administered some type of corticosteroid, while half of the ALHL patients received corticosteroids and a diuretic agent. CONCLUSION: The results suggested that idiopathic SSNHL and ALHL belonged to different categories of inner ear disease.

The effect of initial treatment on hearing prognosis in idiopathic sudden sensorineural hearing loss: a nationwide survey in Japan.

OBJECTIVE: To investigate the hearing prognosis of idiopathic sudden sensorineural hearing loss (SSNHL) treated with different initial therapies. METHODS: Subjects consisted of patients diagnosed with idiopathic SSNHL within 7 days from onset and showing severe hearing loss (≥60 dB), who were registered in a Japanese multicenter database between April 2014 and March 2016. Subjects were divided into four groups according to initial therapy: (1) steroids, (2) steroids + Prostaglandins (PGs), (3) intratympanic steroids (ITS), and (4) no steroids. Hearing outcomes were compared among the groups. RESULTS: In total, 1305 patients were enrolled. The final hearing level and hearing gain of patients treated with steroids + PGs were significantly higher than those of patients treated with steroids alone or no steroids. The ratio of good prognosis (complete recovery or marked improvement) in patients treated with steroids + PGs was higher than that in patients treated with steroids alone or no steroids. There was no difference in the prognosis of patients treated with steroids alone or no steroids. CONCLUSION: A large number of patients with idiopathic SSNHL were registered in a multicenter database. PG use in combination with steroid administration was associated with a good hearing prognosis in patients with severe hearing loss.

A nationwide multicenter study of the Cochlin tomo-protein detection test: clinical characteristics of perilymphatic fistula cases.

OBJECTIVE: To investigate the positive rate for the Cochlin tomo-protein (CTP: an inner ear-specific protein) detection test among patients with inner ear-related clinical manifestations and evaluate the clinical characteristics of definite perilymphatic fistula (PLF). METHODS: We have performed an ELISA-based CTP detection test using middle ear lavage (MEL) samples from 497 cases of suspected PLF enrolled from 70 clinical centers nationwide between 2014 and 2015. In addition to the CTP-positive rate, audio-vestibular symptoms were compared between CTP-positive and -negative cases. RESULTS: 8-50% of patients in category 1 (trauma, middle and inner ear disease cases), and about 20% of those in categories 2, 3 and 4 (external origin antecedent events, internal origin antecedent events, and without antecedent event, respectively) were positive for CTP. In category 1 cases, the earlier tested samples showed a higher CTP-positive rate, whereas no differences were observed in categories 2, 3 or 4. The characteristic clinical features in the earlier tested cases were nystagmus and fistula sign in CTP test-positive cases in category 1, and streaming water-like tinnitus in those in categories 2, 3 and 4. CONCLUSION: The present study clarified that CTP detection test-positive patients exist at considerable rates among patients with inner ear-related manifestations.

Nationwide epidemiological survey of idiopathic sudden sensorineural hearing loss in Japan.

OBJECTIVES: Using a large-scale nationwide survey database, we investigated the epidemiological characteristics for idiopathic SSNHL in Japan. METHODS: The subjects for this analysis were patients registered in a Japanese multicentre database between April 2014 and March 2016. A total of 3419 idiopathic SSNHL patients were registered in the database, and the clinical characteristics of the idiopathic SSNHL patients were obtained. Several factors associated with the severity of hearing impairment and prognosis were then investigated. Statistical analysis was performed to clarify the factors associated with the severity of hearing impairment and prognosis. RESULTS: There were significant correlations between the severity of hearing loss and diabetes mellitus, kidney disease, past history of brain infarction, heart disease, age (under 16 years/elderly), and symptoms of vertigo/dizziness. We also analyzed the prognostic factors for idiopathic SSNHL, and found that the severity of hearing loss (Grade 3 or 4), heart disease, aged 65 years or over, time from onset to treatment (over 7 days), and symptoms of vertigo/dizziness were all significantly related to poor prognosis. CONCLUSION: The present large-scale clinical survey revealed current epidemiological trends for idiopathic sudden sensorineural hearing loss (SSNHL) and various factors associated with the severity of hearing impairment and prognosis.