Causes of Vocal Fold Paralysis.

BACKGROUND: Vocal fold paralysis (VFP) can result from a variety of diseases or surgeries and has various causes. This study determined concurrent etiologies in patients who were treated in a teaching hospital (tertiary medical center). METHODS: A retrospective review of medical records of patients with VFP from September 2010 to December 2019 was performed to determine the etiology. Patients with laryngeal/hypopharyngeal malignancies, those with incomplete examination and follow-up data were excluded from the study. During the follow-ups, cases involving recovery were also excluded. RESULTS: One hundred and ninety-four patients with a determined etiology were included: 113 males and 81 females. Unilateral VFP was present in 178 patients, and 16 presented with bilateral VFP. The causes of unilateral VFP were surgical for 61.3%, neoplastic for 17.5%, idiopathic for 10.3%, traumatic for 1.5%, central for 4.7%, cardiovascular for 2%, radiation-induced for 1.5%, and inflammatory for 1%. Thyroidectomy was the most common surgery for unilateral VFP and was the cause for 54 patients. Lung cancer was responsible for 15 cases and was the most common neoplastic etiology of unilateral VFP. For those who presented with bilateral VFP, surgery was the most common cause and accounted for 56.3% of the incidences. In terms of gender, surgery was the most common cause for both sexes, accounting for 62 of 113 male patients and 57 of 81 female patients. Four cases recovered during the follow-ups and these were excluded. CONCLUSION: Surgery and in particular, thyroidectomy, was the most common cause of VFP for these series. Central nervous system disorders were the cause of VFP (4.5%). Central nervous system disorders, especially cerebrovascular accidents that induced VFP, could not be neglected. Radiation-induced cranial nerve paralysis in the head and neck cancer was possible causes. The percentage for the causes of unilateral VFP, surgery increased and the percentage for neoplasm decreased for Taiwan.

Erratum: Lee, H.H., et al. Histone 2A Family Member J Drives Mesenchymal Transition and Temozolomide Resistance in Glioblastoma Multiforme. Cancers 2020, 12, 98.

The authors wish to make the following changes to this paper [...].

FOXD1 Repression Potentiates Radiation Effectiveness by Downregulating G3BP2 Expression and Promoting the Activation of TXNIP-Related Pathways in Oral Cancer.

Radiotherapy is commonly used to treat oral cancer patients in the current clinics; however, a subpopulation of patients shows poor radiosensitivity. Therefore, the aim of this study is to identify a biomarker or druggable target to enhance the effectiveness of radiotherapy on oral cancer patients. By performing an in silico analysis against public databases, we found that the upregulation of FOXD1, a gene encoding forkhead box d1 (Foxd1), is extensively detected in primary tumors compared to normal tissues and associated with a poor outcome in oral cancer patients receiving irradiation treatment. Moreover, our data showed that the level of FOXD1 transcript is causally relevant to the effective dosage of irradiation in a panel of oral cancer cell lines. The FOXD1 knockdown (FOXD1-KD) dramatically suppressed the colony-forming ability of oral cancer cells after irradiation treatment. Differentially expressed genes analysis showed that G3BP2, a negative regulator of p53, is predominantly repressed after FOXD1-KD and transcriptionally regulated by Foxd1, as judged by a luciferase-based promoter assay in oral cancer cells. Gene set enrichment analysis significantly predicted the inhibition of E2F-related signaling pathway but the activation of the interferons (IFNs) and p53-associated cellular functions, which were further validated by luciferase reporter assays in the FOXD1-KD oral cancer cells. Robustly, our data showed that FOXD1-KD fosters the expression of TXNIP, a downstream effector of IFN signaling and activator of p53, in oral cancer cells. These findings suggest that FOXD1 targeting might potentiate the anti-cancer effectiveness of radiotherapy and promote immune surveillance on oral cancer.

Efficacy of vardenafil in human nasal mucosa.

OBJECTIVE: Levitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. It is applied to treatment of erectile dysfunction. PDE5 inhibitors dilate the penile blood vessels and cause prolonged erections. However, the effects of Levitra on human nasal mucosa are not yet fully explored. MATERIALS AND METHODS: We examined the effectiveness of Levitra on human nasal mucosa directly in vitro by testing: 1) effect on human nasal mucosa resting tension; 2) effect on contraction caused by 10-6 M methoxamine as a sympathetic mimetic; 3) effect of the drugs on electrically induced human nasal mucosa contractions. RESULTS: The results showed that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of Levitra at doses of 10-4 M elicited a significant relaxation response to 10-6 M methoxamine-induced mucosa strip contraction. Levitra could not inhibit electrical field stimulation-induced spike contraction and had a minimal effect on the basal tension of nasal mucosa as the concentration increased. CONCLUSION: This study indicated that high concentrations of Levitra had a significant spasmolytic effect by antagonizing α-adrenoceptors. Moreover, nasal obstruction might not be relieved in patients suffering from erectile dysfunction and stuffy noses who were concomitant using α-adrenergic agonist and Levitra.

Association of rs2651899 Polymorphism in the Positive Regulatory Domain 16 and Common Migraine Subtypes: A Meta-Analysis.

BACKGROUND: Migraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome-wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta-analysis to examine this issue. METHODS: We performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO). RESULTS: Six studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta-analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively. CONCLUSION: Our major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO).

Nicotinic Acetylcholine Receptor Subunit Alpha-5 Promotes Radioresistance via Recruiting E2F Activity in Oral Squamous Cell Carcinoma.

Radiotherapy is commonly used to treat patients with oral squamous cell carcinoma (OSCC), but a subpopulation of OSCC patients shows a poor response to irradiation treatment. Therefore, identifying a biomarker to predict the effectiveness of radiotherapy in OSCC patients is urgently needed. In silico analysis of public databases revealed that upregulation of CHRNA5, the gene encoding nicotinic acetylcholine receptor subunit alpha-5, is extensively detected in primary tumors compared to normal tissues and predicts poor prognosis in OSCC patients. Moreover, CHRNA5 transcript level was causally associated with the effective dose of irradiation in a panel of OSCC cell lines. Artificial silencing of CHRNA5 expression enhanced, but nicotine reduced, the radiosensitivity of OSCC cells. Gene set enrichment analysis demonstrated that the E2F signaling pathway is highly activated in OSCC tissues with high levels of CHRNA5 and in those derived from patients with cancer recurrence after radiotherapy. CHRNA5 knockdown predominantly suppressed E2F activity and decreased the phosphorylation of the Rb protein; however, nicotine treatment dramatically promoted E2F activity and increased Rb phosphorylation, which was mitigated after CHRNA5 knockdown in OSCC cells. Notably, the signature combining increased mRNA levels of CHRNA5 and the E2F signaling gene set was associated with worse recurrence-free survival probability in OSCC patients recorded to be receiving radiotherapy. Our findings suggest that CHRNA5 is not only a useful biomarker for predicting the effectiveness of radiotherapy but also a druggable target to enhance the cancericidal effect of irradiation on OSCC.

Ovatodiolide suppresses inflammatory response in BEAS-2B cells by regulating the CREB/AQP5 pathway, and sensitizes nasopharyngeal carcinoma cells to radiation therapy.

Due to the radiosensitivity of the airway epithelium, radiation-induced sinusitis or bronchitis is not uncommon, and makes mitigation of resulting inflammatory airway diseases a principal goal of many investigations. This study examined whether Ovatodiolide (Ova) sensitizes the human metastatic nasopharyngeal cancer (NPC) cell line, NPC-BM2, to irradiation using viability, clonogenicity and Western blot assays. Concurrently, we used varying concentrations of histamine and/or Ova to determine the anti-inflammatory potential of Ovatodiolide on normal bronchus epithelial BEAS-2B cells, as well as on the subcellular distribution of Aquaporin 5 (AQP5) and expression levels of p-CREB, AQP5, p38 MAPK, NF-κB, PI3K, Akt and ERK proteins. We demonstrated that Ova in synergism with irradiation inhibited NPC-BM2 cell viability and suppressed their clonogenicity. Immunofluorescence analysis revealed low-dose (≤ 2.5 µM) Ova reversed histamine-induced suppression of AQP5 expression, and abrogated histamine-enhanced NF-κB nuclear translocation, indicating Ova modulates the p38 MAPK/NF-κB signaling pathway and elicits p-CREB/AQP5-mediated antihistamine effects. Similarly, Ova deregulates the PI3K/Akt/ERK signaling in BEAS-2B cells, suggesting its cytoprotective potential. In conclusion, this study highlights the radio-sensitizing anticancer efficacy of Ova in human metastatic NPC cells, as well as its putative cytoprotective role in normal bronchial cells, for airway surface liquid maintenance and homeostasis during or after radiotherapy.

A probabilistic model for reducing medication errors: A sensitivity analysis using Electronic Health Records data.

OBJECTIVES: Medication-related clinical decision support systems have already been considered as a sophisticated method to improve healthcare quality, however, its importance has not been fully recognized. This paper's aim was to validate an existing probabilistic model that can automatically identify medication errors by performing a sensitivity analysis from electronic medical record data. METHODS: We first built a knowledge base that consisted of 2.22 million disease-medication (DM) and 0.78 million medication-medication (MM) associations using Taiwan Health and Welfare data science claims data between January 1st, 2009 and December 31st, 2011. Further, we collected 0.6 million outpatient visit prescriptions from six departments across five different medical centers/hospitals. Afterward, we employed the data to our AESOP model and validated it using a sensitivity analysis of 11 various thresholds (α = [0.5; 1.5]) that were used to identify positive DM and MM associations. We randomly selected 2400 randomly prescriptions and compared them to the gold standard of 18 physicians' manual review for appropriateness. RESULTS: One hundred twenty-one results of 2400 prescriptions with various thresholds were tested by the AESOP model. Validation against the gold standard showed a high accuracy (over 80%), sensitivity (80-96%), and positive predictive value (over 85%). The negative predictive values ranged from 45 to 75% across three departments, cardiology, neurology, and ophthalmology. CONCLUSION: We performed a sensitivity analysis and validated the AESOP model in different hospitals. Thus, picking the optimal threshold of the model depended on balancing false negatives with false positives and depending on the specialty and the purpose of the system.

The Epidemiology of Benign Voice Disorders in Taiwan: A Nationwide Population-Based Study.

OBJECTIVE: Because there are few population-based studies regarding the epidemiology of benign voice diseases, the present study used a nationwide population-based claims database (the National Health Insurance Research Database) to investigate the epidemiology of benign voice diseases among the general adult population in Taiwan. METHODS: Study participants were retrieved for those patients who were 20 to 90 years old with a diagnosis of benign voice diseases that were defined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes from 2006 to 2014. Patient visits were grouped into infectious (ICD-9-CM: 012.3, 032.3, 034.0, 090.5, 095.8,101, 464.0, 464.20, 464.21, 465.x, 476.0, 476.1) and noninfectious (ICD-9-CM: 306.1, 478.3x, 478.4, 478.5, 748.3, 784.4x) dysphonia groups. RESULTS: Benign voice disorders have a prevalence of approximately 3.6% in Taiwan as of 2014. The year-to-year prevalence decreased gradually in the query period. Infectious dysphonia diagnoses were higher than noninfectious ones. Dysphonia caused by noninfectious diagnoses was most prevalent in the 60 to 79 years age group. Dysphonia caused by infectious diagnoses was highest in 20 to 39 years group. Noninfectious dysphonia diagnoses were more common in women. CONCLUSION: The prevalence of voice disorders among the adult population in Taiwan was 3.6% in 2014. Voice disorders are more common in women and occur primarily in the 20 to 39 years age group. Infectious dysphonia is more common than noninfectious dysphonia. The results may be underestimated due to limitation of the database. This is the first population-based epidemiology study of adult voice disorders.

Histone 2A Family Member J Drives Mesenchymal Transition and Temozolomide Resistance in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor and has a poor prognosis and is poorly sensitive to radiotherapy or temozolomide (TMZ) chemotherapy. Therefore, identifying new biomarkers to predict therapeutic responses of GBM is urgently needed. By using The Cancer Genome Atlas (TCGA) database, we found that the upregulation of histone 2A family member J (H2AFJ), but not other H2AFs, is extensively detected in the therapeutic-insensitive mesenchymal, IDH wildtype, MGMT unmethylated, or non-G-CIMP GBM and is associated with poor TMZ responsiveness independent of radiation. Similar views were also found in GBM cell lines. Whereas H2AFJ knockdown diminished TMZ resistance, H2AFJ overexpression promoted TMZ resistance in a panel of GBM cell lines. Gene set enrichment analysis (GSEA) revealed that H2AFJ upregulation accompanied by the activation of TNF-α/NF-κB and IL-6/STAT3-related pathways is highly predicted. Luciferase-based promoter activity assay further validated that the activities of NF-κB and STAT3 are causally affected by H2AFJ expression in GBM cells. Moreover, we found that therapeutic targeting HADC3 by tacedinaline or NF-κB by ML029 is likely able to overcome the TMZ resistance in GBM cells with H2AFJ upregulation. Significantly, the GBM cohorts harboring a high-level H2AFJ transcript combined with high-level expression of TNF-α/NF-κB geneset, IL-6/STAT3 geneset or HADC3 were associated with a shorter time to tumor repopulation after initial treatment with TMZ. These findings not only provide H2AFJ as a biomarker to predict TMZ therapeutic effectiveness but also suggest a new strategy to combat TMZ-insensitive GBM by targeting the interaction network constructed by TNF-α/NF-κB, IL-6/STAT3, HDAC3, and H2AFJ.

Enhanced basal tension in isolated rat tracheal smooth muscle stimulated by electric field stimulation under low temperature.

Exposure to cold causes cutaneous vasoconstriction to reduce body heat loss, while the airway warms up the inspired cold air, thus suggesting that cooling might evoke a response in tracheal smooth muscle different from that in cutaneous blood vessels. The aim of this study was to evaluate the effect of temperature on isolated rat trachea, with or without electric field stimulation (EFS). Tissue bath for isolated trachea was used. An in vitro isometric contraction of trachea from healthy male Sprague-Dawley rat (body weight: ≥ 200 g) was continuously recorded. Tension in strips of rat trachea that were untreated and treated with EFS, was continuously recorded in stepwise manner at temperatures varying from 37 °C to 7 °C or from 7 °C to 37 °C. Results indicated that descent and re-ascent of temperature produced temperature-dependent tension changes. Basal tension of the trachea decreased when temperature was reduced if EFS was not applied. EFS-induced spike contraction decreased when temperature was reduced, while basal tension increased at the same time. We concluded that low temperature induced rapid and reproducible contraction in isolated rat tracheal strip only if EFS was applied. Increasing temperature reduced basal tension and enhanced EFS-induced spike contraction of the trachea at the same time.

Vardenafil inhibiting parasympathetic function of tracheal smooth muscle.

BACKGROUND: Levitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. Nowadays, it is applied to treatment of erectile dysfunction. PDE5 inhibitors are employed to induce dilatation of the vascular smooth muscle. The effect of Levitra on impotency is well known; however, its effect on the tracheal smooth muscle has rarely been explored. When administered for sexual symptoms via oral intake or inhalation, Levitra might affect the trachea. METHODS: This study assessed the effects of Levitra on isolated rat tracheal smooth muscle by examining its effect on resting tension of tracheal smooth muscle, contraction caused by 10-6 M methacholine as a parasympathetic mimetic, and electrically induced tracheal smooth muscle contractions. RESULTS: The results showed that adding methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of Levitra at doses of 10-5 M or above elicited a significant relaxation response to 10-6 M methacholine-induced contraction. Levitra could inhibit electrical field stimulation-induced spike contraction. It alone had minimal effect on the basal tension of the trachea as the concentration increased. CONCLUSION: High concentrations of Levitra could inhibit parasympathetic function of the trachea. Levitra when administered via oral intake might reduce asthma attacks in impotent patients because it might inhibit parasympathetic function and reduce methacholine-induced contraction of the tracheal smooth muscle.

Intestinal parasitic infections: Current prevalence and risk factors among schoolchildren in capital area of the Republic of Marshall Islands.

Intestinal parasitic infections (IPIs) among schoolchildren in Republic of Marshall Islands (RMI) largely remains unknown, thus investigation on IPIs status to establish the baseline data is urgently needed. This cross-sectional study intended to investigate the current IPIs status and associated risk factors among schoolchildren at capital of RMI. Single stool sample from 400 schoolchildren (207 boys and 193 girls) aged 9.73±2.50 yrs old was examined by employing merthiolate-iodine-formaldehyde concentration method. Demographic characteristics, uncomfortable symptoms and risk factors were obtained by questionnaires investigation. The overall prevalence of IPIs in schoolchildren was 22.8% (91/400), of them 24.2% harbored at least 2 different parasites. Notably, the majority was infected by waterborne protozoan parasites (82.4%, 75/91). Nine different intestinal parasites have been identified, of which six were pathogenic including Hook worm, Trichuris trichiura, Enterobius vermicularis, Entamoeba histolytica/dispar, Giardia intestinalis and Blastocystis hominis. Schoolchildren who ever complained dizziness or headache showed a significant higher prevalence of pathogenic IPIs than those who did not (p<0.05). Schoolchildren who lived in urban area than rural area had higher chance to acquire pathogenic IPIs (p=0.03). However, none of risk factors were identified to be associated with pathogenic IPIs.

The identification of the TRPM8 channel on primary culture of human nasal epithelial cells and its response to cooling.

BACKGROUND: It has been proposed that the transient receptor potential (TRP) channel Melastatin 8 (TRPM8) is a cold-sensing TRP channel. However, its presence and its role in the nasal cavity have not yet been fully studied. METHODS: Immunohistology was used to study TRPM8 receptors in both the nasal mucosa tissue and the primary cultures of human nasal cells. Cells from primary cultures were immunostained with antibodies to TRPM8, mucin, cytokeratin (CK)-14, CK-18, and vimentin. Western blotting and real-time polymerase chain reaction (PCR) were used to determine the physiological role of TRPM8 in mucus production in the nasal cavity, with and without its agonist and antagonist. RESULTS: The TRPM8 is clearly present in the epithelium, mucous glands, and vessels. No obvious TRPM8-immunoreactive cells were detected in the connective tissue. Immunostaining of cytospin preparations showed that epithelial cells test positive for CK-14, CK-18, TRPM8, and mucin 5AC (MUC5AC). Fibroblastic cells are stained negative for TRPM8. Secreted mucins in the cultured supernatant are detected after exposure to menthol and moderate cooling to 24°C. Both induce a statistically significant increase in the level of MUC5AC mRNA and mucin production. BCTC, a TRPM8 antagonist, has a statistically significant inhibitory effect on MUC5AC mRNA expression and MUC5AC protein production that is induced by menthol and moderate cooling to 24°C. CONCLUSIONS: The study demonstrates that TRPM8 is present in the nasal epithelium. When it is activated by moderate cooling to 24°C or menthol, TRPM8 induces the secretion of mucin. This study shows that TRPM8 channels are important regulators of mucin production. Therefore, TRPM8 antagonists could be used to treat refractory rhinitis.

Survival prognostic factors for metachronous second primary head and neck squamous cell carcinoma.

We examined the overall survival rates of a national cohort to determine optimal treatments and prognostic factors for patients with metachronous second primary head and neck squamous cell carcinomas (mspHNSCCs) at different stages and sites. We analyzed data of mspHNSCC patients collected from the Taiwan Cancer Registry database. The patients were categorized into four groups based on the treatment modality: Group 1 (control arm; chemotherapy [CT] alone), Group 2 (reirradiation [re-RT] alone with intensity-modulated radiotherapy [IMRT]), Group 3 (concurrent chemoradiotherapy alone [irradiation with IMRT]), and Group 4 (salvage surgery with or without RT or CT). We enrolled 1741 mspHNSCC patients without distant metastasis. Multivariate Cox regression analyses revealed that Charlson comorbidity index (CCI) ≥6, stage of second HNSCC, stage of first HNSCC, and duration from first primary HNSCC of <3 years were significant poor independent prognostic risk factors for overall survival. After adjustment, adjusted hazard ratios and 95% confidence intervals for the overall all-cause mortality risk at mspHNSCC clinical stages III and IV were 0.72 (0.40-1.82), 0.52 (0.35-0.75), and 0.32 (0.22-0.45) in Groups 2, 3, and 4, respectively. A Cox regression analysis indicated that a re-RT dose of ≥6000 cGy was an independent protective prognostic factor for treatment modalities. CCI ≥ 6, stage of second HNSCC, stage of first HNSCC, and duration from first primary HNSCC of <3 years were significant poor independent prognostic risk factors for overall survival. A re-RT dose of ≥6000 cGy may be necessary for mspHNSCCs.

Effect of budesonide and azelastine on histamine signaling regulation in human nasal epithelial cells.

Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.

Menthol inhibiting parasympathetic function of tracheal smooth muscle.

Menthol is used as a constituent of food and drink, tobacco and cosmetics nowadays. This cold receptor agonist has been used as a nasal inhalation solution in the daily life. The effect of menthol on nasal mucosa in vivo is well known; however, the effect of the drug on tracheal smooth muscle has been rarely explored. Therefore, during administration of the drug for nasal symptoms, it might also affect the trachea via oral intake or inhalation. We used our preparation to test the effectiveness of menthol on isolated rat tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Krebs solution in a muscle bath at 37ºC. Changes in tracheal contractility in response to the application of a parasympathetic mimetic agent were measured using a transducer connected to a Pentium III computer equipped with polygraph software. The following assessments of menthol were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine as a parasympathetic mimetic; (3) effect of the drug on electrically induced tracheal smooth muscle contractions. Results indicated that addition of a parasympathetic mimetic to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of menthol at doses of 10-5 M or above elicited a relaxation response to 10-6 M methacholine-induced contraction. Menthol could also inhibit electrical field stimulation (EFS) induced spike contraction. However, it alone had a minimal effect on the basal tension of trachea as the concentration increased. We concluded that the degree of drug-induced tracheal contraction or relaxation was dose-dependent. In addition, this study indicated that high concentrations of menthol might actually inhibit parasympathetic function of the trachea.

Pediatric sialendoscopy in Asians: A preliminary report.

BACKGROUND/PURPOSE: The sialendoscopic approach in treating pediatric salivary gland disorders has been reported with great success through the years. Whereas this success has been widely reported in Caucasian populations, relatively little has been reported regarding the use of this procedure in pediatric patients in Asian countries. The purpose of this study is to report our preliminary experience in pediatric sialendoscopy. METHODS: The data from 20 patients (<18years old), who underwent sialendoscopy for obstructive sialoadenitis in the Department of Otorhinolaryngology of Mackay Memorial Hospital between October 2013 and November 2015, were reviewed. RESULTS: Twelve of our 20 patients (60%) were diagnosed with sialolithiasis and 8 of our 20 patients (40%) presented with non-lithiasis obstructive sialoadenitis. Ductal stenosis was found in 13 patients, and 18 patients had debris/mucous plug formation. The overall success rate was 95% (19/20) in our series, and 85% (17/20) of the patients had achieved a complete remission after a single sialendoscopy procedure. CONCLUSIONS: Sialendoscopy is an ideal treatment in the management of obstructive sialoadenitis in Asian pediatric patients. If necessary, Holmium:YAG laser lithotripsy and sialostent placement could be applied, and both procedures are well tolerated in pediatric patients.

Association of Sudden Sensorineural Hearing Loss With Vertebrobasilar Insufficiency.

IMPORTANCE: Little is known about the association between sudden sensorineural hearing loss (SSNHL) and vertebrobasilar insufficiency (VBI). OBJECTIVE: To explore the association between SSNHL and VBI. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a population-based, case-control study. Patients from January 1, 2000, to December 31, 2011, were retrospectively identified from the Taiwan National Health Insurance Research Database, which includes claims data on a random sample of 1 million people. MAIN OUTCOMES AND MEASURES: Using propensity score matching on age and sex, patients were stratified at a 1:4 ratio into a study group comprising 5304 patients with a diagnosis of SSNHL and a control group comprising 21 216 patients. Those with a diagnosis of VBI before the index date (the date each patient was diagnosed as having SSNHL) in both groups were then identified. A conditional logistic regression model was used to estimate the adjusted odds ratios (ORs) and 95% CIs as a measure of the association between SSNHL and VBI. RESULTS: The study cohort comprised 26 520 patients. Their mean (SD) age was 51.3 (17.2) years, and 47.1% (12 500 of 26 520) were female. Vertebrobasilar insufficiency was diagnosed before the index date in 0.5% (26 of 5304) of patients with SSNHL and in 0.2% (38 of 21 216) of controls without SSNHL. After adjusting for comorbid medical disorders, patients with SSNHL were more likely than controls to have had VBI (OR, 1.76; 95% CI, 1.02-3.04). There were no significant differences in the prevalence of VBI among male patients with SSNHL vs male controls (OR, 1.72; 95% CI, 0.87-3.40) or among female patients with SSNHL vs female controls (OR, 1.86; 95% CI, 0.76-4.59). CONCLUSIONS AND RELEVANCE: Patients with VBI appear to be at increased risk of developing SSNHL. Further research is needed to investigate the association among the severity of VBI, the risk of SSNHL, and the pattern of the audiometric curve.

Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index.

For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival.Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments).We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31-0.35), 0.34 (0.31-0.36), and 0.37 (0.28-0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82-1.55), 0.67 (0.62-0.73), and 0.49 (0.46-0.53) for CCI scores of ≥10, 5 to 9, and <5, respectively.Aggressive treatments improve survival in elderly (≥65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for HNSCC patients with CCI scores ≥10.