Sleep status of older adults with sleep apnoea syndrome may vary by body mass index.

Obesity and ageing are the most important risk factors for sleep apnoea syndrome (SAS); however, the role of body mass index (BMI) on sleep status in healthy older adults is unclear. To explore sleep parameters according to BMI among active older adults, we cross-sectionally examined the relationship between sleep-related parameters and BMI in 32 Japanese adults aged from 83 to 95 years without long-term care who were unaware of having SAS. Correlation and linear regression analyses were performed. Moderate or severe SAS prevalence was high in both those with low (68.8%) and high (68.8%) BMI. A higher increase in apnoea-hypopnoea index (AHI) was negatively correlated with sleep depth in the high-BMI group. In the low-BMI group, the number of awakenings and age were positively correlated with AHI. Older adults may have SAS regardless of their BMI, and the sleep status of patients with SAS may vary by BMI.

Cha o 3, a cypress pollen allergen, does not activate basophils in Japanese cypress pollinosis.

Background: In Japan, pollinosis caused by the Japanese cypress (JCy) Chamaecyparis obtusa is among the very common seasonal allergies. In JCy pollinosis, Cha o 1 is the first major allergen, and Cha o 2 is the second major allergen. Recently, Cha o 3 was identified as a new JCy pollen allergen in JCy pollinosis. However, the relative contribution of Cha o 3 to JCy pollinosis compared with that of Cha o 1 and that of Cha o 2 has not been fully elucidated. Objective: This study aimed to clarify the allergenicity of Cha o 3 compared with that of Cha o 1 and Cha o 2 in JCy pollinosis. Methods: We recruited 27 patients with JCy pollinosis and performed the basophil activation test (BAT) with native (n) Cha o 1, Cha o 2, and Cha o 3 purified from JCy pollen. In addition, we a performed JCy-specific IgE suppression test. Results: In the BAT, 26 of 27 patients (96%) and 18 of 27 patients (67%) showed positive basophil activation in response to n Cha o 1 and n Cha o 2, respectively, as judged by CD203c expression. Little CD203c expression in response to n Cha o 3 was seen. The presence of n Cha o 3 marginally reduced the titer levels of JCy-specific IgE. Conclusion: Cha o 3 showed little ability to activate basophils and suppress JCy-specific IgE titers compared with Cha o 1 or Cha o 2 in patients with JCy pollinosis. Thus, Cha o 3 may not be a major allergen in JCy pollinosis.

Executive summary: Japanese guidelines for allergic rhinitis 2020.

The Practical Guideline for the Management of Allergic Rhinitis, the fist guideline for allergic rhinitis in Japan, was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 9th edition was published in 2020 and is widely used today. The most recent collection of evidence from the literature was supplemented to the revised guideline to incorporate evidence-based medicine. The revised guideline includes updated epidemiology of allergic rhinitis in Japan, a figure representing the mechanisms of allergic rhinitis in both the onset and sensitization phases with the introduction of regulatory T cells and type 2 innate lymphoid cells, practical assessment for diagnosis, new pharmacotherapy agents such as anti-IgE mAb and a new drug delivery system for antihistamines, sublingual immunotherapy for children, dual sublingual immunotherapy for house dust mites and Japanese cedar pollen extract, new classification for surgery for allergic rhinitis, and treatment and prescriptions for older adults. An evidence-based step-by-step strategy for treatment is also described.

Complement Factor H Is an Early Predictive Biomarker of the Therapeutic Efficacy of Sublingual Immunotherapy for Japanese Cedar Pollinosis.

Sublingual immunotherapy for Japanese cedar pollinosis can improve the symptoms of allergic rhinitis and modify its natural course. However, sublingual immunotherapy requires a long treatment period and some patients do not respond to treatment. In this study, we aimed to identify biomarkers that could predict the efficacy of sublingual immunotherapy at an early stage. In this study, 40 patients from phase III trials were recruited and divided into good and poor response groups. Using peripheral blood mononuclear cells from before and two months after the start of medication, microarray, discriminant analysis, and real-time polymerase chain reaction were performed to extract candidate genes that could be biomarkers. Furthermore, these genes were validated in 30 patients in general clinical practice. Complement factor H was upregulated in the good response group and downregulated in the poor response group. Complement factor H may be a useful biomarker for predicting the efficacy of sublingual immunotherapy for Japanese cedar pollinosis at early time points after treatment initiation.

Sublingual Immunotherapy for Japanese Cedar Pollinosis: Current Clinical and Research Status.

The incidence of Japanese cedar pollinosis is increasing significantly in Japan, and a recent survey suggested that about 40% of the population will develop this disease. However, spontaneous remission is rare. The increased incident rate of Japanese cedar pollinosis is a huge issue in Japan. Allergen immunotherapy is the only fundamental treatment that modifies the natural course of allergic rhinitis and provides long-term remission that cannot be induced by general drug therapy. Sublingual immunotherapy for Japanese cedar pollinosis has been developed and has been covered by health insurance since 2014 in Japan. The indication for children was expanded in 2018. Clinical trials of sublingual immunotherapy for Japanese cedar pollinosis have demonstrated its long-term efficacy and safety. It is recommended for patients who wish to undergo fundamental treatment regardless of the severity of the practical guidelines for the management of allergic rhinitis in Japan. For sublingual immunotherapy, a long-term treatment period of 3 years or longer is recommended to obtain stable therapeutic effects. In recent years, evidence based on basic research and clinical trials has demonstrated sublingual immunotherapy-induced immunological changes and efficacy in patients; however, biomarkers that objectively predict and judge these therapeutic effects need to be established.

Successful desensitization after hypersensitivity reaction to cisplatin in a patient with nasopharyngeal carcinoma.

Hypersensitivity reaction to cisplatin can result in discontinuation of chemoradiotherapy in patients with head and neck squamous cell carcinoma. We describe a patient with nasopharyngeal carcinoma who developed cisplatin hypersensitivity and was successfully treated with cisplatin desensitization. Furthermore, it had little impact on the therapeutic performance of cisplatin-combined chemoradiotherapy.

Nodular fasciitis arising from the buccal region after segmentectomy with rapid growth mimicking postirradiation myxofibrosarcoma: A case report.

RATIONALE: Nodular fasciitis (NF) can be misdiagnosed as a sarcoma because of its rapid growth and pathological features, such as nuclear atypia and mitoses. PATIENT CONCERNS: We present a rare case of a 72-year-old Japanese man who developed NF with suspected postirradiation myxofibrosarcoma (MFS) after segmentectomy for left-sided osteoradionecrosis (ORN) of the mandible. DIAGNOSIS: A mass appeared in the intraoral postoperative wound 1 year after left-sided mandibular segmentectomy and showed rapid growth, reaching a size of 50 mm within 2 months. Incisional biopsy revealed strongly Ki-67-positive spindle-shaped cells with large irregular nuclei and a diagnosis of postirradiation MFS. INTERVENTIONS: The patient was diagnosed with oropharyngeal cancer (T4aN2bM0) and underwent surgical resection of primary oropharyngeal squamous cell carcinoma with selective neck dissection and reconstruction with a rectus abdominis musculocutaneous flap at the age of 57 years, followed by postoperative 66 Gy of radiotherapy combined with cisplatin administration. No recurrent or metastatic lesions of oropharyngeal squamous cell carcinoma have been detected for > 10 years. However, the ORN of the jaw worsened, and the patient underwent sequestrectomy 3 times on the right side of the mandible, followed by a left-sided segmentectomy at the age of 72 years. One year after segmentectomy, a 10-mm mass with soft-to-firm consistency appeared in the buccal mucosa of the wound and grew rapidly. An incisional biopsy revealed MFS. Complete resection under general anesthesia was immediately performed. OUTCOMES: The histopathological diagnosis of the excised specimen was NF without any malignant findings. Two years after surgery, there was no evidence of recurrence or metastasis. LESSONS: NF grows rapidly and has pathological features similar to sarcoma, making differential diagnosis difficult at the time of incisional biopsy. Further studies should be conducted to determine the clinical and pathological features of this tumor.

Genomic and immune microenvironment profiling in a case of metastatic intrathyroid thymic carcinoma.

Metastatic intrathyroid thymic carcinoma (ITTC) is a rare cancer with no effective drugs for controlling. This case report has shown genomic and immune microenvironment profiles in metastatic ITTC and emphasized an immunosuppression via a PD-1/PD-L1 pathway, possibly strengthening the rationale for immune checkpoint blockade as a novel treatment.

Loss of intercellular bridges in the depth of invasion measurement area is a novel negative prognostic factor for oral squamous cell carcinoma: A retrospective study.

OBJECTIVE: This study aimed to evaluate intercellular bridges in the depth of invasion (DOI) measurement area as prognostic factors in oral squamous cell carcinoma (OSCC). STUDY DESIGN: The mode of invasion was determined based on the Yamamoto-Kohama classification system by observing the hematoxylin-eosin-stained whole-slide images of specimens obtained from 78 patients with OSCC, and the clinicopathologic features were characterized. The presence of intercellular bridges was analyzed in 46 patients with Yamamoto-Kohama classification grade ≥3 whose DOI was measured by dividing the measurement area into 3 parts: the surface, center, and front of the tumor. RESULTS: Univariate analyses identified lymph node metastasis, loss of intercellular bridges in the DOI measurement area, DOI of ≥4500 µm, and pattern of invasion 4C-4D as negative prognostic factors. Multivariate analyses revealed that lymph node metastasis and the loss of intercellular bridges in the entire area were independent factors, with hazard ratios of 9.34 (95% confidence interval, 2.09-42.03; P = .003) and 3.64 (95% confidence interval, 1.10-11.99; P = .045), respectively. CONCLUSIONS: Loss of intercellular bridges in the DOI measurement area is a negative prognostic factor for OSCC and may be useful in selecting treatment.

High expression of protein tyrosine kinase 7 in oral squamous cell carcinoma: Clinicopathological correlation and prognosis relevance.

BACKGROUND: The purpose of this study was to evaluate the association between the　immunohistochemistry (IHC) of protein tyrosine kinase 7 (PTK7) expression and clinicopathological factors of oral squamous cell carcinoma (OSCC). METHODS: Tissue specimens were obtained from 80 patients with primary OSCC. IHC scoring was conducted according to the rate of positive cell and staining intensity. We used the IHC score to classify the degree of PTK7 expression and evaluate clinicopathological factors and prognosis. RESULTS: The number of the high expression group (IHC Score 2 or 3) was 45 cases and that of the low expression group (IHC Score 0 or 1) was 35 cases. A significant difference between high expression and low expression groups was found in the N category (p = .008), degree of differentiation (p < .001), and pattern of invasion (p < .001). In accordance with the exacerbation of OSCC with respect to three parameters (N category, degree of differentiation, and pattern of invasion), the ratio of high expression of PTK7 increased. The overall 5-year survival rate was 59.3% in the high expression group and 87.3% in the low expression group (p < .05). The pathological prognostic signs affecting overall survival were evaluated by univariate analysis and multivariate analysis with Cox proportional hazards model and showed an association with lymph node metastasis and invasion patterns. CONCLUSION: This study suggests that a high IHC score of PTK7 is a potential biomarker for predicting potential metastasis.

A rare case of intracytoplasmic mucin-rich nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated tumor with a high incidence in Asian countries. NPC is a type of squamous cell carcinoma originating from the nasopharyngeal mucosa. Although rare, NPCs show some uncommon histologic variants; these variations remain to be understood. We described the cytologic characteristics of a rare NPC variant with abundant intracytoplasmic mucin. A 37-year-old Japanese man presented to our hospital with bilateral ear discomfort and palpable lymph nodes. Nasopharyngeal biopsy showed tumor cells with abundant intracytoplasmic, Alcian blue-PAS-positive mucin. Immunohistochemical analysis demonstrated that the tumor cells were positive for p40 and p53. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) showed EBV infection of the tumor cells. Fluorescence in situ hybridization (FISH) using MAML2 break-apart probes did not show split signals. Fine needle aspiration biopsy (FNAB) cytology of the metastatic lymph nodes was also performed. Smear samples had a necrotic and inflammatory background with both lymphocyte and neutrophil infiltration. Highly cellular tumor clusters and dispersed cells with naked nuclei were observed. The tumor cells showed a clear cytoplasm with distinct cell borders. Intracytoplasmic mucin pushing the nucleus to the periphery was observed in the scattered tumor cells in a liquid-based cytology sample. Given these findings, the final diagnosis was advanced nasopharyngeal carcinoma; cisplatin-based chemoradiation therapy was performed as the first-line treatment. The tumor recurred 8 months after completing the treatment. The recurrent nasopharyngeal tumor was a typical non-keratinizing NPC and lacked intracytoplasmic mucin.

Erratum for Risk Factors and Assessment Using an Endoscopic Scoring System for Postoperative Respiratory Complications after Anterior Cervical Decompression and Fusion Surgery.

[This corrects the article DOI: 10.22603/ssrr.2020-0104.].

Toxic epidermal necrolysis associated with nivolumab treatment for head and neck cancer.

This report is the first to document TEN caused by nivolumab treatment in head and neck cancer. We believe this article can contribute significantly in understanding the principles of nivolumab treatment in patients with head and neck cancer.

Risk Factors and Assessment Using an Endoscopic Scoring System for Postoperative Respiratory Complications after Anterior Cervical Decompression and Fusion Surgery.

INTRODUCTION: Postoperative respiratory complications (PRC) are one of the most serious complications. Potentially life-threatening accidents can occur after an anterior cervical discectomy and fusion (ADF), such as airway obstruction and aspiration pneumonia. Despite numerous studies, preoperative predictive and preventive methodology has yet to be established. As reported in our previous study, the evaluation of preoperative dysphagia using the eating assessment tool (EAT-10) and a flexible endoscopic evaluation of swallowing (FEES) is useful for predicting the incidence and risk factors of dysphagia after ADF. METHODS: This prospective study comprised 60 consecutive patients who underwent ADF. An otolaryngologist and a speech-language-hearing therapist preoperatively and 1 week postoperatively evaluated dysphagia using EAT-10 and Hyodo-Komagane (H-K) scores during FEES. Patient demographics, comorbidities, and pre- and postoperative dysphagia were compared between patients with and without PRC. RESULTS: Seven of 60 (11.6%) patients had preoperative dysphagia diagnosed using the H-K score. A significant positive correlation existed between the pre- and postoperative H-K scores. Of all 60 cases, eight (13.3%) had PRC. Among them, two required reintubation due to airway obstruction and six had aspiration pneumonia. The PRC(+) group was significantly older and more prone to diabetes and asthma. The preoperative H-K score of the PRC(+) group was significantly higher than that of the PRC(-) group. Postoperatively, but not preoperatively, EAT-10 was significantly higher in the PRC(+) group. CONCLUSIONS: Preoperative dysphagia may potentially exacerbate postoperative dysphagia after ADF. A preoperative evaluation of dysphagia using the H-K score during FEES is a useful method for predicting and reducing the risk of PRC. Level of Evidence: 3.

LPCAT2 Methylation, a Novel Biomarker for the Severity of Cedar Pollen Allergic Rhinitis in Japan.

BACKGROUND: Recently, the role of the epigenome in allergies has been receiving increasing attention. Although several genes that are methylated in relation to serum immunoglobulin E (IgE) concentration have been reported by epigenome-wide association studies, little is known about the DNA methylation sites associated with the symptoms and severity of cedar pollinosis (CP). OBJECTIVE: Our aim was to analyze the association between DNA methylation and the symptoms and severity of CP in peripheral blood mononuclear cells (PBMCs) and nasal mucosa scraping cells (NMSCs). METHODS: We recruited 70 participants during the cedar pollen dispersal season. IgE levels were measured by a fluorescence enzyme immunoassay. We analyzed DNA methylation of acyl-CoA thioesterase 7 (ACOT7), mucin 4 (MUC4), schlafen 12 (SLFN12), lysophosphatidylcholine acyltransferase 2 (LPCAT2), and interleukin-4 (IL4) in PBMCs and NMSCs using bisulfite next-generation sequencing; the correlation of DNA methylation with non-specific IgE and cedar pollen-specific IgE levels in peripheral blood samples was also investigated. Symptom severity and DNA methylation were investigated in 15 untreated CP patients. RESULTS: Non-specific IgE levels showed a significant negative correlation with average IL4 methylation in PBMCs (r = -0.46, P < 0.0001) but not with methylation of ACOT7, MUC4, SLFN12, and LPCAT2. Cedar pollen-specific IgE levels showed a significant negative correlation with average IL4 and MUC4 methylation in PBMCs (r = -0.31, P = 0.01 and r = -0.241, P = 0.046, respectively) but not with methylation of ACOT7, SLFN12, and LPCAT2. The methylation of some genes in NMSCs was not significantly correlated with IgE levels. The mean methylation of LPCAT2 in NMSCs showed a decreasing trend with increasing severity of CP (P = 0.027). CONCLUSION: LPCAT2 methylation in NMSCs may reflect the severity of CP and could be used as a novel biomarker to identify suitable treatment options for CP.

The influence of tonsillectomy on allergic diseases in pediatric patients.

BACKGROUND: The influence of tonsillectomy on allergic airway diseases is not well known. OBJECTIVES: In the present study, the influence of tonsillectomy on perennial allergic rhinitis (PAR) and bronchial asthma (BA) among pediatric subjects was prospectively investigated. METHODS: The tonsillectomy (surgery group) and the age-matched non-surgical subjects (control group) were examined and followed prospectively. In addition, immunological analysis was conducted. RESULTS: After in vitro allergen stimulation, the production of a small number of allergen-specific Th2 cells was induced in the tonsillar cells, even in sensitized subjects. Flow cytometry analysis detected more effector regulatory T cells (Tregs) in the tonsils than in peripheral blood. Clinically, after surgery, the PAR and BA symptoms improved in the surgery group but not in the control group. The total IgE in the surgery group was significantly lower than in the control group; after surgery, IgE levels slightly increased but remained lower. The postoperative Dermatophagoides farina (Der f)-specific IgE level increased in the sensitized subjects but not in the non-sensitized subjects. CONCLUSION: Tonsillectomy did not improve the underlying mechanisms of the allergy, however the decreased risk of infection and upper airway obstruction could lead to improved symptoms of allergic airway diseases.

Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study.

BACKGROUND: To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice. METHODS: This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records. RESULTS: Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1-27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2-12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141. CONCLUSIONS: The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141. TRIAL REGISTRATION NUMBER: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436).