Social anxiety disorder in adolescents who stutter: A risk for school refusal.

BACKGROUND: Stuttering is a childhood-onset fluency disorder. Part of the counseling for middle and high school students with persistent stuttering is related to school refusal. Anxiety disorders are known to contribute to school refusal. However, it is not known whether social anxiety disorder (SAD) is a factor in school refusal among adolescents who stutter. METHODS: In our first study, we examined the relationship between school refusal and SAD in 84 middle and high school students who stutter; 26% of the 84 students were in the school refusal group and the remaining 74% were in the school attendance group. The second study examined whether SAD was associated with 10 factors related to speech and stuttering frequency using the Japanese version of the Liebowitz Social Anxiety Scale for Children and Adolescents to determine the presence of SAD. Of the 84 students in the first study, 40 participated in the second study. RESULTS: The school refusal group of adolescents who stutter had significantly higher rates of SAD than the school attendance group. Fifty percent of adolescents who stutter met the criteria for SAD. Moreover, adolescents who stutter with SAD had significantly higher scores on the items "When speaking in public, do you experience tremors in your limbs?" and "After you stutter, do you have negative thoughts about yourself?" than the adolescents who stutter without SAD. CONCLUSIONS: When examining adolescents who stutter, checking for comorbid SAD may lead to better support. Moreover, noticing their repetitive negative thinking, nervousness, and trembling during speech may help to resolve SAD.

Type I Thyroplasty Is Safe in Patients Undergoing Antithrombotic Therapy.

INTRODUCTION: Type I thyroplasty is one of the most useful surgeries for unilateral vocal fold paralysis. The study objective was to determine whether type I thyroplasty is safe and perioperative antithrombotic management is acceptable in patients undergoing antithrombotic therapy. METHODS: This is a single-hospital retrospective cohort study. The records of 204 patients who underwent type I thyroplasty at a Japanese university hospital, between 2008 and July 2018 were reviewed. We compared the prothrombin time international normalized ratio, prothrombin time, operative time, intraoperative blood loss, and intra- and postoperative complications between patients who did and did not receive antithrombotic therapy. RESULTS: Of 204 patients, 51 (25%) received antithrombotic therapy (antithrombotic group). The remaining 153 patients were assigned to the control group. There were no significant differences in operative time, intraoperative blood loss, or intraoperative complications between the two groups. Sixteen (31%) patients in the antithrombotic group had a hemorrhage or hematoma in the vocal fold mucosa postoperatively, no patient had airway obstruction necessitating tracheostomy, and all patients recovered with follow-up observation only. There were no cases of intraoperative or postoperative complications, such as ischemic heart disease, ischemic stroke, or deep vein thrombosis. CONCLUSION: Type I thyroplasty with careful pre- and postoperative management is safe in patients undergoing antithrombotic therapy.

Awareness of stuttering in Japanese children aged 3-7 years.

BACKGROUND: Boey et al. (2009) devised a questionnaire for measuring children's awareness of stuttering and showed that even very young children were often aware of their stuttering. There has been no replication of studies using Boey et al.'s parent-reported questionnaire. The aim of this study was to test whether using Boey et al.'s seven questions, developed for a Dutch speaking population could be effective for measuring the awareness of stuttering in Japanese children. METHODS: Participants were 54 children who stutter (CWS) aged 3-7 years. Parents answered seven questions about their child's awareness of stuttering according to the questions developed Boey et al. RESULTS: Parental-reported observations of the child responses citing at least one awareness incident were 76%. The percentage of stuttering children with awareness of their own speech difficulties, according to chronological age, were as follows: 70% at age 3 years; 67% at age 4 years; 75% at age 5 years; 81% at age 6 years; and 90% at age 7 years. CONCLUSIONS: We found that even at age 3 years, many CWS were already aware of their stuttering. The similarity of the data with the seminal study by Boey et al. suggests that the question-based assessment is reproducible even in a country with a different spoken language. The seven questions in Boey et al. are useful for evaluating whether children's awareness of stuttering could contribute to a clinical decision as well as stuttering severity.

Safety and efficacy of a new regimen of short-term oral immunotherapy with Cry j 1-galactomannan conjugate for Japanese cedar pollinosis: a prospective, randomized, open-label study.

BACKGROUND: Short-term oral immunotherapy (OIT) using the Cry j1-galactomannan conjugate for Japanese cedar pollinosis may be effective and relatively safe. However, a treatment regimen has not been established. In the present study, we examined a new OIT regimen with a build-up phase and extended the maintenance phase of OIT to the peak period of the pollen season to enhance the therapeutic effect and safety of OIT. METHODS: A prospective, randomized, open-label trial was conducted over a period of 4 months. Participants were randomly divided into two groups. The OIT group comprised 23 subjects. The build-up phase was initiated 1 month before the expected pollen season. The maintenance phase was continued for 51 days during the peak pollen season. The control group comprised 24 subjects. The symptoms and medication score, levels of allergen-specific serum antibodies throughout the pollen season, and adverse effects with OIT were evaluated. RESULTS: Participants receiving OIT showed significant improvements in total symptom scores, medication score, and total symptom-medication scores throughout the pollen season compared with the control group. The levels of allergen-specific serum IgG4 were significantly increased in the OIT group but not in the control group throughout the cedar pollen season. Importantly, no severe adverse effects were observed with OIT. CONCLUSIONS: The new regimen of short-term OIT using the Cry j1-galactomannan conjugate for Japanese cedar pollinosis is effective, relatively safe and induces immune tolerance. Thus, OIT using allergen-galactomannan conjugates may provide a rapid, effective, and thus convenient immunotherapy for pollinosis instead of SLIT or SCIT.

Neuromagnetic detection of the laryngeal area: Sensory-evoked fields to air-puff stimulation.

The sensory projections from the oral cavity, pharynx, and larynx are crucial in assuring safe deglutition, coughing, breathing, and voice production/speaking. Although several studies using neuroimaging techniques have demonstrated cortical activation related to pharyngeal and laryngeal functions, little is known regarding sensory projections from the laryngeal area to the somatosensory cortex. The purpose of this study was to establish the cortical activity evoked by somatic air-puff stimulation at the laryngeal mucosa using magnetoencephalography. Twelve healthy volunteers were trained to inhibit swallowing in response to air stimuli delivered to the larynx. Minimum norm estimates was performed on the laryngeal somatosensory evoked fields (LSEFs) to best differentiate the target activations from non-task-related activations. Evoked magnetic fields were recorded with acceptable reproducibility in the left hemisphere, with a peak latency of approximately 100ms in 10 subjects. Peak activation was estimated at the caudolateral region of the primary somatosensory area (S1). These results establish the ability to detect LSEFs with an acceptable reproducibility within a single subject and among subjects. These results also suggest the existence of laryngeal somatic afferent input to the caudolateral region of S1 in human. Our findings indicate that further investigation in this area is needed, and should focus on laryngeal lateralization, swallowing, and speech processing.

Evaluation of volitional and reflexive swallowing in elderly patients with a history of pneumonia.

OBJECTIVES: Precise assessment of the risk of aspiration is critical in older patients with a history of pneumonia. However, the currently popular videofluoroscopic and videoendoscopic examinations of swallowing only evaluate volitional swallowing. A method for quantitative analysis of reflexive swallowing is not yet available. METHODS: We evaluated volitional swallowing in the sitting position by videoendoscopic examination and then measured the volume of injected water that triggered reflexive swallowing in the supine position in 54 patients with a history of pneumonia and 24 control patients of a similar age who had no history of pneumonia. RESULTS: The volume of injected water that triggered reflexive swallowing was larger in the pneumonia group than in the control group (mean, 1.64 +/- 0.61 mL versus 0.71 +/- 0.28 mL; p < 0.001). Both impaired volitional swallowing and impaired reflexive swallowing independently correlated with a history of pneumonia. CONCLUSIONS: The endoscopic supine swallow-evoking test ("ESSET") may detect previously omitted risk factors for aspiration in patients who can volitionally swallow.

Long-term effectiveness, safety, and quality of life outcomes following endoscopic posterior nasal neurectomy with submucosal turbinectomy for the treatment of intractable severe chronic rhinitis.

OBJECTIVE: In recent decades, posterior nasal neurectomy (PNN) with submucosal inferior turbinectomy (ST) has been increasingly used for the treatment of intractable severe rhinitis; however, to the best of our knowledge, there have been few studies regarding its long-term therapeutic effects or its influence on patient quality of life (QOL). Therefore, this study examined the long-term therapeutic effects in patients who underwent PNN with ST, as well as their QOL and medication use after surgery. METHODS: This retrospective cohort study initially included 16 consecutive patients who underwent PNN with ST from January 2010 to December 2011. Ten of the 16 patients participated in a paper-based survey questionnaire between June 2018 and November 2018; the responses of these 10 patients were used for analysis in this study. To clarify the effects of surgical treatment on symptoms, QOL, and medication status, data recorded before and 3 months after surgery were compared with data recorded at 8 years after surgery using the Japan Rhinoconjunctivitis Quality of Life Questionnaire No. 1 and Classification of the Severity of Allergic Rhinitis Symptoms I and II. RESULTS: Nasal symptoms including runny nose and nasal congestion, medication score, respective total symptoms medication scores (i.e., combined average total symptoms score and medication score), and the scores of troubles with daily life and total QOL were significantly improved at 3 months and 8 years after surgery, compared with before surgery; scores were not significantly worsened at 8 years after surgery, compared with 3 months after surgery. In addition, there were no adverse events requiring treatment after surgery. CONCLUSION: Our findings suggest that PNN with ST is effective and safe for long-term treatment of severe chronic rhinitis symptoms, as well as reduction of medication use and improvement of QOL.

Age-related changes in the hyoepiglottic ligament: functional implications based on histopathologic study.

PURPOSE: The study aimed to identify age-related changes in the hyoepiglottic ligament associated with function of the epiglottis during swallowing and respiration. MATERIALS AND METHODS: Normal postmortem laryngeal tissue samples were obtained at autopsy from 20 individuals with no history of laryngeal disease. The subjects were divided into 2 groups: those aged 81-91 years (elderly group, n = 11) and those aged 31-48 years (non-elderly group, n = 9). Specimens were subjected to Elastica van Gieson and hematoxylin-eosin staining, and characteristics of the hyoepiglottic ligament were compared between groups. RESULTS: The hyoepiglottic ligament extended from the epiglottis to both lingual muscles and the hyoid bone (pars lingualis and pars hyoideus). The numbers of muscle fibers (P < .001), collagenous fibers (P < .01), and elastic fibers (P < .001) were significantly decreased in the elderly group in comparison to those in the non-elderly group. CONCLUSION: Age-related changes in the hyoepiglottic ligament appear to be associated with aspiration, obstructive sleep apnea syndrome, and acquired laryngomalacia in the elderly.

MK615 Suppresses Hypoxia Tolerance by Up-regulation of E-cadherin in Colorectal Cancer Cells With Mutant KRAS.

BACKGROUND/AIM: The Japanese apricot "Prunus mume" is a traditional Japanese medicine. MK615, a compound extract from Prunus mume has been reported to have anti-tumor effects. Herein, we used 3D floating (3DF) culture to evaluate the anticancer effects of MK615 against human colorectal cancer (CRC) cells that contain mutant (mt) KRAS. MATERIALS AND METHODS: HKe3 cells exogenously expressing mtKRAS (HKe3-mtKRAS) were treated with MK615 in 3DF cultures. The protein levels of hypoxia-inducible factor 1 (HIF-1) and E-cadherin were quantified by western blotting. RESULTS: MtKRAS enhanced hypoxia tolerance via up-regulation of HIF-1. The expression of HIF-1 protein was suppressed by constitutive overexpression of E-cadherin in CRC HCT116 spheroids. MK615 increased the expression of E-cadherin and decreased the expression of HIF-1 in HKe3-mtKRAS. These results suggest that MK615 suppresses hypoxia tolerance by up-regulation of E-cadherin in CRC cells with mtKRAS. CONCLUSION: MK615 exhibits properties useful for the potential treatment of CRC patients with mtKRAS.

Clinicopathological analysis of sinonasal malignant lymphoma in an HTLV-1 endemic area in Japan -special focus on primary sinonasal diffuse large B-cell lymphoma.

The present study investigated histological subtypes of lymphoma in patients newly diagnosed with malignant lymphoma in the human T-cell leukemia virus type 1 (HTLV-1) endemic area of Japan, and further analyzed the clinicopathological features and clinical outcomes of patients with primary sinonasal lymphoma. We retrospectively examined 151 patients aged 18-90 years in Fukuoka, Japan. Subtypes of lymphoma were determined according to the WHO classification. Among the 151 patients, 104 were diagnosed with malignant lymphoma, including 96 at the time of initial diagnosis. Ninety-two of the 96 lymphomas (96%) were non-Hodgkin lymphoma. Mature B-cell neoplasms comprised 78% (n = 75). Primary lymphoma of the sinonasal cavity was found in six patients (6%). The histological subtype of sinonasal lymphoma was diffuse large B-cell lymphoma (DLBCL) in all six tumors. Furthermore, overall survival was significantly different among three distinct DLBCL patient groups, including primary sinonasal lymphoma patients (p = 0.0016; 3-year overall survival: sinonasal DLBCL group, 53%; DLBCL of the CNS group, 0%; other DLBCL group, 83%). Our study suggests that primary DLBCL of the sinonasal tract is a distinct disease entity of DLBCL.

Kinematic evaluation of penetration and aspiration in laryngeal elevating and descending periods.

OBJECTIVES: It is important to evaluate swallowing movements by dividing them into periods of laryngeal closure and release. The purpose of this study was to evaluate penetration-aspiration (PA) according to human pathophysiology and to identify the factors for predicting PA. STUDY DESIGN: Case-control study. METHODS: Eighty-one patients with complaints of dysphagia caused by various etiologies were enrolled in this study. Videofluoroscopic swallowing studies were conducted, and the spatial and temporal factors were analyzed by computer-assisted motion analysis. RESULTS: The initiation of laryngeal vestibule closure in the laryngeal elevating period and its duration in the laryngeal descending period were significant factors for evaluating PA. CONCLUSION: A knowledge of the delay of laryngeal vestibule closure in the laryngeal elevating period and its short duration in the laryngeal descending period could make it easier to evaluate the risk of PA. LEVEL OF EVIDENCE: 3b. Laryngoscope, 128:806-811, 2018.

Oral phase dysphagia in facial onset sensory and motor neuronopathy.

INTRODUCTION: Facial onset motor and sensory neuronopathy (FOSMN) is a rare disease whose cardinal features are initial asymmetrical facial sensory deficits followed by bulbar symptoms and spreading of sensory and motor deficits from face to scalp, neck, upper trunk, and upper extremities in a rostral-caudal direction. Although bulbar involvement is frequently observed in FOSMN, dysphagia in these patients has not been fully described. In this study, we aimed to characterize dysphagia as a prognostic factor in FOSMN by investigating our institutional case series. METHODS: We retrospectively reviewed the medical records, including swallowing function tests, of six patients with FOSMN (three men and three women) who were thoroughly examined at Kyushu University Hospital between 1 January 2005 and 30 November 2017. RESULTS: Average age at onset was 58.5 years; average disease duration was 5.7 years. All patients developed bulbar dysfunction and dysphagia (at an average of 1.8 and 2.6 years from onset, respectively), resulting in choking episodes in three patients, percutaneous endoscopic gastrostomy placement in three, and recurrent aspiration pneumonia in one. Four of five patients evaluated with videofluoroscopic swallowing studies had poor oral retention, leading to bolus flowing into the pharynx before swallowing; the fifth patient showed poor lingual transfer. Fiberoptic endoscopic evaluation of swallowing revealed leakage of blue-dyed water from the mouth to the pharynx in three patients because of poor oral retention, but only mild pharyngeal phase dysphagia in all four cases evaluated. CONCLUSIONS: Oral phase dysphagia predominates in the early stage of FOSMN.

A case of multiple system atrophy-parkinsonian type with stuttering- and palilalia-like dysfluencies and putaminal atrophy.

Both developmental and acquired stuttering are related to the function of the basal ganglia-thalamocortical loop, which includes the putamen. Here, we present a case of stuttering- and palilalia-like dysfluencies that manifested as an early symptom of multiple system atrophy-parkinsonian type (MSA-P) and bilateral atrophy of the putamen. The patient was a 72-year-old man with no history of developmental stuttering who presented with a stutter for consultation with our otorhinolaryngology department. The patient was diagnosed with MSA-P based on parkinsonism, autonomic dysfunction, and bilateral putaminal atrophy revealed by T2-weighted magnetic resonance imaging. Treatment with levodopa improved both the motor functional deficits related to MSA-P and stuttering-like dysfluencies while reading; however, the palilalia-like dysfluencies were much less responsive to levodopa therapy. The patient died of aspiration pneumonia two years after his first consultation at our hospital. In conclusion, adult-onset stuttering- and palilalia-like dysfluencies warrant careful examination of the basal ganglia-thalamocortical loop, and especially the putamen, using neuroimaging techniques. Acquired stuttering may be related to deficits in dopaminergic function.

Clinical management of squamous cell carcinoma associated with sinonasal inverted papilloma.

OBJECTIVE: The aim of this study was to investigate the clinical features and prognosis of patients with squamous cell carcinoma (SCC) associated with sinonasal inverted papilloma (IP). METHODS: The medical records of 95 patients who were diagnosed with IP or SCC associated with IP were retrospectively reviewed. Out of 95 patients, 15 were diagnosed with SCC associated with IP. The clinical characteristics, treatment modalities, and survival outcomes of the patients were analyzed. RESULTS: The incidence of SCC associated with IP was 15.8%. Although differential diagnosis between IP and SCC associated with IP is difficult, epistaxis may be the specific symptom in SCC associated with IP cases. The 3-year disease-specific survival rate was higher in cases with T1, 2 and 3 than in cases with T4. There was no significant difference in survival rate between maxillary sinus and other primary sites. On the other hand, there was a significant difference in survival rate between the microscopic SCC with IP cases and the other cases. In addition, the patients with <70 years old better than those with >70 years old with a 3-year disease free survival of 80% versus 0%. CONCLUSIONS: Some T4 patients were found to have a highly aggressive disease. Therefore, complete surgical resection followed by chemo-radiation therapy is the recommended treatment for patients with T4 disease to control of the primary tumor site.

Safety and efficacy of short-term oral immunotherapy with Cry j 1-galactomannan conjugate for Japanese cedar pollinosis: a randomized controlled trial.

Current allergen-specific immunotherapy (AIT) for pollinosis requires long-term treatment with potentially severe side effects. Therefore, development of an AIT that is safe and more convenient with a shorter regimen is needed. This prospective, double-blind, placebo-controlled trial randomized 55 participants with Japanese cedar pollinosis (JCP) to active or placebo groups to test the safety and efficacy of short-term oral immunotherapy (OIT) with Cry j 1-galactomannan conjugate for JCP. Mean symptom-medication score as the primary outcome in the active group improved 27.8% relative to the placebo group during the entire pollen season. As the secondary outcomes, mean medication score in active group improved significantly, by 56.2%, compared with placebo during the entire pollen season. Mean total symptom score was similar between active and placebo groups during the entire pollen season. There were no severe treatment-emergent adverse events in the active and placebo groups. Therefore short-term OIT with Cry j 1-galactomannan conjugate is safe, and effective for reducing the amount of medication use for JCP.

Effect of short-term oral immunotherapy with Cry j1-galactomannan conjugate on quality of life in Japanese cedar pollinosis patients: A prospective, randomized, open-label study.

OBJECTIVE: We have recently reported that a new regimen of short-term oral immunotherapy (OIT) with the Cry j1-galactomannan conjugate for Japanese cedar pollinosis (JCP) is effective to the improvement in the symptoms and medication use during the pollen season and relatively safe. The effect of OIT on quality of life (QOL) of JCP patients has not been assessed. Therefore, we evaluated for the first time the effect of OIT on QOL during the Japanese cedar/cypress pollen season. METHODS: A prospective, randomized, open-label trial was conducted over a period of 4 months. Participants were randomly divided into two groups. The OIT and control groups comprised 23 and 24 subjects, respectively. The build-up phase was initiated 1 month before the expected pollen season. The maintenance phase was continued for 51 days during the peak of the cedar pollen season. The QOL score in the Japan Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) No. 1 and visual analog scale (VAS) throughout the pollen season were evaluated. RESULTS: Participants receiving OIT showed significant improvements in the total QOL score and VAS throughout the pollen season compared with the control group. In addition, the mean total QOL score and VAS correlated in both groups during the pollen season. CONCLUSION: The new regimen of short-term OIT using the Cry j1-galactomannan conjugate results in meaningful improvements in QOL of JCP patients. Our findings suggest that short-term OIT using allergen-galactomannan conjugates, as well as sublingual and subcutaneous immunotherapy, improves QOL of patients with pollinosis. The study was registered in UMIN-CTR (UMIN000013408) as the name of "a prospective, randomized, open study of oral Cry j1-galactomannan conjugate immunotherapy for Japanese cedar pollen allergy".

Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses.

PURPOSE: We used serologic screening of a cDNA expression library of human testis to identify novel cancer/testis antigens that elicit both humoral and cellular immune responses in cancer patients. EXPERIMENTAL DESIGN AND RESULTS: We identified a novel gene designated KM-HN-1 the expression of which is testis-specific among normal tissues; it contains coiled coil domains and a leucine zipper motif and encodes a putative protein consisting of 833 amino acids. KM-HN-1 expression was observed in various cancer tissues and cancer cell lines at both mRNA and protein levels. Immunofluorescence staining of an esophageal cancer cell line revealed that KM-HN-1 protein was present exclusively in the nucleus during mitosis. Recombinant KM-HN-1 protein was produced, and used for ELISA to quantitate levels of IgG antibody specific to KM-HN-1. Higher levels of IgG antibodies specific to KM-HN-1 were detected in many types and numbers of cancer patients but not in healthy donors. The CTL lines specific to KM-HN-1, generated from HLA-A*2402-positive healthy donors and cancer patients, killed human leukocyte antigen (HLA)-A24-positive cancer cells expressing KM-HN-1 but not cell lines that did not express either KM-HN-1 or HLA-A24. CONCLUSIONS: We identified a novel cancer/testis antigen, KM-HN-1, which elicited humoral immune responses in patients with various types of cancer. Furthermore, KM-HN-1-specific CTLs could be generated from both healthy donors and cancer patients, which indicated that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.

Adenoid cystic carcinoma of the lacrimal gland with wide and severe myoepithelial differentiation.

Adenoid cystic carcinoma (ACC) of the lacrimal gland is the second most common epithelial tumor for which different biologic courses can be predicted by histologic criteria. Three main types of growth patterns, cribriform; tubular; and solid have been identified. Tumors with solid components frequently follow a more aggressive clinical course and show worse prognosis than those with other patterns. We herein report a case of ACC with wide and severe myoepithelial differentiation arising from the lacrimal gland and presenting with aggressive clinical behavior. Postoperative radiotherapy may be the treatment of choice to control residual lesions and provide long-term survival even in the case of incomplete resection. Despite extensive surgery and radiation therapy, the prognosis of these tumors, especially with solid components, remains extremely poor. Accurate diagnosis is important because tumor histopathology is generally believed to be the most significant factor in patient survival.